Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible. The American Association of Neurology (AAN) has defined brain death with three cardinal signs, cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
Clinical testing for brain death
1. Coma: Absence of response to noxious stimulus (supraorbital pressure or pressure on the nail bed) with the exception of spinally mediated reflexes
2. . 2. Absent brain stem reflexes (a formal evaluation of the brain stem reflexes is undertaken when the patient has had fixed dilated pupils and absent cranial nerve reflexes for more than 4 h).
3. Apnea test: The aim of this test is to check for the integrity of the brain stem respiratory center at high levels of blood carbon dioxide. Prerequisites include a patient who is normothermic (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralytic drugs, with normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
Troubleshooting during performance of apnea test
1. Patient’s systolic blood pressure (SBP) ≤100 mmHg: Vasopressors, inotropes and fluid boluses need to be administered to keep the blood pressure (BP) above the target. The apnea test is aborted if systolic BP is ≤90 mmHg and the test needs to be repeated after stabilization
2. Oxygen saturation not maintained during apnea testing: The apnea testing is terminated if the saturation is ≤85% for more than 30 s.The test can be retried with T-piece and continuous positive airway pressure of 10 cm H2 O and oxygen flow of 12.0 L/min. Reducing the positive end-expiratory pressure (PEEP) to 5 cm H2 O prior to disconnection from the ventilator for apnea testing can predict the tolerance to apnea.
3. Patient is hypothermic (<36.5°F): Guidelines for apnea testing are not valid and needs to be repeated after correction of hypothermia.
4. Patient repeatedly desaturates or becomes hypotensive during apnea testing: One should consider ancillary tests for confirming brain death (electroencephalography, cerebral angiography, transcranial Doppler and scintigraphy). In India, the laws are not clear about the use of ancillary tests.
Ancillary tests for establishing brain death Ancillary tests can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed. However, the clinician will have to use his or her judgment on the use of these tests to support a brain stem death.
Care of the Potential Organ Donor A brain-dead organ donor needs the same intensity of care with the focus of treatment directed toward organ perfusion and improved quality of grafts. Intensive care with the use of invasive lines is mandatory for improved quality of care and titration of inotropes and fluids.
Pathophysiological changes following brain death and its relevance to organ preservation The time from a diagnosis to declaration of brain death is complicated by fluctuating donor hemodynamics. The instability is greater when the time to organ retrieval from the diagnosis of brain death is longer.Even while ensuring optimum donor care, the inevitable hormonal and inflammatory changes accompanying brain death can result in graft dysfunction and increased chances of rejection.However, in the last two decades, increased awareness of donor management has contributed to improved outcomes following transplant surgery
Cardiovascular system In all patients with brain death, medullary ischemia associated with brain death causes a reflex hypertension and bradycardia (Cushing’s reflex). This is a reflex attempt by the body to maintain the CBF. Subsequent to this is a period of intense vasoconstriction and tachycardia associated with increased circulatory catecholamines, which can increase visceral and myocardial ischemia.
Respiratory system A rise in pulmonary hydrostatic pressure causes damage to the pulmonary endothelium resulting in pulmonary edema that is perpetuated by endogenous epinephrine. The goals of ventilatory management include minimal FiO2 needed to maintain a PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45. Earlier recommendations suggested liberal tidal volumes 8-15 ml/kg, but currently ventilation strategies similar to those used for acute lung injury (ALI) are recommended and have improved the use of lungs for transplant
Endocrine system, stress and metabolic responses The endocrine responses of the body are lost with brain death and form the rationale for hormone replacement therapy for brain-dead patients. The posterior pituitary function is lost early in brain death with occurrence of diabetes insipidus with polyuria and hypernatremia. Arginine vasopressin and desmopressin can be given as replacements. The anterior pituitary functions are preserved for a slightly longer period. Thyroid hormone levels decrease and a state similar to the sick euthyroid state in critical illness can occur. Systemic inflammatory response Brain death and care of the organ donor A systemic inflammatory response occurs and could be quite severe. This is mediated by inflammatory mediators from an ischemic brain, ischemic reperfusion injury, metabolic changes that occur during the catecholamine storm and an inadequately restored cardiovascular state. Increased plasma levels of interleukin-6 in the donor have translated to the poorer graft utilization and graft dysfunctions.
Protocols for donor management The circulatory and biochemical variables are managed by the general principle of the “Rule of 100”suggesting targets of SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted at 100% normal. Other elements of donor management are listed below:
1. Temperature: The aim is to keep the core temperature >35°C prior to organ donation. Circulating hot air blankets, warmed intravenous fluids and adjustments of ambient temperature may be needed to achieve this goal.
2. Fluid management: These patients are often polyuric and dehydrated which is worsened by a vasoplegic state resulting in central volume depletion. Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline as they do not produce hyperchloremic acidosis.Uncorrected hypernatremia could result in graft losses after liver transplant. Hydroxyethylstarches are contraindicated in organ donors because they can damage renal epithelial cells and cause early graft dysfunction in the transplanted kidneys.There is little evidence to date supporting the use of gelatins in donors. A restrictive strategy with monitoring of filling pressures with a PAC may be beneficial particularly in the context of lung transplant. Studies have documented the impact of fluid loading on outcomes in lung transplantation. This does not affect the quality of the renal graft for transplantation.Replacement of blood and blood products could follow guidelines for the care of the critically ill and a hemoglobin of 10 g/L could improve tissue oxygenation indices.
3-Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft. Though it has no renal protective effect and may predispose to arrhythmias, the benefits are probably related to moderation of preservation injury and inflammation, donor cardiovascular effects, or recipient treatment. Nor-adrenaline in doses >0.05 mcg/kg/min resulted in impaired cardiac contractility in transplanted hearts and in particular impairment of right ventricular performance.
4. Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment). The lowest FiO2 needed should be used, and optimal PEEP with a restrictive fluid strategy improves graft harvesting for lung transplants.
5. Replacement of hormones after brain death: Standardization of hormone therapy after brain death in combination with a central venous pressure <10 mmHg significantly improved utilization of the heart and lungs for transplant without affecting other organ systems. The recommended replacements are:
a. Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h (desmopressin intranasally has a selective action on the V2 receptors and a half-life varying from 6 to 20 h.
b. Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly thereafter.
c. Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg.
d. Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. Tri-iodothyronine (T3) given as a 4-mcg bolus followed by an infusion of 3 mcg/h. T4 improves hemodynamics and prevents cardiovascular collapse in hemodynamically unstable organ donors.
Other concerns and considerations Barring overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations. However, infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus preclude organ donation. Registries supported by the state governments, Tamil Nadu Network of Organ Sharing and Kerala Network on Organ Sharing have substantially increased organ donation in south India. Conclusion “Care of the donor” is essentially “the simultaneous care of multiple recipients.” The barriers that exist in limited resource environments are the time to diagnosis and the costs involved in sustaining care for the brain-dead donor to the point when consent is obtained. The recognition and acceptance of brain death, awareness amongst public on the eventuality and resources to support the organ donor to improve the numbers and quality of donor organs will be the immediate goals in our country.
Theepa Mariamutu
2 years ago
Brain death and care of the organ donor
Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible.
The American Association of Neurology (AAN) has defined brain death with three cardinal signs, cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnoea.
The diagnosis of brain death is clinical and can be confirmed by apnoea testing.
Ancillary tests can be considered when the apnoea test cannot be completed or is inconclusive.
Reflexes of spinal origin may be present and should not be confused against the diagnosis of brain death.
Clinical testing for brain death
Coma: Absence of response to noxious stimulus except for spinally mediated reflexes.
Absent brain stem reflexes (a formal evaluation of the brain stem reflexes is undertaken when the patient has had fixed dilated pupils and absent cranial nerve reflexes for more than 4 h).
Apnea test: The aim of this test is to check for the integrity of the brain stem respiratory centre at high levels of blood carbon dioxide.
Include a patient who is normothermic (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralytic drugs, with normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
The test is considered positive if there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO2.
Certification of brain death is after a second apnoea testing, the timing of which varies between countries.
The time of death is the time PaCO2 reaches the target value during the second apnoea test.
The increase in intracranial pressure (ICP) that accompanies brain death spares the rostral portion beyond the second cervical spine and does not compromise blood supply to this area.
This could be the explanation for complex motor movements at the spinal cord level even after diagnosing brain death.
Ancillary tests for establishing brain death
Ancillary tests can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnoea test cannot be performed.
The conventional 4 vessel digital subtraction angiography is the gold standard for CBF documentation.
Brain death is confirmed by demonstrating the absence of intracerebral filling at the level of the carotid bifurcation or vertebral arteries.
Computerized tomography (CT) angiography has emerged as a safer alternative that can accurately document CBF.
Transcranial Doppler is recommended as an ancillary test and is used in Intensive Care Units (ICU) .
The presence of diastolic reverberation flow and little or no forward flow is diagnostic.
Electroencephalography is widely used as an ancillary test for documentation of brain death.
The AAN has discussed the role CT angiography, somatosensory evoked potentials, magnetic resonance angiography and have declared that there is insufficient evidence at this time to determine the accuracy of these tests in confirming cessation of function of the entire brain.
AAN recommends that the physician can decide against a The declaration of brain death rather than ordering ancillary tests if the clinical findings are unreliable.
Care of the Potential Organ Donor
A potential donor is one who is brain-dead or one with catastrophic brain injury with a clearly expressed intent from the physician and the family to withdraw life support.
The organ procurement organization recently has adopted a “presumptive strategy” in counselling wherein grief counsellors communicate with the family with the presumption that organ donation is the natural thing to be done and act both in the interests of the potential donor as well as the pool of recipients.
Protocols for donor management
The circulatory and biochemical variables are managed by the general principle of the “Rule of 100” suggesting targets
SBP ≥100 mmHg,
Urine output ≥100 ml/h,
Haemoglobin of ≥100 g/L,
PaO2 ≥100 mmHg and blood sugar targeted at 100% normal.
Temperature: The aim is to keep the core temperature >35°C prior to organ donation.
.
Fluid management: These patients are often polyureic and dehydrated which is worsened by a vasoplegic state resulting in central volume depletion. Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline as they do not produce hyperchloremic acidosis.[40] Uncorrected hypernatremia could result in graft losses after liver transplant.
Hydroxyethylstarches are contraindicated in organ donors because they can damage renal epithelial cells and cause early graft dysfunction in the transplanted kidney
Replacement of blood and blood products could follow guidelines for the care of the critically ill and a haemoglobin of 10 g/L could improve tissue oxygenation indices.
Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft. Nor-adrenaline in doses >0.05 mcg/kg/min resulted in impaired cardiac contractility in transplanted hearts and in particular impairment of right ventricular performance.
Ventilatory management: optimal PEEP with a restrictive fluid strategy improves graft harvesting for lung transplants -low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment
Replacement of hormones after brain death
Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h (desmopressin intranasally has a selective action on the V2 receptors and a half-life varying from 6 to 20 h.
Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly thereafter.
Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg.
Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. Tri-iodothyronine (T3) given as a 4-mcg bolus followed by an infusion of 3 mcg/h. T4 improves hemodynamics and prevents cardiovascular collapse in hemodynamically unstable organ donors
Amna Khalifa
2 years ago
Brain death and care of the organ donor Introduction Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible.
· The American Association of Neurology (AAN) has defined brain death with three cardinal signs, Cessation of the functions of the brain including the brainstem
· Coma or unresponsiveness
· Apnea.
In India, the Transplantation of Human Organ Bill was introduced in the Lok Sabha on 20th August 1992 and became the Transplantation of Human Organ Act in 1994.[2]
The limited availability of organs amidst a growing demand emphasizes the need for optimal donor care. There is no global consensus in the criteria for establishing brain death, and significant differences exist in the tests used.
In many countries, including India, the diagnosis of brain death is made after fulfilling the mandatory criteria and by the apnea testing which is a safe technique for documentation.
The deceased donor organ donation rate in
· India 0.26 per million
· USA at 25.6 per million
· UK at 18.3 per million
· Spain at 32 per million
are well ahead. A checklist of requirements that need to be fulfilled before proceeding with tests for brain death is indicated.
· Proximate cause for unresponsive state that is incompatible with survival
· Neurological imaging to confirm diagnosis
· Exclusion of associated medical conditions that could account for unresponsiveness
· Exclusion of severe acid-base, metabolic or electrolyte abnormalities
· Exclusion of drugs causing unresponsiveness Sedatives, narcotics, muscle relaxants. In drug overdose allow time for 5 half-lives/measure drug levels
· Normal temperature Core temperature >32°C/90°F Clinical testing for brain death 1. Coma: Absence of response to noxious stimulus (supraorbital pressure or pressure on the nail bed) with the exception of spinally mediated reflexes.
2. Absent brain stem reflexes (a formal evaluation of the brain stem reflexes is undertaken when the patient has had fixed dilated pupils and absent cranial nerve reflexes for more than 4 h.
lists the individual tests for brain stem reflexes.
3. Apnea test: The aim of this test is to check for the integrity of the brain stem respiratory center at high levels of blood carbon dioxide.
Prerequisites include a patient who is normothermic (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralytic drugs, with normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
Oxygen is insufflated through a catheter placed at the level of the carina at 6.0 L/min after disconnection from the ventilator. The observer looks for respiratory movements at 8-10 min after disconnection. Assuming a rate of rise in PaCO2 of 3 mmHg/min,[10] this will result in an increase of 24 mmHg above baseline in 8-10 min.
The test is considered positive if there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO2 .
Certification of brain death is after a second apnea testing, the timing of which varies between countries.
· UK legislation states that the second test can be done at any time after the first when the blood gases have normalized.
· In USA, suggest the performance of the apnea test after giving appropriate time for confirming absence of brain recovery and the use of only one apnea test.
· In India, the apnea test needs to be repeated after an interval of 6 h and certified by four physicians from a recommended panel, one of whom has to be a neurologist.
The time of death is the time PaCO2 reaches the target value during the second apnea test.
The increase in intracranial pressure (ICP) that accompanies brain death spares the rostral portion beyond the second cervical spine and does not compromise blood supply to this area. Troubleshooting during performance of apnea test
1. Patient’s systolic blood pressure (SBP) ≤100 mmHg: The apnea test is aborted if systolic BP is ≤90 mmHg and the test needs to be repeated after stabilization.
2. Oxygen saturation not maintained during apnea testing: The apnea testing is terminated if the saturation is ≤85% for more than 30 s.
3. Patient is hypothermic
4. Patient repeatedly desaturates or becomes hypotensive during apnea testing.
5. Baseline PaCO2 ≥40 mmHg or ≤35 mmHg. Ancillary tests for establishing brain death
Ancillary tests can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed.
These tests are classified as tests that document cerebral blood flow (CBF) and those that evaluate the electrical activity of the brain.
1. The conventional 4 vessel digital subtraction angiography is the gold standard for CBF documentation.
2. Computerized tomography (CT) angiography has emerged as a safer alternative that can accurately document CBF.
3. Transcranial Doppler.
4. Electroencephalography
5. Cerebral tissue perfusion techniques using technetium 99 m hexamethylpropylene amine oxime labeled brain perfusion study
The AAN recommends that the physician can decide against a declaration of brain death rather than ordering ancillary tests if the clinical findings are unreliable.
Care of the Potential Organ Donor A brain-dead organ donor needs the same intensity of care with the focus of treatment directed toward organ perfusion and improved quality of grafts.
brain-dead or one with catastrophic brain injury with a clearly expressed intent from the physician and the family to withdraw life support. Pathophysiological changes following brain death and its relevance to organ preservation
Even while ensuring optimum donor care, the inevitable hormonal and inflammatory changes accompanying brain death can result in graft dysfunction and increased chances of rejection.
increased awareness of donor management has contributed to improved outcomes following transplant surgery.
Cardiovascular system
Respiratory system
Endocrine system, stress and metabolic responses
Systemic inflammatory response Protocols for donor management
“Rule of 100” suggesting targets of
SBP ≥100 mmHg,
urine output ≥100 ml/h,
hemoglobin of ≥100 g/L,
PaO2 ≥100 mmHg and
blood sugar targeted at 100% normal.
Other elements of donor management are listed below:
1. Temperature: core temperature >35°C prior to organ donation.
2. Fluid management: Crystalloids are the first choice and balanced salt solutions.
3. Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension.
4. Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment). The lowest FiO2 needed should be used, and optimal PEEP with a restrictive fluid strategy improves graft harvesting for lung transplants.
5. Replacement of hormones after brain death:
The recommended replacements are:
· Vasopressin
· Methylprednisolone
· Insulin 10 U in 50% dextrose followed by an infusion
· Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. Other concerns and considerations
Barring overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations
infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus preclude organ donation
Continuation of organ support in a pregnant patient who is brain-dead has again been controversial. the mother should be supported until the delivery of the fetus and then can be considered for organ donation
must keep in mind that preoperative donor screening for viruses may be missed in the first 2 weeks of infection. Transmission of HIV and rabies from infected donors has been documented.
amiri elaf
2 years ago
II. Brain death and care of the organ donorPlease provide a summary of this article
Introduction:
*Kidney transplantation provide better survival and quality of life than staying on dialysis for (ESRD) patients, which need to increase the donor pool from deceased donor (brain or cardiac death).
*The definition of brain death is a condition in which there is irreversible cessation of cerebral function.
The (AAN) has defined it with three cardinal signs, cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
Clinical testing for brain death
1. Coma: Absence of response to noxious stimulus.
2. Absent brain stem reflexes.
3. Apnea test: To check the integrity of the brain stem respiratory center at high levels of blood carbon dioxide. Normothermic (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralyticdrugs, with normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
Troubleshooting during performance of apnea test
1. Patient’s (SBP) ≤100 mmHg.
2. Oxygen saturation not maintained during apnea testing:The apnea testing is terminated if the saturation is ≤85% for more than 30 s.
3. Patient is hypothermic (<36.5°F): Guidelines for apnea
needs to be repeated after correction of hypothermia.
4. Patient repeatedly desaturates or becomes hypotensive during apnea testing.
5. Baseline PaCO2 ≥40 mmHg or ≤35 mmHg: A rise of ≥20 mmHg above baseline can be considered a positive apnea test in patients with elevated baseline PaCO2.
Ancillary tests for establishing brain death
*Used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed.
* The conventional 4 vessel digital subtraction angiography is the gold standard for CBF.
*The (CT) angiography is safer alternative that can accurately document CBF.
*Transcranial Doppler is recommended as an ancillary
test and is used in Intensive Care Units.
*Electroencephalography is widely used as an ancillary test
for documentation of brain death.
*Cerebral tissue perfusion techniques using technetium 99 m.
Care of the Potential Organ Donor
*Needs the same intensity of care directed toward organ perfusion and improved quality of grafts.
*A potential donor is one who is brain-dead or one with
catastrophic brain injury with a clearly expressed intent from
the physician and the family to withdraw life support.
Pathophysiological changes following brain death and its relevance to organ preservation Cardiovascular system
Medullary ischemia associated with brain death causes a reflex hypertension and bradycardia (Cushing’s reflex). Respiratory system
A rise in pulmonary hydrostatic pressure causes damage to the pulmonary endothelium resulting in pulmonary edema that is perpetuated by endogenous epinephrine. Endocrine system, stress and metabolic responses
The posterior pituitary function is lost early in brain death with occurrence of diabetes insipidus with polyuria and hypernatremia. The anterior pituitary functions are preserved for a slightly longer period. Thyroid hormone levels decrease, decrease in insulin levels, hyperglycemia worsens with stress. Systemic inflammatory response
Occurs and could be quite severe. DIC occurs after brain death due to the release of tissue thromboplastin from necrotic brain tissue.
Protocols for donor management
The circulatory and biochemical variables are managed by the
general principle of the “Rule of 100” suggesting targets
of SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin
of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted
at 100% normal. Other elements of donor management are listed below:
1. Temperature: The aim is to keep the core temperature
>35°C prior to organ donation.
2. Fluid management: Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline.
3. Inotropes and cardiovascular system: Dopamine is the first
choice of inotrope in hypotension unresponsive to volume
and has beneficial effects on the renal graft.
4. Ventilatory management: The principles are along the
lines of management of ALI (low tidal volume 6-8 ml/
kg, minimum plateau pressure, lung recruitment).
5. Replacement of hormones after brain death:
Standardization of hormone therapy after brain death in
combination with a central venous pressure <10 mmHg improved the heart and lungs for transplant.
without affecting other organ systems.
The recommended replacements are:
a. Vasopressin
b. Methylprednisolone.
c. Insulin.
d. Thyroxine.
Conclusion
“Care of the donor” is essentially “the simultaneous care of multiple recipients.” The recognition and acceptance of brain death, awareness amongst public on the eventuality and resources to support the organ donor to improve the numbers and quality of donor organs in transplantation.
Hamdy Hegazy
2 years ago
Please provide a summary of this article Brain death is defined by American Association of Neurology with 3 signs including loss of brain stem functions, coma or unresponsiveness and apnea. After brain death, spinal cord reflexes may still be present.
clinical diagnosis of brain death is diagnosed by: 1- Coma. 2- Absent brain stem reflexes 4 hours after having dilated fixed pupils and absent cranial nerve reflexes. 3- Apnea test. 4- Other ancillary tests: conventional 4 vessel digital subtraction angiography to document CBF, CTA, transcranial doppler and EEG. The goals in the management DBD donor till organ retrieval include:
Maintenance of BP with minimal use of inotropes, optimizing the fluid management and maintenance of organ perfusion.
ECHO and pulmonary artery catheterization to assess EF for possible heart and lung donation.
Ventilator and oxygenation management aiming O2 sats >95%, normal PH and normal PaCO2.
Replace lost pituitary hormones.
Management of systemic inflammatory response mediated by dead tissues by keeping SBP>100mmHg, Keeping UOP>100 ml/h, Keeping Hb> 100gm/L, PaO2>100 mmHg.
Keep core body temperature>35 C.
Amit Sharma
2 years ago
Please provide a summary of this article
Brain death is irreversible stoppage of cerebral functioning due to a definite cause, clinically defined by the American Association of Neurology (AAN) as apnea (absence of respiratory movement despite rise on PaCO2), brain (including brainstem) function stoppage (absence of pupillary light reflex, corneal reflex, facially and maxillary region reflexes, oculo-cephalic and oculo-vestibular reflexes, and gag and cough reflexes for more than 4 hours), and coma (non-responsive to obnoxious stimuli).
Apnea testing is critical, and needs to be repeated twice before certifying brain death, except in USA where use of only one apnea test is suggested. During performance of apnea test, the systolic blood pressure (SBP) should be kept above 100 mm of Hg, oxygen saturation should be more than 85%, and the patient should not be hypothermic (temperature more than 36.5º F). Ancillary tests should be done if the above conditions are not met. The ancillary tests include tests for cerebral blood flow (CBF), and cerebral electrical activity. CBF can be tested using 4 vessel digital subtraction angiography (gold standard) and CT angiography. Transcranial Doppler as well as brain perfusion studies can also be used. Electroencephalography assesses the electrical activity in brain.
The pathophysiological changes following brain death have a role in organ preservation management. Medullary ischemia causes Cushing’s reflex (hypertension and bradycardia), leading to vasoconstriction and tachycardia, further leading to hypertension (due to increased catecholamines) followed by fall in catecholamines leading to vasodilation and hypotension making it imperative to maintain organ perfusion by optimising BP using minimal dose of inotropes, Ventilatory management includes maintaining PaO2 >100 mm Hg, SpO2 >95%, PaCO2 35-40 mm Hg, and pH 7.35-7.45 using minimal FiO2. Excessive fluid use can be restricted by using pulmonary artery catheter (PAC) insertion, preventing pulmonary edema. Hormone replacement (Arginine vasopressin, desmopressin, and insulin) and maintenance of temperature is required in view of loss of endocrine functions in brain death. Severe systemic inflammatory response and disseminated intravascular coagulation (DIC) can occur post- brain death.
Donor management protocol includes following the ‘rule of 100’ with target of SBP ≥100 mmHg, Hemoglobin ≥100 g/L, PaO2 ≥100 mm Hg, urine output ≥100 ml/hour, and blood sugar targeted at 100% normal. Core temperature should be >35º C, crystalloids and balanced salt solutions should be used for fluid management by monitoring filling pressures using PAC, dopamine can be used in hypotension, optimal ventilatory management (low tidal volume, minimal plateau pressure and lung recruitment), and hormonal replacement (vasopressin, thyroxine, insulin, and methylprednisolone) are essential parts of the management protocol.
Brain death during pregnancy warrants supporting the mother till the delivery of the fetus and proceeding with organ donation after delivery.
Donor care is an essential part of organ transplantation program for optimal graft and patient outcomes.
Tahani Ashmaig
2 years ago
Brain death and care of the organ donor
▪︎Introduction:
Brain death is a condition which is characterized by cessation of cerebral function wherein the proximate cause is known and is considered irreversible. The American Association of Neurology (AAN) has defined brain death with three cardinal signs:
1. Cessation of the brain functions including the brainstem.
2. Coma or unresponsiveness 3. Apnea. In many countries the diagnosis of brain death is made after fulfilling the mandatory criteria and by the apnea testing which is a safe technique for documentation. ▪︎Clinical testing for brain death: 1. Coma: Absence of response to noxious stimulus with the exception of spinally mediated reflexes. 2. Absent brain stem reflexes 3. Apnea test: to check for the integrity of the brain stem respiratory center at high levels blood CO2. Oxygen is insufflated through a catheter placed at the level of the carina at 6.0 L/min after disconnection from the ventilator. The observer looks for respiratory movements at 8-10 min after disconnection. A positive test when there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO Certification of brain death is after a 2nd apnea testing (which varies between
countries). Troubleshooting during performance of apnea test 1. Patient’s systolic blood pressure (SBP) ≤100 mmHg 2. Oxygen saturation not maintained during apnea testing 3. Patient is hypothermic (<36.5°F). 4. Patient repeatedly desaturates or becomes hypotensive during apnea testing. Ancillary tests for establishing brain death Tests that document cerebral blood flow (CBF) and those that evaluate the electrical activity of the brain eg: 1. The conventional 4 vessel digital subtraction angiography (is the gold standard for CBF documentation). 2. Computerized tomography (CT) angiography. 3. Transcranial Doppler used in ICU 4. Electroencephalography 5. Cerebral tissue perfusion techniques using technetium 99 m hexamethylpropylene amine oxime labeled brain perfusion study Care of the Potential Organ Donor * Intensive care with the use of invasive lines is mandatory. * A potential donor is one who is brain-dead or one with catastrophic brain injury with a clearly expressed intent from the physician and the family to withdraw life support. Pathophysiological changes following brain death and its relevance to organ preservation Cardiovascular system: ▪︎Reflex HTN and bradycardia (Cushing’s reflex) with subsequent period of intense vasoconstriction and tachycardia associated with increased circulatory catecholamines, which can increase visceral and myocardial ischemia.
▪︎The goals in the management include maintenance of BP with minimal use of inotropes, optimizing the fluid management
and maintenance of organ perfusion.
An echocardiogram is indicated in all potential donors, and pulmonary artery catheterization (PAC) is indicated for
donors with an ejection fraction (EF) <45% Respiratory syssystem Pulmonary edema The goals of ventilatory management include minimal FiO2 needed to maintain a PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45. Endocrine system, stress and metabolic responses The endocrine responses of the body are lost with brain death and form the rationale for hormone replacement therapy for brain-dead patients. Systemic inflammatory response occurs and could be quite severe. Increased levels of IL-6 in the donor can leads topoorer graft utilization and graft dysfunctions. DIC occurs. Protocols for donor management The circulatory and biochemical variables are managed by the general principle of the “Rule of 100”. (SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted at 100% normal). Other elements of donor management are: 1. Temperature: to keep the core temperature >35°C prior to organ donation. 2. Fluid management: Crystalloids are the first choice and balanced salt solutions may be superior to normal saline 4. Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/kg, minimum plateau pressure, lung recruitment). 5. Replacement of hormones after brain death. The recommended replacements are: a. Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h. b. Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly thereafter. c. Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg. d. Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. Tri-iodothyronine (T3) given as a 4-mcg bolus followed by an infusion of 3 mcg/h. Conclusion ▪︎The barriers that exist in limited resource environments are the time to diagnosis and the costs involved in sustaining care for the brain-dead donor to the point when consent is obtained. ▪︎The recognition and acceptance of brain death, awareness amongst public on the eventuality and resources to support the organ donor is very important to expand the donor pool for transplantation.
Balaji Kirushnan
2 years ago
Brain death is defined as immediate cessation of brain activity wherein the proximate cause is unknown and it is irreversible…The American Academy of Neurology has defined brain death in 3 components namely coma or unresponsiveness, cessation of brain stem reflexes and apnea..
Clinical testing for brain death:
Coma: Absence of response to noxious stimuli or painful stimuli like supraorbital pressure or nail bed with the exception of spinally mediated reflexes…
Absent brain stem reflexes: Formal evaluation of all the brain stem reflexes need to be carried out…the following are the brain stem reflexes
Absent pupillary light reflex: Afferent optic nerve and efferent is 3rd nerve
Absent corneal reflex: Afferent V nerve and efferent VII nerve
Absent gag reflex: afferent 9 and efferent is 10th nerve
Absent oculo -cephalic (dolls eye movement) – lateral movement of the neck to 90 degree will cause movement of the eyeballs to the opposite direction.. Afferent is VIII and efferent is 3rd and 6th cranial nerve
Absent oculo-vestibular reflex – 30 degree position when the lateral semi circular canal becomes vertical, 50 ml of cold saline is injected into the ear.. Nystagmus with the cold component to the side of the injection seen with intact brain stem.. afferent is VIII and efferent is 3rd and 6th nerve
Absent reflexes in the face and maxillary region
3.Apnea testing is the 3rd and the final component in the brain stem death confirmation…The aim of the test is to test the integrity of the brain stem to high levels of carbon dioxide…Pre requisites for apnea testing includes no hypothermia (core temperature of >36.5C), hemodynamic stability (SBP>100), free from sedative and paralytic drugs, normal oxygenation (pao2 >200mm after 100% oxygenation) and normal PCO2 (35-45mm)..Oxygen is insufflated through ET tube placed at the level of carina at 6l/min after disconnection from the ventilator and allowed the Pco2 to build up…The apnea testing is considered positive if there are no respiratory movements after a PC02 level of more than 60mm or 20mm elevation of PCo2 from the baseline…2 apnea testing need to be done to certify the brain death…The time period between 2 apnea testing varies between all the countries. In the UK there is no time difference between the 2 and can be as soon as possible to facilitate organ retrieval…USA amendments were made and the use of only one apnea test is recommended…
In India minimum of 6 hours is needed between 2 apnea testing and it has to be certified by 4 different physicians including a neurologist…
The raise in the ICP after brain death spares the rostral area of the brain sparing the proximal portion of the spinal cord…This is responsible for the complex spinal reflexes which are intact in the brain death patient….
There maybe various problems while performing the apnea testing…SBP maybe less than 100mm which may have to be maintained by fluids, vasopressors and other inotropes. The oxygen saturation needs to be maintained during the apnea testing.. The test is terminated if the spo2<85% for more than 30 seconds…the test maybe repeated with CPAP of 10cm and oxygen flow at 12l/min.. Core body temperature should be maintained above 36.5C by warming the patient…If the patient repeatedly desaturates or doesn’t tolerate the apnea testing the ancillary tests for Brian stem death needs to be carried out
Digital subtraction angiography is needed to demonstrate absent cerebral blood flow at the level of carotid bifurcation can be used to demonstrate cessation of brain activity…Transcranial doppler can be used in ICU bedside as it is inexpensive, easy tool…But the presence of IC bleed, a surgery bleed and operative dependance makes it difficult to do it for everyone ..Absence of forward flow and presence of diastolic reverberation..An EEG is used as an ancillary testing for brain death.. presence of isoelectric recording over 30 min period over 18 -20 fields is suggestive of brain death ..
The AAN recommends that there is no definite guidelines or standardization to use this tests and can be decided on individual case to case basis….
The pathophysiological changes that a brain death donor undergoes is complicated and this may turn a stable brain death donor to have an unstable hemodynamics leading to cardiac arrest before organ retrieval…
Cardiovascular system: initially there is bradycardia and hypertension (Cushings reflex) as a response to brain stem death in order to increase the cerebral blood flow…subsequent to this there is a period of intense of vasoconstriction and catecholamines release in a cytokine storm pattern…This can cause visceral and myocardial ischemia…this causes ATP depletion in the cardiac myocyte and is responsible for transient myocardial ischemia seen in brain dead patients.. Subsequent to this catecholamine surge there is a period of depletion of these hormones leading on to difficulties in organ perfusion.. The goals in the management mainly includes fluids, inotropes etc…In addition to ECHO to guide fluids and vasopressors, cardiac catheterization is indicated if EF<45% especially for heart and lung transplants…
Respiratory system: A low tidal volume strategy to maintain oxygenation is needed like in ALI cases..The goal is to maintain the PaO2 to 100mm with normal Pco2 (35-45mm of Hg) and spo2 >95%..A rise in the pulmonary hydrostatic pressure can result in damage to the pulmonary endothelium…An increase in the fluid levels can cause pulmonary edema if there is pulmonary capillary damage…
Endocrine system: The endocrine system will loose all the functions after brain stem death and this forms the basis of hormone replacement therapy after brain death…the posterior pituitary function is lost early in brain death and this results in polyuria and diabetes insipidus…AVP and Desmopressin are given as replacement ..The anterior pitiutary function are preserved usually longer…Sick euthyroid state is found in critical patients.. Temperature regulation is affected in the hypothalamus and is reflected as initial hyperthermia and followed by hypothermia…Hypothermia is worsened by lack of shivering, peripheral vasodilation and low metabolic rate…Hypothermia worsens coagulopathy, increases risk of arrhythmia, cold induced diuresis and causes shift of the oxygen dissociation curve to the left impairing tissue transfer…Brain death also causes decrease in the insulin levels and lead to hyperglycemia with elevated catecholamines worsening it
Brain death is associated with severe SIRS syndrome and this itself can worsen the graft function
The various protocols in the donor management are basically to follow the rule of 100…SBP>100mm, urine output >100ml/hr, Hb>10gm/dl and PaO2 >100mm of hg..The body core temperature needs to be maintained to >36.5 C by using warm blankets and warming fluids…crystalloids are the fluids of the choice and colloids are avoided in renal transplants as HES could damage the endothelium…Hypernatremia in the donor has reported some poor outcome in Liver transplant patients…Dopamine is the drug of choice if the hypotension is unresponsive to fluids…it has beneficial effects on the heart and although the renal protective effects are not well established it is still preferred…Very high dose of nor adrenaline are associated with myocardial ischemia and maybe deleterious in cardiac transplants….An analysis of the 10 year data from the UNOS shows that combination of thyroid hormones, corticosteroids, insulin and ADH was the best for organ procurement…
The brain death is a state of irreversible complete cessation of function. According to American association of neurology has defined the brain death as cessation of function of brain(1. brainstem, 2. coma, 2. apnea), ancillary testing for confirmation of brain death.
How is care of potential organ donor.
Pathophysiological changes following brain death and its relevance to organ preservation.
Guidelines and protocol for donor management.
Esraa Mohammed
2 years ago
Introduction
Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible. The American Association of Neurology (AAN) has defined brain death with three cardinal signs, cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
Clinical testing for brain death
-Absent pupillary light reflex
-Absent corneal reflex
-Absent reflexes in the face and maxillary region
-Absent oculo-cephalic reflex (doll’s eye movement)
-Absent oculo-vestibular reflex
-Absent pharyngeal (gag) and laryngeal (cough) reflex)
Care of the Potential Organ Donor
A brain-dead organ donor needs the same intensity of care with the focus of treatment directed toward organ perfusion and improved quality of grafts. Intensive care with the use of invasive lines is mandatory for improved quality of care and titration of inotropes and fluids.
Pathophysiological changes following brain death and its relevance to organ preservation
-Cardiovascular system
-Respiratory system
-Endocrine system, stress and metabolic responses
-Systemic inflammatory response
Protocols for donor management
Hemodynamic Goals Mean Arterial Pressure ≥ 60 mm Hg Urine output ≥ 1.0 ml/kg/h Left Ventricular Ejection Fraction > 45% if not met
Inotropes Dopamine ≤ 10 mcg/kg/h Dobutamine ≤ 10 mcg/kg/h
Goals not achieved
Pulmonary Artery Catheter Insertion Goals Cardiac index ≥ 2.4 l/min/m2 Pulmonary Capillary Wedge Pressure (PCWP): 8-12 mm Hg Systemic Vascular Resistance (SVR): 800-1200dynes cm-5 * Trans Esophageal Echocardiography can substitute pulmonary artery catheter for hemodynamic management
*****
Cardiac index < 2.4 l/min/m2
-CVP < 6 mm Hg PCWP < 8 mm Hg >> Fluids
-SVR < 800 dynes cm-5 >> Pressors: Nor epinephrine or Epinephrine ≤ 0.05 mcg/kg/h
-PCWP > 12 mm Hg>.Pressors: Dopamine or Dobutamine ≤ 10 mcg/kg/h Epinephrine < 0.05 mcg/kg/min, diuretics
Conclusion
“Care of the donor” is essentially “the simultaneous care of multiple recipients.”
Hussam Juda
2 years ago
Introduction
· Brain death is defined as: cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea
· Apnea test is considered positive if there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO2.
· Certification of brain death is after a second apnea testing, the timing of which varies between countries.
Troubleshooting during performance of apnea test
1. Patient’s systolic blood pressure (SBP) ≤100 mmHg. Give inotropes and fluids
2. Oxygen saturation not maintained during apnea testing: if the saturation is ≤85% for more than 30 s, the test should be stopped
3. Patient is hypothermic (<36.5°F)
4. Patient repeatedly desaturates or becomes hypotensive during apnea testing: consider ancillary tests to confirm brain death
5. Baseline PaCO2 ≥40 mmHg or ≤35 mmHg
Ancillary tests for establishing brain death
1.The gold standard test is the conventional 4 vessel digital subtraction angiography
2. Transcranial Doppler is used in ICU
3.EEG after exclusion of sedation and hypothermia
4.Some centres may use Cerebral tissue perfusion techniques
Care of the Potential Organ Donor
· Donor with brain death, needs care focussing on organ perfusion and improve quality of grafts
· The use of invasive lines is a must to improve quality of care and titration of inotropes and fluids
· The hormonal and inflammatory changes accompanying brain death can result in graft dysfunction and increased chances of rejection
· 20-25% brain-dead donors showed evidence of myocardial ischemia and 40% have echocardiographic evidence of myocardial dysfunction, due to increased circulatory catecholamines
· pulmonary edema may occur due to the rise in pulmonary hydrostatic pressure, or excessive fluid resuscitation
· The posterior pituitary function is lost early in brain death with occurrence of diabetes insipidus with polyuria and hypernatremia
· In addition to the decrease in insulin levels, hyperglycemia worsens with stress, alteration in carbohydrate metabolism and use of glucose solutions.
· Temperature regulation in the hypothalamus is affected, manifesting with initial hyperthermia followed by hypothermia.
· A systemic inflammatory response occurs and may have poor outcome on the graft
Protocols for donor management
1. Temperature: The aim is to keep the core temperature >35°C prior to organ donation.
2. Fluid management: Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline as they do not produce hyperchloremic acidosis
3. Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft.
4. Ventilatory management: low tidal volume 6-8 ml/ kg, minimum plateau pressure, use lowest FiO2 and optimal PEEP.
5. Replacement of hormones after brain death:
§ Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h
§ Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly thereafter.
§ Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg.
§ Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. T3 given as a 4-mcg bolus followed by an infusion of 3 mcg/h
CONCLUSION
Brain-dead donor care may help in offering good graft for those waiting for kidney donation, and people should be aware about brain death donation benefits.
saja Mohammed
2 years ago
This is review article from India defined the elements of the brain death and the care of organs after brain death, there is no universal agreement about the measures for brain death definition However, the AAN (American association of neurology definition of brain death includes the three major components
1 irreversible cessation of the brain including brain stem functions
2. coma
3. apnea
Agenda prior to proceeding with tests for brain death
1.detailes about the primary cause of death
2. imaging like CT, MRI, Angio
3. rule out other medical, electrolytes and metabolic cause including sedation, narcotics and intoxication like drug over dose.
4.normal core temperature > 32 c0 or 90 F
Clinical tests for brain death 1.Coma, absence of response to stimulus exception may have still spinal reflexes 2. Brain stem death tests includes specific multiple clinical tests like absent of light, corneal, cough, gag, oculovestibular and oculocephalic reflexes,
3 Apnea tests to be done when patient is hemodynamically stable with BP systolic > 1oo and normothermic, free of sedative or paralytic drug effects with Pa CO2 35-45mmHG
Ancillary tests can be consider for confirmation of the brain death in case of clinical tests uncertainty and the apnea test can’t be completed includes EEG, cerebral Angio , transcranial Doppler and scintigraphy to assess the cerebral blood flow and electrical brain activities .
Care of the organs after brain death focused on Intensive care to maintain the organ perfusion and improved quality of organs by stabilizing the volume status and hemodynamics in addition to the cardiopulmonary support and hormonal replacement for certain endocrine dysfunction, maintain adequate UOP> 100ML/H and Left ventricular EF above 45%, cardiac index target >2.4l/min/m2
Inflammatory response syndrome dies to catecholamine storm with increased risk of IRI that can impact the graft survival, IL6 level is an indicator of poor outcome upon donation. Pre operative donor Infection screen including active viral infections like, HCV, HSV, HIV, rabies
Conclusion
this narrative review address the limitations and trouble shouting during the care of brain death donors, limitation in access to such type of donors in India as need more public awareness and acceptance in addition to the logistics and infrastructural support including logistics , limited resources and cost of care and handling such type of donors in order to provide adequate and good quality organs.
Muntasir Mohammed
2 years ago
Introduction Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible.
The American Association of Neurology (AAN) has defined
brain death with three cardinal signs:
1. Cessation of the functions of the brain including the brainstem.
2. Coma or unresponsiveness,
3. Apnea
Clinical testing for brain death
1. Coma: Absence of response to noxious stimulus
2. Absent brain stem reflexes.
3. Apnea test.
Troubleshooting during performance of apnea test
1.Patient’s systolic blood pressure (SBP) ≤100 mmHg:
Vasopressors, inotropes, and fluid boluses need to
be administered to keep the blood pressure (BP)
above the target. The apnea test is aborted if systolic
BP is ≤90 mmHg and the test needs to be repeated
after stabilization.
2. Oxygen saturation not maintained during apnea testing:
The apnea testing is terminated if the saturation is ≤85%
for more than 30 s.[1] The test can be retried with T-piece
and continuous positive airway pressure of 10 cm H2O
and oxygen flow of 12.0 L/min. Reducing the positive
end-expiratory pressure (PEEP) to 5 cm H2O prior to
disconnection from the ventilator for apnea testing can
predict the tolerance to apnea.
3. Patient is hypothermic (<36.5°F): Guidelines for apnea
testing are not valid and needs to be repeated after
correction of hypothermia.
4. Patient repeatedly desaturates or becomes hypotensive
during apnea testing: One should consider ancillary
tests for confirming brain death (electroencephalography,
cerebral angiography, transcranial Doppler and
scintigraphy). In India, the laws are not clear about the
use of ancillary tests. Ancillary tests for establishing brain death
Ancillary tests to be used when there is uncertainty about apnea tests.
Care of the Potential Organ Donor
Brain death donor needs intensive care, despite being clinically dead, to preserve organ perfusion.
Organization of organ procurement has adopted presumptive strategy when counsellor approach the family for donation as the usual scenario and to be in the interest of both donor and recipients.
Pathophysiological changes following brain death and its relevance to hou
Post brain death significant changes affects organ function. Despite improved organ preservation trying to maintain organ function, longer time post brain death could affect its future increased risk of rejection.
Cardiovascular system
Decreased cerebral perfusion after brain death leads to reflex hypertension with brady cardia. This period of intense vasoconstriction leads to myocardial and visceral ischemia, which is followed by hypotension during which organ preservation will be very challenging.
Systemic inflammatory response
Activation ofinflammatory response secondary to brain ischemia mediated by IL 6 leads to poorer organ utilization.
Protocols for donor management
Applying rule of 100s to maintain hemodynamics and biochemical parameters:
1. Systolic BP of >100mmHg
2. Urine out put >100ml/hour
3. PO2 > 100mmHg
4. Blood sugar 100% of normal.
5. Hb level >100gm/L
Other elements include:
1. Core temperature >35
2. Fluid management with crystalloid, ringer lactate or sodium bicarbonate with half saline.
3. Inotropes : dopamine is superior to noradrenaline.
4. Ventilatory management applying ALI protocol and restricted fluid strategy.
5. Replacement of hormones including vasopressin, thyroxine and methylprednisone.
Zahid Nabi
2 years ago
kidney transplant is best option for dialysis patients however there is world wide organ shortage. Lack of deceased donor program in different countries is augmenting the problem. Diagnosis of brain death and best possible care of organs has been discussed in this article
The American Association of Neurology (AAN) has defined brain death with three cardinal signs, cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
Clinical testing for brain death is done by checking for
1. Coma: Absence of response to noxious stimulus (supraorbital pressure or pressure on the nail bed) with the exception of spinally mediated reflexes.
2. Absent brain stem reflexes
3. Apnea test
Ancillary tests for establishing brain death
The conventional 4 vessel digital subtraction angiography is the gold standard for CBF documentation. Brain death is confirmed by demonstrating the absence of intracerebral filling at the level of the carotid bifurcation or vertebral arteries.
Computerized tomography (CT) angiography has emerged as a safer alternative that can accurately document CBF.
Transcranial Doppler is recommended as an ancillary test and is used in Intensive Care Units (ICU) as it is simple, easily available and noninvasive.
Electroencephalography is widely used as an ancillary test for documentation of brain death.
The authors have also discussed patho physiological processes following brain death and it’s importance in preservation of different organs.
like cushings reflex, catecholamine surge after rise in ICP. There is also rise in pulmonary hydrostatic pressure leading to pulmonary edema.
The posterior pituitary function is lost early in brain death with occurrence of diabetes insipidus with polyuria and hypernatremia.
Arginine vasopressin and desmopressin can be given as replacements.
The anterior pituitary functions are preserved for a slightly longer period. Thyroid hormone levels decrease and a state similar to the sick euthyroid state in critical illness can occur.
Hyperglycemia and reduced insulin level can affect pancreatic graft.Temperature regulation in the hypothalamus is affected, manifesting with initial hyperthermia followed by hypothermia.
Systemic inflammatory response
A systemic inflammatory response occurs and could be quite severe. This is mediated by inflammatory mediators from an ischemic brain, ischemic reperfusion injury, metabolic changes that occur during the catecholamine storm and an inadequately restored cardiovascular state. Increased plasma levels of interleukin-6 in the donor have translated to the poorer graft utilization and graft dysfunctions.
Protocols for donor management
The circulatory and biochemical variables are managed by the general principle of the “Rule of 100”[39] suggesting targets of SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted at 100% normal.
Other concerns and considerations
Barring overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations.[52] However, infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus preclude organ donation.
Marius Badal
2 years ago
Please provide a summary of this article
Kidney disease is increasing yearly and the donor pool is limited as such measures were taken to see what’s best to increase the donor pool. This is why the investigation of brain death donors started to increase the pool. The article is based on brain death and the care of the organ donor.
With scientific research, brain death is defined as the cessation of the functions of the brain including the brainstem, coma or unresponsiveness, and apnea. There are clinical tests that help to determine brain death and they are:
1) Coma
2) Absent of brain stem reflexes
3) Apnea test
To diagnose brain death there are prerequisites to ensure the validity of the test and are:
1) Normothermic temperature of 36.5 °C
2) Hemodynamically stable with a BP of 100 mmHg
3) Saturation that is PaO2 greater than 200mmHg after a100% O2 and near normal PaCO2 of 35-45 mmHg
Another complimentary test to help complement the diagnosis of brain death and are:
1) Cerebral flow assessment like angiography is the gold standard, transcranial Doppler, computerized tomography.
2) Assessment of electrical brain activity like performing electroencephalography.
3) Others like technetium 99 m to assess electrical activities.
During the brain, death care must be taken to ensure the proper organ perfusion so that the graft quality may be improved. The pathophysiology to preserve organ function,
1) Cardiovascular system: increased visceral and myocardial ischemic, medullar ischemic associated with brain death that can cause reflex hypertension and bradycardia, the decrease of ATP in the cardiac cells, and the depletion of catecholamine flowed by vasodilatation, low pressure that possesses challenges to maintain organ perfusion.
2) The presence of pulmonary edema secondary to increased pulmonary hydrostatic pressure, and excessive fluid resuscitation will worsen pulmonary edema.
3) Posterior pituitary function is lost early causing pathologies like polyuria, diabetic insipidus, etc, the thyroid gland hormone decrease, there is the presence of hyperglycemia that worsens with stress with carbohydrate metabolism alteration, and the dysregulation of the hypothalamus causes temperature failure.
With these changes, the protocol was placed to ensure proper donor management. They are:
1) Temperature: the aim is to ensure the core temperature remains about 35 degrees.
2) Fluid management with crystalloids, possible blood or blood products, and a Hb of 10g/L to maintain tissue oxygenation.
3) Inotropes and CVS: to ensure proper circulation and organ perfusion medication like dopamine and or nor-adrenaline
4) Ventilatory support is provided to ensure there is proper lung perfusion and proper harvesting
5) Hormone replacement after brain death is given to help brain and lung function to better harvest the organs.
CARLOS TADEU LEONIDIO
2 years ago
Please provide a summary of this article
There has been great progress in keeping the donor brain dead in recent years and the main related milestone is the definition of the indicative signs of brain death: cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
Among the clinical tests to define brain death we have:
– Coma: Absence of response to noxious stimulus (supraorbital pressure or pressure on the nail bed). Being necessary to exclude movements that could represent spinally mediated reflexes.
– Absent brain stem reflexes: pupillary light reflex, corneal reflex, reflexes in the face and maxillary region, oculo-cephalic reflex, pharyngeal (gag) and laryngeal (cough) reflex)
– Apnea test: Your function is to check for the integrity of the brain stem respiratory center at high levels of blood carbon dioxide.
However, some prerequisites are necessary to perform the exam: A) Normothermic (core temperature ≥36.5°C); B) Hemodynamically stable (systolic pressure ≥100 mmHg); C) free from sedative and paralytic drugs; D) normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
In some cases, the apnea test cannot be started, so auxiliary tests are used to make the diagnosis. These tests should assess the absence of brain flow or brain electrical activity. Among them we have:
A) Cerebral flow assessment: angiography is the gold standard, Transcranial Doppler, Computerized tomography (CT) is an alternative to angiography.
B) Assessment of electrical brain activity: Electroencephalography
Others ancillary tests are under study: CT angiography, somatosensory evoked potentials, magnetic resonance angiography, however, there is not sufficient evidence to determine the accuracy of these tests in confirming cessation of function of the entire brain.
O entendimento das mudanças fisiopatológicas associadas com o morte encefálica têm aumentado a possibilidade to organ preservation. Entre a os principais sistemas atingidos temos:
– Cardiac system: medullary ischemia associated with brain death causes a reflex hypertension and bradycardia (Cushing’s reflex), associados com a concentração de catecholamines. The management include use of inotropes, optimizing the fluid management and maintenance of organ perfusion.
– Respiratory system: a rise in pulmonary hydrostatic pressure causes damage to the pulmonary endothelium resulting in pulmonary edema that is perpetuated by endogenous epinephrine. For this, restrict excessive fluid use and diuretic can be considereds.
– Endocrin system: posterior pituitary function is lost early, because this is common diabetes insipidus with polyuria and hypernatremia, for this arginine vasopressin and desmopressin can be given as replacements. The decrease in insulin levels, hyperglycemia worsens with stress for this glycemic control through protocols is necessary. Temperature regulation in the hypothalamus is affected, manifesting with initial hyperthermia followed by hypothermia, requiring heating
Therefore, protocols for donor management and recognition of brain death are needed to guide multiprofessional groups in intensive care units with the intention of making a greater number of captures possible.
Mohammed Sobair
2 years ago
Introduction:
Brain death is a state of cessation of cerebral function wherein the proximate cause is
known and is considered irreversible.
AAN has defined brain death with three cardinal signs,
cessation of the functions of the brain including the brainstem, coma or
unresponsiveness and apnea.
Clinical testing for brain death:
1. Coma: Absence of response to noxious stimulus (supraorbital pressure or pressure on
the nail bed) with the exception of spinally mediated reflexes.
2. Absent brain stem reflexes (a formal evaluation of the brain stem reflexes is
undertaken when the patient has had fixed dilated pupils and absent cranial nerve
PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
Ancillary tests for establishing brain death:
Classified as tests that document cerebral blood flow: Cerebral angiogram or CTA,
Transcranial Doppler and Cerebral tissue perfusion techniques using technetium 99 m
assess electrical activities.
Care of the Potential Organ Donor:
A brain-dead organ donor needs the same intensity of care with the focus of treatment
directed toward organ perfusion and improved quality of grafts.
Pathophysiological changes following brain death and its relevance to organ
preservation:
Cardiovascular system:
Medullary ischemia leads to hypertension and bradycardia to preserve CBF.
Increase circulatory catecholamines, by vasoconstriction which can increase visceral
and myocardial ischemia, catecholamine surge on the myocardium is an altered
metabolism associated with depletion of adenosine triphosphate in the cardiac myocytes.
Subsequent to the catecholamine surge resulting in hypertension is the depletion
accompanied by vasodilatation and hypotension, which contributes to difficulty. In
maintain perfusion.
Respiratory system:
Raise pulmonary hydrostatic pressure leads to pulmonary edema. Use PAC to maintain
fluids.
Endocrine system, stress and metabolic responses:
posterior pituitary function: diabetes insipidus with polyuria and hypernatremia.
Thyroid hormone levels decrease and a state similar to the sick euthyroid state.
decrease in insulin levels, hyperglycemia worsens with stress, alteration in carbohydrate
metabolism and use of glucose solution.
Temperature regulation in the hypothalamus is affected, manifesting with initial
hyperthermia followed by hypothermia.
Systemic inflammatory response:
Can occurs with ischemia and inflammatory. Changes.
DIC also can happen.
Protocols for donor management :
the “Rule of 100”:
suggesting targets of SBP ≥100 mmHg.
urine output ≥100 ml/h.
hemoglobin of ≥100 g/L,
PaO2 ≥100 mmHg .
and blood sugar targeted at 100% normal.
.1. Temperature: the core temperature >35°C prior to organ donation.
2. Fluid management:
Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate,
Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be
superior to normal saline as they do not produce hyperchloremic acidosis.
3. Inotropes and cardiovascular system: Dopamine is the first choice.
4. Ventilatory support.
5. Replacement of hormones after brain death:
1. Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h.
Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly
thereafter.
c. Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose
between 80 and 150 mg.
d. Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. Tri-iodothyronine (T3)
given as a 4-mcg bolus followed by an infusion of 3 mcg/h.
Abhijit Patil
2 years ago
Brain death: cessation of brain functions including brainstem, coma or unresponsiveness and apnoea.
Clinical testing for brain death:
Coma
Absence of brainstem reflexes
Apnea test:
Prerequisites:
Hemodynamically stable
Normothermia
Free from sedative and paralytic drugs
PaO2 > 200 mmHg with 100% oxygenation and PaCO2 of 35-45mmHg
How to test:
Oxygen is insufflated through a catheter placed at the level of the carina at 6.0 L/min after disconnection from the ventilator.
Look for respiratory movements at 8-10 min after disconnection.
The test is considered positive if there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO2.
In India, second apnea test is performed after interval of 6 hours and to be certified by 4 physicians including one neurologist.
The time of death: time when PaCO2 reaches target value suring the second apnea test.
Ancillary tests:
Test measuring cerebral blood flow:
Conventional 4 vessel digital subtraction angiography
Transcranial Doppler
Test measuring electrical activity of brain
EEG
Protocol for donor management:
The circulatory and biochemical variables are managed by the general principle of the “Rule of 100” suggesting targets of SBP =100 mmHg, urine output =100 ml/h, hemoglobin of =100 g/L, PaO2 =100 mmHg and blood sugar targeted O2 at 100% normal.
Maintain core temperature of > 350 C
Fluid management with crystalloids esp Ringer’s lactate
HES is contraindicated as it damages renal epithelial cells
Maintain BP first with fluids, if not then start Dopamine. NA in doses >0.05 mcg/kg/min resulted in impaired cardiac contractility in transplanted hearts and in particular impairment of right ventricular performance.
Combination of thyroid hormone, corticosteroid, insulin and antidiuretic hormone was the best for multiple organ procurement.
Huda Al-Taee
2 years ago
Summary:
Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible.
Clinical testing for brain death:
coma
absent brain-stem reflexes
Apnea testing: Oxygen is insufflated through a catheter placed at the level of the carina at 6.0 L/min after disconnection from the ventilator. The observer looks for respiratory movements at 8-10 min after disconnection. The test is considered positive if there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO2. Certification of brain death is after a second apnea testing.
Troubleshooting during the performance of the apnea test:
Patient’s systolic blood pressure (SBP) ≤100 mmHg: The apnea test is aborted if systolic BP is ≤90 mmHg and the test needs to be repeated after stabilization.
Oxygen saturation not maintained during apnea testing: testing is terminated if the saturation is ≤85% for more than 30 s.
Patient is hypothermic ( less than 36.5)
Patient repeatedly desaturates or becomes hypotensive during apnea testing.
Baseline PaCO2 ≥40 mmHg or ≤35 mmHg.
Ancillary tests for establishing brain death:
Can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed.
These tests are classified as tests that document cerebral blood flow and those that evaluate the electrical activity of the brain.
The conventional 4-vessel digital subtraction angiography is the gold standard for CBF documentation,
Computerized tomography angiography has emerged as a safer alternative that can accurately document CBF.
Transcranial Doppler is recommended as an ancillary test and is used in Intensive Care Units as it is simple, easily available and noninvasive.
Electroencephalography is widely used as an ancillary test for documentation of brain death.
Cerebral tissue perfusion techniques using technetium 99 m hexamethylpropylene amine oxime labeled brain perfusion study is being used in some centers as an ancillary test.
Pathophysiological changes following brain death and its relevance to organ preservation:
Cardiovascular system:
medullary ischemia associated with brain death causes a reflex hypertension and bradycardia (Cushing’s reflex).
increased visceral and myocardial ischemia.
depletion of adenosine triphosphate in the cardiac myocyte.
depletion of catecholamines accompanied by vasodilatation and hypotension, which contributes to the challenges in the maintenance of organ perfusion in brain death.
Respiratory system:
A rise in pulmonary hydrostatic pressure causes damage to the pulmonary endothelium resulting in pulmonary edema.
Excessive fluid resuscitation to correct perfusion can result in pulmonary edema following an increase in extravascular lung water.
Albuterol has been used for reducing pulmonary edema along with diuretics.
Endocrine system, stress and metabolic responses:
The posterior pituitary function is lost early in brain death with occurrence of diabetes insipidus with polyuria and hypernatremia.
The anterior pituitary functions are preserved for a slightly longer period.
Thyroid hormone levels decrease and a state similar to the sick euthyroid state in critical illness can occur.
hyperglycemia worsens with stress, alteration in carbohydrate metabolism and use of glucose solutions.
Insulin levels normalize subsequently with an increase in C peptide levels.
Temperature regulation in the hypothalamus is affected, manifesting with initial hyperthermia followed by hypothermia.
Systemic inflammatory response:
could be quite severe.
mediated by inflammatory mediators from an ischemic brain, ischemic reperfusion injury, metabolic changes that occur during the catecholamine storm and an inadequately restored cardiovascular state.
Increased plasma levels of interleukin-6 in the donor leads to poorer graft utilization and graft dysfunctions
Disseminated intravascular coagulation occurs after brain death due to the release of tissue thromboplastin from necrotic brain tissue.
Protocols for donor management:
Temperature: The aim is to keep the core temperature >35°C prior to organ donation. Circulating hot air blankets, warmed intravenous fluids and adjustments of ambient temperature may be needed to achieve this goal.
Fluid management: Crystalloids are the first choice and balanced salt solutions. Replacement of blood and blood products could follow guidelines for the care of the critically ill and a haemoglobin of 10 g/L could improve tissue oxygenation indices.
Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft. Nor-adrenaline in doses >0.05 mcg/kg/min resulted in impaired cardiac contractility in transplanted hearts and in particular impairment of right ventricular performance.
Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment). The lowest FiO2 needed should be used, and optimal PEEP with a restrictive fluid strategy improves graft harvesting for lung transplants.
Replacement of hormones after brain death: Standardization of hormone therapy after brain death in combination with a central venous pressure <10 mmHg significantly improved utilization of the heart and lungs for transplant without affecting other organ systems.
Mahmud Islam
2 years ago
Brain death definition and confirmation in terms of definition and team diagnosing differ among countries with no rigid consensus criteria. Most countries consider apnea testing mandatory. Clinical testing generally is based on coma evaluation, confirming the absence of brain stem reflexes and apnea tests. Coma is diagnosed by an absence of response to noxious stimuli (supraorbital, nailbed or nipple stimulation etc). Absence of rain stem reflexes (pupillary light reflex, corneal reflex, occulo-vestibular and occulo-cephalic reflexes, gag reflex).
Ancillary tests are needed in case of insufficient neurologic evaluation. The evaluation of cerebral blood flow can be evaluated by transcranial doppler, which may be technically difficult, by CT angiography or radio nuclear studies to show the absence of blood flow in the cranium. ECG can be used as well.
after brain death, the care of potential donors is essential to preserve the function of the organs.
Medullary ischemia may cause reflex HT and bradycardia (Cushing reflex) in an attempt to preserve cranial blood flow. The discharge of catecholamine alters the metabolism in the myocardium and may lead to myocardial ischemia. Hypotension follows. The goal is to maintain BP with minimal use of catecholamine. All potential donors should have Echocardiogram. Pulmonary catheterization is needed in patients with low EF (<45%).
Hemodynamic goals are MAP equal or >60 mmHg and urine output >1.ml/kg/hr, LV EF >45%. PCWP goal is 8-12 mmHg with cardiac index >2.4 L/min/m2. In case of low cardiac index, the CVP and PCWP will help decide fluid and inotropes.
SIRS may occur due to metabolic changes, mediators from the brain and cardiac ischemic reperfusion injury. This may lead to poorer graft utilization.
Protocols for donor management:
The aim of body temperature is >35, crystalloid fluids are used with preferal of plasmalyte ringers and half saline to avoid hypernatremia and hyperchloremic acidosis. Starch-containing volume expanders are contraindicated because they harm the renal epithelium leading to early graft dysfunction. Here the first choice inotrop is Dopamine for fluid nonresponsive hypotension.
Hussein Bagha baghahussein@yahoo.com
2 years ago
Introduction
Deceased organ donation has increased the available donor pool and reduced the waiting time. Brain death has implications for organ donation.
The diagnosis of brain death is clinical. The AAN has defined brain death with 3 cardinal signs:
– Cessation of the functions of the brain including the brain stem
– Coma or unresponsiveness
– Apnea
Clinical testing for brain death include:
– Coma
– Absent brain stem reflexes
– Apnea test.
Prerequisites for the apnea test include:
– Normothermia
– Hemodynamic stability
– No sedatives or paralytic drugs
– PaO2 ≥ 200mmHg
– Near normal PaCO2 (35-45 mmHg)
Oxygen is insufflated through a catheter at the level of the carina at the rate of 6 litres/min after disconnection from the ventilator. The observer looks for respiratory movements at 8-10mm after disconnection.
The test is considered positive if there are no respiratory movements at a PaCO2 of 60mmHg or 20mmHg above baseline in those with an elevated PaCO2.
Certification of brain death is after a second apnea testing. The time of death is the time PaCO2 reaches the target value during the second apnea test.
The prerequisite prior to proceeding with the tests to confirm brain death include:
– Known cause for unresponsiveness that is incompatible with survival
– Neurological imaging to confirm diagnose
– Exclusion of associated medical conditions that could account for unresponsiveness
– Exclusion of drugs causing unresponsiveness Ancillary tests for establishing brain death:
– Used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed
– 4 vessel digital subtraction angiography is the gold standard for cerebral blood flow documentations
– CT angiography can also be used to safely and accurately document CBF
– Transcranial ultrasound is used in the ICUs and is simple, easily available and non-invasive. The presence of diastolic reverberation flow and little or no forward flow is diagnostic. EEG can also be used as an ancillary test. However, hypothermia and use of sedative drugs has to be excluded.
– Cerebral tissue perfusion techniques using technetium 99m hexamethylpropylene amine oxime labeled brain perfusion study is being used in some centers. Care of the potential organ donor
A brain dead organ donor needs the same intensity of care with the focus of treatment directed towards organ perfusion and improved quality of graft.
Pathophysiologic changes following brain death:
1. CVS:
a. Reflex HTN and bradycardia in an attempt to maintain CBF. Subsequent to this, is a period of intense vasoconstriction and tachycardia associated with increased catecholamines, which can cause visceral and myocardial ischemia.
b. The goal in the management include maintenance of BP with minimal use of inotropes, optimizing fluid management and maintenance of organ perfusion.
c. An ECHO is mandatory for all potential donors.
2. Respiratory system
a. A rise in pulmonary hydrostatic pressure causes damage to the pulmonary endothelium resulting in pulmonary edema.
b. The goals in ventilator management includes minimal FiO2 to maintain a PaO2 of > 100mmHg, SPO2 > 95%, PaCO2 of 35 to 45mmHg and pH 7.35 to 7.45.
c. Ventilation strategies similar to those used for AKI are now recommended.
3. Endocrine system, stress and metabolic responses
a. Post pituitary function is lost early in brain death resulting in DI
b. Thyroid hormone levels decrease
c. Reduction in insulin levels causes hyperglycemia
d. Loss of hypothalamic function results in initial hyperthermia followed by hypothermia.
4. SIRS
a. SIRS occurs and can be quite severe.
5. DIC
a. DIC can also occur after brain death. Protocols for donor management
General principle of the ‘Rule of 100’: SBP >100mmHg, urine output >100ml/hour, Hb >100g/L, PaO2 > 100mmHg, and blood sugar >100 mg/dL.
HES is contraindicated in fluid resuscitation as it is known to cause kidney injury.
Replacement of hormones:
1. Vasopressin
a. 1 unit bolus followed by an infusion of 0.5-4.0 units/hour
2. Methylprednisolone
a. 15mg/kg immediately after the diagnosis of brain death
3. Insulin
a. 10 IU in 50% dextrose followed by an infusion to maintain blood glucose between 80-150mg/dL
4. Thyroxine
a. 20mcg bolus followed by infusion of 10mcg/hour. Conclusion
“Care of the donor” is essentially “the simultaneous care of multiple recipients”.
Reem Younis
2 years ago
Please provide a summary of this article
-Brain death is a state of cessation of cerebral function wherein -the proximate cause is known and is considered irreversible.
-It has defined brain death with three cardinal signs, cessation of the functions
of the brain including the brainstem, coma or unresponsiveness and apnea.
-In many countries, the diagnosis of brain death is made after fulfilling the mandatory criteria and by the apnea testing which is a safe technique for documentation.
-Clinical testing for brain death
1. Coma: Absence of response to noxious stimulus (supraorbital pressure or pressure on the nail bed) with the exception of spinally mediated reflexes.
2. Absent brain stem reflexes (a formal evaluation of thebrain stem reflexes is undertaken when the patient has had fixed dilated pupils and absent cranial nerve reflexes for more than 4 h).
3. Apnea test: The aim of this test is to check for the integrity of the brain stem respiratory center at high levels of blood carbon dioxide. Prerequisites include
a patient who is normothermic (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralytic drugs, with normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
-The test is considered positive if there are no respiratory movements at a PaCO2
of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO2.
-Certification of brain death is after a second apnea testing, the timing of which varies between countries.
-The time of death is the time PaCO2 reaches the target value[1] during the second apnea test.
-The increase in intracranial pressure (ICP) that accompanies brain death spares the rostral portion beyond the second cervical spine and does not compromise blood supply to this area.This could be the explanation for complex motor
movements at the spinal cord level even after diagnosing brain death.
-Ancillary tests for establishing brain death
Ancillary tests can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed.
-They are classified as tests that document cerebral blood flow (CBF) and those that evaluate the electrical activity of the brain. The conventional 4 vessel digital subtraction angiography is the gold standard for CBF documentation.
– Computerized tomography (CT) angiography has emerged as a safer alternative that can accurately document CBF.
-Transcranial Doppler is recommended as an ancillary test and is used in Intensive Care Units (ICU) as it is simple, easily available and noninvasive.
-Electroencephalography is widely used as an ancillary test for documentation of brain death
-A brain-dead organ donor needs the same intensity of care with the focus of treatment directed toward organ perfusion and improved quality of grafts.
– The instability is greater when the time to organ retrieval from the diagnosis of brain death is longer.
-The inevitable hormonal and inflammatory changes accompanying brain death can result in graft dysfunction and increased chances of rejection.
-In all patients with brain death, medullary ischemia associated with brain death causes a reflex hypertension and bradycardia (Cushing’s reflex). This is a reflex attempt by the body to maintain the CBF.
-The goals of ventilatory management include minimal FiO2 needed to
maintain a PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45.
-Protocols for donor management
1. Temperature: The aim is to keep the core temperature >35°C prior to organ donation.
2. Fluid management: Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with
sodium bicarbonate) may be superior to normal saline as they do not produce hyperchloremic acidosis.
3. Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft.
4. Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment). The lowest FiO2 needed should be used, and optimal PEEP with a restrictive fluid strategy improves graft harvesting for lung transplants.
5. Replacement of hormones after brain death:
The recommended replacements are:
a. Vasopressin.
b. Methylprednisolone .
c. Insulin
d. Thyroxine
Huda Saadeddin
2 years ago
Care of the donor” is essentially “the simultaneous care of multiple recipients.”
The barriers that exist in limited resource environments are the time to diagnosis and the costs involved in sustaining care for the brain-dead donor to the point when consent is obtained.
Introduction
The American Association of Neurology (AAN) has defined brain death with three cardinal signs, cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
The diagnosis of brain death is made after fulfilling the mandatory criteria and by the apnea testing which is a safe technique for documentation.
Ancillary tests for establishing brain death
Ancillary tests can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed.
These tests are classified as tests that document cerebral blood flow (CBF) and those that evaluate the electrical activity of the brain.
The conventional 4 vessel digital subtraction angiography is the gold standard for CBF documentation.
Computerized tomography (CT) angiography has emerged as a safer alternative that can accurately document CBF.
Transcranial Doppler is recommended as an ancillary test and is used in Intensive Care Units (ICU) as it is simple, easily available and noninvasive.
Electroencephalography is widely used as an ancillary test for documentation of brain death.
Cerebral tissue perfusion techniques using technetium 99 m hexamethylpropylene amine oxime labeled brain perfusion study is being used in some centers as an ancillary test.
AAN recommends that the physician can decide against a declaration of brain death rather than ordering ancillary tests if the clinical findings are unreliable.
Care of the Potential Organ Donor
A brain-dead organ donor needs the same intensity of care with the focus of treatment directed toward organ perfusion and improved quality of grafts. Intensive care with the use of invasive lines is mandatory for improved quality of care and titration of inotropes and fluids.
Pathophysiological changes following brain death and its relevance to organ preservation
The time from a diagnosis to declaration of brain death is complicated by fluctuating donor hemodynamics. The instability is greater when the time to organ retrieval from the diagnosis of brain death is longer.
The goals in the management include maintenance of BP with minimal use of inotropes, optimizing the fluid management and maintenance of organ perfusion .
An echocardiogram is indicated in all potential donors, and pulmonary artery catheterization (PAC) is indicated for donors with an ejection fraction (EF) <45%, more in the background of cardiac and lung transplants.
Protocols for donor management
The circulatory and biochemical variables are managed by the general principle of the “Rule of 100”
>> targets of SBP ≥100 mmHg
>> urine output ≥100 ml/h
>> hemoglobin of ≥100 g/L
>> PaO 2 ≥100 mmHg
>> blood sugar targeted at 100% normal.
Other elements of donor management are listed below:
Temperature: The aim is to keep the core temperature >35°C prior to organ donation.
Fluid management: Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline as they do not produce hyperchloremic acidosis. Uncorrected hypernatremia could result in graft losses after liver transplant. Hydroxyethylstarches are contraindicated in organ donors because they can damage renal epithelial cells and cause early graft dysfunction in the transplanted kidneys.
Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft.
Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment).
Replacement of hormones after brain death:
The recommended replacements are:
a. Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h (desmopressin intranasally has a selective action on the V2 receptors and a half-life varying from 6 to 20 h.
b. Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24 th hourly thereafter.
c. Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg.
d. Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. Tri–iodothyronine (T3) given as a 4-mcg bolus followed by an infusion of 3 mcg/h. T4 improves hemodynamics and prevents cardiovascular collapse in hemodynamically unstable organ donors.
Other concerns and considerations
Infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus preclude organ donation.
In the background of growing enthusiasm to support organ donation and multiple organ transplants one must keep in mind that preoperative donor screening for viruses may be missed in the first 2 weeks of infection. Transmission of HIV and rabies from infected donors has been documented.
Yashu Saini
2 years ago
This is a review article which discusses assessment and evaluation of brain death and what is optimum care needed to be given to the deceased donor so as to improve graft outcome. Brain death has been defined by the American association of neurology with three cardinal signs as follows:
Cessation of brain functions including brainstem
Coma or unresponsiveness
Apnea
Common way of diagnosisng brain death is fulfilling of mandatory criteria and positive apnea test.
CLINICAL TESTING OF BRAIN DEATH
COMA: No response to noxious stimuli like supraorbital or nail bed pressure . Spinal reflexes may be present
ABSENT BRAINSTEM REFLEXES: This is done when pupils are fixed and dilated and cranial nerve reflexes are absent.
APNEA TEST: This helps to check the integrity of brainstem respiratory center at high CO2 levels in blood. This test can only be done if patient is normothermic (core temp > 36.5 C), SBP> 100mmHg, free from sedatives and paralytic agents with normal oxygenation (PaO2 > 200mmHg)
TROUBLESHOOTING DURING PERFORMANCE OF APNEA TEST
Use ionotropes and fluid blouses to achieve target SBP. Apnea test not to be done if SBP<90mmHg
Apnea test to be aborted if oxygen saturation < 85% for more than 30 sec.
In hypothermic patient (< 36.5 F) then apnea test needs to be repeated after correction of same
Ancillary tests may be used for confirming brain death if desaturation or hypotension develops during apnea testing (EEG, cerebral angiography)
A rise of > 20mmHg in PaCO2 above baseline is considered positive.
Regarding ancillary testing AAN ha declared that there is lack of evidence to determine accuracy of ancillary tests for confirming brain death and recommended that in situation of unreliable apnea test declaration of brain death should be deferred rather than going for ancillary tests.
CARE OF POTENTIAL ORGAN DONOR:
Fluctuating donor hemodynamics and hormonal and inflammatory changes increases the risk of graft dysfunction and / or increased chances of graft rejection. Hence, care of potential deceased donor is very important to preserve the quality of graft. Cardiovascular system
The main principle is to maintain BP with minimal use of ionotropes and ensuring adequate fluid management and organ perfusion. Respiratory system
Target ventilatory settings: Minimal FiO2 needed to keep PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45.
pulmonary edema should be prevented with proper fluid management. Endocrine system
With the brain death the body looses the endocrine responses. Posterior pituitary is commonly affected causing DI, polyuria, hypernatremia. other complications are hyperglycemia due to decreased insulin levels and stress, temperature dysregulation. all this need to be managed actively to provide adequate care. Systemic inflammatory response
This is primarily due to ischemic injury leading to DIC and coagulopathy if not taken care off.
Temperature, fluid and BP management is key to preventing systemic inflammatory response.
Abdullah hindawy
2 years ago
summary
the aricle focuss on the donation from brain death patients
The American Association of Neurology (AAN) has defined brain death with three cardinal signs, cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
test for brain death
1-coma
2-Absent brain stem reflexes
3-Apnea test
4-Ancillary tests
Care of the Potential Organ Donor :
brain-dead organ donor needs the same intensity of care with the focus of treatment directed toward organ perfusion and improved quality of grafts. Intensive care with the use of invasive lines is mandatory for improved quality of care and titration of inotropes and fluids.
Protocols for donor management :
1-Temperature :>35°C prior to organ donation.
2-Fluid management:
Ringer’s acetate is preffered
Hydroxyethylstarches are contraindicated in organ donors because they can damage renal epithelial cells and cause early graft dysfunction in the transplanted kidneys.
3-Inotropes and cardiovascular system :: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft
.
4-Ventilatory management:low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment).
5-Replacement of hormones after brain death:
a. Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h (desmopressin intranasally has a selective action on the V2 receptors and a half-life varying from 6 to 20 h.[20]) b. Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly thereafter. c. Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg. d. Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. Tri-iodothyronine (T3) given as a 4-mcg bolus followed by an infusion of 3 mcg/h. T4 improves hemodynamics and prevents cardiovascular collapse in hemodynamically unstable organ donors.
Rahul Yadav rahulyadavdr@gmail.com
2 years ago
Confirmation of Brain death
Brain death is defined as 1. Cessation of brain function including brain stem
Tested by Fixed Dilated Pupils and absent brain stem reflex for more than 4 hours 2. Coma
Absent response to painful stimuli (like supraorbital/nailbed pressure)
Exception of spinally mediated reflex 3. Apnea
No response of brain stem to raised PaCo2 (more than 60 or rise of more than 20 above baseline)
Should be Normothermic (≥36.5), Systolic BP≥100, SpO2>85%, near Normal PaCo2, free from sedatives/hypnotics
In India, Apnea test needs to be certified by 4 physicians and repeated after a gap of 6 hours and one out of them must be a neurologist
Ancillary Tests for Brain death:
If Apnea test can’t be performed or ambiguity with neurological examination, tests should be done for evaluating Cerebral Blood Flow and electrical activity of Brain. These tests include
1. DSA/CTA
2. Doppler (Transcranial)
3. Tc99 based nuclear studies for cerebral perfusion
4. EEG
Care of Potential Donor: Goals
1. Normal Blood Gases on minimal FiO2(PaO2>100, PaCo2 35-45, Spo2>95% and pH 7.35-7.45)
2. Maintenance of BP with Adequate fluids (Crystalloids like RL) with Minimal use of Ionotropes (Dopamine, Nor-adrenaline<0.05mcg/kg/min), correction of Hypernatremia
3. Core Temperature more than 35 degree Celsius
4. Hormone Replacement (Vasopressin, Methyprednisolone, Insulin and thyroxine)
5. Caring for infections
Rule of 100 in care of potential Donors
1. SBP≥100mm of Hg
2. Urine Output≥100ml/hr
3. Hb≥100g/L
4. Pa02≥100mm of Hg
5. RBS around 100
Nandita Sugumar
2 years ago
Summary
This study is about brain death and care of the organ donor. Brain death is a major influence on the availability of donors for kidney recipients. However, proper maintenance is necessary to preserve the needed organs in a manner that can be used.
Brain death can be defined as a state of cessation of cerebral function wherein the cause is known and cannot be reversed. Three signs that indicate brain death include :
cessation of brain function including brainstem
coma
unresponsiveness and apnea
Maintenance of brain dead donor has two major goals – proper perfusion of required organs and improved quality of grafts.
Obtaining consent from guardian is essential to the process of organ donation but along with this the very diagnosis of brain death all takes valuable time away from getting a good quality graft. Hence, quick and decisive action Is needed.,
Care includes :
Maintenance of BP
minimal use of inotropes
optimized fluid management
maintenance of organ perfusion
Echocardiogram performed on all potential donors
avoid excessive fluid resuscitation – albuterol can be used to reduce any potential pulmonary edema
maintain temperature (core) less than 35 degree Celsius before donation of required organ
Replacement of hormones after brain death to standardize hormones is important for heart and lung donations. This can be achieved with vasopressin bolus, methylprednisolone, insulin, thyroxine bolus.
Ghalia sawaf
2 years ago
Clinical testing for brain death
1. Coma
2. Absent brain stem reflexes
• Absent pupillary light reflex
• Absent corneal reflex
• Absent reflexes in the face and maxillary region
• Absent oculo-cephalic reflex (doll’s eye movement)
• Absent oculo-vestibular reflex
• Absent pharyngeal (gag) and laryngeal (cough) reflex)
3. Apnea test
Troubleshooting during performance of apnea test
1. Patient’s systolic blood pressure (SBP) ≤100 mmHg:
2. Oxygen saturation not maintained during apnea testing
3. Patient is hypothermic (<36.5°F):
4. Patient repeatedly desaturates or becomes hypotensive during apnea testing
5. Baseline PaCO2 ≥40 mmHg or ≤35 mmHg
Checklist prior to proceeding with tests for brain death
Prerequisite
• Proximate cause for unresponsive state that is incompatible with survival (Major trauma, intracranial bleed with midline shift)
• Neurological imaging to confirm diagnosis (CT brain, MRI, angiography)
• Exclusion of associated medical conditions that could account for unresponsiveness
• Exclusion of severe acid-base, metabolic or electrolyte abnormalities
• Exclusion of drugs causing unresponsiveness (Sedatives, narcotics, muscle relaxants. In drug overdose allow time for 5 half-lives/measure drug levels)
• Normal temperature Core temperature >32°C/90°F
Ancillary tests for establishing brain death
• Ancillary tests can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed
• conventional 4 vessel digital subtraction angiography is the gold standard for CBF documentation.
• Computerized tomography (CT) angiography
• Transcranial Doppler is recommended as an ancillary
• Electroencephalography is widely used as an ancillary test
Pathophysiological changes following brain death and its relevance to organ preservation
• Cardiovascular system
Cushing’s reflex
The level of rise in catecholamines is dependent upon the rate of rise in ICP
20-25% brain-dead donors showed evidence of myocardial ischemia and 40% have echo evidence of myocardial dysfunction
echocardiogram is indicated in all potential donor
• Respiratory system
A rise in pulmonary hydrostatic pressure causes pulmonary edema
Excessive fluid resuscitation to correct perfusion can result in pulmonary edema
Albuterol has been used for reducing the pulmonary edema
Endocrine system, stress and metabolic responses
• The posterior pituitary function is lost early in brain death( diabetes insipidus ) with polyuria and hypernatremia.
Arginine vasopressin and desmopress for management
• anterior pituitary functions are preserved for a slightly longer period. Thyroid hormone
• decrease in insulin levels, hyperglycemia worsens with stress. Hyperglycemia can also affect the outcomes after renal transplantation.
• Systemic inflammatory response :
Increased plasma levels of interleukin-6 in the donor have translated to the poorer graft utilization and graft dysfunctions.
• Disseminated intravascular coagulation occurs after brain death due to the release of tissue thromboplastin from necrotic brain tissue.
Protocols for donor management
1. the “Rule of 100” suggesting
2. targets of SBP ≥100 mmHg,
3. urine output ≥100 ml/h,
4. hemoglobin of ≥100 g/L,
5. PaO2 ≥100 mmHg
6. blood sugar targeted at 100% normal.
Other elements of donor management are
1. temperature >35°C prior to organ donation. Circulating hot air blankets, warmed intravenous fluids .
2. Fluid management:
Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline
Uncorrected hypernatremia could result in graft losses after liver transplant.
Hydroxyethylstarches are contraindicated in organ donors
4. Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft.
5. Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment). The lowest FiO2 needed should be used, and optimal PEEP with a restrictive fluid strategy improves graft harvesting for lung transplants.
Replacement of hormones after brain death:
The recommended replacements are: a. Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h (desmopressin intranasally has a selective action on the V2 receptors and a half-life varying from 6 to 20 h.
b. Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly thereafter.
c. Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg.
d. Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h.
Tri-iodothyronine (T3) given as a 4-mcg bolus followed by an infusion of 3 mcg/h.
This is a good summary, dear Dr GHalia I like that you have typed headings and sub-headings in bold or underline. That makes it easier to read.
Sahar elkharraz
2 years ago
Brain death and care of the organ donor:
This article done in india focus on care of deceased kidney donor from brain death.
Brain death means cessation of cerebral function and unawareness of persons to surrounding and cessation of respiration and patients should be on ventilation. 4 physicians are involved for diagnosis of brain death; one of them are neurologist.
Criteria of diagnosis of brain death:
Deep coma on mechanical ventilation with full oxygenation
No evidence of electrolytes disturbance
No evidence of hypothermia
No evidence of drug toxicity or effects
Maintenaned systolic blood pressure > 60mmHg
Pco2 > 60
No endocrine abnormalities
Apnea test is positive by absence of cranial reflex / absence of corneal reflex/ absence of vestibule -occular reflex / absence of gag reflex.
If confirmation of brain death is not sufficient advice for CT angiogram to assess cranial blood flow and MRA to confirm diagnosis.
EEG ( electrocephalogram ), to confirm diagnosis.
Care of organ donation:
Maintain fluid balance by central jugular line and pulmonary capillary wedge pressure and intravenous fluid.
Maintain blood pressure on 100/60 and mean arterial pressure above 60mmHg and avoid hypotension by given intropic agents.
Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has good effects on the renal graft.
In case of brain death diabetic inspiduse common so polyuria common; so give vasopressin dose intranasal.
Correct hypothermia by hot blanket.
The care maintenance by role of 100: Systolic blood pressure is more than 100 mmHg, Oxygen saturation is 100, blood sugar above 100, Pco2: 100, heart rate 100.
This is an excellent summary and analysis, Dr Sahar.
I know you have used bold at some places. Please type headings and sub-headings in bold or underline. That will make it easier to read.
Dr. Tufayel Chowdhury
2 years ago
Brain death is a cessation of cerebral function where the cause is known and irreversible.
Checklist before proceeding tests for brain death:
Proximate cause for unresponsive state that is incompatible with survival for example major trauma, intracranial bleed with mid line shift
Neurological imaging to confirm diagnosis- CT brain , MRI, angiography
Exclusion of associated medical conditions that could account for unresponsiveness- exclusion of severe acid base, metabolic or electrolyte abnormalities.
Exclusion of drugs causing unresponsiveness- sedatives, narcotics, muscle relaxants. In drug overdose, allow time for 5 half lives
Normal temperature- core temperature> 32 degree C
Clinical tests for brain death:
Absence of response to noxious stimulus with the exception of spinally mediated reflexes.
Absent brain stem reflex:
Absent pupillary light reflex
Absent corneal reflex
Absent reflex in face and maxillary area
Absent oculo- cephalic reflex
Absent pharyngeal gag reflex and laryngeal cough reflex
SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted at 100% normal. Other elements of donor management are listed below:
1. Temperature: The aim is to keep the core temperature >35°C prior to organ donation. Circulating hot air blankets, warmed intravenous fluids and adjustments of ambient temperature may be needed to achieve this goal.
2. Fluid management: Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline as they do not produce hyperchloremic acidosis.
3. Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft.
4. Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment).
5. Replacement of hormones after brain death:
The recommended replacements are: a. Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h (desmopressin intranasally has a selective action on the V2 receptors and a half-life varying from 6 to 20 h.
b. Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly thereafter.
c. Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg.
d. Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. Tri-iodothyronine (T3) given as a 4mcg bolus followed by an infusion of 3 mcg/h.
This is an excellent summary and analysis, Dr Tufayel, Please type headings and sub-headings in bold or underline. That will make it easier to read.
Mohammed Abdallah
2 years ago
Please provide a summary of this article
Introduction
Definition of death according to the American Association of Neurology (AAN): cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea
Prerequisites before proceeding to tests for brain death are
1. Proximate cause for unresponsive state that is incompatible with survival
2. Neurological imaging to confirm diagnosis
3. Exclusion of associated medical conditions that could account for unresponsiveness
4. Exclusion of drugs causing unresponsiveness
5. Normal temperature
Clinical testing for brain death
1. Coma: no response to noxious stimuli
2. Absent brain stem reflexes: when the pupils fixed and dilated and absent cranial nerve reflexes for more than 4 h. absent of pupillary light reflex, corneal reflex, reflexes in the face and maxillary region, oculo-cephalic reflex, oculo-vestibular reflex, and pharyngeal (gag) and laryngeal (cough) reflex)
3. Apnea test (see below) Apnea test
Prerequisites are
1. Normothermic (core temperature ≥36.5°C)
2. hemodynamically stable (systolic pressure ≥100 mmHg)
3. No sedative and paralytic drugs
4. Normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation)
5. Near normal PaCO2 (35-45 mmHg)
How to do the apnea test
· Disconnect the ventilator
· Oxygen through a catheter placed at the level of the carina at 6.0 L/min
· Observe for respiratory movements at 8-10 min after disconnection
· If there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline, the test is positive
Certification of brain death is after a second apnea testing (timing varies between countries)
Troubleshooting during performance of apnea test
1. Systolic blood pressure (SBP) ≤100 mmHg: give vasopressors, inotropes and fluid boluses
2. Low oxygen saturation (terminate apnea test if O2 saturation is ≤85%). CPAP and oxygen flow of 12.0 L/min
3. Hypothermia ((<36.5°F). repeat the test after correction
4. Repeated desaturation or hypotension during apnea testing. Do ancillary test (below)
5. Baseline PaCO2 ≥40 mmHg or ≤35 mmHg: reduce frequency of of ventilation in high PaCO2
Ancillary tests for establishing brain death
Indicatinos are: 1.uncertainty of the neurologic tests. 2. When the apnea test cannot be performe
These tests classified into:
1. Tests that document cerebral blood flow (CBF). 4 vessel digital subtraction angiography (gold standard), CT angiography and Transcranial Doppler (in ICU)
2. Tests that evaluate the electrical activity of the brain: EEG (caution with sedatives and hypothermia), Cerebral tissue perfusion techniques using technetium 99 m
Pathophysiological changes following brain death
Cardiovascular system:
· Reflex hypertension and bradycardia (Cushing’s reflex) due to medullary ischemia
· Then intense vasoconstriction and tachycardia (catecholamines) Respiratory system
· A rise in pulmonary hydrostatic pressure causes damage to the pulmonary endothelium resulting in pulmonary edema
· Ventiatory set-up: minimal FiO2 needed to maintain a PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45
· Avoid excessive fluid (guide with pulmonary artery catheterization)
· Albuterol and diuretics for pulmonary edema
Endocrine system, stress and metabolic responses
· Diabetes insipidus: give arginine vasopressin and desmopressin
· Thyroid hormones: thyroid replacement
· Hyperglycemia: can affect the outcomes after renal transplantation
· Impaired temperature regulation (initially hyperthermia followed by hypothermia)
Systemic inflammatory response
Inflammatory mediators from an ischemic brain, ischemic reperfusion injury, metabolic changes that occur during the catecholamine storm. Increased interleukin-6 (poor graft function). DIC (release of tissue thromboplastin from necrotic brain tissue)
Protocols for donor management
Rule of 100 (SBP ≥100 mmHg, urine output ≥100 ml/h, Hb ≥100 g/L, PaO2 ≥100 mmHg and RBS targeted at 100% normal)
1. Temperature: keep temperature >35°C (Circulating hot air blankets, warmed intravenous fluids and adjustments of ambient temperature)
2. Fluid management: Crystalloids and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate). Blood/blood products
3. Inotropes: dopamine (first choice), if no response to fluids. Doputamine
4. Ventilatory management: low tidal volume 6-8 ml/ kg, minimum plateau pressure, lowest FiO2, and optimal PEEP
5. Replacement of hormones: vasopressin, Methylprednisolone, insulin, and thyroxine
This is a good summary, dear Dr Abdallah, I like that you have typed headings and sub-headings in bold or underline. That makes it easier to read.
Last edited 2 years ago by Ajay Kumar Sharma
Hinda Hassan
2 years ago
The American Association of Neurology has three cardinal signs for diagnosing brainstem death:
cessation of the brain functions , unresponsiveness and apnea.
Clinical tests of brain death are considered If a patient has a proximate cause for unresponsive state that is incompatible with survival , after exclusion medical conditions, drugs and hypothermia, and the CT MRI confirming his state. These clinical tests include: Coma, absent brain stem reflexes and apnea test.
The apnea test is used to check the integrity of the brain stem respiratory center at high levels of blood CO2. The patient need to have core temperature ≥36.5°C , PaO2 ≥200 mmHg after 100% oxygenation, near normal PaCO2, systolic pressure ≥100 mmHg, free from sedative and paralytic drugs. Positive test is when there is no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above. Two tests need to be performed to certify brain death. Terminate the test if systolic BP is ≤90 mmHg and the test needs to be repeated after stabilization, oxygen saturation is ≤85% for more than 30 s, temperature <36.5°F, baseline PaCO2 ≥40 mmHg or ≤35 mmHg or repeated desaturation during apnea testing. In this case, ancillary tests can be used (electroencephalography, cerebral angiography, transcranial Doppler and scintigraphy). There are classified into:
1- Cerebral blood flow (CBF): conventional 4 vessel digital subtraction angiography which is considered the gold standard test (show absence of intracerebral filling at the level of the carotid bifurcation or vertebral arteries). CTA is a safe alternative. Transcranial Doppler is used in ICU and is considered diagnostic when the diastolic reverberation flow is present and little or no forward flow but it could be affected by many factors,
2- Electrical activity of the brain: Electroencephalography of isoelectric recording from 18 to 20 channels over a 30 min period after exclusion of sedative drugs and hypothermia.
brain death donors need care for organ perfusion and improved quality of grafts. This may involve Intensive care with the use of invasive lines for inotropes and fluids. The donors are subjected to medullary ischemia with a reflex hypertension and bradycardia (Cushing’s reflex). This will cause vasoconstriction and tachycardia due to high circulatory catecholamines that will increase the visceral and myocardial ischemia. This will be followed by catecholamines depletion that will make the maintenance of organ perfusion in brain death a challenge. The goals in the management include:
· maintenance of BP with minimal use of inotropes
· optimizing the fluid management
· maintenance of organ perfusion
All donors need echocardiogram and if ejection fraction is less than 45% they need pulmonary artery catheterization (particularly for cardiac and lung transplants).
The targets of ventilatory management are PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg , pH 7.35-45 and tidal volumes similar to those used for acute lung injury. Avoid excessive fluid resuscitation by the use of a PAC, Albuterol and diuretics.
Those donors are at risk of diabetes insipidus due to loss of posterior pituitary which will result in polyuria and hypernatremia. This can be treated with Arginine vasopressin and desmopressin. The thyroid hormone and insulin are also low with resultant hyperglycemia which may damage pancreatic cells. They are also at risk of hypothermia which will worsen acidosis and coagulopathy leading to arrhythmias .
Systemic inflammatory response can occur due to the release of inflammatory mediators from ischemic tissues with resultant DIC
The targets of donor management are SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg , blood sugar targeted at 100% normal and temperature >35°C prior to organ donation. These can be achieved through the use of crystalloids , balanced salt solutions, replacement of blood and blood products and Dopamine if hypotension is unresponsive to volume expansion.
Ventilatory management includes low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment.
Hormone replacements after brain death include giving Vasopressin, Methylprednisolone, Insulin 10 U in 50% dextrose and Thyroxine.
Preoperative infection screening and exclusion of donors who have infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus .
Regarding pregnancy, the mother should be supported until the delivery of the fetus and then she can be considered for organ donation.
This is an excellent summary and analysis, Dr Hinda Please type headings and sub-headings in bold or underline. That will make it easier to read.
Filipe prohaska Batista
2 years ago
This article shows the discussion about brain or cardiac death using the AAN Concepts and the reality in India, which is similar to a good part of the countries.
The classic concept of brain death is the cessation of functions such as coma, unresponsiveness (absence of central brain reflexes), and apnea. Increased intracranial pressure can trigger reflexes in the spinal cord.
To rule out brain death, there must be a central reflex (pupillary, corneal, facial, oculocephalic, oculovestibular, pharyngeal, and laryngeal). Neuroradiological tests (USG Doppler, magnetic resonance angiography, technetium scintigraphy, angiography), electroencephalographic (EEG), hypothermia, sedatives, narcotics, hydro electrolytic and acid-base disturbances.
Because it is an extremely multicultural country, with several religions, and great spirituality, the concept of death by brain outcome can be confusing, applying the need for cardiac arrest to officially define death for family members.
In the case of the potentially deceased cardiac donor, we have the Maastricht categories, where brain death has not yet occurred but there is severe irreversible damage (Maastricht 3).
Cardiovascular care of the potential donor involves fluid therapy, and vasopressor drugs (dopamine is preferred) to achieve adequate blood pressure values. On the other hand, the pulmonary condition seeks adequate oxygenation rates, avoiding excess fluid therapy, so some centers use pulmonary catheters for adequate control of fluids, pressure, and volume of oxygen to be made available. Endocrine metabolic care such as diabetes insipidus (desmopressin), vasopressin, glycemic control, and thermal control decrease ischemia and ensure the quality of the organ potentially to be donated. Corticosteroids to decrease the systemic inflammatory response are also discussed in this article.
Maintain a temperature above 35 degrees Celsius, crystalloids with Ringer’s Lactate to prevent hyperchlorhydremia, blood replacement when hemoglobin is less than 10, dopamine for inotropic control, protective ventilation, and hormone replacement to increase the quality of the organ to be donated despite brain death or imminent cardiac arrest. Situations such as infections and active malignant neoplasms are still an exclusion factor.
This is an excellent summary and analysis, dear Dr Philpe. Please type headings and sub-headings in bold or underline. That will make it easier to read.
II. Brain death & care of the organ donor 1. Please provide a summary of this article
The AAN defined brain death with 3 main signs:
– Cessation of brain functions that include Brainstem
– Coma or unresponsiveness
– Apnea
Globally great differences exist in criteria & the tests used. Prerequisites required before testing for brain death include:
Proximate cause for unresponsiveness that is incompatible with survival: Major trauma, intracranial bleed with midline shift.
Imaging to confirm diagnosis: CT brain, MRI, angiography.
Exclude conditions that could account for
unresponsiveness: severe acid-base, metabolic or electrolyte abnormalities.
Exclude drugs causing unresponsiveness: Sedatives, narcotics, muscle relaxants. In overdose allow time for 5 half-lives/measure drug levels.
Normal temperature: Core temp >32°C/90°F. Clinical testing for brain death 1.Coma: no response to noxious stimulus (supraorbital pressure or nail bed pressure) with the exception of spinal reflexes. 2.Absent brain stem reflexes: -Pupillary light reflex: afferent II CN,
efferent III CN nerve – Corneal reflex: afferent V CN, efferent
VII nerve
– Reflexes in the face & maxillary region: area
by V CN (trigeminal)
– Oculo-cephalic reflex (doll’s eye movement): afferent VIII, efferent III & VI. Lateral 90°
movements of neck result in deviation of eyes
toopposite direction with an intact brain stem;
rule out cervical spine injury prior to testing – Oculo-vestibular reflex: afferent is VIII &
efferent III & VI CNs; patient at a 30° head up
position (lateral semicircular canal becomes
vertical),50 ml of ice-cold NS injected into ear.
Nystagmus with a slow component toward the
side of injection indicate functioning brain stem (assure intact tympanic membrane. Wait 5 min before testing other ear)
– Pharyngeal (gag) & laryngeal (cough) reflex):
afferent IX & efferent X CNs 3. Apnea test: checks integrity of brain stem respiratory center at high CO2. Prerequisites prior testing are: normothermia (core temp ≥36.5°C), SBP ≥100 mmHg, no sedative & paralytic drugs, normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) & near normal PaCO2 (35-45 mmHg). Steps:
– Disconnect ventilator
– O2 given at 6.0 L/min
– Look respiratory movements 8-10 min after
Disconnection
– Positive test if no respiratory movements at
PaCO2 of 60 mmHg (20 mmHg above baseline
if initially high)
– Certify brain death after a 2nd apnea testing
(timing widely varies between centers).
– Time of death is when PaCO2 reaches target
value during 2ndapnea test. Problems during apnea test
1. The test aborted & repeated if SBP is ≤90 mmHg; vasopressors & fluid needed to keep it above target.
2. SaO2 not maintained during apnea testing:
The test cancelled if SaO2 is ≤85% for >30 s. Retest with T-piece & CPAP of 10 cm H2O & O2 flow 12.0 L/min.Tolerance to apnea can be predicted by reducing the PEEP to 5 cm H2O before ventilator is disconnected.
3. Hypothermia (<36.5°C): repeat test after correction.
4. Repeatedly de-saturation or hypotension testing: ancillary tests (EEG, angiography, trans-cranial Doppler & scintigraphy) considered to confirm brain death.
5. Baseline PaCO2 ≥40: test is +ve if a rise by ≥20 above baseline.
6. Baseline PaCO2 ≤35: reduce ventilation frequency to raise PaCO2 to target before testing. Ancillary tests to support a brain stem death
– Used if neurologic evaluation is uncertain or apnea test cannot be done.
– 4 vessels digital subtraction angiography is the gold standard for CBF testing: absence of filling at carotid bifurcation or vertebral arteries confirms brain death.
– CT angiography: safer alternative & accurately test CBF.
– Transcranial Doppler: used in ICU, is simple & noninvasive. It is operator dependent.
– EEG: widely used to document brain death. Isoelectric recording over 30 min is suggestive.
(sedatives & hypothermia give similar picture).
– Cerebral tissue perfusion (technetium 99 m)
study is used in some centers.
If clinical findings are unreliable, the physician can decide against brain death rather than asking for ancillary tests (AAN recommendations). Care of Organ Donor – Needs the same intensity of care. – Focus treatment (inotropes, fluids) toward organ perfusion & improved quality of grafts. – Potential donor: brain-dead or with severe brain injury with a clear intent by physician & the family to withdraw life support. – Grief counselors can communicate with the family & act in the interests of both the potential donor & the pool of recipients. Pathophysiology & organ preservation ·The hormonal & inflammatory changes that accompany brain death can cause graft dys-function & increased chances of rejection. ·Increased awareness, in recent decades, of donor management has improved outcomes after transplant surgery. CVS ·Medullary ischemia occuring with brain death causes a reflex HTN & bradycardia (Cushing’s reflex) in an attempt to maintain the CBF. ·This is followed by intense vasoconstriction & tachycardia (dt increased catecholamines) which increase visceral & myocardial ischemia. ·Echocardiogram indicated in all potential donors. ·Pulmonary artery catheterization indicated if EF <45% (cardiac & lung transplants). Goals of management: – maintain BP with minimal inotropes – optimize fluid management -maintenance organ perfusion. Respiratory system ·Endogenous epinephrine raises pulmonary hydrostatic pressure causing endothelial damage & pulmonary edema. ·Goals of ventilatory management: -Minimal FiO2 to maintain a PaO2 >100, SpO2 >95%, PaCO2-35-40 & pH 7.35-45. -Ventilation strategies similar to those used for ALI are currently recommended & have improved the use of lungs for transplant. -Excessive fluid to correct perfusion can result in pulmonary edema. Use of a PAC may restrict fluid use. -Albuterol & diuretics can be used in the treatment of pulmonary edema. Endocrine system & metabolic responses ·DI: due to early loss of posterior pituitary function in brain death. Causes polyuria & hypernatremia. AVP & desmopressin are used as replacements. ·Thyroid hormones decreased (sick euthyroid state). ·Decrease in insulin & worsening of hyper-glycemia with stress, alteration in CHO metabolism & use of glucose solutions. Hyperglycemia induced pancreatic cell damage compromise pancreatic graft; strict euglycemia may minimize the risk. Hyperglycemia also affect outcomes after renal transplant. ·Temperature regulation in hypothalamus: initial hyperthermia followed by hypothermia (worsened by lack of shivering, peripheral vasodilatation & reduced metabolic rate). Hypothermia aggravates acidosis & coagulopathy & increase risk for arrhythmias & cold-induced dieresis. SIRS Caused by inflammatory mediators from ischemic brain, IRI, & catecholamine storm. Increased IL-6 in the donor have poorer graft utilization & dysfunction. DIC: occurs dt release of tissue thromboplastin from necrotic brain tissue. Donor management protocols
·The “Rule of 100” normal targets:
– SBP ≥100 mmHg
– UOP ≥100 ml/h
– Hb ≥100 g/L
– PaO2 ≥100 mmHg
– Blood sugar 100mg/dl
· Core temp. >35°C prior to donation (circulating hot air blankets, warm IV fluids,
ambient temp. adjustment.
·Fluid management (patients are polyuric &
dehydrated with central volume depletion):
– Crystalloids: balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate,
½ NS with NaHCO3 may be superior to NS bcz as they do not cause hyperchloremic
acidosis.
– Uncorrected hypernatremia can cause in liver graft losse after transplant.
– Hydroxyethylstarches contraindicated bcz they damage renal epithelial cells & cause
early graft dysfunction in renal grafts.
– PAC may allow restrictive strategy with monitoring of filling pressures in lung
transplant.
– Blood & blood products: follow guidelines for the care of the critically; hemoglobin of
10 g/L improves tissue oxygenation.
·Inotropes & CVS:
-Dopamine has beneficial effect on renal graft probably due to moderation of
preservation injury & inflammation (not reno-protective).
-Noradrenaline (>0.05 mcg/kg/min) impair cardiac contractility in heart transplants.
·Ventilatory management:
-Similar to ALI (low tidal volume 6-8 ml/kg, minimum plateau pressure, lung recruitment).
-Lowest FiO2 needed is used
-Optimal PEEP with a restrictive fluid strategy improves graft harvesting in lung
transplants.
·Replacement of hormones:
– Vasopressin 1 U bolus, then infusion 0.5-4.0 U/h.
– Methylprednisolone 15 mg/kg immediately after brain death & 24 hourly after.
– Insulin 10 U in 50% dextrose, then infusion (keep blood glucose 80 – 150 mg).
– T4 20 mcg bolus, then infusion of 10 mcg/h. T3 (4-mcg bolus, then infusion 3 mcg/h).
UNOS data showed that the combination of thyroid hormone, corticosteroid, insulin & ADH was the best for multiple organ procurement. Infections ·Sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations. ·HIV infections, herpetic meningo-encephalitis & T-cell leukemia-lymphoma virus are contraindications to donation. Other concerns Pregnant patient who is brain-dead: The mother should be supported until the fetus delivered & then considered organ donation.
This is a good summary, dear Dr Mohamed. I like that you have typed headings and sub-headings in bold or underline. That makes it easier to read.
Last edited 2 years ago by Ajay Kumar Sharma
Heba Wagdy
2 years ago
According to AAN, brain death is loss of brainstem function, coma and apnea.
Tests used to confirm it are variable, before testing for brain death, the patient should have a proximate cause incompatible with survival, neurological imaging with exclusion of hypothermia, intake of drugs leading to coma, metabolic and electrolyte imbalance. Clinical tests for brain death:
Coma, absent brainstem reflexes
Apnea test, check brainstem respiratory center at high level of PCO2, 2 positive apnea tests certify brain death, timing between the 2 tests varies between centers. Problems during performing apnea test:
SBP<100mmHg, oxygen saturation not maintained during the test, hypothermia and PCO2 <35 and >40mmHg Ancillary tests for establishing brain death:
Used to support brainstem death when it is uncertain, include CBF documentation using digital subtraction angiography or CT angiography, transcranial doppler may be used but has several limitations.
Electroencephalography is also used but sedative drugs and hypothermia should be excluded.
The AAN recommends avoiding declaration of brain death if the clinical finding are unreliable rather than doing ancillary tests. Care of potential organ donor:
Intensive care is necessary to improve quality of grafts and organ perfusion, potential donor is one who is brain-dead or with brain injury incompatible with life and life support will be withdrawn Pathophysiological changes following brain death and relevance to organ preservation:
The instability of donor hemodynamics increase with increased time for organ retrieval due to inevitable hormonal and inflammatory changes.
Cardiovascular system:
Brain death leads to reflex HTN, bradycardia followed by severe vasoconstriction and tachycardia due to excess catecholamines leading myocardial ischemia resulting in hypotension and decreased organ perfusion.
The aim is to maintain blood pressure with minimal inotropes, proper fluid management and maintained organ perfusion.
Respiratory system:
Ventilatory management includes minimal FiO2 to keep PaO2>100, SpO2>95%, PaCO235-40 and pH 7.35-45 with similar strategies to those used in acute lung injury, PAC is used to guide excessive fluid management.
Endocrine system, stress and metabolic response:
Posterior pituitary function lost leading to polyuria and diabetes insipidus, thyroid hormone decreases as thick euthyroid state, temperature regulation due to hypothalamic affection. Systemic inflammatory response:
Is severe and may affect graft utilization and lead to graft dysfunction, DIC may occur after brain death. Protocols for donor management:
Target SBP >100mmHg, UOP >100ml/hr, Hgb>100g/L, PO2>100, blood sugar 100% normal.
Temperature kept >35 using blanket, warmed IV fluids.
Fluid management, crystalloids using balanced salt solution, replacement of blood products as in critically ill patients
Inotropes and cardiovascular system: dopamine is the first choice
Ventilatory management with same principles as line of management of ALI, lowest FiO2 needed should be used.
Replacement of hormones after brain death, vasopressin, methylprednisolone, Insulin and thyroxine or tri-iodothyronine, combination of these hormones improves multiple organ procurement. Other concerns and considerations:
Overwhelming sepsis, bacteremia and fungemia are not absolute contraindication for donation but HIV, hepatic meningo-encephalitis are contraindication.
Barriers for care of donors are high costs in sustaining care till consent is obtained, awareness among the public and resources to support organ donors.
This is a good summary, dear Dr Heba, I like that your have type headings and sub-headings in bold or underline. That makes it easier to read.
Last edited 2 years ago by Ajay Kumar Sharma
Assafi Mohammed
2 years ago
Summary of the article Brain death and care of the organ donor Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible.
The American Association of Neurology (AAN) has defined brain death with three cardinal signs:
a) Cessation of the functions of the brain including the brainstem.
b) Coma or unresponsiveness.
c) Apnea. Clinical testing for brain death
1. Coma.
2. Absent brain stem reflexes.
3. Apnea test: for performing apnea test, the deceased donor needs to be:
a) Normothermic (core temperature ≥36.5°C).
b) Hemodynamically stable (systolic pressure ≥100 mmHg).
c) Free from sedative and paralytic agents.
d) Normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation).
e) Near normal PaCO2 (35-45 mmHg). Protocols for donor management
“Rule of 100”: a) targets of SBP ≥100 mmHg. b) urine output ≥100 ml/h. c) hemoglobin of ≥100 g/L. d) PaO2 ≥100 mmHg. e) blood sugar targeted at 100% normal. Elements of donor management are: 1. Temperature: The aim is to keep the core temperature >35°C prior to organ donation. 2. Fluid management: Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline as theydonotproducehyperchloremicacidosis. Hydroxyethylstarches are contraindicated in organ donors because they can damage renal epithelial cells and cause early graft dysfunction in the transplanted kidneys. 3. Replacement of blood and blood products could follow guidelines for the care of the critically ill and a hemoglobin of 10 g/L could improve tissue oxygenation indices. 4. Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft. Nor-adrenaline in doses >0.05 mcg/kg/min resulted in impaired cardiac contractility in transplanted hearts and in particular impairment of right ventricular performance. 5. Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment). 6. Replacement of hormones after brain death: 7. Standardization of hormone therapy after brain death in combination with a central venous pressure <10 mmHg significantly improved utilization of the heart and lungs for transplant without affecting other organ systems.[49] The recommended replacements are: a) Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h. b) Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly thereafter. c) Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg. d) Thyroxine (T4) 20 mcg bolus followed by infusions of10mcg/h.Tri-iodothyronine(T3)given as a 4-mcg bolus followed by an infusion of 3 mcg/h. T4 improves hemodynamics and prevents cardiovascular collapse in hemodynamically unstable organ donors. Concerns and Considerations
a) Barring overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations.
b) Infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus preclude organ donation.
This is a good summary, dear Dr Rihab. I like that you have typed headings and sub-headings in bold or underline. That makes it easier to read.
Last edited 2 years ago by Ajay Kumar Sharma
Wael Jebur
2 years ago
This article discusses the contentious topic of donation after brain death DBD, elaborating on its criteria , tests adopted to ascertain the diagnosis of brain death and contemplate on the challenging issue of escalating the supportive measures in order to have as much healthy and preserved harvested organs as possible.
Diagnosing brain death as per the article is established by absence of cerebral function including brain stem and excluding the spinal reflexes which might be still preserved after ward.
the diagnosis of brain death is clinical , supportive tests can be implemented to confirm diagnosis , if still doubtful. the patient has to be in deep coma with a an imminent intra-cranial etiology confirmed by radiology examination , not responsive to deep painful stimuli.Furthermore ,all brain stem reflexes are absent including light reflex, corneal reflux, gag reflex , oculo-cephalic reflex, oculo-vestibular reflex.absent reflexes in the face and and maxillary regions.
When the patient is diagnosed with brain death, then , all consequent features has to be addressed and treated properly in order to have perfect functioning and well preserved organs.
The other important and essential test that is integral in diagnosing brain death is the apnea test, which is basically dependent on eliciting brain stem respiratory center activity by inducing carbon dioxide retention. Failure to do so is consistent with brain stem death.
Other ancillary tests:
Are indicated when apnea test is not available to be performed or physician is not satisfied.
These Include, blood flow or rain electricity tests, such as CT angiography, cerebral dopplar or EEG.
Peculiar conditions have to be present in order to have proper performance.
Consequences of brain death:
1-Cushing effect :damage to medulla would be resultant in bradycardia and hyper tension.
2-Catecholamin surge with consequent tachycardia and hypertension.
3-vasidilation and hypotension.
The challenge in the management is to keep normal blood pressure with inotropes and fluid management to insue proper perfusion of the organs.
4-pulmonary circulation:
Soaring of pulmonary artery hydrostatic pressure might result in endothelial damage with subsequent respiratory distress syndrom perpetuated by adrenalin surge. Management involved ventilatory support with smooth parameters.
Endocrinologically, several perturbations were reported after brain death including:
1-Posterior pituitary function lost early with resultant diabetes inspidus.
2-thyroid hormon deficiency with sick thyroid status supervene.
3-Insuline deficiency with hyperglycemia.
Other changes featured in the context of brain death:
Hypothermia
Severe systemic Inflamatory response
DIC.
Management has to entail hormonal replacement and supportive measures to prevent other complications.
Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible.
Definition of the American Association of Neurology (AAN) of brain death:
1- cessation of the functions of the brain including the brainstem
2- coma or unresponsiveness
3- apnea
In India, the Transplantation of Human Organ Bill was introduced in the Lok Sabha on 20th August 1992 and
became the Transplantation of Human Organ Act in 1994.
Brain death organ donation now becoming increasing field.
In India the deceased donor organ donation rate is
0.26 per million, while USA at 25.6 per million, UK
at 18.3 per million and Spain at 32 per million. Brain death tests:
1- Presence of coma
2- Absent brain stem reflexes
3- Apnea test: testes the brain stem respiratory center at high levels of carbon dioxide. The patient should be normothermic (core temperature ≥36.5°C), hemodynamically stable (systolic pressure
≥100 mmHg), free from sedative and paralytic drugs, with normal oxygenation (PaO2 ≥200 mmHg
after 100% oxygenation) and near normal PaCO2
(35-45 mmHg).
Apnea test should be done twice before certification of brain death. Additional tests for brain death diagnosis:
1- The conventional 4 vessel digital subtraction
angiography is the gold standard for CBF documentation.
Brain death is confirmed by demonstrating the absence of Intracerebral filling at the level of the carotid bifurcation or vertebral arteries.
2- Computerized tomography (CT) angiography also can be used.
3-Transcranial Doppler is used in ICU
4-EEG.
The AAN recommends that the physician can decide against a declaration of brain death rather than ordering ancillary tests if the clinical findings are unreliable. Care of the Potential Organ Donor:
1- Maintenance of BP with minimal use of inotropes
2- Optimal fluid management
3- Good maintenance of organ perfusion
4- Optimal ventilator management
5- Hormonal replacement like insulin, thyroxin, antidiuretic hormone, corticosteroid
6- Optimal temperature control.
All these measures will improve outcomes following transplantation.
Overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations. But infections with human immunodeficiency-virus, herpetic meningio-encephalitis and T-cell leukemia-lymphoma virus prevent organ donation.
Continuation of organ support in a pregnant
patient who is brain-dead is controversial.
A systematic review of brain death during pregnancy has
concluded that the mother should be supported until the
delivery of the fetus and then can be considered for organ donation.
The preoperative donor screening for viruses may be
missed in the first 2 weeks of infection. Transmission of HIV and rabies from infected donors has been documented. Conclusion:
“Care of the donor” is essentially “the simultaneous care of multiple recipients.”
The recognition and acceptance of brain death, awareness amongst public is a major support to organ donation and will improve the numbers
and quality of donor organs.
I
abosaeed mohamed
2 years ago
– Brain death is a state of cessation of cerebral function with irreversible cause . AAN defined brain death with 3 cardinal signs , cessation of brain function including brain stem , coma or unresponsiveness & apnea .
>>Clinical testing of brain death :
1- Coma : absence of response to noxious stimulus ( supra orbital pressure or pressure on nail bed ) with the exception of spinally mediated reflexes .
2- Absent brain stem reflexes with dilated fixed pupil & absent cranial nerve reflexes for > 4hrs .
– Clinical tests for brain death :
Absent pupillary light reflex , absent corneal reflrex , absent refelexes in the face & maxillary region , absent oculocephalic reflex( dolls eye movement ) absent oculo vestibular reflex & absent gag reflex & larengeal reflex .
3- Apnea test : the aim is to check for the brain stem respiratory center at high levels of blood carbon dioxide .it necessitates that patient is normothermic (temp>36.5 ) , hemodynamically stable (SBP>100 mmhg) , free of sedation & paralytic drugs , with normal oxygenation (pao2 >200 mmhg after 100 % oxygenation )& near normal paco2 (35-45 mmhg ) . certification of brain death is after the second apnea test .
– Ancillary tests can be used if uncertain neurological evaluation or if apnea test can not be performed like cerebral blood flow , transcranial doppler , electro encephalography & cerebral tissue perfusion for documentation of brain stem death .
– Brain dead organ needs the same integrity of care & TTT directed to organ perfusion & improved quality of the graft .
>> Pathophysiological changes following brain death :
– Bradycardia & HTN with increased level of catecholamines .
– Rise in pulmonary hydrostatic pressure with damage to pulmonary endothelium & pulmonary edema .
– Posterior piyutary function Is lost early , anterior pituitary preserved for slightly longer period , thyroid hormones decreased with hyperglycemia & hypothermia .
– Systemic inflammatory response is severe & DIC .
>>protocols for donor management :
– General principle of rule of 100 suggesting targets SBP>100 mmhg , UOP>100 ml/h , HB>100g/l , pao2 >100 mmhg & Bl.sugar at 100% of normal , others are :
1- temperature >35
2- fluid management , preferably with ringers acetate or half normal saline with NAHCO3 .
3- inotropic support , dopamine is the first choice
4- ventilatory management , The lowest FiO2 needed should be used
5- replacement hormones , vasopressin , methylprednisolone , insulin & thyroxine .
>>conclusion :
– care of the donor is essential . the barriers exist in limited resource environments like time to diagnosis & the cost.
– we have to raise the awareness , the recognition & the acceptance of brain death to support the deceased organ donation .
This is an excellent summary and analysis, dear Dr Muhamed
KAMAL ELGORASHI
2 years ago
Brain death and care of organ donor: Introduction:
Brain death defined as state of irreversible loss of cerebral function. American Association of Neurology(AAN), has 3 cardinal signs of diagnosing brain death, cessation of functions of the brain, coma, and unresponsiveness and apnea. Clinical testing of the brain death:
Coma; loss of response to stimulus, with the exeption of spinal reflexes.
absent brain stem reflexes.
Apnea test.
Troubleshooting during performing Apnea test;
SBP </100 mmHg, vasopressors, inotrope, and fluid blouses, abort taest if SBP<90 mmHg.
O2 sat not maintained during apnea test, stop if < 88%
hypothermic patient <36.5F
Repeated desaturation of patient.
Baseline PaCO2>/40 or </35.
Ancillary Tests to establish brain death:
To document cerebral blood flow and evaluate the electrical activity of the brain.
4 vessel digital subtraction angiography is the gold standard for CBF.
CT angiography.
Transcranial doppler.
EEG
Pathophysiological changes following brain death and its relevance to organ preservation;
Fluctuating hemodynamics during the time till patient being diagnosed as brain death affect organ for donation,;
CVS;
Cushing reflexes; reflex hypertension and bradycardia, from medullary ischemia, lead to intense vasoconstriction, and tachycardia which lead to incearse visceral and vascular ischemia.
Goal is to maintain organ perfusion by optimizing BP, with minimum inotropes and fluid management.
ECHO is indicated in all potential donor and PAC in indicated in donors with EF <45%.
Respiratory system;
Endogenous epinephrine cause pulmonary edema, so minimum FiCO2 has to be used to maintained saturation and other parameters within target.. Endocrine system, stress and metabolic responses;
posterior pituitary lost earlier in brain death causing DI, with polyuria and hypernatremia.
Decrease thyroid hormone similar to thick euthyroid state.
Worsened hyperglycemia with the stress, with resultant risk of pancreatic damage, which may affect pancreatic graft.
Defective hypothalamic function .with early hyperthermia followed by hypothermia.
Activated inflammatory cascade and possible cytokines storm, may lead to poorer graft survival. Protocol donor management;
Temperature ; core temp,> 35.
Fluid management best used crystalloid ( ringer, half normal saline, better than normal saline ), avoid overload and dehydration .
CVS; dopamine first choice in hypotension unresponsive to volume, and has beneficial effects on renal graft. avoid Nor-ad >0.5 mcg/kg/min lead to impaired cardiac contractility in transplanted heart .
Ventilator management; The lowest FiO2 needed to be used, and optimal PEEP with restrictive fluid strategy improved graft harvesting for lung transplant.
Replace hormone;( vasopressor, methylprednisolone, insulin and thyroxine)m significantly improved utilizing heart and lung transplants.
Other consideration;
treat infection as sepsis and bacteremia are CI donation.
HIV, T-cell leukemia or lymphoma, preclude donation
Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible.
The American Association of Neurology (AAN) has defined brain death with three cardinal signs, cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
The diagnosis of brain death is clinical and can be confirmed by apnea testing.
Ancillary tests can be considered when the apnea test cannot be completed or is inconclusive.
Reflexes of spinal origin may be present and should not be confused against the diagnosis of brain death.
In India the deceased donor organ donation rate is only 0.26 per million , while USA at 25.6 per million, UK at 18.3 per million and Spain at 32 per million, are well ahead.
————————————————————————————————————————————————————————————————————————————–
. Clinical testing for brain death
Coma: Absence of response to noxious stimulus with the exception of spinally mediated reflexes.
Absent brain stem reflexes (a formal evaluation of the brain stem reflexes is undertaken when the patient has had fixed dilated pupils and absent cranial nerve reflexes for more than 4 h).
Apnea test: The aim of this test is to check for the integrity of the brain stem respiratory center at high levels of blood carbon dioxide.
Include a patient who is normothermic (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralytic drugs, with normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
The test is considere positive if there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO2.
Certification of brain death is after a second apnea testing, the timing of which varies between countries.
The time of death is the time PaCO2 reaches the target value[1] during the second apnea test.
The increase in intracranial pressure (ICP) that accompanies brain death spares the rostral portion beyond the second cervical spine and does not compromise blood supply to this area.
This could be the explanation for complex motor movements at the spinal cord level even after diagnosing brain death.
Ancillary tests can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed.
The conventional 4 vessel digital subtraction angiography is the gold standard for CBF documentation.
Brain death is confirmed by demonstrating the absence of intracerebral filling at the level of the carotid bifurcation or vertebral arteries.
Computerized tomography (CT) angiography has emerged as a safer alternative that can accurately document CBF.
Transcranial Doppler is recommended as an ancillary test and is used in Intensive Care Units (ICU) .
The presence of diastolic reverberation flow and little or no forward flow is diagnostic.
.
Electroencephalography is widely used as an ancillary test for documentation of brain death.
The AAN has discussed the role CT angiography, somatosensory evoked potentials, magnetic resonance angiography and have declared that there is insufficient evidence at this time to determine the accuracy of these tests in confirming cessation of function of the entire brain.
AAN recommends that the physician can decide against a The declaration of brain death rather than ordering ancillary tests if the clinical findings are unreliable.
A potential donor is one who is brain-dead or one with catastrophic brain injury with a clearly expressed intent from the physician and the family to withdraw life support.
The organ procurement organization recently has adopted a “presumptive strategy” in counseling wherein grief counselors communicate with the family with the presumption that organ donation is the natural thing to be done and act both in the interests of the potential donor as well as the pool of recipients.
————————————————————————————————————————————————————————————————————————————–
Pathophysiological changes following brain death and its relevance to organ preservation
The time from a diagnosis to declaration of brain death is complicated by fluctuating donor hemodynamics.
The instability is greater when the time to organ retrieval from the diagnosis of brain death is longer.
Even while ensuring optimum donor care, the inevitable hormonal and inflammatory changes accompanying brain death can result in graft dysfunction and increased chances of rejection.
However,, increased awareness of donor management has contributed to improved outcomes following transplant surgery.
In all patients with brain death, medullar y ischemia associated with brain death causes a reflex hypertension and bradycardia (Cushing’s reflex).
This is a reflex attempt by the body to maintain the CBF.
This is a period of intense vasoconstriction and tachycardia associated with increased circulatory catecholamines, which can increase visceral and myocardial ischemia.
The level of rise in catecholamines is dependent upon the rate of rise in ICP and could be as much as 1000 fold elevation from baseline if the rise in ICP is very rapid.
The effects of the catecholamine surge on the myocardium are an altered metabolism associated with depletion of adenosine triphosphate in the cardiac myocyte.
Documented by the fact that 20-25% brain-dead donors showed evidence of myocardial ischemia and 40% have echocardiographic evidence of myocardial dysfunction.
Subsequent to the catecholamine surge resulting in hypertension is the depletion accompanied by vasodilatation and hypotension, which contributes to the challenges in the maintenance of organ perfusion in brain death.
The goals in the management include:
Maintenance of BP with minimal use of inotropes, optimizing the fluid management and maintenance of organ perfusion.
– An echocardiogram is indicated in all potential donors, and pulmonary artery catheterization (PAC) is indicated for donors with an ejection fraction (EF) <45%, more in the cardiac and lung transplants.
Respiratory system
Excessive fluid resuscitation to correct perfusion can result in pulmonary edema. The use of a PAC may restrict excessive fluid use.
The goals of ventilator management include minimal FiO2 needed to maintain a PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45.
The endocrain system /Stress/ and metabolic responces
Hormone replacement therapy to replace the loss of pituitary function.
The endocrine responses of the body are lost with brain death and form the rationale for hormone replacement therapy for brain-dead patients.
Systemic inflammation response
Mediated by inflammatory mediators from an ischemic brain, ischemic reperfusion injury, metabolic changes that occur during the catecholamine storm and an inadequately restored cardiovascular state.
DIC occurs due to the release of tissue thromboplastin from necrotic brain tissue
————————————————————————————————————————————————————————————————————————————–
Protocols for donor management
The circulatory and biochemical variables are managed by the general principle of the “Rule of 100” suggesting targets
A- Of SBP ≥100 mmHg,
B- Urine output ≥100 ml/h,
C- Hemoglobin of ≥100 g/L,
D- PaO2 ≥100 mmHg and blood sugar targeted at 100% normal.
Other elements of donor management are :
Temperature: The aim is to keep the core temperature >35°C prior to organ donation.
.
Fluid management: These patients are often polyuric and dehydrated which is worsened by a vasoplegic state resulting in central volume depletion.
.
Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft.
Ventilatory management: optimal PEEP with a restrictive fluid strategy improves graft harvesting for lung transplants.
“Care of the donor” is essentially “the simultaneous care of multiple recipients.”
The recognition and acceptance of brain death, awareness amongst public on the eventuality and resources to support the organ donor to improve the number and quality of donor organs will be the immediate goals in our country.
This is an excellent summary and analysis, dear Dr Wadi, as usual for you. Please type headings and sub-headings in bold or underline. That will make it easier to read.
So nice of you, Dr Wadi.
For you excellence is normal.
Rihab Elidrisi
2 years ago
Brian death is defined with unresponsiveness with coma ,including brainstem dysfunction and apnea.
once the brain death happened need to be declared by applying group of tests:
absent of brain stem reflexes
apnea test
absence of noxious stimulus
during performing this test the donor needs to be normothermic and normal oxygenation along with normal o2 saturation and normal pco2 .
if the brain death refluxes failed to be done we can go for ancillary test which include cranial doppler ,EEG, CT Brian angiography or MRI .
A lot of physiological changes associated with brain death includes :
CVs;cushing reflex with systemic hypertension and bradycardia
respiratory system; pulmonary odeama
with brain death all endocrine and hormonal secretion will cease and accordingly the donor will be on hormonal therapy .
This is a good summary, dear Dr Rihab. Please type headings and sub-headings in bold or underline. That will make it easier to read.
Hadeel Badawi
2 years ago
Brain death is defined by the American Association of Neurology (AAN) with three cardinal signs, cessation of the brain’s functions, including the brainstem, coma or unresponsiveness and apnea.
There is a significant difference exists in the criteria and tests used.
Requirements that need to be fulfilled before proceeding with tests.
The cause for unresponsive is incompatible with survival.
Neurological imaging to confirm diagnosis CT brain, MRI, angiography
Exclusion of medical conditions that could account for unresponsiveness.
Exclusion of drugs causes of unresponsiveness.
Normal temperature.
Clinical testing for brain death
1. Coma: Absence of response to a noxious stimulus.
2. Absent brain stem reflexes pupillary light reflex, corneal reflex, reflexes in the face and maxillary region, oculo-cephalic reflex (doll’s eye movement), oculo-vestibular reflex and pharyngeal (gag) and laryngeal (cough) reflex. 3. Apnea test Prerequisites: Normothermia (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralytic drugs, normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) near normal PaCO2 (35-45 mmHg).
The test is considered positive if there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO2. Certification of brain death is after a second apnea testing. The time of death is when PaCO2 reaches the target value during the second apnea test.
Ancillary tests for establishing brain death can be used when uncertainty exists. However, AAN recommends that the physician can decide against a declaration of brain death rather than ordering ancillary tests if the clinical findings are unreliable.
I-Documentation for cerebral blood flow (CBF)
Conventional 4-vessel digital subtraction angiography is the gold standard.
Computerized tomography (CT) angiography
Transcranial Doppler
Cerebral tissue perfusion techniques using technetium 99 m
II-Evaluate the electrical activity of the brain.
EEG
Pathophysiological changes following brain death and its relevance to organ preservation
Even while ensuring optimum donor care, the inevitable hormonal and inflammatory changes accompanying brain death can result in graft dysfunction and increased chances of rejection.
Cardiovascular system
–Medullary ischemia causes Cushing’s reflex. (reflux HTN and bradycardia).
-Followed by a period of intense vasoconstriction and tachycardia associated with catecholamine surge resulting in hypertension which can increase visceral and myocardial ischemia.
– After the depletion accompanied by vasodilatation and hypotension.
An echocardiogram is indicated in all potential donors, and PAC is indicated for donors with an EF <45%, more in the background of cardiac and lung transplants.
The goals in the management include maintenance of BP with minimal use of inotropes, optimizing fluid management and maintenance of organ perfusion.
Respiratory system
Excessive fluid resuscitation to correct perfusion can result in pulmonary edema. The use of a PAC may restrict excessive fluid use.
The endocrine system, stress and metabolic responses.
Hormone replacement therapy to replace the loss of pituitary function.
Systemic inflammatory response
Mediated by inflammatory mediators from an ischemic brain, ischemic reperfusion injury, metabolic
changes that occur during the catecholamine storm and an inadequately restored cardiovascular state.
DIC occurs due to the release of tissue thromboplastin from necrotic brain tissue.
Protocols for donor management.
“Rule of 100” suggests targets of SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and BSL targeted at 100% normal.
Temperature: keep temperature >35°C prior to organ donation. Circulating hot air blankets or warmed intravenous fluids.
Fluid management:
A restrictive strategy with monitoring of filling pressures with a PAC, particularly in lung transplants.
Crystalloids are the first choice and balanced salt solutions
Replacement of blood and blood products could follow guidelines for the care of the critically ill, and a hemoglobin of 10 g/L could improve tissue oxygenation indices.
Inotropes and the cardiovascular system:
Dopamine is the first choice of inotrope in hypotension, unresponsive to volume and has beneficial effects on the renal graft are probably related to the moderation of preservation injury and inflammation.
Noradrenaline in doses >0.05 mcg/kg/min resulted in impaired cardiac contractility in transplanted hearts
and in particular, impairment of right ventricular performance.
Ventilatory management;
The goals of ventilatory management include:
– minimal FiO2 needed to maintain a PaO2 >100 mmHg
– SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45.
– Tidal volumes similar to those used for ALI to be used for lung transplant
Replacement of hormones
The recommended replacements are:
a. Vasopressin
b. Methylprednisolone
c. Insulin infusion to maintain blood glucose between 80-150 mg.
d. Thyroxine (T4), Tri-iodothyronine (T3)
Other concerns and considerations
Overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations.
However, infections with HIV, herpetic meningoencephalitis and T-cell leukemia-lymphoma virus preclude organ donation.
This is an excellent summary and analysis, dear Dr Hadeel. Yes, it is level 5 evidence.
Isaac Abiola
2 years ago
SUMMARY
Introduction
The growing concern for scarcity of organs for donation has brought about the legalization of retrieval of organs from dead donors, but this has also come up with challenges like truly certifying the person is dead and the preservation of the organs to make viable after transplantation. The diagnosis of brain dead is fulfilled after meeting certain stringent criteria in many parts of the world
The Clinical Testing for Brain Dead
absent response to noxious stimulus except spinal mediated reflexes
absent brain stem reflexes
positive apnea test
In the event of uncertainty on brain dead, the following ancillary tests can be used
electroencephalography
transcranial doppler
cerebral angiography
scintigraphy
Care of potential organ donors
Following an irreversible traumatic brain injury, grief counsellors are deployed to communicate with the family the benefits of early organ donation which will enhance perfusion and preservation of the organ through use of inotropes and other hormones. This will ultimately reduce waiting pool and of great benefit to the recipients. Great attention is paid to systems like, cardiovascular, respiratory, endocrine with prevention of infection, temperature instability or fluctuating hemodynamics.
Protocols for Donor managements
Various fluctuation in several systems in the body are managed by rule of 100
SBP >100mmHG
urine output >100ml/hr
hemoglobin > 100g/L
PaO2 > 100mmHg
targeted glucose 100%normal
Other requirements for preservation of organs are:
temperature >35-degree Celsius prior to donation
fluid managements
use of inotropes for cardiovascular system
ventilatory managements
hormone replacements
Conclusion
The importance of brain-dead donor needs to be emphasized the more so as to gain public trust in accepting this as a way to reduce the waiting pool and also to help in early retrieving viable organs.
This is an excellent summary and analysis, dear Dr Issac
Mohamad Habli
2 years ago
Brain death is the termination of brain function for which the immediate cause is recognized and is regarded as irreversible.Brain death is described by the American Association of Neurology (AAN) as the cessation of all brain functions, including those of the brainstem, coma or unresponsiveness, and apnea.
Brain death is a clinical diagnosis. The key criteria for determining brain death are as follows:
1- Complete unresponsiveness- coma
2-No brainstem reflexes
Pupillary response to strong light is absent in both eyes. Typically, the pupils are fixed at a medium to dilated size (4-9 mm)
– Absence of ocular movements utilizing oculocephalic testing and oculovestibular reflex testing
– Insufficient corneal reflexes
–Lack of facial muscular contraction in response to a painful stimulus.
– Absence of the gag and cough reflexes in the pharynx and trachea
3-Permanent apnea An apnea test should be performed to ensure permanent apnea. After disconnecting from the ventilator, oxygen is insufflated through a catheter placed at the level of the carina at a rate of 6.0 L/min. The observer searches for respiration eight to ten minutes after separation. Assuming a rate of rise in PaCO2 of 3 mmHg/min, this will result in a 24 mmHg increase over baseline after 8 to 10 minutes. If there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in people with an increased PaCO2, the test is deemed positive. Brain death is certified following a second apnea test.
Troubleshooting during performance of apnea test
1. Systolic blood pressure (SBP) less than 100 mmHg
2. Failure to maintain oxygen saturation during apnea testing
3.The patient is hypothermic (36.5 degrees Fahrenheit).
4. During apnea testing, the patient continually desaturates or becomes hypotensive.
5. Baseline PaCO2 ≥40 mmHg or ≤35 mmHg
Ancillary tests for establishing brain death
When the reliability of the neurologic examination is unknown or when the apnea test cannot be administered, ancillary tests may be conducted. These tests are categorized into those that measure cerebral blood flow (CBF) and those that assess the electrical activity of the brain.
Care of the Potential Organ Donor
A brain-dead organ donor requires the same level of care, with an emphasis on organ perfusion and the improvement of graft quality. For increased quality of care and titration of inotropes and fluids, intensive care with the use of invasive lines is required.
Pathophysiological changes following brain death and its relevance to organ preservation
The period between a diagnosis thend a pronouncement of brain death is compounded by donor hemodynamic fluctuations.
Cardiovascular system
Medullary ischemia linked with brain death generates reflex hypertension and bradycardia (Cushing’s response) in all individuals with brain death. This is the body’s reflexive effort to sustain CBF. This is followed by a period of acute vasoconstriction and tachycardia accompanied by elevated circulatory catecholamines, which can exacerbate visceral and myocardial ischemia.
Respiratory system
A rise in pulmonary hydrostatic pressure causes damage to the pulmonary endothelium resulting in pulmonary edema that is perpetuated by endogenous epinephrine. The goals of ventilatory management include minimal FiO2 needed to maintain a PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45.
Endocrine system, stress and metabolic responses
The endocrine responses of the body are lost with brain death and form the rationale for hormone replacement therapy for brain-dead patients.
Systemic inflammatory response
There is a systemic inflammatory reaction that may be fairly severe. This is caused by inflammatory mediators from an ischemic brain, ischemic reperfusion damage, metabolic alterations during the catecholamine storm, and an insufficiently recovered circulatory state.
Protocols for donor management
The circulatory and biochemical variables are managed by the general principle of the “Rule of 100” suggesting targets of SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted at 100% normal.
Other concerns and considerations
Barring overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations.[52] However, infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus preclude organ donation
This is an excellent summary and analysis, dear Dr Habli. Please type headings and sub-headings in bold or underline. That will make it easier to read.
Sherif Yusuf
2 years ago
Brain death is defined as the triad of coma, cessation of the function of brain death and apnea
Coma:
No response (motor, verbal, eye opening) to painful stimuli, spinal reflexes are not included
Cessation of brain stem function:
Confirmed by absent brain stem reflexes for more than 4 hours
Brain stem reflexes includes pupillary, corneal, oculo-cephalic reflex, oculo-vestibular, gag and cough reflexes
After brain death, the function of the spinal cord is usually preserved with subsequent occurrence of reflexes in response to stimulation
Apnea:
Apnea test is done to confirm the presence of apnea
Patient should have normal temperature, vitally stable, normal oxygenation (PaO2 ≥200 mmHg with 100% oxygen), normal PaCO2 and all sedatives and paralytic drugs should be withheld
Technique: ABG is done first , patient is disconnected from ventilator and given only O2 at 6L/min, then observed for the respiratory muscle movement and ABG is repeated after 8-10 min
Positive test: if no respiratory movement observed over 8-10 min with PaCO2 ≥ 60 or 20 mmHg above baseline if the baseline PaCO2 is ≥40 mmHg or ≤35 mmHg
Death certificate is written if 2 apnea tests are positive
Problems during apnea test includes, hypotension with SBP ≤100 mmHg (treated by IV fluids, vasopressors), Hypoxia, the test should be terminated if O2 saturation ≤85% for more than 30 seconds, and can be repeated on T piece with positive pressure of 10 cm H2O and oxygen of 12.0 L/min.
If apnea test cannot be done or there is problems during the test that interfere with the result, other ancillary tests should be considered for confirmation of brain death (although all are not reliable) including EEG (isoelectric pattern), cerebral angiography, transcranial Doppler and scintigraphy
Pathophysiological changes after brain death and its management
Cardiovascular system
Following brain death the patient typically develop massive sympathetic discharge (autonomic storm) manifested as hypertension and tachycardia and myocardial ischemia then followed by hypotensive stage and in some cases vasoplegia which is manifested by low SVR associated with normal COP
Hypertensive stage is managed by low dose of short acting beta blockers such as esmolol
Hypotension is managed by IV crystalloids (ringers lactate or half normal salien) since the patient is usually polyuric and has tendency for hypernatremia, Hydroxyethylstarches should not be used due to the possibility of AKI, blood transfusion may be needed if HB less than 10 gm/dl
Persistent hypotension is treated by vasopressors (dopamine is preferred over norepinephrine) and desmopressin if there is vasplegia
If there is still hypotension the patient should be evaluated for cardiovascular disease
Respiratory system
Rise in pulmonary venous pressure can lead to pulmonary edema which can be exacerbated by fluid resuscitation
Target PaO2 >100 mmHg, O2 saturation of > 95% and PaCO2 of 35-45 mmHg and pH 7.35-45 should be achieved using the lowest FIO2
Metabolic and endocrinological system
Diabetes insipidus (DI) should be treated with vasopressin or desmopressin.
Hypothyroidism due to secondary hypothyroidism or euthyroid sick syndrome, indication for thyroid replacement includes secondary hypothyroidism and it can be given as infusion in any patient with hemodynamic instability or low ejection fraction to improved hemodynamic and prevent cardiovascular collapse
Secondary adrenocortical insufficiency, which can be corrected with steroids, a Methylprednisolone dose of 15 mg/kg should be given immediately after diagnosis of brain death and then every 24 hours
Hyperglycemia which can be avoided by avoiding glucose containing IV fluids, and can be treated by insulin infusion
Fluctuation of temperature due to affection of hypothalamus manifested by hyperthermia followed by hypothermia, hypothermia can be treated by hot air, warm blanckets or iv fluids and adjustment of room temperature, the aim is to keep temperature >35°C
This is an excellent summary and analysis, dear Dr Yusuf
Nahla Allam
2 years ago
Introduction:
The American Association of Neurology (AAN) has defined brain death with three cardinal signs, cessation of the brain’s functions, including the brainstem, coma or unresponsiveness, and apnea.
Clinical testing for brain death
1. Coma: Absence of response to a noxious stimulus.
2. Absent brain stem reflexes, fixed dilated pupils, and absent cranial nerve reflexes for more than four h).
3. Apnea test: (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralytic drugs, with normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
Ancillary tests for establishing brain death:
1- Brain death is confirmed by demonstrating the absence of intracerebral filling at the level of the carotid bifurcation or vertebral arteries. Computerized tomography (CT) angiography
2- Electroencephalography is widely used as an ancillary test for documentation of brain death.
3- Cerebral tissue perfusion techniques
Care of the Potential Organ Donor:
Maintained organ perfusion and improved the quality of grafts.
Patho physiological changes following brain death:
Cardiovascular system medullary ischemia (Cushing’s reflex).
Respiratory system: endothelial injury and pulmonary edema.
The endocrine responses: diabetes insipidus with polyuria. The anterior pituitary functions are preserved for a slightly more extended period of decrease in insulin levels during Hypothermia.
Systemic inflammatory responseDisseminated intravascular coagulation occurs after brain death due to the release of tissue thromboplastin from necrotic brain tissue.
Protocols for donor management
The circulatory and biochemical variables are managed by the general principle of the “Rule of 100, SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted at 100% standard.
1-Temperature: >35°C
2- Fluid management Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate)
3-Inotropes and the cardiovascular system: Dopamine is the first choice
5- Replacement of hormones: insulin, thyroxin, vasopressin, and methylprednisolone.
Ø The recognition and acceptance of brain death, awareness amongst the public on the eventuality, and resources to support the organ donor to improve the numbers and quality of donor organs
Weam Elnazer
2 years ago
Introduction
Brain death is when the brain stops working and the exact cause is known. It is thought to be irreversible.
The American Association of Neurology (AAN) says that brain death is when the brain and brainstem stop working, the person is in a coma or is not responding, and they stop breathing.
Brain death testing
1. Coma: No reaction to painful stimuli (supraorbital pressure or nail bed pressure) save spinally mediated reflexes.
2. Missing brain stem reflexes (when a patient has fixed dilated pupils and absent cranial nerve reflexes for more than 4 h.
3- Apnea: This test checks the brain stem respiratory centre at elevated blood carbon dioxide levels. A normothermic (core temperature 36.5°C), hemodynamically stable (systolic pressure 100 mmHg) the patient is required.
-Apnea test troubleshooting
. Patient’s systolic blood pressure (SBP) 100 mmHg: Administer vasopressors, inotropes, and fluid boluses to maintain BP. If systolic BP is 90 mmHg, the apnea test must be redone.
. Oxygen saturation 85% for more than 30 seconds during apnea testing.
Retest with T-piece, 10 cm H2O constant positive airway pressure, and 12.0 L/min oxygen flow. Reducing PEEP to 5 cm H2O before disconnecting the ventilator helps predict apnea tolerance.
. Hypothermic patient: Apnea testing guidelines are invalid and must be redone after correction.
. Patient frequently desaturates or becomes hypotensive during apnea testing: Consider auxiliary procedures to prove brain death (EEG, cerebral angiography, transcranial Doppler, scintigraphy). India’s legislation on auxiliary testing are unclear.
Pathophysiological changes following brain death :
1-Brain death induces reflex hypertension and bradycardia due to medullary ischemia.
2-A increase in pulmonary hydrostatic pressure damages the pulmonary endothelium, causing pulmonary edema that endogenous epinephrine perpetuates.
3-Early brain death causes diabetes insipidus, polyuria, hyperglycemia,and hypernatremia. Protocols for donor management: –The aim is to keep the core temperature >35°C
-“Rule of 100”: SBP 100 mmHg, urine output 100 ml/h, hemoglobin 100 g/L, PaO2 100 mmHg, blood sugar 100% normal.
-In volume-resistant hypotension, dopamine is the first-choice inotrope.
This is an excellent summary and analysis, dear Waem
Fatima AlTaher
2 years ago
Organ transplantion from brain dead donors is still very limited worldwide but gaining more interest with the improvement in solid organ donation field. The potential donors are either brain dead or suffer catastrophic brain damage and the family and physicians agree to withdraw life support equipment from those patients. Sepsis , bacteria and fungemia are not contraindications for donation except HIV , T cell leukemia lymphoma virus and hepatic meningio -encephalitis.
Diagnosis of brain death is mainly clinical through
1- coma :absence of response to noxious stimuli
2- Absense of brain stem reflexes including light, corneal and doll’s eye reflexes
3- Apnea test that prerequires ( heamodynamic stability , no hypothermia , Pao2 >100)
If apnea test couldn’t be done , other tests as EEG , cerebral angiography and Doppler can be used
Consequences of brain death that can lead to organ dysfunction:
1- Cardiovascular
– Cushing reflex ( reflex hypertension and bradicardia from medulla ischemia) , then hypertension and tachycardia due to excess catecholamines.
2- hormonal changes: loss of endocrinal function requiring replacement with thyroixin , vasopressin, insulin and methylprednisolone immediately after diagnosis of brain death.
3- altered body temperature ( hyperthyrmia followed by hypothyrmia that may cause coagulopathy).
4- Systemic inflammatory response.
Requirements for organ donation: summarized by role of 100
– Po2 100
– Hb 100 gm /dl
– SBP >100 mg/dl
– UOP>100 ml/h
So invasive lines are needed to keep the patient hemodynamics and adequate tissue perfusion using IV fluid therapy ( better ringer lactate , half tonic saline , ringer acetate rather than normal saline )
Also minimize the use of inotropes with dopamine is the preferred inotrope to use.
This is an excellent summary and analysis, dear Dr Fatima. Please type headings and sub-headings in bold or underline. That will make it easier to read.
Mohamed Saad
2 years ago
Brain death and care of the organ donor.
Brain death is defined as cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea. Clinical testing for brain death.
1- Coma: Absence of response to noxious stimulus.
2- Absent brain stem reflexes ( no brain stem function):(Absent pupillary reflexes, absent corneal reflexes, absent cranial motor function, absent gag reflexes & absent vestibule-ocular reflex).
3- Absent respiratory drive No response to hypercapnia (PaCO2 above 6.5 kPa) and apnea test should be repeated twice after unspecified length of time. Troubleshooting during performance of apnea test.
1- Patient’s systolic blood pressure (SBP) ≤100 mmHg:
So inotropic support with isotonic saline needed and the test should be aborted if systolic BP<90 mmhg.
2- Oxygen saturation not maintained during apnea testing: If saturation is ≤85% for more than 30 s, apnea test should be aborted and using T-piece and continuous positive airway pressure of 10 cm H2 O and oxygen flow of 12.0 L/min.
3- Correction of hypothermia.
4- Ancillary tests for confirming brain death (electroencephalography, cerebral angiography, transcranial Doppler and scintigraphy) could be used if patient repeatedly desaturases or becomes hypotensive during apnea testing.
N.B: The AAN recommends that the physician can decide against a declaration of brain death rather than ordering ancillary tests if the clinical findings are unreliable. Care of the Potential Organ Donor.
Hormonal and inflammatory changes accompanying brain death can result in graft dysfunction and increased chances of rejection. Cardiovascular system.
Percentage of 20-25% brain-dead donors showed evidence of myocardial ischemia and 40% have echocardiographic evidence of myocardial dysfunction due to effects of the catecholamine surge which is mainly due to Cushing reflex after brain death and increasing ICP after that patient developed hypotension and vasodilatation which need use of inotropes, optimizing the fluid management and maintenance of organ perfusion.
An echocardiogram is indicated in all potential donors, and pulmonary artery catheterization (PAC) is indicated for donors with an ejection fraction (EF). Respiratory system.
The goals of ventilatory management include minimal FiO2 needed to maintain a PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45. Try to avoid pulmonary edema with excessive fluid to avoid pulmonary endothelial damage to preserve lung or transplantation. Endocrine system, stress and metabolic responses.
Arginine vasopressin and desmopressin can be given as replacements due to loss of posterior pituitary function , strict euglycemia may minimize this risk as hyperglycemia can also affect the outcomes after renal transplantation.
Hypothalamus dysfunction lead to hyperthermia followed by hypothermia which lead to worsen acidosis and coagulopathy, increase the risk for arrhythmias and cold-induced diuresis. Systemic inflammatory response.
Due to release of tissue thromboplastin from necrotic brain tissue that lead to Disseminated intravascular coagulation. Protocols for donor management.
“Rule of 100”suggesting targets of SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted at 100% normal.
1- Temperature: The aim is to keep the core temperature >35°C prior to organ donation. Circulating hot air blankets, and warmed intravenous fluids.
2- Fluid management: crystalloid superior to normal saline and hydroxyethyl starches are contraindicated in organ donor and monitoring of filling pressures with a PAC may be beneficial particularly in the context of lung transplant.
3- Inotropes and cardiovascular system: dopamine is the first choice and Nor-adrenaline in doses >0.05 mcg/kg/min resulted in impaired cardiac contractility in transplanted hearts.
4- Ventilatory management: the lowest FiO2 needed should be used, and optimal PEEP with a restrictive fluid strategy improves graft harvesting for lung transplants this is the consideration in ventilation support.
5- Replacement of hormones after brain death: such as Vasopressin, Methylprednisolone, Insulin 10 U in 50% dextrose and Thyroxine.
Conclusion:
The recognition and acceptance of brain death, awareness amongst public on the eventuality and resources to support the organ donor to improve the numbers and quality of donor organs will be the immediate goals in our country.
Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible. The American Association of Neurology (AAN) has defined brain death with three cardinal signs, cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
Clinical testing for brain death
1. Coma: Absence of response to noxious stimulus (supraorbital pressure or pressure on the nail bed) with the exception of spinally mediated reflexes
2. . 2. Absent brain stem reflexes (a formal evaluation of the brain stem reflexes is undertaken when the patient has had fixed dilated pupils and absent cranial nerve reflexes for more than 4 h).
3. Apnea test: The aim of this test is to check for the integrity of the brain stem respiratory center at high levels of blood carbon dioxide. Prerequisites include a patient who is normothermic (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralytic drugs, with normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
Troubleshooting during performance of apnea test
1. Patient’s systolic blood pressure (SBP) ≤100 mmHg: Vasopressors, inotropes and fluid boluses need to be administered to keep the blood pressure (BP) above the target. The apnea test is aborted if systolic BP is ≤90 mmHg and the test needs to be repeated after stabilization
2. Oxygen saturation not maintained during apnea testing: The apnea testing is terminated if the saturation is ≤85% for more than 30 s.The test can be retried with T-piece and continuous positive airway pressure of 10 cm H2 O and oxygen flow of 12.0 L/min. Reducing the positive end-expiratory pressure (PEEP) to 5 cm H2 O prior to disconnection from the ventilator for apnea testing can predict the tolerance to apnea.
3. Patient is hypothermic (<36.5°F): Guidelines for apnea testing are not valid and needs to be repeated after correction of hypothermia.
4. Patient repeatedly desaturates or becomes hypotensive during apnea testing: One should consider ancillary tests for confirming brain death (electroencephalography, cerebral angiography, transcranial Doppler and scintigraphy). In India, the laws are not clear about the use of ancillary tests.
Ancillary tests for establishing brain death Ancillary tests can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed. However, the clinician will have to use his or her judgment on the use of these tests to support a brain stem death.
Care of the Potential Organ Donor A brain-dead organ donor needs the same intensity of care with the focus of treatment directed toward organ perfusion and improved quality of grafts. Intensive care with the use of invasive lines is mandatory for improved quality of care and titration of inotropes and fluids.
Pathophysiological changes following brain death and its relevance to organ preservation The time from a diagnosis to declaration of brain death is complicated by fluctuating donor hemodynamics. The instability is greater when the time to organ retrieval from the diagnosis of brain death is longer.Even while ensuring optimum donor care, the inevitable hormonal and inflammatory changes accompanying brain death can result in graft dysfunction and increased chances of rejection.However, in the last two decades, increased awareness of donor management has contributed to improved outcomes following transplant surgery
Cardiovascular system In all patients with brain death, medullary ischemia associated with brain death causes a reflex hypertension and bradycardia (Cushing’s reflex). This is a reflex attempt by the body to maintain the CBF. Subsequent to this is a period of intense vasoconstriction and tachycardia associated with increased circulatory catecholamines, which can increase visceral and myocardial ischemia.
Respiratory system A rise in pulmonary hydrostatic pressure causes damage to the pulmonary endothelium resulting in pulmonary edema that is perpetuated by endogenous epinephrine. The goals of ventilatory management include minimal FiO2 needed to maintain a PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45. Earlier recommendations suggested liberal tidal volumes 8-15 ml/kg, but currently ventilation strategies similar to those used for acute lung injury (ALI) are recommended and have improved the use of lungs for transplant
Endocrine system, stress and metabolic responses The endocrine responses of the body are lost with brain death and form the rationale for hormone replacement therapy for brain-dead patients. The posterior pituitary function is lost early in brain death with occurrence of diabetes insipidus with polyuria and hypernatremia. Arginine vasopressin and desmopressin can be given as replacements. The anterior pituitary functions are preserved for a slightly longer period. Thyroid hormone levels decrease and a state similar to the sick euthyroid state in critical illness can occur.
Systemic inflammatory response Brain death and care of the organ donor A systemic inflammatory response occurs and could be quite severe. This is mediated by inflammatory mediators from an ischemic brain, ischemic reperfusion injury, metabolic changes that occur during the catecholamine storm and an inadequately restored cardiovascular state. Increased plasma levels of interleukin-6 in the donor have translated to the poorer graft utilization and graft dysfunctions.
Protocols for donor management The circulatory and biochemical variables are managed by the general principle of the “Rule of 100”suggesting targets of SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted at 100% normal. Other elements of donor management are listed below:
1. Temperature: The aim is to keep the core temperature >35°C prior to organ donation. Circulating hot air blankets, warmed intravenous fluids and adjustments of ambient temperature may be needed to achieve this goal.
2. Fluid management: These patients are often polyuric and dehydrated which is worsened by a vasoplegic state resulting in central volume depletion. Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline as they do not produce hyperchloremic acidosis.Uncorrected hypernatremia could result in graft losses after liver transplant. Hydroxyethylstarches are contraindicated in organ donors because they can damage renal epithelial cells and cause early graft dysfunction in the transplanted kidneys.There is little evidence to date supporting the use of gelatins in donors. A restrictive strategy with monitoring of filling pressures with a PAC may be beneficial particularly in the context of lung transplant. Studies have documented the impact of fluid loading on outcomes in lung transplantation. This does not affect the quality of the renal graft for transplantation.Replacement of blood and blood products could follow guidelines for the care of the critically ill and a hemoglobin of 10 g/L could improve tissue oxygenation indices.
3-Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft. Though it has no renal protective effect and may predispose to arrhythmias, the benefits are probably related to moderation of preservation injury and inflammation, donor cardiovascular effects, or recipient treatment. Nor-adrenaline in doses >0.05 mcg/kg/min resulted in impaired cardiac contractility in transplanted hearts and in particular impairment of right ventricular performance.
4. Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment). The lowest FiO2 needed should be used, and optimal PEEP with a restrictive fluid strategy improves graft harvesting for lung transplants.
5. Replacement of hormones after brain death: Standardization of hormone therapy after brain death in combination with a central venous pressure <10 mmHg significantly improved utilization of the heart and lungs for transplant without affecting other organ systems. The recommended replacements are:
a. Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h (desmopressin intranasally has a selective action on the V2 receptors and a half-life varying from 6 to 20 h.
b. Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly thereafter.
c. Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg.
d. Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. Tri-iodothyronine (T3) given as a 4-mcg bolus followed by an infusion of 3 mcg/h. T4 improves hemodynamics and prevents cardiovascular collapse in hemodynamically unstable organ donors.
Other concerns and considerations Barring overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations. However, infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus preclude organ donation. Registries supported by the state governments, Tamil Nadu Network of Organ Sharing and Kerala Network on Organ Sharing have substantially increased organ donation in south India.
Conclusion “Care of the donor” is essentially “the simultaneous care of multiple recipients.” The barriers that exist in limited resource environments are the time to diagnosis and the costs involved in sustaining care for the brain-dead donor to the point when consent is obtained. The recognition and acceptance of brain death, awareness amongst public on the eventuality and resources to support the organ donor to improve the numbers and quality of donor organs will be the immediate goals in our country.
Brain death and care of the organ donor
Clinical testing for brain death
Include a patient who is normothermic (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralytic drugs, with normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
The test is considered positive if there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO2.
Certification of brain death is after a second apnoea testing, the timing of which varies between countries.
The time of death is the time PaCO2 reaches the target value during the second apnoea test.
The increase in intracranial pressure (ICP) that accompanies brain death spares the rostral portion beyond the second cervical spine and does not compromise blood supply to this area.
This could be the explanation for complex motor movements at the spinal cord level even after diagnosing brain death.
Ancillary tests for establishing brain death
Ancillary tests can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnoea test cannot be performed.
The conventional 4 vessel digital subtraction angiography is the gold standard for CBF documentation.
Brain death is confirmed by demonstrating the absence of intracerebral filling at the level of the carotid bifurcation or vertebral arteries.
Computerized tomography (CT) angiography has emerged as a safer alternative that can accurately document CBF.
Transcranial Doppler is recommended as an ancillary test and is used in Intensive Care Units (ICU) .
The presence of diastolic reverberation flow and little or no forward flow is diagnostic.
Electroencephalography is widely used as an ancillary test for documentation of brain death.
The AAN has discussed the role CT angiography, somatosensory evoked potentials, magnetic resonance angiography and have declared that there is insufficient evidence at this time to determine the accuracy of these tests in confirming cessation of function of the entire brain.
AAN recommends that the physician can decide against a The declaration of brain death rather than ordering ancillary tests if the clinical findings are unreliable.
Care of the Potential Organ Donor
A potential donor is one who is brain-dead or one with catastrophic brain injury with a clearly expressed intent from the physician and the family to withdraw life support.
The organ procurement organization recently has adopted a “presumptive strategy” in counselling wherein grief counsellors communicate with the family with the presumption that organ donation is the natural thing to be done and act both in the interests of the potential donor as well as the pool of recipients.
Protocols for donor management
The circulatory and biochemical variables are managed by the general principle of the “Rule of 100” suggesting targets
Temperature: The aim is to keep the core temperature >35°C prior to organ donation.
.
Fluid management: These patients are often polyureic and dehydrated which is worsened by a vasoplegic state resulting in central volume depletion. Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline as they do not produce hyperchloremic acidosis.[40] Uncorrected hypernatremia could result in graft losses after liver transplant.
Hydroxyethylstarches are contraindicated in organ donors because they can damage renal epithelial cells and cause early graft dysfunction in the transplanted kidney
Replacement of blood and blood products could follow guidelines for the care of the critically ill and a haemoglobin of 10 g/L could improve tissue oxygenation indices.
Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft. Nor-adrenaline in doses >0.05 mcg/kg/min resulted in impaired cardiac contractility in transplanted hearts and in particular impairment of right ventricular performance.
Ventilatory management: optimal PEEP with a restrictive fluid strategy improves graft harvesting for lung transplants -low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment
Replacement of hormones after brain death
Brain death and care of the organ donor
Introduction Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible.
· The American Association of Neurology (AAN) has defined brain death with three cardinal signs, Cessation of the functions of the brain including the brainstem
· Coma or unresponsiveness
· Apnea.
In India, the Transplantation of Human Organ Bill was introduced in the Lok Sabha on 20th August 1992 and became the Transplantation of Human Organ Act in 1994.[2]
The limited availability of organs amidst a growing demand emphasizes the need for optimal donor care. There is no global consensus in the criteria for establishing brain death, and significant differences exist in the tests used.
In many countries, including India, the diagnosis of brain death is made after fulfilling the mandatory criteria and by the apnea testing which is a safe technique for documentation.
The deceased donor organ donation rate in
· India 0.26 per million
· USA at 25.6 per million
· UK at 18.3 per million
· Spain at 32 per million
are well ahead. A checklist of requirements that need to be fulfilled before proceeding with tests for brain death is indicated.
· Proximate cause for unresponsive state that is incompatible with survival
· Neurological imaging to confirm diagnosis
· Exclusion of associated medical conditions that could account for unresponsiveness
· Exclusion of severe acid-base, metabolic or electrolyte abnormalities
· Exclusion of drugs causing unresponsiveness Sedatives, narcotics, muscle relaxants. In drug overdose allow time for 5 half-lives/measure drug levels
· Normal temperature Core temperature >32°C/90°F
Clinical testing for brain death
1. Coma: Absence of response to noxious stimulus (supraorbital pressure or pressure on the nail bed) with the exception of spinally mediated reflexes.
2. Absent brain stem reflexes (a formal evaluation of the brain stem reflexes is undertaken when the patient has had fixed dilated pupils and absent cranial nerve reflexes for more than 4 h.
lists the individual tests for brain stem reflexes.
3. Apnea test: The aim of this test is to check for the integrity of the brain stem respiratory center at high levels of blood carbon dioxide.
Prerequisites include a patient who is normothermic (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralytic drugs, with normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
Oxygen is insufflated through a catheter placed at the level of the carina at 6.0 L/min after disconnection from the ventilator. The observer looks for respiratory movements at 8-10 min after disconnection. Assuming a rate of rise in PaCO2 of 3 mmHg/min,[10] this will result in an increase of 24 mmHg above baseline in 8-10 min.
The test is considered positive if there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO2 .
Certification of brain death is after a second apnea testing, the timing of which varies between countries.
· UK legislation states that the second test can be done at any time after the first when the blood gases have normalized.
· In USA, suggest the performance of the apnea test after giving appropriate time for confirming absence of brain recovery and the use of only one apnea test.
· In India, the apnea test needs to be repeated after an interval of 6 h and certified by four physicians from a recommended panel, one of whom has to be a neurologist.
The time of death is the time PaCO2 reaches the target value during the second apnea test.
The increase in intracranial pressure (ICP) that accompanies brain death spares the rostral portion beyond the second cervical spine and does not compromise blood supply to this area.
Troubleshooting during performance of apnea test
1. Patient’s systolic blood pressure (SBP) ≤100 mmHg: The apnea test is aborted if systolic BP is ≤90 mmHg and the test needs to be repeated after stabilization.
2. Oxygen saturation not maintained during apnea testing: The apnea testing is terminated if the saturation is ≤85% for more than 30 s.
3. Patient is hypothermic
4. Patient repeatedly desaturates or becomes hypotensive during apnea testing.
5. Baseline PaCO2 ≥40 mmHg or ≤35 mmHg.
Ancillary tests for establishing brain death
Ancillary tests can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed.
These tests are classified as tests that document cerebral blood flow (CBF) and those that evaluate the electrical activity of the brain.
1. The conventional 4 vessel digital subtraction angiography is the gold standard for CBF documentation.
2. Computerized tomography (CT) angiography has emerged as a safer alternative that can accurately document CBF.
3. Transcranial Doppler.
4. Electroencephalography
5. Cerebral tissue perfusion techniques using technetium 99 m hexamethylpropylene amine oxime labeled brain perfusion study
The AAN recommends that the physician can decide against a declaration of brain death rather than ordering ancillary tests if the clinical findings are unreliable.
Care of the Potential Organ Donor A brain-dead organ donor needs the same intensity of care with the focus of treatment directed toward organ perfusion and improved quality of grafts.
brain-dead or one with catastrophic brain injury with a clearly expressed intent from the physician and the family to withdraw life support.
Pathophysiological changes following brain death and its relevance to organ preservation
Even while ensuring optimum donor care, the inevitable hormonal and inflammatory changes accompanying brain death can result in graft dysfunction and increased chances of rejection.
increased awareness of donor management has contributed to improved outcomes following transplant surgery.
Cardiovascular system
Respiratory system
Endocrine system, stress and metabolic responses
Systemic inflammatory response
Protocols for donor management
“Rule of 100” suggesting targets of
SBP ≥100 mmHg,
urine output ≥100 ml/h,
hemoglobin of ≥100 g/L,
PaO2 ≥100 mmHg and
blood sugar targeted at 100% normal.
Other elements of donor management are listed below:
1. Temperature: core temperature >35°C prior to organ donation.
2. Fluid management: Crystalloids are the first choice and balanced salt solutions.
3. Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension.
4. Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment). The lowest FiO2 needed should be used, and optimal PEEP with a restrictive fluid strategy improves graft harvesting for lung transplants.
5. Replacement of hormones after brain death:
The recommended replacements are:
· Vasopressin
· Methylprednisolone
· Insulin 10 U in 50% dextrose followed by an infusion
· Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h.
Other concerns and considerations
Barring overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations
infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus preclude organ donation
Continuation of organ support in a pregnant patient who is brain-dead has again been controversial. the mother should be supported until the delivery of the fetus and then can be considered for organ donation
must keep in mind that preoperative donor screening for viruses may be missed in the first 2 weeks of infection. Transmission of HIV and rabies from infected donors has been documented.
II. Brain death and care of the organ donorPlease provide a summary of this article
Introduction:
*Kidney transplantation provide better survival and quality of life than staying on dialysis for (ESRD) patients, which need to increase the donor pool from deceased donor (brain or cardiac death).
*The definition of brain death is a condition in which there is irreversible cessation of cerebral function.
The (AAN) has defined it with three cardinal signs, cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
Clinical testing for brain death
1. Coma: Absence of response to noxious stimulus.
2. Absent brain stem reflexes.
3. Apnea test: To check the integrity of the brain stem respiratory center at high levels of blood carbon dioxide. Normothermic (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralyticdrugs, with normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
Troubleshooting during performance of apnea test
1. Patient’s (SBP) ≤100 mmHg.
2. Oxygen saturation not maintained during apnea testing:The apnea testing is terminated if the saturation is ≤85% for more than 30 s.
3. Patient is hypothermic (<36.5°F): Guidelines for apnea
needs to be repeated after correction of hypothermia.
4. Patient repeatedly desaturates or becomes hypotensive during apnea testing.
5. Baseline PaCO2 ≥40 mmHg or ≤35 mmHg: A rise of ≥20 mmHg above baseline can be considered a positive apnea test in patients with elevated baseline PaCO2.
Ancillary tests for establishing brain death
*Used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed.
* The conventional 4 vessel digital subtraction angiography is the gold standard for CBF.
*The (CT) angiography is safer alternative that can accurately document CBF.
*Transcranial Doppler is recommended as an ancillary
test and is used in Intensive Care Units.
*Electroencephalography is widely used as an ancillary test
for documentation of brain death.
*Cerebral tissue perfusion techniques using technetium 99 m.
Care of the Potential Organ Donor
*Needs the same intensity of care directed toward organ perfusion and improved quality of grafts.
*A potential donor is one who is brain-dead or one with
catastrophic brain injury with a clearly expressed intent from
the physician and the family to withdraw life support.
Pathophysiological changes following brain death and its relevance to organ preservation
Cardiovascular system
Medullary ischemia associated with brain death causes a reflex hypertension and bradycardia (Cushing’s reflex).
Respiratory system
A rise in pulmonary hydrostatic pressure causes damage to the pulmonary endothelium resulting in pulmonary edema that is perpetuated by endogenous epinephrine.
Endocrine system, stress and metabolic responses
The posterior pituitary function is lost early in brain death with occurrence of diabetes insipidus with polyuria and hypernatremia. The anterior pituitary functions are preserved for a slightly longer period. Thyroid hormone levels decrease, decrease in insulin levels, hyperglycemia worsens with stress.
Systemic inflammatory response
Occurs and could be quite severe. DIC occurs after brain death due to the release of tissue thromboplastin from necrotic brain tissue.
Protocols for donor management
The circulatory and biochemical variables are managed by the
general principle of the “Rule of 100” suggesting targets
of SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin
of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted
at 100% normal. Other elements of donor management are listed below:
1. Temperature: The aim is to keep the core temperature
>35°C prior to organ donation.
2. Fluid management: Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline.
3. Inotropes and cardiovascular system: Dopamine is the first
choice of inotrope in hypotension unresponsive to volume
and has beneficial effects on the renal graft.
4. Ventilatory management: The principles are along the
lines of management of ALI (low tidal volume 6-8 ml/
kg, minimum plateau pressure, lung recruitment).
5. Replacement of hormones after brain death:
Standardization of hormone therapy after brain death in
combination with a central venous pressure <10 mmHg improved the heart and lungs for transplant.
without affecting other organ systems.
The recommended replacements are:
a. Vasopressin
b. Methylprednisolone.
c. Insulin.
d. Thyroxine.
Conclusion
“Care of the donor” is essentially “the simultaneous care of multiple recipients.” The recognition and acceptance of brain death, awareness amongst public on the eventuality and resources to support the organ donor to improve the numbers and quality of donor organs in transplantation.
Please provide a summary of this article
Brain death is defined by American Association of Neurology with 3 signs including loss of brain stem functions, coma or unresponsiveness and apnea.
After brain death, spinal cord reflexes may still be present.
clinical diagnosis of brain death is diagnosed by:
1- Coma.
2- Absent brain stem reflexes 4 hours after having dilated fixed pupils and absent cranial nerve reflexes.
3- Apnea test.
4- Other ancillary tests: conventional 4 vessel digital subtraction angiography to document CBF, CTA, transcranial doppler and EEG.
The goals in the management DBD donor till organ retrieval include:
Brain death is irreversible stoppage of cerebral functioning due to a definite cause, clinically defined by the American Association of Neurology (AAN) as apnea (absence of respiratory movement despite rise on PaCO2), brain (including brainstem) function stoppage (absence of pupillary light reflex, corneal reflex, facially and maxillary region reflexes, oculo-cephalic and oculo-vestibular reflexes, and gag and cough reflexes for more than 4 hours), and coma (non-responsive to obnoxious stimuli).
Apnea testing is critical, and needs to be repeated twice before certifying brain death, except in USA where use of only one apnea test is suggested. During performance of apnea test, the systolic blood pressure (SBP) should be kept above 100 mm of Hg, oxygen saturation should be more than 85%, and the patient should not be hypothermic (temperature more than 36.5º F). Ancillary tests should be done if the above conditions are not met. The ancillary tests include tests for cerebral blood flow (CBF), and cerebral electrical activity. CBF can be tested using 4 vessel digital subtraction angiography (gold standard) and CT angiography. Transcranial Doppler as well as brain perfusion studies can also be used. Electroencephalography assesses the electrical activity in brain.
The pathophysiological changes following brain death have a role in organ preservation management. Medullary ischemia causes Cushing’s reflex (hypertension and bradycardia), leading to vasoconstriction and tachycardia, further leading to hypertension (due to increased catecholamines) followed by fall in catecholamines leading to vasodilation and hypotension making it imperative to maintain organ perfusion by optimising BP using minimal dose of inotropes, Ventilatory management includes maintaining PaO2 >100 mm Hg, SpO2 >95%, PaCO2 35-40 mm Hg, and pH 7.35-7.45 using minimal FiO2. Excessive fluid use can be restricted by using pulmonary artery catheter (PAC) insertion, preventing pulmonary edema. Hormone replacement (Arginine vasopressin, desmopressin, and insulin) and maintenance of temperature is required in view of loss of endocrine functions in brain death. Severe systemic inflammatory response and disseminated intravascular coagulation (DIC) can occur post- brain death.
Donor management protocol includes following the ‘rule of 100’ with target of SBP ≥100 mmHg, Hemoglobin ≥100 g/L, PaO2 ≥100 mm Hg, urine output ≥100 ml/hour, and blood sugar targeted at 100% normal. Core temperature should be >35º C, crystalloids and balanced salt solutions should be used for fluid management by monitoring filling pressures using PAC, dopamine can be used in hypotension, optimal ventilatory management (low tidal volume, minimal plateau pressure and lung recruitment), and hormonal replacement (vasopressin, thyroxine, insulin, and methylprednisolone) are essential parts of the management protocol.
Brain death during pregnancy warrants supporting the mother till the delivery of the fetus and proceeding with organ donation after delivery.
Donor care is an essential part of organ transplantation program for optimal graft and patient outcomes.
Brain death and care of the organ donor
▪︎Introduction:
Brain death is a condition which is characterized by cessation of cerebral function wherein the proximate cause is known and is considered irreversible.
The American Association of Neurology (AAN) has defined brain death with three cardinal signs:
1. Cessation of the brain functions including the brainstem.
2. Coma or unresponsiveness
3. Apnea.
In many countries the diagnosis of brain death is made after fulfilling the mandatory criteria and by the apnea testing which is a safe technique for documentation.
▪︎Clinical testing for brain death:
1. Coma: Absence of response to noxious stimulus with the exception of spinally mediated reflexes.
2. Absent brain stem reflexes
3. Apnea test: to check for the integrity of the brain stem respiratory center at high
levels blood CO2. Oxygen is insufflated through a catheter placed at the level
of the carina at 6.0 L/min after disconnection from the ventilator. The observer looks for respiratory movements at 8-10 min after disconnection. A positive test when there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO
Certification of brain death is after a 2nd apnea testing (which varies between
countries).
Troubleshooting during performance of apnea test
1. Patient’s systolic blood pressure (SBP) ≤100 mmHg
2. Oxygen saturation not maintained during apnea testing
3. Patient is hypothermic (<36.5°F).
4. Patient repeatedly desaturates or becomes hypotensive
during apnea testing.
Ancillary tests for establishing brain death
Tests that document cerebral blood flow (CBF) and those that evaluate the electrical activity of the brain eg:
1. The conventional 4 vessel digital subtraction angiography (is the gold standard for CBF documentation).
2. Computerized tomography (CT) angiography.
3. Transcranial Doppler used in ICU
4. Electroencephalography
5. Cerebral tissue perfusion techniques using technetium 99 m hexamethylpropylene amine oxime labeled brain perfusion study
Care of the Potential Organ Donor
* Intensive care with the use of invasive lines is mandatory.
* A potential donor is one who is brain-dead or one with catastrophic brain injury with a clearly expressed intent from the physician and the family to withdraw life support.
Pathophysiological changes following brain death and its relevance to organ preservation Cardiovascular system:
▪︎Reflex HTN and bradycardia (Cushing’s reflex) with subsequent period of intense vasoconstriction and tachycardia associated with increased circulatory catecholamines, which can increase visceral and myocardial ischemia.
▪︎The goals in the management include maintenance of BP with minimal use of inotropes, optimizing the fluid management
and maintenance of organ perfusion.
An echocardiogram is indicated in all potential donors, and pulmonary artery catheterization (PAC) is indicated for
donors with an ejection fraction (EF) <45%
Respiratory syssystem
Pulmonary edema
The goals of ventilatory management include minimal FiO2 needed to maintain a PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45.
Endocrine system, stress and metabolic responses
The endocrine responses of the body are lost with brain death and form the rationale for hormone replacement therapy for
brain-dead patients.
Systemic inflammatory response
occurs and could be quite severe. Increased levels of IL-6 in the donor can leads topoorer
graft utilization and graft dysfunctions. DIC occurs.
Protocols for donor management
The circulatory and biochemical variables are managed by the general principle of the “Rule of 100”. (SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted at 100% normal).
Other elements of donor management are:
1. Temperature: to keep the core temperature
>35°C prior to organ donation.
2. Fluid management: Crystalloids are the first choice and balanced salt solutions may be superior to normal saline
4. Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/kg, minimum plateau pressure, lung recruitment).
5. Replacement of hormones after brain death.
The recommended replacements are:
a. Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h.
b. Methylprednisolone 15 mg/kg immediately after
diagnosis of brain death and 24th hourly thereafter.
c. Insulin 10 U in 50% dextrose followed by an infusion
to maintain blood glucose between 80 and 150 mg.
d. Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. Tri-iodothyronine (T3) given as a 4-mcg bolus followed by an infusion of 3 mcg/h.
Conclusion
▪︎The barriers that exist in limited resource environments are the time to diagnosis and the costs involved in sustaining care for the brain-dead donor to the point when consent is obtained.
▪︎The recognition and acceptance of brain death, awareness amongst public on the eventuality and resources to support the organ donor is very important to expand the donor pool for transplantation.
Brain death is defined as immediate cessation of brain activity wherein the proximate cause is unknown and it is irreversible…The American Academy of Neurology has defined brain death in 3 components namely coma or unresponsiveness, cessation of brain stem reflexes and apnea..
Clinical testing for brain death:
3.Apnea testing is the 3rd and the final component in the brain stem death confirmation…The aim of the test is to test the integrity of the brain stem to high levels of carbon dioxide…Pre requisites for apnea testing includes no hypothermia (core temperature of >36.5C), hemodynamic stability (SBP>100), free from sedative and paralytic drugs, normal oxygenation (pao2 >200mm after 100% oxygenation) and normal PCO2 (35-45mm)..Oxygen is insufflated through ET tube placed at the level of carina at 6l/min after disconnection from the ventilator and allowed the Pco2 to build up…The apnea testing is considered positive if there are no respiratory movements after a PC02 level of more than 60mm or 20mm elevation of PCo2 from the baseline…2 apnea testing need to be done to certify the brain death…The time period between 2 apnea testing varies between all the countries. In the UK there is no time difference between the 2 and can be as soon as possible to facilitate organ retrieval…USA amendments were made and the use of only one apnea test is recommended…
In India minimum of 6 hours is needed between 2 apnea testing and it has to be certified by 4 different physicians including a neurologist…
The raise in the ICP after brain death spares the rostral area of the brain sparing the proximal portion of the spinal cord…This is responsible for the complex spinal reflexes which are intact in the brain death patient….
There maybe various problems while performing the apnea testing…SBP maybe less than 100mm which may have to be maintained by fluids, vasopressors and other inotropes. The oxygen saturation needs to be maintained during the apnea testing.. The test is terminated if the spo2<85% for more than 30 seconds…the test maybe repeated with CPAP of 10cm and oxygen flow at 12l/min.. Core body temperature should be maintained above 36.5C by warming the patient…If the patient repeatedly desaturates or doesn’t tolerate the apnea testing the ancillary tests for Brian stem death needs to be carried out
Digital subtraction angiography is needed to demonstrate absent cerebral blood flow at the level of carotid bifurcation can be used to demonstrate cessation of brain activity…Transcranial doppler can be used in ICU bedside as it is inexpensive, easy tool…But the presence of IC bleed, a surgery bleed and operative dependance makes it difficult to do it for everyone ..Absence of forward flow and presence of diastolic reverberation..An EEG is used as an ancillary testing for brain death.. presence of isoelectric recording over 30 min period over 18 -20 fields is suggestive of brain death ..
The AAN recommends that there is no definite guidelines or standardization to use this tests and can be decided on individual case to case basis….
The pathophysiological changes that a brain death donor undergoes is complicated and this may turn a stable brain death donor to have an unstable hemodynamics leading to cardiac arrest before organ retrieval…
The various protocols in the donor management are basically to follow the rule of 100…SBP>100mm, urine output >100ml/hr, Hb>10gm/dl and PaO2 >100mm of hg..The body core temperature needs to be maintained to >36.5 C by using warm blankets and warming fluids…crystalloids are the fluids of the choice and colloids are avoided in renal transplants as HES could damage the endothelium…Hypernatremia in the donor has reported some poor outcome in Liver transplant patients…Dopamine is the drug of choice if the hypotension is unresponsive to fluids…it has beneficial effects on the heart and although the renal protective effects are not well established it is still preferred…Very high dose of nor adrenaline are associated with myocardial ischemia and maybe deleterious in cardiac transplants….An analysis of the 10 year data from the UNOS shows that combination of thyroid hormones, corticosteroids, insulin and ADH was the best for organ procurement…
The brain death is a state of irreversible complete cessation of function. According to American association of neurology has defined the brain death as cessation of function of brain(1. brainstem, 2. coma, 2. apnea), ancillary testing for confirmation of brain death.
How is care of potential organ donor.
Pathophysiological changes following brain death and its relevance to organ preservation.
Guidelines and protocol for donor management.
Introduction
Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible. The American Association of Neurology (AAN) has defined brain death with three cardinal signs, cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
Clinical testing for brain death
-Absent pupillary light reflex
-Absent corneal reflex
-Absent reflexes in the face and maxillary region
-Absent oculo-cephalic reflex (doll’s eye movement)
-Absent oculo-vestibular reflex
-Absent pharyngeal (gag) and laryngeal (cough) reflex)
Care of the Potential Organ Donor
A brain-dead organ donor needs the same intensity of care with the focus of treatment directed toward organ perfusion and improved quality of grafts. Intensive care with the use of invasive lines is mandatory for improved quality of care and titration of inotropes and fluids.
Pathophysiological changes following brain death and its relevance to organ preservation
-Cardiovascular system
-Respiratory system
-Endocrine system, stress and metabolic responses
-Systemic inflammatory response
Protocols for donor management
Hemodynamic Goals Mean Arterial Pressure ≥ 60 mm Hg Urine output ≥ 1.0 ml/kg/h Left Ventricular Ejection Fraction > 45%
if not met
Inotropes Dopamine ≤ 10 mcg/kg/h Dobutamine ≤ 10 mcg/kg/h
Goals not achieved
Pulmonary Artery Catheter Insertion Goals Cardiac index ≥ 2.4 l/min/m2 Pulmonary Capillary Wedge Pressure (PCWP): 8-12 mm Hg Systemic Vascular Resistance (SVR): 800-1200dynes cm-5 * Trans Esophageal Echocardiography can substitute pulmonary artery catheter for hemodynamic management
*****
Cardiac index < 2.4 l/min/m2
-CVP < 6 mm Hg PCWP < 8 mm Hg >> Fluids
-SVR < 800 dynes cm-5 >> Pressors: Nor epinephrine or Epinephrine ≤ 0.05 mcg/kg/h
-PCWP > 12 mm Hg>.Pressors: Dopamine or Dobutamine ≤ 10 mcg/kg/h Epinephrine < 0.05 mcg/kg/min, diuretics
Conclusion
“Care of the donor” is essentially “the simultaneous care of multiple recipients.”
Introduction
· Brain death is defined as: cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea
· Apnea test is considered positive if there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO2.
· Certification of brain death is after a second apnea testing, the timing of which varies between countries.
Troubleshooting during performance of apnea test
1. Patient’s systolic blood pressure (SBP) ≤100 mmHg. Give inotropes and fluids
2. Oxygen saturation not maintained during apnea testing: if the saturation is ≤85% for more than 30 s, the test should be stopped
3. Patient is hypothermic (<36.5°F)
4. Patient repeatedly desaturates or becomes hypotensive during apnea testing: consider ancillary tests to confirm brain death
5. Baseline PaCO2 ≥40 mmHg or ≤35 mmHg
Ancillary tests for establishing brain death
1.The gold standard test is the conventional 4 vessel digital subtraction angiography
2. Transcranial Doppler is used in ICU
3.EEG after exclusion of sedation and hypothermia
4.Some centres may use Cerebral tissue perfusion techniques
Care of the Potential Organ Donor
· Donor with brain death, needs care focussing on organ perfusion and improve quality of grafts
· The use of invasive lines is a must to improve quality of care and titration of inotropes and fluids
· The hormonal and inflammatory changes accompanying brain death can result in graft dysfunction and increased chances of rejection
· 20-25% brain-dead donors showed evidence of myocardial ischemia and 40% have echocardiographic evidence of myocardial dysfunction, due to increased circulatory catecholamines
· pulmonary edema may occur due to the rise in pulmonary hydrostatic pressure, or excessive fluid resuscitation
· The posterior pituitary function is lost early in brain death with occurrence of diabetes insipidus with polyuria and hypernatremia
· In addition to the decrease in insulin levels, hyperglycemia worsens with stress, alteration in carbohydrate metabolism and use of glucose solutions.
· Temperature regulation in the hypothalamus is affected, manifesting with initial hyperthermia followed by hypothermia.
· A systemic inflammatory response occurs and may have poor outcome on the graft
Protocols for donor management
1. Temperature: The aim is to keep the core temperature >35°C prior to organ donation.
2. Fluid management: Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline as they do not produce hyperchloremic acidosis
3. Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft.
4. Ventilatory management: low tidal volume 6-8 ml/ kg, minimum plateau pressure, use lowest FiO2 and optimal PEEP.
5. Replacement of hormones after brain death:
§ Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h
§ Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly thereafter.
§ Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg.
§ Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. T3 given as a 4-mcg bolus followed by an infusion of 3 mcg/h
CONCLUSION
Brain-dead donor care may help in offering good graft for those waiting for kidney donation, and people should be aware about brain death donation benefits.
This is review article from India defined the elements of the brain death and the care of organs after brain death, there is no universal agreement about the measures for brain death definition However, the AAN (American association of neurology definition of brain death includes the three major components
1 irreversible cessation of the brain including brain stem functions
2. coma
3. apnea
Agenda prior to proceeding with tests for brain death
1.detailes about the primary cause of death
2. imaging like CT, MRI, Angio
3. rule out other medical, electrolytes and metabolic cause including sedation, narcotics and intoxication like drug over dose.
4.normal core temperature > 32 c0 or 90 F
Clinical tests for brain death
1.Coma, absence of response to stimulus exception may have still spinal reflexes
2. Brain stem death tests includes specific multiple clinical tests like absent of light, corneal, cough, gag, oculovestibular and oculocephalic reflexes,
3 Apnea tests to be done when patient is hemodynamically stable with BP systolic > 1oo and normothermic, free of sedative or paralytic drug effects with Pa CO2 35-45mmHG
Ancillary tests can be consider for confirmation of the brain death in case of clinical tests uncertainty and the apnea test can’t be completed includes EEG, cerebral Angio , transcranial Doppler and scintigraphy to assess the cerebral blood flow and electrical brain activities .
Care of the organs after brain death focused on Intensive care to maintain the organ perfusion and improved quality of organs by stabilizing the volume status and hemodynamics in addition to the cardiopulmonary support and hormonal replacement for certain endocrine dysfunction, maintain adequate UOP> 100ML/H and Left ventricular EF above 45%, cardiac index target >2.4l/min/m2
Inflammatory response syndrome dies to catecholamine storm with increased risk of IRI that can impact the graft survival, IL6 level is an indicator of poor outcome upon donation. Pre operative donor Infection screen including active viral infections like, HCV, HSV, HIV, rabies
Conclusion
this narrative review address the limitations and trouble shouting during the care of brain death donors, limitation in access to such type of donors in India as need more public awareness and acceptance in addition to the logistics and infrastructural support including logistics , limited resources and cost of care and handling such type of donors in order to provide adequate and good quality organs.
Introduction
Brain death is a state of cessation of cerebral function wherein
the proximate cause is known and is considered irreversible.
The American Association of Neurology (AAN) has defined
brain death with three cardinal signs:
1. Cessation of the functions of the brain including the brainstem.
2. Coma or unresponsiveness,
3. Apnea
Clinical testing for brain death
1. Coma: Absence of response to noxious stimulus
2. Absent brain stem reflexes.
3. Apnea test.
Troubleshooting during performance of apnea test
1.Patient’s systolic blood pressure (SBP) ≤100 mmHg:
Vasopressors, inotropes, and fluid boluses need to
be administered to keep the blood pressure (BP)
above the target. The apnea test is aborted if systolic
BP is ≤90 mmHg and the test needs to be repeated
after stabilization.
2. Oxygen saturation not maintained during apnea testing:
The apnea testing is terminated if the saturation is ≤85%
for more than 30 s.[1] The test can be retried with T-piece
and continuous positive airway pressure of 10 cm H2O
and oxygen flow of 12.0 L/min. Reducing the positive
end-expiratory pressure (PEEP) to 5 cm H2O prior to
disconnection from the ventilator for apnea testing can
predict the tolerance to apnea.
3. Patient is hypothermic (<36.5°F): Guidelines for apnea
testing are not valid and needs to be repeated after
correction of hypothermia.
4. Patient repeatedly desaturates or becomes hypotensive
during apnea testing: One should consider ancillary
tests for confirming brain death (electroencephalography,
cerebral angiography, transcranial Doppler and
scintigraphy). In India, the laws are not clear about the
use of ancillary tests.
Ancillary tests for establishing brain death
Ancillary tests to be used when there is uncertainty about apnea tests.
Care of the Potential Organ Donor
Brain death donor needs intensive care, despite being clinically dead, to preserve organ perfusion.
Organization of organ procurement has adopted presumptive strategy when counsellor approach the family for donation as the usual scenario and to be in the interest of both donor and recipients.
Pathophysiological changes following brain death and its relevance to hou
Post brain death significant changes affects organ function. Despite improved organ preservation trying to maintain organ function, longer time post brain death could affect its future increased risk of rejection.
Cardiovascular system
Decreased cerebral perfusion after brain death leads to reflex hypertension with brady cardia. This period of intense vasoconstriction leads to myocardial and visceral ischemia, which is followed by hypotension during which organ preservation will be very challenging.
Systemic inflammatory response
Activation of inflammatory response secondary to brain ischemia mediated by IL 6 leads to poorer organ utilization.
Protocols for donor management
Applying rule of 100s to maintain hemodynamics and biochemical parameters:
1. Systolic BP of >100mmHg
2. Urine out put >100ml/hour
3. PO2 > 100mmHg
4. Blood sugar 100% of normal.
5. Hb level >100gm/L
Other elements include:
1. Core temperature >35
2. Fluid management with crystalloid, ringer lactate or sodium bicarbonate with half saline.
3. Inotropes : dopamine is superior to noradrenaline.
4. Ventilatory management applying ALI protocol and restricted fluid strategy.
5. Replacement of hormones including vasopressin, thyroxine and methylprednisone.
kidney transplant is best option for dialysis patients however there is world wide organ shortage. Lack of deceased donor program in different countries is augmenting the problem. Diagnosis of brain death and best possible care of organs has been discussed in this article
The American Association of Neurology (AAN) has defined brain death with three cardinal signs, cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
Clinical testing for brain death is done by checking for
1. Coma: Absence of response to noxious stimulus (supraorbital pressure or pressure on the nail bed) with the exception of spinally mediated reflexes.
2. Absent brain stem reflexes
3. Apnea test
Ancillary tests for establishing brain death
The conventional 4 vessel digital subtraction angiography is the gold standard for CBF documentation. Brain death is confirmed by demonstrating the absence of intracerebral filling at the level of the carotid bifurcation or vertebral arteries.
Computerized tomography (CT) angiography has emerged as a safer alternative that can accurately document CBF.
Transcranial Doppler is recommended as an ancillary test and is used in Intensive Care Units (ICU) as it is simple, easily available and noninvasive.
Electroencephalography is widely used as an ancillary test for documentation of brain death.
The authors have also discussed patho physiological processes following brain death and it’s importance in preservation of different organs.
like cushings reflex, catecholamine surge after rise in ICP. There is also rise in pulmonary hydrostatic pressure leading to pulmonary edema.
The posterior pituitary function is lost early in brain death with occurrence of diabetes insipidus with polyuria and hypernatremia.
Arginine vasopressin and desmopressin can be given as replacements.
The anterior pituitary functions are preserved for a slightly longer period. Thyroid hormone levels decrease and a state similar to the sick euthyroid state in critical illness can occur.
Hyperglycemia and reduced insulin level can affect pancreatic graft.Temperature regulation in the hypothalamus is affected, manifesting with initial hyperthermia followed by hypothermia.
Systemic inflammatory response
A systemic inflammatory response occurs and could be quite severe. This is mediated by inflammatory mediators from an ischemic brain, ischemic reperfusion injury, metabolic changes that occur during the catecholamine storm and an inadequately restored cardiovascular state. Increased plasma levels of interleukin-6 in the donor have translated to the poorer graft utilization and graft dysfunctions.
Protocols for donor management
The circulatory and biochemical variables are managed by the general principle of the “Rule of 100”[39] suggesting targets of SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted at 100% normal.
Other concerns and considerations
Barring overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations.[52] However, infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus preclude organ donation.
Kidney disease is increasing yearly and the donor pool is limited as such measures were taken to see what’s best to increase the donor pool. This is why the investigation of brain death donors started to increase the pool. The article is based on brain death and the care of the organ donor.
With scientific research, brain death is defined as the cessation of the functions of the brain including the brainstem, coma or unresponsiveness, and apnea. There are clinical tests that help to determine brain death and they are:
1) Coma
2) Absent of brain stem reflexes
3) Apnea test
To diagnose brain death there are prerequisites to ensure the validity of the test and are:
1) Normothermic temperature of 36.5 °C
2) Hemodynamically stable with a BP of 100 mmHg
3) Saturation that is PaO2 greater than 200mmHg after a100% O2 and near normal PaCO2 of 35-45 mmHg
Another complimentary test to help complement the diagnosis of brain death and are:
1) Cerebral flow assessment like angiography is the gold standard, transcranial Doppler, computerized tomography.
2) Assessment of electrical brain activity like performing electroencephalography.
3) Others like technetium 99 m to assess electrical activities.
During the brain, death care must be taken to ensure the proper organ perfusion so that the graft quality may be improved. The pathophysiology to preserve organ function,
1) Cardiovascular system: increased visceral and myocardial ischemic, medullar ischemic associated with brain death that can cause reflex hypertension and bradycardia, the decrease of ATP in the cardiac cells, and the depletion of catecholamine flowed by vasodilatation, low pressure that possesses challenges to maintain organ perfusion.
2) The presence of pulmonary edema secondary to increased pulmonary hydrostatic pressure, and excessive fluid resuscitation will worsen pulmonary edema.
3) Posterior pituitary function is lost early causing pathologies like polyuria, diabetic insipidus, etc, the thyroid gland hormone decrease, there is the presence of hyperglycemia that worsens with stress with carbohydrate metabolism alteration, and the dysregulation of the hypothalamus causes temperature failure.
With these changes, the protocol was placed to ensure proper donor management. They are:
1) Temperature: the aim is to ensure the core temperature remains about 35 degrees.
2) Fluid management with crystalloids, possible blood or blood products, and a Hb of 10g/L to maintain tissue oxygenation.
3) Inotropes and CVS: to ensure proper circulation and organ perfusion medication like dopamine and or nor-adrenaline
4) Ventilatory support is provided to ensure there is proper lung perfusion and proper harvesting
5) Hormone replacement after brain death is given to help brain and lung function to better harvest the organs.
There has been great progress in keeping the donor brain dead in recent years and the main related milestone is the definition of the indicative signs of brain death: cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
Among the clinical tests to define brain death we have:
– Coma: Absence of response to noxious stimulus (supraorbital pressure or pressure on the nail bed). Being necessary to exclude movements that could represent spinally mediated reflexes.
– Absent brain stem reflexes: pupillary light reflex, corneal reflex, reflexes in the face and maxillary region, oculo-cephalic reflex, pharyngeal (gag) and laryngeal (cough) reflex)
– Apnea test: Your function is to check for the integrity of the brain stem respiratory center at high levels of blood carbon dioxide.
However, some prerequisites are necessary to perform the exam: A) Normothermic (core temperature ≥36.5°C); B) Hemodynamically stable (systolic pressure ≥100 mmHg); C) free from sedative and paralytic drugs; D) normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
In some cases, the apnea test cannot be started, so auxiliary tests are used to make the diagnosis. These tests should assess the absence of brain flow or brain electrical activity. Among them we have:
A) Cerebral flow assessment: angiography is the gold standard, Transcranial Doppler, Computerized tomography (CT) is an alternative to angiography.
B) Assessment of electrical brain activity: Electroencephalography
Others ancillary tests are under study: CT angiography, somatosensory evoked potentials, magnetic resonance angiography, however, there is not sufficient evidence to determine the accuracy of these tests in confirming cessation of function of the entire brain.
O entendimento das mudanças fisiopatológicas associadas com o morte encefálica têm aumentado a possibilidade to organ preservation. Entre a os principais sistemas atingidos temos:
– Cardiac system: medullary ischemia associated with brain death causes a reflex hypertension and bradycardia (Cushing’s reflex), associados com a concentração de catecholamines. The management include use of inotropes, optimizing the fluid management and maintenance of organ perfusion.
– Respiratory system: a rise in pulmonary hydrostatic pressure causes damage to the pulmonary endothelium resulting in pulmonary edema that is perpetuated by endogenous epinephrine. For this, restrict excessive fluid use and diuretic can be considereds.
– Endocrin system: posterior pituitary function is lost early, because this is common diabetes insipidus with polyuria and hypernatremia, for this arginine vasopressin and desmopressin can be given as replacements. The decrease in insulin levels, hyperglycemia worsens with stress for this glycemic control through protocols is necessary. Temperature regulation in the hypothalamus is affected, manifesting with initial hyperthermia followed by hypothermia, requiring heating
Therefore, protocols for donor management and recognition of brain death are needed to guide multiprofessional groups in intensive care units with the intention of making a greater number of captures possible.
Introduction:
Brain death is a state of cessation of cerebral function wherein the proximate cause is
known and is considered irreversible.
AAN has defined brain death with three cardinal signs,
cessation of the functions of the brain including the brainstem, coma or
unresponsiveness and apnea.
Clinical testing for brain death:
1. Coma: Absence of response to noxious stimulus (supraorbital pressure or pressure on
the nail bed) with the exception of spinally mediated reflexes.
2. Absent brain stem reflexes (a formal evaluation of the brain stem reflexes is
undertaken when the patient has had fixed dilated pupils and absent cranial nerve
reflexes for more than 4 h
3. Apnea test:
Twice done.
Prerequisites include a patient who is
normothermic (core temperature ≥36.5°C),
hemodynamically stable (systolic pressure ≥100 mmHg).
PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
Ancillary tests for establishing brain death:
Classified as tests that document cerebral blood flow: Cerebral angiogram or CTA,
Transcranial Doppler and Cerebral tissue perfusion techniques using technetium 99 m
assess electrical activities.
Care of the Potential Organ Donor:
A brain-dead organ donor needs the same intensity of care with the focus of treatment
directed toward organ perfusion and improved quality of grafts.
Pathophysiological changes following brain death and its relevance to organ
preservation:
Cardiovascular system:
Medullary ischemia leads to hypertension and bradycardia to preserve CBF.
Increase circulatory catecholamines, by vasoconstriction which can increase visceral
and myocardial ischemia, catecholamine surge on the myocardium is an altered
metabolism associated with depletion of adenosine triphosphate in the cardiac myocytes.
Subsequent to the catecholamine surge resulting in hypertension is the depletion
accompanied by vasodilatation and hypotension, which contributes to difficulty. In
maintain perfusion.
Respiratory system:
Raise pulmonary hydrostatic pressure leads to pulmonary edema. Use PAC to maintain
fluids.
Endocrine system, stress and metabolic responses:
posterior pituitary function: diabetes insipidus with polyuria and hypernatremia.
Thyroid hormone levels decrease and a state similar to the sick euthyroid state.
decrease in insulin levels, hyperglycemia worsens with stress, alteration in carbohydrate
metabolism and use of glucose solution.
Temperature regulation in the hypothalamus is affected, manifesting with initial
hyperthermia followed by hypothermia.
Systemic inflammatory response:
Can occurs with ischemia and inflammatory. Changes.
DIC also can happen.
Protocols for donor management :
the “Rule of 100”:
suggesting targets of SBP ≥100 mmHg.
urine output ≥100 ml/h.
hemoglobin of ≥100 g/L,
PaO2 ≥100 mmHg .
and blood sugar targeted at 100% normal.
.1. Temperature: the core temperature >35°C prior to organ donation.
2. Fluid management:
Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate,
Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be
superior to normal saline as they do not produce hyperchloremic acidosis.
3. Inotropes and cardiovascular system: Dopamine is the first choice.
4. Ventilatory support.
5. Replacement of hormones after brain death:
1. Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h.
Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly
thereafter.
c. Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose
between 80 and 150 mg.
d. Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. Tri-iodothyronine (T3)
given as a 4-mcg bolus followed by an infusion of 3 mcg/h.
Brain death: cessation of brain functions including brainstem, coma or unresponsiveness and apnoea.
Clinical testing for brain death:
Hemodynamically stable
Normothermia
Free from sedative and paralytic drugs
PaO2 > 200 mmHg with 100% oxygenation and PaCO2 of 35-45mmHg
How to test:
Ancillary tests:
Test measuring cerebral blood flow:
Conventional 4 vessel digital subtraction angiography
Transcranial Doppler
Test measuring electrical activity of brain
EEG
Protocol for donor management:
Summary:
Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible.
Clinical testing for brain death:
Troubleshooting during the performance of the apnea test:
Ancillary tests for establishing brain death:
Can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed.
These tests are classified as tests that document cerebral blood flow and those that evaluate the electrical activity of the brain.
Pathophysiological changes following brain death and its relevance to organ preservation:
Cardiovascular system:
Respiratory system:
Endocrine system, stress and metabolic responses:
Systemic inflammatory response:
Protocols for donor management:
Brain death definition and confirmation in terms of definition and team diagnosing differ among countries with no rigid consensus criteria. Most countries consider apnea testing mandatory. Clinical testing generally is based on coma evaluation, confirming the absence of brain stem reflexes and apnea tests. Coma is diagnosed by an absence of response to noxious stimuli (supraorbital, nailbed or nipple stimulation etc). Absence of rain stem reflexes (pupillary light reflex, corneal reflex, occulo-vestibular and occulo-cephalic reflexes, gag reflex).
Ancillary tests are needed in case of insufficient neurologic evaluation. The evaluation of cerebral blood flow can be evaluated by transcranial doppler, which may be technically difficult, by CT angiography or radio nuclear studies to show the absence of blood flow in the cranium. ECG can be used as well.
after brain death, the care of potential donors is essential to preserve the function of the organs.
Medullary ischemia may cause reflex HT and bradycardia (Cushing reflex) in an attempt to preserve cranial blood flow. The discharge of catecholamine alters the metabolism in the myocardium and may lead to myocardial ischemia. Hypotension follows. The goal is to maintain BP with minimal use of catecholamine. All potential donors should have Echocardiogram. Pulmonary catheterization is needed in patients with low EF (<45%).
Hemodynamic goals are MAP equal or >60 mmHg and urine output >1.ml/kg/hr, LV EF >45%. PCWP goal is 8-12 mmHg with cardiac index >2.4 L/min/m2. In case of low cardiac index, the CVP and PCWP will help decide fluid and inotropes.
SIRS may occur due to metabolic changes, mediators from the brain and cardiac ischemic reperfusion injury. This may lead to poorer graft utilization.
Protocols for donor management:
The aim of body temperature is >35, crystalloid fluids are used with preferal of plasmalyte ringers and half saline to avoid hypernatremia and hyperchloremic acidosis. Starch-containing volume expanders are contraindicated because they harm the renal epithelium leading to early graft dysfunction. Here the first choice inotrop is Dopamine for fluid nonresponsive hypotension.
Introduction
Deceased organ donation has increased the available donor pool and reduced the waiting time. Brain death has implications for organ donation.
The diagnosis of brain death is clinical. The AAN has defined brain death with 3 cardinal signs:
– Cessation of the functions of the brain including the brain stem
– Coma or unresponsiveness
– Apnea
Clinical testing for brain death include:
– Coma
– Absent brain stem reflexes
– Apnea test.
Prerequisites for the apnea test include:
– Normothermia
– Hemodynamic stability
– No sedatives or paralytic drugs
– PaO2 ≥ 200mmHg
– Near normal PaCO2 (35-45 mmHg)
Oxygen is insufflated through a catheter at the level of the carina at the rate of 6 litres/min after disconnection from the ventilator. The observer looks for respiratory movements at 8-10mm after disconnection.
The test is considered positive if there are no respiratory movements at a PaCO2 of 60mmHg or 20mmHg above baseline in those with an elevated PaCO2.
Certification of brain death is after a second apnea testing. The time of death is the time PaCO2 reaches the target value during the second apnea test.
The prerequisite prior to proceeding with the tests to confirm brain death include:
– Known cause for unresponsiveness that is incompatible with survival
– Neurological imaging to confirm diagnose
– Exclusion of associated medical conditions that could account for unresponsiveness
– Exclusion of drugs causing unresponsiveness
Ancillary tests for establishing brain death:
– Used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed
– 4 vessel digital subtraction angiography is the gold standard for cerebral blood flow documentations
– CT angiography can also be used to safely and accurately document CBF
– Transcranial ultrasound is used in the ICUs and is simple, easily available and non-invasive. The presence of diastolic reverberation flow and little or no forward flow is diagnostic. EEG can also be used as an ancillary test. However, hypothermia and use of sedative drugs has to be excluded.
– Cerebral tissue perfusion techniques using technetium 99m hexamethylpropylene amine oxime labeled brain perfusion study is being used in some centers.
Care of the potential organ donor
A brain dead organ donor needs the same intensity of care with the focus of treatment directed towards organ perfusion and improved quality of graft.
Pathophysiologic changes following brain death:
1. CVS:
a. Reflex HTN and bradycardia in an attempt to maintain CBF. Subsequent to this, is a period of intense vasoconstriction and tachycardia associated with increased catecholamines, which can cause visceral and myocardial ischemia.
b. The goal in the management include maintenance of BP with minimal use of inotropes, optimizing fluid management and maintenance of organ perfusion.
c. An ECHO is mandatory for all potential donors.
2. Respiratory system
a. A rise in pulmonary hydrostatic pressure causes damage to the pulmonary endothelium resulting in pulmonary edema.
b. The goals in ventilator management includes minimal FiO2 to maintain a PaO2 of > 100mmHg, SPO2 > 95%, PaCO2 of 35 to 45mmHg and pH 7.35 to 7.45.
c. Ventilation strategies similar to those used for AKI are now recommended.
3. Endocrine system, stress and metabolic responses
a. Post pituitary function is lost early in brain death resulting in DI
b. Thyroid hormone levels decrease
c. Reduction in insulin levels causes hyperglycemia
d. Loss of hypothalamic function results in initial hyperthermia followed by hypothermia.
4. SIRS
a. SIRS occurs and can be quite severe.
5. DIC
a. DIC can also occur after brain death.
Protocols for donor management
General principle of the ‘Rule of 100’: SBP >100mmHg, urine output >100ml/hour, Hb >100g/L, PaO2 > 100mmHg, and blood sugar >100 mg/dL.
HES is contraindicated in fluid resuscitation as it is known to cause kidney injury.
Replacement of hormones:
1. Vasopressin
a. 1 unit bolus followed by an infusion of 0.5-4.0 units/hour
2. Methylprednisolone
a. 15mg/kg immediately after the diagnosis of brain death
3. Insulin
a. 10 IU in 50% dextrose followed by an infusion to maintain blood glucose between 80-150mg/dL
4. Thyroxine
a. 20mcg bolus followed by infusion of 10mcg/hour.
Conclusion
“Care of the donor” is essentially “the simultaneous care of multiple recipients”.
Please provide a summary of this article
-Brain death is a state of cessation of cerebral function wherein -the proximate cause is known and is considered irreversible.
-It has defined brain death with three cardinal signs, cessation of the functions
of the brain including the brainstem, coma or unresponsiveness and apnea.
-In many countries, the diagnosis of brain death is made after fulfilling the mandatory criteria and by the apnea testing which is a safe technique for documentation.
-Clinical testing for brain death
1. Coma: Absence of response to noxious stimulus (supraorbital pressure or pressure on the nail bed) with the exception of spinally mediated reflexes.
2. Absent brain stem reflexes (a formal evaluation of thebrain stem reflexes is undertaken when the patient has had fixed dilated pupils and absent cranial nerve reflexes for more than 4 h).
3. Apnea test: The aim of this test is to check for the integrity of the brain stem respiratory center at high levels of blood carbon dioxide. Prerequisites include
a patient who is normothermic (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralytic drugs, with normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
-The test is considered positive if there are no respiratory movements at a PaCO2
of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO2.
-Certification of brain death is after a second apnea testing, the timing of which varies between countries.
-The time of death is the time PaCO2 reaches the target value[1] during the second apnea test.
-The increase in intracranial pressure (ICP) that accompanies brain death spares the rostral portion beyond the second cervical spine and does not compromise blood supply to this area.This could be the explanation for complex motor
movements at the spinal cord level even after diagnosing brain death.
-Ancillary tests for establishing brain death
Ancillary tests can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed.
-They are classified as tests that document cerebral blood flow (CBF) and those that evaluate the electrical activity of the brain. The conventional 4 vessel digital subtraction angiography is the gold standard for CBF documentation.
– Computerized tomography (CT) angiography has emerged as a safer alternative that can accurately document CBF.
-Transcranial Doppler is recommended as an ancillary test and is used in Intensive Care Units (ICU) as it is simple, easily available and noninvasive.
-Electroencephalography is widely used as an ancillary test for documentation of brain death
-A brain-dead organ donor needs the same intensity of care with the focus of treatment directed toward organ perfusion and improved quality of grafts.
– The instability is greater when the time to organ retrieval from the diagnosis of brain death is longer.
-The inevitable hormonal and inflammatory changes accompanying brain death can result in graft dysfunction and increased chances of rejection.
-In all patients with brain death, medullary ischemia associated with brain death causes a reflex hypertension and bradycardia (Cushing’s reflex). This is a reflex attempt by the body to maintain the CBF.
-The goals of ventilatory management include minimal FiO2 needed to
maintain a PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45.
-Protocols for donor management
1. Temperature: The aim is to keep the core temperature >35°C prior to organ donation.
2. Fluid management: Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with
sodium bicarbonate) may be superior to normal saline as they do not produce hyperchloremic acidosis.
3. Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft.
4. Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment). The lowest FiO2 needed should be used, and optimal PEEP with a restrictive fluid strategy improves graft harvesting for lung transplants.
5. Replacement of hormones after brain death:
The recommended replacements are:
a. Vasopressin.
b. Methylprednisolone .
c. Insulin
d. Thyroxine
Care of the donor” is essentially “the simultaneous care of multiple recipients.”
The barriers that exist in limited resource environments are the time to diagnosis and the costs involved in sustaining care for the brain-dead donor to the point when consent is obtained.
Introduction
The American Association of Neurology (AAN) has defined brain death with three cardinal signs, cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
The diagnosis of brain death is made after fulfilling the mandatory criteria and by the apnea testing which is a safe technique for documentation.
Ancillary tests for establishing brain death
Ancillary tests can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed.
These tests are classified as tests that document cerebral blood flow (CBF) and those that evaluate the electrical activity of the brain.
AAN recommends that the physician can decide against a declaration of brain death rather than ordering ancillary tests if the clinical findings are unreliable.
Care of the Potential Organ Donor
A brain-dead organ donor needs the same intensity of care with the focus of treatment directed toward organ perfusion and improved quality of grafts. Intensive care with the use of invasive lines is mandatory for improved quality of care and titration of inotropes and fluids.
Pathophysiological changes following brain death and its relevance to organ preservation
The time from a diagnosis to declaration of brain death is complicated by fluctuating donor hemodynamics. The instability is greater when the time to organ retrieval from the diagnosis of brain death is longer.
The goals in the management include maintenance of BP with minimal use of inotropes, optimizing the fluid management and maintenance of organ perfusion .
An echocardiogram is indicated in all potential donors, and pulmonary artery catheterization (PAC) is indicated for donors with an ejection fraction (EF) <45%, more in the background of cardiac and lung transplants.
Protocols for donor management
The circulatory and biochemical variables are managed by the general principle of the “Rule of 100”
>> targets of SBP ≥100 mmHg
>> urine output ≥100 ml/h
>> hemoglobin of ≥100 g/L
>> PaO 2 ≥100 mmHg
>> blood sugar targeted at 100% normal.
Other elements of donor management are listed below:
The recommended replacements are:
a. Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h (desmopressin intranasally has a selective action on the V2 receptors and a half-life varying from 6 to 20 h.
b. Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24 th hourly thereafter.
c. Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg.
d. Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. Tri–iodothyronine (T3) given as a 4-mcg bolus followed by an infusion of 3 mcg/h. T4 improves hemodynamics and prevents cardiovascular collapse in hemodynamically unstable organ donors.
Other concerns and considerations
Infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus preclude organ donation.
In the background of growing enthusiasm to support organ donation and multiple organ transplants one must keep in mind that preoperative donor screening for viruses may be missed in the first 2 weeks of infection. Transmission of HIV and rabies from infected donors has been documented.
This is a review article which discusses assessment and evaluation of brain death and what is optimum care needed to be given to the deceased donor so as to improve graft outcome.
Brain death has been defined by the American association of neurology with three cardinal signs as follows:
Common way of diagnosisng brain death is fulfilling of mandatory criteria and positive apnea test.
CLINICAL TESTING OF BRAIN DEATH
TROUBLESHOOTING DURING PERFORMANCE OF APNEA TEST
Regarding ancillary testing AAN ha declared that there is lack of evidence to determine accuracy of ancillary tests for confirming brain death and recommended that in situation of unreliable apnea test declaration of brain death should be deferred rather than going for ancillary tests.
CARE OF POTENTIAL ORGAN DONOR:
Fluctuating donor hemodynamics and hormonal and inflammatory changes increases the risk of graft dysfunction and / or increased chances of graft rejection. Hence, care of potential deceased donor is very important to preserve the quality of graft.
Cardiovascular system
The main principle is to maintain BP with minimal use of ionotropes and ensuring adequate fluid management and organ perfusion.
Respiratory system
Target ventilatory settings: Minimal FiO2 needed to keep PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45.
pulmonary edema should be prevented with proper fluid management.
Endocrine system
With the brain death the body looses the endocrine responses. Posterior pituitary is commonly affected causing DI, polyuria, hypernatremia. other complications are hyperglycemia due to decreased insulin levels and stress, temperature dysregulation. all this need to be managed actively to provide adequate care.
Systemic inflammatory response
This is primarily due to ischemic injury leading to DIC and coagulopathy if not taken care off.
Temperature, fluid and BP management is key to preventing systemic inflammatory response.
summary
the aricle focuss on the donation from brain death patients
The American Association of Neurology (AAN) has defined brain death with three cardinal signs, cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
test for brain death
1-coma
2-Absent brain stem reflexes
3-Apnea test
4-Ancillary tests
Care of the Potential Organ Donor :
brain-dead organ donor needs the same intensity of care with the focus of treatment directed toward organ perfusion and improved quality of grafts. Intensive care with the use of invasive lines is mandatory for improved quality of care and titration of inotropes and fluids.
Protocols for donor management :
1-Temperature :>35°C prior to organ donation.
2-Fluid management:
Ringer’s acetate is preffered
Hydroxyethylstarches are contraindicated in organ donors because they can damage renal epithelial cells and cause early graft dysfunction in the transplanted kidneys.
3-Inotropes and cardiovascular system :: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft
.
4-Ventilatory management:low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment).
5-Replacement of hormones after brain death:
a. Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h (desmopressin intranasally has a selective action on the V2 receptors and a half-life varying from 6 to 20 h.[20]) b. Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly thereafter. c. Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg. d. Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. Tri-iodothyronine (T3) given as a 4-mcg bolus followed by an infusion of 3 mcg/h. T4 improves hemodynamics and prevents cardiovascular collapse in hemodynamically unstable organ donors.
Confirmation of Brain death
Brain death is defined as
1. Cessation of brain function including brain stem
Tested by Fixed Dilated Pupils and absent brain stem reflex for more than 4 hours
2. Coma
Absent response to painful stimuli (like supraorbital/nailbed pressure)
Exception of spinally mediated reflex
3. Apnea
No response of brain stem to raised PaCo2 (more than 60 or rise of more than 20 above baseline)
Should be Normothermic (≥36.5), Systolic BP≥100, SpO2>85%, near Normal PaCo2, free from sedatives/hypnotics
In India, Apnea test needs to be certified by 4 physicians and repeated after a gap of 6 hours and one out of them must be a neurologist
Ancillary Tests for Brain death:
If Apnea test can’t be performed or ambiguity with neurological examination, tests should be done for evaluating Cerebral Blood Flow and electrical activity of Brain. These tests include
1. DSA/CTA
2. Doppler (Transcranial)
3. Tc99 based nuclear studies for cerebral perfusion
4. EEG
Care of Potential Donor: Goals
1. Normal Blood Gases on minimal FiO2(PaO2>100, PaCo2 35-45, Spo2>95% and pH 7.35-7.45)
2. Maintenance of BP with Adequate fluids (Crystalloids like RL) with Minimal use of Ionotropes (Dopamine, Nor-adrenaline<0.05mcg/kg/min), correction of Hypernatremia
3. Core Temperature more than 35 degree Celsius
4. Hormone Replacement (Vasopressin, Methyprednisolone, Insulin and thyroxine)
5. Caring for infections
Rule of 100 in care of potential Donors
1. SBP≥100mm of Hg
2. Urine Output≥100ml/hr
3. Hb≥100g/L
4. Pa02≥100mm of Hg
5. RBS around 100
Summary
This study is about brain death and care of the organ donor. Brain death is a major influence on the availability of donors for kidney recipients. However, proper maintenance is necessary to preserve the needed organs in a manner that can be used.
Brain death can be defined as a state of cessation of cerebral function wherein the cause is known and cannot be reversed. Three signs that indicate brain death include :
Maintenance of brain dead donor has two major goals – proper perfusion of required organs and improved quality of grafts.
Obtaining consent from guardian is essential to the process of organ donation but along with this the very diagnosis of brain death all takes valuable time away from getting a good quality graft. Hence, quick and decisive action Is needed.,
Care includes :
Clinical testing for brain death
1. Coma
2. Absent brain stem reflexes
• Absent pupillary light reflex
• Absent corneal reflex
• Absent reflexes in the face and maxillary region
• Absent oculo-cephalic reflex (doll’s eye movement)
• Absent oculo-vestibular reflex
• Absent pharyngeal (gag) and laryngeal (cough) reflex)
3. Apnea test
Troubleshooting during performance of apnea test
1. Patient’s systolic blood pressure (SBP) ≤100 mmHg:
2. Oxygen saturation not maintained during apnea testing
3. Patient is hypothermic (<36.5°F):
4. Patient repeatedly desaturates or becomes hypotensive during apnea testing
5. Baseline PaCO2 ≥40 mmHg or ≤35 mmHg
Checklist prior to proceeding with tests for brain death
Prerequisite
• Proximate cause for unresponsive state that is incompatible with survival (Major trauma, intracranial bleed with midline shift)
• Neurological imaging to confirm diagnosis (CT brain, MRI, angiography)
• Exclusion of associated medical conditions that could account for unresponsiveness
• Exclusion of severe acid-base, metabolic or electrolyte abnormalities
• Exclusion of drugs causing unresponsiveness (Sedatives, narcotics, muscle relaxants. In drug overdose allow time for 5 half-lives/measure drug levels)
• Normal temperature Core temperature >32°C/90°F
Ancillary tests for establishing brain death
• Ancillary tests can be used when uncertainty exists about the reliability of the neurologic evaluation or when the apnea test cannot be performed
• conventional 4 vessel digital subtraction angiography is the gold standard for CBF documentation.
• Computerized tomography (CT) angiography
• Transcranial Doppler is recommended as an ancillary
• Electroencephalography is widely used as an ancillary test
Pathophysiological changes following brain death and its relevance to organ preservation
• Cardiovascular system
Cushing’s reflex
The level of rise in catecholamines is dependent upon the rate of rise in ICP
20-25% brain-dead donors showed evidence of myocardial ischemia and 40% have echo evidence of myocardial dysfunction
echocardiogram is indicated in all potential donor
• Respiratory system
A rise in pulmonary hydrostatic pressure causes pulmonary edema
Excessive fluid resuscitation to correct perfusion can result in pulmonary edema
Albuterol has been used for reducing the pulmonary edema
Endocrine system, stress and metabolic responses
• The posterior pituitary function is lost early in brain death( diabetes insipidus ) with polyuria and hypernatremia.
Arginine vasopressin and desmopress for management
• anterior pituitary functions are preserved for a slightly longer period. Thyroid hormone
• decrease in insulin levels, hyperglycemia worsens with stress. Hyperglycemia can also affect the outcomes after renal transplantation.
• Systemic inflammatory response :
Increased plasma levels of interleukin-6 in the donor have translated to the poorer graft utilization and graft dysfunctions.
• Disseminated intravascular coagulation occurs after brain death due to the release of tissue thromboplastin from necrotic brain tissue.
Protocols for donor management
1. the “Rule of 100” suggesting
2. targets of SBP ≥100 mmHg,
3. urine output ≥100 ml/h,
4. hemoglobin of ≥100 g/L,
5. PaO2 ≥100 mmHg
6. blood sugar targeted at 100% normal.
Other elements of donor management are
1. temperature >35°C prior to organ donation. Circulating hot air blankets, warmed intravenous fluids .
2. Fluid management:
Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline
Uncorrected hypernatremia could result in graft losses after liver transplant.
Hydroxyethylstarches are contraindicated in organ donors
4. Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft.
5. Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment). The lowest FiO2 needed should be used, and optimal PEEP with a restrictive fluid strategy improves graft harvesting for lung transplants.
Replacement of hormones after brain death:
The recommended replacements are: a. Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h (desmopressin intranasally has a selective action on the V2 receptors and a half-life varying from 6 to 20 h.
b. Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly thereafter.
c. Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg.
d. Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h.
Tri-iodothyronine (T3) given as a 4-mcg bolus followed by an infusion of 3 mcg/h.
This is a good summary, dear Dr GHalia
I like that you have typed headings and sub-headings in bold or underline. That makes it easier to read.
Brain death and care of the organ donor:
This article done in india focus on care of deceased kidney donor from brain death.
Brain death means cessation of cerebral function and unawareness of persons to surrounding and cessation of respiration and patients should be on ventilation.
4 physicians are involved for diagnosis of brain death; one of them are neurologist.
Criteria of diagnosis of brain death:
If confirmation of brain death is not sufficient advice for CT angiogram to assess cranial blood flow and MRA to confirm diagnosis.
EEG ( electrocephalogram ), to confirm diagnosis.
Care of organ donation:
Maintain fluid balance by central jugular line and pulmonary capillary wedge pressure and intravenous fluid.
Maintain blood pressure on 100/60 and mean arterial pressure above 60mmHg and avoid hypotension by given intropic agents.
Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has good effects on the renal graft.
In case of brain death diabetic inspiduse common so polyuria common; so give vasopressin dose intranasal.
Correct hypothermia by hot blanket.
The care maintenance by role of 100: Systolic blood pressure is more than 100 mmHg, Oxygen saturation is 100, blood sugar above 100, Pco2: 100, heart rate 100.
This is an excellent summary and analysis, Dr Sahar.
I know you have used bold at some places.
Please type headings and sub-headings in bold or underline. That will make it easier to read.
Brain death is a cessation of cerebral function where the cause is known and irreversible.
Checklist before proceeding tests for brain death:
Clinical tests for brain death:
Absent pupillary light reflex
Absent corneal reflex
Absent reflex in face and maxillary area
Absent oculo- cephalic reflex
Absent pharyngeal gag reflex and laryngeal cough reflex
3.Apnea test
Ancillary tests:
Conventional 4 vessel digital subtraction angiography
CT angiography
Transcranial doppler
EEG
Cerebral tissue perfusion technique
Protocol for donor management:
Rule of 100:
SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted at 100% normal. Other elements of donor management are
listed below:
1. Temperature: The aim is to keep the core temperature >35°C prior to organ donation. Circulating hot air blankets, warmed intravenous fluids and adjustments of ambient temperature may be needed to achieve this goal.
2. Fluid management: Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline as they do not produce hyperchloremic acidosis.
3. Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft.
4. Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment).
5. Replacement of hormones after brain death:
The recommended replacements are:
a. Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h (desmopressin intranasally has a selective action on the V2 receptors and a half-life varying from 6 to 20 h.
b. Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly thereafter.
c. Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg.
d. Thyroxine (T4) 20 mcg bolus followed by infusions of 10 mcg/h. Tri-iodothyronine (T3) given as a 4mcg bolus followed by an infusion of 3 mcg/h.
This is an excellent summary and analysis, Dr Tufayel,
Please type headings and sub-headings in bold or underline. That will make it easier to read.
Please provide a summary of this article
Introduction
Definition of death according to the American Association of Neurology (AAN): cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea
Prerequisites before proceeding to tests for brain death are
1. Proximate cause for unresponsive state that is incompatible with survival
2. Neurological imaging to confirm diagnosis
3. Exclusion of associated medical conditions that could account for unresponsiveness
4. Exclusion of drugs causing unresponsiveness
5. Normal temperature
Clinical testing for brain death
1. Coma: no response to noxious stimuli
2. Absent brain stem reflexes: when the pupils fixed and dilated and absent cranial nerve reflexes for more than 4 h. absent of pupillary light reflex, corneal reflex, reflexes in the face and maxillary region, oculo-cephalic reflex, oculo-vestibular reflex, and pharyngeal (gag) and laryngeal (cough) reflex)
3. Apnea test (see below)
Apnea test
Prerequisites are
1. Normothermic (core temperature ≥36.5°C)
2. hemodynamically stable (systolic pressure ≥100 mmHg)
3. No sedative and paralytic drugs
4. Normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation)
5. Near normal PaCO2 (35-45 mmHg)
How to do the apnea test
· Disconnect the ventilator
· Oxygen through a catheter placed at the level of the carina at 6.0 L/min
· Observe for respiratory movements at 8-10 min after disconnection
· If there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline, the test is positive
Certification of brain death is after a second apnea testing (timing varies between countries)
Troubleshooting during performance of apnea test
1. Systolic blood pressure (SBP) ≤100 mmHg: give vasopressors, inotropes and fluid boluses
2. Low oxygen saturation (terminate apnea test if O2 saturation is ≤85%). CPAP and oxygen flow of 12.0 L/min
3. Hypothermia ((<36.5°F). repeat the test after correction
4. Repeated desaturation or hypotension during apnea testing. Do ancillary test (below)
5. Baseline PaCO2 ≥40 mmHg or ≤35 mmHg: reduce frequency of of ventilation in high PaCO2
Ancillary tests for establishing brain death
Indicatinos are: 1.uncertainty of the neurologic tests. 2. When the apnea test cannot be performe
These tests classified into:
1. Tests that document cerebral blood flow (CBF). 4 vessel digital subtraction angiography (gold standard), CT angiography and Transcranial Doppler (in ICU)
2. Tests that evaluate the electrical activity of the brain: EEG (caution with sedatives and hypothermia), Cerebral tissue perfusion techniques using technetium 99 m
Pathophysiological changes following brain death
Cardiovascular system:
· Reflex hypertension and bradycardia (Cushing’s reflex) due to medullary ischemia
· Then intense vasoconstriction and tachycardia (catecholamines)
Respiratory system
· A rise in pulmonary hydrostatic pressure causes damage to the pulmonary endothelium resulting in pulmonary edema
· Ventiatory set-up: minimal FiO2 needed to maintain a PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45
· Avoid excessive fluid (guide with pulmonary artery catheterization)
· Albuterol and diuretics for pulmonary edema
Endocrine system, stress and metabolic responses
· Diabetes insipidus: give arginine vasopressin and desmopressin
· Thyroid hormones: thyroid replacement
· Hyperglycemia: can affect the outcomes after renal transplantation
· Impaired temperature regulation (initially hyperthermia followed by hypothermia)
Systemic inflammatory response
Inflammatory mediators from an ischemic brain, ischemic reperfusion injury, metabolic changes that occur during the catecholamine storm. Increased interleukin-6 (poor graft function). DIC (release of tissue thromboplastin from necrotic brain tissue)
Protocols for donor management
Rule of 100 (SBP ≥100 mmHg, urine output ≥100 ml/h, Hb ≥100 g/L, PaO2 ≥100 mmHg and RBS targeted at 100% normal)
1. Temperature: keep temperature >35°C (Circulating hot air blankets, warmed intravenous fluids and adjustments of ambient temperature)
2. Fluid management: Crystalloids and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate). Blood/blood products
3. Inotropes: dopamine (first choice), if no response to fluids. Doputamine
4. Ventilatory management: low tidal volume 6-8 ml/ kg, minimum plateau pressure, lowest FiO2, and optimal PEEP
5. Replacement of hormones: vasopressin, Methylprednisolone, insulin, and thyroxine
This is a good summary, dear Dr Abdallah,
I like that you have typed headings and sub-headings in bold or underline. That makes it easier to read.
The American Association of Neurology has three cardinal signs for diagnosing brainstem death:
cessation of the brain functions , unresponsiveness and apnea.
Clinical tests of brain death are considered If a patient has a proximate cause for unresponsive state that is incompatible with survival , after exclusion medical conditions, drugs and hypothermia, and the CT MRI confirming his state. These clinical tests include: Coma, absent brain stem reflexes and apnea test.
The apnea test is used to check the integrity of the brain stem respiratory center at high levels of blood CO2. The patient need to have core temperature ≥36.5°C , PaO2 ≥200 mmHg after 100% oxygenation, near normal PaCO2, systolic pressure ≥100 mmHg, free from sedative and paralytic drugs. Positive test is when there is no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above. Two tests need to be performed to certify brain death. Terminate the test if systolic BP is ≤90 mmHg and the test needs to be repeated after stabilization, oxygen saturation is ≤85% for more than 30 s, temperature <36.5°F, baseline PaCO2 ≥40 mmHg or ≤35 mmHg or repeated desaturation during apnea testing. In this case, ancillary tests can be used (electroencephalography, cerebral angiography, transcranial Doppler and scintigraphy). There are classified into:
1- Cerebral blood flow (CBF): conventional 4 vessel digital subtraction angiography which is considered the gold standard test (show absence of intracerebral filling at the level of the carotid bifurcation or vertebral arteries). CTA is a safe alternative. Transcranial Doppler is used in ICU and is considered diagnostic when the diastolic reverberation flow is present and little or no forward flow but it could be affected by many factors,
2- Electrical activity of the brain: Electroencephalography of isoelectric recording from 18 to 20 channels over a 30 min period after exclusion of sedative drugs and hypothermia.
brain death donors need care for organ perfusion and improved quality of grafts. This may involve Intensive care with the use of invasive lines for inotropes and fluids. The donors are subjected to medullary ischemia with a reflex hypertension and bradycardia (Cushing’s reflex). This will cause vasoconstriction and tachycardia due to high circulatory catecholamines that will increase the visceral and myocardial ischemia. This will be followed by catecholamines depletion that will make the maintenance of organ perfusion in brain death a challenge. The goals in the management include:
· maintenance of BP with minimal use of inotropes
· optimizing the fluid management
· maintenance of organ perfusion
All donors need echocardiogram and if ejection fraction is less than 45% they need pulmonary artery catheterization (particularly for cardiac and lung transplants).
The targets of ventilatory management are PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg , pH 7.35-45 and tidal volumes similar to those used for acute lung injury. Avoid excessive fluid resuscitation by the use of a PAC, Albuterol and diuretics.
Those donors are at risk of diabetes insipidus due to loss of posterior pituitary which will result in polyuria and hypernatremia. This can be treated with Arginine vasopressin and desmopressin. The thyroid hormone and insulin are also low with resultant hyperglycemia which may damage pancreatic cells. They are also at risk of hypothermia which will worsen acidosis and coagulopathy leading to arrhythmias .
Systemic inflammatory response can occur due to the release of inflammatory mediators from ischemic tissues with resultant DIC
The targets of donor management are SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg , blood sugar targeted at 100% normal and temperature >35°C prior to organ donation. These can be achieved through the use of crystalloids , balanced salt solutions, replacement of blood and blood products and Dopamine if hypotension is unresponsive to volume expansion.
Ventilatory management includes low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment.
Hormone replacements after brain death include giving Vasopressin, Methylprednisolone, Insulin 10 U in 50% dextrose and Thyroxine.
Preoperative infection screening and exclusion of donors who have infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus .
Regarding pregnancy, the mother should be supported until the delivery of the fetus and then she can be considered for organ donation.
This is an excellent summary and analysis, Dr Hinda
Please type headings and sub-headings in bold or underline. That will make it easier to read.
This article shows the discussion about brain or cardiac death using the AAN Concepts and the reality in India, which is similar to a good part of the countries.
The classic concept of brain death is the cessation of functions such as coma, unresponsiveness (absence of central brain reflexes), and apnea. Increased intracranial pressure can trigger reflexes in the spinal cord.
To rule out brain death, there must be a central reflex (pupillary, corneal, facial, oculocephalic, oculovestibular, pharyngeal, and laryngeal). Neuroradiological tests (USG Doppler, magnetic resonance angiography, technetium scintigraphy, angiography), electroencephalographic (EEG), hypothermia, sedatives, narcotics, hydro electrolytic and acid-base disturbances.
Because it is an extremely multicultural country, with several religions, and great spirituality, the concept of death by brain outcome can be confusing, applying the need for cardiac arrest to officially define death for family members.
In the case of the potentially deceased cardiac donor, we have the Maastricht categories, where brain death has not yet occurred but there is severe irreversible damage (Maastricht 3).
Cardiovascular care of the potential donor involves fluid therapy, and vasopressor drugs (dopamine is preferred) to achieve adequate blood pressure values. On the other hand, the pulmonary condition seeks adequate oxygenation rates, avoiding excess fluid therapy, so some centers use pulmonary catheters for adequate control of fluids, pressure, and volume of oxygen to be made available. Endocrine metabolic care such as diabetes insipidus (desmopressin), vasopressin, glycemic control, and thermal control decrease ischemia and ensure the quality of the organ potentially to be donated. Corticosteroids to decrease the systemic inflammatory response are also discussed in this article.
Maintain a temperature above 35 degrees Celsius, crystalloids with Ringer’s Lactate to prevent hyperchlorhydremia, blood replacement when hemoglobin is less than 10, dopamine for inotropic control, protective ventilation, and hormone replacement to increase the quality of the organ to be donated despite brain death or imminent cardiac arrest. Situations such as infections and active malignant neoplasms are still an exclusion factor.
This is an excellent summary and analysis, dear Dr Philpe.
Please type headings and sub-headings in bold or underline. That will make it easier to read.
Ok professor. I will get better organized
II. Brain death & care of the organ donor
1. Please provide a summary of this article
The AAN defined brain death with 3 main signs:
– Cessation of brain functions that include Brainstem
– Coma or unresponsiveness
– Apnea
Globally great differences exist in criteria & the tests used.
Prerequisites required before testing for brain death include:
Proximate cause for unresponsiveness that is incompatible with survival: Major trauma, intracranial bleed with midline shift.
Imaging to confirm diagnosis: CT brain, MRI, angiography.
Exclude conditions that could account for
unresponsiveness: severe acid-base, metabolic or electrolyte abnormalities.
Exclude drugs causing unresponsiveness: Sedatives, narcotics, muscle relaxants. In overdose allow time for 5 half-lives/measure drug levels.
Normal temperature: Core temp >32°C/90°F.
Clinical testing for brain death
1. Coma: no response to noxious stimulus
(supraorbital pressure or nail bed pressure) with the exception of spinal reflexes.
2. Absent brain stem reflexes:
-Pupillary light reflex: afferent II CN,
efferent III CN nerve
– Corneal reflex: afferent V CN, efferent
VII nerve
– Reflexes in the face & maxillary region: area
by V CN (trigeminal)
– Oculo-cephalic reflex (doll’s eye movement):
afferent VIII, efferent III & VI. Lateral 90°
movements of neck result in deviation of eyes
to opposite direction with an intact brain stem;
rule out cervical spine injury prior to testing
– Oculo-vestibular reflex: afferent is VIII &
efferent III & VI CNs; patient at a 30° head up
position (lateral semicircular canal becomes
vertical),50 ml of ice-cold NS injected into ear.
Nystagmus with a slow component toward the
side of injection indicate functioning brain stem (assure intact tympanic membrane. Wait 5 min before testing other ear)
– Pharyngeal (gag) & laryngeal (cough) reflex):
afferent IX & efferent X CNs
3. Apnea test: checks integrity of brain stem respiratory center at high CO2.
Prerequisites prior testing are: normothermia (core temp ≥36.5°C), SBP ≥100 mmHg, no sedative & paralytic drugs, normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) & near normal PaCO2 (35-45 mmHg).
Steps:
– Disconnect ventilator
– O2 given at 6.0 L/min
– Look respiratory movements 8-10 min after
Disconnection
– Positive test if no respiratory movements at
PaCO2 of 60 mmHg (20 mmHg above baseline
if initially high)
– Certify brain death after a 2nd apnea testing
(timing widely varies between centers).
– Time of death is when PaCO2 reaches target
value during 2ndapnea test.
Problems during apnea test
1. The test aborted & repeated if SBP is ≤90 mmHg; vasopressors & fluid needed to keep it above target.
2. SaO2 not maintained during apnea testing:
The test cancelled if SaO2 is ≤85% for >30 s. Retest with T-piece & CPAP of 10 cm H2O & O2 flow 12.0 L/min.Tolerance to apnea can be predicted by reducing the PEEP to 5 cm H2O before ventilator is disconnected.
3. Hypothermia (<36.5°C): repeat test after correction.
4. Repeatedly de-saturation or hypotension testing: ancillary tests (EEG, angiography, trans-cranial Doppler & scintigraphy) considered to confirm brain death.
5. Baseline PaCO2 ≥40: test is +ve if a rise by ≥20 above baseline.
6. Baseline PaCO2 ≤35: reduce ventilation frequency to raise PaCO2 to target before testing.
Ancillary tests to support a brain stem death
– Used if neurologic evaluation is uncertain or apnea test cannot be done.
– 4 vessels digital subtraction angiography is the gold standard for CBF testing: absence of filling at carotid bifurcation or vertebral arteries confirms brain death.
– CT angiography: safer alternative & accurately test CBF.
– Transcranial Doppler: used in ICU, is simple & noninvasive. It is operator dependent.
– EEG: widely used to document brain death. Isoelectric recording over 30 min is suggestive.
(sedatives & hypothermia give similar picture).
– Cerebral tissue perfusion (technetium 99 m)
study is used in some centers.
If clinical findings are unreliable, the physician can decide against brain death rather than asking for ancillary tests (AAN recommendations).
Care of Organ Donor
– Needs the same intensity of care.
– Focus treatment (inotropes, fluids) toward
organ perfusion & improved quality of grafts.
– Potential donor: brain-dead or with severe
brain injury with a clear intent by physician
& the family to withdraw life support.
– Grief counselors can communicate with the
family & act in the interests of both the
potential donor & the pool of recipients.
Pathophysiology & organ preservation
·The hormonal & inflammatory changes that accompany brain death can cause graft dys-function & increased chances of rejection.
·Increased awareness, in recent decades, of donor management has improved outcomes after transplant surgery.
CVS
·Medullary ischemia occuring with brain death causes a reflex HTN & bradycardia (Cushing’s reflex) in an attempt to maintain the CBF.
·This is followed by intense vasoconstriction & tachycardia (dt increased
catecholamines) which increase visceral & myocardial ischemia.
·Echocardiogram indicated in all potential donors.
·Pulmonary artery catheterization indicated if EF <45% (cardiac & lung transplants).
Goals of management:
– maintain BP with minimal inotropes
– optimize fluid management
-maintenance organ perfusion.
Respiratory system
·Endogenous epinephrine raises pulmonary hydrostatic pressure causing endothelial damage & pulmonary edema.
·Goals of ventilatory management:
-Minimal FiO2 to maintain a PaO2 >100, SpO2 >95%, PaCO2-35-40 & pH 7.35-45.
-Ventilation strategies similar to those used for ALI are currently recommended & have improved the use of lungs for transplant.
-Excessive fluid to correct perfusion can result in pulmonary edema. Use of a PAC may restrict fluid use.
-Albuterol & diuretics can be used in the treatment of pulmonary edema.
Endocrine system & metabolic responses
·DI: due to early loss of posterior pituitary function in brain death. Causes polyuria &
hypernatremia. AVP & desmopressin are used as replacements.
·Thyroid hormones decreased (sick euthyroid state).
·Decrease in insulin & worsening of hyper-glycemia with stress, alteration in CHO
metabolism & use of glucose solutions. Hyperglycemia induced pancreatic cell damage
compromise pancreatic graft; strict euglycemia may minimize the risk. Hyperglycemia
also affect outcomes after renal transplant.
·Temperature regulation in hypothalamus: initial hyperthermia followed by hypothermia
(worsened by lack of shivering, peripheral vasodilatation & reduced metabolic rate). Hypothermia aggravates acidosis & coagulopathy & increase risk for arrhythmias & cold-induced dieresis.
SIRS
Caused by inflammatory mediators from ischemic brain, IRI, & catecholamine storm.
Increased IL-6 in the donor have poorer graft utilization & dysfunction.
DIC: occurs dt release of tissue thromboplastin from necrotic brain tissue.
Donor management protocols
·The “Rule of 100” normal targets:
– SBP ≥100 mmHg
– UOP ≥100 ml/h
– Hb ≥100 g/L
– PaO2 ≥100 mmHg
– Blood sugar 100mg/dl
· Core temp. >35°C prior to donation (circulating hot air blankets, warm IV fluids,
ambient temp. adjustment.
·Fluid management (patients are polyuric &
dehydrated with central volume depletion):
– Crystalloids: balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate,
½ NS with NaHCO3 may be superior to NS bcz as they do not cause hyperchloremic
acidosis.
– Uncorrected hypernatremia can cause in liver graft losse after transplant.
– Hydroxyethylstarches contraindicated bcz they damage renal epithelial cells & cause
early graft dysfunction in renal grafts.
– PAC may allow restrictive strategy with monitoring of filling pressures in lung
transplant.
– Blood & blood products: follow guidelines for the care of the critically; hemoglobin of
10 g/L improves tissue oxygenation.
·Inotropes & CVS:
-Dopamine has beneficial effect on renal graft probably due to moderation of
preservation injury & inflammation (not reno-protective).
-Noradrenaline (>0.05 mcg/kg/min) impair cardiac contractility in heart transplants.
·Ventilatory management:
-Similar to ALI (low tidal volume 6-8 ml/kg, minimum plateau pressure, lung recruitment).
-Lowest FiO2 needed is used
-Optimal PEEP with a restrictive fluid strategy improves graft harvesting in lung
transplants.
·Replacement of hormones:
– Vasopressin 1 U bolus, then infusion 0.5-4.0 U/h.
– Methylprednisolone 15 mg/kg immediately after brain death & 24 hourly after.
– Insulin 10 U in 50% dextrose, then infusion (keep blood glucose 80 – 150 mg).
– T4 20 mcg bolus, then infusion of 10 mcg/h. T3 (4-mcg bolus, then infusion 3 mcg/h).
UNOS data showed that the combination of thyroid hormone, corticosteroid, insulin & ADH was the best for multiple organ procurement.
Infections
·Sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations.
·HIV infections, herpetic meningo-encephalitis & T-cell leukemia-lymphoma virus are
contraindications to donation.
Other concerns
Pregnant patient who is brain-dead:
The mother should be supported until the fetus delivered & then considered organ donation.
This is a good summary, dear Dr Mohamed.
I like that you have typed headings and sub-headings in bold or underline. That makes it easier to read.
According to AAN, brain death is loss of brainstem function, coma and apnea.
Tests used to confirm it are variable, before testing for brain death, the patient should have a proximate cause incompatible with survival, neurological imaging with exclusion of hypothermia, intake of drugs leading to coma, metabolic and electrolyte imbalance.
Clinical tests for brain death:
Coma, absent brainstem reflexes
Apnea test, check brainstem respiratory center at high level of PCO2, 2 positive apnea tests certify brain death, timing between the 2 tests varies between centers.
Problems during performing apnea test:
SBP<100mmHg, oxygen saturation not maintained during the test, hypothermia and PCO2 <35 and >40mmHg
Ancillary tests for establishing brain death:
Used to support brainstem death when it is uncertain, include CBF documentation using digital subtraction angiography or CT angiography, transcranial doppler may be used but has several limitations.
Electroencephalography is also used but sedative drugs and hypothermia should be excluded.
The AAN recommends avoiding declaration of brain death if the clinical finding are unreliable rather than doing ancillary tests.
Care of potential organ donor:
Intensive care is necessary to improve quality of grafts and organ perfusion, potential donor is one who is brain-dead or with brain injury incompatible with life and life support will be withdrawn
Pathophysiological changes following brain death and relevance to organ preservation:
The instability of donor hemodynamics increase with increased time for organ retrieval due to inevitable hormonal and inflammatory changes.
Brain death leads to reflex HTN, bradycardia followed by severe vasoconstriction and tachycardia due to excess catecholamines leading myocardial ischemia resulting in hypotension and decreased organ perfusion.
The aim is to maintain blood pressure with minimal inotropes, proper fluid management and maintained organ perfusion.
Ventilatory management includes minimal FiO2 to keep PaO2>100, SpO2>95%, PaCO235-40 and pH 7.35-45 with similar strategies to those used in acute lung injury, PAC is used to guide excessive fluid management.
Posterior pituitary function lost leading to polyuria and diabetes insipidus, thyroid hormone decreases as thick euthyroid state, temperature regulation due to hypothalamic affection.
Systemic inflammatory response:
Is severe and may affect graft utilization and lead to graft dysfunction, DIC may occur after brain death.
Protocols for donor management:
Target SBP >100mmHg, UOP >100ml/hr, Hgb>100g/L, PO2>100, blood sugar 100% normal.
Temperature kept >35 using blanket, warmed IV fluids.
Fluid management, crystalloids using balanced salt solution, replacement of blood products as in critically ill patients
Inotropes and cardiovascular system: dopamine is the first choice
Ventilatory management with same principles as line of management of ALI, lowest FiO2 needed should be used.
Replacement of hormones after brain death, vasopressin, methylprednisolone, Insulin and thyroxine or tri-iodothyronine, combination of these hormones improves multiple organ procurement.
Other concerns and considerations:
Overwhelming sepsis, bacteremia and fungemia are not absolute contraindication for donation but HIV, hepatic meningo-encephalitis are contraindication.
Barriers for care of donors are high costs in sustaining care till consent is obtained, awareness among the public and resources to support organ donors.
This is a good summary, dear Dr Heba,
I like that your have type headings and sub-headings in bold or underline. That makes it easier to read.
Summary of the article
Brain death and care of the organ donor
Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible.
The American Association of Neurology (AAN) has defined brain death with three cardinal signs:
a) Cessation of the functions of the brain including the brainstem.
b) Coma or unresponsiveness.
c) Apnea.
Clinical testing for brain death
1. Coma.
2. Absent brain stem reflexes.
3. Apnea test: for performing apnea test, the deceased donor needs to be:
a) Normothermic (core temperature ≥36.5°C).
b) Hemodynamically stable (systolic pressure ≥100 mmHg).
c) Free from sedative and paralytic agents.
d) Normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation).
e) Near normal PaCO2 (35-45 mmHg).
Protocols for donor management
“Rule of 100”:
a) targets of SBP ≥100 mmHg.
b) urine output ≥100 ml/h.
c) hemoglobin of ≥100 g/L.
d) PaO2 ≥100 mmHg.
e) blood sugar targeted at 100% normal.
Elements of donor management are:
1. Temperature: The aim is to keep the core temperature >35°C prior to organ donation.
2. Fluid management: Crystalloids are the first choice and balanced salt solutions (Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate) may be superior to normal saline as theydonotproducehyperchloremicacidosis. Hydroxyethylstarches are contraindicated in organ donors because they can damage renal epithelial cells and cause early graft dysfunction in the transplanted kidneys.
3. Replacement of blood and blood products could follow guidelines for the care of the critically ill and a hemoglobin of 10 g/L could improve tissue oxygenation indices.
4. Inotropes and cardiovascular system: Dopamine is the first choice of inotrope in hypotension unresponsive to volume and has beneficial effects on the renal graft. Nor-adrenaline in doses >0.05 mcg/kg/min resulted in impaired cardiac contractility in transplanted hearts and in particular impairment of right ventricular performance.
5. Ventilatory management: The principles are along the lines of management of ALI (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment).
6. Replacement of hormones after brain death:
7. Standardization of hormone therapy after brain death in combination with a central venous pressure <10 mmHg significantly improved utilization of the heart and lungs for transplant without affecting other organ systems.[49] The recommended replacements are:
a) Vasopressin 1 U bolus followed by an infusion of 0.5-4.0 U/h.
b) Methylprednisolone 15 mg/kg immediately after diagnosis of brain death and 24th hourly thereafter.
c) Insulin 10 U in 50% dextrose followed by an infusion to maintain blood glucose between 80 and 150 mg.
d) Thyroxine (T4) 20 mcg bolus followed by infusions of10mcg/h.Tri-iodothyronine(T3)given as a 4-mcg bolus followed by an infusion of 3 mcg/h. T4 improves hemodynamics and prevents cardiovascular collapse in hemodynamically unstable organ donors.
Concerns and Considerations
a) Barring overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations.
b) Infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus preclude organ donation.
This is a good summary, dear Dr Rihab.
I like that you have typed headings and sub-headings in bold or underline. That makes it easier to read.
This article discusses the contentious topic of donation after brain death DBD, elaborating on its criteria , tests adopted to ascertain the diagnosis of brain death and contemplate on the challenging issue of escalating the supportive measures in order to have as much healthy and preserved harvested organs as possible.
Diagnosing brain death as per the article is established by absence of cerebral function including brain stem and excluding the spinal reflexes which might be still preserved after ward.
the diagnosis of brain death is clinical , supportive tests can be implemented to confirm diagnosis , if still doubtful. the patient has to be in deep coma with a an imminent intra-cranial etiology confirmed by radiology examination , not responsive to deep painful stimuli.Furthermore ,all brain stem reflexes are absent including light reflex, corneal reflux, gag reflex , oculo-cephalic reflex, oculo-vestibular reflex.absent reflexes in the face and and maxillary regions.
When the patient is diagnosed with brain death, then , all consequent features has to be addressed and treated properly in order to have perfect functioning and well preserved organs.
The other important and essential test that is integral in diagnosing brain death is the apnea test, which is basically dependent on eliciting brain stem respiratory center activity by inducing carbon dioxide retention. Failure to do so is consistent with brain stem death.
Other ancillary tests:
Are indicated when apnea test is not available to be performed or physician is not satisfied.
These Include, blood flow or rain electricity tests, such as CT angiography, cerebral dopplar or EEG.
Peculiar conditions have to be present in order to have proper performance.
Consequences of brain death:
1-Cushing effect :damage to medulla would be resultant in bradycardia and hyper tension.
2-Catecholamin surge with consequent tachycardia and hypertension.
3-vasidilation and hypotension.
The challenge in the management is to keep normal blood pressure with inotropes and fluid management to insue proper perfusion of the organs.
4-pulmonary circulation:
Soaring of pulmonary artery hydrostatic pressure might result in endothelial damage with subsequent respiratory distress syndrom perpetuated by adrenalin surge. Management involved ventilatory support with smooth parameters.
Endocrinologically, several perturbations were reported after brain death including:
1-Posterior pituitary function lost early with resultant diabetes inspidus.
2-thyroid hormon deficiency with sick thyroid status supervene.
3-Insuline deficiency with hyperglycemia.
Other changes featured in the context of brain death:
Hypothermia
Severe systemic Inflamatory response
DIC.
Management has to entail hormonal replacement and supportive measures to prevent other complications.
This is a good summary, dear Dr Jebur.
Brain death is a state of cessation of cerebral function wherein the proximate cause is known and is considered irreversible.
Definition of the American Association of Neurology (AAN) of brain death:
1- cessation of the functions of the brain including the brainstem
2- coma or unresponsiveness
3- apnea
In India, the Transplantation of Human Organ Bill was introduced in the Lok Sabha on 20th August 1992 and
became the Transplantation of Human Organ Act in 1994.
Brain death organ donation now becoming increasing field.
In India the deceased donor organ donation rate is
0.26 per million, while USA at 25.6 per million, UK
at 18.3 per million and Spain at 32 per million.
Brain death tests:
1- Presence of coma
2- Absent brain stem reflexes
3- Apnea test: testes the brain stem respiratory center at high levels of carbon dioxide. The patient should be normothermic (core temperature ≥36.5°C), hemodynamically stable (systolic pressure
≥100 mmHg), free from sedative and paralytic drugs, with normal oxygenation (PaO2 ≥200 mmHg
after 100% oxygenation) and near normal PaCO2
(35-45 mmHg).
Apnea test should be done twice before certification of brain death.
Additional tests for brain death diagnosis:
1- The conventional 4 vessel digital subtraction
angiography is the gold standard for CBF documentation.
Brain death is confirmed by demonstrating the absence of Intracerebral filling at the level of the carotid bifurcation or vertebral arteries.
2- Computerized tomography (CT) angiography also can be used.
3-Transcranial Doppler is used in ICU
4-EEG.
The AAN recommends that the physician can decide against a declaration of brain death rather than ordering ancillary tests if the clinical findings are unreliable.
Care of the Potential Organ Donor:
1- Maintenance of BP with minimal use of inotropes
2- Optimal fluid management
3- Good maintenance of organ perfusion
4- Optimal ventilator management
5- Hormonal replacement like insulin, thyroxin, antidiuretic hormone, corticosteroid
6- Optimal temperature control.
All these measures will improve outcomes following transplantation.
Overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations. But infections with human immunodeficiency-virus, herpetic meningio-encephalitis and T-cell leukemia-lymphoma virus prevent organ donation.
Continuation of organ support in a pregnant
patient who is brain-dead is controversial.
A systematic review of brain death during pregnancy has
concluded that the mother should be supported until the
delivery of the fetus and then can be considered for organ donation.
The preoperative donor screening for viruses may be
missed in the first 2 weeks of infection. Transmission of HIV and rabies from infected donors has been documented.
Conclusion:
“Care of the donor” is essentially “the simultaneous care of multiple recipients.”
The recognition and acceptance of brain death, awareness amongst public is a major support to organ donation and will improve the numbers
and quality of donor organs.
I
– Brain death is a state of cessation of cerebral function with irreversible cause . AAN defined brain death with 3 cardinal signs , cessation of brain function including brain stem , coma or unresponsiveness & apnea .
>>Clinical testing of brain death :
1- Coma : absence of response to noxious stimulus ( supra orbital pressure or pressure on nail bed ) with the exception of spinally mediated reflexes .
2- Absent brain stem reflexes with dilated fixed pupil & absent cranial nerve reflexes for > 4hrs .
– Clinical tests for brain death :
Absent pupillary light reflex , absent corneal reflrex , absent refelexes in the face & maxillary region , absent oculocephalic reflex( dolls eye movement ) absent oculo vestibular reflex & absent gag reflex & larengeal reflex .
3- Apnea test : the aim is to check for the brain stem respiratory center at high levels of blood carbon dioxide .it necessitates that patient is normothermic (temp>36.5 ) , hemodynamically stable (SBP>100 mmhg) , free of sedation & paralytic drugs , with normal oxygenation (pao2 >200 mmhg after 100 % oxygenation )& near normal paco2 (35-45 mmhg ) . certification of brain death is after the second apnea test .
– Ancillary tests can be used if uncertain neurological evaluation or if apnea test can not be performed like cerebral blood flow , transcranial doppler , electro encephalography & cerebral tissue perfusion for documentation of brain stem death .
– Brain dead organ needs the same integrity of care & TTT directed to organ perfusion & improved quality of the graft .
>> Pathophysiological changes following brain death :
– Bradycardia & HTN with increased level of catecholamines .
– Rise in pulmonary hydrostatic pressure with damage to pulmonary endothelium & pulmonary edema .
– Posterior piyutary function Is lost early , anterior pituitary preserved for slightly longer period , thyroid hormones decreased with hyperglycemia & hypothermia .
– Systemic inflammatory response is severe & DIC .
>>protocols for donor management :
– General principle of rule of 100 suggesting targets SBP>100 mmhg , UOP>100 ml/h , HB>100g/l , pao2 >100 mmhg & Bl.sugar at 100% of normal , others are :
1- temperature >35
2- fluid management , preferably with ringers acetate or half normal saline with NAHCO3 .
3- inotropic support , dopamine is the first choice
4- ventilatory management , The lowest FiO2 needed should be used
5- replacement hormones , vasopressin , methylprednisolone , insulin & thyroxine .
>>conclusion :
– care of the donor is essential . the barriers exist in limited resource environments like time to diagnosis & the cost.
– we have to raise the awareness , the recognition & the acceptance of brain death to support the deceased organ donation .
This is an excellent summary and analysis, dear Dr Muhamed
Brain death and care of organ donor:
Introduction:
Brain death defined as state of irreversible loss of cerebral function. American Association of Neurology(AAN), has 3 cardinal signs of diagnosing brain death, cessation of functions of the brain, coma, and unresponsiveness and apnea.
Clinical testing of the brain death:
Troubleshooting during performing Apnea test;
Ancillary Tests to establish brain death:
To document cerebral blood flow and evaluate the electrical activity of the brain.
4 vessel digital subtraction angiography is the gold standard for CBF.
Pathophysiological changes following brain death and its relevance to organ preservation;
Fluctuating hemodynamics during the time till patient being diagnosed as brain death affect organ for donation,;
CVS;
Respiratory system;
Endogenous epinephrine cause pulmonary edema, so minimum FiCO2 has to be used to maintained saturation and other parameters within target..
Endocrine system, stress and metabolic responses;
posterior pituitary lost earlier in brain death causing DI, with polyuria and hypernatremia.
Decrease thyroid hormone similar to thick euthyroid state.
Worsened hyperglycemia with the stress, with resultant risk of pancreatic damage, which may affect pancreatic graft.
Defective hypothalamic function .with early hyperthermia followed by hypothermia.
Activated inflammatory cascade and possible cytokines storm, may lead to poorer graft survival.
Protocol donor management;
Other consideration;
This is an excellent summary and analysis, dear Dr Kamal
II. Brain death and care of the organ donor
————————————————————————————————————————————————————————————————————————————-
————————————————————————————————————————————————————————————————————————————–
. Clinical testing for brain death
Ancillary tests for establishing brain death
.
————————————————————————————————————————————————————————————————————————————-
Care of the Potential Organ Donor
————————————————————————————————————————————————————————————————————————————–
Pathophysiological changes following brain death and its relevance to organ preservation
Cardiovascular system
The goals in the management include:
– An echocardiogram is indicated in all potential donors, and pulmonary artery catheterization (PAC) is indicated for donors with an ejection fraction (EF) <45%, more in the cardiac and lung transplants.
Respiratory system
The endocrain system /Stress/ and metabolic responces
Systemic inflammation response
————————————————————————————————————————————————————————————————————————————–
Protocols for donor management
A- Of SBP ≥100 mmHg,
B- Urine output ≥100 ml/h,
C- Hemoglobin of ≥100 g/L,
D- PaO2 ≥100 mmHg and blood sugar targeted at 100% normal.
Other elements of donor management are :
.
.
————————————————————————————————————————————————————————————————————————————–
Conclusion
This is an excellent summary and analysis, dear Dr Wadi, as usual for you.
Please type headings and sub-headings in bold or underline. That will make it easier to read.
In Sha-ALAH
Thanks alot for you Prof .Sharma
So nice of you, Dr Wadi.
For you excellence is normal.
Brian death is defined with unresponsiveness with coma ,including brainstem dysfunction and apnea.
once the brain death happened need to be declared by applying group of tests:
absent of brain stem reflexes
apnea test
absence of noxious stimulus
during performing this test the donor needs to be normothermic and normal oxygenation along with normal o2 saturation and normal pco2 .
if the brain death refluxes failed to be done we can go for ancillary test which include cranial doppler ,EEG, CT Brian angiography or MRI .
A lot of physiological changes associated with brain death includes :
CVs;cushing reflex with systemic hypertension and bradycardia
respiratory system; pulmonary odeama
with brain death all endocrine and hormonal secretion will cease and accordingly the donor will be on hormonal therapy .
Protocol for donor management:
This is a good summary, dear Dr Rihab.
Please type headings and sub-headings in bold or underline. That will make it easier to read.
Brain death is defined by the American Association of Neurology (AAN) with three cardinal signs, cessation of the brain’s functions, including the brainstem, coma or unresponsiveness and apnea.
There is a significant difference exists in the criteria and tests used.
Requirements that need to be fulfilled before proceeding with tests.
The cause for unresponsive is incompatible with survival.
Neurological imaging to confirm diagnosis CT brain, MRI, angiography
Exclusion of medical conditions that could account for unresponsiveness.
Exclusion of drugs causes of unresponsiveness.
Normal temperature.
Clinical testing for brain death
1. Coma: Absence of response to a noxious stimulus.
2. Absent brain stem reflexes pupillary light reflex, corneal reflex, reflexes in the face and maxillary region, oculo-cephalic reflex (doll’s eye movement), oculo-vestibular reflex and pharyngeal (gag) and laryngeal (cough) reflex.
3. Apnea test
Prerequisites: Normothermia (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralytic drugs, normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) near normal PaCO2 (35-45 mmHg).
The test is considered positive if there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in those with an elevated PaCO2.
Certification of brain death is after a second apnea testing. The time of death is when PaCO2 reaches the target value during the second apnea test.
Ancillary tests for establishing brain death can be used when uncertainty exists. However, AAN recommends that the physician can decide against a declaration of brain death rather than ordering ancillary tests if the clinical findings are unreliable.
I-Documentation for cerebral blood flow (CBF)
Conventional 4-vessel digital subtraction angiography is the gold standard.
Computerized tomography (CT) angiography
Transcranial Doppler
Cerebral tissue perfusion techniques using technetium 99 m
II-Evaluate the electrical activity of the brain.
EEG
Pathophysiological changes following brain death and its relevance to organ preservation
Even while ensuring optimum donor care, the inevitable hormonal and inflammatory changes accompanying brain death can result in graft dysfunction and increased chances of rejection.
Cardiovascular system
–Medullary ischemia causes Cushing’s reflex. (reflux HTN and bradycardia).
-Followed by a period of intense vasoconstriction and tachycardia associated with catecholamine surge resulting in hypertension which can increase visceral and myocardial ischemia.
– After the depletion accompanied by vasodilatation and hypotension.
An echocardiogram is indicated in all potential donors, and PAC is indicated for donors with an EF <45%, more in the background of cardiac and lung transplants.
The goals in the management include maintenance of BP with minimal use of inotropes, optimizing fluid management and maintenance of organ perfusion.
Respiratory system
Excessive fluid resuscitation to correct perfusion can result in pulmonary edema. The use of a PAC may restrict excessive fluid use.
The endocrine system, stress and metabolic responses.
Hormone replacement therapy to replace the loss of pituitary function.
Systemic inflammatory response
Mediated by inflammatory mediators from an ischemic brain, ischemic reperfusion injury, metabolic
changes that occur during the catecholamine storm and an inadequately restored cardiovascular state.
DIC occurs due to the release of tissue thromboplastin from necrotic brain tissue.
Protocols for donor management.
“Rule of 100” suggests targets of SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and BSL targeted at 100% normal.
Temperature: keep temperature >35°C prior to organ donation. Circulating hot air blankets or warmed intravenous fluids.
Fluid management:
A restrictive strategy with monitoring of filling pressures with a PAC, particularly in lung transplants.
Crystalloids are the first choice and balanced salt solutions
Replacement of blood and blood products could follow guidelines for the care of the critically ill, and a hemoglobin of 10 g/L could improve tissue oxygenation indices.
Inotropes and the cardiovascular system:
Dopamine is the first choice of inotrope in hypotension, unresponsive to volume and has beneficial effects on the renal graft are probably related to the moderation of preservation injury and inflammation.
Noradrenaline in doses >0.05 mcg/kg/min resulted in impaired cardiac contractility in transplanted hearts
and in particular, impairment of right ventricular performance.
Ventilatory management;
The goals of ventilatory management include:
– minimal FiO2 needed to maintain a PaO2 >100 mmHg
– SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45.
– Tidal volumes similar to those used for ALI to be used for lung transplant
Replacement of hormones
The recommended replacements are:
a. Vasopressin
b. Methylprednisolone
c. Insulin infusion to maintain blood glucose between 80-150 mg.
d. Thyroxine (T4), Tri-iodothyronine (T3)
Other concerns and considerations
Overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations.
However, infections with HIV, herpetic meningoencephalitis and T-cell leukemia-lymphoma virus preclude organ donation.
Level of evidence 5
This is an excellent summary and analysis, dear Dr Hadeel.
Yes, it is level 5 evidence.
SUMMARY
Introduction
The growing concern for scarcity of organs for donation has brought about the legalization of retrieval of organs from dead donors, but this has also come up with challenges like truly certifying the person is dead and the preservation of the organs to make viable after transplantation. The diagnosis of brain dead is fulfilled after meeting certain stringent criteria in many parts of the world
The Clinical Testing for Brain Dead
In the event of uncertainty on brain dead, the following ancillary tests can be used
Care of potential organ donors
Following an irreversible traumatic brain injury, grief counsellors are deployed to communicate with the family the benefits of early organ donation which will enhance perfusion and preservation of the organ through use of inotropes and other hormones. This will ultimately reduce waiting pool and of great benefit to the recipients. Great attention is paid to systems like, cardiovascular, respiratory, endocrine with prevention of infection, temperature instability or fluctuating hemodynamics.
Protocols for Donor managements
Various fluctuation in several systems in the body are managed by rule of 100
Other requirements for preservation of organs are:
Conclusion
The importance of brain-dead donor needs to be emphasized the more so as to gain public trust in accepting this as a way to reduce the waiting pool and also to help in early retrieving viable organs.
This is an excellent summary and analysis, dear Dr Issac
Brain death is the termination of brain function for which the immediate cause is recognized and is regarded as irreversible.Brain death is described by the American Association of Neurology (AAN) as the cessation of all brain functions, including those of the brainstem, coma or unresponsiveness, and apnea.
Brain death is a clinical diagnosis. The key criteria for determining brain death are as follows:
1- Complete unresponsiveness- coma
2-No brainstem reflexes
Pupillary response to strong light is absent in both eyes. Typically, the pupils are fixed at a medium to dilated size (4-9 mm)
– Absence of ocular movements utilizing oculocephalic testing and oculovestibular reflex testing
– Insufficient corneal reflexes
–Lack of facial muscular contraction in response to a painful stimulus.
– Absence of the gag and cough reflexes in the pharynx and trachea
3-Permanent apnea An apnea test should be performed to ensure permanent apnea. After disconnecting from the ventilator, oxygen is insufflated through a catheter placed at the level of the carina at a rate of 6.0 L/min. The observer searches for respiration eight to ten minutes after separation. Assuming a rate of rise in PaCO2 of 3 mmHg/min, this will result in a 24 mmHg increase over baseline after 8 to 10 minutes. If there are no respiratory movements at a PaCO2 of 60 mmHg or 20 mmHg above baseline in people with an increased PaCO2, the test is deemed positive. Brain death is certified following a second apnea test.
Troubleshooting during performance of apnea test
1. Systolic blood pressure (SBP) less than 100 mmHg
2. Failure to maintain oxygen saturation during apnea testing
3.The patient is hypothermic (36.5 degrees Fahrenheit).
4. During apnea testing, the patient continually desaturates or becomes hypotensive.
5. Baseline PaCO2 ≥40 mmHg or ≤35 mmHg
Ancillary tests for establishing brain death
When the reliability of the neurologic examination is unknown or when the apnea test cannot be administered, ancillary tests may be conducted. These tests are categorized into those that measure cerebral blood flow (CBF) and those that assess the electrical activity of the brain.
Care of the Potential Organ Donor
A brain-dead organ donor requires the same level of care, with an emphasis on organ perfusion and the improvement of graft quality. For increased quality of care and titration of inotropes and fluids, intensive care with the use of invasive lines is required.
Pathophysiological changes following brain death and its relevance to organ preservation
The period between a diagnosis thend a pronouncement of brain death is compounded by donor hemodynamic fluctuations.
Cardiovascular system
Medullary ischemia linked with brain death generates reflex hypertension and bradycardia (Cushing’s response) in all individuals with brain death. This is the body’s reflexive effort to sustain CBF. This is followed by a period of acute vasoconstriction and tachycardia accompanied by elevated circulatory catecholamines, which can exacerbate visceral and myocardial ischemia.
Respiratory system
A rise in pulmonary hydrostatic pressure causes damage to the pulmonary endothelium resulting in pulmonary edema that is perpetuated by endogenous epinephrine. The goals of ventilatory management include minimal FiO2 needed to maintain a PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45.
Endocrine system, stress and metabolic responses
The endocrine responses of the body are lost with brain death and form the rationale for hormone replacement therapy for brain-dead patients.
Systemic inflammatory response
There is a systemic inflammatory reaction that may be fairly severe. This is caused by inflammatory mediators from an ischemic brain, ischemic reperfusion damage, metabolic alterations during the catecholamine storm, and an insufficiently recovered circulatory state.
Protocols for donor management
The circulatory and biochemical variables are managed by the general principle of the “Rule of 100” suggesting targets of SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted at 100% normal.
Other concerns and considerations
Barring overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations.[52] However, infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus preclude organ donation
This is an excellent summary and analysis, dear Dr Habli.
Please type headings and sub-headings in bold or underline. That will make it easier to read.
Brain death is defined as the triad of coma, cessation of the function of brain death and apnea
Coma:
Cessation of brain stem function:
Apnea:
Pathophysiological changes after brain death and its management
Cardiovascular system
Respiratory system
Metabolic and endocrinological system
Systemic inflammatory response
This is an excellent summary and analysis, dear Dr Yusuf
Introduction:
The American Association of Neurology (AAN) has defined brain death with three cardinal signs, cessation of the brain’s functions, including the brainstem, coma or unresponsiveness, and apnea.
Clinical testing for brain death
1. Coma: Absence of response to a noxious stimulus.
2. Absent brain stem reflexes, fixed dilated pupils, and absent cranial nerve reflexes for more than four h).
3. Apnea test: (core temperature ≥36.5°C), hemodynamically stable (systolic pressure ≥100 mmHg), free from sedative and paralytic drugs, with normal oxygenation (PaO2 ≥200 mmHg after 100% oxygenation) and near normal PaCO2 (35-45 mmHg).
Ancillary tests for establishing brain death:
1- Brain death is confirmed by demonstrating the absence of intracerebral filling at the level of the carotid bifurcation or vertebral arteries. Computerized tomography (CT) angiography
2- Electroencephalography is widely used as an ancillary test for documentation of brain death.
3- Cerebral tissue perfusion techniques
Care of the Potential Organ Donor:
Maintained organ perfusion and improved the quality of grafts.
Patho physiological changes following brain death:
Cardiovascular system medullary ischemia (Cushing’s reflex).
Respiratory system: endothelial injury and pulmonary edema.
The endocrine responses: diabetes insipidus with polyuria. The anterior pituitary functions are preserved for a slightly more extended period of decrease in insulin levels during Hypothermia.
Systemic inflammatory responseDisseminated intravascular coagulation occurs after brain death due to the release of tissue thromboplastin from necrotic brain tissue.
Protocols for donor management
The circulatory and biochemical variables are managed by the general principle of the “Rule of 100, SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted at 100% standard.
1-Temperature: >35°C
2- Fluid management Ringer’s lactate, Plasmalyte-A, Ringer’s acetate, half normal saline with sodium bicarbonate)
3-Inotropes and the cardiovascular system: Dopamine is the first choice
4- Ventilatory management: (low tidal volume 6-8 ml/ kg, minimum plateau pressure, lung recruitment
5- Replacement of hormones: insulin, thyroxin, vasopressin, and methylprednisolone.
Ø The recognition and acceptance of brain death, awareness amongst the public on the eventuality, and resources to support the organ donor to improve the numbers and quality of donor organs
Introduction
Brain death is when the brain stops working and the exact cause is known. It is thought to be irreversible.
The American Association of Neurology (AAN) says that brain death is when the brain and brainstem stop working, the person is in a coma or is not responding, and they stop breathing.
Brain death testing
1. Coma: No reaction to painful stimuli (supraorbital pressure or nail bed pressure) save spinally mediated reflexes.
2. Missing brain stem reflexes (when a patient has fixed dilated pupils and absent cranial nerve reflexes for more than 4 h.
3- Apnea: This test checks the brain stem respiratory centre at elevated blood carbon dioxide levels. A normothermic (core temperature 36.5°C), hemodynamically stable (systolic pressure 100 mmHg) the patient is required.
-Apnea test troubleshooting
. Patient’s systolic blood pressure (SBP) 100 mmHg: Administer vasopressors, inotropes, and fluid boluses to maintain BP. If systolic BP is 90 mmHg, the apnea test must be redone.
. Oxygen saturation 85% for more than 30 seconds during apnea testing.
Retest with T-piece, 10 cm H2O constant positive airway pressure, and 12.0 L/min oxygen flow. Reducing PEEP to 5 cm H2O before disconnecting the ventilator helps predict apnea tolerance.
. Hypothermic patient: Apnea testing guidelines are invalid and must be redone after correction.
. Patient frequently desaturates or becomes hypotensive during apnea testing: Consider auxiliary procedures to prove brain death (EEG, cerebral angiography, transcranial Doppler, scintigraphy). India’s legislation on auxiliary testing are unclear.
Pathophysiological changes following brain death :
1-Brain death induces reflex hypertension and bradycardia due to medullary ischemia.
2-A increase in pulmonary hydrostatic pressure damages the pulmonary endothelium, causing pulmonary edema that endogenous epinephrine perpetuates.
3-Early brain death causes diabetes insipidus, polyuria, hyperglycemia,and hypernatremia.
Protocols for donor management:
–The aim is to keep the core temperature >35°C
-“Rule of 100”: SBP 100 mmHg, urine output 100 ml/h, hemoglobin 100 g/L, PaO2 100 mmHg, blood sugar 100% normal.
-In volume-resistant hypotension, dopamine is the first-choice inotrope.
This is an excellent summary and analysis, dear Waem
Organ transplantion from brain dead donors is still very limited worldwide but gaining more interest with the improvement in solid organ donation field. The potential donors are either brain dead or suffer catastrophic brain damage and the family and physicians agree to withdraw life support equipment from those patients. Sepsis , bacteria and fungemia are not contraindications for donation except HIV , T cell leukemia lymphoma virus and hepatic meningio -encephalitis.
Diagnosis of brain death is mainly clinical through
1- coma :absence of response to noxious stimuli
2- Absense of brain stem reflexes including light, corneal and doll’s eye reflexes
3- Apnea test that prerequires ( heamodynamic stability , no hypothermia , Pao2 >100)
If apnea test couldn’t be done , other tests as EEG , cerebral angiography and Doppler can be used
Consequences of brain death that can lead to organ dysfunction:
1- Cardiovascular
– Cushing reflex ( reflex hypertension and bradicardia from medulla ischemia) , then hypertension and tachycardia due to excess catecholamines.
2- hormonal changes: loss of endocrinal function requiring replacement with thyroixin , vasopressin, insulin and methylprednisolone immediately after diagnosis of brain death.
3- altered body temperature ( hyperthyrmia followed by hypothyrmia that may cause coagulopathy).
4- Systemic inflammatory response.
Requirements for organ donation: summarized by role of 100
– Po2 100
– Hb 100 gm /dl
– SBP >100 mg/dl
– UOP>100 ml/h
So invasive lines are needed to keep the patient hemodynamics and adequate tissue perfusion using IV fluid therapy ( better ringer lactate , half tonic saline , ringer acetate rather than normal saline )
Also minimize the use of inotropes with dopamine is the preferred inotrope to use.
This is an excellent summary and analysis, dear Dr Fatima.
Please type headings and sub-headings in bold or underline. That will make it easier to read.
Brain death and care of the organ donor.
Brain death is defined as cessation of the functions of the brain including the brainstem, coma or unresponsiveness and apnea.
Clinical testing for brain death.
1- Coma: Absence of response to noxious stimulus.
2- Absent brain stem reflexes ( no brain stem function):(Absent pupillary reflexes, absent corneal reflexes, absent cranial motor function, absent gag reflexes & absent vestibule-ocular reflex).
3- Absent respiratory drive No response to hypercapnia (PaCO2 above 6.5 kPa) and apnea test should be repeated twice after unspecified length of time.
Troubleshooting during performance of apnea test.
1- Patient’s systolic blood pressure (SBP) ≤100 mmHg:
So inotropic support with isotonic saline needed and the test should be aborted if systolic BP<90 mmhg.
2- Oxygen saturation not maintained during apnea testing: If saturation is ≤85% for more than 30 s, apnea test should be aborted and using T-piece and continuous positive airway pressure of 10 cm H2 O and oxygen flow of 12.0 L/min.
3- Correction of hypothermia.
4- Ancillary tests for confirming brain death (electroencephalography, cerebral angiography, transcranial Doppler and scintigraphy) could be used if patient repeatedly desaturases or becomes hypotensive during apnea testing.
N.B: The AAN recommends that the physician can decide against a declaration of brain death rather than ordering ancillary tests if the clinical findings are unreliable.
Care of the Potential Organ Donor.
Hormonal and inflammatory changes accompanying brain death can result in graft dysfunction and increased chances of rejection.
Cardiovascular system.
Percentage of 20-25% brain-dead donors showed evidence of myocardial ischemia and 40% have echocardiographic evidence of myocardial dysfunction due to effects of the catecholamine surge which is mainly due to Cushing reflex after brain death and increasing ICP after that patient developed hypotension and vasodilatation which need use of inotropes, optimizing the fluid management and maintenance of organ perfusion.
An echocardiogram is indicated in all potential donors, and pulmonary artery catheterization (PAC) is indicated for donors with an ejection fraction (EF).
Respiratory system.
The goals of ventilatory management include minimal FiO2 needed to maintain a PaO2 >100 mmHg, SpO2 >95%, PaCO2 of 35-40 mmHg and pH 7.35-45. Try to avoid pulmonary edema with excessive fluid to avoid pulmonary endothelial damage to preserve lung or transplantation.
Endocrine system, stress and metabolic responses.
Arginine vasopressin and desmopressin can be given as replacements due to loss of posterior pituitary function , strict euglycemia may minimize this risk as hyperglycemia can also affect the outcomes after renal transplantation.
Hypothalamus dysfunction lead to hyperthermia followed by hypothermia which lead to worsen acidosis and coagulopathy, increase the risk for arrhythmias and cold-induced diuresis.
Systemic inflammatory response.
Due to release of tissue thromboplastin from necrotic brain tissue that lead to Disseminated intravascular coagulation.
Protocols for donor management.
“Rule of 100”suggesting targets of SBP ≥100 mmHg, urine output ≥100 ml/h, hemoglobin of ≥100 g/L, PaO2 ≥100 mmHg and blood sugar targeted at 100% normal.
1- Temperature: The aim is to keep the core temperature >35°C prior to organ donation. Circulating hot air blankets, and warmed intravenous fluids.
2- Fluid management: crystalloid superior to normal saline and hydroxyethyl starches are contraindicated in organ donor and monitoring of filling pressures with a PAC may be beneficial particularly in the context of lung transplant.
3- Inotropes and cardiovascular system: dopamine is the first choice and Nor-adrenaline in doses >0.05 mcg/kg/min resulted in impaired cardiac contractility in transplanted hearts.
4- Ventilatory management: the lowest FiO2 needed should be used, and optimal PEEP with a restrictive fluid strategy improves graft harvesting for lung transplants this is the consideration in ventilation support.
5- Replacement of hormones after brain death: such as Vasopressin, Methylprednisolone, Insulin 10 U in 50% dextrose and Thyroxine.
Conclusion:
The recognition and acceptance of brain death, awareness amongst public on the eventuality and resources to support the organ donor to improve the numbers and quality of donor organs will be the immediate goals in our country.
This is an excellent summary and analysis, dear Dr Saad.