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.