Thank you, All Will you change your practice based on this article? What is the role of (ab)normal saline played in the post-transplant fluid management at your work place?
Dear Professor Halawa
We have changed our practice especially when choosing fluids for our transplant patients. Initially, the anesthetists would use normal saline intra-operatively that would result in metabolic acidosis and hyperkalemia. But now we have changed to Hartmanns.
If the patient has hyponatremia, thats the time we would use normal saline
We already changed the concept of considering normal saline as just a fluid, especially when we are giving large volume and we restrict the use to the cases of hyponatremia and hyperchloremic metabolic alkalosis
It was clear for me that NS is associated with hyperchloremia, hypernatremia and normal anion gab metabolic acidosis which was noticed in patients with high volume intake such as in cases of rhabdomyolysis and sepsis and DKA , but it is new that it is associated with higher risk of infection, AKI, hyperkalemia and mortality
Hi prof Ahmad Halawa.
For sure those articles will direct me to choose balanced fluid for the right patient, to avoid such undesirable effects. And defenitly NS will be a better fluid for hypochloremia associated with metabolic acidosis or alkalosis. In my place LR ususally dominating in perioperative period, as well as NS has still normal, so it has been used frequently.
Definitely I will change my practice. Many patients on long standing 0.9 % saline develop hypokalemia, renal impairment, over load, hypernatremia, and hyperchloremia
yes I will change my practise to use based balanced solution rather than normal saline unless is indicated such as vomiting or loss of chloride
really in our practise we use normal saline in postrenal transplant,it will change sooner.
yes, sure
we were using only normal saline for fluid replacement in the kidney transplant recipients, now it is used only in the operating room and we use ringer lactate and saline. the issue of cost of hartmann’s and osmolytes limited it use in our governmental hospital.
The article has enlightened me and hopefully one day I will be able to apply my knowledge when my hospital start to introduce kidney transplant. so yes I will change the practice.
Hartman solution is the main solution used post transplantation in addition to normal saline .I will encourage changing entirely to a balanced solution.
Mohammed Sobair
2 years ago
Ab-normal saline in abnormal kidney function: risks and alternatives: Administration of intravenous fluid directly affects patients’ extracellular fluid and electrolyte status. While these effects can be therapeutic, some are unintended, and have the potential to cause harm. The most commonly prescribed intravenous crystalloid in pediatric practice is currently 0.9% saline. Chloride in intravenous fluid:
Pediatric practice has changed over the last decade with a shift away from hypotonic intravenous fluids such as 0.45% saline or 0.2% saline to predominantly 0.9% saline.
The rationale for this change is avoidance of iatrogenic hyponatremia.
Systematic reviews have highlighted the risk of hyponatremia from hypotonic intravenous fluid,
For the majority of children, isotonic intravenous fluids mitigate these risks, although specific disorders such as diabetes insipidus mandate hypotonic solutions because isotonic fluids lead to hypernatremia and cerebral myelinosis
The most commonly prescribed intravenous fluid is currently 0.9% saline which was developed at the turn of the twentieth century.
Balanced intravenous fluids have chloride concentrations closely aligned to that of plasma. Traditional balanced solutions are Hartmann’s or Ringer’s lactate.
Solutions with even closer alignment to plasma constituents have subsequently been developed such as PlasmaLyte. Effects of chloride Chloride and mortality:
In sepsis, fluid resuscitation with 0.9% saline was associated with more metabolic acidosis and inferior survival than balanced resuscitation fluid.
The association of chloride-rich intravenous fluid and mortality is increasingly recognized in critically ill adult and children.
A higher rate of a composite outcome of death, new renal replacement therapy, or persistent renal dysfunction in patients who received 0.9% saline as opposed to balanced intravenous crystalloid hypochloremia is also associated with adverse outcomes. Low serum chloride levels were a strong predictor of mortally. Chloride and acid-base balance:
Hyperchloremic metabolic acidosis is consistently observed in both adult and pediatric patients following fluid resuscitation with 0.9% saline. Etiology of saline-induced hyperchloremic metabolic acidosis
If a large volume of intravenous 0.9% saline is administered, this will reduce the plasma strong ion difference via a higher relative increase in plasma [Cl−] than [Na+]. This reduction in strong ion difference will increase dissociation of water to H+ and OH−, thereby driving metabolic acidosis.
Metabolic acidosis affects myocardial function, renal and intestinal perfusion, nerve function, and extracellular potassium buffering, it is likely to play a role in the increased mortality observed in critically ill patients who receive large volumes of 0.9% saline. Chloride and kidney perfusion:
Data from preclinical studies and clinical trials suggest a direct effect of chloride on intra-renal perfusion, vasoconstriction, and glomerular filtration.
Chloride fluid strategy was associated with more AKI and renal replacement therapy than a chloride-restrictive strategy. Chloride and coagulation:
Adults undergoing major surgery that chloride rich resuscitation fluid impairs coagulation. Chloride and fluid overload:
Intravenous fluid can be highly effective in restoring tissue perfusion in patients with intravascular depletion. Conversely, injudicious use can result in fluid overload. Chloride and blood pressure:
Several lines of evidence implicate chloride in systemic hypertension. The case for abandoning 0.9% saline:
Given the accruing evidence for deleterious effects of excess chloride, should physicians abandon chloride-rich crystalloid, which was developed over a century ago, in favor of isotonic balanced solutions such as PlasmaLyte.
When used as resuscitation fluid in children on intensive care, balanced fluids were associated with lower mortality, lower prevalence of AKI, and lower inotrope requirements in a propensity matched analysis of over 3000 children from 43 centers.
Similarly, adult studies demonstrate a consistent link between chloride-rich resuscitation fluid and subsequent mortality in critically ill patients.
Postoperative use of 0.9% saline was associated with metabolic acidosis, increased mortality, increased infection rates, and increased blood product requirement, compared to PlasmaLyte.
In AKI and mechanical ventilation time in patients in whom chloride rich resuscitation fluid was used.
Kidney transplantation is a further scenario in which 0.9% saline may impact outcome:
With more metabolic acidosis than balanced solutions.
PlasmaLyte (containing 5 mmol/l potassium) has also been shown to reduce the risk of hyperkalemia relative to potassium-free 0.9% saline in adults with end stage kidney disease undergoing transplantation. The case for keeping 0.9% saline:
There are some clinical scenarios in which chloride-rich crystalloid will remain the intravenous fluid of choice.
For children with hypochloremic metabolic alkalosis and intravascular volume depletion, the electrolyte composition of 0.9% saline can aid restoration of physiological electrolyte and acid-base balance.
Salt losing tubulopathies such as Bartter syndrome.
Cystic fibrosis.
Severe persistent vomiting can develop hypochloremic alkalosis as a result of gastric hydrochloric acid loss. Individualized intravenous fluid prescriptions:
All children who require intravenous fluid need an individualized prescription that is based on their medical condition and tailored in response to changes in their fluid, electrolyte, and acid-base Status. Summary:
In adult patients, balanced fluids are associated with lower mortality, less AKI, and less perioperative complications than 0.9% saline. Concerns about the potassium content of balanced fluids in patients with abnormal kidney function are not justified, since hyperchloremic acidosis from 0.9% saline confers a greater risk of hyperkalemia.
Pediatric data are scant, balanced isotonic fluids such as PlasmaLyte are probably better suited to the majority of children, particularly those with abnormal kidney function and reduced capacity to excrete excess chloride.
level of evidence V
Nasrin Esfandiar
2 years ago
Normal saline (0.9) is a widespread crystalloid that resulted in saving many lives. On the other hand, there are some disadvantages regarding its use in critically ill and especially transplanted recipients due to its high chloride content.
Balanced intravenous fluids such as Ringer lactate or plasmalyte, have chloride content closer to that of plasma.
Effect of chloride:
In critically ill or septic patients use of chloride rich IV fluids was associated with increased mortality.
This is probably related to hyperchloremic metabolic acidosis.
In a systematic review by Cochran, infusion of sodium chloride was associated with high risk of metabolic acidosis.
The effect of 50 ml/kg infusion of different types of crystalloids is 10 kg infant in production of metabolic acidosis is due to their change in strong on different which is highest in normal saline and followed by Hartmans solution and plasmalyte, respectively.
Chloride-rich fluid infusion results in vasoconstriction and reduced intra-renal perfusion and GFR which increase the rate of AKI.
The other effect of normal saline infusion is coagulopathy and increased risk of fluid over load and hypertension (via WNK activity)
In supporting this idea, analysis of over 3000 children showed superior results for balanced solution vs normal saline.
Another study in over 15,802 adults balanced solution were associated with lower risk of AKI, mortality or CKD.
A Cochran systematic review showed increased rate of metabolic acidosis by using perioperative N/S compared to balanced solutions.
This metabolic acidosis may result in hyperkalemia due to trans cellular shift.
There are some cases such as hypo-chloremia metabolic acidosis or some tubulopathies like Bartter syndrome which need chloride-rich IV fluid.
Other indication for N/S infusions are dehydrated patients with CF or persistent Vomiting.
In case with traumatic brain injury, IV infusion of N/S may reduce the risk of cerebral edema.
In addition, monitoring of patient hydration and urine and plasma electrolytes are important for making –decision
The level of evidence is 5.
Ghalia sawaf
2 years ago
Introduction
most recently in a large randomized trial there is increased mortality in critically ill adults
May be due to the excess chloride concentration of 0.9% saline relative to plasma.
Patients with abnormal kidney function have reduced capacity to excrete excess chloride
In recent years, balanced intravenous solutions with physiological chloride concentration have been developed as isotonic alternatives to 0.9% saline.
The aim of this review outlines current evidence for the effects of excess chloride in 0.9% saline and considers whether its use in clinical practice is still justified.
Chloride in intravenous fluid
Pediatric practice has changed over the last decade with a shift away from hypotonic intravenous fluids such as 0.45% saline or 0.2% saline to predominantly 0.9% saline. To avoid hyponatremia
While the tonicity and sodium concentration of 0.9% saline are within 10% of physiological levels, its chloride concentration exceeds that of plasma by approximately 60%
In contrast, balanced intravenous fluids have chloride concentrations closely aligned to that of plasma.
Traditional balanced solutions are Hartmann’s or Ringer’s lactate then recently PlasmaLyte.
Effects of chloride Chloride and mortality
In an analysis of 53,448 adults with sepsis and acute kidney injury (AKI), patients who received greater proportions of chloride rich fluid experienced increased mortality
A recent cluster-randomized, multiple crossover trial in 15,802 adults on intensive care found a higher rate of a composite outcome of death, new renal replacement therapy, or persistent renal dysfunction in patients who received 0.9% saline as opposed to balanced intravenous crystalloid
In an analysis of 890 children with septic shock in 29 pediatric intensive care units in the USA, hyperchloremia was independently associated with inferior outcomes including mortality and complicated clinical course
The mechanism underlying increased mortality not been definitively established; however hyperchloremic metabolic acidosis is strongly implicated.
Chloride and acid-base balance
A Cochrane systematic review of postoperative intravenous fluid management in adult patients concluded that chloride-rich fluid, as opposed to balanced fluid, significantly increases the risk of metabolic acidosis
Etiology of saline-induced hyperchloremic metabolic acidosis There are two schools of thought The first one depend on the traditional Henderson-Hasselbalch and Siggaard-Anderson line of thinking
Alternative explanations ; dilutional acidosis, which suggests that infusion of buffer-free crystalloid dilutes the bicarbonate concentration in extracellular fluid thereby precipitating acidosis.
A Chloride and kidney perfusion
in animal studies, infusion of chloride-rich fluid in denervated kidneys resulted in vasoconstriction and reduction in glomerular filtration rate
In healthy adult volunteers, renal artery flow velocity and renal cortical tissue perfusion fell significantly from baseline after infusion of 2 litres 0.9% saline, but not after PlasmaLyte
A chloride-liberal intravenous fluid strategy was associated with more AKI and renal replacement therapy than a chloride-restrictive strategy in a study of 760 adult patients on intensive care
These findings were not corroborated in the SPLIT trial, which compared incidence of AKI in adults receiving 0.9% saline with PlasmaLyte; however, the power of this study was limited by small volumes of fluid infused in patients with moderate severity of disease
Chloride and coagulation
chloride rich resuscitation fluid impairs coagulation and increases blood product requirements
The anticoagulant effect has been ascribed to dilutional coagulopathy related to the significantly larger volume of saline required for resuscitation relative to balanced fluids
the underlying pathophysiology need more researches
Chloride and fluid overload Intravenous
injudicious use can result in fluid overload.
In a study of healthy adult volunteers, urinary excretion of water and sodium were inferior following infusion of 2 litres 0.9% saline when compared to Hartmann’s solution
Overload is a key contributor to cardiovascular morbidity and mortality in children with CKD
Chloride and blood pressure
Several lines of evidence implicate chloride in systemic hypertension.
Preclinical data suggest a specific effect of chloride and on blood pressure and renal vascular resistance.
With-no-lysine kinases (WNKs) are serine threonine kinases which play a major role in the regulation of sodium and potassium transport in the distal nephron [and in monogenic hypertension
( Drosophila model)
The case for abandoning 0.9% saline
When used as resuscitation fluid in children on intensive care, balanced fluids were associated with lower mortality, lower prevalence of AKI, and lower inotrope requirements in a propensity matched analysis of over 3000 children from 43 centers
Observational data , randomized study, over 15,802 adults , confirmed that balanced crystalloids result in a lower rate of a composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than 0.9% saline
Further observational analysis of over 30,000 adult patients undergoing abdominal surgery, postoperative use of 0.9% saline was associated with metabolic acidosis, increased mortality, increased infection rates, and increased blood product requirement, compared to PlasmaLyte
These findings were not corroborated in the randomized SPLIT trial
A meta-analysis found an increase in AKI and mechanical ventilation time in patients in whom chloride rich resuscitation fluid was used
A Cochrane systematic review of studies in adult kidney transplant recipients concluded that perioperative normal saline was associated with more metabolic acidosis than balanced solutions
PlasmaLyte has also been shown to reduce the risk of hyperkalemia relative to potassium-free 0.9% saline in adults with ESRD undergoing transplantation
Although no pediatric data are available, these findings are noteworthy because pediatric transplant recipients receive large volumes of intravenous crystalloid to maintain allograft perfusion perioperatively
The case for keeping 0.9% saline
For children with hypochloremic metabolic alkalosis and intravascular volume depletion, the electrolyte composition of 0.9% saline can aid restoration of physiological electrolyte and acid-base balance.
Salt losing tubulopathies such as
• Bartter syndrome
• Cystic fibrosis.
• Infants with pyloric stenosis
• children with traumatic brain injury
Enteral supplementation with a combination of sodium and potassium chloride is preferable, intravenous fluid is required in some situations.
Level v
Will you change your practice based on this article?
For pediatric transplantation patients there is no evidence based. However, if the balanced solutions is available in our center, it would be better to improve our practice using this new generation of solutions
Jamila Elamouri
2 years ago
Ab-normal saline in abnormal kidney function: risks and alternatives
Currently 0.9% saline is the most commonly prescribed intravenous crystalloid. Administration of intravenous saline affects patient’s extracellular fluid and electrolyte status. While some of these effects are therapeutic others may be unintentional and can be harmful. Recently there is evidence for adverse effects with increased mortality in critically ill adults. Excess chloride concentration of 0.9% saline relative to the plasma appears to be the cause specially when kidney function is unable to excrete excess chloride. Recently, balanced intravenous solutions with physiological chloride concentration have been developed alternative to 0.9% saline. Chloride in intravenous fluid
While the tonicity and sodium concentration of 0.9% saline are within 10% of physiological
levels, its chloride concentration exceeds that of plasma by approximately 60%. In contrast, balanced intravenous fluids have chloride concentrations closely aligned to that of plasma. Paediatric practice has been shifted from the use of hypotonic saline to 0.9% normal saline, to avoid hyponatremia, for which many hospitalized children are at its risk, due to vasopressin release stimulated by pain, nausea, gastroenteritis, lung pathology or postoperative. Hyponatremia causes intracellular fluid shifts and brain oedema Which, is of grave outcome. Rapid correction of hyponatremia can also cause osmotic demyelination. Ringer’s lactate is a traditional balanced solution. PlasmaLyte solution recently developed with closer similarity to plasma. Effects of chloride Chloride and mortality
fluid resuscitation with 0.9% saline was associated with more metabolic acidosis and inferior survival than balanced resuscitation fluid. In critically ill patient’s administration of chloride-rich solution is associated with increased mortality especially those with AKI. In keeping with adult studies, pediatric evidence for a link between excess chloride and mortality is emerging. Hypochloremia is also associated with adverse outcomes. The physiology underlying this association remains to be elucidated, but the effect appears to be independent of plasma sodium or potassium concentrations.
The mechanism underlying increased mortality in patients who receive large volumes of chloride-rich crystalloid has not been definitively established. Chloride and acid-base balance
Hyperchloremic metabolic acidosis is consistently observed in both adult and pediatric patients following fluid resuscitation with 0.9% saline.
Etiology of saline-induced hyperchloremic metabolic acidosis
Two theories explain the acute change in PH.
1- Henderson-Hasselbalch theory:
Explain change in PH by changes in partial pressure of Carbone dioxide (PCO2) and thereby carbonic acid.
Henderson-Hasselbalch equation:
PH = PK + log (HCO3-/PCO2 X 0.225)
By this equation the link between excess chloride from 0.9% saline and metabolic acidosis is not immediately obvious.
2- Stewart’s approach:
Based on strong ion theory which gives a physiological explain for excess chloride driving metabolic acidosis. Strong ion theory refers to principles of:
· electroneutrality (all negative and positive charged ions must balance). And
· conservation of mass (total amount of a substance remains constant unless added to, generated, removed or destroyed).
From the above, Stewart’s explanation of acid-base balance is determined by CO2, weak acids, and the strong ion difference.
Plasma strong ion difference is defined as:
= {(Na+) + (K+) + (Ca+) + (Mg+)} – {(Cl-) + (lactate)}
Change in the strong ion difference directly alter plasma PH.
Large volume of iv 0.9% normal saline reduces the plasma strong ion difference via a higher relative increase in plasma Cl- than Na. this will increase dissociation of water to H+ and OH-, thereby driving metabolic acidosis.
The effect on PH is more with N/S 0.90% > Hartmann’s solution > plasmaLyte.
Another theory by which N/S 0.90% induces acidosis is dilutional acidosis, (buffer-free crystalloid dilutes the bicarbonate concentration leads to acidosis). Chloride and kidney perfusion:
Chloride has a direct effect on intra-renal perfusion, vasoconstriction, and glomerular filtration. Many studies strongly implicate chloride-rich iv fluid in acutely reducing kidney blood flow and function. In one study, administration of 2 Ls 0.9% saline shown to decrease renal artery flow velocity ad renal cortical tissue perfusion significantly, but not after plasmaLyte infusion.
Chloride and coagulation:
Chloride-rich fluid impairs coagulation which is not seen in Ringer’s lactate solution. This could be explained by dilutional coagulopathy. In adult undergoing abdominal surgery chloride-rich iv fluid was associated with increase blood product requirement. These make balanced iv fluid preferred in surgical care. Chloride and fluid overload:
Patients with intravascular fluid depletion, injudious use of iv fluid can result in fluid overload. If kidney function is normal, fluid overload is uncommon. But, in AKI or CKD risk of overload is high. Chloride-rich solution use carry risk of fluid overload more than balanced solution. Also, in surgical patients using large volium of 0.9% saline required more blood products than balanced crystalloids. Blood transfusion associated with increased mortality and cardiovascular morbidity and mortality in AKI and CKD patients.
Chloride and blood pressure:
Chloride may influence blood pressure in its ownright. Several studies support this. Hypertensive effect of enteral sodium chloride was not replicated with sodium citrate or phosphate. Recent data explain that sequestration of hypertonic electrolyte in skin and the role of macrophages in regulation of this storage, has led to suggestion that skin chloride accumulation is associated with systemic hypertension.
The case for abandoning 0.9% saline
Because of deleterious effects of excess chloride, many studies are in favor of isotonic balanced solutions such as plasmaLyte.
Balanced fluids were associated with lower mortality, lower prevalence of AKI, and lower inotropic requirements, new renal-replacement therapy or persistent renal dysfunction than 0.9% saline.
Kidney transplant recipient:
Perioperative normal saline was associated with more metabolic acidosis than balanced solution (more hyperchloremic hyperkalemic metabolic acidosis). Finding of more hyperkalemia with 0.9% saline than lactate Ringer,s (contain 4 mmol/l K) was documented in many studies.
PlasmaLyte ( has 5 mmol/L K) has reduced risk of hyperkalemia relative to K-free 0.9% saline. This noteworthy in paediatric patients.
Hyperchloremic acidosis caused by 0.9% saline impairs cellular buffering of K+ thereby predisposing to hyperkalemia.
In contrast; the balanced fluid electrolyte composition and the HCO3 produced from metabolism of gluconate and acetate in these fluids serve to maintain K+ buffering. The small amount of K+ in the balanced fluid is needed to decrease risk of hypokalemia. Case in keeping 0.9%: Hypochloremic metabolic alkalosis conditions that may occur in the following:
1- Bartter syndrome (chloride wasting)
2- Cystic fibrosis
3- Persistent vomiting
4- Pyloric stenosis
5- Traumatic brain injury
Hypertonicity of 0.9% saline may mitigate the risk of cerebral edema more effectively than balanced isotonic saline. Individualized IV fluid prescription:
No one fit for all, children especially those with AKI or CKD need individual prescription of their fluid requirement. According to the medical condition and the response to the fluid.
Wael Jebur
2 years ago
There has been an increasing body of evidence to elucidate high risk of complications integral to utilization of normal saline with its supra-physiologic dose,9s its concentration in is 154 in normal saline vs 106 in plasma).
This variation in concentration was speculatively blamed for inflicting several complications reported, such as metabolic acidosis, increased mortality in intensive care units patients treated with normal saline , AKI and coagulopathy.
The underlying mechanism mediating chloride induced metabolic acidosis was addressed elaboratively by Stewarts proposition for explaining metabolic acidosis, in which the concept of strong ions difference drive the chloride induced acidosis .
The strong ions concept reflect equal numbers of Cations and Anions as follow:
Na+K+Mg+Ca- Cl + lactate. The reduction of this difference stimulate dissociation of H2O to H and OH. Chloride and renal function:
Renal perfusion was found to fall significantly after infusing 2 Liters of normal saline.A phenomenon that was not seen with balanced solutions like Plasmalyte and hartman solution. Chloride and coagulation:
There is increased incidence of thrombosis in patient on normal saline infusion. Chloride and fluid overload:
It was shown evidently that normal saline infusion is associated with reduced diuresis and natriuresis in contrast to Hartmann’s solution use. Chloride and Hypertension:
Chloride storage in skin was linked to hypertension.
It s a narrative study
level of evidence 5
Abdulrahman Ishag
2 years ago
Intravenous 0.9 saline is found to be associated with deleterious effects . These include increased mortality, acute kidney injury (AKI), metabolic acidosis, and coagulopathy. The predominant cause for these sequelae appears to be the excess chloride concentration of 0.9% saline relative to plasma. There is now overwhelming evidence that large volumes of 0.9% saline increase the risk of mortality, metabolic acidosis, and AKI in critically ill adults, and some data suggesting increased postoperative and transplant complications including hyperkalemia. The initial fluid prescription can be based on the presenting plasma chemistry and acid-base status, careful monitoring of patients’ fluid status, plasma, and urine electrolytes is paramount in order to tailor the prescription appropriately. Standard intravenous fluid prescriptions are rarely appropriate; choice of intravenous crystalloid should be guided by patients’ individual clinical status and adjusted in response to monitoring.
What is the evidence provided by this article?
Level V
Mohamad Habli
2 years ago
Intravenous fluid impacts the patient’s extracellular fluid and electrolytes. The higher chloride concentration of 0.9% saline has been associated with increased mortality in critically ill patients, despite its widespread use.
To minimize issues such as osmotic demyelination owing to iatrogenic hyponatremia (due to tonicity and sodium concentration within 10% of physiological values), the intravenous fluid used in pediatric patients was changed from 0.45% or 0.2% saline to 0.9% saline. However, when the chloride concentration exceeds plasma levels, the patient is exposed to the harmful consequences of elevated chloride levels.
Higher chloride levels are related to increased metabolic acidosis and mortality, as well as increased rates of chronic renal impairment, new renal replacement therapy (RRT), and worse outcomes. Higher chloride concentrations exacerbate metabolic acidosis by decreasing the strong ion difference, hence increasing the dissociation of water into H+ and OH–. The effects of metabolic acidosis on cardiac function, renal and intestinal perfusion, neuronal function, and extracellular potassium buffering result in an increase in mortality. A higher chloride concentration causes greater vasoconstriction and decreased GFR, leading to AKI and the requirement for RRT. Rehydration with chloride-rich fluids impairs coagulation due to dilutional coagulopathy. Additionally, chloride-rich fluid causes fluid overload (due to an increased need for blood products), which increases cardiovascular morbidity and death. A greater chloride concentration also results in an increase in blood pressure, an effect observed only with sodium chloride and not with sodium citrate or sodium phosphate.
Why 0.9% saline should no longer be used: Balanced fluids are preferred in transplant recipients due to increased mortality, acute kidney injury, higher inotrope requirements, persistent renal dysfunction, new RRT use, inferior surgical outcomes, increased infection rates, increased blood product requirements, and increased metabolic acidosis and hyperkalemia.
In children with intravascular volume depletion and hypochloremic metabolic alkalosis, such as salt-losing tubulopathies (Bartter syndrome), cystic fibrosis, excessive sweating, persistent vomiting, infants with pyloric stenosis, diabetes insipidus, and traumatic brain injury, 0.9% saline is still useful.
Therefore, the intravenous fluid prescription should be customized based on the patient’s clinical characteristics.
Thank you professor, it has changed our practice based on these articles your lecture and discussion.
Marius Badal
2 years ago
Summarise this article
What is the evidence provided by this article?
The article is about Ab-normal saline in abnormal kidney function risk and alternatives. Normal saline has been the most widely used solution when is related to the other types of solutions. It has been associated with increased mortality, especially in critically ill patients. It has been noted that the dangerous part of the normal saline solution has to do with the concentration of the chloride. Due to the problem with NS other solutions have been developed as a better choice than normal saline.
The aim of the study is to address the effects of chloride content in NS
As it relates to NS it and the plasma concentration of the electrolytes, IV sodium is within the 10% physiological range but it is found that Cl is over 60 % over the plasma requirement. This is why it has effects like metabolic acidosis. When comparing NS with other solutions like Hartmann’s and LR their Cl concentration is less or closer to plasma concentration.
What are the possible effects of high chloride concentration?
1) It increases the mortality rate secondary to the formation of hyperchloremic metabolic acidosis.
2) The high level of Cl and its hyperchloremic acidosis can be found in both adults and children as a complication.
3) The kidney is the organ that regulates most electrolytes and with a high level of Cl, it can affect the tubular-glomerular feedback mechanism reducing GFR.
4) It can cause fluid overload when compare with balanced solutions
5) It has been related to high blood pressure having an impact on intravascular volume.
6) Chloride-rich fluids used in resuscitation can inhibit coagulation.
Reasons to avoid NS:
1) It increases mortality
2) It increases metabolic acidosis
3) Increase infection rate
4) Increase the need for blood products
5) Causes an increase in AKI and high K
Reasons to use NS:
1) Cystic fibrosis
2) Batters syndrome
3) Brain injury
4) Persistent vomiting
In conclusion:
There is no ideal solution for any given situation but one has to look for a better solution to ensure patient survival and reduce mortality and hospitalization. NS although still, the most used solution has more side effects when compared to balanced solutions.
This article’s level of evidence is level 5
Amit Sharma
2 years ago
Summarise this article
Intravenous fluid affects extracellular fluid and electrolytes of the patient. Use of 0.9% saline, although very common, has been shown to be associated with increased mortality in critically ill patients, due to the increased chloride content.
Intravenous fluid use in pediatric population changed from 0.45% or 0.2% saline to 0.9% saline to avoid complications like osmotic demyelination due to iatrogenic hyponatremia (due to tonicity and sodium concentration within 10% of physiological levels). But the chloride concentration being higher than plasma levels, the patient is exposed to deleterious effects of higher chloride levels.
Effects of chloride: Higher chloride levels are associated with higher metabolic acidosis and mortality, higher rates of persistent renal dysfunction, new renal replacement therapy (RRT) and poorer outcomes. Higher chloride levels increase metabolic acidosis by reducing the strong ion difference causing increased dissociation of water to H+ and OH–. Metabolic acidosis affects myocardial function, renal and intestinal perfusion, nerve function and extracellular potassium buffering leading to increased mortality. Higher chloride leads to increased vasoconstriction and reduced GFR causing AKI and need for RRT. Chloride rich fluid resuscitation leads to impairment of coagulation due to dilutional coagulopathy. Chloride-rich fluid also leads to fluid overload (due to increased requirement of blood products) leading to increased cardiovascular morbidity and mortality. Higher chloride also leads to higher blood pressure, the effect seen specifically with sodium chloride, and not with sodium citrate or sodium phosphate.
Why 0.9% saline should be abandoned: Due to increased mortality, AKI, higher inotrope requirement, persistent renal dysfunction, new RRT use, inferior surgical outcomes, increased infection rates, increased blood product requirements, and increased metabolic acidosis and hyperkalemia in transplant recipients associated with 0.9% saline, balanced fluids are preferred.
When to use 0.9% saline: It can still be useful in children with intravascular volume depletion and hypochloremic metabolic alkalosis like in salt-losing tubulopathies (Bartter syndrome), cystic fibrosis, excessive sweating, persistent vomiting, infants with pyloric stenosis, diabetes insipidus and traumatic brain injury.
Hence the intravenous fluid prescription should be individualized depending on the clinical aspects of the patient.
What is the evidence provided by this article?
Level of evidence: Level 5 – Narrative review
Abhijit Patil
2 years ago
Summary:
The tonicity and sodium concentration of 0.9% saline are within 10% of physiological levels
Its chloride concentration exceeds that of plasma by approximately 60%
Recent evidence shows increased mortality with administration of chloride rich IV fluids
NS causes hyperchloremic metabolic acidosis, and thus affects myocardial function, renal and intestinal perfusion, nerve function, and extracellular potassium buffering increasing mortality in critically ill patients
It also causes fluid overload, hyperkalemia and AKI in critically ill patients
The indications for NS would be
hypochloremic metabolic alkalosis
Salt losing tubulopathies such as Bartter syndrome
Cystic fibrosis
severe persistent vomiting (pyloric stenosis)
Traumatic brain injury in children
Balanced fluids may have particular advantages when used as isotonic resuscitation fluid and in kidney transplant recipients.
Children who do not need IV fluids, should be encouraged for enteral route which is safer
We have shifted from NS to balanced fluids especially RL in our country.
Assafi Mohammed
2 years ago
Summary of the article “Abnormal saline in abnormal kidney function- risks and alternatives
Intravenous 0.9% saline, although a widely used solution and has saved countless lives, it has recently found to be associated with deleterious effects because of excess chloride concentration of 0.9% saline relative to plasma: 1. Increased mortality:hyperchloremic metabolic acidosis is strongly implicated. 2. Acute kidney injury (AKI):infusion of chloride-rich fluid in denervated kidneys resulted in vasoconstriction and reduction in glomerular filtration rate. 3. Metabolic acidosis: hyperchloremic metabolic acidosis. 4. Coagulopathy:The anticoagulant effect of 0.9% saline has been ascribed to dilutional coagulopathy related to the significantly larger volume of saline required for resuscitation relative to balanced fluids. 5. Fluid overload:Studies in adult patients suggest that chloride-rich crystal- loid may increase the risk of fluid overload to a greater degree than balanced solutions. In a study of healthy adult volunteers, urinary excretion of water and sodium were inferior following infusion of 2 litres 0.9% saline when compared to Hartmann’s solution. 6. HTN: Several lines of evidence implicate chloride in systemic hypertension.Animal and clinical studies found that the hypertensive effect of enteral sodium chloride was not replicated with sodium citrate or phosphate. 7. Hyperkalemia:Hyperchloremic acidosis from 0.9% saline impairs cellular buffering of potassium, thereby predisposing to hyperkalemia. In favor of 0.9 saline administration: 1. Hypochloremic metabolic alkalosis and intravascular volume depletion. · Salt losing tubulopathies such as Bartter syndrome. · Cystic fibrosis predisposes to excessive chloride loss; excessive sweating can lead to hypochloremic metabolic alkalosis. · Pyloric stenosis: Severe persistent vomiting can develop hypochloremic alkalosis as a result of gastric hydrochloric acid loss. 2. For children with traumatic brain injury, the hypertonicity of 0.9% saline may mitigate the risk of cerebral edema more effectively than balanced isotonic fluids. What is the evidence provided by this article?
This is a narrative review article.
Level of evidence grade 5.
Mohammad Alshaikh
2 years ago
Summarise this article
Introduction: IV normal saline resuscitation saved lives since it was introduced, however the components of intravenous fluids affects the extracellular fluid and electrolytes status. This study highlights the effect of these isotonic fluids solutions on EC fluid and electrolytes as well on patient’s outcomes, this is proposed to be due to excess chloride content of 0.9% saline, so balanced fluids with physiological chloride have been developed. Chloride in intravenous fluid: The rationale of avoiding hypotonic fluids is to it hyponatremic effect that contribute to symptomatic hyponatremia that cause brain edema, permanent neurological deficit, and even increase death. The rapid correction of hyponatremia can cause osmotic demyelination and neurological deficit. Makes the isotonic fluid solutions safe and more in use, however the normal saline content of sodium is 10% of physiological level, and the chloride content is 60% more than plasma chloride levels. This mandate development of solutions with closer alignment to plasma constituents such as Hartmann’s, Ringer’s lactate, and lately PlasmaLyte. Effects of chloride: On mortality: Hyperchloremic metabolic acidosis is highly implicated in increased mortality in patients receiving large volumes of chloride-rich crystalloid solutions. Etiology of saline-induced hyperchloremic metabolic acidosis: 1. Stewart’s strong ion theory gives a physiological rationale for excess chloride driving metabolic acidosis. Strong ion difference= ([Na]+[K]+[Ca]+[Mg] postively charged)-([Cl]+[Lactate] negatively charged) changes in the strong ion difference directly alter plasma pH. Thus reduction in strong ion difference by 0.9% N/S will increase dissociation of water to H+ and OH−, thereby driving metabolic acidosis. 2. Dilutional acidosis – the infusion of buffer-free crystalloid dilutes the bicarbonate concentration in extracellular fluid thereby precipitating acidosis. Metabolic acidosis affects myocardial function, renal and intestinal perfusion, nerve function, and extracellular potassium buffering, it is likely to play a role in the increased mortality observed in critically ill patients who receive large volumes of 0.9% saline. Chloride and renal perfusion: In healthy adult volunteers, renal artery flow velocity and renal cortical tissue perfusion fell significantly from baseline after infusion of 2 liters 0.9% saline, but not with osmolyte. And was associated with more AKI and renal replacement therapy in critically ill patients. This was not the case in SPLIT trial used low fluid volumes. Chloride and coagulation: The anticoagulant effect of 0.9% saline due dilutional coagulopathy related to the significantly larger volume of saline required for resuscitation relative to balanced fluids. Chloride and fluid overload: This could be due to larger volumes needed or the increased requirement of blood product transfusion in normal saline resuscitated patients. Fluid overload has is associated with increased mortality in critically ill children and neonates with AKI. Chloride and blood pressure: 1. The skin chloride accumulation is associated with systemic hypertension. 2. Reduction in intracellular chloride in combination with the regulatory protein Mo25 were found to stimulate WNK activity in distal nephron and transcellular ion flux in the renal epithelium, thus affecting blood pressure.
The case for abandoning 0.9% saline: Chloride-rich resuscitation fluid associated with higher mortality, metabolic acidosis, increased infection rate, AKI, longer time on mechanical ventilation, and the more need of blood product transfusion. Balanced fluids were associated with lower mortality, lower prevalence of AKI, and lower inotrope requirements. In kidney transplantation, N/S 0.9% infusion associated with hyperchloremic metabolic acidosis, hyperkalemia when compared to balanced fluids infusion. The case for keeping 0.9% saline: In cases of hypochloremic metabolic alkalosis such as : Bartter syndrome, cystic fibrosis, persistant vomiting, and intravascular volume depletion. Individualized intravenous fluid prescriptions: The initial crystalloid fluid prescription should be based on the patients clinical presentation, plasma chemistry and acid-base status, careful monitoring of patients’ fluid status, plasma, and urine electrolytes is mandatory.
Conclusion: The deleterious effect of excess chloride in 0.9% N/S, makes the balanced fluids used more. Hyperchloremic acidosis from 0.9% saline has a greater risk of hyperkalemia when compared to balanced potassium containing fluids. Balanced fluids may have particular advantages when used as isotonic resuscitation fluid and in kidney transplant recipients. The fluid prescription should be based on patient’s clinical condition, plasma chemistry and fluid status. Enteral fluids and electrolytes should be encouraged when possible due to it’s major safety.
What is the evidence provided by this article? Level of evidence V
Manal Malik
2 years ago
Summary of Ab-normal saline in abnormal kidney function- risks and alternativesIntroduction:
0.9% Saline is most common IV crystalloid given in paediatric .
Excess chloride of 0.9% saline relative to plasma may be result in increasing mortality in critical ill adults in large randomized trial.
This review outlines current evidence for the effects of excess chloride in 0.9% saline and whether its use in clinical practice is still justified Chloride in intravenous fluid:
0.9% saline is the most commonly intravenous fluid and its tonicity and sodium concentration are within 10% of physiological levels it chloride concentration exceed that of plasma by approximately 60%
Balanced intravenous fluids have chloride concentration closely aligned to the plasma.
Included Hartmann’s or Ringer Lactate and plasma-Lyte
Excess chloride which result from 0.9% saline has serious effects especially in children with impaired kidney function. Effects of chloride: Chloride and metabolites:
0.9% saline was associated with more metabolic acidosis and inferior survival than balanced resuscitation fluid
In some of the studies chloride-rich intravenous fluid result in mortality in critically ill adults and even death new renal replacement therapy or persistent renal dysfunction in patients received 0.9% saline opposed to balanced intravenous crystalloid. Chloride and acid-base balance:
Hyperchloremic metabolic acidosis is observed in both adult and paediatric patients following resuscitation with 0.9% saline Aetiology of saline induced hyperchloremic metabolic acidosis:
The underline mechanism of acute acid disturbance :
1. Hendreson and Siggaard think that acute change in plasma PH are explained by changes in partial pressure of carbon dioxide PCO2 and there by carbonic acid. But using an approach the link of excess chloride form 0.9% saline and metabolic acidosis is not obvious.
2-St ewart theory it refers to principle of electrolytes neutrality.
He proposed that changes in the strong was differences directly after plasma PH
3-Also dilutional acidosis by saline can induce metabolic acidosis
However anon linear relationship between extracellular volume expansion and reduction in bicarbonate concentration doesn’t support this concept. Chloride and kidney perfusion:
Some of studies suggest direct effect of chloride an inter-renal perfusion, vasoconstriction and glomerular filtration so data from preclinical models and adult patients strongly implicate chloride-rich intravenous fluid in acutely reducing in day blood flow and function. Chloride and coagulation:
0.9% saline has dilutional coagulopathy related to the significantly larger volume of saline for resuscitation relative to balanced fluid. Chloride and fluid overload:
As haemostasis is disrupt in AKI or CKD children
Studies in adult patients suggest that chloride-rich crystalloid may increase the risk of fluid overload to a greater degree than balanced solutions Chloride and blood pressure:
Several lines of evidence implicate chloride in a systemic hypertension and renal vascular resistance but still further studies are needed for chloride in BP regulation.
A systematic review of studies in adult kidney transplant recipient concluded that perioperative normal saline was associated with more metabolic than balanced solutions.
Now there is evidence that large volume of 0.9% saline increase the risk of mortality metabolic acidosis and AKI in critical ill adults and some data suggest increased postoperative and transplant complications including hyperkalaemia
In clinical condition which can cause hyperchloremic alkalosis and intravascular depletion 0.9% saline is preferable to balanced solution. Summary:
· Balanced fluid in adult patients result in lower mortality, less AKI and less perioperative complications than 0.9% saline
· 0.9% saline causing hyperchloremic acidosis has a greater risk of hyperkalaemia
· Although paediatric date are scant
· Balanced fluids have advantage in kidney transplant recipient
· Underline medical condition, plasma concentration and fluid status need to be consider before given fluid to the child.
· The higher Cl content of isotonic saline (60 % highrer than the plasma) was accused to cause hyperchloremic metabolic acidosis and higher incidence of AKI, metabolic acidosis and coagulopathy.
· In children, the use of isotonic saline is the standard to avoid risk of hyponatremia and brain edema. however, rapid correction of hyponatremia leads to central pontine myelinosis.
· Risk and hazards associated with high Cl content of isotonic saline:
o Higher mortality.
o Higher incidence of hyperchloremic metabolic acidosis.
o Higher incidence of AKI (in chloride rich solutions than Cl restrictive strategy), However, no RCT in pediatric patients and opposing results was found in SPLIT trial that AKI was comparable between saline and ringer fluid resuscitation.
o Higher risk of bleeding, coagulopathy and need for blood products transfusion.
o Edema and hypervolemia especially in patients with AKI and CKD (unable to maintain the fluid balance), which is independent risk factor of cardiovascular mortality in critically patients with AKI.
o Hypertension mediated by renal vessels vasoconstriction.
· Why to stop isotonic saline (what is against)?
o As plasma lyte 148 (balanced crystalloid solution) was associated with lower mortality, AKI, less need to positive inotropes, persistent renal dysfunction and need to RRT.
o Saline 0.9 % was associated with higher incidence of post operative infection, mortality and need for blood component transfusion, after major abdominal surgery. Also it increased need for mechanical ventilation in critically ill patients.
o Use of saline in KT was associated with higher incidence of metabolic acidosis and hyperkalemia, due to impaired renal ability to handle the fluid and acid base balance. Plasmalyte decreased incidence of hyperkalemia in adult kidney transplant recipients.
o The relatively small quantity of K in balanced solutions is able to mitigate the risk of hypokalemia. In addition, the physiology of K homeostasis, keeps the balanced solutions reduce the risk of hyperkalemia in such patients with impaired kidney function.
· Why to keep isotonic saline as a standard resuscitation fluid (what is with?)
o In cases with hypochloremic metabolic alkalosis and intravascular volume depletion as in children with Bartter syndrome and pseudo-Bartter as (cystic fibrosis and persistent vomiting as in pyloric stenosis).
· Conclusion:
o Fluid therapy should be individualized according to the volume status , acid base status and biochemical composition and serum electrolytes (one size does not fit all).
o Patients with either AKI or CKD are at the highest risk from inappropriate IV fluids (saline may be harmful as those kidneys can not excrete excess chloride, balanced solution does not increase risk of hyperkalemia).
o Diabetes inspidus needs hypotonic fluids (saline is harmful).
o Children with hypocholoremic alkalosis, needs saline (balanced crystalloid solution does not compensate them).
Level of evidence: narrative review (level V)
Huda Al-Taee
2 years ago
Summary:
Administration of intravenous fluid directly affects patients’ extracellular fluid and electrolyte status. Some of these fluids have the potential to cause harm. A large randomised trial showed that 0.9% NS administration is associated with increased mortality due to excess chloride. Patients with abnormal kidney function have a reduced capacity to excrete excess chloride.
Balanced intravenous solutions with physiological chloride concentration have been developed.
Effects of chloride
Chloride and mortality
In cases of sepsis, fluid resuscitation with 0.9% saline was associated with more metabolic acidosis and inferior survival than balanced resuscitation fluid.
A cluster-randomized, multiple crossover trial in 15,802 adults in intensive care found a higher rate of death, new renal replacement therapy, and persistent renal dysfunction in patients who received 0.9% saline as opposed to balanced intravenous crystalloid.
Low serum chloride levels were a strong predictor of mortality in a 10-year follow-up study of over 9000 adults.
Chloride and kidney perfusion
Data from preclinical studies and clinical trials suggest a direct effect of chloride on intra-renal perfusion, vasoconstriction, and glomerular filtration.
In healthy adult volunteers, renal artery flow velocity and renal cortical tissue perfusion fell significantly from baseline after infusion of 2 litres 0.9% saline, but not after PlasmaLyte.
In a multiple crossover trial comparing 0.9% saline with balanced crystalloids in 13,347 non-critically ill adults attending an emergency department, a higher incidence of major adverse kidney events following 0.9% saline.
Chloride and coagulation
In adult patients undergoing major abdominal surgery, chloride-rich intravenous fluid was associated with increased blood product requirements.
The anticoagulant effect of 0.9% saline has been ascribed to dilutional coagulopathy related to the significantly larger volume of saline required for resuscitation relative to balanced fluids.
Chloride and fluid overload
In a study of healthy adult volunteers, urinary excretion of water and sodium was inferior following infusion of 2 litres 0.9% saline when compared to Hartmann’s solution.
Chloride and blood pressure
Several lines of evidence implicate chloride in systemic hypertension.
Recent understanding of hypertonic electrolyte sequestration in the skin, and the role of macrophages in the regulation of this storage, has led to the observation that skin chloride accumulation is associated with systemic hypertension.
The case for abandoning 0.9% saline
0.9% saline was the resuscitation fluid of choice to manage intravascular depletion; data suggest that this is no longer appropriate.
When used as a resuscitation fluid in children in intensive care, balanced fluids were associated with lower mortality, lower prevalence of AKI, and lower inotrope requirements in a propensity-matched analysis of over 3000 children from 43 centers.
A randomized study of over 15,802 adults confirmed that balanced crystalloids result in a lower rate of a composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than 0.9% saline.
Evidence showed inferior surgical outcomes in patients receiving 0.9% saline.
Inferior outcomes are consistently reported in patients at risk of AKI who receive 0.9% saline.
A Cochrane systematic review of studies in adult kidney transplant recipients concluded that perioperative normal saline was associated with more metabolic acidosis than balanced solutions.
PlasmaLyte (containing 5 mmol/l potassium) has also been shown to reduce the risk of hyperkalemia relative to potassium-free 0.9% saline in adults with end-stage kidney disease undergoing transplantation.
The case for keeping 0.9% saline
For children with hypochloremic metabolic alkalosis and intravascular volume depletion, the electrolyte composition of 0.9% saline can aid the restoration of physiological electrolyte and acid-base balance.
Salt-losing tauopathies such as Bartter syndrome.
Cystic fibrosis is a further disorder which predisposes to excessive chloride loss; excessive sweating can lead to hypochloremic metabolic alkalosis.
Children who experience severe persistent vomiting.
Infants with pyloric stenosis.
children with traumatic brain injury.
Level of evidence:
Level 5 ( review article).
Hussam Juda
2 years ago
· There is evidence that 0.9% saline increased mortality in critically ill adults could be due to hyperchloremia
· Patients with impaired kidney function have more risk oh hyperchloremia
· Pediatric practice has changed over the last decade with a shift away from hypotonic (0.45% or 0.2% saline) to predominantly 0.9% saline to prevent hyponatremia
· The association of chloride-rich intravenous fluid and mortality is increasingly recognized in critically ill adults
· Hyperchloremic metabolic acidosis is consistently observed in both adult and pediatric patients following fluid resuscitation with 0.9% saline
Etiology of saline-induced hyperchloremic metabolic acidosis. There are 2 schools:
1.Henderson-Hasselbalch and Siggaard-Anderson school: acute alterations in plasma pH are explained by changes in partial pressure of carbon dioxide (pCO2) and thereby carbonic acid
2.Stewart’s strong ion theory gives a physiological rationale for excess chloride driving metabolic acidosis
· The effect of metabolic acidosis on myocardial function, renal and intestinal perfusion, nerve function, and extracellular potassium buffering, make the Stewart’s theory more likely
Chloride and kidney perfusion
· Data from pre-clinical models and adult patients strongly implicate chloride-rich intravenous fluid in acutely reducing kidney blood flow and function.
Chloride and coagulation
· In adult patients undergoing major abdominal surgery, chloride-rich intravenous fluid was associated with increased blood product requirements
Chloride and fluid overload
· Data suggestive of increased risk of fluid overload in patients receiving 0.9% saline as opposed to balanced solutions
Chloride and blood pressure
· Several lines of evidence implicate chloride in systemic hypertension.
· Recent observation that skin chloride accumulation is associated with systemic hypertension.
The case for abandoning 0.9% saline
· Now there is evidence that large volumes of 0.9% saline increase the risk of mortality, metabolic acidosis, AKI in critically ill adults, and increased postoperative and transplant complications
The case for keeping 0.9% saline
· 0.9% saline still needed for Bartter syndrome, Cystic fibrosis, children with hypochloremic alkalosis due to severe vomiting (e.g., pyloric stenosis)
· For children with traumatic brain injury, of 0.9% saline may reduce the risk of cerebral edema more effectively than balanced isotonic fluids
Summary
· In adult patients, balanced fluids are associated with lower mortality, less AKI, and less perioperative complications than 0.9% saline
· No evidence that potassium content of balanced fluids in patients with abnormal kidney function induced hyperkalemia, while hyperchloremic acidosis from 0.9% saline confers a greater risk of hyperkalemia
· PlasmaLyte could be better for the majority of children, particularly those with abnormal kidney function and reduced capacity to excrete excess chloride
· IV fluids should be prescribed case by case and if not indicated, enteral feeding is advised if tolerated
This is a narrative review evidence 5
Heba Wagdy
2 years ago
Introduction:
0.9% saline is a commonly used IV fluid, recently several trials showed its association with many adverse effects due to excess chloride concentration relative to plasma, patients with renal impairment are at increased risk for these adverse effects.
Balanced isotonic solutions are considered more physiological and a better alternative to 0.9% saline. Chloride in IV fluid:
The chloride concentration of 0.9% saline exceed that of plasma by approximately 60% while balanced IV fluids have chloride concentration similar to plasma.
Excess chloride in normal saline is associated with several side effects and children with renal impairment are at increased risk for these effects. Effects of chloride: Chloride and mortality:
Recent evidence showed an association between chloride rich fluids and mortality in critically ill patients, hyperchloremia was attributed as a strong predictor of mortality independent of plasma sodium and potassium concentration Chloride and acid base balance:
Chloride rich fluids increase the risk of metabolic acidosis, 2 proposals are available, the Handerson-Hasselbalch approach and Steward strong ion therapy that explain changes in plasma pH according to changes in strong ion differences, alternative explanation is dilutional acidosis. Chloride and kidney perfusion:
Preclinical studies and clinical trials showed that chloride rich IV fluid cause acute reduction in kidney blood flow and function. Chloride and coagulation:
Chloride rich fluids are associated with impaired coagulation may be due to dilutional coagulopathy related to relatively larger volume of saline required for resuscitation. Chloride and fluid overload:
In adults, using normal saline was associated with higher risk of fluid overload compared to balanced solutions. Chloride and blood pressure:
Several preclinical and clinical trials implicate chloride in systemic HTN, its effect in blood pressure regulation is important when selecting IV fluid. The case for abandoning 0.9% saline:
Resuscitation with balanced fluids was associated with lower mortality, lower prevalence of AKI compared to chloride rich fluids.
0.9% saline was associated with inferior surgical outcomes and more use of blood products compared to plasmaLyte.
In kidney transplantation, perioperative normal saline was associated with more metabolic acidosis than balanced solutions, significantly higher hyperkalemia due to hyperchloremic metabolic acidosis that lead to extracellular shift of potassium while risk of hyperkalemia from potassium in balanced solution is not justified. The case of keeping 0.9% saline:
Clinical conditions with hypochloremic alkalosis and intravascular volume depletion as in children with salt losing tubulopathies, cystic fibrosis and those with severe persistent vomiting. Individualization of IV fluid prescription:
Should be according to medical condition and choice of fluid should be guided by patient individual clinical status and adjusted in response to monitoring.
Level of evidence: 5
KAMAL ELGORASHI
2 years ago
Summary of the erticle; Intravenous fluid affects extracellular fluid and electrolytes content, with evidence noted harm effects of 0.9 NS as an undesirable effects, which lead to development of balanced IV fluid with physiological chloride to avoid metabolic acidosis and hyperkalemia associated with NS administration. In recent randomized trial found that IV NS associated with increased mortality in critically ill adults, this is because of hyperchloremia in NS, and the patients with reduced kidney function have a reduce capacity to excrete excess chloride.
Balanced fluid with physiological saline recently develop to substitute NS. Chloride in intravenous fluid;
NS have chloride content more by about 60% the physiological level.
Present balanced solution, like LR or Hartman solution contain chloride similar to that of plasma.
There is increasing evidence that NS has a harm effect due to hyperchloremic effect.
Effect of chloride;
Chloride excess- IV fluid associated with increased mortality.
Analysis of 53,448 adults with sepsis and AKI, patients receive chloride-rich IV fluid experience increased mortality.
A recent cluster-randomized trial in 15,802 adults, in ICCU, found that a higher out come of composite (death, new RRT, or CKD, in patients who receive NS, as opposed to balanced solution.
Analysis of 890 children with septic shock in 29 PICU in USA, hyperchloremia was associated with inferior outcome (mortality, complicated clinical coarse).
In a study of 9000 adults, found that hypochloremia associated with adverse outcome, and independent predictor of mortality, in a 10 years follow up study.
Chloride and acid-base balance;
Hyperchloremic metabolic acidosis observed in patient with 0.9% NS in both adults and pediatrics, with infusion with NS.
A Cochrane systematic review of postoperative IV fluid management in adult patients concluded that chloride-rich fluid , compared to balanced solution, associated with the risk of metabolic acidosis.
Acidosis caused by (according to Stewart) reduction of strong ion difference, which lead to increase dissociation of water into H and OH, so deriving metabolic acidosis.
Another explanation is the dilution of bicarbonate by excess buffer free solution.
Chloride and kidney perfusion;
In healthy adults volunteer, renal artery flow velocity, and renal cortical tissue perfusion fell after infusion of 2 L of 0.9% saline, but not after plasmaLyte.
A chloride-rich IV associated with AKI and RRT, than chloride-restrictive fluid in a study of 760 adult patients in ICU.
Another recent multiple crossover trial compare 0.9% saline with balanced crystalloids in 13,347 noncritical ill adults, found a higher incidence of major adverse kidney event following 0.9% saline.
Chloride and coagulation;
In adult patient undergoing major abdominal surgery, chloride-rich IV was associated with increased blood products requirements.
0.9% saline associated with dilutional coagulopathy, but this point need more work to prove.
Chloride and fluid overload;
Adult patient with impaired kidney function may develop fluid overload with injudicious use of IV fluid.
Urinary excretion of water and sodium were inferior following infusion of 2L of 0.9% saline, compared to Hartmann’s solution.
In other hand blood product’s associated with 0.9% saline also give a chance for volume overload.
Fluid overload increase mortality rate in critically ill children and neonates with AKI.
When to choose 0.9% saline;
0.9% saline should be kept as fluid of choice if patient have hypochloremia metabolic acidosis, and intravascular volume depletion.
Salt losing tubulopathy, (e.g. Bartter S).
Cystic fibrosis., associated with excessive chloride loss , excessive sweating lead to hypochloremia metabolic acidosis.
Sever persistent vomiting, associated with hyperchloremic metabolic alkalosis.
Traumatic brain injury, hypertonicity of 0.9% saline help to protect against brain edema.
Summary;
Balanced solution is better than 0.9% saline on account of adverse effect that associated with chloride-rich fluid .
0.9% saline is better in cases of hypochloremia.
Fluid management should be individualized.
Level of evidence ((V)) Review
Huda Mazloum
2 years ago
● 0.9% saline is the most crystalloid in both adult and pediatric practice.
● Recently there is accruing evidence for adverse effects of normal saline
● The predominant cause for these sequelae is the excess chloride concentration of 0.9% saline relative to plasma
● Patients with abnormal kidney function have reduced capacity to excrete excess chloride, which increases their risk of these complications.
● Pediatric practice has changed with a
shift away from hypotonic intravenous fluids to predominantly 0.9% saline to avoid hyponatremia due to vasopressin release stimulated by nausea, pain, gastroenteritis, lung pathology, or the postoperative state
● Hyponatremia predisposes to brain edema which can cause permanent neurological impairment or even death
● Rapid correction of hyponatremia can also result in osmotic demyelination.
● The most commonly prescribed intravenous fluid is currently 0.9% saline
● Traditional balanced solutions are Hartmann’s or Ringer’s lactate Solutions
● Effects of chloride
** increased mortality
** more metabolic acidosis
** inferior survival than balanced resuscitation fluid
● metabolic acidosis affects myocardial function, renal and intestinal perfusion, nerve function, and extracellular potassium buffering so increased mortality observed in critically ill patients who receive large volumes of 0.9% saline.
● Chloride has a direct effect on intra-renal perfusion, vasoconstriction, and glomerular filtration.
● renal artery flow velocity and renal cortical tissue perfusion fell significantly from baseline after infusion of 2 litres 0.9% saline,but not after PlasmaLyte
● Chloride-rich resuscitation fluid impairs coagulation that were not observed with lactated Ringer’s solution
● in children with AKI or chronic kidney disease (CKD), extracellular fluid volume homeostasis is often perturbed.
● patients receiving 0.9% saline for volume resuscitation required more blood products than those who received balanced crystalloids
● Blood products increase the risk of circulatory overload and which increased mortality in critically ill children and neonates with AKI
● Overload is a key contributor to cardiovascular morbidity and mortality in children with CKD
● skin chloride accumulation is associated with systemic hypertension
● balanced fluids were associated with lower mortality, lower prevalence of AKI, and lower inotrope requirements
● postoperative use of 0.9% saline was associated with
** metabolic acidosis
** increased mortality
** increased infection rates
** increased blood product requirement
** Inferior outcomes in patients at risk of AKI
** Increased incidence of AKI
compared to PlasmaLyte
● PlasmaLyte (containing 5 mmol/l potassium) shown to reduce the risk of hyperkalemia relative to potassium-free 0.9% saline in adults with end-stage kidney disease undergoing transplantation
● For patients with Salt losing tubulopathies such as Bartter syndrome , Cystic fibroses , traumatic brain injury, and pyloric stenosis , 0.9% saline is preferable to a balanced solution.
● Balanced fluids may have particular advantages when used as isotonic
resuscitation fluid and in kidney transplant recipients.
● However Prescriptions must be tailored to each individual child’s needs considering their underlying medical condition, plasma chemistry, and fluid status.
Level 5
III. Ab-normal saline in abnormal kidney function- risks and alternatives
1. Summarise this article This study evaluates current evidence for the effects of excess Cl- in 0.9% saline & assess whether its use in clinical practice is still justifiable. Chloride in IV fluid Iatrogenic hyponatremia is a concern when hypo-tonic IV fluids (0.45% saline or 0.2% saline) are used in children; the rational for recent shift to 0.9% saline, as isotonic IV fluids reduce this risk. Although the tonicity & Na+ conc. of 0.9% saline are within 10% of physiological levels, its Cl- conc. exceeds that of plasma by 60%; while balanced IV fluids have Cl- conc. close to that of plasma. Effects of chloride 1.Increased mortality than balanced resuscitation fluid; hyperchloremic metabolic acidosis is implicated as a possible mechanism. 2.Hyperchloremic metabolic acidosis in both adult & pediatric patients following fluid resuscitation with 0.9% saline. 3.Reduced intra-renal perfusion & GFR, more AKI & RRT. 4.Impairs coagulation & increases blood product requirements. 5.Increases fluid overload especially in children with AKI or CKD. 6.Increase blood pressure & implicated in systemic HTN. Why to abandon 0.9% saline? 1.When used in children in ICU, balanced fluids were associated with lower mortality, lower prevalence of AKI, & lower inotrope requirements (analysis of >3000 children, 43 centers). 2.Adult studies show a strong link between chloride-rich resuscitation fluid & subsequent mortality in critically ill patients; balanced crystalloids result in a lower rate of death, new RRT, or persistent renal dysfunction than 0.9% saline. 3.An observational analysis of > 30,000 adults undergoing abdominal surgery, pos-top use of 0.9% saline was associated with metabolic acidosis, increased mortality, increased infection rates, & increased blood product requirement, compared to PlasmaLyte. 4.Inferior outcomes are seen in patients at risk of AKI who receive 0.9% saline. 5.Increased incidence of AKI was seen in a study of 760 adults when a chloride liberal IV fluid was used, as opposed to a chloride-restrictive strategy. 6.A meta-analysis found an increase in AKI & mechanical ventilation time in patients in whom chloride rich resuscitation fluid was used. 7.A Cochrane systematic review of adult KTX recipients found that peri-op normal saline was associated with more metabolic acidosis than balanced solutions. The reasons for keeping 0.9% saline 1.For children with hypochloremic metabolic alkalosis (salt losing tubulopathies such as Bartter syndrome) & volume depletion, 0.9% saline can restore physiological electrolyte & acid-base balance. 2.Cystic fibrosis predisposes to excessive chloride loss; excessive sweating can lead to hypo-chloremic metabolic alkalosis. 0.9% saline is a better choice of crystalloid in context of volume depletion in these cases. 3.Infants with pyloric stenosis are at risk of hypo-chloremic alkalosis due to gastric losses; 0.9% saline + KCl can normalize electrolyte & acid-base balance. 4.0.9% saline may reduce the risk of cerebral edema more effectively than balanced isotonic fluids in chilfren with traumatic brain injury. ///////////////////////////////// 2. What is the evidence provided by this article? Level V
Introduction
Intravenous normal saline has been used for many decades. However, recently large trials in adults have shown that it results in increased mortality, acidosis, coagulopathy and acute kidney injury. Balanced solutions like PlasmaLyte and Hartmanns solutions have been developed that are more physiological than normal saline. The review aimed to outline the current evidence of the effects of excess chloride in 0.9% saline, and if it is still justified to use it as the intravenous (IV) fluid of choice in patients with renal disease. This is important to assess as the use of IV fluids affects the patient’s fluid and electrolyte status
Chloride in intravenous fluid
Pediatric practice has recently shifted away from using hypotonic IV fluids due to the risk of iatrogenic hyponatremia. Hospitalized pediatric patients have a higher risk of hyponatremia as nausea, pain gastroenteritis and post-operative status may result in the release of vasopressin. Hyponatremia can be especially worrying as it may cause brain edema which can lead to permanent neurological deficits and even death. Osmotic demyelination may occur if the low sodium is corrected too fast. For most of the pediatric patients, using isotonic solutions reduces the risk of hyponatremia. However, isotonic solutions cannot be used in all situations, such as diabetes insipidus. Children are at a particular risk of developing hyponatremia if they have impaired renal function as they have a reduced capacity to excrete the extra chloride.
Effects of chloride Chloride and mortality
In patients with sepsis, using 0.9% saline was associated with increased incidence of metabolic acidosis and poor rates of survival, when compared to a balanced resuscitation fluid. This was seen in a study conducted in critically ill adults and also a study conducted in pediatric patients, with a diagnosis of sepsis and acute kidney injury.
Chloride and acid-base balance
In adult and pediatric patients resuscitated with 0.9% saline, hyperchloremic metabolic acidosis is frequently observed. This is because, when large volumes of 0.9% saline are administered, there will be an increase in chloride ions compared to sodium ions in plasma, which will increase the dissociation of water to hydrogen and OH ions, thereby causing metabolic acidosis. This is known as Stewart’s strong ion theory.
Chloride and kidney perfusion
Chloride directly reduces intra-renal perfusion, causes vasoconstriction and reduces glomerular filtration rates. This results in AKI and eventual renal replacement therapy. No pediatric studies have been published for the same.
Chloride and coagulation
There are studies that show that 0.9% saline used for resuscitation have resulted in coagulopathy. This was not observed when the choice of IV fluid was Ringer’s lactate.
Chloride and fluid overload
In children with AKI or CKD, the risk of fluid overload is greater, and studies have shown that the use 0.9% saline has a higher risk of circulatory overload when compared to balanced fluids. Fluid overload has been shown to lead to increased mortality in critically ill children with AKI.
Chloride and blood pressure
Animal and clinical studies have shown that chloride may have a direct effect on the blood pressure. The exact mechanism is still under debate.
The case for abandoning 0.9% saline
The use of balanced fluids in critically ill children have been associated with lower mortality, lower prevalence of AKI and lower requirements of ionotropic support. This has also been replicated in adult studies. Poor outcomes were reported in patients at risk of AKI who received 0.9% saline. For patients undergoing renal transplantation, systematic reviews have observed that patients receiving 0.9% saline during the surgery resulted in a higher incidence of metabolic acidosis. Studies showed that the incidence of hyperkalemia was also greater in patients receiving normal saline, as compared to a more balanced fluid, during kidney transplantation.
The case for keeping 0.9% saline
For patients with hyperchloremic metabolic acidosis and intravascular fluid depletion, 0.9% saline will aid in restoring normal acid-base balance. In patients suffering with conditions that result in urine chloride wasting, such as Bartter syndrome, high chloride therapy is required, and hence will benefit from 0.9% saline. Cystic fibrosis leads excessive chloride loss, and the appropriate fluid of choice is normal saline. Persistent vomiting may lead to hypochloremic metabolic acidosis, due to gastric hydrochloric acid loss, and therefore, normal saline is the preferred IV fluid. For children with traumatic brain injury, using 0.9% saline may reduce the risk of cerebral edema.
Summary
The above arguments show us that an individualistic approach should be used in IV fluid selection. Normal saline has been associated with increased mortality, metabolic acidosis, coagulopathy and AKI. The pathogenesis of acidosis with normal saline is due to a reduction in the strong ion difference which leads to dissociation of water in to hydrogen and oxygen. The other theory is dilutional acidosis. Balanced solutions have been shown to reduce the risks associated with normal saline. Pediatric data is scant but still shows that balanced solutions are better than normal saline.
The most widespread crystalloid fluid in both adult and pediatric remains Normal saline.
However, there is an evidence of deleterious effects resulting from excess chloride concentration of 0.9% saline relative to plasma. This has led to development of balanced isotonic solutions such as PlasmaLyte.
Chloride in intravenous fluid The tonicity and sodium concentration of NS are within 10% of physiological levels, its chloride concentration exceeds that of plasma by approximately 60%. In contrast balance solutions have chloride concentration similar to plasma.
Children with impaired kidney function are at particular risk of these sequelae due to reduced capacity to excrete excess chloride.
Effects of chloride Chloride and mortality: both in adult and pediatric a growing evidence link hyperchloremia as independently associated with inferior outcomes including mortality and complicated clinical course. The exact pathophysiology not yet definitive, but likely linked to development of hyperchloremic metabolic acidosis.
Chloride and acid-base balance: NS and CL-rich fluid significantly increases the risk of metabolic acidosis which affects myocardial function, renal and intestinal perfusion, nerve function, and extracellular potassium buffering.
Chloride and kidney perfusion renal perfusion fell significantly from vasoconstriction and reduction in GFR, resulted in higher incidence of major adverse kidney events; AKI and RRT.
Chloride and coagulation increased blood product requirements. The anticoagulant effect has been ascribed to dilutional coagulopathy.
Chloride and fluid overload :resulted from disturbed feedback mechanisms and adjustment of urine volume and natriuresis, reduce urinary excretion of water and sodium. Fluid overload has serious sequelae, increased mortality Avoiding fluid overload is therefore a key priority by avoiding CL-rich fluid.
Chloride and blood pressure increase risk of systemic HTN.
The case for abandoning 0.9% saline: Taken together, there is now overwhelming evidence that large volumes of 0.9% saline increase the risk of mortality, metabolic acidosis, and AKI in critically ill adults, and some data suggesting increased postoperative and transplant complications including hyperkalemia.
Pediatric data are scant so definitive conclusions cannot be drawn; however, for volume resuscitation and kidney transplant care, the case for abandoning 0.9% saline in favor of balanced solutions is compelling.
The case for keeping 0.9% saline: In clinical conditions which predispose to hypochloremic alkalosis and intravascular volume depletion (i.e: salt losing tubulopathies, Cystic fibrosis, persistent vomiting) 0.9% saline is preferable to balanced solutions which may not adequately compensate chloride loss. It can therefore be argued that 0.9% saline should never be completely abandoned, because it is the most appropriate crystalloid for some children as part of an individualized fluid prescription.
Individualized intravenous fluid prescriptions: All children who require intravenous fluid need an individualized prescription that is based on their medical condition and tailored in response to changes in their fluid, electrolyte, and acid-base status.
Level of evidence: 5 narrative review.
This article gave an insight about the effect of commonly used fluid in practice, however, if both balanced and NS are available, balanced solution provides more favorable outcome. Treatment needs to be individualized according to the patient condition and available fluid.
I liked reading your summary, strengths of study and your conclusions. Ajay
Mohamed Saad
2 years ago
Ab-normal saline in abnormal kidney function: risks and alternatives. Introduction.
Normal saline 0.9 is considered the most common intravenous fluid used worldwide and has many benefits but recently some studies revealed the deleterious effect of it specially with CKD patients, mainly due to chloride content which led to metabolic acidosis, coagulopathy and hyperkalemia.This review outlines current evidence for the effects of excess chloride in 0.9% saline. Chloride in intravenous fluid.
Using of hypotonic saline has risk effect of developing hyponatremia with neurological manifestation and so isotonic saline started to replace it, Isotonic saline is with accepted sodium concentration but its chloride concentration exceeds that of plasma by approximately 60%, correspondingly traditional balanced solutions are Hartmann’s or Ringer’s lactate has close chloride concentration to plasma and there is solutions with even closer alignment to plasma constituents have subsequently
been developed such as PlasmaLyte. Effects of chloride.
Chloride and mortality.
RCs done on 15,802 adults on intensive care found a higher rate of a composite outcome of death, new renal replacement therapy, or persistent renal dysfunction in patients who received 0.9% saline as opposed to balanced intravenous crystalloid. Chloride and acid-base balance.
Hyperchloremic metabolic acidosis is consistently following fluid resuscitation with 0.9% saline which occur mainly due to strong ions difference, so with NS 0.9 associated with higher relative increase in plasma [Cl−] than [Na+] and this will increase dissociation of water to H+ and OH−, thereby driving metabolic acidosis which affects myocardial function, renal and intestinal perfusion, nerve function, and extracellular potassium buffering, it is likely to play a role in the increased mortality observed in critically ill patients who receive large volumes of 0.9% saline which is not occurred with PlasmaLyte. Chloride and kidney perfusion.
Multiple crossover trial comparing 0.9% saline with balanced crystalloids in 13,347 noncritically ill adults attending an emergency department found a higher incidence of major adverse kidney events following 0.9% saline versus SPLIT study but still larger study waited. Chloride and coagulation.
Still more studies needed to proof this relation but may be dilutional cause or due to the acidosis. Chloride and fluid overload.
Study shown that chloride-rich crystalloid may increase the risk of fluid overload to a greater degree than balanced solutions specially with AKI, post kidney transplant and CKD patient as normal feedback lead to increasing diuresis. Chloride and blood pressure.
Sure all chloride dietary associated with sodium but clinical studies shown that chloride itself led to hypertension specially if in large amount. The case for abandoning 0.9% saline.
-Using as volume resuscitation, studies shown that balanced fluids were associated with lower mortality, lower prevalence of AKI, and lower inotrope requirements.
-Further studies evidence inferior surgical outcomes in patients receiving 0.9% saline.
-Post KTX normal saline was associated with more metabolic
Acidosis and hyperkalemia than balanced solutions.
-Many studies shown that large volumes of 0.9% saline increase the risk of mortality, metabolic acidosis, and AKI in critically ill adults, and some data suggesting increased postoperative and transplant complications including hyperkalemia. The case for keeping 0.9% saline.
In clinical conditions which predispose to hypochloremic alkalosis and intravascular volume depletion,0.9% saline is preferable to balanced solutions which may not adequately compensate chloride loss. It can therefore be argued that 0.9% saline should never be completely abandoned. Summary.
Many studies shown the benefits of balanced solution over 0.9 NaCl in regards side effects on acid-base equilibrium, electrolytes dysfunction, AKI incidence, postoperative morbidity and mortality in critically ill patients, post kidney transplant and also in children but still 0.9 NS has special clinical situation that will have great beneficial effect which is indicated only for it. We should dealing with our cases as case by case management as every clinical situation should be followed strictly and professionally .
Level of evidence (V)(Narrative study).
Yes,
Specially in critically ill patients , post surgical
We should keep our patients under strict F/U regarding Acid-base and potassium
Mahmoud Wadi
2 years ago
III. Ab-normal saline in abnormal kidney function- risks and alternatives
Summarise this article
What is the evidence provided by this article?
——————————————————————————————————————
Summarise this article
Introduction
Intravenous 0.9% saline has saved , remains the most widespread crystalloid in both adult and pediatric practice.
While the tonicity and sodium concentration of 0.9% saline are within 10% of physiological levels, its chloride concentration exceeds that of plasma by approximately 60% .
There is accruing evidence for deleterious effects resulting from excess chloride in patients receiving intravenous 0.9% saline.
Children with impaired kidney function are at particular risk of these sequelae due to reduced capacity to excrete excess chloride.
Effects of chloride
Chloride and mortality
The mechanism underlying increased mortality in patients who receive large volumes of chloride-rich crystalloid has not been definitively established; however hyperchloremic metabolic acidosis is strongly implicated.
Chloride and acid-base balance
Hyperchloremic metabolic acidosis is consistently observed in both adult and pediatric patients following fluid resuscitation with 0.9% saline.
Chloride and kidney perfusion
Intra-renal perfusion, vasoconstriction,and reduction in glomerular filtration rate.(AKI and RRT).
Chloride and coagulation
The anticoagulant effect of 0.9% saline has been ascribed to dilutional coagulopathy related to the significantly larger volume of saline required for resuscitation relative to balanced fluids.
Chloride and fluid overload
Intravenous fluid can be highly effective in restoring tissue perfusion in patients with intravascular depletion .
However, in children with AKI or chronic kidney disease (CKD), extracellular fluid volume homeostasis is often perturbed.
In adult patients suggest that chloride-rich crystalloid may increase the risk of fluid overload to a greater degree than balanced solutions.
In the surgical setting, patients receiving 0.9% saline for volume resuscitation required more blood products than those who received balanced crystalloids increase the risk of circulatory overload .
Fluid overload is associated with increased mortality in critically ill children and neonates with AKI.
Chloride and blood pressure
Due to the effect of intracellular chloride on with-no-lysine kinases. With-no-lysine kinases (WNKs) are serine threonine kinases which play a major role in the regulation of sodium and potassium transport in the distal nephron.
The case for abandoning 0.9% salin
Associated with lower mortality, lower prevalence of AKI, and lower inotrope requirements in a propensity matched analysis of over 3000 children from 43 centers.
Large volumes of 0.9% saline increase the risk of mortality, metabolic acidosis, and AKI in critically ill adults, and some data suggesting increased postoperative and transplant complications including hyperkalemia.
The case for keeping 0.9% saline
Cystic fibrosis
Bartter syndrome
Hypochloremic alkalosis
Traumatic brain injury
Individualized intravenous fluid prescriptions
This is particularly important in children with abnormal kidney function, whether AKI or CKD.
AKI is common in critically ill children and associated with increased mortality .
Maintenance fluid^ can be a dangerous concept for these patients in whom homeostatic mechanisms to regulate fluid, electrolytes, and acid-base are disturbed.
Children with diabetes insipidus need hypotonic fluid, and isotonic solutions are harmful.
Those with traumatic brain injury may require hypertonic solutions.
Children with hypochloremic alkalosis secondary to chloride loss require chloride-rich fluid, often with added potassium chloride.
Individual clinical status and adjusted in response to monitoring.
Summary
In adult patients, balanced fluids are associated with lower mortality, less AKI, and less perioperative complications than 0.9% saline.
Concerns about the potassium content of balanced fluids in patients with abnormal kidney function are not justified, since hyperchloremic acidosis from 0.9% saline confers a greater risk of hyperkalemia.
Balanced fluids may have particular advantages when used as isotonic resuscitation fluid and in kidney transplant recipients.
However, a Bone-size-fits allapproach to intravenous fluid must be avoided.
Fluid prescriptions individual child’s needs considering their underlying medical condition, plasma chemistry, and fluid status.
Certainly, after this article, I will be reconsidered, patients will be monitored and the required examinations will be performed for them.
Mohammed Abdallah
2 years ago
Summarise this article Introduction
Currently, 0.9% saline is the most widely intravenous crystalloid used in pediatric. It is associated with an increased mortality in critically ill adults according to recent large randomized trial
The deleterious effects of 0.9% saline is largely related to the excess chloride content
More physiologic solutions have been developed recently as an alternative to 0.9% saline
The study addressed the effects of excess chloride content in 0.9% saline
Chloride in intravenoud fluids
The most commonly prescribed intravenous fluid is currently 0.9% saline. Its tonicity and sodium concentration are within 10% of physiological levels, but chloride concentration exceeds that of plasma by approximately 60%
Chloride concentrations in balanced fluids (Hartmann’s, Ringer’s lactate and PlasmaLyte) is closely to that of the plasma
Effects of chloride
Increase mortality
May be due to hyperchloremic meta- bolic acidosis
Chloride and acid-base balance
Hyperchloremic metabolic acidosis in both adult and pediatric patients
May be explained by traditional Henderson-Hasselbalch equation/ Siggaard-Anderson or dilutional acidosis
Chloride and kidney perfusion
Reduce kidney blood flow and function (vasoconstriction and reduction in GFR)
Chloride and coagulation
Dilutional coagulopathy related to the significantly larger volume of saline required for resuscitation relative to balanced fluids
Chloride and fluid overload
Chloride-rich crystalloid may increase the risk of fluid overload to a greater degree than balanced solutions
Also patients receiving 0.9% saline for volume resuscitation required more blood products than those who received balanced crystalloids (blood products increase the risk of circulatory overload)
Fluid overload is associated with increased mortality in critically ill children and neonates with AKI
Chloride and blood pressure
May be due to the effect of intracellular chloride on with-no-lysine kinases. With-no-lysine kinases (WNKs) are serine threonine ki- nases which play a major role in the regulation of sodium and potassium transport in the distal nephron
The case for abandoning 0.9% saline
0.9% saline was associated with metabolic acidosis, increased mortality, increased infection rates, and increased blood product requirement, when compared to PlasmaLyte
Large volumes of 0.9% saline increase the risk of mortality, metabolic acidosis, and AKI in critically ill adults, and some data suggesting increased postoperative and transplant complications including hyperkalemia The case for keeping 0.9% saline
0.9%saline is preferable to balanced solutions in conditions which predispose to hypochloremic alkalosis and intravascular volume depletion (Bartter syndrome, cystic fibrosis, and severe persistent vomiting)
Individualized intravenous fluid prescriptions
Fluid prescription in children should be individualized and guided by patients’ clinical status. For example, Children with diabetes insipidus need hypotonic fluid, traumatic brain injury patients may require hypertonic solutions, and children with hypochloremic alkalosis secondary to chloride loss require chloride-rich fluid
Conclusion
When compared to 0.9% saline, balanced fluids are associated with lower mortality, less AKI, and less perioperative complications
The greater risk of hyperkalemia not comes from K content of solution but from chloride
Balanced solutions are preferred for resuscitation fluid and in kidney transplant recipients
Fluid prescription should be individualized according to the underlying medical condition, plasma chemistry, and fluid status
What is the evidence provided by this article?
Level 5 (narrative study)
Introduction
The most commonly used intravenous fluid in clinical practice over a century ago is 0.9% normal saline and it directly affect the extracellular fluid and electrolytes status of patients. However, there is growing evidence of deleterious effects of this chloride rich fluid which include hyperchloremic metabolic acidosis, AKI, post operative mortality and prolong hospital stay for critically ill patients. Nevertheless, the development of balanced intravenous fluid has reduced some of this side effects known with 0.9% normal saline
The tonicity and sodium concentration of 0.9% normal saline is 10% of physiological level and its chloride concentration exceed that of plasma by 60%
Effect of Chloride
Chloride and mortality- resuscitation with 0.9% normal saline in pre-clinical setting of sepsis was found to be associated with metabolic acidosis with reduced survival when compared to balanced solution.
Chloride and acid base balance- Cochrane study concluded that chloride rich fluid caused more metabolic acidosis than balanced intravenous fluid
Chloride and kidney perfusion- preclinical and clinical trial suggest an intra renal perfusion, vasoconstriction, and GFR with attendant AKI using a chloride rich fluid compared to balanced fluid
Chloride and fluid overload- the risk of development fluid overload is higher in chloride rich fluid than balanced fluid.
Chloride and blood pressure- a lot of studies have substantiated the development of hypertension in chloride rich fluid
Case for abandoning 0.9% normal saline
increased metabolic acidosis
increased rate of mortality
increased infection rate
increased need for blood products
increase risk of AKI
increase risk of hyperkalemia
ALL THE ABOVE HAVE BEEN REPORTED COMPARED TO USE OF BALANCED SOLUTION
Case for keeping 0.9% normal saline as it has a place for use in the following conditions
Batter syndrome
Cystic fibrosis
severe persistent vomiting
traumatic brain injury
Conclusion
In fluid therapy, there is no size that fit all, however fluid like 0.9% saline have been shown to have several side effects on patient survival as compared to balanced intravenous fluid. However, in spite of these many deleterious side effects 0.9% still has a place in some clinical condition.
Thank you, Will you change your practice based on this article?
Weam Elnazer
2 years ago
Summary:
-In certain therapeutic contexts, balanced intravenous fluids offset excess chloride in 0.9% saline.
-Balanced fluids reduce mortality, AKI, and perioperative complications in adults. Hyperchloremic acidosis from 0.9% saline increases the risk of hyperkalemia in individuals with impaired kidney function.
-Balanced isotonic fluids like PlasmaLyte may be preferable for most children, especially those with impaired kidney function and low chloride excretion.
-Balanced fluids may benefit isotonic resuscitation and kidney transplant patients.
Intravenous fluids should not be standardized.
-Prescriptions must be customized to each child’s condition, plasma chemistry, and fluid state. Many hospitalized youngsters don’t require IV fluids; enteral should be the default.
-0.9% saline is superior to balanced solutions in clinical situations predisposing to hypochloremic alkalosis and intravascular volume depletion. As part of a personalized fluid prescription, 0.9% saline may be the best crystalloid for certain children.
Effects of chloride -Chloride and mortality:
There is mounting evidence that there is an elevated risk of death associated with the administration of chloride-rich intravenous fluid.
-Chloride and acid-base balance :
Hyperchloremic metabolic acidosis is consistently observed in both adult and pediatric patients following fluid resuscitation with 0.9% saline.
-Chloride and kidney perfusion:
Data from preclinical studies and clinical trials suggest a direct effect of chloride on intra-renal perfusion, vasoconstriction, and glomerular filtration.
-Chloride and fluid overload :
Intravenous fluid can be highly effective in restoring tissue perfusion in patients with intravascular depletion. Conversely, injudicious use can result in fluid overload.
-Chloride-coagulation:
Chloride-rich resuscitation fluid inhibits coagulation in preclinical models and clinical investigations in individuals having major surgery.
In an animal model of hemorrhagic shock, 0.9% saline resuscitation was linked with hyperchloremic acidosis and coagulopathy.
-Chloride and blood pressure:
Even while it is well knowledge that salt has an impact on intravascular volume, there is mounting evidence to indicate that chloride may also have an independent effect on blood pressure.
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Doaa Elwasly
2 years ago
-Introduction
Recently large randomised trial demonstrated the adverse effects of normal saline use that can reach mortality due to the excess Cl concentration in the normal saline that cannot be excreted in critically ill patients particularly with renal impairment.
Therefore balanced solutions with nearly physiological chloride concentration had been recently introduced as an isotonic alternative to normal saline. Cl in IV fluids
Iatrogenic hyponatremia is avoided by substituting the use of 0.45% and 0.2% saline by o.9% saline.
Hyponatremia is common in hospitalised children with dehydration or lung pathology due to vasopressin release causing hyponatremia that can lead to intracellular fluid shift and brain oedema , on the other hand rapid hyponatremia correction can cause osmotic demyelination.
Na concentration of 0.9% saline represents 10% of physiological levels, but Cl concentration is 60 % higher than that of plasma .
While Cl concentration in balanced fluids is close to that of the plasma as Hartman’s and Ringer’s lactate .
Plasma Lyte concentrations are the closest one to plasma Cl effects Cl and mortality
Cl rich solutions usage is associated with increased mortality risk specially in critically ill patients.
Fluid resuscitation of sepsis cases with normal saline was accompanied with metabolic acidosis which was not found with cases treated with balanced fluids.
Multiple studies proved the complications of using Cl rich normal saline for critically ill cases with sepsis in the forum of AKI ,RRT , and even mortality which was not associated with the use of balanced fluids.
Regarding the pediatric population, hyperchloremia caused by the normal saline was an independent factor for adverse outcomes and even mortality. Cl and acid base balance
Cochrane systematic review of postoperative intravenous fluid therapy in adults concluded that Cl rich fluid opposite to balanced solutions are associated with metabolic acidosis .
Henderson-Hasselbalch and Siggaard-Anderson explained the acute changes in plasma pH by changes
in partial pressure of carbon dioxide (pCO2) and carbonic acid.
Stewart declared that changes in the strong ion difference can change plasma pH directly. If a large volume of IV normal saline is given this will decrease the plasma strong ion difference due to a higher relative increase in plasma Cl− than Na+ which will increase dissociation of water to H+ and OH−
, therefore causing metabolic acidosis.
The effect of normal saline on SID is much higher than Plasma Lyte and Hartmann’s effect . Cl and kidney perfusion
Cl affects intra-renal perfusion, vasoconstriction,
and decreases glomerular filtration.
A study published that ICU cases whom received 0.9% saline 2 liters experienced higher incidence of AKI and RRT compared to Cl restrictive fluid therapy.
Also another study applied on noncritically ill patients demonstrated that normal saline intake lead to major renal negative outcomes compared to balanced solutions. Cl and coagulation
Cl rich fluids had negative effects on coagulation.
Animal models manged with normal saline for haemorrhagic shock , had metabolic acidosis and coagulopathy ,while those complications weren’t associated with LR.
In adults undergoing major abdominal surgeries, the use of Cl rich solutions were associated with increased use of blood products.
This could be explained by infusion of large volumes of normal saline which can lead to dilutional coagulopathy. Cl and fluid overload
Children with AKI or CKD are more liable to extracellular fluid overload.
Studies conducted on adults revealed that Cl rich fluids are associated with fluid overload more than balanced solutions ,this could be justified by the association of Cl rich solutions with blood products transfusion rather than balanced solutions.
Fluid overload can lead to cardiovascular morbidity and mortality particularly in children with CKD and critically ill cases.
Animal and clinical studies revealed that oral NaCl intake effect on hypertension did not increase with sodium citrate or phosphate use,meanwhile Cl was suggested to have an effect on blood pressure and renal vascular resistance.
It was recently suggested that systemic hypertension can be attributed to accumulation of skin chloride.
Cl mechanism of affecting BP could be through decrease of intracellular Cl in combination with the regulatory protein Mo25 can stimulate WNK activity and transcellular ion flux in the renal epithelium. Abandon of 0.9% saline
Recent data supports the necessity of substitution of normal saline with balanced solutions as resuscitation fluid for children and adults.
Multiple studies published that balanced fluids were associated with less mortality, less AKI prevalence, less RRT and lower inotrope need compared to normal saline.
Another observational study on candidates underwent abdominal surgeries showed that postoperative use of 0.9% saline was associated with metabolic acidosis, increased mortality, increased infection rates, and increased blood product requirement,compared to PlasmaLyte.
A metanalysis study published that normal saline use was associated with increased risk of AKI and ventilation time.
Another study conducted on kidney transplant recipients showed that normal saline use as fluid replacement for those cases was accompanied by hyperkalemia and metabolic acidosis compared to LR use.
Balanced crystalloids containing K can lower the risk of hyperkalemia relative to K-free saline in patients with renal impairment function because normal saline induces hyperchloremic metabolic acidosis that can impair cellular K buffering while plasma HCO3 resulting from gluconate and acetate metabolism can maintain K buffering. Keeping 0.9% normal saline
For certain conditions as
· Hypochloremic metabolic alkalosis and intravascular volume depletion normal saline will be needed, as in salt wasting tubulopathy as Barter syndrome and in cases of persistent vomiting and gastric HCL loss and pyloric stenosis
· Cystic fibrosis causing Cl loss ,so 0.9% saline can be a suitable fluid replacement.
· Children with traumatic brain injury , normal saline hypertonicity can protect from cerebral oedema.
Individualization of IV fluid therapy
Is a must to tailor the fluid therapy according to the patient needs ,as in AKI and CKD cases.
Special cases need to be treated accordingly as cases with brain injury can need hypertonic solutions , and Diabetes insipidus cases can need hypotonic solutions .
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Sherif Yusuf
2 years ago
The current study (level of evidence V)is evaluating the adverse effects of normal saline including AKI, hyperchloremic metabolic acidosis, hyperkalemia, coagulopathy and increase mortality compared to balanced solutions like PlasmaLyte
Normal saline has a chloride content that is 60% more than the plasma compared to balanced solution in which the chloride content is near to that of plasma. Moreover, patients with impaired kidney function cannot excrete these excess chloride leading to the development of hyperchloremia
Deleterious effect of hyperchloremia
A- Metabolic acidosis (normal anion gab metabolic acidosis) which can be explained by 2 theories
First theory suggests that hyperchloremia decrease the strong ion deference ((Na + K + Ca, + Mg )-( Cl + Lactate )) that in turn increase the dissociation of water into H+ and OH, leading to metabolic acidosis (strong concept)
Second theory suggests that metabolic acidosis is occurring due to dilution of bicarbonate by administrating large volume of buffer free fluids (no strong evidence of this concept)
B- hyperkalemia
Metabolic acidosis is associated with extracellular shift of potassium with subsequent development of hyperkalemia
On the other hand potassium containing balanced solutions are not associated with significant hyperkalemia
C- Impaired kidney perfusion
It was suggested from previous studies that hyperchloremia can induce renal vasoconstriction, thus decreasing renal perfusion and GFR
D- Coagulopathy
Hypercloremia may cause impaired coagulation, and surgical patients receiving high volume on normal saline was found to need more blood produces compared to those receiving more balance solutions, and this was explained by dilution of coagulation factors with administration of larger volume of normal saline
E- Volume overload
It was found that administration of normal saline is associated with some degree of salt and water retention compared to balanced solution and this is more significant in patient with acute or chronic kidney disease, more over as described before the use of normal saline in surgical patients is associated with more infusion of blood products due to coagulopathy which may lead to volume overload
Volume overload in critically ill patients is associated with higher incidence of mortality
F- Hypertension
Not Na alone can cause hypertension, but also hyperchloremia can induce hypertension, this can be explained by the increase in vascular resistance observed in patients with hyperchloremia Mortality
G- Increased mortality
The use of normal saline in critically ill, AKI and sepsis patients was found to be associated with higher mortality compared to balanced solutions; this could be explained by the occurrence of hypercloremic metabolic acidosis, hyperkalemia and volume overload
On the other hand normal saline is beneficial in cases of hypochloremic metabolic alkalosis observed in case of severe volume depletion, persistent vomiting (loss of HCL), barters syndrome and cystic fibrosis
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Zahid Nabi
2 years ago
0.9% saline remains the most widespread crystalloid used in both adult and pediatric practice. While the tonicity and sodium con- centration of 0.9% saline are within 10% of physiological levels, its chloride concentration exceeds that of plasma by approximately 60% . There is accruing evidence for deleterious effects resulting from excess chloride in patients receiving intravenous 0.9% saline. Children with impaired kidney function are at particular risk of these sequelae due to reduced capacity to excrete excess chloride.
In a preclinical model of sepsis, fluid resuscitation with 0.9% saline was associated with more metabolic acidosis and inferior survival than balanced resuscitation fluid .
A Cochrane systematic review of postoperative intravenous fluid management in adult patients concluded that chloride-rich fluid, as opposed to balanced fluid, significantly increases the risk of metabolic acidosis.
Strong ion difference=Na+K+Ca+Mg-Cl+lactate
Stewart proposed that changes in the strong ion difference directly alter plasma pH. If a large volume of intravenous 0.9% saline is administered, this will reduce the plasma strong ion dif- ference via a higher relative increase in plasma [Cl−] than [Na+]. This reduction in strong ion difference will increase dissociation of water to H+ and OH−, thereby driving metabolic acidosis. The effect of Hartmann’s solution on plasma strong ion difference is smaller, and that of PlasmaLyte is negligible, thereby having no significant effect on the patient’s acid base balance.
Chloride and kidney perfusion
Data from preclinical studies and clinical trials suggest a direct effect of chloride on intra-renal perfusion, vasoconstriction, and glomerular filtration.
Chloride and coagulation
There is a consistent theme from preclinical models and clin- ical studies in adults undergoing major surgery that chloride- rich resuscitation fluid impairs coagulation.
Chloride and fluid overload
Studies in adult patients suggest that chloride-rich crystal- loid may increase the risk of fluid overload to a greater degree than balanced solutions.
Chloride and blood pressure
Several lines of evidence implicate chloride in systemic hypertension.
CONCLUSION
Evidence is accruing that balanced intravenous fluids mitigate the deleterious effects of excess chloride in 0.9% saline in some clinical settings. In adult patients, balanced fluids are associated with
lower mortality
less AKI
and less perioperative complications than 0.9% saline.
Concerns about the po- tassium content of balanced fluids in patients with abnormal kidney function are not justified, since hyperchloremic acidosis from 0.9% saline confers a greater risk of hyperkalemia. Although pediatric data are scant, balanced isotonic fluids such as PlasmaLyte are probably better suited to the majority of children, particularly those with abnormal kidney function and reduced capacity to excrete excess chloride. Balanced fluids may have particular advantages when used as isotonic resuscitation fluid and in kidney transplant recipients. However, a One -size-fits all approach to intravenous fluid must be avoided. Prescriptions must be tailored to each individual child’s needs considering their underlying medical condition, plasma chemistry, and fluid status.
Normal saline can be considered as Ab Normal in few conditions however it’s utility in certain conditions can not be undermined.
I am thinking about it as to date we use normal saline .
Nahla Allam
2 years ago
Ø Administration of intravenous fluid directly affects patients’ extracellular fluid and electrolyte status.
Ø The most commonly prescribed intravenous crystalloid in pediatric practice is currently 0.9% saline.
Ø Balanced intravenous solutions with physiological chloride concentration have been developed as isotonic alternatives to 0.9% saline.
Ø This review outlines the effects of excess chloride in 0.9% saline and considers whether its use in clinical practice is still justified.
Chloride in intravenous fluid:
1-The most commonly prescribed intravenous fluid is currently 0.9% saline .chloride concentration exceeds that of plasma by approximately 60%
2-patients who received more significant proportions of chloride-rich fluid experienced increased mortality [ the association of chloride-rich intravenous fluid and hyperchloremia with increased mortality
3-Hyperchloremic metabolic acidosis is consistently observed in both adult and pediatric patients following fluid resuscitation with 0.9% saline
4- chloride-rich fluid, as opposed to balanced juice, significantly increases the risk of metabolic acidosis
5-Data from preclinical studies and clinical trials suggest a direct effect of chloride on intra-renal perfusion, vasoconstriction, and glomerular filtration
6-In adult patients undergoing major abdominal surgery, chloride-rich intravenous fluid was associated with increased blood product requirements
7-Intravenous fluid can be highly effective in restoring tissue perfusion in patients with intravascular depletion .mConversely, injudicious use can result in fluid overload.
8- Fluid overload has serious sequelae. It is associated with increased mortality in critically ill children and neonates with AKI.
9-In adult patients undergoing major abdominal surgery, chloride-rich intravenous fluid was associated with increased blood product requirements
10- Studies in adult patients suggest that chloride-rich crystalloids may increase the risk of fluid overload to a greater degree than balanced solutions
11-Fluid overload has serious sequelae. In addition, it is associated with increased mortality in critically ill children and neonates with AKI.
12-All children who require intravenous fluid need an individualized prescription based on their medical condition and tailored to changes in their fluid, electrolyte, and acid-base status.
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Ban Mezher
2 years ago
IV fluid can directly affect extracellular fluid & electrolytes.
IV fluid used for therapy in special condition, but it may cause harm.
Chloride in IV fluid:
NS used widely in pediatric to avoid hyponatremia that result from increase secretion of vasopressin due to pain, nausea, post operation.
DI need hyponatremic fluid.
NS tonicity ~10% of physiological level, & chloride concentration can exceed 60%.
In balanced saline (RL, PL) chloride concentration similar to plasma level.
Effects of Chloride:
Fluid rich in chloride associated with increase mortality
NS associated with higher rate of hyperchloremic metabolic acidosis & inferior survival when compared to balanced fluid.
Metabolic acidosis induced by NS infusion can explained by Henderson-Hasselbach equation, Strong ion difference & dilution acidosis.
In animal chloride can cause vasoconstriction & reduce GFR, in human NS associated with significantt reduction in arterial flow velocity & renal cortical perfusion.
NS use associated with increase blood products requirement & induce dilution coagulopathy.
Chloride rich crystalloid fluid increase risk of fluid overload.
Peri-operative use of NS associated with increase need for blood products & this will increase risk of fluid overload.
Chloride can increase blood pressure.
Using of NS is inappropriate due to:
associated with higher mortality, higher rate of AKI when used in pediatric for resuscitation (ICU).
high mortality in adults.
inferior surgical outcome ( increase risk of infection, & need of blood products).
inferior AKI outcome when use NS.
increase risk of metabolic acidosis & hyperkalemia in kidney transplant recipients when use NS during surgery.
Conditions preferred NS use:
Children with hypochloremic metabolic alkalosis e.g. Bartter syndrome, cystic fibrosis.
Sure I will use balanced solution more & I can still use NS in special conditions
Eusha Ansary
2 years ago
Summary:
· Normal saline is the most used crystalloid in both adult and pediatric practice.
· Due higher chloride concentration of 0.9% saline relative to plasma leads to some adverse effects.
· There is association of chloride-rich intravenous fluid and hyperchloremia with increased mortality, though the mechanism yet to established.
· Hyperchloremic metabolic acidosis is consistently observed in both adult and pediatric patients following fluid resuscitation with 0.9% saline. It is also associated with hyperkalemia.
· Clinical trials suggest a direct effect of chloride on intra-renal perfusion, vasoconstriction, and glomerular filtration lead to AKI.
· Chloride rich resuscitation fluid impairs coagulation, though the exact mechanism is yet to know.
· Chloride rich crystalloid may increase the risk of fluid overload to a greater degree than balanced solutions.
· Evidence suggests chloride causing systemic hypertension.
· Adverse events due to chloride rich solution has led to development of balanced isotonic solutions such as PlasmaLyte.
Thank you, All
Will you change your practice based on this article?
What is the role of (ab)normal saline played in the post-transplant fluid management at your work place?
Dear Professor Halawa
We have changed our practice especially when choosing fluids for our transplant patients. Initially, the anesthetists would use normal saline intra-operatively that would result in metabolic acidosis and hyperkalemia. But now we have changed to Hartmanns.
If the patient has hyponatremia, thats the time we would use normal saline
Many thanks Dr Bagha for your feedback.
Ajay
We already changed the concept of considering normal saline as just a fluid, especially when we are giving large volume and we restrict the use to the cases of hyponatremia and hyperchloremic metabolic alkalosis
It was clear for me that NS is associated with hyperchloremia, hypernatremia and normal anion gab metabolic acidosis which was noticed in patients with high volume intake such as in cases of rhabdomyolysis and sepsis and DKA , but it is new that it is associated with higher risk of infection, AKI, hyperkalemia and mortality
Hi prof Ahmad Halawa.
For sure those articles will direct me to choose balanced fluid for the right patient, to avoid such undesirable effects.
And defenitly NS will be a better fluid for hypochloremia associated with metabolic acidosis or alkalosis.
In my place LR ususally dominating in perioperative period, as well as NS has still normal, so it has been used frequently.
Definitely I will change my practice. Many patients on long standing 0.9 % saline develop hypokalemia, renal impairment, over load, hypernatremia, and hyperchloremia
we still use saline 0.9 % in pediatric kidney transplantation
yes I will change my practise to use based balanced solution rather than normal saline unless is indicated such as vomiting or loss of chloride
really in our practise we use normal saline in postrenal transplant,it will change sooner.
yes, sure
we were using only normal saline for fluid replacement in the kidney transplant recipients, now it is used only in the operating room and we use ringer lactate and saline. the issue of cost of hartmann’s and osmolytes limited it use in our governmental hospital.
Need to discuss the issue with the transplant team as we usually use NS.
The protocol in our transplant unit involves use of Plasma-Lyte
The article has enlightened me and hopefully one day I will be able to apply my knowledge when my hospital start to introduce kidney transplant. so yes I will change the practice.
Hartman solution is the main solution used post transplantation in addition to normal saline .I will encourage changing entirely to a balanced solution.
Ab-normal saline in abnormal kidney function: risks and alternatives:
Administration of intravenous fluid directly affects patients’ extracellular fluid and electrolyte status. While these effects can be therapeutic, some are unintended, and have the potential to cause harm. The most commonly prescribed intravenous crystalloid in pediatric practice is currently 0.9% saline.
Chloride in intravenous fluid:
Pediatric practice has changed over the last decade with a shift away from hypotonic intravenous fluids such as 0.45% saline or 0.2% saline to predominantly 0.9% saline.
The rationale for this change is avoidance of iatrogenic hyponatremia.
Systematic reviews have highlighted the risk of hyponatremia from hypotonic intravenous fluid,
For the majority of children, isotonic intravenous fluids mitigate these risks, although specific disorders such as diabetes insipidus mandate hypotonic solutions because isotonic fluids lead to hypernatremia and cerebral myelinosis
The most commonly prescribed intravenous fluid is currently 0.9% saline which was developed at the turn of the twentieth century.
Balanced intravenous fluids have chloride concentrations closely aligned to that of plasma. Traditional balanced solutions are Hartmann’s or Ringer’s lactate.
Solutions with even closer alignment to plasma constituents have subsequently been developed such as PlasmaLyte.
Effects of chloride
Chloride and mortality:
In sepsis, fluid resuscitation with 0.9% saline was associated with more metabolic acidosis and inferior survival than balanced resuscitation fluid.
The association of chloride-rich intravenous fluid and mortality is increasingly recognized in critically ill adult and children.
A higher rate of a composite outcome of death, new renal replacement therapy, or persistent renal dysfunction in patients who received 0.9% saline as opposed to balanced intravenous crystalloid hypochloremia is also associated with adverse outcomes. Low serum chloride levels were a strong predictor of mortally.
Chloride and acid-base balance:
Hyperchloremic metabolic acidosis is consistently observed in both adult and pediatric patients following fluid resuscitation with 0.9% saline.
Etiology of saline-induced hyperchloremic metabolic acidosis
If a large volume of intravenous 0.9% saline is administered, this will reduce the plasma strong ion difference via a higher relative increase in plasma [Cl−] than [Na+]. This reduction in strong ion difference will increase dissociation of water to H+ and OH−, thereby driving metabolic acidosis.
Metabolic acidosis affects myocardial function, renal and intestinal perfusion, nerve function, and extracellular potassium buffering, it is likely to play a role in the increased mortality observed in critically ill patients who receive large volumes of 0.9% saline.
Chloride and kidney perfusion:
Data from preclinical studies and clinical trials suggest a direct effect of chloride on intra-renal perfusion, vasoconstriction, and glomerular filtration.
Chloride fluid strategy was associated with more AKI and renal replacement therapy than a chloride-restrictive strategy.
Chloride and coagulation:
Adults undergoing major surgery that chloride rich resuscitation fluid impairs coagulation.
Chloride and fluid overload:
Intravenous fluid can be highly effective in restoring tissue perfusion in patients with intravascular depletion. Conversely, injudicious use can result in fluid overload.
Chloride and blood pressure:
Several lines of evidence implicate chloride in systemic hypertension.
The case for abandoning 0.9% saline:
Given the accruing evidence for deleterious effects of excess chloride, should physicians abandon chloride-rich crystalloid, which was developed over a century ago, in favor of isotonic balanced solutions such as PlasmaLyte.
When used as resuscitation fluid in children on intensive care, balanced fluids were associated with lower mortality, lower prevalence of AKI, and lower inotrope requirements in a propensity matched analysis of over 3000 children from 43 centers.
Similarly, adult studies demonstrate a consistent link between chloride-rich resuscitation fluid and subsequent mortality in critically ill patients.
Postoperative use of 0.9% saline was associated with metabolic acidosis, increased mortality, increased infection rates, and increased blood product requirement, compared to PlasmaLyte.
In AKI and mechanical ventilation time in patients in whom chloride rich resuscitation fluid was used.
Kidney transplantation is a further scenario in which 0.9% saline may impact outcome:
With more metabolic acidosis than balanced solutions.
PlasmaLyte (containing 5 mmol/l potassium) has also been shown to reduce the risk of hyperkalemia relative to potassium-free 0.9% saline in adults with end stage kidney disease undergoing transplantation.
The case for keeping 0.9% saline:
There are some clinical scenarios in which chloride-rich crystalloid will remain the intravenous fluid of choice.
For children with hypochloremic metabolic alkalosis and intravascular volume depletion, the electrolyte composition of 0.9% saline can aid restoration of physiological electrolyte and acid-base balance.
Salt losing tubulopathies such as Bartter syndrome.
Cystic fibrosis.
Severe persistent vomiting can develop hypochloremic alkalosis as a result of gastric hydrochloric acid loss.
Individualized intravenous fluid prescriptions:
All children who require intravenous fluid need an individualized prescription that is based on their medical condition and tailored in response to changes in their fluid, electrolyte, and acid-base Status.
Summary:
In adult patients, balanced fluids are associated with lower mortality, less AKI, and less perioperative complications than 0.9% saline. Concerns about the potassium content of balanced fluids in patients with abnormal kidney function are not justified, since hyperchloremic acidosis from 0.9% saline confers a greater risk of hyperkalemia.
Pediatric data are scant, balanced isotonic fluids such as PlasmaLyte are probably better suited to the majority of children, particularly those with abnormal kidney function and reduced capacity to excrete excess chloride.
level of evidence V
Normal saline (0.9) is a widespread crystalloid that resulted in saving many lives. On the other hand, there are some disadvantages regarding its use in critically ill and especially transplanted recipients due to its high chloride content.
Balanced intravenous fluids such as Ringer lactate or plasmalyte, have chloride content closer to that of plasma.
Effect of chloride:
In critically ill or septic patients use of chloride rich IV fluids was associated with increased mortality.
This is probably related to hyperchloremic metabolic acidosis.
In a systematic review by Cochran, infusion of sodium chloride was associated with high risk of metabolic acidosis.
The effect of 50 ml/kg infusion of different types of crystalloids is 10 kg infant in production of metabolic acidosis is due to their change in strong on different which is highest in normal saline and followed by Hartmans solution and plasmalyte, respectively.
Chloride-rich fluid infusion results in vasoconstriction and reduced intra-renal perfusion and GFR which increase the rate of AKI.
The other effect of normal saline infusion is coagulopathy and increased risk of fluid over load and hypertension (via WNK activity)
In supporting this idea, analysis of over 3000 children showed superior results for balanced solution vs normal saline.
Another study in over 15,802 adults balanced solution were associated with lower risk of AKI, mortality or CKD.
A Cochran systematic review showed increased rate of metabolic acidosis by using perioperative N/S compared to balanced solutions.
This metabolic acidosis may result in hyperkalemia due to trans cellular shift.
There are some cases such as hypo-chloremia metabolic acidosis or some tubulopathies like Bartter syndrome which need chloride-rich IV fluid.
Other indication for N/S infusions are dehydrated patients with CF or persistent Vomiting.
In case with traumatic brain injury, IV infusion of N/S may reduce the risk of cerebral edema.
In addition, monitoring of patient hydration and urine and plasma electrolytes are important for making –decision
The level of evidence is 5.
Introduction
most recently in a large randomized trial there is increased mortality in critically ill adults
May be due to the excess chloride concentration of 0.9% saline relative to plasma.
Patients with abnormal kidney function have reduced capacity to excrete excess chloride
In recent years, balanced intravenous solutions with physiological chloride concentration have been developed as isotonic alternatives to 0.9% saline.
The aim of this review outlines current evidence for the effects of excess chloride in 0.9% saline and considers whether its use in clinical practice is still justified.
Chloride in intravenous fluid
Pediatric practice has changed over the last decade with a shift away from hypotonic intravenous fluids such as 0.45% saline or 0.2% saline to predominantly 0.9% saline. To avoid hyponatremia
While the tonicity and sodium concentration of 0.9% saline are within 10% of physiological levels, its chloride concentration exceeds that of plasma by approximately 60%
In contrast, balanced intravenous fluids have chloride concentrations closely aligned to that of plasma.
Traditional balanced solutions are Hartmann’s or Ringer’s lactate then recently PlasmaLyte.
Effects of chloride
Chloride and mortality
In an analysis of 53,448 adults with sepsis and acute kidney injury (AKI), patients who received greater proportions of chloride rich fluid experienced increased mortality
A recent cluster-randomized, multiple crossover trial in 15,802 adults on intensive care found a higher rate of a composite outcome of death, new renal replacement therapy, or persistent renal dysfunction in patients who received 0.9% saline as opposed to balanced intravenous crystalloid
In an analysis of 890 children with septic shock in 29 pediatric intensive care units in the USA, hyperchloremia was independently associated with inferior outcomes including mortality and complicated clinical course
The mechanism underlying increased mortality not been definitively established; however hyperchloremic metabolic acidosis is strongly implicated.
Chloride and acid-base balance
A Cochrane systematic review of postoperative intravenous fluid management in adult patients concluded that chloride-rich fluid, as opposed to balanced fluid, significantly increases the risk of metabolic acidosis
Etiology of saline-induced hyperchloremic metabolic acidosis
There are two schools of thought
The first one depend on the traditional Henderson-Hasselbalch and Siggaard-Anderson line of thinking
Alternative explanations ; dilutional acidosis, which suggests that infusion of buffer-free crystalloid dilutes the bicarbonate concentration in extracellular fluid thereby precipitating acidosis.
A Chloride and kidney perfusion
in animal studies, infusion of chloride-rich fluid in denervated kidneys resulted in vasoconstriction and reduction in glomerular filtration rate
In healthy adult volunteers, renal artery flow velocity and renal cortical tissue perfusion fell significantly from baseline after infusion of 2 litres 0.9% saline, but not after PlasmaLyte
A chloride-liberal intravenous fluid strategy was associated with more AKI and renal replacement therapy than a chloride-restrictive strategy in a study of 760 adult patients on intensive care
These findings were not corroborated in the SPLIT trial, which compared incidence of AKI in adults receiving 0.9% saline with PlasmaLyte; however, the power of this study was limited by small volumes of fluid infused in patients with moderate severity of disease
Chloride and coagulation
chloride rich resuscitation fluid impairs coagulation and increases blood product requirements
The anticoagulant effect has been ascribed to dilutional coagulopathy related to the significantly larger volume of saline required for resuscitation relative to balanced fluids
the underlying pathophysiology need more researches
Chloride and fluid overload Intravenous
injudicious use can result in fluid overload.
In a study of healthy adult volunteers, urinary excretion of water and sodium were inferior following infusion of 2 litres 0.9% saline when compared to Hartmann’s solution
Overload is a key contributor to cardiovascular morbidity and mortality in children with CKD
Chloride and blood pressure
Several lines of evidence implicate chloride in systemic hypertension.
Preclinical data suggest a specific effect of chloride and on blood pressure and renal vascular resistance.
With-no-lysine kinases (WNKs) are serine threonine kinases which play a major role in the regulation of sodium and potassium transport in the distal nephron [and in monogenic hypertension
( Drosophila model)
The case for abandoning 0.9% saline
PlasmaLyte has also been shown to reduce the risk of hyperkalemia relative to potassium-free 0.9% saline in adults with ESRD undergoing transplantation
Although no pediatric data are available, these findings are noteworthy because pediatric transplant recipients receive large volumes of intravenous crystalloid to maintain allograft perfusion perioperatively
The case for keeping 0.9% saline
For children with hypochloremic metabolic alkalosis and intravascular volume depletion, the electrolyte composition of 0.9% saline can aid restoration of physiological electrolyte and acid-base balance.
Salt losing tubulopathies such as
• Bartter syndrome
• Cystic fibrosis.
• Infants with pyloric stenosis
• children with traumatic brain injury
Enteral supplementation with a combination of sodium and potassium chloride is preferable, intravenous fluid is required in some situations.
Level v
Will you change your practice based on this article?
For pediatric transplantation patients there is no evidence based. However, if the balanced solutions is available in our center, it would be better to improve our practice using this new generation of solutions
Ab-normal saline in abnormal kidney function: risks and alternatives
Currently 0.9% saline is the most commonly prescribed intravenous crystalloid. Administration of intravenous saline affects patient’s extracellular fluid and electrolyte status. While some of these effects are therapeutic others may be unintentional and can be harmful. Recently there is evidence for adverse effects with increased mortality in critically ill adults. Excess chloride concentration of 0.9% saline relative to the plasma appears to be the cause specially when kidney function is unable to excrete excess chloride. Recently, balanced intravenous solutions with physiological chloride concentration have been developed alternative to 0.9% saline.
Chloride in intravenous fluid
While the tonicity and sodium concentration of 0.9% saline are within 10% of physiological
levels, its chloride concentration exceeds that of plasma by approximately 60%. In contrast, balanced intravenous fluids have chloride concentrations closely aligned to that of plasma. Paediatric practice has been shifted from the use of hypotonic saline to 0.9% normal saline, to avoid hyponatremia, for which many hospitalized children are at its risk, due to vasopressin release stimulated by pain, nausea, gastroenteritis, lung pathology or postoperative. Hyponatremia causes intracellular fluid shifts and brain oedema Which, is of grave outcome. Rapid correction of hyponatremia can also cause osmotic demyelination. Ringer’s lactate is a traditional balanced solution. PlasmaLyte solution recently developed with closer similarity to plasma.
Effects of chloride
Chloride and mortality
fluid resuscitation with 0.9% saline was associated with more metabolic acidosis and inferior survival than balanced resuscitation fluid. In critically ill patient’s administration of chloride-rich solution is associated with increased mortality especially those with AKI. In keeping with adult studies, pediatric evidence for a link between excess chloride and mortality is emerging. Hypochloremia is also associated with adverse outcomes. The physiology underlying this association remains to be elucidated, but the effect appears to be independent of plasma sodium or potassium concentrations.
The mechanism underlying increased mortality in patients who receive large volumes of chloride-rich crystalloid has not been definitively established.
Chloride and acid-base balance
Hyperchloremic metabolic acidosis is consistently observed in both adult and pediatric patients following fluid resuscitation with 0.9% saline.
Etiology of saline-induced hyperchloremic metabolic acidosis
Two theories explain the acute change in PH.
1- Henderson-Hasselbalch theory:
Explain change in PH by changes in partial pressure of Carbone dioxide (PCO2) and thereby carbonic acid.
Henderson-Hasselbalch equation:
PH = PK + log (HCO3-/PCO2 X 0.225)
By this equation the link between excess chloride from 0.9% saline and metabolic acidosis is not immediately obvious.
2- Stewart’s approach:
Based on strong ion theory which gives a physiological explain for excess chloride driving metabolic acidosis. Strong ion theory refers to principles of:
· electroneutrality (all negative and positive charged ions must balance). And
· conservation of mass (total amount of a substance remains constant unless added to, generated, removed or destroyed).
From the above, Stewart’s explanation of acid-base balance is determined by CO2, weak acids, and the strong ion difference.
Plasma strong ion difference is defined as:
= {(Na+) + (K+) + (Ca+) + (Mg+)} – {(Cl-) + (lactate)}
Change in the strong ion difference directly alter plasma PH.
Large volume of iv 0.9% normal saline reduces the plasma strong ion difference via a higher relative increase in plasma Cl- than Na. this will increase dissociation of water to H+ and OH-, thereby driving metabolic acidosis.
The effect on PH is more with N/S 0.90% > Hartmann’s solution > plasmaLyte.
Another theory by which N/S 0.90% induces acidosis is dilutional acidosis, (buffer-free crystalloid dilutes the bicarbonate concentration leads to acidosis).
Chloride and kidney perfusion:
Chloride has a direct effect on intra-renal perfusion, vasoconstriction, and glomerular filtration. Many studies strongly implicate chloride-rich iv fluid in acutely reducing kidney blood flow and function. In one study, administration of 2 Ls 0.9% saline shown to decrease renal artery flow velocity ad renal cortical tissue perfusion significantly, but not after plasmaLyte infusion.
Chloride and coagulation:
Chloride-rich fluid impairs coagulation which is not seen in Ringer’s lactate solution. This could be explained by dilutional coagulopathy. In adult undergoing abdominal surgery chloride-rich iv fluid was associated with increase blood product requirement. These make balanced iv fluid preferred in surgical care.
Chloride and fluid overload:
Patients with intravascular fluid depletion, injudious use of iv fluid can result in fluid overload. If kidney function is normal, fluid overload is uncommon. But, in AKI or CKD risk of overload is high. Chloride-rich solution use carry risk of fluid overload more than balanced solution. Also, in surgical patients using large volium of 0.9% saline required more blood products than balanced crystalloids. Blood transfusion associated with increased mortality and cardiovascular morbidity and mortality in AKI and CKD patients.
Chloride and blood pressure:
Chloride may influence blood pressure in its ownright. Several studies support this. Hypertensive effect of enteral sodium chloride was not replicated with sodium citrate or phosphate. Recent data explain that sequestration of hypertonic electrolyte in skin and the role of macrophages in regulation of this storage, has led to suggestion that skin chloride accumulation is associated with systemic hypertension.
The case for abandoning 0.9% saline
Because of deleterious effects of excess chloride, many studies are in favor of isotonic balanced solutions such as plasmaLyte.
Balanced fluids were associated with lower mortality, lower prevalence of AKI, and lower inotropic requirements, new renal-replacement therapy or persistent renal dysfunction than 0.9% saline.
Kidney transplant recipient:
Perioperative normal saline was associated with more metabolic acidosis than balanced solution (more hyperchloremic hyperkalemic metabolic acidosis). Finding of more hyperkalemia with 0.9% saline than lactate Ringer,s (contain 4 mmol/l K) was documented in many studies.
PlasmaLyte ( has 5 mmol/L K) has reduced risk of hyperkalemia relative to K-free 0.9% saline. This noteworthy in paediatric patients.
Hyperchloremic acidosis caused by 0.9% saline impairs cellular buffering of K+ thereby predisposing to hyperkalemia.
In contrast; the balanced fluid electrolyte composition and the HCO3 produced from metabolism of gluconate and acetate in these fluids serve to maintain K+ buffering. The small amount of K+ in the balanced fluid is needed to decrease risk of hypokalemia.
Case in keeping 0.9%:
Hypochloremic metabolic alkalosis conditions that may occur in the following:
1- Bartter syndrome (chloride wasting)
2- Cystic fibrosis
3- Persistent vomiting
4- Pyloric stenosis
5- Traumatic brain injury
Hypertonicity of 0.9% saline may mitigate the risk of cerebral edema more effectively than balanced isotonic saline.
Individualized IV fluid prescription:
No one fit for all, children especially those with AKI or CKD need individual prescription of their fluid requirement. According to the medical condition and the response to the fluid.
There has been an increasing body of evidence to elucidate high risk of complications integral to utilization of normal saline with its supra-physiologic dose,9s its concentration in is 154 in normal saline vs 106 in plasma).
This variation in concentration was speculatively blamed for inflicting several complications reported, such as metabolic acidosis, increased mortality in intensive care units patients treated with normal saline , AKI and coagulopathy.
The underlying mechanism mediating chloride induced metabolic acidosis was addressed elaboratively by Stewarts proposition for explaining metabolic acidosis, in which the concept of strong ions difference drive the chloride induced acidosis .
The strong ions concept reflect equal numbers of Cations and Anions as follow:
Na+K+Mg+Ca- Cl + lactate. The reduction of this difference stimulate dissociation of H2O to H and OH.
Chloride and renal function:
Renal perfusion was found to fall significantly after infusing 2 Liters of normal saline.A phenomenon that was not seen with balanced solutions like Plasmalyte and hartman solution.
Chloride and coagulation:
There is increased incidence of thrombosis in patient on normal saline infusion.
Chloride and fluid overload:
It was shown evidently that normal saline infusion is associated with reduced diuresis and natriuresis in contrast to Hartmann’s solution use.
Chloride and Hypertension:
Chloride storage in skin was linked to hypertension.
It s a narrative study
level of evidence 5
Intravenous 0.9 saline is found to be associated with deleterious effects . These include increased mortality, acute kidney injury (AKI), metabolic acidosis, and coagulopathy. The predominant cause for these sequelae appears to be the excess chloride concentration of 0.9% saline relative to plasma. There is now overwhelming evidence that large volumes of 0.9% saline increase the risk of mortality, metabolic acidosis, and AKI in critically ill adults, and some data suggesting increased postoperative and transplant complications including hyperkalemia. The initial fluid prescription can be based on the presenting plasma chemistry and acid-base status, careful monitoring of patients’ fluid status, plasma, and urine electrolytes is paramount in order to tailor the prescription appropriately. Standard intravenous fluid prescriptions are rarely appropriate; choice of intravenous crystalloid should be guided by patients’ individual clinical status and adjusted in response to monitoring.
What is the evidence provided by this article?
Level V
Intravenous fluid impacts the patient’s extracellular fluid and electrolytes. The higher chloride concentration of 0.9% saline has been associated with increased mortality in critically ill patients, despite its widespread use.
To minimize issues such as osmotic demyelination owing to iatrogenic hyponatremia (due to tonicity and sodium concentration within 10% of physiological values), the intravenous fluid used in pediatric patients was changed from 0.45% or 0.2% saline to 0.9% saline. However, when the chloride concentration exceeds plasma levels, the patient is exposed to the harmful consequences of elevated chloride levels.
Higher chloride levels are related to increased metabolic acidosis and mortality, as well as increased rates of chronic renal impairment, new renal replacement therapy (RRT), and worse outcomes. Higher chloride concentrations exacerbate metabolic acidosis by decreasing the strong ion difference, hence increasing the dissociation of water into H+ and OH–. The effects of metabolic acidosis on cardiac function, renal and intestinal perfusion, neuronal function, and extracellular potassium buffering result in an increase in mortality. A higher chloride concentration causes greater vasoconstriction and decreased GFR, leading to AKI and the requirement for RRT. Rehydration with chloride-rich fluids impairs coagulation due to dilutional coagulopathy. Additionally, chloride-rich fluid causes fluid overload (due to an increased need for blood products), which increases cardiovascular morbidity and death. A greater chloride concentration also results in an increase in blood pressure, an effect observed only with sodium chloride and not with sodium citrate or sodium phosphate.
Why 0.9% saline should no longer be used: Balanced fluids are preferred in transplant recipients due to increased mortality, acute kidney injury, higher inotrope requirements, persistent renal dysfunction, new RRT use, inferior surgical outcomes, increased infection rates, increased blood product requirements, and increased metabolic acidosis and hyperkalemia.
In children with intravascular volume depletion and hypochloremic metabolic alkalosis, such as salt-losing tubulopathies (Bartter syndrome), cystic fibrosis, excessive sweating, persistent vomiting, infants with pyloric stenosis, diabetes insipidus, and traumatic brain injury, 0.9% saline is still useful.
Therefore, the intravenous fluid prescription should be customized based on the patient’s clinical characteristics.
Thank you professor, it has changed our practice based on these articles your lecture and discussion.
The article is about Ab-normal saline in abnormal kidney function risk and alternatives. Normal saline has been the most widely used solution when is related to the other types of solutions. It has been associated with increased mortality, especially in critically ill patients. It has been noted that the dangerous part of the normal saline solution has to do with the concentration of the chloride. Due to the problem with NS other solutions have been developed as a better choice than normal saline.
The aim of the study is to address the effects of chloride content in NS
As it relates to NS it and the plasma concentration of the electrolytes, IV sodium is within the 10% physiological range but it is found that Cl is over 60 % over the plasma requirement. This is why it has effects like metabolic acidosis. When comparing NS with other solutions like Hartmann’s and LR their Cl concentration is less or closer to plasma concentration.
What are the possible effects of high chloride concentration?
1) It increases the mortality rate secondary to the formation of hyperchloremic metabolic acidosis.
2) The high level of Cl and its hyperchloremic acidosis can be found in both adults and children as a complication.
3) The kidney is the organ that regulates most electrolytes and with a high level of Cl, it can affect the tubular-glomerular feedback mechanism reducing GFR.
4) It can cause fluid overload when compare with balanced solutions
5) It has been related to high blood pressure having an impact on intravascular volume.
6) Chloride-rich fluids used in resuscitation can inhibit coagulation.
Reasons to avoid NS:
1) It increases mortality
2) It increases metabolic acidosis
3) Increase infection rate
4) Increase the need for blood products
5) Causes an increase in AKI and high K
Reasons to use NS:
1) Cystic fibrosis
2) Batters syndrome
3) Brain injury
4) Persistent vomiting
In conclusion:
There is no ideal solution for any given situation but one has to look for a better solution to ensure patient survival and reduce mortality and hospitalization. NS although still, the most used solution has more side effects when compared to balanced solutions.
This article’s level of evidence is level 5
Intravenous fluid affects extracellular fluid and electrolytes of the patient. Use of 0.9% saline, although very common, has been shown to be associated with increased mortality in critically ill patients, due to the increased chloride content.
Intravenous fluid use in pediatric population changed from 0.45% or 0.2% saline to 0.9% saline to avoid complications like osmotic demyelination due to iatrogenic hyponatremia (due to tonicity and sodium concentration within 10% of physiological levels). But the chloride concentration being higher than plasma levels, the patient is exposed to deleterious effects of higher chloride levels.
Effects of chloride: Higher chloride levels are associated with higher metabolic acidosis and mortality, higher rates of persistent renal dysfunction, new renal replacement therapy (RRT) and poorer outcomes. Higher chloride levels increase metabolic acidosis by reducing the strong ion difference causing increased dissociation of water to H+ and OH–. Metabolic acidosis affects myocardial function, renal and intestinal perfusion, nerve function and extracellular potassium buffering leading to increased mortality. Higher chloride leads to increased vasoconstriction and reduced GFR causing AKI and need for RRT. Chloride rich fluid resuscitation leads to impairment of coagulation due to dilutional coagulopathy. Chloride-rich fluid also leads to fluid overload (due to increased requirement of blood products) leading to increased cardiovascular morbidity and mortality. Higher chloride also leads to higher blood pressure, the effect seen specifically with sodium chloride, and not with sodium citrate or sodium phosphate.
Why 0.9% saline should be abandoned: Due to increased mortality, AKI, higher inotrope requirement, persistent renal dysfunction, new RRT use, inferior surgical outcomes, increased infection rates, increased blood product requirements, and increased metabolic acidosis and hyperkalemia in transplant recipients associated with 0.9% saline, balanced fluids are preferred.
When to use 0.9% saline: It can still be useful in children with intravascular volume depletion and hypochloremic metabolic alkalosis like in salt-losing tubulopathies (Bartter syndrome), cystic fibrosis, excessive sweating, persistent vomiting, infants with pyloric stenosis, diabetes insipidus and traumatic brain injury.
Hence the intravenous fluid prescription should be individualized depending on the clinical aspects of the patient.
Level of evidence: Level 5 – Narrative review
Summary:
We have shifted from NS to balanced fluids especially RL in our country.
Summary of the article
“Abnormal saline in abnormal kidney function- risks and alternatives
Intravenous 0.9% saline, although a widely used solution and has saved countless lives, it has recently found to be associated with deleterious effects because of excess chloride concentration of 0.9% saline relative to plasma:
1. Increased mortality:hyperchloremic metabolic acidosis is strongly implicated.
2. Acute kidney injury (AKI): infusion of chloride-rich fluid in denervated kidneys resulted in vasoconstriction and reduction in glomerular filtration rate.
3. Metabolic acidosis: hyperchloremic metabolic acidosis.
4. Coagulopathy: The anticoagulant effect of 0.9% saline has been ascribed to dilutional coagulopathy related to the significantly larger volume of saline required for resuscitation relative to balanced fluids.
5. Fluid overload: Studies in adult patients suggest that chloride-rich crystal- loid may increase the risk of fluid overload to a greater degree than balanced solutions. In a study of healthy adult volunteers, urinary excretion of water and sodium were inferior following infusion of 2 litres 0.9% saline when compared to Hartmann’s solution.
6. HTN: Several lines of evidence implicate chloride in systemic hypertension. Animal and clinical studies found that the hypertensive effect of enteral sodium chloride was not replicated with sodium citrate or phosphate.
7. Hyperkalemia: Hyperchloremic acidosis from 0.9% saline impairs cellular buffering of potassium, thereby predisposing to hyperkalemia.
In favor of 0.9 saline administration:
1. Hypochloremic metabolic alkalosis and intravascular volume depletion.
· Salt losing tubulopathies such as Bartter syndrome.
· Cystic fibrosis predisposes to excessive chloride loss; excessive sweating can lead to hypochloremic metabolic alkalosis.
· Pyloric stenosis: Severe persistent vomiting can develop hypochloremic alkalosis as a result of gastric hydrochloric acid loss.
2. For children with traumatic brain injury, the hypertonicity of 0.9% saline may mitigate the risk of cerebral edema more effectively than balanced isotonic fluids.
What is the evidence provided by this article?
This is a narrative review article.
Level of evidence grade 5.
Summarise this article
Introduction:
IV normal saline resuscitation saved lives since it was introduced, however the components of intravenous fluids affects the extracellular fluid and electrolytes status.
This study highlights the effect of these isotonic fluids solutions on EC fluid and electrolytes as well on patient’s outcomes, this is proposed to be due to excess chloride content of 0.9% saline, so balanced fluids with physiological chloride have been developed.
Chloride in intravenous fluid:
The rationale of avoiding hypotonic fluids is to it hyponatremic effect that contribute to symptomatic hyponatremia that cause brain edema, permanent neurological deficit, and even increase death.
The rapid correction of hyponatremia can cause osmotic demyelination and neurological deficit.
Makes the isotonic fluid solutions safe and more in use, however the normal saline content of sodium is 10% of physiological level, and the chloride content is 60% more than plasma chloride levels. This mandate development of solutions with closer alignment to plasma constituents such as Hartmann’s, Ringer’s lactate, and lately PlasmaLyte.
Effects of chloride:
On mortality:
Hyperchloremic metabolic acidosis is highly implicated in increased mortality in patients receiving large volumes of chloride-rich crystalloid solutions.
Etiology of saline-induced hyperchloremic metabolic acidosis:
1. Stewart’s strong ion theory gives a physiological rationale for excess chloride driving metabolic acidosis. Strong ion difference= ([Na]+[K]+[Ca]+[Mg] postively charged)-([Cl]+[Lactate] negatively charged) changes in the strong ion difference directly alter plasma pH.
Thus reduction in strong ion difference by 0.9% N/S will increase dissociation of water to H+ and OH−, thereby driving metabolic acidosis.
2. Dilutional acidosis – the infusion of buffer-free crystalloid dilutes the bicarbonate concentration in extracellular fluid thereby precipitating acidosis.
Metabolic acidosis affects myocardial function, renal and intestinal perfusion, nerve function, and extracellular potassium buffering, it is likely to play a role in the increased mortality observed in critically ill patients who receive large volumes of 0.9% saline.
Chloride and renal perfusion:
In healthy adult volunteers, renal artery flow velocity and renal cortical tissue perfusion fell significantly from baseline after infusion of 2 liters 0.9% saline, but not with osmolyte. And was associated with more AKI and renal replacement therapy in critically ill patients. This was not the case in SPLIT trial used low fluid volumes.
Chloride and coagulation:
The anticoagulant effect of 0.9% saline due dilutional coagulopathy related to the significantly larger volume of saline required for resuscitation relative to balanced fluids.
Chloride and fluid overload:
This could be due to larger volumes needed or the increased requirement of blood product transfusion in normal saline resuscitated patients.
Fluid overload has is associated with increased mortality in critically ill children and neonates with AKI.
Chloride and blood pressure:
1. The skin chloride accumulation is associated with systemic hypertension.
2. Reduction in intracellular chloride in combination with the regulatory protein Mo25 were found to stimulate WNK activity in distal nephron and transcellular ion flux in the renal epithelium, thus affecting blood pressure.
The case for abandoning 0.9% saline:
Chloride-rich resuscitation fluid associated with higher mortality, metabolic acidosis, increased infection rate, AKI, longer time on mechanical ventilation, and the more need of blood product transfusion.
Balanced fluids were associated with lower mortality, lower prevalence of AKI, and lower inotrope requirements.
In kidney transplantation, N/S 0.9% infusion associated with hyperchloremic metabolic acidosis, hyperkalemia when compared to balanced fluids infusion.
The case for keeping 0.9% saline:
In cases of hypochloremic metabolic alkalosis such as : Bartter syndrome, cystic fibrosis, persistant vomiting, and intravascular volume depletion.
Individualized intravenous fluid prescriptions:
The initial crystalloid fluid prescription should be based on the patients clinical presentation, plasma chemistry and acid-base status, careful monitoring of patients’ fluid status, plasma, and urine electrolytes is mandatory.
Conclusion:
The deleterious effect of excess chloride in 0.9% N/S, makes the balanced fluids used more.
Hyperchloremic acidosis from 0.9% saline has a greater risk of hyperkalemia when compared to balanced potassium containing fluids.
Balanced fluids may have particular advantages when used as isotonic resuscitation fluid and in kidney transplant recipients.
The fluid prescription should be based on patient’s clinical condition, plasma chemistry and fluid status.
Enteral fluids and electrolytes should be encouraged when possible due to it’s major safety.
What is the evidence provided by this article?
Level of evidence V
Summary of Ab-normal saline in abnormal kidney function- risks and alternativesIntroduction:
0.9% Saline is most common IV crystalloid given in paediatric .
Excess chloride of 0.9% saline relative to plasma may be result in increasing mortality in critical ill adults in large randomized trial.
This review outlines current evidence for the effects of excess chloride in 0.9% saline and whether its use in clinical practice is still justified
Chloride in intravenous fluid:
0.9% saline is the most commonly intravenous fluid and its tonicity and sodium concentration are within 10% of physiological levels it chloride concentration exceed that of plasma by approximately 60%
Balanced intravenous fluids have chloride concentration closely aligned to the plasma.
Included Hartmann’s or Ringer Lactate and plasma-Lyte
Excess chloride which result from 0.9% saline has serious effects especially in children with impaired kidney function.
Effects of chloride:
Chloride and metabolites:
0.9% saline was associated with more metabolic acidosis and inferior survival than balanced resuscitation fluid
In some of the studies chloride-rich intravenous fluid result in mortality in critically ill adults and even death new renal replacement therapy or persistent renal dysfunction in patients received 0.9% saline opposed to balanced intravenous crystalloid.
Chloride and acid-base balance:
Hyperchloremic metabolic acidosis is observed in both adult and paediatric patients following resuscitation with 0.9% saline
Aetiology of saline induced hyperchloremic metabolic acidosis:
The underline mechanism of acute acid disturbance :
1. Hendreson and Siggaard think that acute change in plasma PH are explained by changes in partial pressure of carbon dioxide PCO2 and there by carbonic acid. But using an approach the link of excess chloride form 0.9% saline and metabolic acidosis is not obvious.
2-St ewart theory it refers to principle of electrolytes neutrality.
He proposed that changes in the strong was differences directly after plasma PH
3-Also dilutional acidosis by saline can induce metabolic acidosis
However anon linear relationship between extracellular volume expansion and reduction in bicarbonate concentration doesn’t support this concept.
Chloride and kidney perfusion:
Some of studies suggest direct effect of chloride an inter-renal perfusion, vasoconstriction and glomerular filtration so data from preclinical models and adult patients strongly implicate chloride-rich intravenous fluid in acutely reducing in day blood flow and function.
Chloride and coagulation:
0.9% saline has dilutional coagulopathy related to the significantly larger volume of saline for resuscitation relative to balanced fluid.
Chloride and fluid overload:
As haemostasis is disrupt in AKI or CKD children
Studies in adult patients suggest that chloride-rich crystalloid may increase the risk of fluid overload to a greater degree than balanced solutions
Chloride and blood pressure:
Several lines of evidence implicate chloride in a systemic hypertension and renal vascular resistance but still further studies are needed for chloride in BP regulation.
A systematic review of studies in adult kidney transplant recipient concluded that perioperative normal saline was associated with more metabolic than balanced solutions.
Now there is evidence that large volume of 0.9% saline increase the risk of mortality metabolic acidosis and AKI in critical ill adults and some data suggest increased postoperative and transplant complications including hyperkalaemia
In clinical condition which can cause hyperchloremic alkalosis and intravascular depletion 0.9% saline is preferable to balanced solution.
Summary:
· Balanced fluid in adult patients result in lower mortality, less AKI and less perioperative complications than 0.9% saline
· 0.9% saline causing hyperchloremic acidosis has a greater risk of hyperkalaemia
· Although paediatric date are scant
· Balanced fluids have advantage in kidney transplant recipient
· Underline medical condition, plasma concentration and fluid status need to be consider before given fluid to the child.
level evidence 5
Vi
Club 3; normal saline in KT
Summary
· The higher Cl content of isotonic saline (60 % highrer than the plasma) was accused to cause hyperchloremic metabolic acidosis and higher incidence of AKI, metabolic acidosis and coagulopathy.
· In children, the use of isotonic saline is the standard to avoid risk of hyponatremia and brain edema. however, rapid correction of hyponatremia leads to central pontine myelinosis.
· Risk and hazards associated with high Cl content of isotonic saline:
o Higher mortality.
o Higher incidence of hyperchloremic metabolic acidosis.
o Higher incidence of AKI (in chloride rich solutions than Cl restrictive strategy), However, no RCT in pediatric patients and opposing results was found in SPLIT trial that AKI was comparable between saline and ringer fluid resuscitation.
o Higher risk of bleeding, coagulopathy and need for blood products transfusion.
o Edema and hypervolemia especially in patients with AKI and CKD (unable to maintain the fluid balance), which is independent risk factor of cardiovascular mortality in critically patients with AKI.
o Hypertension mediated by renal vessels vasoconstriction.
· Why to stop isotonic saline (what is against)?
o As plasma lyte 148 (balanced crystalloid solution) was associated with lower mortality, AKI, less need to positive inotropes, persistent renal dysfunction and need to RRT.
o Saline 0.9 % was associated with higher incidence of post operative infection, mortality and need for blood component transfusion, after major abdominal surgery. Also it increased need for mechanical ventilation in critically ill patients.
o Use of saline in KT was associated with higher incidence of metabolic acidosis and hyperkalemia, due to impaired renal ability to handle the fluid and acid base balance. Plasmalyte decreased incidence of hyperkalemia in adult kidney transplant recipients.
o The relatively small quantity of K in balanced solutions is able to mitigate the risk of hypokalemia. In addition, the physiology of K homeostasis, keeps the balanced solutions reduce the risk of hyperkalemia in such patients with impaired kidney function.
· Why to keep isotonic saline as a standard resuscitation fluid (what is with?)
o In cases with hypochloremic metabolic alkalosis and intravascular volume depletion as in children with Bartter syndrome and pseudo-Bartter as (cystic fibrosis and persistent vomiting as in pyloric stenosis).
· Conclusion:
o Fluid therapy should be individualized according to the volume status , acid base status and biochemical composition and serum electrolytes (one size does not fit all).
o Patients with either AKI or CKD are at the highest risk from inappropriate IV fluids (saline may be harmful as those kidneys can not excrete excess chloride, balanced solution does not increase risk of hyperkalemia).
o Diabetes inspidus needs hypotonic fluids (saline is harmful).
o Children with hypocholoremic alkalosis, needs saline (balanced crystalloid solution does not compensate them).
Level of evidence: narrative review (level V)
Summary:
Administration of intravenous fluid directly affects patients’ extracellular fluid and electrolyte status. Some of these fluids have the potential to cause harm. A large randomised trial showed that 0.9% NS administration is associated with increased mortality due to excess chloride. Patients with abnormal kidney function have a reduced capacity to excrete excess chloride.
Balanced intravenous solutions with physiological chloride concentration have been developed.
Effects of chloride
Chloride and mortality
Chloride and kidney perfusion
Chloride and coagulation
Chloride and fluid overload
Chloride and blood pressure
The case for abandoning 0.9% saline
The case for keeping 0.9% saline
Level of evidence:
Level 5 ( review article).
· There is evidence that 0.9% saline increased mortality in critically ill adults could be due to hyperchloremia
· Patients with impaired kidney function have more risk oh hyperchloremia
· Pediatric practice has changed over the last decade with a shift away from hypotonic (0.45% or 0.2% saline) to predominantly 0.9% saline to prevent hyponatremia
· The association of chloride-rich intravenous fluid and mortality is increasingly recognized in critically ill adults
· Hyperchloremic metabolic acidosis is consistently observed in both adult and pediatric patients following fluid resuscitation with 0.9% saline
Etiology of saline-induced hyperchloremic metabolic acidosis. There are 2 schools:
1.Henderson-Hasselbalch and Siggaard-Anderson school: acute alterations in plasma pH are explained by changes in partial pressure of carbon dioxide (pCO2) and thereby carbonic acid
2.Stewart’s strong ion theory gives a physiological rationale for excess chloride driving metabolic acidosis
· The effect of metabolic acidosis on myocardial function, renal and intestinal perfusion, nerve function, and extracellular potassium buffering, make the Stewart’s theory more likely
Chloride and kidney perfusion
· Data from pre-clinical models and adult patients strongly implicate chloride-rich intravenous fluid in acutely reducing kidney blood flow and function.
Chloride and coagulation
· In adult patients undergoing major abdominal surgery, chloride-rich intravenous fluid was associated with increased blood product requirements
Chloride and fluid overload
· Data suggestive of increased risk of fluid overload in patients receiving 0.9% saline as opposed to balanced solutions
Chloride and blood pressure
· Several lines of evidence implicate chloride in systemic hypertension.
· Recent observation that skin chloride accumulation is associated with systemic hypertension.
The case for abandoning 0.9% saline
· Now there is evidence that large volumes of 0.9% saline increase the risk of mortality, metabolic acidosis, AKI in critically ill adults, and increased postoperative and transplant complications
The case for keeping 0.9% saline
· 0.9% saline still needed for Bartter syndrome, Cystic fibrosis, children with hypochloremic alkalosis due to severe vomiting (e.g., pyloric stenosis)
· For children with traumatic brain injury, of 0.9% saline may reduce the risk of cerebral edema more effectively than balanced isotonic fluids
Summary
· In adult patients, balanced fluids are associated with lower mortality, less AKI, and less perioperative complications than 0.9% saline
· No evidence that potassium content of balanced fluids in patients with abnormal kidney function induced hyperkalemia, while hyperchloremic acidosis from 0.9% saline confers a greater risk of hyperkalemia
· PlasmaLyte could be better for the majority of children, particularly those with abnormal kidney function and reduced capacity to excrete excess chloride
· IV fluids should be prescribed case by case and if not indicated, enteral feeding is advised if tolerated
This is a narrative review evidence 5
Introduction:
0.9% saline is a commonly used IV fluid, recently several trials showed its association with many adverse effects due to excess chloride concentration relative to plasma, patients with renal impairment are at increased risk for these adverse effects.
Balanced isotonic solutions are considered more physiological and a better alternative to 0.9% saline.
Chloride in IV fluid:
The chloride concentration of 0.9% saline exceed that of plasma by approximately 60% while balanced IV fluids have chloride concentration similar to plasma.
Excess chloride in normal saline is associated with several side effects and children with renal impairment are at increased risk for these effects.
Effects of chloride:
Chloride and mortality:
Recent evidence showed an association between chloride rich fluids and mortality in critically ill patients, hyperchloremia was attributed as a strong predictor of mortality independent of plasma sodium and potassium concentration
Chloride and acid base balance:
Chloride rich fluids increase the risk of metabolic acidosis, 2 proposals are available, the Handerson-Hasselbalch approach and Steward strong ion therapy that explain changes in plasma pH according to changes in strong ion differences, alternative explanation is dilutional acidosis.
Chloride and kidney perfusion:
Preclinical studies and clinical trials showed that chloride rich IV fluid cause acute reduction in kidney blood flow and function.
Chloride and coagulation:
Chloride rich fluids are associated with impaired coagulation may be due to dilutional coagulopathy related to relatively larger volume of saline required for resuscitation.
Chloride and fluid overload:
In adults, using normal saline was associated with higher risk of fluid overload compared to balanced solutions.
Chloride and blood pressure:
Several preclinical and clinical trials implicate chloride in systemic HTN, its effect in blood pressure regulation is important when selecting IV fluid.
The case for abandoning 0.9% saline:
Resuscitation with balanced fluids was associated with lower mortality, lower prevalence of AKI compared to chloride rich fluids.
0.9% saline was associated with inferior surgical outcomes and more use of blood products compared to plasmaLyte.
In kidney transplantation, perioperative normal saline was associated with more metabolic acidosis than balanced solutions, significantly higher hyperkalemia due to hyperchloremic metabolic acidosis that lead to extracellular shift of potassium while risk of hyperkalemia from potassium in balanced solution is not justified.
The case of keeping 0.9% saline:
Clinical conditions with hypochloremic alkalosis and intravascular volume depletion as in children with salt losing tubulopathies, cystic fibrosis and those with severe persistent vomiting.
Individualization of IV fluid prescription:
Should be according to medical condition and choice of fluid should be guided by patient individual clinical status and adjusted in response to monitoring.
Level of evidence: 5
Summary of the erticle;
Intravenous fluid affects extracellular fluid and electrolytes content, with evidence noted harm effects of 0.9 NS as an undesirable effects, which lead to development of balanced IV fluid with physiological chloride to avoid metabolic acidosis and hyperkalemia associated with NS administration.
In recent randomized trial found that IV NS associated with increased mortality in critically ill adults, this is because of hyperchloremia in NS, and the patients with reduced kidney function have a reduce capacity to excrete excess chloride.
Balanced fluid with physiological saline recently develop to substitute NS.
Chloride in intravenous fluid;
Effect of chloride;
Chloride and acid-base balance;
Chloride and kidney perfusion;
Chloride and coagulation;
Chloride and fluid overload;
When to choose 0.9% saline;
Summary;
Level of evidence ((V)) Review
● 0.9% saline is the most crystalloid in both adult and pediatric practice.
● Recently there is accruing evidence for adverse effects of normal saline
● The predominant cause for these sequelae is the excess chloride concentration of 0.9% saline relative to plasma
● Patients with abnormal kidney function have reduced capacity to excrete excess chloride, which increases their risk of these complications.
● Pediatric practice has changed with a
shift away from hypotonic intravenous fluids to predominantly 0.9% saline to avoid hyponatremia due to vasopressin release stimulated by nausea, pain, gastroenteritis, lung pathology, or the postoperative state
● Hyponatremia predisposes to brain edema which can cause permanent neurological impairment or even death
● Rapid correction of hyponatremia can also result in osmotic demyelination.
● The most commonly prescribed intravenous fluid is currently 0.9% saline
● Traditional balanced solutions are Hartmann’s or Ringer’s lactate Solutions
● Effects of chloride
** increased mortality
** more metabolic acidosis
** inferior survival than balanced resuscitation fluid
● metabolic acidosis affects myocardial function, renal and intestinal perfusion, nerve function, and extracellular potassium buffering so increased mortality observed in critically ill patients who receive large volumes of 0.9% saline.
● Chloride has a direct effect on intra-renal perfusion, vasoconstriction, and glomerular filtration.
● renal artery flow velocity and renal cortical tissue perfusion fell significantly from baseline after infusion of 2 litres 0.9% saline,but not after PlasmaLyte
● Chloride-rich resuscitation fluid impairs coagulation that were not observed with lactated Ringer’s solution
● in children with AKI or chronic kidney disease (CKD), extracellular fluid volume homeostasis is often perturbed.
● patients receiving 0.9% saline for volume resuscitation required more blood products than those who received balanced crystalloids
● Blood products increase the risk of circulatory overload and which increased mortality in critically ill children and neonates with AKI
● Overload is a key contributor to cardiovascular morbidity and mortality in children with CKD
● skin chloride accumulation is associated with systemic hypertension
● balanced fluids were associated with lower mortality, lower prevalence of AKI, and lower inotrope requirements
● postoperative use of 0.9% saline was associated with
** metabolic acidosis
** increased mortality
** increased infection rates
** increased blood product requirement
** Inferior outcomes in patients at risk of AKI
** Increased incidence of AKI
compared to PlasmaLyte
● PlasmaLyte (containing 5 mmol/l potassium) shown to reduce the risk of hyperkalemia relative to potassium-free 0.9% saline in adults with end-stage kidney disease undergoing transplantation
● For patients with Salt losing tubulopathies such as Bartter syndrome , Cystic fibroses , traumatic brain injury, and pyloric stenosis , 0.9% saline is preferable to a balanced solution.
● Balanced fluids may have particular advantages when used as isotonic
resuscitation fluid and in kidney transplant recipients.
● However Prescriptions must be tailored to each individual child’s needs considering their underlying medical condition, plasma chemistry, and fluid status.
Level 5
Thank you, see my question above.
III. Ab-normal saline in abnormal kidney function- risks and alternatives
1. Summarise this article
This study evaluates current evidence for the effects of excess Cl- in 0.9% saline & assess whether its use in clinical practice is still justifiable.
Chloride in IV fluid
Iatrogenic hyponatremia is a concern when hypo-tonic IV fluids (0.45% saline or 0.2% saline) are used in children; the rational for recent shift to 0.9% saline, as isotonic IV fluids reduce this risk.
Although the tonicity & Na+ conc. of 0.9% saline are within 10% of physiological levels, its Cl- conc. exceeds that of plasma by 60%; while balanced IV fluids have Cl- conc. close to that of plasma.
Effects of chloride
1.Increased mortality than balanced resuscitation fluid; hyperchloremic metabolic acidosis is implicated as a possible mechanism.
2.Hyperchloremic metabolic acidosis in both adult & pediatric patients following fluid resuscitation with 0.9% saline.
3.Reduced intra-renal perfusion & GFR, more AKI & RRT.
4.Impairs coagulation & increases blood product requirements.
5.Increases fluid overload especially in children with AKI or CKD.
6.Increase blood pressure & implicated in systemic HTN.
Why to abandon 0.9% saline?
1.When used in children in ICU, balanced fluids were associated with lower mortality, lower prevalence of AKI, & lower inotrope requirements (analysis of >3000 children, 43 centers).
2.Adult studies show a strong link between chloride-rich resuscitation fluid & subsequent mortality in critically ill patients; balanced crystalloids result in a lower rate of death, new RRT, or persistent renal dysfunction than 0.9% saline.
3.An observational analysis of > 30,000 adults undergoing abdominal surgery, pos-top use of 0.9% saline was associated with metabolic acidosis, increased mortality, increased infection rates, & increased blood product requirement, compared to PlasmaLyte.
4.Inferior outcomes are seen in patients at risk of AKI who receive 0.9% saline.
5.Increased incidence of AKI was seen in a study of 760 adults when a chloride liberal IV fluid was used, as opposed to a chloride-restrictive strategy.
6.A meta-analysis found an increase in AKI & mechanical ventilation time in patients in whom chloride rich resuscitation fluid was used.
7.A Cochrane systematic review of adult KTX recipients found that peri-op normal saline was associated with more metabolic acidosis than balanced solutions.
The reasons for keeping 0.9% saline
1.For children with hypochloremic metabolic alkalosis (salt losing tubulopathies such as Bartter syndrome) & volume depletion, 0.9% saline can restore physiological electrolyte & acid-base balance.
2.Cystic fibrosis predisposes to excessive chloride loss; excessive sweating can lead to hypo-chloremic metabolic alkalosis. 0.9% saline is a better choice of crystalloid in context of volume depletion in these cases.
3.Infants with pyloric stenosis are at risk of hypo-chloremic alkalosis due to gastric losses; 0.9% saline + KCl can normalize electrolyte & acid-base balance.
4.0.9% saline may reduce the risk of cerebral edema more effectively than balanced isotonic fluids in chilfren with traumatic brain injury.
/////////////////////////////////
2. What is the evidence provided by this article?
Level V
Thank you, see my question above.
Introduction
Intravenous normal saline has been used for many decades. However, recently large trials in adults have shown that it results in increased mortality, acidosis, coagulopathy and acute kidney injury. Balanced solutions like PlasmaLyte and Hartmanns solutions have been developed that are more physiological than normal saline. The review aimed to outline the current evidence of the effects of excess chloride in 0.9% saline, and if it is still justified to use it as the intravenous (IV) fluid of choice in patients with renal disease. This is important to assess as the use of IV fluids affects the patient’s fluid and electrolyte status
Chloride in intravenous fluid
Pediatric practice has recently shifted away from using hypotonic IV fluids due to the risk of iatrogenic hyponatremia. Hospitalized pediatric patients have a higher risk of hyponatremia as nausea, pain gastroenteritis and post-operative status may result in the release of vasopressin. Hyponatremia can be especially worrying as it may cause brain edema which can lead to permanent neurological deficits and even death. Osmotic demyelination may occur if the low sodium is corrected too fast. For most of the pediatric patients, using isotonic solutions reduces the risk of hyponatremia. However, isotonic solutions cannot be used in all situations, such as diabetes insipidus. Children are at a particular risk of developing hyponatremia if they have impaired renal function as they have a reduced capacity to excrete the extra chloride.
Effects of chloride
Chloride and mortality
In patients with sepsis, using 0.9% saline was associated with increased incidence of metabolic acidosis and poor rates of survival, when compared to a balanced resuscitation fluid. This was seen in a study conducted in critically ill adults and also a study conducted in pediatric patients, with a diagnosis of sepsis and acute kidney injury.
Chloride and acid-base balance
In adult and pediatric patients resuscitated with 0.9% saline, hyperchloremic metabolic acidosis is frequently observed. This is because, when large volumes of 0.9% saline are administered, there will be an increase in chloride ions compared to sodium ions in plasma, which will increase the dissociation of water to hydrogen and OH ions, thereby causing metabolic acidosis. This is known as Stewart’s strong ion theory.
Chloride and kidney perfusion
Chloride directly reduces intra-renal perfusion, causes vasoconstriction and reduces glomerular filtration rates. This results in AKI and eventual renal replacement therapy. No pediatric studies have been published for the same.
Chloride and coagulation
There are studies that show that 0.9% saline used for resuscitation have resulted in coagulopathy. This was not observed when the choice of IV fluid was Ringer’s lactate.
Chloride and fluid overload
In children with AKI or CKD, the risk of fluid overload is greater, and studies have shown that the use 0.9% saline has a higher risk of circulatory overload when compared to balanced fluids. Fluid overload has been shown to lead to increased mortality in critically ill children with AKI.
Chloride and blood pressure
Animal and clinical studies have shown that chloride may have a direct effect on the blood pressure. The exact mechanism is still under debate.
The case for abandoning 0.9% saline
The use of balanced fluids in critically ill children have been associated with lower mortality, lower prevalence of AKI and lower requirements of ionotropic support. This has also been replicated in adult studies. Poor outcomes were reported in patients at risk of AKI who received 0.9% saline. For patients undergoing renal transplantation, systematic reviews have observed that patients receiving 0.9% saline during the surgery resulted in a higher incidence of metabolic acidosis. Studies showed that the incidence of hyperkalemia was also greater in patients receiving normal saline, as compared to a more balanced fluid, during kidney transplantation.
The case for keeping 0.9% saline
For patients with hyperchloremic metabolic acidosis and intravascular fluid depletion, 0.9% saline will aid in restoring normal acid-base balance. In patients suffering with conditions that result in urine chloride wasting, such as Bartter syndrome, high chloride therapy is required, and hence will benefit from 0.9% saline. Cystic fibrosis leads excessive chloride loss, and the appropriate fluid of choice is normal saline. Persistent vomiting may lead to hypochloremic metabolic acidosis, due to gastric hydrochloric acid loss, and therefore, normal saline is the preferred IV fluid. For children with traumatic brain injury, using 0.9% saline may reduce the risk of cerebral edema.
Summary
The above arguments show us that an individualistic approach should be used in IV fluid selection. Normal saline has been associated with increased mortality, metabolic acidosis, coagulopathy and AKI. The pathogenesis of acidosis with normal saline is due to a reduction in the strong ion difference which leads to dissociation of water in to hydrogen and oxygen. The other theory is dilutional acidosis. Balanced solutions have been shown to reduce the risks associated with normal saline. Pediatric data is scant but still shows that balanced solutions are better than normal saline.
The level of evidence is level V
I liked reading your summary and your conclusions.
Ajay
Thank you Professor Ajay
The most widespread crystalloid fluid in both adult and pediatric remains Normal saline.
However, there is an evidence of deleterious effects resulting from excess chloride concentration of 0.9% saline relative to plasma. This has led to development of balanced isotonic solutions such as PlasmaLyte.
Chloride in intravenous fluid
The tonicity and sodium concentration of NS are within 10% of physiological levels, its chloride concentration exceeds that of plasma by approximately 60%. In contrast balance solutions have chloride concentration similar to plasma.
Children with impaired kidney function are at particular risk of these sequelae due to reduced capacity to excrete
excess chloride.
Effects of chloride
Chloride and mortality: both in adult and pediatric a growing evidence link hyperchloremia as independently associated with inferior outcomes including mortality and complicated clinical course. The exact pathophysiology not yet definitive, but likely linked to development of hyperchloremic metabolic acidosis.
Chloride and acid-base balance: NS and CL-rich fluid significantly increases the risk of metabolic acidosis which affects myocardial function, renal and intestinal perfusion, nerve function, and extracellular potassium buffering.
Chloride and kidney perfusion renal perfusion fell significantly from vasoconstriction and reduction in GFR, resulted in higher incidence of major adverse kidney events; AKI and RRT.
Chloride and coagulation increased blood product requirements. The anticoagulant effect has been ascribed to
dilutional coagulopathy.
Chloride and fluid overload :resulted from disturbed feedback mechanisms and adjustment of urine volume and natriuresis, reduce urinary excretion of water and sodium. Fluid overload has serious sequelae, increased mortality Avoiding fluid overload is therefore a key priority by avoiding CL-rich fluid.
Chloride and blood pressure increase risk of systemic HTN.
The case for abandoning 0.9% saline:
Taken together, there is now overwhelming evidence that large volumes of 0.9% saline increase the risk of mortality, metabolic acidosis, and AKI in critically ill adults, and some data suggesting increased postoperative and transplant complications including hyperkalemia.
Pediatric data are scant so definitive conclusions cannot be drawn; however, for volume resuscitation and kidney transplant care, the case for abandoning 0.9% saline in favor of balanced solutions is compelling.
The case for keeping 0.9% saline:
In clinical conditions which predispose to hypochloremic alkalosis and intravascular volume depletion (i.e: salt losing tubulopathies, Cystic fibrosis, persistent vomiting) 0.9% saline is preferable to balanced solutions which may not adequately compensate chloride loss.
It can therefore be argued that 0.9% saline should never be completely abandoned, because it is the most appropriate crystalloid for some children as part of an individualized fluid prescription.
Individualized intravenous fluid prescriptions:
All children who require intravenous fluid need an individualized prescription that is based on their medical condition and tailored in response to changes in their fluid, electrolyte, and acid-base status.
Level of evidence: 5 narrative review.
This article gave an insight about the effect of commonly used fluid in practice, however, if both balanced and NS are available, balanced solution provides more favorable outcome. Treatment needs to be individualized according to the patient condition and available fluid.
I liked reading your summary, strengths of study and your conclusions.
Ajay
Ab-normal saline in abnormal kidney function: risks and alternatives.
Introduction.
Normal saline 0.9 is considered the most common intravenous fluid used worldwide and has many benefits but recently some studies revealed the deleterious effect of it specially with CKD patients, mainly due to chloride content which led to metabolic acidosis, coagulopathy and hyperkalemia. This review outlines current evidence for the effects of excess chloride in 0.9% saline.
Chloride in intravenous fluid.
Using of hypotonic saline has risk effect of developing hyponatremia with neurological manifestation and so isotonic saline started to replace it, Isotonic saline is with accepted sodium concentration but its chloride concentration exceeds that of plasma by approximately 60%, correspondingly traditional balanced solutions are Hartmann’s or Ringer’s lactate has close chloride concentration to plasma and there is solutions with even closer alignment to plasma constituents have subsequently
been developed such as PlasmaLyte.
Effects of chloride.
Chloride and mortality.
RCs done on 15,802 adults on intensive care found a higher rate of a composite outcome of death, new renal replacement therapy, or persistent renal dysfunction in patients who received 0.9% saline as opposed to balanced intravenous crystalloid.
Chloride and acid-base balance.
Hyperchloremic metabolic acidosis is consistently following fluid resuscitation with 0.9% saline which occur mainly due to strong ions difference, so with NS 0.9 associated with higher relative increase in plasma [Cl−] than [Na+] and this will increase dissociation of water to H+ and OH−, thereby driving metabolic acidosis which affects myocardial function, renal and intestinal perfusion, nerve function, and extracellular potassium buffering, it is likely to play a role in the increased mortality observed in critically ill patients who receive large volumes of 0.9% saline which is not occurred with PlasmaLyte.
Chloride and kidney perfusion.
Multiple crossover trial comparing 0.9% saline with balanced crystalloids in 13,347 noncritically ill adults attending an emergency department found a higher incidence of major adverse kidney events following 0.9% saline versus SPLIT study but still larger study waited.
Chloride and coagulation.
Still more studies needed to proof this relation but may be dilutional cause or due to the acidosis.
Chloride and fluid overload.
Study shown that chloride-rich crystalloid may increase the risk of fluid overload to a greater degree than balanced solutions specially with AKI, post kidney transplant and CKD patient as normal feedback lead to increasing diuresis.
Chloride and blood pressure.
Sure all chloride dietary associated with sodium but clinical studies shown that chloride itself led to hypertension specially if in large amount.
The case for abandoning 0.9% saline.
-Using as volume resuscitation, studies shown that balanced fluids were associated with lower mortality, lower prevalence of AKI, and lower inotrope requirements.
-Further studies evidence inferior surgical outcomes in patients receiving 0.9% saline.
-Post KTX normal saline was associated with more metabolic
Acidosis and hyperkalemia than balanced solutions.
-Many studies shown that large volumes of 0.9% saline increase the risk of mortality, metabolic acidosis, and AKI in critically ill adults, and some data suggesting increased postoperative and transplant complications including hyperkalemia.
The case for keeping 0.9% saline.
In clinical conditions which predispose to hypochloremic alkalosis and intravascular volume depletion,0.9% saline is preferable to balanced solutions which may not adequately compensate chloride loss. It can therefore be argued that 0.9% saline should never be completely abandoned.
Summary.
Many studies shown the benefits of balanced solution over 0.9 NaCl in regards side effects on acid-base equilibrium, electrolytes dysfunction, AKI incidence, postoperative morbidity and mortality in critically ill patients, post kidney transplant and also in children but still 0.9 NS has special clinical situation that will have great beneficial effect which is indicated only for it. We should dealing with our cases as case by case management as every clinical situation should be followed strictly and professionally .
Level of evidence (V)(Narrative study).
Thank you,
Will you change your practice based on this article?
Yes,
Specially in critically ill patients , post surgical
We should keep our patients under strict F/U regarding Acid-base and potassium
III. Ab-normal saline in abnormal kidney function- risks and alternatives
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Summarise this article
Introduction
Effects of chloride
Chloride and mortality
Chloride and acid-base balance
Chloride and kidney perfusion
Chloride and coagulation
Chloride and fluid overload
Chloride and blood pressure
The case for abandoning 0.9% salin
The case for keeping 0.9% saline
Individualized intravenous fluid prescriptions
Summary
What is the evidence provided by this article?
The evidence is V
Thank you,
Will you change your practice based on this article?
Thank very much our Prof.HJalawa
Certainly, after this article, I will be reconsidered, patients will be monitored and the required examinations will be performed for them.
Summarise this article
Introduction
Currently, 0.9% saline is the most widely intravenous crystalloid used in pediatric. It is associated with an increased mortality in critically ill adults according to recent large randomized trial
The deleterious effects of 0.9% saline is largely related to the excess chloride content
More physiologic solutions have been developed recently as an alternative to 0.9% saline
The study addressed the effects of excess chloride content in 0.9% saline
Chloride in intravenoud fluids
The most commonly prescribed intravenous fluid is currently 0.9% saline. Its tonicity and sodium concentration are within 10% of physiological levels, but chloride concentration exceeds that of plasma by approximately 60%
Chloride concentrations in balanced fluids (Hartmann’s, Ringer’s lactate and PlasmaLyte) is closely to that of the plasma
Effects of chloride
Increase mortality
May be due to hyperchloremic meta- bolic acidosis
Chloride and acid-base balance
Hyperchloremic metabolic acidosis in both adult and pediatric patients
May be explained by traditional Henderson-Hasselbalch equation/ Siggaard-Anderson or dilutional acidosis
Chloride and kidney perfusion
Reduce kidney blood flow and function (vasoconstriction and reduction in GFR)
Chloride and coagulation
Dilutional coagulopathy related to the significantly larger volume of saline required for resuscitation relative to balanced fluids
Chloride and fluid overload
Chloride-rich crystalloid may increase the risk of fluid overload to a greater degree than balanced solutions
Also patients receiving 0.9% saline for volume resuscitation required more blood products than those who received balanced crystalloids (blood products increase the risk of circulatory overload)
Fluid overload is associated with increased mortality in critically ill children and neonates with AKI
Chloride and blood pressure
May be due to the effect of intracellular chloride on with-no-lysine kinases. With-no-lysine kinases (WNKs) are serine threonine ki- nases which play a major role in the regulation of sodium and potassium transport in the distal nephron
The case for abandoning 0.9% saline
0.9% saline was associated with metabolic acidosis, increased mortality, increased infection rates, and increased blood product requirement, when compared to PlasmaLyte
Large volumes of 0.9% saline increase the risk of mortality, metabolic acidosis, and AKI in critically ill adults, and some data suggesting increased postoperative and transplant complications including hyperkalemia
The case for keeping 0.9% saline
0.9%saline is preferable to balanced solutions in conditions which predispose to hypochloremic alkalosis and intravascular volume depletion (Bartter syndrome, cystic fibrosis, and severe persistent vomiting)
Individualized intravenous fluid prescriptions
Fluid prescription in children should be individualized and guided by patients’ clinical status. For example, Children with diabetes insipidus need hypotonic fluid, traumatic brain injury patients may require hypertonic solutions, and children with hypochloremic alkalosis secondary to chloride loss require chloride-rich fluid
Conclusion
When compared to 0.9% saline, balanced fluids are associated with lower mortality, less AKI, and less perioperative complications
The greater risk of hyperkalemia not comes from K content of solution but from chloride
Balanced solutions are preferred for resuscitation fluid and in kidney transplant recipients
Fluid prescription should be individualized according to the underlying medical condition, plasma chemistry, and fluid status
What is the evidence provided by this article?
Level 5 (narrative study)
Thank you,
Will you change your practice based on this article?
Yes sir
SUMMARY
Introduction
The most commonly used intravenous fluid in clinical practice over a century ago is 0.9% normal saline and it directly affect the extracellular fluid and electrolytes status of patients. However, there is growing evidence of deleterious effects of this chloride rich fluid which include hyperchloremic metabolic acidosis, AKI, post operative mortality and prolong hospital stay for critically ill patients. Nevertheless, the development of balanced intravenous fluid has reduced some of this side effects known with 0.9% normal saline
The tonicity and sodium concentration of 0.9% normal saline is 10% of physiological level and its chloride concentration exceed that of plasma by 60%
Effect of Chloride
Case for abandoning 0.9% normal saline
ALL THE ABOVE HAVE BEEN REPORTED COMPARED TO USE OF BALANCED SOLUTION
Case for keeping 0.9% normal saline as it has a place for use in the following conditions
Conclusion
In fluid therapy, there is no size that fit all, however fluid like 0.9% saline have been shown to have several side effects on patient survival as compared to balanced intravenous fluid. However, in spite of these many deleterious side effects 0.9% still has a place in some clinical condition.
The level of evidence is 5
Thank you,
Will you change your practice based on this article?
Summary:
-In certain therapeutic contexts, balanced intravenous fluids offset excess chloride in 0.9% saline.
-Balanced fluids reduce mortality, AKI, and perioperative complications in adults. Hyperchloremic acidosis from 0.9% saline increases the risk of hyperkalemia in individuals with impaired kidney function.
-Balanced isotonic fluids like PlasmaLyte may be preferable for most children, especially those with impaired kidney function and low chloride excretion.
-Balanced fluids may benefit isotonic resuscitation and kidney transplant patients.
Intravenous fluids should not be standardized.
-Prescriptions must be customized to each child’s condition, plasma chemistry, and fluid state. Many hospitalized youngsters don’t require IV fluids; enteral should be the default.
-0.9% saline is superior to balanced solutions in clinical situations predisposing to hypochloremic alkalosis and intravascular volume depletion. As part of a personalized fluid prescription, 0.9% saline may be the best crystalloid for certain children.
Effects of chloride
-Chloride and mortality:
There is mounting evidence that there is an elevated risk of death associated with the administration of chloride-rich intravenous fluid.
-Chloride and acid-base balance :
Hyperchloremic metabolic acidosis is consistently observed in both adult and pediatric patients following fluid resuscitation with 0.9% saline.
-Chloride and kidney perfusion:
Data from preclinical studies and clinical trials suggest a direct effect of chloride on intra-renal perfusion, vasoconstriction, and glomerular filtration.
-Chloride and fluid overload :
Intravenous fluid can be highly effective in restoring tissue perfusion in patients with intravascular depletion. Conversely, injudicious use can result in fluid overload.
-Chloride-coagulation:
Chloride-rich resuscitation fluid inhibits coagulation in preclinical models and clinical investigations in individuals having major surgery.
In an animal model of hemorrhagic shock, 0.9% saline resuscitation was linked with hyperchloremic acidosis and coagulopathy.
-Chloride and blood pressure:
Even while it is well knowledge that salt has an impact on intravascular volume, there is mounting evidence to indicate that chloride may also have an independent effect on blood pressure.
Level of evidence V
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Will you change your practice based on this article?
-Introduction
Recently large randomised trial demonstrated the adverse effects of normal saline use that can reach mortality due to the excess Cl concentration in the normal saline that cannot be excreted in critically ill patients particularly with renal impairment.
Therefore balanced solutions with nearly physiological chloride concentration had been recently introduced as an isotonic alternative to normal saline.
Cl in IV fluids
Iatrogenic hyponatremia is avoided by substituting the use of 0.45% and 0.2% saline by o.9% saline.
Hyponatremia is common in hospitalised children with dehydration or lung pathology due to vasopressin release causing hyponatremia that can lead to intracellular fluid shift and brain oedema , on the other hand rapid hyponatremia correction can cause osmotic demyelination.
Na concentration of 0.9% saline represents 10% of physiological levels, but Cl concentration is 60 % higher than that of plasma .
While Cl concentration in balanced fluids is close to that of the plasma as Hartman’s and Ringer’s lactate .
Plasma Lyte concentrations are the closest one to plasma
Cl effects
Cl and mortality
Cl rich solutions usage is associated with increased mortality risk specially in critically ill patients.
Fluid resuscitation of sepsis cases with normal saline was accompanied with metabolic acidosis which was not found with cases treated with balanced fluids.
Multiple studies proved the complications of using Cl rich normal saline for critically ill cases with sepsis in the forum of AKI ,RRT , and even mortality which was not associated with the use of balanced fluids.
Regarding the pediatric population, hyperchloremia caused by the normal saline was an independent factor for adverse outcomes and even mortality.
Cl and acid base balance
Cochrane systematic review of postoperative intravenous fluid therapy in adults concluded that Cl rich fluid opposite to balanced solutions are associated with metabolic acidosis .
Henderson-Hasselbalch and Siggaard-Anderson explained the acute changes in plasma pH by changes
in partial pressure of carbon dioxide (pCO2) and carbonic acid.
Stewart declared that changes in the strong ion difference can change plasma pH directly. If a large volume of IV normal saline is given this will decrease the plasma strong ion difference due to a higher relative increase in plasma Cl− than Na+ which will increase dissociation of water to H+ and OH−
, therefore causing metabolic acidosis.
The effect of normal saline on SID is much higher than Plasma Lyte and Hartmann’s effect .
Cl and kidney perfusion
Cl affects intra-renal perfusion, vasoconstriction,
and decreases glomerular filtration.
A study published that ICU cases whom received 0.9% saline 2 liters experienced higher incidence of AKI and RRT compared to Cl restrictive fluid therapy.
Also another study applied on noncritically ill patients demonstrated that normal saline intake lead to major renal negative outcomes compared to balanced solutions.
Cl and coagulation
Cl rich fluids had negative effects on coagulation.
Animal models manged with normal saline for haemorrhagic shock , had metabolic acidosis and coagulopathy ,while those complications weren’t associated with LR.
In adults undergoing major abdominal surgeries, the use of Cl rich solutions were associated with increased use of blood products.
This could be explained by infusion of large volumes of normal saline which can lead to dilutional coagulopathy.
Cl and fluid overload
Children with AKI or CKD are more liable to extracellular fluid overload.
Studies conducted on adults revealed that Cl rich fluids are associated with fluid overload more than balanced solutions ,this could be justified by the association of Cl rich solutions with blood products transfusion rather than balanced solutions.
Fluid overload can lead to cardiovascular morbidity and mortality particularly in children with CKD and critically ill cases.
Animal and clinical studies revealed that oral NaCl intake effect on hypertension did not increase with sodium citrate or phosphate use,meanwhile Cl was suggested to have an effect on blood pressure and renal vascular resistance.
It was recently suggested that systemic hypertension can be attributed to accumulation of skin chloride.
Cl mechanism of affecting BP could be through decrease of intracellular Cl in combination with the regulatory protein Mo25 can stimulate WNK activity and transcellular ion flux in the renal epithelium.
Abandon of 0.9% saline
Recent data supports the necessity of substitution of normal saline with balanced solutions as resuscitation fluid for children and adults.
Multiple studies published that balanced fluids were associated with less mortality, less AKI prevalence, less RRT and lower inotrope need compared to normal saline.
Another observational study on candidates underwent abdominal surgeries showed that postoperative use of 0.9% saline was associated with metabolic acidosis, increased mortality, increased infection rates, and increased blood product requirement,compared to PlasmaLyte.
A metanalysis study published that normal saline use was associated with increased risk of AKI and ventilation time.
Another study conducted on kidney transplant recipients showed that normal saline use as fluid replacement for those cases was accompanied by hyperkalemia and metabolic acidosis compared to LR use.
Balanced crystalloids containing K can lower the risk of hyperkalemia relative to K-free saline in patients with renal impairment function because normal saline induces hyperchloremic metabolic acidosis that can impair cellular K buffering while plasma HCO3 resulting from gluconate and acetate metabolism can maintain K buffering.
Keeping 0.9% normal saline
For certain conditions as
· Hypochloremic metabolic alkalosis and intravascular volume depletion normal saline will be needed, as in salt wasting tubulopathy as Barter syndrome and in cases of persistent vomiting and gastric HCL loss and pyloric stenosis
· Cystic fibrosis causing Cl loss ,so 0.9% saline can be a suitable fluid replacement.
· Children with traumatic brain injury , normal saline hypertonicity can protect from cerebral oedema.
Individualization of IV fluid therapy
Is a must to tailor the fluid therapy according to the patient needs ,as in AKI and CKD cases.
Special cases need to be treated accordingly as cases with brain injury can need hypertonic solutions , and Diabetes insipidus cases can need hypotonic solutions .
-Level of evidence is 5 as a review article
Thank you,
Will you change your practice based on this article?
The current study (level of evidence V)is evaluating the adverse effects of normal saline including AKI, hyperchloremic metabolic acidosis, hyperkalemia, coagulopathy and increase mortality compared to balanced solutions like PlasmaLyte
Normal saline has a chloride content that is 60% more than the plasma compared to balanced solution in which the chloride content is near to that of plasma. Moreover, patients with impaired kidney function cannot excrete these excess chloride leading to the development of hyperchloremia
Deleterious effect of hyperchloremia
A- Metabolic acidosis (normal anion gab metabolic acidosis) which can be explained by 2 theories
B- hyperkalemia
C- Impaired kidney perfusion
D- Coagulopathy
E- Volume overload
F- Hypertension
G- Increased mortality
On the other hand normal saline is beneficial in cases of hypochloremic metabolic alkalosis observed in case of severe volume depletion, persistent vomiting (loss of HCL), barters syndrome and cystic fibrosis
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Will you change your practice based on this article?
0.9% saline remains the most widespread crystalloid used in both adult and pediatric practice. While the tonicity and sodium con- centration of 0.9% saline are within 10% of physiological levels, its chloride concentration exceeds that of plasma by approximately 60% . There is accruing evidence for deleterious effects resulting from excess chloride in patients receiving intravenous 0.9% saline. Children with impaired kidney function are at particular risk of these sequelae due to reduced capacity to excrete excess chloride.
In a preclinical model of sepsis, fluid resuscitation with 0.9% saline was associated with more metabolic acidosis and inferior survival than balanced resuscitation fluid .
A Cochrane systematic review of postoperative intravenous fluid management in adult patients concluded that chloride-rich fluid, as opposed to balanced fluid, significantly increases the risk of metabolic acidosis.
Strong ion difference=Na+K+Ca+Mg-Cl+lactate
Stewart proposed that changes in the strong ion difference directly alter plasma pH. If a large volume of intravenous 0.9% saline is administered, this will reduce the plasma strong ion dif- ference via a higher relative increase in plasma [Cl−] than [Na+]. This reduction in strong ion difference will increase dissociation of water to H+ and OH−, thereby driving metabolic acidosis. The effect of Hartmann’s solution on plasma strong ion difference is smaller, and that of PlasmaLyte is negligible, thereby having no significant effect on the patient’s acid base balance.
Chloride and kidney perfusion
Data from preclinical studies and clinical trials suggest a direct effect of chloride on intra-renal perfusion, vasoconstriction, and glomerular filtration.
Chloride and coagulation
There is a consistent theme from preclinical models and clin- ical studies in adults undergoing major surgery that chloride- rich resuscitation fluid impairs coagulation.
Chloride and fluid overload
Studies in adult patients suggest that chloride-rich crystal- loid may increase the risk of fluid overload to a greater degree than balanced solutions.
Chloride and blood pressure
Several lines of evidence implicate chloride in systemic hypertension.
CONCLUSION
Evidence is accruing that balanced intravenous fluids mitigate the deleterious effects of excess chloride in 0.9% saline in some clinical settings. In adult patients, balanced fluids are associated with
lower mortality
less AKI
and less perioperative complications than 0.9% saline.
Concerns about the po- tassium content of balanced fluids in patients with abnormal kidney function are not justified, since hyperchloremic acidosis from 0.9% saline confers a greater risk of hyperkalemia. Although pediatric data are scant, balanced isotonic fluids such as PlasmaLyte are probably better suited to the majority of children, particularly those with abnormal kidney function and reduced capacity to excrete excess chloride. Balanced fluids may have particular advantages when used as isotonic resuscitation fluid and in kidney transplant recipients. However, a One -size-fits all approach to intravenous fluid must be avoided. Prescriptions must be tailored to each individual child’s needs considering their underlying medical condition, plasma chemistry, and fluid status.
Normal saline can be considered as Ab Normal in few conditions however it’s utility in certain conditions can not be undermined.
Thank you,
Will you change your practice based on this article?
I am thinking about it as to date we use normal saline .
Ø Administration of intravenous fluid directly affects patients’ extracellular fluid and electrolyte status.
Ø The most commonly prescribed intravenous crystalloid in pediatric practice is currently 0.9% saline.
Ø Balanced intravenous solutions with physiological chloride concentration have been developed as isotonic alternatives to 0.9% saline.
Ø This review outlines the effects of excess chloride in 0.9% saline and considers whether its use in clinical practice is still justified.
Chloride in intravenous fluid:
1-The most commonly prescribed intravenous fluid is currently 0.9% saline .chloride concentration exceeds that of plasma by approximately 60%
2-patients who received more significant proportions of chloride-rich fluid experienced increased mortality [ the association of chloride-rich intravenous fluid and hyperchloremia with increased mortality
3-Hyperchloremic metabolic acidosis is consistently observed in both adult and pediatric patients following fluid resuscitation with 0.9% saline
4- chloride-rich fluid, as opposed to balanced juice, significantly increases the risk of metabolic acidosis
5-Data from preclinical studies and clinical trials suggest a direct effect of chloride on intra-renal perfusion, vasoconstriction, and glomerular filtration
6-In adult patients undergoing major abdominal surgery, chloride-rich intravenous fluid was associated with increased blood product requirements
7-Intravenous fluid can be highly effective in restoring tissue perfusion in patients with intravascular depletion .mConversely, injudicious use can result in fluid overload.
8- Fluid overload has serious sequelae. It is associated with increased mortality in critically ill children and neonates with AKI.
9-In adult patients undergoing major abdominal surgery, chloride-rich intravenous fluid was associated with increased blood product requirements
10- Studies in adult patients suggest that chloride-rich crystalloids may increase the risk of fluid overload to a greater degree than balanced solutions
11-Fluid overload has serious sequelae. In addition, it is associated with increased mortality in critically ill children and neonates with AKI.
12-All children who require intravenous fluid need an individualized prescription based on their medical condition and tailored to changes in their fluid, electrolyte, and acid-base status.
level 5
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Will you change your practice based on this article?
Chloride in IV fluid:
Effects of Chloride:
Using of NS is inappropriate due to:
Conditions preferred NS use:
Level of evidence is 5
Thank you,
Will you change your practice based on this article?
Sure I will use balanced solution more & I can still use NS in special conditions
Summary:
· Normal saline is the most used crystalloid in both adult and pediatric practice.
· Due higher chloride concentration of 0.9% saline relative to plasma leads to some adverse effects.
· There is association of chloride-rich intravenous fluid and hyperchloremia with increased mortality, though the mechanism yet to established.
· Hyperchloremic metabolic acidosis is consistently observed in both adult and pediatric patients following fluid resuscitation with 0.9% saline. It is also associated with hyperkalemia.
· Clinical trials suggest a direct effect of chloride on intra-renal perfusion, vasoconstriction, and glomerular filtration lead to AKI.
· Chloride rich resuscitation fluid impairs coagulation, though the exact mechanism is yet to know.
· Chloride rich crystalloid may increase the risk of fluid overload to a greater degree than balanced solutions.
· Evidence suggests chloride causing systemic hypertension.
· Adverse events due to chloride rich solution has led to development of balanced isotonic solutions such as PlasmaLyte.
Level of evidence: 5
Hi Dr Ansary,
I liked reading your summary and analysis, Will you change your practice based on this article?
Ajay
Hi Dr Ben,
I liked reading your summary and analysis, Will you change your practice based on this article?
Ajay
Absolutely prof