Both colloids and crystalloids may affect patient-centered clinical outcomes, including survival.
Balanced fluids intravenous solutions whose electrolyte composition is closer to the composition of plasma.
Balanced solutions should minimally affect acid-base equilibrium, as compared to the commonly reported 0.9% NaCl-related hyperchloremic metabolic acidosis. WHAT DOES “BALANCED” SOLUTION MEAN?
Theoretically, an ideal balanced solution should have the entire content of all electrolytes equal to the electrolyte content of plasma.
Two categories of intravenous “balanced” solutions available:
1) those with a minimal effect on acid-base equilibrium, having a SID close to a value of 24−29 mEq L-1; intravenous solutions such as Lactated Ringer’s, Acetated Ringer’s, Hart-man. , Sterofundin ISO, Hextend, and Tetraspan.
2) Those with a Cl– content equal or lower than 110 mEq L-1. Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan STEWART’S APPROACH AND THE MECHANISMS REGULATING ACID-BASE DURING FLUID INFUSION.
A “balanced” crystalloid solution should be a crystalloid solution that has an in-vivo SID, i.e., after the metabolism of organic anions, very similar to the patient HCO3. ELECTROLYTE CONTENT AND BALANCED SOLUTIONS:
Another important aspect related to the concept of “balanced” solutions concerns the content of specific electrolytes other than Na+ and Cl–, in particular of magnesium, calcium and potassium (K+). MAGNESIU
Hypomagnesemia,
Severe hypomagnesemia may be associated with a higher incidence of cardiac arrhythmias and alterations in electrocardiographic findings, as well as alterations of the cerebral nervous system.
have reported a reduction in glomerular filtration rate (GFR) and of renal blood flow (RBF) in relation with a concentration of magnesium lower than normal values, Recently, both hypomagnesemia and ionized hypomagnesemia have been reported as being associated with a worse prognosis, especially for a non-recovery renal function after development of acute kidney injury (AKI) [, as well as longer ICU stay and greater mortality.
It may be reasonable to employ intravenous fluids also including magnesium, in order to prevent hypomagnesemia.
This is the rationale upon which the novel generation of “balanced” solutions (such as the crystalloid solutions Plasma-Lyte or Sterofundin ISO) have been developed with the inclusion of magnesium, as compared to the old generation (Lactated Ringer’s, Acetated Ringer’s or Hartmann’s solution). CALCIUM:
Hypocalcemia, especially if measured as total Ca2+ content,
The possible symptoms and clinical consequences are well known: alterations in muscle contractility, of peripheral and central nervous system function, cardiac arrhythmias and others. POTASSIUM:
Hypokalemia is a further life-threatening electrolyte abnormality often observed in critically ill patients [16]. Moreover, it is often associated with abnormalities of the content of other electrolytes. Symptoms include both alterations of muscle contractility, and alterations in cardiac rhythm. THE IMPORTANCE OF CHLORIDE CONTENT AND ITS PATHOPHYSIOLOGIC EFFECTS:
Chloride is the main anion of the extracellular fluid, and although its concentration in plasma is not as tightly regulated as that of Na+ and K+, it has a central role in acid base equilibrium, Because of such physiological features, Cl– is also the main anion of any crystalloid solution given intravenously for fluid resuscitation and volume maintenance. Clinical consequences
Hyperchloremic metabolic acidosis.
Slower diuretic response to the infusion of Cl–-rich crystalloids may be fluid overload.
Increased extracellular volume can in fact cause an increase in central venous pressure and renal venous engorgement, which reduce trans-renal pressure gradient and flow, as well as interstitial edema which increases renal interstitial pressure due to the relatively non-expansible kidney capsule Moreover, increased central venous pressure is commonly associated with increased intra-abdominal pres0.9% NaCl perioperative showed a higher probability of developing a major postoperative infection, as compared to patients receiving only Plasma-Lytesure. RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS:
Patients undergoing renal transplantation still receive, large amounts of intravenous fluids (up to 30 mL kg-1h-1), in the attempt to increase their intravascular volume and therefore improve graft function.
randomized controlled studies have compared, in patients undergoing renal transplantation, the intravenous administration of 0.9% NaCl with the intravenous administration of different balanced solutions, all of which containing K+ within plasmatic ranges . While no significant difference in graft function was observed, all studies clearly documented a higher incidence of hyperchloremia and acidosis in patients receiving 0.9% NaCl as compared to patients receiving intravenous balanced solutions. It is noteworthy that no difference was observed regarding plasmatic concentrations of K+ and events of hyperkalemia between the two groups. UNBALANCED INTRAVENOUS SOLUTIONS IN RELATION TO OUTCOME:
Patients receiving 0.9% NaCl showed a higher incidence of postoperative infections, a greater incidence of the use of renal replacement therapy and a higher unadjusted mortality rate, as compared to those receiving intravenous balanced solution.
The 0.9% NaCl group showed greater in-hospital mortality, length of hospital stay and frequency of readmission at 90 days than patients in the Ca2+-free balanced group, even after adjustments for Acute Physiology Score and baseline. INTRAVENOUS CHLORIDE LOAD IN RELATION TO OUTCOME:
a reduction in the incidence of AKI, as assessed according to the Risk, Injury, Failure, Loss and End-stage kidney injury (RIFLE) criteria, especially in the injury and risk classes (14% vs. 8.4%, P < 0.001), as well as a reduction in the use of renal replacement therapies in reduction chloride use strategy. BALANCED INTRAVENOUS SOLUTIONS IN RELATION TO SAFETY AND SURVIVAL:
A decrease in in-hospital mortality for any increase in the fraction of balanced solutions over the total amount of fluids intravenously received for the initial resuscitation (2 days), irrespective of the total amount of fluids received.
Administration of intravenous balanced solutions in association with 0.9% NaCl appeared to be associated with a lower in-hospital mortality and a similar length of stay and costs per day as compared to the exclusive administration of 0.9% NaCl. THE SPLIT TRIAL:
In October 2015, the SPLIT trial (the 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy), the first large randomized controlled trial comparing the clinical effects of two different types of crystalloid. An identical proportion of patients developing AKI in the two groups of treatments (9.6% in the balanced solutions group vs. 9.2% in the 0.9% NaCl group), as well as a similar use of renal replacement therapy and in-hospital mortality. CONCLUSIONS:
Both the introduction in clinical practice of intravenous balanced crystalloids solutions and the findings collected on their use in comparison with the traditional administration of 0.9% NaCl, have brought a new awareness in the field of fluid therapy.
Sahar elkharraz
2 years ago
This study focus on different types of intravenous fluid and comparison between 0.9% normal saline and balanced fluid.
However normal saline associated with hyperchloremic metabolic acidosis and balance fluid has electrolytes content near to normal plasma level and minimal effects on acid base balance.
SPLIT trial shows no difference between the 0.9% saline vs. Plasma- Lyte 148 for Intensive Care Unit Fluid Therapy.
Balance fluid like ringer’s lactate and hartmans solutions and acetate fluid contain amino acid and it’s tonicity near to plasma level.
ELECTROLYTE CONTENT AND BALANCED SOLUTIONS:
It’s important to focus on magnesium because 0.9 % normal saline has low magnesium level less than 1.5 mEq/l which may associate with cardiac arrhythmia and reduce renal blood flow and decrease estimate glomerular filtration rate and CNS manifestations.
Hypocalcemia and hypokalemia
So balanced fluid avoid electrolytes disturbance especially high chloride content in normal saline.
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS:
All clinicians use of normal saline because free potassium in transplant patients to avoid hyperkalemia but randomised control studies Shows better to avoid 0.9% normal saline because of hyperchloremic metabolic acidosis which may lead to hyperkalemia and better to use balance fluid rather than normal saline.
Intravenous balance fluid is safer especially in patients with sepsis in comparison to unbalanced fluid.
Balance crystalloids solutions are important in improving outcomes of patients even survival rate in comparison to traditional 0.9% normal saline.
Nasrin Esfandiar
2 years ago
An ideal intravenous solution is shifting from normal saline to more balanced solution in recent years. Their electrolyte composition is closer to the plasma. They minimally induce acid-base disturbances. In addition, they should have zero electro-neutrality. This was shown in a large randomized control trial named SPLIT trial. NaCl 0.9% has a high Cl concentration and induces hyperchloremic metabolic acidosis. There are two categories of balanced solutions: 1- Those with SID close to 24-29 mEq/L (according to Stewart approach) like ringer’s lactate and Hartman solution 2- Low chloride content solutions like plasma-Lyte. Another aspect of a balanced solution is electrolyte content of specific electrolytes such as Mg, Ca and Potassium that should be near the plasma content. Therefore, novel generation like plasma-Lyte contain these electrolytes compared to the old ones (Lactated Ringer’s). Normal saline administration is associated with lower diversis and natriuresis compared to balanced solution which may resulted in fluid overload, increased CVP, intrabdominal pressure and finally kidney hypoperfusion. Hyperchloremic metabolic acidosis may result in increased IL-6, AKI and higher mortality. In renal transplantation usually normal saline without potassium was used to avoid hyperkalemia, but there was no difference regarding potassium between balanced solutions with normal saline. Patients with a major abdominal receiving NaCl surgery showed higher incidence of infection, AKI and mortality compared to those receiving balanced solutions. SPLIT trial performed in 2015 compared NS infusion with Plasma-Lyte 148 in ICU patients. In this double blinded RCT in New Zealand, 2278 patients received either NS or PL. Two groups were similar regarding the development of AKI or RRT or mortality. So, fluid should be considered as “drugs”.
Fatima AlTaher
2 years ago
Fluid therapy is lifesaving for patients with critically illness and renal impairment. The best IV fluid should be of normal tonicity close to plasma osmolality, has no or minimal effect on acid –base balance with near physiological Cl content,. However ,till now this ideal IV solution is not present , instead there are several IV fluids described as balanced solution that are also ChCh by minimal impact on acid base balance and plasma osmolaity and are classified into two types
1- Minimal effect on acid base as acetated and lactated ringer
2- Low Cl content as lactated ringer and hartamm solution.
According to Stewart physicochemical approach to acid-base and electrolyte equilibrium
The normal biologic fluid has 3 components ; water that contain dissolve strong electrolytes. Non volatile weak acids specially albumen and Co2. Thus IV fliud can affect blood PH via altering either electrolytes content , Paco2 or altering SID ( Difference between strong anions and cataions ).
The most commonly used Iv fluid is 0.9%NaCl that carries the risk of hypercholaremic MA with all the associated hazardous effects of both increased Cl and MA. Hypercholaremia can cause altered vascular smooth muscle response to vasopressor drugs beside its effect on argentine vasopressin secretion and rennin activation as well as affecting tubule-glomerular feed back systems even more than Na do. While MA is complicated by myocardial suppression ,decrease vascular response to vasopressor drugs as well s GIT symptoms as anorexia , neasea and vomiting that all lead to further volume depletion and acid base disturbance. Comparison between effects of IV normal saline therapy Vs balanced solutions:
1) In healthy individuals : lower incidence of dieresis ,natruiesis and renal perfusion compared with balanced solution.
2) In critically ill patient : normal saline increase IL6 production , increase risk of AKI and patient mortality.
3) In kidney transplant recipient : the most commonly used IV fluid is normal saline , except in cases of decreased GFR where low K containing fluids are preferred to avoid hyperkalemia. Only few randomized controlled studies compared between the effects of normal saline and balanced solution in kidney transplant populations and revealed no significant difference between them regarding graft function as well as no significant difference regarding incidence of hyperkalemic episodes.
The SPLIT trial was the first randomized , double blinded trial to compare between normal saline and balanced solution as Plasma Lyte 148 regarding the incidence of AKI during 90 days hospital admission and the investigators found that there was no difference between the two groups of patients regarding AKI incidence.
Limitations of this study
1. the population included were low risk post-operative patients who needed small amounts of IV fluids .
2. the effects of the two types of fliud therapy on plasma Cl concentration were not measure
CONCLUSIONS
1. Fliud therapy is a critical issue to consider that must be carefully determined including fluid type , rate of infusion and duration of treatment with monitoring of possible complications.
Ghalia sawaf
2 years ago
WHAT DOES “BALANCED” SOLUTION MEAN?
• The osmolarity as close as possible to plasma osmolarity.
• The need, in specific clinical situations, for an oncotic pressure, or oncoticity, of the fluid
• Theoretically, an ideal balanced solution should have the entire content of all electrolytes equal to the electrolyte content of plasma.
• The total amount of free cations always equals the total amount of free anions.
• all the intravenous solutions available (with the exception of 0.9% NaCl and pure dextrose-containing solutions) have included organic anions (such as acetate, lactate, malate, gluconate, etc.), as precursors of HCO3–
• the necessity of electrical-neutrality and to avoid both hypotonicity and a high Strong Ion Difference.
• the 0.9% NaCl induces hyperchloremic metabolic acidosis
• balanced solutions have been conceived as intravenous solution with a normal (or lower than normal) Cl– content.
• there are two categories of intravenous “balanced” solutions available:
1) those with a minimal effect on acid-base equilibrium, having a SID close to a value of 24−29 mEq L-1; such as Lactated Ringer’s, Acetated Ringer’
Hartmann’s solution, Sterofundin ISO, Hextend, and Tetraspan.
2) those with a Cl– content equal or lower than 110 mEq L-1. Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan
• no ideal balanced solution has become available so far.
STEWART’S APPROACH AND THE MECHANISMS REGULATING ACID-BASE DURING FLUID INFUSION
a) water, the solvent
b) strong electrolytes (such as Na+, K+, Cl–), chemically non-reacting; c) weak, non-volatile acids (mainly albumin and phosphates)
d) carbon dioxide (CO2) system — in equilibrium with carbonic acid (H2CO3)
Stewart pointed out three constraints under which the system,
1) electrical neutrality
2) dissociation equilibria
3) conservation of mass
Subsequently, Stewart set up a system of how (H+) concentration (i.e., pH) varied according to these changes.
The dependent variables were defined as H+, OH–, HCO3–, CO3 2–, weak acid, and weak ions (A–).
1) the partial pressure of (PCO2);
2) the concentration of non-volatile weak acids (ATOT), mainly albumin and phosphates;
3) the Strong Ion Difference (SID),
• according to the total amount infused, the SIDinf and the content of weak acids, intravenous fluids can alter both SID and ATOT of plasma, with consequent effects on plasma pH.
• The fluid that does not alter plasma pH, at constant PCO2, regardless of the total amount infused and the degree of plasma dilution, should therefore balance the variations of these two independent variables
• crystalloid solutions, not containing weak acids (albumin or phosphates), the following general rule has been identified based upon in vitro and in vivo studies
1) If SIDinf is greater than the baseline concentration of plasma HCO3–, then pH will tend toward alkalosis during the intravenous infusion
2) If SIDinf is lower than the baseline concentration of HCO3–, then pH will tend toward acidosis during the intravenous infusion
3) If SIDinf equals the baseline concentration of HCO3–, then pH will not change, regardless of the extent of the dilution.
we can state that a “balanced” crystalloid solution should be a crystalloid solution that has an in-vivo SID, i.e., after the metabolism of organic anions, very similar to the patient HCO3– concentration.
It is noteworthy that this rule should apply also for non-ionic colloids, on the other hand, ionic colloids
should have a greater SIDinf, in order to balance the acidifying effect of the administered weak acid.
ELECTROLYTE CONTENT AND BALANCED SOLUTIONS MAGNESIUM
• Hypomagnesemia, below 1.5 mg dL-1, is a relatively common finding in both critically ill patients and patients admitted to ICU
• severe hypomagnesemia may be associated with a higher incidence of cardiac arrhythmias as well as alterations of the cerebral nervous system.
• reduction in GFR and of (RBF) in relation with a concentration
• hypomagnesemia has been reported as being associated with a worse prognosis non-recovery renal function after AKI
• the novel generation of “balanced” solutions (such as the crystalloid solutions Plasma-Lyte or Sterofundin ISO) have been developed with the inclusion of magnesium
CALCIUM
Hypocalcemia, especially total Ca2+ content, may be considered the most common abnormality in plasma electrolyte concentration observed in acutely ill patients
Replacement with either Ca2+-gluconate or Ca2+-chloride.
However, the possible limitation, as related to the risk of Ca2+ precipitation as Ca2+-citrate or Ca2+carbonate.
POTASSIUM
Hypokalemia is a life-threatening electrolyte abnormality in critically ill patients
intravenous balanced solutions present a concentration of K+ within normal ranges.
This feature has been erroneously considered a reason for preferring the use of 0.9% NaCl as the only intravenous solution potentially applicable in the case of patients with acute or chronic renal failure.
THE IMPORTANCE OF CHLORIDE CONTENT AND ITS PATHOPHYSIOLOGIC EFFECTS
• Chloride is the main anion of the extracellular fluid,
• it is is not as tightly regulated
• it has a central role in acidbase equilibrium
• over the years, it has become evident that the Cl– content of intravenous fluids, especially at supra-physiologic levels, may have relevant clinical consequences.
Normal saline presents a high non-physiological content of Cl– (and Na+),
0.9% NaCl induced metabolic acidosis will be added to any other possible causes of acidosis, especially in critically ill patients and diabetic ketoacidosis
• Several reports have observed that Cl– mediates vascular smooth muscle may affect plasma renin activity and systemic blood pressure
• The tubule-glomerular feedback (TGF), has been shown to be dependent on Cl– delivery, rather than Na+ delivery, to the distal tubule and its uptake by the macula densa
Studies on healthy individuals receiving an IV administration of 0.9% NaCl, as compared to balanced solutions, was associated with a lower diuresis and natriuresis, and a lower renal artery blood flow velocity and cortical renal perfusion
The consequence of the relatively slower diuretic may be
• fluid overload,
• increase in CVP
• renal venous engorgement,
• increases renal interstitial pressure
• increased intra-abdominal pressure,
• reduction in venous return and cardiac outpu,
• kidney hypoperfusion and damage.
intravenous administration of a bolus of 0.9% NaCl may causes
• abdominal discomfort
• decrease in gastric mucosal perfusion
An effect of hyperchloremic acidosis on the function of the immune system has been postulated based upon experimental studies in septic animals
a study on septic rats resuscitated with intravenous administration of either 0.9% NaCl
• increased IL-6 levels,
• incident (AKI)
• higher mortality rate in those receiving 0.9% NaCl
In retrospective analysis , patients receiving only 0.9% NaCl perioperatively showed a higher probability of developing a major postoperative infection, as compared to patients receiving only Plasma-Lyte
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS
The choice of intravenous fluids is challenging,
In renal transplantation, intravenous fluids are administered normally to patients with ESRD
in many centres, large amounts of intravenous fluids (up to 30 mL kg-1h-1), to improve graft function
A survey recently performed in the United States pointed out that 0.9% NaCl, based intravenous solutions, were the most commonly employed intravenous solutions during renal transplantation.
the selection of a K+-free solution to avoid hyperkalemia in patients with reduced potassium excretion capabilities.
However, large amounts of 0.9% NaCl, induces hyperchloremic metabolic acidosis, leading to the development of hyperkalemia, and may affect renal function.
A few randomized controlled studies have compared, in patients undergoing renal transplantation, the intravenous administration of 0.9% NaCl with the intravenous administration of different balanced solutions, all of which containing K+ within plasmatic ranges
no significant difference in graft function was observed
no difference was observed regarding plasmatic concentrations of K+ and events of hyperkalemia between the two groups.
CLINICAL EVIDENCE
the first large RCT investigating a possible long-term and clinically relevant benefit of a balanced solution over an unbalanced solution for fluid resuscitation or volume maintenance, has been concluded just very recently
In association with the modification of the fluid strategy, the authors observed
a reduction in the incidence of AKI, as assessed according to (RIFLE) criteria, especially in the injury and risk classes (14% vs. 8.4%, P < 0.001),
as well as a reduction in the use of renal replacement therapies (10% vs. 6.3%, P = 0.005), even after adjustments for covariates
a retrospective analysis of a large cohort of patients with SIRS, Shaw et al. observed a direct correlation of both the total amount of Cl– intravenously received and the associated increase in serum Cl– concentration during fluid resuscitation with an increased risk of death
BALANCED INTRAVENOUS SOLUTIONS IN RELATION TO SAFETY AND SURVIVAL
in two large retrospective studies performed on the same large clinical database in two different cohorts of patients with sepsis
In the first one showed a decrease in in-hospital mortality in balanced solutions , irrespective of the total amount of fluids received
In the second study, appeared to be associated with a lower in-hospital mortality and a similar length of stay and costs per day as compared to the exclusive administration of 0.9% NaCl
THE SPLIT TRIAL
• In October 2015
• (the 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy)
• the first large RCT comparing the clinical effects of two different types of crystalloids
• double-blind
• cluster randomized,
• double-crossover trial,
• in 4 ICUs
• in New Zealand,
• 2,278 ICU patients in need of crystalloid fluid therapy
• receive either 0.9% NaCl or Plasma-Lyte 148, as a balanced solution,
1. the primary outcome; the proportion of patients with AKI during the first 90 days after enrolment,
2. several endpoints as secondary outcomes.
• In contrast to the hypothesis, the authors observed an identical proportion of patients developing AKI in the two groups of treatments (9.6% in the balanced solutions group vs. 9.2% in the 0.9% NaCl group),
• as well as a similar use of renal replacement therapy and in-hospital mortality.
• study’s limitations,
1. the study population included was composed of post-operative patients, after elective surgery with low risk
Consequently, most of the patients in both groups received very small amounts of intravenous study fluids (2L as median values, during the study period),
2. no data on the effects of the two treatments on plasma Cl– concentration have been measured, making therefore impossible to assess the potential determinant of the deterioration of renal function during fluid therapy.
CONCLUSIONS
fluids should be considered as “drugs”
The type of fluid, the dose, the rate of administration, the timing and the duration of the treatment are all equally important.
the “ideal” intravenous balanced solution has not yet become available.
The SPLIT trial, showed precise equipoise between the two treatments, although presenting important limitations
Further researchers on the potential mechanisms underlying the clinical effects observed on specific types of crystalloid solutions is warranted.
Wael Jebur
2 years ago
The article reviewed in depth, different aspects of conventional intravenous fluids focusing on the complications related to its use. The major drawback encountered in daily practice stemmed from the supraphysiologic concentration of some ions particularly Chloride. Resultant hyperchloremic metabolic acidosis is a common complication reported with overzealous administration of normal saline. Furthermore, the article elaborated on the newly introduced balanced solution, which is not inflicting hyperchloremia or metabolic acidosis and dose not result in derangement of other electrolytes concentration. Similarly, it shed light on the mechanism of renal function abnormality reported in the context of infusing normal saline, directly through its chloride content. The tubulo-glomerular feedback mechanism TGR operate to protect against the wasting of electrolytes and water by the kidneys in response to fluctuating systemic blood pressure. This mechanism is essentially mediated via chloride absorbed by Macula Densa cells in distal convoluted tubules promoting adjacent afferent arteriole vasoconstriction to prevent distal delivery and ultimate over excretion of salt. This exact mechanism is utilized by chloride content of normal saline to trigger same consequences. This putative mechanism is bolstered by common findings of diminished diuresis and natriuresis during the administration of normal saline excessively.
Utilization of this physiologic mechanism by Cl overload is aberrant and non-physiological. Other phenomena were developed linked to administration of Cl is reduction of renal blood flow and renal vasoconstriction triggered by the same.
The major effect of intravenous fluids used currently were conceptualized according to Stewart’s theory. Conclusively the Acid base balance and PH
is dependent on 3 parameters as follows:
1-dissolving pressure of CO2, PCO2
2-presence of weak acids in the solvent such as Albumin and phosphate
3- Strong Ionic Difference SID. which reflect the sum of cations minus sum of anions.
summarized as Na +K – Cl.
Cl is interplaying a pivotal role in mounting an acidic milieu,
Rihab Elidrisi
2 years ago
This article is demonstrating a type of iv fluid which suppose to be used in surgical patients safely. We prefer the balanced iv fluid and according to the study it showed lower morbidity and mortality
Generally, using of balanced solution which is similar to the plasma is better with a similar concentration of electrolytes that do not affect osmolality, and maintain the same oncotic pressure and the ions both anions and cations are balanced.
In this article,we can see in the SPLIT trial showed was a 90-day double-blind randomized double-crossover experiment in ICU patients to detect AKI. No replacement fluid affected AKI incidence, RT use, or mortality. This study had significant limitations, including a low number of high-risk patients, a group of post-operative choice surgery patients, and a tiny intravenous fluid dose.
Mohamad Habli
2 years ago
Summary
A balanced solution is defined asintravenous fluid with electrolytes closer to plasma than prior intravenous fluids (such 0.9% NaCl), impacting acid-base balance less than 0.9% NaCl-associated hyperchloremic metabolic acidosis. An electrically neutral balanced solution has plasma-like electrolyte content. Balanced solutions have typical chloride levels.
Intravenous “balanced” solutions are categorized in two types:
1- Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan.
2- Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Sterofundin ISO, Hextrend, and Tetraspan have a strong ion difference (SID) of 24-29 mEq/L and minimally affect acid-base balance.
Stewart’s acid-base principles: Water (weakly dissociated solvent with high molality), strong electrolytes (Na+, K+, Cl–, chemically non-reacting and fully dissociated), weak acids (albumin, phosphates, partially dissociated), and carbon dioxide system make up biologic fluid (CO2, H2CO3). Electrical neutrality, dissociation equilibrium, and mass conservation are required.
The partial pressure of CO2, the concentration of non-volatile weak acids (albumin and phosphates), and the strong ion difference (SID) affect biologic fluid pH.
Besides salt and chloride, “balanced” solutions contain magnesium, calcium, and potassium, which have physiological functions. Low magnesium levels are linked to decreased GFR, renal blood flow, cardiac arrhythmias, and ECG abnormalities. 90% of critically ill patients have low calcium levels, causing muscular contractility and arrhythmias. Low potassium levels affect muscle contractility and arrhythmias.
Crystalloid solutions’ principal anion, chloride, controls acid-base equilibrium. 0.9% saline causes hyperchloremic metabolic acidosis. Increased norepinephrine and angiotension-II constrict vascular smooth muscle. Reduced tubule-glomerular feedback reduces renal blood flow and GFR, lowering diuresis and producing fluid overload, nausea, vomiting, abdominal pain, reduced gastric mucosal blood flow, increased nitric oxide and pro-inflammatory cytokines, and systemic blood pressure reduction.
0.9% NaCl intravenous fluid in renal transplantation has been linked to hyperchloremic metabolic acidosis, hyperkalemia, and renal function, unlike “balanced” solutions. AKI, CKD, and renal transplant patients should avoid 0.9% NaCl.
Several research show the benefits of “balanced” solution. 0.9% NaCl use is linked to higher infections, RRT use, death, length of stay, and re-admission. Replacement fluid chloride level increases AKI, RRT use, and death. “Balanced” methods cut mortality and hospital stay and expense. SPLIT was a 90-day double-blind randomized double-crossover experiment in ICU patients to detect AKI. No replacement fluid affected AKI incidence, RT use, or mortality. This study had significant limitations, including a low number of high-risk patients, a group of post-operative choice surgery patients, and a tiny intravenous fluid dose.
In conclusion, intravenous fluids are medications and should be prescribed after answering questions about type, dose, rate of delivery, timing, and duration.
rindhabibgmail-com
2 years ago
This article discussed the IVF choices and differences on physiological bases to clinical evidence, so all fluids are medicine, they can be used as volume replacement, correction of hemostasis, correction of electrolytes etc. so in conclusion the balanced solution composition, tonicity, osmolality must be close to physiological need. Because every drug has its potential risk and complications. So before prescribing IVF drug it should be in mind to plan the type, dose, rate of administration, and need of the patient.
Marius Badal
2 years ago
Summarise this article The article is based on a critical appraisal of intravenous fluids from the physiological basis to clinical evidence. Fluid balance is important as it must be used in patients for various reasons and as such its constituents must be close to the plasma. The study was one in which a large randomized control trial comparing how intravenous balanced solution vs 0.9% NaCl how will impact renal function and hospitalized survival. In doing so, whatever fluid is used even though it may be safe but may have some harm to it depending on what one is treating. As such a balanced fluid is one that is similar to plasma where pH. So by definition, a balanced solution is one in which: 1) The fluid that is equal to the volume desired for the replacement contains a similar the concentration of electrolytes that do not affect osmolality, maintain the same oncotic pressure and the ions both anions and cations are balanced. 2) Haemostasis is an important mechanism of the body to prevent bleeding. 3) Fluid balance is the difference between the input and output of fluid. 4) There is no ideal solution but there are solutions that can assist depending on was it is being treated. Based on what is mentioned, there are two main types of balanced fluids are: 1) The one with little effect on the acid-based equilibrium with a SID close to 24-29 mEq L 2) The ones with CL content equal to or lower than 110 mEq/l The examples of group one are: 1) Lactated ringers 2) Acetated ringers. 3) Hartmann solution 4) Sterofundin ISO 5) Hextend and 6) Tetraspan. Examples of the second group are: 1) Lactated ringer 2) Acetated ringers. 3) Hartmann solution 4) Plasma lye, 5) Elo mel Isoton 6) Isoplex 7) Gelespan. Stewart’s approach and the mechanism of acid-base regulation during fluid infusion: 1) Water is the universal solvent with high molality and doesn’t dissociate easily 2) Electrolytes like sodium, potassium, and chloride can disassociate in a biological solution 3) Weak non-volatile acids like albumin and phosphate partially dissociate 4) There is equilibrium with CO2 and H2CO3 The criteria of the solutions are: 1) Must be electrically neutral 2) Must have dissociation equilibrium 3) Can conserve mass, etc. Based on fluids and the pH, there are factors that can affect it: 1) The presence of weak acid but volatile 2) The concentration of CO2 3) The presence of strong ion Looking at the electrolytes and their importance: 1) Magnesium: very low Mg may be associated with cardiovascular arrhythmias and will changes in the electrocardiogram. Crystalloid solutions plasma Lyte or sterofundin ISO has Mg. 2) Calcium: low calcium can cause muscle contraction, cardiac arrhythmias, and abnormal function of the nervous system. It is not part of the solutions but can be added due to the possibility of causing precipitation. 3) Potassium: some solutions may contain potassium like lactate ringer or Hartmann solution and are normally at a normal range as serum. Low K can cause cardiac arrhythmias and muscular contraction. High potassium will also cause cardiovascular arrhythmias also. 4) Chloride: Cl is mostly found in high-concentration extracellular and plays a role in acid-base equilibrium. It is the most commonly used electrolyte but can cause hyperchloremic metabolic acidosis. The high concentration of Cl may cause affectation at the level of the kidneys by affecting the tubular-glomerular feedback mechanism. Kidney transplantation and the use of intravenous fluids: There have been studies that compare the use of sodium chloride with other solutions post-transplantation. What the result suggested was that there weren’t significant differences between the solutions but there was a higher incidence of hyperchloremic metabolic acidosis in those receiving sodium chloride than those not receiving it. As it relates to potassium there were no differences. So in conclusion it is noted that in causes of AKI and CKD sodium chloride must be carefully used to avoid metabolic acidosis. The outcome of unbalanced solutions from balanced solutions: 1) It has been found that patients that do major surgery with the use of normal saline have shown a higher incidence of infection, increased need for RRT, and higher mortality when compares to Ca-free balance solutions. 2) It has shown that balanced solutions have a survival advantage and safety compared to unbalanced solutions. So in conclusion, one must consider the aspect of the solution to give the patient and the type, duration, and amount given must be noted. Also, balanced solutions have a better physiological advantage over unbalanced solutions and one must ensure that the balanced solution doesn’t have any effect on the patient’s electrolytes and acid-base equilibrium. More needs to be learned about solutions and as such care must be taken in the decision of which solution to be used.
Mohammad Alshaikh
2 years ago
Summarise this article
Definition of balanced solutions: Balanced solutions are an intravenous fluids having an electrolyte composition close to that of plasma, that minimally affect acid-base equilibrium. The target water hemostasis is to maintain the effective circulatory volume (by water and electrolyte contents), pertaining euvolemia. IV fluids for volume restorment should be: Keeping similar osmolarity to the serum. Keeping the fluid with close tonicity (by dissolved electrolytes) close to serum osmolality. In specific clinical situations, for an oncotic pressure, or oncoticity, of the fluid and, therefore, for an oncotic molecule dissolved in the solution, ideally aimed. Electrical neutrality (cations = anions).
STEWART’S APPROACH AND THE MECHANISMS REGULATING ACID-BASE DURING FLUID INFUSION: Peter Stewart began with describing the components of biologic fluid: a) Water, the solvent, which has a high molality and is very weakly dissociated. b) Strong electrolytes (such as Na+, K+, Cl–), which are always entirely dissociated in biologic solution, and can be considered as chemically non-reacting. c) Weak, non-volatile acids (mainly albumin and phosphates), which are defined as substances only partially dissociated in aqueous solution, according to their dissociation constant. d) Carbon dioxide (CO2) system — dissolved molecular CO2 in equilibrium with carbonic acid (H2CO3) and its dissociation products. He also put a three constraints: 1) Electrical neutrality. 2) Dissociation equilibrium. 3) Conservation of mass PH of biologic fluids maintained by: 1) the partial pressure of carbon dioxide (PCO2). 2) the concentration of non-volatile weak acids (ATOT), mainly albumin and phosphates. 3) the Strong Ion Difference (SID), defined as the difference between the sum of strong cations (mainly Na+, K+, Mg2+, Ca2+) and the sum of strong anions (mainly Cl–, lactate, and other possible unmeasured anions), according to the following formulas: a) SID = (Na+ + K+ + Ca2+ + Mg2+) – (Cl– + other strong anions). b) Abbreviated SID = (Na+ + K+) – (Cl–). However, no solution considered totally balanced.
ELECTROLYTE CONTENT AND BALANCED SOLUTIONS: Magnesium: Plasma-Lyte or Sterofundin have been developed with the inclusion of magnesium, as compared to the old generation (Lactated Ringer’s, Acetated Ringer’s or Hartmann’s solution), as the magnesium level lower than 1.5 mg/dl usually seen in critically ill patients and even lower level associated with cardiac arrhythmia, ECG changes, CNS alteration, muscle weakness, reduction in glomerular filtration, and renal blood flow leads to AKI. Calcium: the calcium cannot be a composition of an IV fluid as it easily precipitates. So can be transfused separately. Hypocalcemia is seen in almost 90% of critically ill patients, manifest as alterations in muscle contractility, of peripheral and central nervous system function, cardiac arrhythmias. Potassium: All the available intravenous bal[1]anced solutions present a concentration of K+ within normal ranges that does not meet the daily required potassium need that can be taken orally, hypokalemia manifest as h alterations of muscle contractility, and alterations in cardiac rhythm.
THE IMPORTANCE OF CHLORIDE CONTENT AND ITS PATHOPHYSIOLOGIC EFFECTS: Chloride is the main extracellular anion nad play central role in acid- base equilibrium, and should be in its physiological concentration in IV fluids, in order not to alter the acid –base equilibrium. In high concentration as present in 0.9% N/S can lead to hyperchloremic metabolic acidosis and hyperkalemia.
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS: Data strongly support the avoidance of 0.9% N/S and other possible intravenous fluids causing metabolic acidosis in patients with acute or chronic renal failure, as well as during renal transplantation, and provide the first solid data on the safety of employing K+- containing balanced solutions for volume replacement and maintenance in this specific clinical setting.
CLINICAL EVIDENCE: UNBALANCED INTRAVENOUS SOLUTIONS IN RELATION TO OUTCOME- N/S 0.9%, showed a higher incidence of postoperative infections, a greater incidence of the use of renal replacement therapy as compared to those receiving intravenous balanced solutions, but no difference in mortality rates was observed between the two groups. Patients in the 0.9% N/S group have greater in-hospital mortality, length of hospital stay and frequency of readmission at 90 days than patients in the Ca2+-free balanced group. INTRAVENOUS CHLORIDE LOAD IN RELATION TO OUTCOME- A chloride restrictive strategy showed a reduction in the incidence of AKI, as assessed according to the Risk, Injury, Failure, Loss and End-stage kidney injury (RIFLE) criteria, as well as a reduction in the use of renal replacement therapies. Shaw et al. observed a direct correlation of both the total amount of Cl– intravenously received and the associated increase in serum Cl– concentration during fluid resuscitation with an increased risk of death. BALANCED INTRAVENOUS SOLUTIONS IN RELATION TO SAFETY AND SURVIVAL- The administration of intravenous balanced solutions is associated with a lower in-hospital mortality and a similar length of stay and costs per day as compared to the exclusive administration of 0.9% N/S.
THE SPLIT TRIAL: In October 2015, double blinded randomized controlled trial comparing OsmoLyte to N/S infusion in patients in ICU setting showed no difference between two groups in AKI within 90 days, the need for RRT, or mortality. The limitations are: most patient are after an elective cardiac surgery with small number of seriously ill patients, the fluids used are around 2 liters only that might not interrupt the acid base equilibrium, and no n plasma Cl– concentration have been measured.
CONCLUSIONS:
IV fluid resuscitation should be considered as a drug with its potential risks and complications, that the physicians should be aware of.
Timing and duration of IV fluid administration should be taken in consideration wile choosing which fluid to use.
N/S large infusion was associated with increased risk of AKI/ reduced GFR and decreased renal blood flow rate.
Balanced fluids has less side effect than the metabolic derangement observed with normal saline massive infusion.
Balanced fluids should be considered as resuscitation fluid of choice in acute or chronic kidney disease patients, as well as patients undergoing kidney transplantation.
Amit Sharma
2 years ago
Summarise this article
A ‘balanced solution’ is intravenous fluid with electrolyte composition closer to that of plasma as compared to the previously available intravenous fluids (like 0.9% NaCl), minimally affecting the acid-base balance (unlike 0.9% NaCl associated hyperchloremic metabolic acidosis). An ideal balanced solution should have the electrolyte content equal to that of plasma and hence should be electrically neutral. Ns showing harmful effects of supra-physiological chloride levels, the balanced solutions have a normal or lower chloride levels.
Two categories of intravenous ‘balanced’ solutions are available:
a) Those with chloride content less than or equal to 110 mEq/L: Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan.
b) Those with strong ion difference (SID) of 24-29 mEq/L, having minimal effect on acid-base balance: Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Sterofundin ISO, Hextrend, and Tetraspan.
Principles of Stewart’s approach to acid-base balance: The components of biologic fluid include water (weakly dissociated solvent with high molality), strong electrolytes (Na+, K+, Cl–, chemically non-reacting and entirely dissociated), weak acids (albumin, phosphates – only partially dissociated), and carbon dioxide system (CO2, H2CO3). These should have electrical neutrality, must be in dissociation equilibrium, with conservation of mass.
The pH of biologic fluids gets influenced by 3 variables, namely the partial pressure of CO2, the concentration of non-volatile weak acids (albumin and phosphates) and the strong ion difference (SID, Na+ + K+ – Cl–).
Other electrolytes like magnesium, calcium and potassium also have a physiological role, and hence are added in ‘balanced’ solutions, in addition to sodium and chloride. Low magnesium levels have been shown to be associated with reduced GFR and renal blood flow, and increased incidence of cardiac arrhythmias and ECG changes. Low calcium levels are seen in upto 90% of critically ill patients, leading to altered muscle contractility and arrhythmias. Low potassium levels are also associated with altered muscular contractility and arrhythmias.
Chloride is the main anion of any crystalloid solution with central role in acid-base equilibrium. 0.9% saline induces hyperchloremic metabolic acidosis. There is contraction of vascular smooth muscle with increased norepinephrine and angiotension-II. Reduction in tubule-glomerular feedback leads to reduced renal blood flow and GFR decreasing diuresis leading to fluid overload, nausea, vomiting, abdominal discomfort, reduced gastric mucosal blood flow with increased production of nitric oxide and pro-inflammatory cytokines causing reduction in systemic blood pressure.
Comparing intravenous fluid in renal transplant, 0.9% NaCl has been shown to be associated with hyperchloremic metabolic acidosis and hyperkalemia, and may affect renal function, findings not seen with use of ‘balanced’ solutions. Hence 0.9% NaCl should be avoided in patients with AKI, CKD, or renal transplant.
Clinical evidence regarding the benefit of using ‘balanced’ solution has come from several studies. Studies have shown that 0.9% NaCl use is associated with increased infections, RRT use, and death with increased length of stay and re-admission. Increased chloride content in the replacement fluids is associated with increased AKI, RRT use and death. Use of ‘balanced’ solutions has been shown to be associated with reduced mortality and similar length of hospital stay and costs. The SPLIT trial was double-blind randomized double-crossover trial in ICU patients designed to look for AKI in first 90 days. It showed that there was no difference in AKI incidence, RT use or mortality with respect to the replacement fluid used. But this study had many limitations including low number of high-risk patients, study population mainly involving post-operative patients after elective surgery, and use of very small amount of intravenous fluid.
Inconclusion, intravenous fluids should be considered as drugs and questions regarding their type, dose, rate of administration, timing and duration of treatment should be addressed before prescribing.
What is the evidence provided by this article?
Level of evidence: Level 5 – Narrative review
Assafi Mohammed
2 years ago
SUMMARY OF THE ARTICLE “A critical appraisal of intravenous fluids- from the physiological basis to clinical evidence”
This review article about balanced solutions, comprehensively provided: · A full physiological background of balanced solutions. · The potential pathophysiologic effects of balanced solutions. · The clinical evidence available at the moment to support their use or not.
The ideal balanced solution: · Should be the same as plasma regarding the electrolytes content. · Should display the characteristic of electrical-neutrality(dissolved free positive charges = dissolved free negative charges). · With a normal (or lower than normal) Cl– content. The characteristic of balanced solution: · Minimal effect on acid-base equilibrium. · The physiological content of Cl–.
Indeed; · no ideal balanced solution has become available so far. · Available solutions, either they belong to just one category (having an effect on acid-base equilibrium while having a normal Cl– content, and vice versa). · Available solutions, may present some limitations, such as relative hypotonicity (in the case of Lactated Ringer’s, Acetated Ringer’s, or Hartmann’s solution) Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan. · A balanced crystalloid solution should be a crystalloid solution that has an in-vivo SID, very similar to the patient HCO3– concentration.
Renal transplantation and IV fluids: 1. A few randomized controlled studies documented a higher incidence of hyperchloremia and acidosis in patients receiving 0.9% NaCl as compared to patients receiving intravenous balanced solutions; · data strongly support the avoidance of 0.9% NaCl and other possible intravenous fluids causing metabolic acidosis in patients with acute or chronic renal failure, as well as during renal transplantation. · provide the first solid data on the safety of employing K+– containing balanced solutions for volume replacement and maintenance in renal transplantation. 2. 0.9% NaCl administration is associated with greater in-hospital mortality, length of hospital stay and frequency of readmission at 90 days than patients in the Ca2+-free balanced group, even after adjustments for Acute Physiology Score and baseline covariates. 3. The type of fluid, the dose, the rate of administration, the timing and the duration of the treatment are all equally important.
mai shawky
2 years ago
Club 1; Intravenous balanced solutions: from physiology to clinical evidence
Summary:
· Simply, balanced crystalloid solution is the most similar to plasma osmolality and electrolytes composition and is elctroneutral (dissolved cations equal to the dissolved anions).
· The studies want to find balanced crystalloid solution with less chloride content than isotonic NaCL 0.9 % (to avoid hyper-chloremic metabolic acidosis of the supraphysiological amount of Cl in isotonic saline and its effect on the graft outcome).
· Most of available solutions include organic substances as acetate, lactate, malate, gluconate, etc to act as bicarb precursors.
· Till now, no available solution with the target 2 objectives: minimal effect on acid base balance and physiological content of chloride.
· Solutions with minimal effect on acid base as: ringer lactate, acetate and hartmann solution.
· However, Lactated Ringer’s, Acetated Ringer’s and Hartmann’s solution have lower tonicity than the plasma.
· Hypomagnesemia in critically ill patients is associated with AKI. decreased renal blood flow, GFR and cardiovascular mortality. Hence, novel generation of “balanced” solutions (as Plasma-Lyte or Sterofundin ISO) have been developed to contain magnesium, in comparison to the old generation (Lactated Ringer’s, Acetated Ringer’s or Hartmann’s solution).
· Hypocalcemia has detrimental effect on the muscles, CNS and arrhythmia, hence, need to supply it in large amount within the balanced solutions. However, the risk of ca precipitation, it is supplied in the form of ca gluconate or citrate in a separate line.
· Hypokalemia has serious effects on the heart and muscles,but the normal K content of available balanced solutions was falsely considered inappropriate for patients with AKI or CKD and so isotonic saline was the preferred solution in renal patients to avoid hyperkalemia.
· Isotonic saline is the most commonly used solution in resuscitation, but it causes hypercholremic metabolic acidosis that worsen acidosis in case of shock, hypoperfusion and DKA in addition to misleading the clinical decision in trial to search for underlying cause of acidosis and its treatment.
· The adverse effects observed with isotonic saline induced acidosis:
o Cl mediated vasoconstriction of blood vessels>>. ↑RAAS>> hypertension.
o Tubule-glomerular feedback (TGF) which depends on CL (rather than Na) delivered to the distal nephron>>. decreased natriuresis so volume overload and edema.
o Decreased gastric mucosal blood supply and abdominal discomfort.
o Animal studies done on septic rats concluded that the hypercholremia increased release of pro-inflammatory cytokines as IL6, but still an association and can be considered as a causation.
o In addition, it was observed that it has higher incidence of post operative infections, sepsis, hospital stay, higher incidence of AKI that required renal replacement therapy with isotonic saline used in major surgery. However, other concomitant factors may be responsible for the worse outcome.
· kidney transplantation patients have 2 problems:
o Need for large amount of fluid administration to enhance the graft perfusion.
o Fear from the hyperkalemia.
· Isotonic saline is still the most commonly used due to its low K content, however, the hyperchloremic acidosis cause hyperkalemia beside deleterious effect of hyperchloremia on allograft outcome.
· Studies comparing isotonic saline and other balanced solutions concluded that balanced solution has no worse effect on hyperkalemia and has less incidence of hypercholermic acidosis. hence, the use of K containing solutions can be used safely in transplant patients.
· However, RCTs are still needed to study the long term effect on the graft and patient survival.
· Use of Cl restrictive approach was associated with less incidence of AKI, need for RRT,
· RCT comparing plasma- lyte 148 and isotonic saline, published in 2015. concluded that both have similar rates of AKI, RRT and mortality. however, this study has many limitations as most of patients received relatively small amount of IV fluids due to cardiovascular problems.
· Conclusion:
o IV fluids are considered a drug with crucial need to determine its use, dose and adverse effects.
o Ideal balanced crystalloid solution is not available yet.
level of evidence” V (narrative review).
Hussein Bagha baghahussein@yahoo.com
2 years ago
Introduction
Current studies have debated the use of the ideal type and amount of fluid usage in the critical care and emergency units, for better patient outcomes. The study aims to provide a comprehensive review of the same, by providing a physiological background of balanced solutions and summarizing their potential pathophysiologic effects, and presenting the clinical evidence available to support their use or not.
What does “balance” solution mean?
Homeostasis is essential in human physiology. Our daily fluid input should ideally match the output, to maintain effective circulating blood volume, overall content of water and electrolytes. Intravenous administration of fluid alters this process.
In theory, a balanced solution should have the electrolyte content equal to that of plasma, and it should have minimal effect on the acid-base equilibrium.
Currently, the available “balanced” solutions available meet the criteria of either having minimal effects of the acid-base equilibrium, by having a SID close to the value of 24-19mEq/L (as seen in Ringer’s Lactacte, acetated Ringer’s, Hartmann’s solution, Sterofundin ISO, Hextend and Tetraspan), and has chloride ion content equal or lower than 110 mEq/L (as seen in Ringer’s lactate, acetated Ringer’s, Hartmann’s solution, Plasma-lyte, Elo-Mel Isoton, Isoplex and Gelaspan). Stewart’s approach and the mechanisms regulating acid-base during fluid infusion
Peter Stewart describes the components of biological fluids as follows:
1. Water – the solvent
2. Strong electrolytes – Na+, K+, Cl-
3. Weak, non-volatile acids – albumin and phosphates
4. Carbon dioxide (CO2) system
The acid-base system needs to operate under the following criteria; electrical neutrality, dissociation equilibria, and conservation of mass.
The dependent variables of his system that affected the pH of biological fluids included H+, OH-, HCO3-, CO32-, weak acid and weak ions. The independent variables were the partial pressure of CO2, the concentration of non-volatile weak acids and the strong ion difference (SID).
The following mechanisms clearly suggest that intravenous fluids may have an effect of the pH of plasma. It is also important to remember that the effects of intravenous solutions may vary in different patients and there is no available solution that is ideally balanced.
Electrolyte content and balanced solutions
1. Magnesium
Hypomagnesemia is often seen in patients that are critically ill
It is associated with a higher incidence of cardiac arrhythmias and CNS changes
“Balanced” fluids may have the potential to supplement a small percentage of magnesium
2. Calcium
Hypocalcemia is also often seen in critically ill patients
It causes alterations in muscle contractions, alterations in the function of the peripheral and central nervous system, cardiac arrhythmias
It may be a benefit to be able to supplement calcium in the ideal “balanced” solution, but it may cause calcium ion precipitation when used in the same access as blood components or bicarbonate
3. Potassium
Hypokalemia causes alterations in muscle contractility and cardiac rhythm
“Balanced” solutions have a percentage of potassium supplementation, and hence 0.9% NaCl is usually used in patients with renal dysfunction. But this theory may be misguided.
The importance of chloride content and its pathophysiologic effects
Normal saline has a high levels of chloride and sodium ions. Using it liberally will therefore cause hyperchloremic metabolic acidosis. In critically ill patients, this will exacerbate the acidosis that is possibly ongoing from other causes, worsening the clinical status of the patient.
There are also other side effects of chloride toxicity. Chloride ions mediate vascular smooth muscle cell Ca+-dependent contraction, it may modify vascular responses to vasoconstrictor agents in the kidney and it may affect plasma renin activity (and thereby affecting systemic blood pressure). The tubule-glomerular feedback, that regulates the sodium and water balance in the kidneys, is also dependent on Cl-. Studies on healthy individuals showed that the use of normal saline was associated with reduced diuresis and natriuresis, and lower renal artery blood flow and cortical renal perfusion. This may lead to a state of fluid overload, and increased extracellular volume can cause an increase in central venous pressure and renal venous enlargement, both of which will lead to a reduced venous return and cardiac output. All these mechanisms may lead to kidney hypoperfusion and damage.
Hyperchloremic metabolic acidosis has also been associated with an increase in IL-6 levels, incident acute kidney injury and a higher rate of mortality.
Renal transplantation and intravenous fluids
Patients with renal dysfunction have impaired handling of water and electrolytes. During renal transplantation, large amounts of fluids are required for patients with end-stage renal disease, in the attempt to increase intravascular volume and hence improve graft function. Usually, the preferred choice of fluids is normal saline, as it does not have potassium, and therefore it avoids hyperkalemia.
Recent studies have shown that “balanced” solutions did not cause hyperkalemia, and normal saline was associated with a higher incidence of hyperchloremic metabolic acidosis.
Clinical evidence
Shaw AD et al. examined patients undergoing a major abdominal surgery and receiving either only normal saline or only receiving Ca2+-free balanced solutions on the day of surgery. It was a retrospective study. Patients receiving only normal saline showed a higher incidence of postoperative infections, a higher incidence of the use of renal replacement therapy and a higher rate of mortalities, compared to the patients who used the balanced solution.
Yunos et al., in a prospective study, compared a Cl–restrictive strategy, which was applied to fluid therapy of all consecutive ICU admissions over 6 months, to the Cl—permissive strategy over the same 6 month period of the previous year. The authors observed a reduced incidence of AKI and the use of renal replacement therapies after the introduction of the Cl- restriction.
Studies have also shown a reduction in in-hospital mortalities, in patients who received “balanced” solutions during resuscitation for septic shock.
The SPLIT trial
The SPLIT trial was published in October 2015. It was a double blind, randomized controlled trial comparing normal saline versus Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy. It was conducted in 4 ICUs in New Zealand. The study was designed to evaluate the proportion of patients with AKI during the first 90 days after enrolment. The authors observed an identical proportion of patients developing AKI in the two groups. The study also revealed a similar incidence in the use of renal replacement therapy and in-hospital mortality.
Most of the patients were post-operative patients who had undergone elective surgery (mainly cardiovascular procedures) with fewer co-morbidities. Therefore, the participants received small amounts of intravenous fluids. And therefore, there is not enough evidence to support the results in patients who are at high-risk of AKI when exposed to the fluid therapy.
Conclusion
The type of fluid, dose, rate of administration, the timing, duration and patient characteristics should be considered when using fluid therapy. The SPLIT trial was the first large RCT comparing NS versus a balanced solution (plasmalyte 148) and the results showed precise equipose between the two groups. There is still a requirement for further studies evaluating the patients in the high-risk categories, and the mechanisms that cause the clinical effects of the different types of fluids.
Rehab Fahmy
2 years ago
Balanced solution should have :
1-the entire content of all electrolytes equal to the electrolyte con- tent of plasma.
2-each water solution must display (and actually does display) the characteristic of elec- trical-neutrality: the total amount of free positive charges dissolved in the solution (as cations) always equals the total amount of free negative charges dissolved in the solution (as anions)
3-low content of Chloride
two categories of intravenous “balanced”solutions available:
1) those with a minimal effect on acid-base equilibrium, having a SID close to a value of 24−29 mEq L)e.g Lactated Ringer’s, Acetated Ringer’s, Hart-mann’s solution, Sterofundin ISO, Hextend, and Tetraspan.
2)those with a Cl– content equal or lower than 110 mEq L e.g Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan.
Off-note: Among the entire balanced solutions available, either they belong to just one category (having an effect on acid- base equilibrium while having a normal Cl– content, and vice versa), or present some limitations, such as relative hypotonicity (in the case of Lactated Ringer’s, Acetated Ringer’s, or Hartmann’s solution) .
As per stewards approach :balanced”crystalloid solution should be a crystalloid solution that has an in-vivo SID, i.e., after the metabolism of organic anions, very similar to the patient HCO3– concentration.
The theoretical understanding of the effects of intrave- nous solutions on acid-base equilibrium has two important consequences Firstly, the effect on acid-base of a specific intravenous solution may vary in different patients, hav-ing different HCO3– concentrations. Secondly, no available solution may be considered as totally balanced, and may be considered as the “ideal” balanced solution. In fact, since normal HCO3– concentration is about 24 mEq L-1, and electrical neutrality must be satisfied, either we aim at not affecting acid-base at the cost of an increased Cl– content in order to have a SIDinf close to 24 mEq/L, or we aim at having a physiological Cl– concentration at the cost of a greater SIDinf.
Magnesium: severe hypomagnesemia may be associated with a higher incidence of cardiac arrhythmias and altera- tions in electrocardiographic findings, as well as alterations of the cerebral nervous system. Interestingly, experimental data have reported a reduction in glomerular filtration rate (GFR) and of renal blood flow (RBF) in relation with a con- centration of magnesium lower than normal values, and a restoration of GFR and RBF after magnesium adminis- tration .Recently, both hypomagnesemia and ionized hypomagnesemia have been reported as being associated with a worse prognosis, especially for a non-recovery renal function after development of acute kidney injury (AKI) .as well as longer ICU stay and greater mortality .
novel generation of “balanced” solutions (such as the crystalloid solutions Plasma-Lyte or Sterofundin ISO) have been developed with the inclusion of magne- sium, as compared to the old generation (Lactated Ringer’s, Acetated Ringer’s or Hartmann’s solution)
Calcium:
disturbance in plasma calcium level:
alterations in muscle contractility, of peripheral and central nervous system function, cardiac arrhythmias and others. Replacement of plasma Ca2+ content is obtained generally with the intravenous administra- tion of either Ca2+-gluconate or Ca2+-chloride to avoid calcium precipitation .
potassium:
Hypokalemia: causes alterations of muscle contractility, and alterations in cardiac rhythm. All the available intravenous bal- anced solutions present a concentration of K+ within normal ranges, which does not necessarily cope with the normal daily intake K+ requirement [21]. This feature has been considered a reason for preferring the use of 0.9% NaCl as the only intravenous solution potentially applicable in the case of patients with acute or chronic renal failure
Chloride:
Hyperchloremia :can cause :
Smooth vascular muscle cell contraction ,increase epinephrine and angiotensin II induced vasoconstriction,decrease renal blood flow and increase congestion and decrease dieresis
Increase risk of metabolic acidosis (nausea,vomiting and abdominal discomfort,decrease in gastric blood flow,decrease in systolic blood pressure and increase in pro inflammatory cytokines and immmunomodulation).in case of metabolic acidosis ,in critically I’ll patient ,physicians may search for other causes of acidosis like dehydration and volume depletion end this will make them increase dose of Normal saline and further worsening of acidosis .
Kidney transplantation and IV Fluids:
While no significant difference in graft function was observed, all studies clearly documented a higher incidence of hyperchloremia and acidosis in patients receiving 0.9% NaCl as compared to patients receiving intravenous balanced solutions. It is note- worthy that no difference was observed regarding plasmatic concentrations of K+ and events of hyperkalemia between the two groups.so better to avoid normal saline .
Clinical evidence:
Shaw AD et al. examined patients undergoing major abdominal surgery and receiving only 0.9% NaCl, and compared them to patients receiving only Ca2+-free balanced solutions on the day of surgery :patients receiving 0.9% NaCl showed a higher incidence of postoperative infections, a greater incidence of the use of renal replacement therapy and a higher unadjusted ,,They investigated patients receiving crystalloids during the first 48 hours after the development of systemic inflamma- tory response syndrome (SIRS) >patients in the 0.9% NaCl group showed greater in-hospital mortality, length of hospital stay and frequency of readmission at 90 days than patients in the Ca2+-free balanced group, also they found total amount of Cl– intravenously received and the associated increase in serum Cl– concentration during fluid resuscitation with an increased risk of death .
Yunos et al ,observational ,avoidance of Cl- rich fluids and gelatins >> reduction in incidence of AKI and renal replacement therapy .
the SPLIT trial (the 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy), the first large randomized controlled trial comparing the clini- cal effects of two different types of crystalloids, In contrast to the hypothesis, the authors observed an identical proportion of patients developing AKI in the two groups of treatments (9.6% in the balanced solutions group vs. 9.2% in the 0.9% NaCl group), as well as a similar use of renal replacement therapy and in-hospital mortality.it has also some limitations:1- the study population included was composed, in its vast majority, of post-operative patients, after elective surgery (especially cardiovascular procedures), 2-with small incidence of comorbidities, 3-a low severity (as assessed by[APACHE] II score 4-and including small percentages of high-risk patients (less than 5% for patients with sep-sis). Consequently, most of the patients in both groups received very small amounts of intravenous study fluids (2L as median values, during the study period), limiting, therefore, their exposure to the treatment under investigation. 5-no data on the effects of the two treatments on plasma Cl– concentration have been measured, making therefore impossible to assess the potential determinant of the deterioration of renal function during fluid therapy.
Conclusion:
The type of fluid, the dose, the rate of administration, the timing and the dura- tion of the treatment are all equally important.
Still no ideal balanced IV fluid available
Further studies in this field are needed
Hussam Juda
2 years ago
· Balanced fluids defined as intravenous solutions whose electrolyte composition is closer to the composition of plasma, as compared to previously available solutions
· Balanced solution indicates intravenous solutions with a low content of chloride, as hyperchloremia may alter renal function
· While 0.9% NaCl induces hyperchloremic metabolic acidosis, balanced solutions thought to have minimal effects on acid-base equilibrium
· There are two categories of intravenous “balanced” solutions available:
1) Those with a minimal effect on acid-base equilibrium, SID close to 24−29 mEq L ( Lactated Ringer’s, Acetated Ringer’s, Hart mann’s solution, Sterofundin ISO, Hextend, and Tetraspan)
2) Those with a Cl– content equal or lower than 110 mEq L (s Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan)
· A “balanced” crystalloid solution should be a crystalloid solution that has an in-vivo SID, i.e., after the metabolism of organic anions, very similar to the patient HCO3 – concentration
· Ionic colloids (such as gelatins and albumins) should have a greater SIDinf, in order to balance the acidifying effect of the administered weak acid
· Hypomagnesemia, < 1.5 mg dL, is a relatively common finding in both critically ill patients and patients admitted to ICU, therefore, it may be reasonable to employ intravenous fluids replacement contains Mg.
· Hypocalcemia could be the most common abnormal plasma electrolyte observed in acutely ill patients, up to 90% of critically ill patients may have hypocalcemia
· Hypokalemia is a further life-threatening electrolyte abnormality seen in critically ill patients. All the available IV balanced solutions contain K+ within normal ranges
· Chloride is the main anion of the extracellular fluid, and it has a central role in acid-base equilibrium, and it is the main anion of any IV crystalloid solution given for fluid resuscitation and volume maintenance
· Normal saline contains a high, non-physiological content of Cl– , and known to induce, as a side-effect, hyperchloremic metabolic acidosis.
· Cl– mediates vascular smooth muscle cell Ca2+-dependent contraction, may modify vascular responses to vasoconstrictor agents in the kidney and may affect plasma renin activity and systemic blood pressure
· In patients undergoing renal transplantation, there was no difference was regarding events of hyperkalemia between in patients given 0.9NaCl and balanced solutions containing K+
CONCLUSIONS
· Fluids should be considered as drugs, as it may affect survival
· The type of fluid, the dose, the rate of administration, the timing and the duration of the treatment are all equally important
· balanced solutions have potentially several physiologically relevant advantages
· the “ideal” intravenous balanced solution contains acid-base, and electrolyte content equal to that of plasma, still unavailable
· The SPLIT trial, which compared the effects of a balanced solution (Plasma-Lyte 148) with those of 0.9% NaCl in critically ill patients showed the same results between the two treatments
Limitations of SPLIT trial:
· Population included, in vast majority, of post-operative patients, after elective surgery, with small incidence of co-morbidities, a low severity and including small percentages of high-risk patients
· Most of the patients in both groups received very small amounts of intravenous study fluids
· No data on the effects of the two treatments on plasma Cl– concentration have been measured, making therefore impossible to assess the effect on renal function
Ban Mezher
2 years ago
Balanced solution( novel crystalloid fluid) minimally affect acid base balance, while 0.9% NS associated with hyperchloremic metabolic acidosis.
Euvolumia is a state of normal body fluid volume & in certain circumstances IV fluid needed to maintain hemostasis.The need for IV fluid have 2 implication for IV fluid design:
IV fluid osmolarity
need for an oncotic pressure by dissolving an oncotic molecules.
All solutions ( except 0.9% NS & pure glucodse solution) should include organic anions as precursor go HCO3
IV fluid design should include avoidance of hypotonicity & high strong ion difference.
Types of balanced solutions:
Fluid with very low effect on acid base balance, SID 24-29meq/L e.g. RL, Acetated Ringer, Hartmans.
Cl content <110meq/L e.g. PL, lactated ringer & others.
Lactated Ringer, Hartman & Acetated Ringers are relatively hypotonic solution.
According Stewart, the component of biological fluid should include water, strong electrolytes( Na, K, & Cl), & weak non volatile acid ( albumin, phosphate), these component operate on electrically neutrality, dissociation equitibria & conservation mass.
Crystalloid fluid classified according SID:
SID >HCO3 baseline concentration & it associated with higher PH( toward alkalosis)
SID< HCO3 baseline concentration & it associated with lower PH( toward acidosis).
SID= HCO3 baseline concentration ( PH not changed).
Oncotic solution SID >HCO3 baseline concentration to to balance acidifying effect of administer weak acid.
Magnesium:
Low serum Mg associated with reduced GFR & RBF, worse prognosis in AKI with longer ICU stay & increase mortality.
LP solution contain Mg to reduce risk of hyomagnesemia
Calcium:
Low serum calcium associated with cardiac arrhythmia, peripheral & central function disturbance.
Addition of calcium to balanced solution increase risk of calcium precipitation when infused with blood component or HCO3 through same vascular access.
Potassium:
Low serum potassium is a threatening condition observed in ICU patients.
Potassium can be replaced with IV solution contained potassium.
Importance of Cl content in IV solution:
Cl is the main anion of extracellular fluid & crystalloid solution that used in resuscitation.
High non physiological Cl content in 0.9% NS associated with increased risk of hperchloremic metabolic acidosis.
Metabolic acidosis may be misdiagnosed as tissue hypo-perfusion induce acidosis.
Cl can mediate vasoconstriction & reduce blood flow in splanchnic level.
Increase level of IL-6, AKI & higher mortality found in patient receive 0.9%NS.
Patient receive 0.9% NS during surgery were have in crease risk of post operative infection when compared to patients receive PL.
Renal transplantation & IV fluid:
0.9%NS is the most common IV fluid used in renal transplantation.
0.9%NS associated with hyperchloremic metabolic acidosis .
it was found that balanced solution can be used safely in renal transplantation.
Use of higher Cl concentration fluids in ICU patients was associated with higher risk of AKI & RRT. Balanced fluid was associated with lower inhospitable mortality compared to 0.9%NS.
Split study:
Split study found the rate of AKI was similar in patients receive balanced & 0.9%NS in addition to similar rate of RRT & inhospital mortality.
But this trial have a limitation:
used sample as majority of of patients were post operative with low severity & low co-morbidities( APATCH II score).
No data was available about the effect of NS & balanced fluid on plasma Cl concentration.
Mohamed Mohamed
2 years ago
I. A critical appraisal of intravenous fluids- from the physiological basis to clinical evidence 1. Summarise this article Definitions “Balanced” solutions:
IV fluids with electrolyte composition close to that of plasma; so, they minimally affect acid-base status compared to 0.9% NaCl-related hyperchloremic metabolic acidosis.
Also used to indicate IV fluids with low chloride content compared to 0.9% NaCl. Ideal balanced solution (not yet existing) is characterized by:
Minimal effects on acid-base status
Low chloride content
Adequate tonicity Content of all electrolytes similar to that of plasma Physicochemical approach (Stewart’s approach): Components: Water: solvent, high molality, v. weakly dissociated. Strong electrolytes (Na+, K+, Cl–): completely dissociated in biologic solution (chemically non-reacting) Weak, non-volatile acids(albumin & phosphates):partially dissociated in aqueous solution Dissolved molecular CO2in equilibrium with H2CO3 & its dissociation products.
Constraints under which an aqueous solution has to operate:
1.Electrical neutrality —+ve charges equal to -ve charges
2.Dissociation equilibria of incompletely dissociated substances
3.Conservation of mass —sum of concentrations of dissociated & un-dissociated forms of substance.
Variables influencing pH of fluids:
1. PCO2
2. Concentration of non-volatile weak acids.
3. The Strong Ion Difference (SID) —difference bet sums of strong cations (Na+, K+, Mg2+, Ca2+) & strong anions (Cl–, lactate, & other unmeasured anions); the formulas:
For crystalloid solutions (IV fluids with no weak acids), studies identified the below rules:
-If SIDinf is > baseline HCO3–, pH goes toward alkalosis during the IV infusion
-If SIDinf is < baseline HCO3–, pH goes toward acidosis
-If SIDinf = baseline HCO3–, pH will not change.
So, a “balanced” crystalloid should be a crystalloid solution that has an in-vivo SID (after the metabolism of organic anions) very similar to the patient HCO3– conc.
Effects of IV solutions on acid-base equilibrium:
1. May vary in different patients, having different HCO3– conc.
2. No solution is totally balanced (no “ideal” balanced solution).
Content of electrolytes other than Na+ & Cl– in “balanced” solutions:
Magnesium
Novel “balanced” crystalloids (Plasma-Lyte or Sterofundin ISO) contain magnesium, vs old generation (LR, AR or Hartmann) to guard against A/Es of ↓Mg (arrhythmias, CNS disturbance, ↓ GFR & RBF).
Calcium
Reasonable to include in an ideal “balanced” solution; ↓ Ca2+ is common in acutely ill patients; however, fear of Ca2+ precipitation when infused with other components is the rationale behind the use of Ca2+ -free IV balanced solutions.
Potassium
Hypokalemia is life-threatening in critically ill patients. IV K+ may be needed in severe cases.
All IV balanced solutions have K+ within normal ranges which may not cope with the normal daily intake K+ requirement. Chloride content & pathophysiology:
Cl– is the main anion of the ECF & has a central role in acid-base balance.
It is the main anion of any IV crystalloid solution for resuscitation & volume maintenance.
Normal saline has a high content of Cl– (& Na+), & can induce hyperchloremic metabolic acidosis which, although benign & self-limiting, can potentiate any other possible causes of acidosis.
Cl– mediates vascular smooth muscle cell Ca2+-dependent contraction & may alter responses to vasoconstrictor agents in the kidney & may affect plasma renin activity & systemic BP.
TGF also depends on Cl– delivery, rather than Na+ delivery, to the distal tubule & its uptake by the macula densa. Renal transplantation & IV fluids
Large volumes of IV fluids are typically used.
0.9% NaCl & 0.9% NaCl-based IV solutions are the most commonly used; the rationale was the use of a K+-free solution, to avoid ↑ K+ in patients with reduced K+ excretion.
Large amounts of 0.9% NaCl induces hyperchloremic metabolic acidosis, & potentially leading to ↑ K+ & ↓ renal function.
Data support the avoidance of 0.9% NaCl & other fluids causing metabolic acidosis in patients with ARF or CRF, as well as during KTX.
Data also support the safety of using K+- containing balanced solutions for volume replacement & maintenance in these settings.
Clinical evidence: The SPLIT trial (October 2015) The SPLIT trial (the 0.9% saline vs. Plasma-Lyte 148 for ICU Fluid Therapy) is the 1st large RCT comparing effects of 2 different crystalloids.
Primary outcome was to evaluate the % of patients with AKI in the 1st 90 days, & to assess other secondary outcomes.
Identical % of patients developed AKI in the 2 groups of treatments, & a similar use of RRT & in-hospital mortality.
Limitations: Study population was mainly post-op patients, after elective surgery, with small incidence of co-morbidities, a low severity (APACHE II score), & only small % of high-risk patients (<5% for patients with sepsis). No data on the effects of the 2 treatments on plasma Cl– conc.
ummary of the article. Although intravenous fluid is important in critical and emergency condition to restore the defective hemodynamics, also the following researches concentrate on the other aspect and effects of each fluid in different condition and the effect of colloids vs crystalloids, as such fluid may have survival impacts. In general, regarding intravenous fluids, which was proofed to be definitely safe, may proofed to had some harm, so (normal saline is abnormal saline). Balanced fluid is that fluid similar to plasma concentrations and minimally affect acid-bace balance, comparing to 0.9 normal saline with hyperchloremic metabolic acidosis. Balanced solution;
Define as the fluid that equal to the volume desired for replacement, containing the similar concentration of electrolyte that does not affect osmolarity, and contain similar content that kept similar oncotic pressure that make fluid inside the vascular system, and the total amount of cations contained in the fluid is equal to the total amount of anions dissolved, and that contain normal or lower than normal chloride contents.
Hemostasis is the corner stone of human physiology.
Fluid balance refer to the amount of fluid lost from the body per day is equal to the amount of fluid intake.
Fluid consider as volume and as electrolytes and concentration in the fluid.
No ideal balance solution avilable , but the balanced solution avilable now, either
they have an effect on acid-base equilibrium, or having normal chloride content Stewarts approach and the mechanism of acid-base regulation during fluid infusion;
Water , the solvent contain high molality, very weaklly dissociated.
Strong electrolytes (Na, K, Cl), entirely dissociate in biologi solution, consider as chemically non-reacting.
Weak- nonvolatile acids, (Alb, phosphate), partially dissociated in a solution.
Dissolved molecular CO2 in equilibrium with H2CO3.
So solution with the above mentioned characteristic have the following criteria;
Electrical neutrality.
Dissociation equilibrium.
Conservation of mass, means equally amount of dissolved and non-dissolved substance of partially dissolved substance.
According to Stewart’s , there is 3 variables that affects pH of the fluid;
The partial pressure of CO2.
The concentration of volatile weak acids,(Alb, PO4).
The strong Ion difference, SID describe the sum of difference between strong cations (Na, K, Mg, and Ca) and strong anions, (Cl, Lactate), abbreviated as SID= (Na + K) – (Cl).
Crystalloid solution; not containing weak acids, they have the following character;
If SIDinf is greater than base line concentration of plasma HCO3, ten the pH shifted towards alkalosis during infusion.
If SIDinf is lower than the base line concentration of plasma HCO3, then the pH tends towards acidosis side during infusion.
If SIDinf is equal to the concentration of the HCO3, then the pH will not change , regardless of the extent of dilution.
Electrolytes and balanced solutions, other than Na, Cl; Magnesium;
Hypomagnesemia (<1.5 mg/dl) is relatively common in critical ill and in ICU patients.
Sever hypomagnesemia may be associated with cardiac arrhythmia, ECG changes, cerebral nervous system abnormality, as well as reduction of eGFR, RBF, prolonged hospital stay and greater mortlaity.
This the rationale behined the noval balanced solution involved the magnesium compared with the old generation, (Lactated ringer, acetated ringer, and hartman solution)
Calcium;
Hypocalcemia, (especially total hypocalcemia), the most common abnormality of acutely ill patients, with prevalence as high as 90%.
Clinically appear as defective muscle contractility, cardiac arrhythmia and other.
Noval balanced solution is difficult to contain Ca, as Ca precipitate, so rationale is to consider Ca free balanced solution.
Pottasium;
Hypokalemia often observed in critically and acutely ill patients.
Symptoms include alteration in muscle contraction and in cardiac rhythm.
All balanced solution present are containing normal range of K level.
Chloride content solution and its physiological effects;
Chloride is the main anion of the extracellular fluid, although its concentration is not tightly regulated as Na and K, but it plays a major rule in acid-base equilibrium.
Developing over the years, Cl consider having a clinical consequence.
Saline infusion cause hypercholremic metabolic acidosis, because it cause increase SID differences.
Normal saline is the most common used crystalloid solution, having high Cl and Na content, cause hyperchloremic metabolic acidosis, it used commonly in critical cndition which it may worsen the condition, also it may mislead clinicians that are use to treat metabolic acidosis caused by NaCl solution in a healthy patient.
Unwanted side effects of normal saline had been focused on as compared to balanced solution; (hyperchloremic metabolic acidosis, Cl mediates smooth muscle Ca-dependent contraction, may modify the vascular response to vasoconstrictor agents in the kidney, and may affect the plasma-renin activity, systemic blood pressure, affect tubular-glomerular feedback which is dependent on chloride delivery in the distal tubules, (this mechanism is kept GFR fairly constant and not affected by systemic pressure).
According to study, administeration of 0.9 NS associated with less diuresis and naturesis, lower renal blood flow and reduce cortical perfusion, with in the other hand lower diuretic response, and hence greater chance of fluid overload.
Renal transplantation and intravenous fluids;
infection, a higher need of post-operative RRT, and a higher mortality, compared with those receiving a Ca-free balanced solution.
Other Cohort study showed that patient receive NaCl had a higher incidence of in-hospital mortality, long hospital stay, and higher frequency of readmission at 90 days than those receiving Ca free balanced solution.
Recent survey done in the US sowed that 0.9 NaCl was the dominant fluid used in the transplant centers, because of need of K free solution, to avoid hyperkalemia in patent with reduce K capabilities, but hyperchloremic metabolic acidosis caused by excessive use of 0.9 NaCl it self cause hyperkalemia, and inversely may affect renal function.
Few randomized control trial comparing use of 0.9 NaCl and other balanced solution, noted that; patient receiving 0.9 NaCl had high incidence of hyperchloremic metabolic acidosis, while no difference in graft function, and no hyperkalemia developed in patient receive solutions other than NaCl. So these studies strongly suggesting avoid of 0.9 NaCl, and the safety of using K containing balance dsolution for volume replacement and maintenance.
Unbalanced IV solution in relation to outcome;
In a large retrospective study of hospital claim data base, AD et al; patient undergoing major abdominal surgery receiving 0.9 NaCl, had higher incidence of infection, a higher need of post-operative RRT, and a higher mortality, compared with those receiving a Ca-free balanced solution.
Other Cohort study showed that patient receive NaCl had a higher incidence of in-hospital mortality, long hospital stay, and higher frequency of readmission at 90 days than those receiving Ca free balanced solution.
Intravenous chloride load in relation to outcome;
Yunos et al.; Compared two groups, in ICU admission , group receive a Cl restrictive strategy, and other use a Cl-permissive strategy, showed that a Cl-permissive strategy had a higher incidence of AKI acciording to RIFLE criteria, specially in injury and risk classes, as well as need of RRT.
Show et al.; showed higher increase risk of death associated with patients receive Cl- containing fluids.
Balance IV solution in relation to safety and survival;
IV balanced solution had a survival advantages, and safety, compared to IV unbalanced solution, specially in patients with sepsis. The Split trial;
In October 2015, compared the use of 0.9 NaCl vs Plasma-lyte in 2278 ICU patients need of crystalloid fluid therapy.
Identical development of AKI between tow group during the first 90 days, as well as a similar use of RRT and in-hospital mortality.
the study had a limitations; study used an elective surgery, small incidence of comormidity, a low severity, and small percent of high risk pateints.
Conclusion;
Different aspect of IV fluid are considered; type, amount, rate of administration, and duration are equally important.
Balance dsolution had many relavant physiological advantages over unbalanced solution.
Balanced solution has to be with no effect on acid-base, and electrolyte content equall to that of plasma, with no chloride load.
Summary of a critical appraisal of intravenous fluids- from the physiological basis to clinical evidence Balanced fluid is intravenous solutions whose electrolyte composition of plasma of plasma and minimally affect acid-base equilibrium.
Large randomized control trial comparing the effects on renal function and hospital survival of intravenous balanced solution, vs 0.9%Nacl in critically ill patients showing no difference. Meanings of balanced solution:
Tow aspects characterizing balanced solution:
Minimal effect on acid-base physiological content of cl and osmolarity close to that of plasma
Two types of intravenous balanced solutions:
1. Solution with a minimal effect on acid-base equilibrium having SID close to value of 24-29mEqu/L
2. Those with a cl content equal or lower than 110mg.
First category belong to intravenous solution such as lactated Ringers, acetated Ringers, Hartmann’s solution, sterofindin ISO, Hextend, and tetraspam.
Second type of intravenous solution such as Lactated Ringer, acetated Ringer, Hartmann solution, plasma lyte ,El-oMel isoton, Isoplex and gelaspan.
Stewart pointed ant three constraints under which the system has to operate :
1. Electrical neutrality
2. Dissociation equilibrium – incompletely dissociated substances
3. Conservation of mass sum of concentration of its dissociated and un-dissociated forms Electrolyte content and balanced solution:
Balanced solution contains electrolytes other than Na and cl, include magnesium, calcium, and potassium. Magnesium:
Plasmatic contents of magnesium below 1.5 mg/dl is common in critical all patients which is increase incidence of cardiac arrhythmias. Calcium:
Hypocalcaemia is common among acute ill patients calcium-free intravenous balanced solution because of the risk of calcium precipitation when infused through the same vascular access of either blood component or bicarbonate. Potassium:
Hypokalaemia is recognized in critically ill patients.
All the available intravenous balanced solution present concentration of potassium with normal range . The importance of chloride content and its pathophysiologic effects:
Chloride is the main anion of the extracellular fluid
Chloride is main anion of any crystalloid solution if given in supra physiologic levels, may have relevant clinical consequences.
Normal saline has a high non-physiological content of chloride and sodium which result in hyperchloremic metabolic acidosis, in critical ill patients worsen the clinical pictures.
Study on septic rats given intravenous 0.9 Nacl or balanced solution (plasma-lyte)
Development of hyperchloremic metabolic acidosis -associated with an increased IL6 levels, incident of acute kidney injury and higher mortality rate in those receiving 0.9 Nacl. Renal transplantation and intravenous fluids:
A few randomized controlled studies have compared in patient undergoing renal transplantation, the IV 0.9 Nacl with IV administration of different balanced solutions-no significant difference in graft function . all studies observed a higher incidence of hyperchloremia and acidosis in patients receiving 0.9 Nacl compared to patients receiving intravenous balanced solution.
No difference was observed regarding plasmatic concentration of potassium and event of hyperkalaemia between the tow groups.
These data support avoidance of 0.9 Nacl and other possible IV fluid concern metabolic acidosis in patients with a cute or chronic renal faluire as well as during renal transplantation Clinical evidence:
Lack of solid evidence supporting the use of specific types of crystalloids or colloids may rely on an unclear focus of the research conducted so far unbalanced intravenous solution in relating to outcome.
In large retrospective analysis examined patients undergoing major abdominal surgery and receiving only 0.9Nacl and compared them to the patients receiving only calcium free balanced solution on the day of surgery.
Patients receiving 0.9 Nacl showed a higher postoperative infection. A greater incidence of the use of renal replacement therapy and a higher un adjusted mortality rate as compared to those receiving IV balanced solutions.
Intravenous balanced solutions safer are all and do they provide a survival advantage as compared to intravenous unbalanced solutions especially in patients with sepsis in the SPLIT trial which is the first large randomized controlled trials comparing tow different types of crystalloid . Conclusion:
The type of fluid, the dose, the rate of administration, the timing, and duration of the treatment
IV balanced solution have several physiological relevant advantage but clinically relevant outcomes is still unclear.
The Split trial:
The first large randomized trial comparing the effects of a balanced solution with those of 0.9% Nacl in critically ill patients showed equipoise between the two treatment
Further research needed on the presented mechanism underling the clinical effects on specific types of crystalloid solutions.
having an electrolyte composition close to that of plasma.
minimally affect acid-base equilibrium.
low chloride content.
there are two categories of intravenous “balanced” solutions available:
those with a minimal effect on acid-base equilibrium have a SID close to a value of 24−29 mEq L.
those with a Cl– content equal to or lower than 110 mEq L.
The first category belongs to intravenous solutions such as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Sterofundin ISO, Hextend, and Tetraspan.
The second category belong to intravenous solutions such as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan.
STEWART’S APPROACH AND THE MECHANISMS REGULATING ACID-BASE DURING FLUID INFUSION:
The components of biological fluids:
water, the solvent, has a high molality (~55.5 mol kg-1) and is very weakly dissociated.
strong electrolytes (such as Na+, K+, Cl–), which are always entirely dissociated in biological solution, and can be considered as chemically non-reacting.
weak, non-volatile acids (mainly albumin and phosphates), which are defined as substances only partially dissociated in an aqueous solution, according to their dissociation constant.
carbon dioxide (CO2) system — dissolved molecular CO2 in equilibrium with carbonic acid (H2CO3) and its dissociation products.
ELECTROLYTE CONTENT AND BALANCED SOLUTIONS:
MAGNESIUM:
severe hypomagnesemia may be associated with a higher incidence of cardiac arrhythmias and alterations in electrocardiographic findings.
experimental data have reported a reduction in glomerular filtration rate and renal blood flow in relation to a concentration of magnesium lower than normal values, and restoration of GFR and RBF after magnesium administration.
crystalloid solutions Plasma-Lyte or Sterofundin ISO contain mg.
CALCIUM:
symptoms of hypocalcemia are: alterations in muscle contractility, of peripheral and central nervous system function, cardiac arrhythmias and others.
Replacement of plasma Ca2+ content is obtained generally with the intravenous administration of either Ca2+-gluconate or Ca2+-chloride.
it may be reasonable to include also Ca2+ in an ideal “balanced” solution.
the possible limitation of having a Ca2+-containing intravenous solution, as related to the risk of Ca2+ precipitation when infused through the same vascular access of either blood components (precipitation of Ca2+ as Ca2+-citrate) or bicarbonate (as Ca2+- carbonate).
POTASSIUM:
Hypokalemia Symptoms include both alterations of muscle contractility and alterations in cardiac rhythm.
. Although the common route of K+ replacement is oral administration, intravenous administration may be required in severe cases.
All the available intravenous balanced solutions present a concentration of K+ within normal ranges, which does not necessarily cope with the normal daily intake K+ requirement.
THE IMPORTANCE OF CHLORIDE CONTENT AND ITS PATHOPHYSIOLOGIC EFFECTS
Several reports have observed that Cl– mediates vascular smooth muscle cell Ca2+-dependent contraction, may modify vascular responses to vasoconstrictor agents in the kidney and may affect plasma renin activity and systemic blood pressure.
the tubule-glomerular feedback has been shown to be dependent on Cl– delivery, rather than Na+ delivery, to the distal tubule and its uptake by the macula densa.
an effect of hyperchloremic acidosis on the function of the immune system has been postulated based on experimental studies.
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS
patients undergoing renal transplantation still receive large amounts of intravenous fluids (up to 30 mL kg-1h-1), in an attempt to increase their intravascular volume and therefore improve graft function.
0.9% NaCl, and 0.9% NaCl-based intravenous solutions, were the most commonly employed intravenous solutions during renal transplantation.
the intravenous administration of large amounts of 0.9% NaCl, having a SIDinf equal to zero, always induces hyperchloremic metabolic acidosis, thereby potentially leading per se to the development of hyperkalemia and may affect renal function.
data strongly support the avoidance of 0.9% NaCl and other possible intravenous fluids causing metabolic acidosis in patients with acute or chronic renal failure, as well as during renal transplantation, and provide the first solid data on the safety of employing K+- containing balanced solutions for volume replacement and maintenance in this specific clinical setting.
CLINICAL EVIDENCE
Several clinical trials, even designed as prospective and randomized studies, had been conducted aimed at comparing several physiological effects of the two categories of intravenous solutions, whereas the scientific community still needed an understanding of whether such physiological effects (i.e. on acid-base equilibrium, on renal function and other organs) translated into a survival difference.
Although the SPLIT trial has made an important step ahead in this issue, many questions are still open regarding the possible efficacy (or neutral clinical effect) of intravenous balanced solutions.
THE SPLIT TRIAL
, the first large randomized controlled trial comparing the clinical effects of two different types of crystalloids (the 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy).
In October 2015, this trial was published.
double-blind, cluster randomized, double-crossover trial, conducted in 4 ICUs in New Zealand.
2,278 ICU patients in need of crystalloid fluid therapy were enrolled to receive either 0.9% NaCl or Plasma-Lyte 148, as a balanced solution, according to an alternating block of 7-weeks for each specific ICU.
the primary outcome: the proportion of patients with AKI during the first 90 days after enrolment.
e authors observed an identical proportion of patients developing AKI in the two groups of treatments (9.6% in the balanced solutions group vs. 9.2% in the 0.9% NaCl group), as well as a similar use of renal replacement therapy and in-hospital mortality.
Balanced solution is defined as solutions with low content of chloride or a solution with electrolyte composition closer to the composition of the plasma. It is minimally affects the acid base balance
A large randomized controlled trial (SPLIT trial) compared the effects on renal function and hospital survival of an intravenous balanced solution vs. 0.9% NaCl in critically ill patients and showed no differences between the two treatments
The aim of the study
Address the pathophysiology and pathophysiologic effects of these balanced solutions and presenting theclinical evidence to support their use
WHAT DOES “BALANCED” SOLUTION MEAN?
The ideal balanced intravenous solution should include organic anions (acetate, lactate, malate, gluconate, etc.) and be electrically neutral
Two categories of intravenous balanced solutions available now:
1. those with a minimal effect on acid-base balance (Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Sterofundin ISO, Hextend, and Tetraspan)
2. those with a Cl– content equal or lower than 110 mEq/L (Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan)
No ideal balanced solution available now
STEWART’S APPROACH AND THE MECHANISMS REGULATING ACID-BASE
Components of biologic fluids are water, strong electrolytes (Na+, K+, Cl–), weak, non-volatile acids (mainly albumin and phosphates), and carbon dioxide (CO2) system
Constraints of the system are electrical neutrality, dissociation equilibria, and conservation of mass
Stewart set up a system of different equations
ELECTROLYTE CONTENT AND BALANCED SOLUTIONS
In addition to Na+ and Cl– other electrolytes are magnesium, calcium and potassium
Hypomagnesemia may be associated with a higher incidence of cardiac arrhythmias and alterations of the cerebral nervous system. New balanced solutions (such as the crystalloid solutions Plasma-Lyte or Sterofundin ISO) contain magnesium
Ca2+-containing intravenous solutions have the risk of Ca2+ precipitation when infused through the same vascular access
THE IMPORTANCE OF CHLORIDE CONTENT AND ITS PATHOPHYSIOLOGIC EFFECTS
Smooth muscle vascular cell contraction
Increase in norepinephrine and angiotensin II-induced vasoconstriction
Tubuloglomerular feedbacK
Decreased dieresis, fluid overload and interstitial edema
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS
When comparing 0.9% NaCl with balanced solution containing K in patients undergoing renal transplantation, no significant difference in graft function but a higher incidence of hyperchloremia and acidosis
Avoidance of 0.9% NaCl and other fluids causing metabolic acidosis in patients with acute or chronic renal failure, as well as during renal transplantation is strongly recommended
CLINICAL EVIDENCE
Several clinical trials have addressed the question of whether the use of balanced solutions has beneficial effects as compared to the standard of care, sometimes even suggesting an improvement in survival
THE SPLIT TRIAL
The first large randomized controlled trial comparing the effects of a balanced vs. unbalanced solutions on renal function in critically-ill patients and showed no differences between the two treatments
CONCLUSIONS
Intravenous balanced crystalloids solutions when compared to 0.9% NaCl may affect clinical outcome and survival
Although balanced solutions have potentially several relevant advantages, the ideal balanced solution, with minimal effects on acid-base status, low chloride content, and adequate tonicity, is not yet available
SPLIT trial compared the effects on renal function and hospital survival of an intravenous balanced solution vs. 0.9% NaCl in critically ill patients and showed no differences between the two treatments
Recent researches focus on the effects of different types of fluids on clinical outcomes, looking for the ideal IV fluid. IV balanced solutions is a novel solution available in practice.
Normally the body maintained in homeostasis, when an acute process alters such homeostasis, an IV fluids may become necessary, need to have appropriate tonicity, electrolytes composition and electrical-neutrality
Balanced” solutions are commonly defined as IVF having an electrolyte composition close to that of plasma. As such, they should minimally affect acid-base equilibrium, as compared to the commonly reported 0.9% NaCl-related hyperchloremic metabolic acidosis.
Recently, the term “balanced” solution has been also employed to indicate IVF with low chloride content, being the concentration of this electrolyte the most altered in 0.9% NaCl as compared to plasma, and based upon a suggested detrimental alteration of renal function associated with hyperchloremia.
“balanced” crystalloid solution should be a crystalloid solution that has an in-vivo SID, i.e., after the metabolism of organic anions, very similar to the patient HCO3– concentration.
Indeed, no ideal balanced solution has become available so far.
Categories of IV balanced solutions available:
1) those with a minimal effect on acid-base equilibrium, such as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Sterofundin ISO, Hextend, and Tetraspan.
2) those with a Cl– content equal or lower than 110 mEq/L. such as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan
The importance of chloride content and its pathophysiological effects:
The detrimental effects of hyperchloremia of IV (supra-physiologic ):
-NS induce hyperchloremic metabolic acidosis especially in critically ill patients, which may erroneously attributed to tissue hypoperfusion, a vicious cycle may derive, in which the treatment for the misdiagnosed acid-base disturbance with further fluid administration will worsen hyperchloremia and acidosis. – Cl– mediates vascular smooth muscle cell Ca2+-dependent contraction. – Modify vascular responses to vasoconstrictor agents in the kidney.
– Affect plasma renin activity and systemic blood pressure
– Reduction in renal blood flow and glomerular filtration rate.
– Decreased diuresis with fluid overload, decrease in systemic blood pressure.
– Abdominal discomfort and decrease in gastric mucosal perfusion by Cl–-mediated vasoconstriction. – Increased plasma nitric oxide levels and pro-inflammatory cytokines.
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS:
-The choice of intravenous fluids in patients with renal failure is challenging.
– 0.9% NaCl, and 0.9% NaCl-based IVF, were the most commonly employed during KT, mainly for K free nature. – All studies clearly documented a higher incidence of hyperchloremia and acidosis in patients receiving 0.9% NaCl as compared to patients receiving intravenous balanced solutions, while no significant difference in graft function was observed.
CLINICAL EVIDENCE
Several clinical trials have addressed the question of whether the use of balanced solutions has beneficial effects as compared to the standard of care, sometimes even suggesting an improvement in survival.
THE SPLIT TRIAL
The first large randomized controlled trial comparing the effects of a balanced vs. unbalanced solutions on renal function in critically-ill patients (SPLIT trial, the 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy).
The study was designed to evaluate, as the primary outcome, the proportion of patients with AKI during the first 90 days after enrolment, and to assess several clinically relevant endpoints as secondary outcomes.
They concluded a neutral effects of the two strategies in post-operative patients in term of AKI development, use of RRT and in-hospital mortality.
CONCLUSIONS
– Fluids should be considered as “drugs”.
– The type of fluid, the dose, the rate of administration, the timing and the duration of the treatment are all equally important.
– IV balanced solutions have potentially several physiologically relevant advantages, although translation into clinically relevant outcomes is still unclear.
Intravenous fluids are either unbalanced (normal saline) or balanced solution (ringers lactate, plasmalyte)
Balanced solution has electrolytes (potassium, magnesium, calcium and most importantly chloride) composition near to that of plasma so can maintain plasma PH and osmolarity
A- Several studies on non-renal transplant patients reported that normal saline infusion is associated with the following adverse effects
Hyperchloremic metabolic acidosis which can in turn cause hyperkalemia especially in the setting of preexisting renal dysfunction
Higher incidence of AKI and RRT requirements was reported in patients using NS compared to balanced solutions
Higher incidence of post-operative infection in patients using normal saline compared to balanced solutions
B- In renal transplantation
There is a concern of hyperkalemia that can occur with large infusion of potassium containing IV fluid especially in kidney transplantation
Studies reported higher incidence of metabolic acidosis and hyperkalemia with normal saline used compared to balanced solutions but with similar graft function in both groups
C- SPLIT trial
SPLIT trial is alarge prospective double-blind, cluster randomized study evaluated 2,278 ICU patients in 4 ICUS regarding the effect of normal saline versus Plasmalyte on Serum creatinine, AKI during the first 3 months of enrollment, need for RRT, in-hospital and ICU length of stay and mortality
No significant difference was found in the incidence of AKI, hospital stay and mortality between both groups
Limitation of this study are including low risk post-operative(elective surgery) patients with low comorbidity and only 5% of patient were high risk , so the amount of IV fluids received are small not sufficient to cause complication. Also assessment of chloride was not included in the study which is important since chloride is the main factor responsible for adverse outcome
Conclusions
Intravenous fluids should be considered as drugs, with precise prescription of the type, dose, rate and duration of this fluid since they are associated with possible side effects
The use of balanced solutions is more physiologic
The use of normal saline may be associated with adverse outcomes up to mortality
The ideal balanced solution should have an electrolyte composition near to the plasma and should not change acid base status or osmolality
Although the SPLIT trial did not show difference in AKI and mortality at 90 days but it has several limitations
Balanced solutions are the preferred solutions in high risk patients who need large amounts of IV fluids such as in case of trauma, sepsis and burns
A critical appraisal of intravenous fluids- from the physiological basis to clinical evidence
Summarise this article
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Principles of fluid management in critical and emergency care.
“Balanced” solutions are commonly defined as intravenous fluids having an electrolyte composition close to that of plasma.
The term “balanced” solution has been also employed to indicate intravenous fluids with low chloride content, being the concentration of this electrolyte the most altered and supra-physiologic in 0.9% NaCl as compared to plasma, and based upon a suggested detrimental effect on renal function associated with hyperchloremia.
What dose balanced solution?
Fluid balance denotes a constraint of human homeostasis for which the amount of fluids lost from the body, in normal conditions, should equal the amount of fluid intake.
Human beings, we normally match the daily output of water with oral water intake
Two important implications in designing a fluid for intravenous administration.( for osmolarity and,oncotic pressure, or oncoticity, of the fluid and, therefore, for an oncotic molecule dissolved in the solution,).
– Two categories of intravenous “balanced” solutions available:
A minimal effect on acid-base equilibrium, having a SID close to a value of 24−29 mEq .(as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Sterofundin ISO, Hextend, and Tetraspan).
And with a Cl– content equal or lower than 110 mEq.(as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan).
Stewarts approach and the mechanisms regulating acid -base during fluid
The components of biologic fluids:
Water and strong electrolytes,
Weak non-volatile acids and carbon dioxide (CO2) .
Stewart pointed out three constraints:
Electrical neutrality .
Dissociation equilibria.
Conservation of mass .
Balanced” crystalloid solution should be a crystalloid solution that has an in-vivo SID, i.e., after the metabolism of organic anions, very similar to the patient HCO3– concentration.
Electrolyte content and balanced solutions:-
Magnesium
Calcium
Potassium
Renal transplantion and intravenous fluids
Patients undergoing renal transplantation still receive, in many centres, large amounts of intravenous fluids (up to 30 mL kg/h), in the attempt to increase their intravascular volume and therefore improve graft function.
0.9% NaCl, and 0.9% NaCl-based intravenous solutions, were the most commonly employed intravenous solutions during renal transplantation.
Large amounts of 0.9% NaCl, having a SIDinf equal to zero, induces always hyperchloremic metabolic acidosis, thereby potentially leading per se to the development of hyperkalemia, and may affect renal function, in relation to the detrimental effects of hyperchloremia.
Clinical evidence
Unbalanced IV solution in relation to outcome:
Large retrospective study showed that 0.9%NaCl is associated with higher incidence of postoperative infection, RRT and higher mortality rate compared to balanced solutions.
IV chloride load in relation to outcome:
A large prospective study showed that Cl restrictive strategy is associated with lower incidence of AKI and less use of RRT.
Balanced IV solutions in relation to safety and survival:
Large retrospective study showed that hospital mortality decrease with with the increase in fraction of balanced solutions used in resuscitation.
The SPLIT trial
In October 2015, the SPLIT trial (the 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy).
Double blind cluster randomized trial
Identical proportion of patient with AKI in the two group (9.6% in balanced solution group vs 9.2% in 0.9% fluid group.
Concolusion
Whether or not the use of intravenous balanced solutions is beneficial in high-risk patient categories (sepsis, trauma, burns), when exposed to larger amounts of fluids or when at higher risk of AKI, still needs to be investigated.
Intravenous balanced crystalloids solutions and the findings collected on their use in comparison with the traditional administration of 0.9% NaCl, have brought a new awareness in the field of fluid therapy.
The type of solutions may affect patient-centred clinical outcome, including survival, such fluids should be considered as “drugs.
Certainly, after this article, the use of Normal Saline will be reconsidered, patients will be monitored and the required examinations will be performed for them.
The importance of hemodynamic balance in critically ill patient cannot be overemphasized, but beyond this, their survival and length of hospital stay can be significantly affected by the type of intravenous fluid use for them during resuscitation while in critical stage. The traditional known 0.9% normal saline has been frosted with complication like hyperchloremic metabolic acidosis and hence researchers are looking toward a more balance fluid for critically ill patient. To this end, a balanced solution has been defined as the intravenous fluid having an electrolyte composition as close as to that human plasma.
What is a balanced solution
human hemostasis is the amount of fluid loss must be equal to the amount taken
an ideal balanced solution should have the same electrolytes content like that of plasma
balance solution must be able to maintain plasma osmolarity and oncoticity
two categories of balanced solution are
-those with minimal effect on acid-base equilibrium, SID close to 24-29meq
-those with chloride content equal or lower than 110meq
Stewart’s approach
the component of biologic fluid is water, strong electrolytes, weak nonvolatile acid and carbon dioxide
the constraint pointed out is electrolyte neutrality, dissociation equilibria, and conservation of mass
balanced crystalloid solution should be solution that has an in vivo strong ion difference (SID)
Electrolytes content in balanced solution
magnesium
potassium
calcium
Clinical evidence
A) unbalanced intravenous solutions in relation to outcome
AD et al reported higher incidence of post operative infection and increase use of RRT among those using 0.9% solution compared to those that used intravenous balanced solution.
B) Intravenous chloride load in relation to outcome
there was reduction in incidence on AKI using RIFLE criteria among those that were on chloride restricted solution compared those not on it
C) Balance intravenous solution in term of safety and survival
intravenous balance solution is found to be safer with better survival advantage over the unbalanced intravenous solution
The SPLIT trial
double blind cluster randomized trial
identical proportion of patient with AKI in the two group (9.6% in balanced solution group vs 9.2% in 0.9% fluid group
Conclusion
Fluid therapy should be henceforth seen as administration of drug that could have either negative or positive impact on patient safety and survival. The right decision on the type of fluids, whether traditional 0.9% saline that has been shown to have some side effect on patient or the use of a balanced solution with relatively close electrolytes content like plasma will always be key to optimal patient care
Hi Dr Issac, I liked reading your detailed summary. Will you change your practice based on this article? Ajay
Heba Wagdy
2 years ago
IV balanced solutions are recently available in clinical practice. What does balanced solution mean?
They are IV solutions with either minimal effect on acid base balance or with normal chloride content, they include crystalloids and colloids.
No ideal balanced solution is available, available solutions either belong to one category or have limitations due to relative hypotonicity. Steward’s approach and the mechanism regulating acid base balance during fluid infusion:
The theoretical explanation of the effect of IV solutions on acid base balance showed that the effect of specific solution may vary in different patients according to their HCO3 concentration and yet, no available solution is totally balanced. Electrolyte content and balanced solution: Magnesium:
hypomagnesemia is common in critically ill patients and is associated with arrhythmia and CNS abnormalities.
Novel balanced solution as Plasma-Lyte include Mg and may be useful in clinical condition requiring large volume replacement. Calcium:
hypocalcemia is the most common electrolyte imbalance in critically ill patients, leads to arrhythmia and alterations in CNS.
Balance solution containing Ca may be useful when large volume replacement therapy is needed but limited by possibility of Ca precipitation when infused with blood or bicarbonate in the same vascular access. Potassium:
Hypokalemia is life threatening, associated with arrhythmia.
Available balanced solution have potassium concentration within the normal range and is not coping with daily potassium requirements. The importance of chloride content and its pathophysiological effects:
It has a central role in acid base balance, normal saline contains high non-physiological content of chloride and result in hyperchloremic metabolic acidosis which may worsen clinical picture and mislead the cause of metabolic acidosis.
Other side effects of normal saline include affection of plasma renin activity and blood pressure, alter tubuloglomerular feedback, associated with decreased diuresis and natriuresis and lower cortical renal perfusion, it may lead to fluid overload, renal venous engorgement resulting in kidney hypoperfusion and damage. Renal transplantation and IV fluids:
Recipients usually receive large amounts of IV fluids to increase intravascular volume and improve graft function, 0.9%NaCl is commonly used and may result in hyperchloremic metabolic acidosis which may lead to hyperkalemia and impair renal function
A RCT showed that 0.9%NaCl and balanced solutions are associated with similar graft function and higher incidence of acidosis with 0.9%NaCl. It is suggested to avoid 0.9%NaCl in patients with acute or chronic renal failure and kidney transplants. Clinical evidence: Unbalanced IV solution in relation to outcome: Large retrospective study showed that 0.9%NaCl is associated with higher incidence of postoperative infection, RRT and higher mortality rate compared to balanced solutions. IV chloride load in relation to outcome: A large prospective study showed that Cl restrictive strategy is associated with lower incidence of AKI and less use of RRT Balanced IV solutions in relation to safety and survival: Large retrospective study showed that hospital mortality decrease with with the increase in fraction of balanced solutions used in resuscitation. The SPLIT trial: A large RCT, double blinded, compare the effect of 0.9%NaCl and Plasma-Lyte 148in ICU patients receiving fluid therapy, the primary outcome was AKI. It showed similar incidence of AKI, RRT and hospital mortality in both groups, however, it has several limitations as most of included patients were post operative with small rate of comorbidities, also small percent of included patients had sepsis, most patients received small amount of IV fluids and the effect on plasma Cl concentration was not measured so its potential role in AKI was not determined.
IV fluids should be considered as drugs, balanced solutions are more physiological but their clinical outcome is not proved yet
In our practice, we prefer using lactated ringer for replacement in kidney transplant recipients postoperatively, the use of normal saline is restricted to certain indications.
Fluid therapy is determined according to each case individually
Weam Elnazer
2 years ago
“Balanced” intravenous fluids have a composition similar to plasma. They should impact an acid-base balance of less than 0.9% NaCl-related hyperchloremic metabolic acidosis.
Recently, the phrase “balanced” solution has been used to designate intravenous fluids with low chloride content.
-The concentration of this electrolyte is most affected in 0.9% NaCl compared to plasma, and hyperchloremia is thought to harm renal function.
-The optimal balanced solution with minimum acid-base effects, low chloride level, and acceptable tonicity is not yet known.
WHAT DOES “BALANCED” SOLUTION MEAN?
assumptions have highlighted two elements of an ideal balanced intravenous solution.
First, All intravenous solutions (excluding 0.9% NaCl and pure dextrose-containing solutions) include organic anions (such as acetate, lactate, malate, gluconate, etc.) as precursors of HCO3 to balance the overall amount of positive charges, i.e., organic components quickly converted to HCO3.
This is due to the difficulties of incorporating HCO3 – directly in intravenous solution, since the technique to produce one (8.4% NaHCO3) is complicated.
Second, for electrical-neutrality and to prevent hypotonicity and a large Strong Ion Difference (SID, keeping the Na+-Cl– difference within 2430 mEq L-1), we have noticed the creation of balanced solutions with a supra-physiological concentration of Cl– .
Intravenous administration of significant volumes of 0.9% NaCl with a SIDinf of zero generates hyperchloremic metabolic acidosis, which may lead to hyperkalemia and compromise renal function due to hyperchloremia’s harmful consequences.
The result of previous studies:
A few randomized controlled investigations compared 0.9% NaCl with balanced solutions containing K+ within plasmatic limits.
All investigations found a greater frequency of hyperchloremia and acidosis in individuals receiving 0.9% NaCl compared to intravenous balanced solutions. Both groups had similar plasmatic K+ concentrations and hyperkalemia episodes.
These data strongly support avoiding 0.9% NaCl and other intravenous fluids causing metabolic acidosis in patients with acute or chronic renal failure and during renal transplantation.
They also provide the first solid data on the safety of using K+- containing balanced solutions for volume replacement and maintenance in this clinical setting.
UNBALANCED INTRAVENOUS SOLUTIONS IN RELATION TO OUTCOME:
-Show AD et al. compared patients having major abdominal surgery with 0.9% NaCl and Ca2+-free balanced fluids. Compared to intravenous balanced solutions, 0.9% NaCl patients had a higher incidence of postoperative infections, renal replacement treatment, and unadjusted mortality.
–Intravenous chloride load and outcome:
– In the first big prospective before-and-after trial, Yunos et al. compared a Cl-restrictive approach to fluid treatment of all consecutive ICU admissions over 6 months to a Cl-permissive strategy during the same 6 months the previous year.
-After introducing. Clinical studies on the use of fluids following kidney transplantation intravenous fluid approach reduced the quantity of 0.9% NaCl and gelatins provided to patients. The risk, injury, failure, loss, and end-stage kidney injury (RIFLE) criteria showed a decrease in AKI.
SAFE AND SURVIVAL-BASED INTRAVENOUS SOLUTIONS:
-the authors found a reduction in in-hospital mortality for any increase in the proportion of balanced solutions over the total volume of intravenous fluids administered during the first resuscitation (2 days).
– intravenous balanced solutions in combination with 0.9% NaCl were linked with decreased in-hospital mortality, equivalent duration of stay, and similar daily expenses.
SPLIT TRIAL:
-Despite the strong physiological rationale and the accumulation of data suggesting possible harms for the use of 0.9% NaCl for several years, the first large randomized controlled trial investigating a possible long-term and clinically relevant benefit of a balanced solution over an unbalanced solution for fluid resuscitation or volume maintenance has just been concluded.
-The first big randomized controlled experiment comparing balanced vs. unbalanced solutions on renal function in critically-ill patients (SPLIT trial, 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy) demonstrated no difference between the two.
Hi Dr Weam, I liked reading your detailed summary. Will you change your practice based on this article? Ajay
Abdulrahman Ishag
2 years ago
“BALANCED” SOLUTION ;
————————————–
Balanced solutions have been thought as the intravenous solutions causing minimal effects on acid-base equilibrium and have a physiological content of Cl–.
The “ideal” intravenous balanced solution including all the characteristics necessary for such definition (least effect on acid-base, and electrolyte content equal to that of plasma), has instead of have not yet become available.
There are two categories of intravenous “balanced” solutions available:
1- Those with a minimal effect on acid-base equilibrium, having a SID close to a value of 24−29 mEq L , such as Lactated Ringer’s, Acetated Ringer’s, Hart-mann’s solution, Sterofundin ISO, Hextend, and Tetraspan .
2- Those with a Cl– content equal or lower than 110 mEq L , such as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan .
LECTROLYTE CONTENT AND BALANCED SOLUTIONS;
——————————————————————————–
1-MAGNESIUM;
———————–
Both hypomagnesemia and ionized hypomagnesemia have been reported as being associated with a worse prognosis, especially for a non-recovery renal function after development of acute kidney injury (AKI) , as well as longer ICU stay and greater mortality .
Novel generation of “balanced” solutions have been developed with the inclusion of magnesium such as the crystalloid solutions Plasma-Lyte or Sterofundin ISO.
2-CALCIUM;
————————-
The prevalence of hypocalcaemia is 90% of critically ill patients. It causes alterations in muscle contractility, of peripheral and central nervous system function, cardiac arrhythmias.
It may be reasonable to include also Ca2+ in an ideal “balanced” solution, especially in the necessity of large volume replacement therapies.
A Ca2+-containing intravenous solution, carries a risk of Ca2+ precipitation when infused through the same vascular access of either blood components (precipitation of Ca2+ as Ca2+-citrate) or bicarbonate (as Ca2+- carbonate).
3-POTASSIUM;
————————–
All the available intravenous balanced solutions present a concentration of K+ within normal ranges, which does not necessarily cope with the normal daily intake K+ requirement .
THE IMPORTANCE OF CHLORIDE CONTENTAND ITS PATHOPHYSIOLOGIC EFFECTS;
——————————————————————————————————-
Chloride is the main anion of the extracellular fluid, and although its concentration in plasma is not as tightly regulated as that of Na+ and K+, it has a central role in acid-base equilibrium .
Normal saline, still one of the most employed intravenous crystalloid solutions, presents a high, non-physiological content of Cl– (and Na+), and has long been known to induce, as a side-effect of its liberal administration, hyperchloremic metabolic acidosis.
Even if it is often considered self-limiting and benign in nature, 0.9% NaCl-induced metabolic acidosis will be added to any other possible causes of acidosis, especially in critically ill patients, thereby potentially complicating or worsening the clinical picture.
(1) Is 0.9% NaCl intravenous solution more dangerous than intravenous balanced solutions?
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In a large retrospective analysis, patients receiving 0.9% NaCl showed a higher incidence of postoperative infections, a greater incidence of the use of renal replacement therapy and a higher unadjusted mortality rate, as compared to those receiving intravenous balanced solutions.
(2) Is the total Cl– load intravenously administered to patients associated with worse outcome?
————————————————————————————————————–
Yunos et al., in the first large prospective before-and-after study, compared a Cl–-restrictive strategy, which was applied to fluid therapy of all consecutive ICU admissions over 6 months, to the Cl-permissive strategy over the same 6 months period of the previous year , the authors observed a reduction in the incidence of AKI, as assessed according to the Risk, Injury, Failure, Loss and End-stage kidney injury (RIFLE) criteria, especially in the injury and risk classes , as well as a reduction in the use of renal replacement therapies , even after adjustments for covariates.
Following the same hypothesis, although through a retrospective analysis of a large cohort of patients with SIRS, Shaw et al. observed a direct correlation of both the total amount of Cl– intravenously received and the associated increase in serum Cl– concentration during fluid resuscitation with an increased risk of death . Such an association appeared to be independent of the total amount of fluids administered.
(3) Are intravenous balanced solutions safer overall and do they provide a survival advantage as compared to intravenous unbalanced solutions, especially in patients
with sepsis, in whom early fluid therapy is a crucial part of the clinical treatment?
————————————————————————————————————-
This issue has been addressed by the same group of investigators in two large retrospective studies performed on the same large clinical database in two
different cohorts of patients with sepsis .
The first one;
———————
Showed a decrease in in-hospital mortality for any increase in the fraction of balanced solutions over the total amount of fluids intravenously received for the initial resuscitation (2 days), irrespective of the total amount of fluids received .
The second study;
————————–
The administration of intravenous balanced solutions in association with 0.9% NaCl appeared to be associated with a lower in-hospital mortality and a similar length of stay and costs per day as compared to the exclusive administration of 0.9% NaCl .
THE SPLIT TRIAL;
————————–
The first large randomized controlled trial comparing the clinical effects of two different types of crystalloids, was finally published, after the conclusion of patient enrolment in October 2014 .
The study was designed to evaluate, as the primary outcome, the proportion of patients
with AKI during the first 90 days after enrollment, and to assess several clinically relevant endpoints as secondary out- comes.
The study was conducted in 4 ICUs in New Zealand, 2,278 ICU patients in need of crystalloid fluid therapy were enrolled to receive either 0.9% NaCl or Plasma-Lyte 148, as a balanced solution, according to an alternating block of 7-weeks for each specific ICU.
The authors observed an identical proportion of patients developing AKI in the two groups of treatments (9.6% in the balanced solutions group vs. 9.2% in the 0.9% NaCl group), as well as a similar use of renal replacement therapy and in-hospital mortality.
The authors concluded, these findings, whereas showing neutral effects of the two strategies in post-operative patients, leave unsolved the potential effects of intravenous
balanced solutions in high-risk populations, more exposed to fluid therapy and at risk of AK
Dear Dr Ishag,
I liked reading your detailed summary. Will you change your practice based on this article? Ajay
Nahla Allam
2 years ago
research in urgent and emergency care has experienced an incredible explosion of experimental and clinical studies.
“balanced fluids”:
Ø In intravenous solutions, electrolyte composition is closer to the plasma design, and balanced solutions should minimally affect acid-base equilibrium, compared to the commonly reported 0.9% NaCl-related hyperchloremic metabolic acidosis.
Ø . Fluid balance should equal the amount of fluid intake.
Ø Euvolemia defines the state of average body fluid volume.
Designing a fluid for intravenous administration:
Firstly: osmolarity, the need for electrolytes dissolved in the solution, appropriate tonicity (as close as possible to plasma osmolarity)
Secondly: an oncotic molecule dissolved in the solution, ideally aimed at maintaining the volume infused within the intravascular compartment.
There are two categories of intravenous “balanced” solutions available:
1) those with a minimal effect on acid-base equilibrium, having a SID close to a value of 24−29 mEq L-1
2) those with a Cl– content equal to or lower than 110 mEq L-1
the first category belongs to intravenous solutions such as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s, Sterofundin ISO, Hextend, and Tetraspan.
The second category belongs to intravenous solutions such as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s, Plasma-Lyte, Elo-Mel Isotonic, Complex, and Gelaspan.
STEWART’S APPROACH AND THE MECHANISMS REGULATING ACID-BASE DURING FLUID INFUSION:
a) water, the solvent, which has a high molality (~55.5 mol kg-1) and is very weakly dissociated;
b) vital electrolytes (such as Na+, K+, Cl–), which are always entirely dissociated in biological solution and can be considered as chemically non-reacting;
c) weak, non-volatile acids (mainly albumin and phosphates), which are defined as substances only partially dissociated in an aqueous solution, according to their dissociation constant;
d) carbon dioxide (CO2) system — dissolved molecular CO2 in equilibrium with carbonic acid (H2CO3) and its dissociation products.
An aqueous solution, including solid electrolytes, non-volatile weak anions, and CO2, has to operate::
1-electrical neutrality
2-dissociation equilibria
3- conservation of mass —
three variables with the ability to influence, independently, the pH of biological fluids
1) the partial pressure of carbon dioxide (PCO2);
2) the concentration of non-volatile weak acids (ATOT), mainly albumin and phosphates;
3) the Strong Ion Difference (SID), defined as the difference between the sum of stable cations (mainly Na+, K+, Mg2+, Ca2+) and the sum of solid anions (mainly Cl–, lactate, and other possible unmeasured anions), according to the following formulas:
a) SID = (Na+ + K+ + Ca2+ + Mg2+) – (Cl– + other strong anions);
Abbreviated SID = (Na+ + K+) – (Cl–)
1) If SID inf is greater than the baseline concentration of plasma HCO3 –, then pH will tend toward alkalosis during the intravenous infusion;
2) If SID inf is lower than the baseline concentration of HCO3 –, then pH will tend toward acidosis during the intravenous infusion;
3) If SID inf equals the baseline concentration of HCO3 –, then pH will not change, regardless of the extent of the dilution.
ELECTROLYTE CONTENT AND BALANCED SOLUTIONS
MAGNESIUM:
Ø Hypomagnesemia, i.e., a plasmatic concentration of magnesium below 1.5 mg dL
Ø Severe hypomagnesemia may be associated with a higher incidence of cardiac arrhythmias, alterations in electrocardiographic findings, and modifications of the cerebral nervous system.
Ø “balanced” solutions (such as the crystalloid solutions Plasma-Lyte or Sterofundin ISO)
CALCIUM:
Ø Symptoms and clinical consequences of hypocalcemia are alterations in muscle contractility, peripheral and central nervous system function, and cardiac arrhythmias.
Ø treatment intravenous administration of either Ca2+-gluconate or Ca2+-chloride
POTASSIUM:
Ø Hypokalemia Symptoms include both alterations of muscle contractility and changes in cardiac rhythm.
Ø The standard route of K+ replacement is oral administration and may require intravenous administration in severe cases.
THE IMPORTANCE OF CHLORIDE CONTENT AND ITS PATHOPHYSIOLOGIC EFFECTS::
1- Chloride is the primary anion of the extracellular fluid
2-physiological features, Cl– is also the primary anion of any crystalloid solution given intravenously for fluid resuscitation and volume maintenance
3-Normal saline presents high, non-physiological content of Cl– (and Na+) and has long been known to induce, as a side-effect of its liberal administration, hyperchloremic metabolic acidosis
4- Cl– mediates vascular smooth muscle cell Ca2+-dependent contraction, may modify vascular responses to vasoconstrictor agents in the kidney and may affect plasma renin activity and systemic blood pressure.
5-Physiological mechanism maintains GFR constant and relatively independent from systemic blood pressure
6- the regulation of Na+ and water balance in the renal system, i.e., the tubule-glomerular feedback (TGF), is dependent on Cl– delivery, rather than Na+ delivery, to the distal tubule and its uptake by the macula densa
7-administration of 0.9% NaCl, as compared to balanced solutions, was associated with a lower diuresis and natriuresis and a lower renal artery blood flow velocity and cortical renal perfusion.
8-the infusion of Cl–-rich crystalloids may be fluid overload. Increased extracellular volume can cause an increase in central venous pressure and renal venous engorgement, which reduce trans-renal pressure gradient and flow, as well as interstitial edema, which increases renal interstitial pressure due to the relatively non-expansible kidney capsula]. Moreover, increased central venous pressure is commonly associated with increased intra-abdominal pressure, a situation that, in turn, can lead to fluid accumulation about reduction in venous return and cardiac output. All these mechanisms can cause kidney hypoperfusion and damage
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS:
Ø The choice of intravenous fluids in patients with renal failure (either acute or chronic) is particularly challenging,
Ø avoidance of 0.9% NaCl and other possible intravenous fluids causing metabolic acidosis in patients with acute or chronic renal failure, as well as during renal transplantation, and provide the first solid data on the safety of employing K+- containing balanced solutions for volume replacement and maintenance in this specific clinical setting
CLINICAL EVIDENCE:
Ø An important aspect related to the apparent lack of solid evidence supporting the use of particular types of crystalloids (or colloids
UNBALANCED INTRAVENOUS SOLUTIONS TO OUTCOME
Ø Firstly, is 0.9% NaCl intravenous solution more dangerous than balanced intravenous solutions
INTRAVENOUS CHLORIDE LOAD WITH OUTCOME:
Ø In a retrospective analysis of a large cohort of patients with SIRS, Shaw et al. observed a direct correlation between the total amount of Cl– intravenously received and the associated increase in serum Cl– concentration during fluid resuscitation with an increased risk of death.
BALANCED INTRAVENOUS SOLUTIONS TO SAFETY AND SURVIVAL:
Ø The administration of balanced intravenous solutions with 0.9% NaCl appeared to be associated with lower in-hospital mortality and a similar length of stay and costs per day compared to the exclusive administration of 0.9% NaCl.
THE SPLIT TRIAL:
Ø The SPLIT trial, the first large randomized controlled trial prospectively comparing the effects of a balanced solution (Plasma-Lyte 148) with those of 0.9% NaCl in critically ill patients, showed, unexpectedly, precise equipoise between the two treatments, although presenting significant limitations [9]. Whether or not balanced intravenous solutions are beneficial in high-risk patient categories (sepsis, trauma, burns), when exposed to more significant amounts of fluids, or when at higher risk of AKI still needs to be investigated.
Conclusion :
1-the type of solutions that may affect patient-centered clinical outcomes, including survival, such fluids should be considered “drugs.”
2-The type of fluid, the dose, the rate of administration, the timing, and the duration of the treatment are all equally important
3-.Intravenous balanced solutions potentially have several physiologically relevant advantages, but the actual translation of such rationale into clinically relevant outcomes still needs to be clarified.
Thank you, Nahla Please do not copy and paste. Can you summarise the SPLIT trial, please? what is the conclusion
Zahid Nabi
2 years ago
Balanced” solutions are commonly defined as intravenous fluids having an electrolyte composition close to that of plasma. It is well known that 0.9% saline is associated with hypercholremic metabolic acidosis so may be a balance solution is one with reduced content of chloride.
uptil now a balanced solution having low Chloride contact , no effect on acid base balance and adequate tonocity is not available.The available literature also does not support one solution upon other.
SPLIT trial
The first large randomized controlled trial comparing the effects of a balanced vs. unbalanced solutions on renal function in critically-ill patients (showed identical equipoise between the two treatments.
Among the entire balanced solutions available, either they belong to just one category (having an effect on acid- base equilibrium while having a normal Cl– content, and vice versa), or present some limitations, such as relative hypotonicity (in the case of Lactated Ringer’s, Acetated Ringer’s, or Hartmann’s solution).
Another important aspect related to the concept of “balanced” solutions concerns the content of specific electrolytes other than Na+ and Cl–, in particular of magnesium, calcium and potassium (K+).
Intravenous balanced solutions have potentially several physiologically relevant advantages, although the actual translation of such rationale into clinically relevant outcomes is still uncleared.
Whether or not the use of intravenous balanced solutions is beneficial in high-risk patient categories (sepsis, trauma, burns), when exposed to larger amounts of fluids or when at higher risk of AKI, still needs to be investigated as these questions were not answered by split trial.
Intravenous fluids should be considered as DRUGS and prescribed accordingly.
· “Balanced” solutions are those intravenous fluids having an electrolyte composition close to that of plasma with minimal affect on acid-base equilibrium.
· Mostly used 0.9% NaCl solution causes hyperchloremic metabolic acidosis.
· Now a days “balanced” indicates intravenous fluids with low chloride content.
· Though, the ideal balanced solution, with minimal effects on acid-base status, low chloride content, and adequate tonicity, is not yet available.
· Magnesium, Calcium, Potassium also very important to supplement in critically ill deficient patient.
· Chloride rich solution causing a vicious cycle to develop hyperchloremic metabolic acidosis as well as hyperkalemia.
· SPLIT trial, the 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy, showed identical equipoise between the two treatments.
· The type of fluid, the dose, the rate of administration, the timing and the duration of the treatment are all equally important. Intravenous balanced solutions have potentially several physiologically relevant advantages, although the actual translation of such rationale into clinically relevant outcomes is still unclear.
Hi Dr Ansary, I liked reading your summary. Will you change your practice based on this article? Ajay
Doaa Elwasly
2 years ago
Introduction
The colloid and crystalloid type can affect the patient’s prognosis.
It is debatable whether 0.9% normal saline could be harmful or not.
New IV balanced solutions are available.
Balanced fluids are those solutions with the closest electrolyte composition to the plasma compared to other fluids therefore will not majorly change the acid base equilibrium.
Those balance solutions have low content of chloride compared to normal saline which cause hyperchloremic metabolic acidosis.
SPLIT trial recently published no difference between the effect of use of normal saline and the use of Plasma Lyte 148 on critically ill patients. Balanced solution definition
Roughly the amount of fluid loss from the body need to be substituted with an equal fluid intake to maintain the fluid balance.
When euvolemia is subjected to dysregulation ,IV fluid administration would be needed.
This IV fluid osmolarity need to be adjusted to be as close as possible to plasma also an oncotic molecule dissolved in the solution need to keep this fluid intravascular.
The solution electrolyte content has to be similar to plasma electrolyte content theoretically.
The solution has to be electrically neutral .
All IV solutions have included organic anions except normal saline and pure dextrose-containing solutions.
Balanced solutions with a relative above physiological
concentration of Cl– to preserve the electric neutrality.
Balanced solutions had to be done with normal (or lower than normal) Cl– content.
Having solutions with acid base balance coexisting with low CL content is difficult.
As each one can be available separately where solutions with least effect on acid base balance including Lactated Ringer’s, Acetated Ringer’s, Hart mann’s solution, Sterofundin ISO, Hextend, and Tetraspan.
Solutions with low chloride includeLactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan. Stewart’s approach and the mechanisms regulating acid base balance during fluid infusion.
Includes
· water as a solvent with very low dissociation
· Electrolytes that are strong but non reactive.
· Weak non volatile acids.
· CO2 system involving dissolved molecular CO2
in equilibrium with carbonic acid (H2CO3)
Also pointed to 3 constraints that must be applied to solutions
Which are
Electric neutrality, dissociation equilibrium and conservation of mass.
He discovered 3 variables that can affect the PH of the biological fluids independently which are the partial pressure of carbon dioxide (PCO2); the concentration of non-volatile weak acids (ATOT) and the Strong Ion Difference (SID).
The SID inf and the content of weak acids intravenous fluids can change both SID and ATOT of plasma, and plasma pH .
For crystalloid solutions
If SID inf is more than plasma HCO3 then pH will tend toward alkalosis and the opposite is correct.
If SIDinf equals the baseline concentration of HCO3, then PH will be constant.
Electrically charged ionic colloids have a greater SIDinf
The effect of a specific
Specific Intravenous solution’s effect on acid-base is variable.
There is not ideal balanced solution. Electrolytes in balanced solution Magnesium
Hypomagnesemia can lead to cardiac arrhythmia and alteration of CNS function and it is associated with low GFR and renal blood flow.
Balance solutions include Mg opposite to older solutions. Calcium
Hypocalcemia is the most common electrolyte disturbance in acutely ill patients presenting by cardiac arrhythmias and muscular contractility alterations .
So balanced solutions contain Ca but it can precipitate in the intravascular access, rendering the importance of having Ca free balanced solutions. Potassium
Hypokalemia is a life threatening electrolyte disturbance in critically ill patients presented by cardiac arrhythmias and change of the muscular contractility .
Most solutions contain potassium concentration within normal range .
Therefore normal saline is the preferred solution of use in AKI and CKD cases but many trials had proofed that this tendency is not correct. Chloride pathophysiological effects
Cl- has a significant impact on acid base equiliribium.
Supraphysiological levels of Cl-content in IV fluids have an important clinical impact.
Normal saline being the most popular fluid use can cause hyperchloremic metabolic acidosis ,it is self limited but it can superadd metabolic acidosis particularly in critically ill patients.
The critically ill patients are liable to a vicious circle of metabolic acidosis as hypoperfusion is the most common cause of metabolic acidosis in those cases leading to misdiagnosis and infusing the patient with more normal saline that is in fact could by the actual cause of hyperchloremic metabolic acidosis therefore worsening the metabolic acidosis.
Also another hazardous effect of the Cl- high concentration in normal saline is affecting the Ca in the smooth muscles of vessels leading to alteration of vasoconstriction in the renal vessels ,affecting GFR and RBF.
Tubuloglomerular feedback is dependent on Cl delivery to the distal tubule rather than Na delivery.
This feedback is responsible for maintaining the GFR regardless of systemic blood pressure changes , preserving salt and water
It was noticed that normal saline infusion is associated with less diuresis and naturesis and more fluid overload leading to kidney hypoperfusion compared to balanced solutions.
Normal saline as Cl rich fluid had a negative effect on healthy volunteers in the forum of abdominal cramps and on elderly candidates in the forum of decreasing gastric mucosa perfusion.
Hyperchloremic acidosis effect on immune system was tested on septic animals receiving HCL leading to increase of plasma nitric oxide and proinflammatory cytokines.
Another study compared normal saline effect to plasma lyte effect on septic rates ,it revealed that normal saline group experienced hyperchloremic metabolic acidosis leading to increased IL6 , AKI and higher mortality rate.
A retrospective study analysed patient’s data postoperatively concluded that those whom recived normal saline were more susceptible to postoperative infection compared to those who received plasma lyte solution. IV fluids in Renal transplant
Renal transplant recipients are receiving large amount of fluid replacement to enhance graft function in most centers.
Normal saline is the chosen solution due to being K free thereby avoiding hyperkalemia in such risky patients .
But in fact normal saline can cause hyperkalemia through hyperchloremic acidosis.
A study compared the use of normal saline to the use of balanced solutions with plasmatic range potassium in renal transplant candidates and concluded that normal saline group had hyperchloremic acidosis in comparison to the other group and they found that there was no difference in graft function and potassium levels between the 2 groups.
This study shedded the light on the safety of using K containing balanced fluids for volume replacement in transplant candidates rather than the use of normal saline. Clinical evidence
Recently the first large randomized controlled trial was conducted assessing the long-term clinically relevant benefit of a balanced solution over an unbalanced solution for fluid resuscitation .
Till now there is no a solid evidence to recommend the use of certain crystalloids (or colloids) due to the unclear focus of the research conducted so far. The outcome of unbalanced solutions
A study conducted on patients undergoing major abdominal surgeries ,compared the outcome in one group that received normal saline and another group that received Ca free balanced solution , they noticed higher rate of postoperative infection and higher need for RRT and mortality in the normal saline group . The outcome of IV Cl- load
Yunos et al compared the use of Cl restrictive strategy of fluid therapy for ICU cases versus Cl permissive strategy in a 6 months prospective study , concluding that cases on Cl restrictive fluid therapy experienced reduction of AKI as per RIFLE criteria and reduction of the need of RRT .
Shaw et al. revealed a direct association of both the total amount of Cl– given IV received and the increased risk of death. Balanced IV solution effect on safety and survival
IV balanced solutions are safer and provide a shorter hospital stay and overall outcome particularly in patients having sepsis as proved by studies. SPLIT trial
This trial is a large randomised controlled study conducted on 2015 on ICU patients comparing the clinical outcomes of using normal saline versus using plasma lyte , they published that there was no significant difference between the 2 studies groups regarding AKI, the need of RRT and the in hospital mortality.
This trial has limitations as including postoperative patients after elective surgeries with small comorbidity incidence and less risk APACHE II score while high risk cases were small in number.
Those cases received small volume of tested IV solutions and Cl levels effects were not evaluated. Conclusion
The type of fluid used for fluid replacement , the amount , duration and multiple aspect can affect survival outcome of the patients.
Fluids must be considered as drugs.
The ideal balanced solution is not available yet.
The benefit of use of balanced IV fluids in large amounts for critically ill patients needs further investigations.
Thanks prof, Sharma
Still , the large study SPLIT not showing different between NS and balanced solution but better to deal case by case decision
Mohamed Saad
2 years ago
Intravenous balanced solutions: from physiology to clinical evidence.
Most recent studies looking for the ideal balanced intravenous solution which is characterized by less harmful effect on acid-base equilibrium and near to physiological character of the plasma.
Simply, term of balanced solution mean low chloride solution, as hyperchloremia in 0.9 NACL has harmful effect on renal function but SPLIT trial showing no differences between the two treatments. WHAT DOES “BALANCED” SOLUTION MEAN? –Solution with dissolved electrolytes as close as possible to plasma osmolarity.
-Solution with an oncotic molecule dissolved which maintain volume infused intravenously.
-Most IV solution contain organic anions as precursors of HCO3– to balance the total content of positive charges.
-Intravenous solution with a normal (or lower than normal) Cl– content, equal or lower than 110 mEq L. ELECTROLYTE CONTENT AND BALANCED SOLUTIONS. MAGNESIUM.
Hypomagnesemia is common in both critically ill patients and patients admitted to ICU, which may be may be associated with a higher incidence of cardiac arrhythmias and other CNS manifestations, also hypomagnesemia have been reported as being associated with a worse prognosis, especially for a non-recovery renal function after development of acute kidney injury (AKI) and still no studies have ever investigated the effects of balanced solutions on the incidence of hypomagnesemia. CALCIUM.
Hypocalcemia is corrected by Replacement of plasma Ca2+ content which is obtained generally with the intravenous administration of either Ca2+-gluconate or Ca2+-chloride and not in balanced solution due to risk of Ca2+ precipitation. POTASSIUM.
Hypokalemia one of the common complications in ill- critical patient and the common route of K+ replacement is oral administration, intravenous administration may be required in severe cases. THE IMPORTANCE OF CHLORIDE CONTENT AND ITS PATHOPHYSIOLOGIC EFFECTS.
Chloride has a central role in acid-base equilibrium so it is considered the main anion of any crystalloid solution given intravenously for fluid resuscitation and volume maintenance as normal saline which contain high, non-physiological content of Cl– (and Na+) that lead to hyperchloremia metabolic acidosis and we should keep it in mind to avoid mis-diagnosis .
Cl– toxicity has bad impact on small blood vessels and vasoconstriction and affect renal blood flow and affect GFR.
slower diuretic response to the infusion of Cl–-rich crystalloids may be fluid overload, increased central venous pressure is commonly associated with increased intra-abdominal pressure all these factors lead to kidney perfusion.
Hyperchloremic acidosis has also many harmful impacts on GIT, immune system and inflammatory response. RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS.
Most common IV fluid used post KTX is 0.9 NACL, mainly because its potassium free solution in patient still has impaired renal function, correspondingly normal saline lead to Hyperchloremic acidosis which lead to hyperkalemia, but some studies shown that no difference bet balanced solution and 0.9 NACL regarding hyperkalemia. CLINICAL EVIDENCE.
Large randomized control study e.g. SPLIT shown no differences between the two treatments , unless the physiological effect is clear so , we still need large randomized studies to focus on this issues from different aspects. UNBALANCED INTRAVENOUS SOLUTIONS IN RELATION TO OUTCOME.
Some studies shown that patients receiving 0.9% NaCl showed a higher incidence of postoperative infections, a greater incidence of the use of renal replacement therapy and a higher unadjusted mortality rate, as compared to those receiving intravenous balanced solutions. INTRAVENOUS CHLORIDE LOAD IN RELATION TO OUTCOME.
Restrictive CL balanced solution versus high CL solution shown reduction in the incidence of AKI, as assessed according to the Risk, Injury, Failure, Loss and End-stage kidney injury (RIFLE) criteria, especially in the injury and risk classes. BALANCED INTRAVENOUS SOLUTIONS IN RELATION TO SAFETY AND SURVIVAL.
One large retrospective studies shown that intravenous balanced solutions in association with 0.9% NaCl appeared to be associated with a lower in-hospital mortality and a similar length of stay and costs per day as compared to the exclusive administration of 0.9% NaCl. THE SPLIT TRIAL.
(the 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy), that compare the clinical effects of two different types of crystalloids on 2,278 ICU patients to detect the primary outcome, the proportion of patients with AKI during the first 90 days, showing the same effect in developing AKI, use of renal replacement therapy and in-hospital mortality. Conclusion.
Balanced solution is has the least effect on acid-base, and electrolyte content equal to that of plasma, solution is a drug that also has side effects so balanced solution is considered is beneficial in high-risk patient categories (sepsis, trauma, burns), when exposed to larger amounts of fluids or when at higher risk of AKI, still needs to be investigated.
Thanks prof, Sharma
Still , the large study SPLIT not showing difference between NS and balanced solution but we are design our IV fluid case by case, trying to avoid NS induced hyperchloremic metabolic acidosis or hyperkalemia by ringer lactate and we prefer LR with critical cases than NS.
Ben Lomatayo
2 years ago
Balanced solution is the iv solution with electrolytes composition nearer to that of the plasma. It may be more physiological compared to 0.9 saline which causes more hypercholemic metabolic acidosis. This can lead to vasoconstriction, volume overload, immunomodulation and hypotension.
The word’ balanced’ is now means low chloride content
Unfortunately the ideal’ balanced’ solution is no yet available i.e. small effect on acid-base balance,low Cl content and adequate tonicity.
IV fluid is a drug and therefore,indications, types, dose, and rate of administration, and the timing are all important
The SPLIT trial the first RCT compared the effect of a balanced solution(plasma Lyte 148 with 0.9% NS. It revealed that, both may be the equivalent. SPLIT limitation are ; 1. most patients were postoperative patients following cardiovascular procedures and they were having less volume of comorbidity conditions 2. low severity evaluated by APACTH II score 3 small number of high risk patients e.g sepsis <5% 4given small amounts of IV fluids
The use of large volume balanced solution in high risk patients such as those with sepsis, trauma or burn is not clear whether it is beneficial or harmful and further studies are required.
Both colloids and crystalloids may affect patient-centered clinical outcomes, including survival.
Balanced fluids intravenous solutions whose electrolyte composition is closer to the composition of plasma.
Balanced solutions should minimally affect acid-base equilibrium, as compared to the commonly reported 0.9% NaCl-related hyperchloremic metabolic acidosis.
WHAT DOES “BALANCED” SOLUTION MEAN?
Theoretically, an ideal balanced solution should have the entire content of all electrolytes equal to the electrolyte content of plasma.
Two categories of intravenous “balanced” solutions available:
1) those with a minimal effect on acid-base equilibrium, having a SID close to a value of 24−29 mEq L-1; intravenous solutions such as Lactated Ringer’s, Acetated Ringer’s, Hart-man. , Sterofundin ISO, Hextend, and Tetraspan.
2) Those with a Cl– content equal or lower than 110 mEq L-1. Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan
STEWART’S APPROACH AND THE MECHANISMS REGULATING ACID-BASE DURING FLUID INFUSION.
A “balanced” crystalloid solution should be a crystalloid solution that has an in-vivo SID, i.e., after the metabolism of organic anions, very similar to the patient HCO3.
ELECTROLYTE CONTENT AND BALANCED SOLUTIONS:
Another important aspect related to the concept of “balanced” solutions concerns the content of specific electrolytes other than Na+ and Cl–, in particular of magnesium, calcium and potassium (K+). MAGNESIU
Hypomagnesemia,
Severe hypomagnesemia may be associated with a higher incidence of cardiac arrhythmias and alterations in electrocardiographic findings, as well as alterations of the cerebral nervous system.
have reported a reduction in glomerular filtration rate (GFR) and of renal blood flow (RBF) in relation with a concentration of magnesium lower than normal values, Recently, both hypomagnesemia and ionized hypomagnesemia have been reported as being associated with a worse prognosis, especially for a non-recovery renal function after development of acute kidney injury (AKI) [, as well as longer ICU stay and greater mortality.
It may be reasonable to employ intravenous fluids also including magnesium, in order to prevent hypomagnesemia.
This is the rationale upon which the novel generation of “balanced” solutions (such as the crystalloid solutions Plasma-Lyte or Sterofundin ISO) have been developed with the inclusion of magnesium, as compared to the old generation (Lactated Ringer’s, Acetated Ringer’s or Hartmann’s solution).
CALCIUM:
Hypocalcemia, especially if measured as total Ca2+ content,
The possible symptoms and clinical consequences are well known: alterations in muscle contractility, of peripheral and central nervous system function, cardiac arrhythmias and others.
POTASSIUM:
Hypokalemia is a further life-threatening electrolyte abnormality often observed in critically ill patients [16]. Moreover, it is often associated with abnormalities of the content of other electrolytes. Symptoms include both alterations of muscle contractility, and alterations in cardiac rhythm.
THE IMPORTANCE OF CHLORIDE CONTENT AND ITS PATHOPHYSIOLOGIC EFFECTS:
Chloride is the main anion of the extracellular fluid, and although its concentration in plasma is not as tightly regulated as that of Na+ and K+, it has a central role in acid base equilibrium, Because of such physiological features, Cl– is also the main anion of any crystalloid solution given intravenously for fluid resuscitation and volume maintenance.
Clinical consequences
Hyperchloremic metabolic acidosis.
Slower diuretic response to the infusion of Cl–-rich crystalloids may be fluid overload.
Increased extracellular volume can in fact cause an increase in central venous pressure and renal venous engorgement, which reduce trans-renal pressure gradient and flow, as well as interstitial edema which increases renal interstitial pressure due to the relatively non-expansible kidney capsule Moreover, increased central venous pressure is commonly associated with increased intra-abdominal pres0.9% NaCl perioperative showed a higher probability of developing a major postoperative infection, as compared to patients receiving only Plasma-Lytesure.
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS:
Patients undergoing renal transplantation still receive, large amounts of intravenous fluids (up to 30 mL kg-1h-1), in the attempt to increase their intravascular volume and therefore improve graft function.
randomized controlled studies have compared, in patients undergoing renal transplantation, the intravenous administration of 0.9% NaCl with the intravenous administration of different balanced solutions, all of which containing K+ within plasmatic ranges . While no significant difference in graft function was observed, all studies clearly documented a higher incidence of hyperchloremia and acidosis in patients receiving 0.9% NaCl as compared to patients receiving intravenous balanced solutions. It is noteworthy that no difference was observed regarding plasmatic concentrations of K+ and events of hyperkalemia between the two groups.
UNBALANCED INTRAVENOUS SOLUTIONS IN RELATION TO OUTCOME:
Patients receiving 0.9% NaCl showed a higher incidence of postoperative infections, a greater incidence of the use of renal replacement therapy and a higher unadjusted mortality rate, as compared to those receiving intravenous balanced solution.
The 0.9% NaCl group showed greater in-hospital mortality, length of hospital stay and frequency of readmission at 90 days than patients in the Ca2+-free balanced group, even after adjustments for Acute Physiology Score and baseline.
INTRAVENOUS CHLORIDE LOAD IN RELATION TO OUTCOME:
a reduction in the incidence of AKI, as assessed according to the Risk, Injury, Failure, Loss and End-stage kidney injury (RIFLE) criteria, especially in the injury and risk classes (14% vs. 8.4%, P < 0.001), as well as a reduction in the use of renal replacement therapies in reduction chloride use strategy.
BALANCED INTRAVENOUS SOLUTIONS IN RELATION TO SAFETY AND SURVIVAL:
A decrease in in-hospital mortality for any increase in the fraction of balanced solutions over the total amount of fluids intravenously received for the initial resuscitation (2 days), irrespective of the total amount of fluids received.
Administration of intravenous balanced solutions in association with 0.9% NaCl appeared to be associated with a lower in-hospital mortality and a similar length of stay and costs per day as compared to the exclusive administration of 0.9% NaCl.
THE SPLIT TRIAL:
In October 2015, the SPLIT trial (the 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy), the first large randomized controlled trial comparing the clinical effects of two different types of crystalloid. An identical proportion of patients developing AKI in the two groups of treatments (9.6% in the balanced solutions group vs. 9.2% in the 0.9% NaCl group), as well as a similar use of renal replacement therapy and in-hospital mortality.
CONCLUSIONS:
Both the introduction in clinical practice of intravenous balanced crystalloids solutions and the findings collected on their use in comparison with the traditional administration of 0.9% NaCl, have brought a new awareness in the field of fluid therapy.
This study focus on different types of intravenous fluid and comparison between 0.9% normal saline and balanced fluid.
However normal saline associated with hyperchloremic metabolic acidosis and balance fluid has electrolytes content near to normal plasma level and minimal effects on acid base balance.
SPLIT trial shows no difference between the 0.9% saline vs. Plasma- Lyte 148 for Intensive Care Unit Fluid Therapy.
Balance fluid like ringer’s lactate and hartmans solutions and acetate fluid contain amino acid and it’s tonicity near to plasma level.
ELECTROLYTE CONTENT AND BALANCED SOLUTIONS:
It’s important to focus on magnesium because 0.9 % normal saline has low magnesium level less than 1.5 mEq/l which may associate with cardiac arrhythmia and reduce renal blood flow and decrease estimate glomerular filtration rate and CNS manifestations.
Hypocalcemia and hypokalemia
So balanced fluid avoid electrolytes disturbance especially high chloride content in normal saline.
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS:
All clinicians use of normal saline because free potassium in transplant patients to avoid hyperkalemia but randomised control studies Shows better to avoid 0.9% normal saline because of hyperchloremic metabolic acidosis which may lead to hyperkalemia and better to use balance fluid rather than normal saline.
Intravenous balance fluid is safer especially in patients with sepsis in comparison to unbalanced fluid.
Balance crystalloids solutions are important in improving outcomes of patients even survival rate in comparison to traditional 0.9% normal saline.
An ideal intravenous solution is shifting from normal saline to more balanced solution in recent years. Their electrolyte composition is closer to the plasma. They minimally induce acid-base disturbances. In addition, they should have zero electro-neutrality. This was shown in a large randomized control trial named SPLIT trial.
NaCl 0.9% has a high Cl concentration and induces hyperchloremic metabolic acidosis. There are two categories of balanced solutions:
1- Those with SID close to 24-29 mEq/L (according to Stewart approach) like ringer’s lactate and Hartman solution
2- Low chloride content solutions like plasma-Lyte.
Another aspect of a balanced solution is electrolyte content of specific electrolytes such as Mg, Ca and Potassium that should be near the plasma content. Therefore, novel generation like plasma-Lyte contain these electrolytes compared to the old ones (Lactated Ringer’s). Normal saline administration is associated with lower diversis and natriuresis compared to balanced solution which may resulted in fluid overload, increased CVP, intrabdominal pressure and finally kidney hypoperfusion.
Hyperchloremic metabolic acidosis may result in increased IL-6, AKI and higher mortality. In renal transplantation usually normal saline without potassium was used to avoid hyperkalemia, but there was no difference regarding potassium between balanced solutions with normal saline. Patients with a major abdominal receiving NaCl surgery showed higher incidence of infection, AKI and mortality compared to those receiving balanced solutions. SPLIT trial performed in 2015 compared NS infusion with Plasma-Lyte 148 in ICU patients. In this double blinded RCT in New Zealand, 2278 patients received either NS or PL. Two groups were similar regarding the development of AKI or RRT or mortality. So, fluid should be considered as “drugs”.
Fluid therapy is lifesaving for patients with critically illness and renal impairment. The best IV fluid should be of normal tonicity close to plasma osmolality, has no or minimal effect on acid –base balance with near physiological Cl content,. However ,till now this ideal IV solution is not present , instead there are several IV fluids described as balanced solution that are also ChCh by minimal impact on acid base balance and plasma osmolaity and are classified into two types
1- Minimal effect on acid base as acetated and lactated ringer
2- Low Cl content as lactated ringer and hartamm solution.
According to Stewart physicochemical approach to acid-base and electrolyte equilibrium
The normal biologic fluid has 3 components ; water that contain dissolve strong electrolytes. Non volatile weak acids specially albumen and Co2. Thus IV fliud can affect blood PH via altering either electrolytes content , Paco2 or altering SID ( Difference between strong anions and cataions ).
The most commonly used Iv fluid is 0.9%NaCl that carries the risk of hypercholaremic MA with all the associated hazardous effects of both increased Cl and MA. Hypercholaremia can cause altered vascular smooth muscle response to vasopressor drugs beside its effect on argentine vasopressin secretion and rennin activation as well as affecting tubule-glomerular feed back systems even more than Na do. While MA is complicated by myocardial suppression ,decrease vascular response to vasopressor drugs as well s GIT symptoms as anorexia , neasea and vomiting that all lead to further volume depletion and acid base disturbance.
Comparison between effects of IV normal saline therapy Vs balanced solutions:
1) In healthy individuals : lower incidence of dieresis ,natruiesis and renal perfusion compared with balanced solution.
2) In critically ill patient : normal saline increase IL6 production , increase risk of AKI and patient mortality.
3) In kidney transplant recipient : the most commonly used IV fluid is normal saline , except in cases of decreased GFR where low K containing fluids are preferred to avoid hyperkalemia. Only few randomized controlled studies compared between the effects of normal saline and balanced solution in kidney transplant populations and revealed no significant difference between them regarding graft function as well as no significant difference regarding incidence of hyperkalemic episodes.
The SPLIT trial was the first randomized , double blinded trial to compare between normal saline and balanced solution as Plasma Lyte 148 regarding the incidence of AKI during 90 days hospital admission and the investigators found that there was no difference between the two groups of patients regarding AKI incidence.
Limitations of this study
1. the population included were low risk post-operative patients who needed small amounts of IV fluids .
2. the effects of the two types of fliud therapy on plasma Cl concentration were not measure
CONCLUSIONS
1. Fliud therapy is a critical issue to consider that must be carefully determined including fluid type , rate of infusion and duration of treatment with monitoring of possible complications.
WHAT DOES “BALANCED” SOLUTION MEAN?
• The osmolarity as close as possible to plasma osmolarity.
• The need, in specific clinical situations, for an oncotic pressure, or oncoticity, of the fluid
• Theoretically, an ideal balanced solution should have the entire content of all electrolytes equal to the electrolyte content of plasma.
• The total amount of free cations always equals the total amount of free anions.
• all the intravenous solutions available (with the exception of 0.9% NaCl and pure dextrose-containing solutions) have included organic anions (such as acetate, lactate, malate, gluconate, etc.), as precursors of HCO3–
• the necessity of electrical-neutrality and to avoid both hypotonicity and a high Strong Ion Difference.
• the 0.9% NaCl induces hyperchloremic metabolic acidosis
• balanced solutions have been conceived as intravenous solution with a normal (or lower than normal) Cl– content.
• there are two categories of intravenous “balanced” solutions available:
1) those with a minimal effect on acid-base equilibrium, having a SID close to a value of 24−29 mEq L-1; such as Lactated Ringer’s, Acetated Ringer’
Hartmann’s solution, Sterofundin ISO, Hextend, and Tetraspan.
2) those with a Cl– content equal or lower than 110 mEq L-1. Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan
• no ideal balanced solution has become available so far.
STEWART’S APPROACH AND THE MECHANISMS REGULATING ACID-BASE DURING FLUID INFUSION
a) water, the solvent
b) strong electrolytes (such as Na+, K+, Cl–), chemically non-reacting; c) weak, non-volatile acids (mainly albumin and phosphates)
d) carbon dioxide (CO2) system — in equilibrium with carbonic acid (H2CO3)
Stewart pointed out three constraints under which the system,
1) electrical neutrality
2) dissociation equilibria
3) conservation of mass
Subsequently, Stewart set up a system of how (H+) concentration (i.e., pH) varied according to these changes.
The dependent variables were defined as H+, OH–, HCO3–, CO3 2–, weak acid, and weak ions (A–).
1) the partial pressure of (PCO2);
2) the concentration of non-volatile weak acids (ATOT), mainly albumin and phosphates;
3) the Strong Ion Difference (SID),
SID = (Na+ + K+ + Ca2+ + Mg2+) – (Cl– + other strong anions)
Abbreviated SID = (Na+ + K+) – (Cl–)
• according to the total amount infused, the SIDinf and the content of weak acids, intravenous fluids can alter both SID and ATOT of plasma, with consequent effects on plasma pH.
• The fluid that does not alter plasma pH, at constant PCO2, regardless of the total amount infused and the degree of plasma dilution, should therefore balance the variations of these two independent variables
• crystalloid solutions, not containing weak acids (albumin or phosphates), the following general rule has been identified based upon in vitro and in vivo studies
1) If SIDinf is greater than the baseline concentration of plasma HCO3–, then pH will tend toward alkalosis during the intravenous infusion
2) If SIDinf is lower than the baseline concentration of HCO3–, then pH will tend toward acidosis during the intravenous infusion
3) If SIDinf equals the baseline concentration of HCO3–, then pH will not change, regardless of the extent of the dilution.
we can state that a “balanced” crystalloid solution should be a crystalloid solution that has an in-vivo SID, i.e., after the metabolism of organic anions, very similar to the patient HCO3– concentration.
It is noteworthy that this rule should apply also for non-ionic colloids, on the other hand, ionic colloids
should have a greater SIDinf, in order to balance the acidifying effect of the administered weak acid.
ELECTROLYTE CONTENT AND BALANCED SOLUTIONS
MAGNESIUM
• Hypomagnesemia, below 1.5 mg dL-1, is a relatively common finding in both critically ill patients and patients admitted to ICU
• severe hypomagnesemia may be associated with a higher incidence of cardiac arrhythmias as well as alterations of the cerebral nervous system.
• reduction in GFR and of (RBF) in relation with a concentration
• hypomagnesemia has been reported as being associated with a worse prognosis non-recovery renal function after AKI
• the novel generation of “balanced” solutions (such as the crystalloid solutions Plasma-Lyte or Sterofundin ISO) have been developed with the inclusion of magnesium
CALCIUM
Hypocalcemia, especially total Ca2+ content, may be considered the most common abnormality in plasma electrolyte concentration observed in acutely ill patients
Replacement with either Ca2+-gluconate or Ca2+-chloride.
However, the possible limitation, as related to the risk of Ca2+ precipitation as Ca2+-citrate or Ca2+carbonate.
POTASSIUM
Hypokalemia is a life-threatening electrolyte abnormality in critically ill patients
intravenous balanced solutions present a concentration of K+ within normal ranges.
This feature has been erroneously considered a reason for preferring the use of 0.9% NaCl as the only intravenous solution potentially applicable in the case of patients with acute or chronic renal failure.
THE IMPORTANCE OF CHLORIDE CONTENT AND ITS PATHOPHYSIOLOGIC EFFECTS
• Chloride is the main anion of the extracellular fluid,
• it is is not as tightly regulated
• it has a central role in acidbase equilibrium
• over the years, it has become evident that the Cl– content of intravenous fluids, especially at supra-physiologic levels, may have relevant clinical consequences.
Normal saline presents a high non-physiological content of Cl– (and Na+),
0.9% NaCl induced metabolic acidosis will be added to any other possible causes of acidosis, especially in critically ill patients and diabetic ketoacidosis
• Several reports have observed that Cl– mediates vascular smooth muscle may affect plasma renin activity and systemic blood pressure
• The tubule-glomerular feedback (TGF), has been shown to be dependent on Cl– delivery, rather than Na+ delivery, to the distal tubule and its uptake by the macula densa
Studies on healthy individuals receiving an IV administration of 0.9% NaCl, as compared to balanced solutions, was associated with a lower diuresis and natriuresis, and a lower renal artery blood flow velocity and cortical renal perfusion
The consequence of the relatively slower diuretic may be
• fluid overload,
• increase in CVP
• renal venous engorgement,
• increases renal interstitial pressure
• increased intra-abdominal pressure,
• reduction in venous return and cardiac outpu,
• kidney hypoperfusion and damage.
intravenous administration of a bolus of 0.9% NaCl may causes
• abdominal discomfort
• decrease in gastric mucosal perfusion
An effect of hyperchloremic acidosis on the function of the immune system has been postulated based upon experimental studies in septic animals
a study on septic rats resuscitated with intravenous administration of either 0.9% NaCl
• increased IL-6 levels,
• incident (AKI)
• higher mortality rate in those receiving 0.9% NaCl
In retrospective analysis , patients receiving only 0.9% NaCl perioperatively showed a higher probability of developing a major postoperative infection, as compared to patients receiving only Plasma-Lyte
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS
The choice of intravenous fluids is challenging,
In renal transplantation, intravenous fluids are administered normally to patients with ESRD
in many centres, large amounts of intravenous fluids (up to 30 mL kg-1h-1), to improve graft function
A survey recently performed in the United States pointed out that 0.9% NaCl, based intravenous solutions, were the most commonly employed intravenous solutions during renal transplantation.
the selection of a K+-free solution to avoid hyperkalemia in patients with reduced potassium excretion capabilities.
However, large amounts of 0.9% NaCl, induces hyperchloremic metabolic acidosis, leading to the development of hyperkalemia, and may affect renal function.
A few randomized controlled studies have compared, in patients undergoing renal transplantation, the intravenous administration of 0.9% NaCl with the intravenous administration of different balanced solutions, all of which containing K+ within plasmatic ranges
CLINICAL EVIDENCE
the first large RCT investigating a possible long-term and clinically relevant benefit of a balanced solution over an unbalanced solution for fluid resuscitation or volume maintenance, has been concluded just very recently
In association with the modification of the fluid strategy, the authors observed
a retrospective analysis of a large cohort of patients with SIRS, Shaw et al. observed a direct correlation of both the total amount of Cl– intravenously received and the associated increase in serum Cl– concentration during fluid resuscitation with an increased risk of death
BALANCED INTRAVENOUS SOLUTIONS IN RELATION TO SAFETY AND SURVIVAL
in two large retrospective studies performed on the same large clinical database in two different cohorts of patients with sepsis
In the first one showed a decrease in in-hospital mortality in balanced solutions , irrespective of the total amount of fluids received
In the second study, appeared to be associated with a lower in-hospital mortality and a similar length of stay and costs per day as compared to the exclusive administration of 0.9% NaCl
THE SPLIT TRIAL
• In October 2015
• (the 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy)
• the first large RCT comparing the clinical effects of two different types of crystalloids
• double-blind
• cluster randomized,
• double-crossover trial,
• in 4 ICUs
• in New Zealand,
• 2,278 ICU patients in need of crystalloid fluid therapy
• receive either 0.9% NaCl or Plasma-Lyte 148, as a balanced solution,
1. the primary outcome; the proportion of patients with AKI during the first 90 days after enrolment,
2. several endpoints as secondary outcomes.
• In contrast to the hypothesis, the authors observed an identical proportion of patients developing AKI in the two groups of treatments (9.6% in the balanced solutions group vs. 9.2% in the 0.9% NaCl group),
• as well as a similar use of renal replacement therapy and in-hospital mortality.
• study’s limitations,
1. the study population included was composed of post-operative patients, after elective surgery with low risk
Consequently, most of the patients in both groups received very small amounts of intravenous study fluids (2L as median values, during the study period),
2. no data on the effects of the two treatments on plasma Cl– concentration have been measured, making therefore impossible to assess the potential determinant of the deterioration of renal function during fluid therapy.
CONCLUSIONS
The article reviewed in depth, different aspects of conventional intravenous fluids focusing on the complications related to its use. The major drawback encountered in daily practice stemmed from the supraphysiologic concentration of some ions particularly Chloride. Resultant hyperchloremic metabolic acidosis is a common complication reported with overzealous administration of normal saline. Furthermore, the article elaborated on the newly introduced balanced solution, which is not inflicting hyperchloremia or metabolic acidosis and dose not result in derangement of other electrolytes concentration. Similarly, it shed light on the mechanism of renal function abnormality reported in the context of infusing normal saline, directly through its chloride content. The tubulo-glomerular feedback mechanism TGR operate to protect against the wasting of electrolytes and water by the kidneys in response to fluctuating systemic blood pressure. This mechanism is essentially mediated via chloride absorbed by Macula Densa cells in distal convoluted tubules promoting adjacent afferent arteriole vasoconstriction to prevent distal delivery and ultimate over excretion of salt. This exact mechanism is utilized by chloride content of normal saline to trigger same consequences. This putative mechanism is bolstered by common findings of diminished diuresis and natriuresis during the administration of normal saline excessively.
Utilization of this physiologic mechanism by Cl overload is aberrant and non-physiological. Other phenomena were developed linked to administration of Cl is reduction of renal blood flow and renal vasoconstriction triggered by the same.
The major effect of intravenous fluids used currently were conceptualized according to Stewart’s theory. Conclusively the Acid base balance and PH
is dependent on 3 parameters as follows:
1-dissolving pressure of CO2, PCO2
2-presence of weak acids in the solvent such as Albumin and phosphate
3- Strong Ionic Difference SID. which reflect the sum of cations minus sum of anions.
summarized as Na +K – Cl.
Cl is interplaying a pivotal role in mounting an acidic milieu,
This article is demonstrating a type of iv fluid which suppose to be used in surgical patients safely. We prefer the balanced iv fluid and according to the study it showed lower morbidity and mortality
Generally, using of balanced solution which is similar to the plasma is better with a similar concentration of electrolytes that do not affect osmolality, and maintain the same
oncotic pressure and the ions both anions and cations are balanced.
In this article,we can see in the SPLIT trial showed was a 90-day double-blind randomized double-crossover experiment in ICU patients to detect AKI. No replacement fluid affected AKI incidence, RT use, or mortality. This study had significant limitations, including a low number of high-risk patients, a group of post-operative choice surgery patients, and a tiny intravenous fluid dose.
Summary
A balanced solution is defined asintravenous fluid with electrolytes closer to plasma than prior intravenous fluids (such 0.9% NaCl), impacting acid-base balance less than 0.9% NaCl-associated hyperchloremic metabolic acidosis. An electrically neutral balanced solution has plasma-like electrolyte content. Balanced solutions have typical chloride levels.
Intravenous “balanced” solutions are categorized in two types:
1- Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan.
2- Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Sterofundin ISO, Hextrend, and Tetraspan have a strong ion difference (SID) of 24-29 mEq/L and minimally affect acid-base balance.
Stewart’s acid-base principles: Water (weakly dissociated solvent with high molality), strong electrolytes (Na+, K+, Cl–, chemically non-reacting and fully dissociated), weak acids (albumin, phosphates, partially dissociated), and carbon dioxide system make up biologic fluid (CO2, H2CO3). Electrical neutrality, dissociation equilibrium, and mass conservation are required.
The partial pressure of CO2, the concentration of non-volatile weak acids (albumin and phosphates), and the strong ion difference (SID) affect biologic fluid pH.
Besides salt and chloride, “balanced” solutions contain magnesium, calcium, and potassium, which have physiological functions. Low magnesium levels are linked to decreased GFR, renal blood flow, cardiac arrhythmias, and ECG abnormalities. 90% of critically ill patients have low calcium levels, causing muscular contractility and arrhythmias. Low potassium levels affect muscle contractility and arrhythmias.
Crystalloid solutions’ principal anion, chloride, controls acid-base equilibrium. 0.9% saline causes hyperchloremic metabolic acidosis. Increased norepinephrine and angiotension-II constrict vascular smooth muscle. Reduced tubule-glomerular feedback reduces renal blood flow and GFR, lowering diuresis and producing fluid overload, nausea, vomiting, abdominal pain, reduced gastric mucosal blood flow, increased nitric oxide and pro-inflammatory cytokines, and systemic blood pressure reduction.
0.9% NaCl intravenous fluid in renal transplantation has been linked to hyperchloremic metabolic acidosis, hyperkalemia, and renal function, unlike “balanced” solutions. AKI, CKD, and renal transplant patients should avoid 0.9% NaCl.
Several research show the benefits of “balanced” solution. 0.9% NaCl use is linked to higher infections, RRT use, death, length of stay, and re-admission. Replacement fluid chloride level increases AKI, RRT use, and death. “Balanced” methods cut mortality and hospital stay and expense. SPLIT was a 90-day double-blind randomized double-crossover experiment in ICU patients to detect AKI. No replacement fluid affected AKI incidence, RT use, or mortality. This study had significant limitations, including a low number of high-risk patients, a group of post-operative choice surgery patients, and a tiny intravenous fluid dose.
In conclusion, intravenous fluids are medications and should be prescribed after answering questions about type, dose, rate of delivery, timing, and duration.
This article discussed the IVF choices and differences on physiological bases to clinical evidence, so all fluids are medicine, they can be used as volume replacement, correction of hemostasis, correction of electrolytes etc. so in conclusion the balanced solution composition, tonicity, osmolality must be close to physiological need. Because every drug has its potential risk and complications. So before prescribing IVF drug it should be in mind to plan the type, dose, rate of administration, and need of the patient.
Summarise this article
The article is based on a critical appraisal
of intravenous fluids from the physiological basis to clinical
evidence. Fluid balance is important as it must be used in patients for
various reasons and as such its constituents must be close to the plasma. The
study was one in which a large randomized control trial comparing how
intravenous balanced solution vs 0.9% NaCl how will impact renal function and
hospitalized survival. In doing so, whatever fluid is used even though it
may be safe but may have some harm to it depending on what one is
treating. As such a balanced fluid is one that is similar to plasma where
pH.
So by definition, a balanced solution is one
in which:
1) The fluid
that is equal to the volume desired for the replacement contains a similar
the concentration of electrolytes that do not affect osmolality, maintain the same
oncotic pressure and the ions both anions and cations are balanced.
2) Haemostasis
is an important mechanism of the body to prevent bleeding.
3) Fluid balance
is the difference between the input and output of fluid.
4) There is no
ideal solution but there are solutions that can assist depending on was it is
being treated.
Based on what is mentioned, there are two
main types of balanced fluids are:
1) The one with
little effect on the acid-based equilibrium with a SID close to 24-29 mEq L
2) The ones
with CL content equal to or lower than 110 mEq/l
The examples of group one are:
1) Lactated
ringers
2) Acetated
ringers.
3) Hartmann
solution
4) Sterofundin
ISO
5) Hextend and
6) Tetraspan.
Examples of the second group are:
1) Lactated
ringer
2) Acetated
ringers.
3) Hartmann
solution
4) Plasma
lye,
5) Elo
mel Isoton
6) Isoplex
7) Gelespan.
Stewart’s approach and the mechanism of
acid-base regulation during fluid infusion:
1) Water is the
universal solvent with high molality and doesn’t dissociate easily
2) Electrolytes
like sodium, potassium, and chloride can disassociate in a biological solution
3) Weak
non-volatile acids like albumin and phosphate partially dissociate
4) There is
equilibrium with CO2 and H2CO3
The criteria of the solutions are:
1) Must be
electrically neutral
2) Must have
dissociation equilibrium
3) Can conserve
mass, etc.
Based on fluids and the pH, there are
factors that can affect it:
1) The presence
of weak acid but volatile
2) The
concentration of CO2
3) The presence
of strong ion
Looking at the electrolytes and their
importance:
1) Magnesium: very
low Mg may be associated with cardiovascular arrhythmias and will changes in
the electrocardiogram. Crystalloid solutions plasma Lyte or sterofundin
ISO has Mg.
2) Calcium: low
calcium can cause muscle contraction, cardiac arrhythmias, and abnormal
function of the nervous system. It is not part of the solutions but can be
added due to the possibility of causing precipitation.
3) Potassium: some
solutions may contain potassium like lactate ringer or Hartmann solution and
are normally at a normal range as serum. Low K can cause cardiac
arrhythmias and muscular contraction. High potassium will also cause
cardiovascular arrhythmias also.
4) Chloride: Cl
is mostly found in high-concentration extracellular and plays a role in
acid-base equilibrium. It is the most commonly used electrolyte but can
cause hyperchloremic metabolic acidosis. The high concentration of Cl may
cause affectation at the level of the kidneys by affecting the
tubular-glomerular feedback mechanism.
Kidney transplantation and the use of
intravenous fluids:
There have been studies that compare the use
of sodium chloride with other solutions post-transplantation. What the result
suggested was that there weren’t significant differences between the solutions
but there was a higher incidence of hyperchloremic metabolic acidosis in those
receiving sodium chloride than those not receiving it. As it relates to
potassium there were no differences. So in conclusion it is noted that in
causes of AKI and CKD sodium chloride must be carefully used to avoid metabolic
acidosis.
The outcome of unbalanced solutions from
balanced solutions:
1) It has been
found that patients that do major surgery with the use of normal saline have
shown a higher incidence of infection, increased need for RRT, and higher
mortality when compares to Ca-free balance solutions.
2) It has shown
that balanced solutions have a survival advantage and safety compared to
unbalanced solutions.
So in conclusion, one must consider the
aspect of the solution to give the patient and the type, duration, and amount
given must be noted. Also, balanced solutions have a better physiological
advantage over unbalanced solutions and one must ensure that the balanced
solution doesn’t have any effect on the patient’s electrolytes and acid-base
equilibrium. More needs to be learned about solutions and as such care
must be taken in the decision of which solution to be used.
Summarise this article
Definition of balanced solutions:
Balanced solutions are an intravenous fluids having an electrolyte composition close to that of plasma, that minimally affect acid-base equilibrium.
The target water hemostasis is to maintain the effective circulatory volume (by water and electrolyte contents), pertaining euvolemia.
IV fluids for volume restorment should be:
Keeping similar osmolarity to the serum.
Keeping the fluid with close tonicity (by dissolved electrolytes) close to serum osmolality.
In specific clinical situations, for an oncotic pressure, or oncoticity, of the fluid and, therefore, for an oncotic molecule dissolved in the solution, ideally aimed.
Electrical neutrality (cations = anions).
STEWART’S APPROACH AND THE MECHANISMS REGULATING ACID-BASE DURING FLUID INFUSION:
Peter Stewart began with describing the components of biologic fluid:
a) Water, the solvent, which has a high molality and is very weakly dissociated.
b) Strong electrolytes (such as Na+, K+, Cl–), which are always entirely dissociated in biologic solution, and can be considered as chemically non-reacting.
c) Weak, non-volatile acids (mainly albumin and phosphates), which are defined as substances only partially dissociated in aqueous solution, according to their dissociation constant.
d) Carbon dioxide (CO2) system — dissolved molecular CO2 in equilibrium with carbonic acid (H2CO3) and its dissociation products.
He also put a three constraints:
1) Electrical neutrality.
2) Dissociation equilibrium.
3) Conservation of mass
PH of biologic fluids maintained by:
1) the partial pressure of carbon dioxide (PCO2).
2) the concentration of non-volatile weak acids (ATOT), mainly albumin and phosphates.
3) the Strong Ion Difference (SID), defined as the difference between the sum of strong cations (mainly Na+, K+, Mg2+, Ca2+) and the sum of strong anions (mainly Cl–, lactate, and other possible unmeasured anions), according to the following formulas:
a) SID = (Na+ + K+ + Ca2+ + Mg2+) – (Cl– + other strong anions).
b) Abbreviated SID = (Na+ + K+) – (Cl–).
However, no solution considered totally balanced.
ELECTROLYTE CONTENT AND BALANCED SOLUTIONS:
Magnesium: Plasma-Lyte or Sterofundin have been developed with the inclusion of magnesium, as compared to the old generation (Lactated Ringer’s, Acetated Ringer’s or Hartmann’s solution), as the magnesium level lower than 1.5 mg/dl usually seen in critically ill patients and even lower level associated with cardiac arrhythmia, ECG changes, CNS alteration, muscle weakness, reduction in glomerular filtration, and renal blood flow leads to AKI.
Calcium: the calcium cannot be a composition of an IV fluid as it easily precipitates. So can be transfused separately. Hypocalcemia is seen in almost 90% of critically ill patients, manifest as alterations in muscle contractility, of peripheral and central nervous system function, cardiac arrhythmias.
Potassium: All the available intravenous bal[1]anced solutions present a concentration of K+ within normal ranges that does not meet the daily required potassium need that can be taken orally, hypokalemia manifest as h alterations of muscle contractility, and alterations in cardiac rhythm.
THE IMPORTANCE OF CHLORIDE CONTENT AND ITS PATHOPHYSIOLOGIC EFFECTS:
Chloride is the main extracellular anion nad play central role in acid- base equilibrium, and should be in its physiological concentration in IV fluids, in order not to alter the acid –base equilibrium. In high concentration as present in 0.9% N/S can lead to hyperchloremic metabolic acidosis and hyperkalemia.
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS:
Data strongly support the avoidance of 0.9% N/S and other possible intravenous fluids causing metabolic acidosis in patients with acute or chronic renal failure, as well as during renal transplantation, and provide the first solid data on the safety of employing K+- containing balanced solutions for volume replacement and maintenance in this specific clinical setting.
CLINICAL EVIDENCE:
UNBALANCED INTRAVENOUS SOLUTIONS IN RELATION TO OUTCOME-
N/S 0.9%, showed a higher incidence of postoperative infections, a greater incidence of the use of renal replacement therapy as compared to those receiving intravenous balanced solutions, but no difference in mortality rates was observed between the two groups.
Patients in the 0.9% N/S group have greater in-hospital mortality, length of hospital stay and frequency of readmission at 90 days than patients in the Ca2+-free balanced group.
INTRAVENOUS CHLORIDE LOAD IN RELATION TO OUTCOME-
A chloride restrictive strategy showed a reduction in the incidence of AKI, as assessed according to the Risk, Injury, Failure, Loss and End-stage kidney injury (RIFLE) criteria, as well as a reduction in the use of renal replacement therapies.
Shaw et al. observed a direct correlation of both the total amount of Cl– intravenously received and the associated increase in serum Cl– concentration during fluid resuscitation with an increased risk of death.
BALANCED INTRAVENOUS SOLUTIONS IN RELATION TO SAFETY AND SURVIVAL-
The administration of intravenous balanced solutions is associated with a lower in-hospital mortality and a similar length of stay and costs per day as compared to the exclusive administration of 0.9% N/S.
THE SPLIT TRIAL:
In October 2015, double blinded randomized controlled trial comparing OsmoLyte to N/S infusion in patients in ICU setting showed no difference between two groups in AKI within 90 days, the need for RRT, or mortality.
The limitations are: most patient are after an elective cardiac surgery with small number of seriously ill patients, the fluids used are around 2 liters only that might not interrupt the acid base equilibrium, and no n plasma Cl– concentration have been measured.
CONCLUSIONS:
A ‘balanced solution’ is intravenous fluid with electrolyte composition closer to that of plasma as compared to the previously available intravenous fluids (like 0.9% NaCl), minimally affecting the acid-base balance (unlike 0.9% NaCl associated hyperchloremic metabolic acidosis). An ideal balanced solution should have the electrolyte content equal to that of plasma and hence should be electrically neutral. Ns showing harmful effects of supra-physiological chloride levels, the balanced solutions have a normal or lower chloride levels.
Two categories of intravenous ‘balanced’ solutions are available:
a) Those with chloride content less than or equal to 110 mEq/L: Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan.
b) Those with strong ion difference (SID) of 24-29 mEq/L, having minimal effect on acid-base balance: Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Sterofundin ISO, Hextrend, and Tetraspan.
Principles of Stewart’s approach to acid-base balance: The components of biologic fluid include water (weakly dissociated solvent with high molality), strong electrolytes (Na+, K+, Cl–, chemically non-reacting and entirely dissociated), weak acids (albumin, phosphates – only partially dissociated), and carbon dioxide system (CO2, H2CO3). These should have electrical neutrality, must be in dissociation equilibrium, with conservation of mass.
The pH of biologic fluids gets influenced by 3 variables, namely the partial pressure of CO2, the concentration of non-volatile weak acids (albumin and phosphates) and the strong ion difference (SID, Na+ + K+ – Cl–).
Other electrolytes like magnesium, calcium and potassium also have a physiological role, and hence are added in ‘balanced’ solutions, in addition to sodium and chloride. Low magnesium levels have been shown to be associated with reduced GFR and renal blood flow, and increased incidence of cardiac arrhythmias and ECG changes. Low calcium levels are seen in upto 90% of critically ill patients, leading to altered muscle contractility and arrhythmias. Low potassium levels are also associated with altered muscular contractility and arrhythmias.
Chloride is the main anion of any crystalloid solution with central role in acid-base equilibrium. 0.9% saline induces hyperchloremic metabolic acidosis. There is contraction of vascular smooth muscle with increased norepinephrine and angiotension-II. Reduction in tubule-glomerular feedback leads to reduced renal blood flow and GFR decreasing diuresis leading to fluid overload, nausea, vomiting, abdominal discomfort, reduced gastric mucosal blood flow with increased production of nitric oxide and pro-inflammatory cytokines causing reduction in systemic blood pressure.
Comparing intravenous fluid in renal transplant, 0.9% NaCl has been shown to be associated with hyperchloremic metabolic acidosis and hyperkalemia, and may affect renal function, findings not seen with use of ‘balanced’ solutions. Hence 0.9% NaCl should be avoided in patients with AKI, CKD, or renal transplant.
Clinical evidence regarding the benefit of using ‘balanced’ solution has come from several studies. Studies have shown that 0.9% NaCl use is associated with increased infections, RRT use, and death with increased length of stay and re-admission. Increased chloride content in the replacement fluids is associated with increased AKI, RRT use and death. Use of ‘balanced’ solutions has been shown to be associated with reduced mortality and similar length of hospital stay and costs. The SPLIT trial was double-blind randomized double-crossover trial in ICU patients designed to look for AKI in first 90 days. It showed that there was no difference in AKI incidence, RT use or mortality with respect to the replacement fluid used. But this study had many limitations including low number of high-risk patients, study population mainly involving post-operative patients after elective surgery, and use of very small amount of intravenous fluid.
Inconclusion, intravenous fluids should be considered as drugs and questions regarding their type, dose, rate of administration, timing and duration of treatment should be addressed before prescribing.
Level of evidence: Level 5 – Narrative review
SUMMARY OF THE ARTICLE
“A critical appraisal of intravenous fluids- from the physiological basis to clinical evidence”
This review article about balanced solutions, comprehensively provided:
· A full physiological background of balanced solutions.
· The potential pathophysiologic effects of balanced solutions.
· The clinical evidence available at the moment to support their use or not.
The ideal balanced solution:
· Should be the same as plasma regarding the electrolytes content.
· Should display the characteristic of electrical-neutrality(dissolved free positive charges = dissolved free negative charges).
· With a normal (or lower than normal) Cl– content.
The characteristic of balanced solution:
· Minimal effect on acid-base equilibrium.
· The physiological content of Cl–.
Indeed;
· no ideal balanced solution has become available so far.
· Available solutions, either they belong to just one category (having an effect on acid-base equilibrium while having a normal Cl– content, and vice versa).
· Available solutions, may present some limitations, such as relative hypotonicity (in the case of Lactated Ringer’s, Acetated Ringer’s, or Hartmann’s solution) Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan.
· A balanced crystalloid solution should be a crystalloid solution that has an in-vivo SID, very similar to the patient HCO3– concentration.
Renal transplantation and IV fluids:
1. A few randomized controlled studies documented a higher incidence of hyperchloremia and acidosis in patients receiving 0.9% NaCl as compared to patients receiving intravenous balanced solutions;
· data strongly support the avoidance of 0.9% NaCl and other possible intravenous fluids causing metabolic acidosis in patients with acute or chronic renal failure, as well as during renal transplantation.
· provide the first solid data on the safety of employing K+– containing balanced solutions for volume replacement and maintenance in renal transplantation.
2. 0.9% NaCl administration is associated with greater in-hospital mortality, length of hospital stay and frequency of readmission at 90 days than patients in the Ca2+-free balanced group, even after adjustments for Acute Physiology Score and baseline covariates.
3. The type of fluid, the dose, the rate of administration, the timing and the duration of the treatment are all equally important.
Club 1; Intravenous balanced solutions: from physiology to clinical evidence
Summary:
· Simply, balanced crystalloid solution is the most similar to plasma osmolality and electrolytes composition and is elctroneutral (dissolved cations equal to the dissolved anions).
· The studies want to find balanced crystalloid solution with less chloride content than isotonic NaCL 0.9 % (to avoid hyper-chloremic metabolic acidosis of the supraphysiological amount of Cl in isotonic saline and its effect on the graft outcome).
· Most of available solutions include organic substances as acetate, lactate, malate, gluconate, etc to act as bicarb precursors.
· Till now, no available solution with the target 2 objectives: minimal effect on acid base balance and physiological content of chloride.
· Solutions with minimal effect on acid base as: ringer lactate, acetate and hartmann solution.
· solutions with physiological Cl content (< 110 mmol/L) as: Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte.
· However, Lactated Ringer’s, Acetated Ringer’s and Hartmann’s solution have lower tonicity than the plasma.
· Hypomagnesemia in critically ill patients is associated with AKI. decreased renal blood flow, GFR and cardiovascular mortality. Hence, novel generation of “balanced” solutions (as Plasma-Lyte or Sterofundin ISO) have been developed to contain magnesium, in comparison to the old generation (Lactated Ringer’s, Acetated Ringer’s or Hartmann’s solution).
· Hypocalcemia has detrimental effect on the muscles, CNS and arrhythmia, hence, need to supply it in large amount within the balanced solutions. However, the risk of ca precipitation, it is supplied in the form of ca gluconate or citrate in a separate line.
· Hypokalemia has serious effects on the heart and muscles, but the normal K content of available balanced solutions was falsely considered inappropriate for patients with AKI or CKD and so isotonic saline was the preferred solution in renal patients to avoid hyperkalemia.
· Isotonic saline is the most commonly used solution in resuscitation, but it causes hypercholremic metabolic acidosis that worsen acidosis in case of shock, hypoperfusion and DKA in addition to misleading the clinical decision in trial to search for underlying cause of acidosis and its treatment.
· The adverse effects observed with isotonic saline induced acidosis:
o Cl mediated vasoconstriction of blood vessels>>. ↑RAAS>> hypertension.
o Tubule-glomerular feedback (TGF) which depends on CL (rather than Na) delivered to the distal nephron>>. decreased natriuresis so volume overload and edema.
o Decreased gastric mucosal blood supply and abdominal discomfort.
o Animal studies done on septic rats concluded that the hypercholremia increased release of pro-inflammatory cytokines as IL6, but still an association and can be considered as a causation.
o In addition, it was observed that it has higher incidence of post operative infections, sepsis, hospital stay, higher incidence of AKI that required renal replacement therapy with isotonic saline used in major surgery. However, other concomitant factors may be responsible for the worse outcome.
· kidney transplantation patients have 2 problems:
o Need for large amount of fluid administration to enhance the graft perfusion.
o Fear from the hyperkalemia.
· Isotonic saline is still the most commonly used due to its low K content, however, the hyperchloremic acidosis cause hyperkalemia beside deleterious effect of hyperchloremia on allograft outcome.
· Studies comparing isotonic saline and other balanced solutions concluded that balanced solution has no worse effect on hyperkalemia and has less incidence of hypercholermic acidosis. hence, the use of K containing solutions can be used safely in transplant patients.
· However, RCTs are still needed to study the long term effect on the graft and patient survival.
· Use of Cl restrictive approach was associated with less incidence of AKI, need for RRT,
· RCT comparing plasma- lyte 148 and isotonic saline, published in 2015. concluded that both have similar rates of AKI, RRT and mortality. however, this study has many limitations as most of patients received relatively small amount of IV fluids due to cardiovascular problems.
· Conclusion:
o IV fluids are considered a drug with crucial need to determine its use, dose and adverse effects.
o Ideal balanced crystalloid solution is not available yet.
level of evidence” V (narrative review).
Introduction
Current studies have debated the use of the ideal type and amount of fluid usage in the critical care and emergency units, for better patient outcomes. The study aims to provide a comprehensive review of the same, by providing a physiological background of balanced solutions and summarizing their potential pathophysiologic effects, and presenting the clinical evidence available to support their use or not.
What does “balance” solution mean?
Homeostasis is essential in human physiology. Our daily fluid input should ideally match the output, to maintain effective circulating blood volume, overall content of water and electrolytes. Intravenous administration of fluid alters this process.
In theory, a balanced solution should have the electrolyte content equal to that of plasma, and it should have minimal effect on the acid-base equilibrium.
Currently, the available “balanced” solutions available meet the criteria of either having minimal effects of the acid-base equilibrium, by having a SID close to the value of 24-19mEq/L (as seen in Ringer’s Lactacte, acetated Ringer’s, Hartmann’s solution, Sterofundin ISO, Hextend and Tetraspan), and has chloride ion content equal or lower than 110 mEq/L (as seen in Ringer’s lactate, acetated Ringer’s, Hartmann’s solution, Plasma-lyte, Elo-Mel Isoton, Isoplex and Gelaspan).
Stewart’s approach and the mechanisms regulating acid-base during fluid infusion
Peter Stewart describes the components of biological fluids as follows:
1. Water – the solvent
2. Strong electrolytes – Na+, K+, Cl-
3. Weak, non-volatile acids – albumin and phosphates
4. Carbon dioxide (CO2) system
The acid-base system needs to operate under the following criteria; electrical neutrality, dissociation equilibria, and conservation of mass.
The dependent variables of his system that affected the pH of biological fluids included H+, OH-, HCO3-, CO32-, weak acid and weak ions. The independent variables were the partial pressure of CO2, the concentration of non-volatile weak acids and the strong ion difference (SID).
The following mechanisms clearly suggest that intravenous fluids may have an effect of the pH of plasma. It is also important to remember that the effects of intravenous solutions may vary in different patients and there is no available solution that is ideally balanced.
Electrolyte content and balanced solutions
1. Magnesium
2. Calcium
3. Potassium
The importance of chloride content and its pathophysiologic effects
Normal saline has a high levels of chloride and sodium ions. Using it liberally will therefore cause hyperchloremic metabolic acidosis. In critically ill patients, this will exacerbate the acidosis that is possibly ongoing from other causes, worsening the clinical status of the patient.
There are also other side effects of chloride toxicity. Chloride ions mediate vascular smooth muscle cell Ca+-dependent contraction, it may modify vascular responses to vasoconstrictor agents in the kidney and it may affect plasma renin activity (and thereby affecting systemic blood pressure). The tubule-glomerular feedback, that regulates the sodium and water balance in the kidneys, is also dependent on Cl-. Studies on healthy individuals showed that the use of normal saline was associated with reduced diuresis and natriuresis, and lower renal artery blood flow and cortical renal perfusion. This may lead to a state of fluid overload, and increased extracellular volume can cause an increase in central venous pressure and renal venous enlargement, both of which will lead to a reduced venous return and cardiac output. All these mechanisms may lead to kidney hypoperfusion and damage.
Hyperchloremic metabolic acidosis has also been associated with an increase in IL-6 levels, incident acute kidney injury and a higher rate of mortality.
Renal transplantation and intravenous fluids
Patients with renal dysfunction have impaired handling of water and electrolytes. During renal transplantation, large amounts of fluids are required for patients with end-stage renal disease, in the attempt to increase intravascular volume and hence improve graft function. Usually, the preferred choice of fluids is normal saline, as it does not have potassium, and therefore it avoids hyperkalemia.
Recent studies have shown that “balanced” solutions did not cause hyperkalemia, and normal saline was associated with a higher incidence of hyperchloremic metabolic acidosis.
Clinical evidence
Shaw AD et al. examined patients undergoing a major abdominal surgery and receiving either only normal saline or only receiving Ca2+-free balanced solutions on the day of surgery. It was a retrospective study. Patients receiving only normal saline showed a higher incidence of postoperative infections, a higher incidence of the use of renal replacement therapy and a higher rate of mortalities, compared to the patients who used the balanced solution.
Yunos et al., in a prospective study, compared a Cl–restrictive strategy, which was applied to fluid therapy of all consecutive ICU admissions over 6 months, to the Cl—permissive strategy over the same 6 month period of the previous year. The authors observed a reduced incidence of AKI and the use of renal replacement therapies after the introduction of the Cl- restriction.
Studies have also shown a reduction in in-hospital mortalities, in patients who received “balanced” solutions during resuscitation for septic shock.
The SPLIT trial
The SPLIT trial was published in October 2015. It was a double blind, randomized controlled trial comparing normal saline versus Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy. It was conducted in 4 ICUs in New Zealand. The study was designed to evaluate the proportion of patients with AKI during the first 90 days after enrolment. The authors observed an identical proportion of patients developing AKI in the two groups. The study also revealed a similar incidence in the use of renal replacement therapy and in-hospital mortality.
Most of the patients were post-operative patients who had undergone elective surgery (mainly cardiovascular procedures) with fewer co-morbidities. Therefore, the participants received small amounts of intravenous fluids. And therefore, there is not enough evidence to support the results in patients who are at high-risk of AKI when exposed to the fluid therapy.
Conclusion
The type of fluid, dose, rate of administration, the timing, duration and patient characteristics should be considered when using fluid therapy. The SPLIT trial was the first large RCT comparing NS versus a balanced solution (plasmalyte 148) and the results showed precise equipose between the two groups. There is still a requirement for further studies evaluating the patients in the high-risk categories, and the mechanisms that cause the clinical effects of the different types of fluids.
Balanced solution should have :
1-the entire content of all electrolytes equal to the electrolyte con- tent of plasma.
2-each water solution must display (and actually does display) the characteristic of elec- trical-neutrality: the total amount of free positive charges dissolved in the solution (as cations) always equals the total amount of free negative charges dissolved in the solution (as anions)
3-low content of Chloride
two categories of intravenous “balanced”solutions available:
1) those with a minimal effect on acid-base equilibrium, having a SID close to a value of 24−29 mEq L)e.g Lactated Ringer’s, Acetated Ringer’s, Hart-mann’s solution, Sterofundin ISO, Hextend, and Tetraspan.
2)those with a Cl– content equal or lower than 110 mEq L e.g Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan.
Off-note: Among the entire balanced solutions available, either they belong to just one category (having an effect on acid- base equilibrium while having a normal Cl– content, and vice versa), or present some limitations, such as relative hypotonicity (in the case of Lactated Ringer’s, Acetated Ringer’s, or Hartmann’s solution) .
As per stewards approach :balanced”crystalloid solution should be a crystalloid solution that has an in-vivo SID, i.e., after the metabolism of organic anions, very similar to the patient HCO3– concentration.
The theoretical understanding of the effects of intrave- nous solutions on acid-base equilibrium has two important consequences
Firstly, the effect on acid-base of a specific intravenous solution may vary in different patients, hav-ing different HCO3– concentrations.
Secondly, no available solution may be considered as totally balanced, and may be considered as the “ideal” balanced solution. In fact, since normal HCO3– concentration is about 24 mEq L-1, and electrical neutrality must be satisfied, either we aim at not affecting acid-base at the cost of an increased Cl– content in order to have a SIDinf close to 24 mEq/L, or we aim at having a physiological Cl– concentration at the cost of a greater SIDinf.
Magnesium: severe hypomagnesemia may be associated with a higher incidence of cardiac arrhythmias and altera- tions in electrocardiographic findings, as well as alterations of the cerebral nervous system. Interestingly, experimental data have reported a reduction in glomerular filtration rate (GFR) and of renal blood flow (RBF) in relation with a con- centration of magnesium lower than normal values, and a restoration of GFR and RBF after magnesium adminis- tration .Recently, both hypomagnesemia and ionized hypomagnesemia have been reported as being associated with a worse prognosis, especially for a non-recovery renal function after development of acute kidney injury (AKI) .as well as longer ICU stay and greater mortality .
Calcium:
disturbance in plasma calcium level:
alterations in muscle contractility, of peripheral and central nervous system function, cardiac arrhythmias and others. Replacement of plasma Ca2+ content is obtained generally with the intravenous administra- tion of either Ca2+-gluconate or Ca2+-chloride to avoid calcium precipitation .
potassium:
Hypokalemia: causes alterations of muscle contractility, and alterations in cardiac rhythm. All the available intravenous bal- anced solutions present a concentration of K+ within normal ranges, which does not necessarily cope with the normal daily intake K+ requirement [21]. This feature has been considered a reason for preferring the use of 0.9% NaCl as the only intravenous solution potentially applicable in the case of patients with acute or chronic renal failure
Chloride:
Hyperchloremia :can cause :
Smooth vascular muscle cell contraction ,increase epinephrine and angiotensin II induced vasoconstriction,decrease renal blood flow and increase congestion and decrease dieresis
Increase risk of metabolic acidosis (nausea,vomiting and abdominal discomfort,decrease in gastric blood flow,decrease in systolic blood pressure and increase in pro inflammatory cytokines and immmunomodulation).in case of metabolic acidosis ,in critically I’ll patient ,physicians may search for other causes of acidosis like dehydration and volume depletion end this will make them increase dose of Normal saline and further worsening of acidosis .
Kidney transplantation and IV Fluids:
Clinical evidence:
Conclusion:
The type of fluid, the dose, the rate of administration, the timing and the dura- tion of the treatment are all equally important.
Still no ideal balanced IV fluid available
Further studies in this field are needed
· Balanced fluids defined as intravenous solutions whose electrolyte composition is closer to the composition of plasma, as compared to previously available solutions
· Balanced solution indicates intravenous solutions with a low content of chloride, as hyperchloremia may alter renal function
· While 0.9% NaCl induces hyperchloremic metabolic acidosis, balanced solutions thought to have minimal effects on acid-base equilibrium
· There are two categories of intravenous “balanced” solutions available:
1) Those with a minimal effect on acid-base equilibrium, SID close to 24−29 mEq L ( Lactated Ringer’s, Acetated Ringer’s, Hart mann’s solution, Sterofundin ISO, Hextend, and Tetraspan)
2) Those with a Cl– content equal or lower than 110 mEq L (s Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan)
· A “balanced” crystalloid solution should be a crystalloid solution that has an in-vivo SID, i.e., after the metabolism of organic anions, very similar to the patient HCO3 – concentration
· Ionic colloids (such as gelatins and albumins) should have a greater SIDinf, in order to balance the acidifying effect of the administered weak acid
· Hypomagnesemia, < 1.5 mg dL, is a relatively common finding in both critically ill patients and patients admitted to ICU, therefore, it may be reasonable to employ intravenous fluids replacement contains Mg.
· Hypocalcemia could be the most common abnormal plasma electrolyte observed in acutely ill patients, up to 90% of critically ill patients may have hypocalcemia
· Hypokalemia is a further life-threatening electrolyte abnormality seen in critically ill patients. All the available IV balanced solutions contain K+ within normal ranges
· Chloride is the main anion of the extracellular fluid, and it has a central role in acid-base equilibrium, and it is the main anion of any IV crystalloid solution given for fluid resuscitation and volume maintenance
· Normal saline contains a high, non-physiological content of Cl– , and known to induce, as a side-effect, hyperchloremic metabolic acidosis.
· Cl– mediates vascular smooth muscle cell Ca2+-dependent contraction, may modify vascular responses to vasoconstrictor agents in the kidney and may affect plasma renin activity and systemic blood pressure
· In patients undergoing renal transplantation, there was no difference was regarding events of hyperkalemia between in patients given 0.9NaCl and balanced solutions containing K+
CONCLUSIONS
· Fluids should be considered as drugs, as it may affect survival
· The type of fluid, the dose, the rate of administration, the timing and the duration of the treatment are all equally important
· balanced solutions have potentially several physiologically relevant advantages
· the “ideal” intravenous balanced solution contains acid-base, and electrolyte content equal to that of plasma, still unavailable
· The SPLIT trial, which compared the effects of a balanced solution (Plasma-Lyte 148) with those of 0.9% NaCl in critically ill patients showed the same results between the two treatments
Limitations of SPLIT trial:
· Population included, in vast majority, of post-operative patients, after elective surgery, with small incidence of co-morbidities, a low severity and including small percentages of high-risk patients
· Most of the patients in both groups received very small amounts of intravenous study fluids
· No data on the effects of the two treatments on plasma Cl– concentration have been measured, making therefore impossible to assess the effect on renal function
Magnesium:
Calcium:
Potassium:
Importance of Cl content in IV solution:
Renal transplantation & IV fluid:
Use of higher Cl concentration fluids in ICU patients was associated with higher risk of AKI & RRT. Balanced fluid was associated with lower inhospitable mortality compared to 0.9%NS.
Split study:
I. A critical appraisal of intravenous fluids- from the physiological basis to clinical evidence
1. Summarise this article
Definitions
“Balanced” solutions:
IV fluids with electrolyte composition close to that of plasma; so, they minimally affect acid-base status compared to 0.9% NaCl-related hyperchloremic metabolic acidosis.
Also used to indicate IV fluids with low chloride content compared to 0.9% NaCl.
Ideal balanced solution (not yet existing) is characterized by:
Minimal effects on acid-base status
Low chloride content
Adequate tonicity
Content of all electrolytes similar to that of plasma
Physicochemical approach (Stewart’s approach):
Components:
Water: solvent, high molality, v. weakly dissociated.
Strong electrolytes (Na+, K+, Cl–): completely dissociated in biologic solution (chemically non-reacting)
Weak, non-volatile acids (albumin & phosphates):partially dissociated in aqueous solution
Dissolved molecular CO2 in equilibrium with H2CO3 & its dissociation products.
Constraints under which an aqueous solution has to operate:
1.Electrical neutrality —+ve charges equal to -ve charges
2.Dissociation equilibria of incompletely dissociated substances
3.Conservation of mass —sum of concentrations of dissociated & un-dissociated forms of substance.
Variables influencing pH of fluids:
1. PCO2
2. Concentration of non-volatile weak acids.
3. The Strong Ion Difference (SID) —difference bet sums of strong cations (Na+, K+, Mg2+, Ca2+) & strong anions (Cl–, lactate, & other unmeasured anions); the formulas:
-SID = (Na+ + K+ + Ca2+ + Mg2+) – (Cl– + other strong anions)
-Abbreviated SID = (Na+ + K+) – (Cl–)
For crystalloid solutions (IV fluids with no weak acids), studies identified the below rules:
-If SIDinf is > baseline HCO3–, pH goes toward alkalosis during the IV infusion
-If SIDinf is < baseline HCO3–, pH goes toward acidosis
-If SIDinf = baseline HCO3–, pH will not change.
So, a “balanced” crystalloid should be a crystalloid solution that has an in-vivo SID (after the metabolism of organic anions) very similar to the patient HCO3– conc.
Effects of IV solutions on acid-base equilibrium:
1. May vary in different patients, having different HCO3– conc.
2. No solution is totally balanced (no “ideal” balanced solution).
Content of electrolytes other than Na+ & Cl– in “balanced” solutions:
Magnesium
Novel “balanced” crystalloids (Plasma-Lyte or Sterofundin ISO) contain magnesium, vs old generation (LR, AR or Hartmann) to guard against A/Es of ↓Mg (arrhythmias, CNS disturbance, ↓ GFR & RBF).
Calcium
Reasonable to include in an ideal “balanced” solution; ↓ Ca2+ is common in acutely ill patients; however, fear of Ca2+ precipitation when infused with other components is the rationale behind the use of Ca2+ -free IV balanced solutions.
Potassium
Hypokalemia is life-threatening in critically ill patients. IV K+ may be needed in severe cases.
All IV balanced solutions have K+ within normal ranges which may not cope with the normal daily intake K+ requirement.
Chloride content & pathophysiology:
Cl– is the main anion of the ECF & has a central role in acid-base balance.
It is the main anion of any IV crystalloid solution for resuscitation & volume maintenance.
Normal saline has a high content of Cl– (& Na+), & can induce hyperchloremic metabolic acidosis which, although benign & self-limiting, can potentiate any other possible causes of acidosis.
Cl– mediates vascular smooth muscle cell Ca2+-dependent contraction & may alter responses to vasoconstrictor agents in the kidney & may affect plasma renin activity & systemic BP.
TGF also depends on Cl– delivery, rather than Na+ delivery, to the distal tubule & its uptake by the macula densa.
Renal transplantation & IV fluids
Large volumes of IV fluids are typically used.
0.9% NaCl & 0.9% NaCl-based IV solutions are the most commonly used; the rationale was the use of a K+-free solution, to avoid ↑ K+ in patients with reduced K+ excretion.
Large amounts of 0.9% NaCl induces hyperchloremic metabolic acidosis, & potentially leading to ↑ K+ & ↓ renal function.
Data support the avoidance of 0.9% NaCl & other fluids causing metabolic acidosis in patients with ARF or CRF, as well as during KTX.
Data also support the safety of using K+- containing balanced solutions for volume replacement & maintenance in these settings.
Clinical evidence:
The SPLIT trial (October 2015)
The SPLIT trial (the 0.9% saline vs. Plasma-Lyte 148 for ICU Fluid Therapy) is the 1st large RCT comparing effects of 2 different crystalloids.
Primary outcome was to evaluate the % of patients with AKI in the 1st 90 days, & to assess other secondary outcomes.
Identical % of patients developed AKI in the 2 groups of treatments, & a similar use of RRT & in-hospital mortality.
Limitations:
Study population was mainly post-op patients, after elective surgery, with small incidence of co-morbidities, a low severity (APACHE II score), & only small % of high-risk patients (<5% for patients with sepsis).
No data on the effects of the 2 treatments on plasma Cl– conc.
Thank you
ummary of the article.
Although intravenous fluid is important in critical and emergency condition to restore the defective hemodynamics, also the following researches concentrate on the other aspect and effects of each fluid in different condition and the effect of colloids vs crystalloids, as such fluid may have survival impacts.
In general, regarding intravenous fluids, which was proofed to be definitely safe, may proofed to had some harm, so (normal saline is abnormal saline).
Balanced fluid is that fluid similar to plasma concentrations and minimally affect acid-bace balance, comparing to 0.9 normal saline with hyperchloremic metabolic acidosis.
Balanced solution;
they have an effect on acid-base equilibrium, or having normal chloride content
Stewarts approach and the mechanism of acid-base regulation during fluid infusion;
So solution with the above mentioned characteristic have the following criteria;
According to Stewart’s , there is 3 variables that affects pH of the fluid;
Crystalloid solution; not containing weak acids, they have the following character;
Electrolytes and balanced solutions, other than Na, Cl;
Magnesium;
Calcium;
Pottasium;
Chloride content solution and its physiological effects;
Renal transplantation and intravenous fluids;
Unbalanced IV solution in relation to outcome;
Intravenous chloride load in relation to outcome;
Balance IV solution in relation to safety and survival;
IV balanced solution had a survival advantages, and safety, compared to IV unbalanced solution, specially in patients with sepsis.
The Split trial;
Conclusion;
I liked reading your summary and conclusions.
Ajay
Thank u Prof
Summary of a critical appraisal of intravenous fluids- from the physiological basis to clinical evidence Balanced fluid is intravenous solutions whose electrolyte composition of plasma of plasma and minimally affect acid-base equilibrium.
Large randomized control trial comparing the effects on renal function and hospital survival of intravenous balanced solution, vs 0.9%Nacl in critically ill patients showing no difference.
Meanings of balanced solution:
Tow aspects characterizing balanced solution:
Minimal effect on acid-base physiological content of cl and osmolarity close to that of plasma
Two types of intravenous balanced solutions:
1. Solution with a minimal effect on acid-base equilibrium having SID close to value of 24-29mEqu/L
2. Those with a cl content equal or lower than 110mg.
First category belong to intravenous solution such as lactated Ringers, acetated Ringers, Hartmann’s solution, sterofindin ISO, Hextend, and tetraspam.
Second type of intravenous solution such as Lactated Ringer, acetated Ringer, Hartmann solution, plasma lyte ,El-oMel isoton, Isoplex and gelaspan.
Stewart pointed ant three constraints under which the system has to operate :
1. Electrical neutrality
2. Dissociation equilibrium – incompletely dissociated substances
3. Conservation of mass sum of concentration of its dissociated and un-dissociated forms
Electrolyte content and balanced solution:
Balanced solution contains electrolytes other than Na and cl, include magnesium, calcium, and potassium.
Magnesium:
Plasmatic contents of magnesium below 1.5 mg/dl is common in critical all patients which is increase incidence of cardiac arrhythmias.
Calcium:
Hypocalcaemia is common among acute ill patients calcium-free intravenous balanced solution because of the risk of calcium precipitation when infused through the same vascular access of either blood component or bicarbonate.
Potassium:
Hypokalaemia is recognized in critically ill patients.
All the available intravenous balanced solution present concentration of potassium with normal range .
The importance of chloride content and its pathophysiologic effects:
Chloride is the main anion of the extracellular fluid
Chloride is main anion of any crystalloid solution if given in supra physiologic levels, may have relevant clinical consequences.
Normal saline has a high non-physiological content of chloride and sodium which result in hyperchloremic metabolic acidosis, in critical ill patients worsen the clinical pictures.
Study on septic rats given intravenous 0.9 Nacl or balanced solution (plasma-lyte)
Development of hyperchloremic metabolic acidosis -associated with an increased IL6 levels, incident of acute kidney injury and higher mortality rate in those receiving 0.9 Nacl.
Renal transplantation and intravenous fluids:
A few randomized controlled studies have compared in patient undergoing renal transplantation, the IV 0.9 Nacl with IV administration of different balanced solutions-no significant difference in graft function . all studies observed a higher incidence of hyperchloremia and acidosis in patients receiving 0.9 Nacl compared to patients receiving intravenous balanced solution.
No difference was observed regarding plasmatic concentration of potassium and event of hyperkalaemia between the tow groups.
These data support avoidance of 0.9 Nacl and other possible IV fluid concern metabolic acidosis in patients with a cute or chronic renal faluire as well as during renal transplantation
Clinical evidence:
Lack of solid evidence supporting the use of specific types of crystalloids or colloids may rely on an unclear focus of the research conducted so far unbalanced intravenous solution in relating to outcome.
In large retrospective analysis examined patients undergoing major abdominal surgery and receiving only 0.9Nacl and compared them to the patients receiving only calcium free balanced solution on the day of surgery.
Patients receiving 0.9 Nacl showed a higher postoperative infection. A greater incidence of the use of renal replacement therapy and a higher un adjusted mortality rate as compared to those receiving IV balanced solutions.
Intravenous balanced solutions safer are all and do they provide a survival advantage as compared to intravenous unbalanced solutions especially in patients with sepsis in the SPLIT trial which is the first large randomized controlled trials comparing tow different types of crystalloid .
Conclusion:
The type of fluid, the dose, the rate of administration, the timing, and duration of the treatment
IV balanced solution have several physiological relevant advantage but clinically relevant outcomes is still unclear.
The Split trial:
The first large randomized trial comparing the effects of a balanced solution with those of 0.9% Nacl in critically ill patients showed equipoise between the two treatment
Further research needed on the presented mechanism underling the clinical effects on specific types of crystalloid solutions.
I liked reading your summary.
Ajay
WHAT DOES “BALANCED” SOLUTION MEAN?
IVF that is:
there are two categories of intravenous “balanced” solutions available:
The first category belongs to intravenous solutions such as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Sterofundin ISO, Hextend, and Tetraspan.
The second category belong to intravenous solutions such as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan.
STEWART’S APPROACH AND THE MECHANISMS REGULATING ACID-BASE DURING FLUID INFUSION:
The components of biological fluids:
ELECTROLYTE CONTENT AND BALANCED SOLUTIONS:
MAGNESIUM:
CALCIUM:
POTASSIUM:
THE IMPORTANCE OF CHLORIDE CONTENT AND ITS PATHOPHYSIOLOGIC EFFECTS
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS
CLINICAL EVIDENCE
Several clinical trials, even designed as prospective and randomized studies, had been conducted aimed at comparing several physiological effects of the two categories of intravenous solutions, whereas the scientific community still needed an understanding of whether such physiological effects (i.e. on acid-base equilibrium, on renal function and other organs) translated into a survival difference.
Although the SPLIT trial has made an important step ahead in this issue, many questions are still open regarding the possible efficacy (or neutral clinical effect) of intravenous balanced solutions.
THE SPLIT TRIAL
I liked reading your summary. Will you change your practice based on this article?
Ajay
Yes sir, NS need to be reconsidered.
Summarise this article
INTRODUCTION
Balanced solution is defined as solutions with low content of chloride or a solution with electrolyte composition closer to the composition of the plasma. It is minimally affects the acid base balance
A large randomized controlled trial (SPLIT trial) compared the effects on renal function and hospital survival of an intravenous balanced solution vs. 0.9% NaCl in critically ill patients and showed no differences between the two treatments
The aim of the study
Address the pathophysiology and pathophysiologic effects of these balanced solutions and presenting theclinical evidence to support their use
WHAT DOES “BALANCED” SOLUTION MEAN?
The ideal balanced intravenous solution should include organic anions (acetate, lactate, malate, gluconate, etc.) and be electrically neutral
Two categories of intravenous balanced solutions available now:
1. those with a minimal effect on acid-base balance (Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Sterofundin ISO, Hextend, and Tetraspan)
2. those with a Cl– content equal or lower than 110 mEq/L (Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan)
No ideal balanced solution available now
STEWART’S APPROACH AND THE MECHANISMS REGULATING ACID-BASE
Components of biologic fluids are water, strong electrolytes (Na+, K+, Cl–), weak, non-volatile acids (mainly albumin and phosphates), and carbon dioxide (CO2) system
Constraints of the system are electrical neutrality, dissociation equilibria, and conservation of mass
Stewart set up a system of different equations
ELECTROLYTE CONTENT AND BALANCED SOLUTIONS
In addition to Na+ and Cl– other electrolytes are magnesium, calcium and potassium
Hypomagnesemia may be associated with a higher incidence of cardiac arrhythmias and alterations of the cerebral nervous system. New balanced solutions (such as the crystalloid solutions Plasma-Lyte or Sterofundin ISO) contain magnesium
Ca2+-containing intravenous solutions have the risk of Ca2+ precipitation when infused through the same vascular access
THE IMPORTANCE OF CHLORIDE CONTENT AND ITS PATHOPHYSIOLOGIC EFFECTS
Smooth muscle vascular cell contraction
Increase in norepinephrine and angiotensin II-induced vasoconstriction
Tubuloglomerular feedbacK
Decreased dieresis, fluid overload and interstitial edema
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS
When comparing 0.9% NaCl with balanced solution containing K in patients undergoing renal transplantation, no significant difference in graft function but a higher incidence of hyperchloremia and acidosis
Avoidance of 0.9% NaCl and other fluids causing metabolic acidosis in patients with acute or chronic renal failure, as well as during renal transplantation is strongly recommended
CLINICAL EVIDENCE
Several clinical trials have addressed the question of whether the use of balanced solutions has beneficial effects as compared to the standard of care, sometimes even suggesting an improvement in survival
THE SPLIT TRIAL
The first large randomized controlled trial comparing the effects of a balanced vs. unbalanced solutions on renal function in critically-ill patients and showed no differences between the two treatments
CONCLUSIONS
Intravenous balanced crystalloids solutions when compared to 0.9% NaCl may affect clinical outcome and survival
Although balanced solutions have potentially several relevant advantages, the ideal balanced solution, with minimal effects on acid-base status, low chloride content, and adequate tonicity, is not yet available
SPLIT trial compared the effects on renal function and hospital survival of an intravenous balanced solution vs. 0.9% NaCl in critically ill patients and showed no differences between the two treatments
I liked reading your summary. Will you change your practice based on this article?
Ajay
Yes, definitely professor
Recent researches focus on the effects of different types of fluids on clinical outcomes, looking for the ideal IV fluid. IV balanced solutions is a novel solution available in practice.
Normally the body maintained in homeostasis, when an acute process alters such homeostasis, an IV fluids may become necessary, need to have appropriate tonicity, electrolytes composition and electrical-neutrality
Balanced” solutions are commonly defined as IVF having an electrolyte composition close to that of plasma. As such, they should minimally affect acid-base equilibrium, as compared to the commonly reported 0.9% NaCl-related hyperchloremic metabolic acidosis.
Recently, the term “balanced” solution has been also employed to indicate IVF with low chloride content, being the concentration of this electrolyte the most altered in 0.9% NaCl as compared to plasma, and based upon a suggested detrimental alteration of renal function associated with hyperchloremia.
“balanced” crystalloid solution should be a crystalloid solution that has an in-vivo SID, i.e., after the metabolism of organic anions, very similar to the patient HCO3– concentration.
Indeed, no ideal balanced solution has become available so far.
Categories of IV balanced solutions available:
1) those with a minimal effect on acid-base equilibrium, such as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Sterofundin ISO, Hextend, and Tetraspan.
2) those with a Cl– content equal or lower than 110 mEq/L. such as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan
The importance of chloride content and its pathophysiological effects:
The detrimental effects of hyperchloremia of IV (supra-physiologic ):
-NS induce hyperchloremic metabolic acidosis especially in critically ill patients, which may erroneously attributed to tissue hypoperfusion, a vicious cycle may derive, in which the treatment for the misdiagnosed acid-base disturbance with further fluid administration will worsen hyperchloremia and acidosis.
– Cl– mediates vascular smooth muscle cell Ca2+-dependent contraction.
– Modify vascular responses to vasoconstrictor agents in the kidney.
– Affect plasma renin activity and systemic blood pressure
– Reduction in renal blood flow and glomerular filtration rate.
– Decreased diuresis with fluid overload, decrease in systemic blood pressure.
– Abdominal discomfort and decrease in gastric mucosal perfusion by Cl–-mediated vasoconstriction.
– Increased plasma nitric oxide levels and pro-inflammatory cytokines.
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS:
-The choice of intravenous fluids in patients with renal failure is challenging.
– 0.9% NaCl, and 0.9% NaCl-based IVF, were the most commonly employed during KT, mainly for K free nature.
– All studies clearly documented a higher incidence of hyperchloremia and acidosis in patients receiving 0.9% NaCl as compared to patients receiving intravenous balanced solutions, while no significant difference in graft function was observed.
CLINICAL EVIDENCE
Several clinical trials have addressed the question of whether the use of balanced solutions has beneficial effects as compared to the standard of care, sometimes even suggesting an improvement in survival.
THE SPLIT TRIAL
The first large randomized controlled trial comparing the effects of a balanced vs. unbalanced solutions on renal function in critically-ill patients (SPLIT trial, the 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy).
The study was designed to evaluate, as the primary outcome, the proportion of patients with AKI during the first 90 days after enrolment, and to assess several clinically relevant endpoints as secondary outcomes.
They concluded a neutral effects of the two strategies in post-operative patients in term of AKI development, use of RRT and in-hospital mortality.
CONCLUSIONS
– Fluids should be considered as “drugs”.
– The type of fluid, the dose, the rate of administration, the timing and the duration of the treatment are all equally important.
– IV balanced solutions have potentially several physiologically relevant advantages, although translation into clinically relevant outcomes is still unclear.
Thank you
Intravenous fluids are either unbalanced (normal saline) or balanced solution (ringers lactate, plasmalyte)
Balanced solution has electrolytes (potassium, magnesium, calcium and most importantly chloride) composition near to that of plasma so can maintain plasma PH and osmolarity
A- Several studies on non-renal transplant patients reported that normal saline infusion is associated with the following adverse effects
B- In renal transplantation
C- SPLIT trial
Conclusions
Thank you
A critical appraisal of intravenous fluids- from the physiological basis to clinical evidence
——————————————————————————————————————-
What dose balanced solution?
– Two categories of intravenous “balanced” solutions available:
Stewarts approach and the mechanisms regulating acid -base during fluid
The components of biologic fluids:
Stewart pointed out three constraints:
Balanced” crystalloid solution should be a crystalloid solution that has an in-vivo SID, i.e., after the metabolism of organic anions, very similar to the patient HCO3– concentration.
Electrolyte content and balanced solutions:-
Renal transplantion and intravenous fluids
Clinical evidence
The SPLIT trial
Concolusion
Hi Dr Wadi,
I liked reading your detailed summary. Will you change your practice based on this article?
Ajay
Thank you very much Prof.Sharma
Certainly, after this article, the use of Normal Saline will be reconsidered, patients will be monitored and the required examinations will be performed for them.
Thanks alot for you Prof.Sharma
Certainly, after this article, t will be reconsidered, patients will be monitored and the required examinations will be performed for them.
Yes Dr Wadi
. Ajay
Thanks alot Prof.Sharma
SUMMARY
Introduction
The importance of hemodynamic balance in critically ill patient cannot be overemphasized, but beyond this, their survival and length of hospital stay can be significantly affected by the type of intravenous fluid use for them during resuscitation while in critical stage. The traditional known 0.9% normal saline has been frosted with complication like hyperchloremic metabolic acidosis and hence researchers are looking toward a more balance fluid for critically ill patient. To this end, a balanced solution has been defined as the intravenous fluid having an electrolyte composition as close as to that human plasma.
What is a balanced solution
-those with minimal effect on acid-base equilibrium, SID close to 24-29meq
-those with chloride content equal or lower than 110meq
Stewart’s approach
Electrolytes content in balanced solution
Clinical evidence
A) unbalanced intravenous solutions in relation to outcome
B) Intravenous chloride load in relation to outcome
C) Balance intravenous solution in term of safety and survival
The SPLIT trial
Conclusion
Fluid therapy should be henceforth seen as administration of drug that could have either negative or positive impact on patient safety and survival. The right decision on the type of fluids, whether traditional 0.9% saline that has been shown to have some side effect on patient or the use of a balanced solution with relatively close electrolytes content like plasma will always be key to optimal patient care
Hi Dr Issac,
I liked reading your detailed summary. Will you change your practice based on this article?
Ajay
IV balanced solutions are recently available in clinical practice.
What does balanced solution mean?
They are IV solutions with either minimal effect on acid base balance or with normal chloride content, they include crystalloids and colloids.
No ideal balanced solution is available, available solutions either belong to one category or have limitations due to relative hypotonicity.
Steward’s approach and the mechanism regulating acid base balance during fluid infusion:
The theoretical explanation of the effect of IV solutions on acid base balance showed that the effect of specific solution may vary in different patients according to their HCO3 concentration and yet, no available solution is totally balanced.
Electrolyte content and balanced solution:
Magnesium:
hypomagnesemia is common in critically ill patients and is associated with arrhythmia and CNS abnormalities.
Novel balanced solution as Plasma-Lyte include Mg and may be useful in clinical condition requiring large volume replacement.
Calcium:
hypocalcemia is the most common electrolyte imbalance in critically ill patients, leads to arrhythmia and alterations in CNS.
Balance solution containing Ca may be useful when large volume replacement therapy is needed but limited by possibility of Ca precipitation when infused with blood or bicarbonate in the same vascular access.
Potassium:
Hypokalemia is life threatening, associated with arrhythmia.
Available balanced solution have potassium concentration within the normal range and is not coping with daily potassium requirements.
The importance of chloride content and its pathophysiological effects:
It has a central role in acid base balance, normal saline contains high non-physiological content of chloride and result in hyperchloremic metabolic acidosis which may worsen clinical picture and mislead the cause of metabolic acidosis.
Other side effects of normal saline include affection of plasma renin activity and blood pressure, alter tubuloglomerular feedback, associated with decreased diuresis and natriuresis and lower cortical renal perfusion, it may lead to fluid overload, renal venous engorgement resulting in kidney hypoperfusion and damage.
Renal transplantation and IV fluids:
Recipients usually receive large amounts of IV fluids to increase intravascular volume and improve graft function, 0.9%NaCl is commonly used and may result in hyperchloremic metabolic acidosis which may lead to hyperkalemia and impair renal function
A RCT showed that 0.9%NaCl and balanced solutions are associated with similar graft function and higher incidence of acidosis with 0.9%NaCl.
It is suggested to avoid 0.9%NaCl in patients with acute or chronic renal failure and kidney transplants.
Clinical evidence:
Unbalanced IV solution in relation to outcome:
Large retrospective study showed that 0.9%NaCl is associated with higher incidence of postoperative infection, RRT and higher mortality rate compared to balanced solutions.
IV chloride load in relation to outcome:
A large prospective study showed that Cl restrictive strategy is associated with lower incidence of AKI and less use of RRT
Balanced IV solutions in relation to safety and survival:
Large retrospective study showed that hospital mortality decrease with with the increase in fraction of balanced solutions used in resuscitation.
The SPLIT trial:
A large RCT, double blinded, compare the effect of 0.9%NaCl and Plasma-Lyte 148in ICU patients receiving fluid therapy, the primary outcome was AKI.
It showed similar incidence of AKI, RRT and hospital mortality in both groups, however, it has several limitations as most of included patients were post operative with small rate of comorbidities, also small percent of included patients had sepsis, most patients received small amount of IV fluids and the effect on plasma Cl concentration was not measured so its potential role in AKI was not determined.
IV fluids should be considered as drugs, balanced solutions are more physiological but their clinical outcome is not proved yet
Hi Dr Heba,
I liked reading your detailed summary. Will you change your practice based on this article?
Ajay
In our practice, we prefer using lactated ringer for replacement in kidney transplant recipients postoperatively, the use of normal saline is restricted to certain indications.
Fluid therapy is determined according to each case individually
“Balanced” intravenous fluids have a composition similar to plasma. They should impact an acid-base balance of less than 0.9% NaCl-related hyperchloremic metabolic acidosis.
Recently, the phrase “balanced” solution has been used to designate intravenous fluids with low chloride content.
-The concentration of this electrolyte is most affected in 0.9% NaCl compared to plasma, and hyperchloremia is thought to harm renal function.
-The optimal balanced solution with minimum acid-base effects, low chloride level, and acceptable tonicity is not yet known.
WHAT DOES “BALANCED” SOLUTION MEAN?
assumptions have highlighted two elements of an ideal balanced intravenous solution.
First, All intravenous solutions (excluding 0.9% NaCl and pure dextrose-containing solutions) include organic anions (such as acetate, lactate, malate, gluconate, etc.) as precursors of HCO3 to balance the overall amount of positive charges, i.e., organic components quickly converted to HCO3.
This is due to the difficulties of incorporating HCO3 – directly in intravenous solution, since the technique to produce one (8.4% NaHCO3) is complicated.
Second, for electrical-neutrality and to prevent hypotonicity and a large Strong Ion Difference (SID, keeping the Na+-Cl– difference within 2430 mEq L-1), we have noticed the creation of balanced solutions with a supra-physiological concentration of Cl– .
Intravenous administration of significant volumes of 0.9% NaCl with a SIDinf of zero generates hyperchloremic metabolic acidosis, which may lead to hyperkalemia and compromise renal function due to hyperchloremia’s harmful consequences.
The result of previous studies:
A few randomized controlled investigations compared 0.9% NaCl with balanced solutions containing K+ within plasmatic limits.
All investigations found a greater frequency of hyperchloremia and acidosis in individuals receiving 0.9% NaCl compared to intravenous balanced solutions. Both groups had similar plasmatic K+ concentrations and hyperkalemia episodes.
These data strongly support avoiding 0.9% NaCl and other intravenous fluids causing metabolic acidosis in patients with acute or chronic renal failure and during renal transplantation.
They also provide the first solid data on the safety of using K+- containing balanced solutions for volume replacement and maintenance in this clinical setting.
UNBALANCED INTRAVENOUS SOLUTIONS IN RELATION TO OUTCOME:
-Show AD et al. compared patients having major abdominal surgery with 0.9% NaCl and Ca2+-free balanced fluids. Compared to intravenous balanced solutions, 0.9% NaCl patients had a higher incidence of postoperative infections, renal replacement treatment, and unadjusted mortality.
–Intravenous chloride load and outcome:
– In the first big prospective before-and-after trial, Yunos et al. compared a Cl-restrictive approach to fluid treatment of all consecutive ICU admissions over 6 months to a Cl-permissive strategy during the same 6 months the previous year.
-After introducing. Clinical studies on the use of fluids following kidney transplantation intravenous fluid approach reduced the quantity of 0.9% NaCl and gelatins provided to patients. The risk, injury, failure, loss, and end-stage kidney injury (RIFLE) criteria showed a decrease in AKI.
SAFE AND SURVIVAL-BASED INTRAVENOUS SOLUTIONS:
-the authors found a reduction in in-hospital mortality for any increase in the proportion of balanced solutions over the total volume of intravenous fluids administered during the first resuscitation (2 days).
– intravenous balanced solutions in combination with 0.9% NaCl were linked with decreased in-hospital mortality, equivalent duration of stay, and similar daily expenses.
SPLIT TRIAL:
-Despite the strong physiological rationale and the accumulation of data suggesting possible harms for the use of 0.9% NaCl for several years, the first large randomized controlled trial investigating a possible long-term and clinically relevant benefit of a balanced solution over an unbalanced solution for fluid resuscitation or volume maintenance has just been concluded.
-The first big randomized controlled experiment comparing balanced vs. unbalanced solutions on renal function in critically-ill patients (SPLIT trial, 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy) demonstrated no difference between the two.
Hi Dr Weam,
I liked reading your detailed summary. Will you change your practice based on this article?
Ajay
“BALANCED” SOLUTION ;
————————————–
Balanced solutions have been thought as the intravenous solutions causing minimal effects on acid-base equilibrium and have a physiological content of Cl–.
The “ideal” intravenous balanced solution including all the characteristics necessary for such definition (least effect on acid-base, and electrolyte content equal to that of plasma), has instead of have not yet become available.
There are two categories of intravenous “balanced” solutions available:
1- Those with a minimal effect on acid-base equilibrium, having a SID close to a value of 24−29 mEq L , such as Lactated Ringer’s, Acetated Ringer’s, Hart-mann’s solution, Sterofundin ISO, Hextend, and Tetraspan .
2- Those with a Cl– content equal or lower than 110 mEq L , such as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan .
LECTROLYTE CONTENT AND BALANCED SOLUTIONS;
——————————————————————————–
1-MAGNESIUM;
———————–
Both hypomagnesemia and ionized hypomagnesemia have been reported as being associated with a worse prognosis, especially for a non-recovery renal function after development of acute kidney injury (AKI) , as well as longer ICU stay and greater mortality .
Novel generation of “balanced” solutions have been developed with the inclusion of magnesium such as the crystalloid solutions Plasma-Lyte or Sterofundin ISO.
2-CALCIUM;
————————-
The prevalence of hypocalcaemia is 90% of critically ill patients. It causes alterations in muscle contractility, of peripheral and central nervous system function, cardiac arrhythmias.
It may be reasonable to include also Ca2+ in an ideal “balanced” solution, especially in the necessity of large volume replacement therapies.
A Ca2+-containing intravenous solution, carries a risk of Ca2+ precipitation when infused through the same vascular access of either blood components (precipitation of Ca2+ as Ca2+-citrate) or bicarbonate (as Ca2+- carbonate).
3-POTASSIUM;
————————–
All the available intravenous balanced solutions present a concentration of K+ within normal ranges, which does not necessarily cope with the normal daily intake K+ requirement .
THE IMPORTANCE OF CHLORIDE CONTENTAND ITS PATHOPHYSIOLOGIC EFFECTS;
——————————————————————————————————-
Chloride is the main anion of the extracellular fluid, and although its concentration in plasma is not as tightly regulated as that of Na+ and K+, it has a central role in acid-base equilibrium .
Normal saline, still one of the most employed intravenous crystalloid solutions, presents a high, non-physiological content of Cl– (and Na+), and has long been known to induce, as a side-effect of its liberal administration, hyperchloremic metabolic acidosis.
Even if it is often considered self-limiting and benign in nature, 0.9% NaCl-induced metabolic acidosis will be added to any other possible causes of acidosis, especially in critically ill patients, thereby potentially complicating or worsening the clinical picture.
(1) Is 0.9% NaCl intravenous solution more dangerous than intravenous balanced solutions?
————————————————————————————————-
In a large retrospective analysis, patients receiving 0.9% NaCl showed a higher incidence of postoperative infections, a greater incidence of the use of renal replacement therapy and a higher unadjusted mortality rate, as compared to those receiving intravenous balanced solutions.
(2) Is the total Cl– load intravenously administered to patients associated with worse outcome?
————————————————————————————————————–
Yunos et al., in the first large prospective before-and-after study, compared a Cl–-restrictive strategy, which was applied to fluid therapy of all consecutive ICU admissions over 6 months, to the Cl-permissive strategy over the same 6 months period of the previous year , the authors observed a reduction in the incidence of AKI, as assessed according to the Risk, Injury, Failure, Loss and End-stage kidney injury (RIFLE) criteria, especially in the injury and risk classes , as well as a reduction in the use of renal replacement therapies , even after adjustments for covariates.
Following the same hypothesis, although through a retrospective analysis of a large cohort of patients with SIRS, Shaw et al. observed a direct correlation of both the total amount of Cl– intravenously received and the associated increase in serum Cl– concentration during fluid resuscitation with an increased risk of death . Such an association appeared to be independent of the total amount of fluids administered.
(3) Are intravenous balanced solutions safer overall and do they provide a survival advantage as compared to intravenous unbalanced solutions, especially in patients
with sepsis, in whom early fluid therapy is a crucial part of the clinical treatment?
————————————————————————————————————-
This issue has been addressed by the same group of investigators in two large retrospective studies performed on the same large clinical database in two
different cohorts of patients with sepsis .
The first one;
———————
Showed a decrease in in-hospital mortality for any increase in the fraction of balanced solutions over the total amount of fluids intravenously received for the initial resuscitation (2 days), irrespective of the total amount of fluids received .
The second study;
————————–
The administration of intravenous balanced solutions in association with 0.9% NaCl appeared to be associated with a lower in-hospital mortality and a similar length of stay and costs per day as compared to the exclusive administration of 0.9% NaCl .
THE SPLIT TRIAL;
————————–
The first large randomized controlled trial comparing the clinical effects of two different types of crystalloids, was finally published, after the conclusion of patient enrolment in October 2014 .
The study was designed to evaluate, as the primary outcome, the proportion of patients
with AKI during the first 90 days after enrollment, and to assess several clinically relevant endpoints as secondary out- comes.
The study was conducted in 4 ICUs in New Zealand, 2,278 ICU patients in need of crystalloid fluid therapy were enrolled to receive either 0.9% NaCl or Plasma-Lyte 148, as a balanced solution, according to an alternating block of 7-weeks for each specific ICU.
The authors observed an identical proportion of patients developing AKI in the two groups of treatments (9.6% in the balanced solutions group vs. 9.2% in the 0.9% NaCl group), as well as a similar use of renal replacement therapy and in-hospital mortality.
The authors concluded, these findings, whereas showing neutral effects of the two strategies in post-operative patients, leave unsolved the potential effects of intravenous
balanced solutions in high-risk populations, more exposed to fluid therapy and at risk of AK
Dear Dr Ishag,
I liked reading your detailed summary. Will you change your practice based on this article?
Ajay
research in urgent and emergency care has experienced an incredible explosion of experimental and clinical studies.
“balanced fluids”:
Ø In intravenous solutions, electrolyte composition is closer to the plasma design, and balanced solutions should minimally affect acid-base equilibrium, compared to the commonly reported 0.9% NaCl-related hyperchloremic metabolic acidosis.
Ø . Fluid balance should equal the amount of fluid intake.
Ø Euvolemia defines the state of average body fluid volume.
Designing a fluid for intravenous administration:
Firstly: osmolarity, the need for electrolytes dissolved in the solution, appropriate tonicity (as close as possible to plasma osmolarity)
Secondly: an oncotic molecule dissolved in the solution, ideally aimed at maintaining the volume infused within the intravascular compartment.
There are two categories of intravenous “balanced” solutions available:
1) those with a minimal effect on acid-base equilibrium, having a SID close to a value of 24−29 mEq L-1
2) those with a Cl– content equal to or lower than 110 mEq L-1
the first category belongs to intravenous solutions such as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s, Sterofundin ISO, Hextend, and Tetraspan.
The second category belongs to intravenous solutions such as Lactated Ringer’s, Acetated Ringer’s, Hartmann’s, Plasma-Lyte, Elo-Mel Isotonic, Complex, and Gelaspan.
STEWART’S APPROACH AND THE MECHANISMS REGULATING ACID-BASE DURING FLUID INFUSION:
a) water, the solvent, which has a high molality (~55.5 mol kg-1) and is very weakly dissociated;
b) vital electrolytes (such as Na+, K+, Cl–), which are always entirely dissociated in biological solution and can be considered as chemically non-reacting;
c) weak, non-volatile acids (mainly albumin and phosphates), which are defined as substances only partially dissociated in an aqueous solution, according to their dissociation constant;
d) carbon dioxide (CO2) system — dissolved molecular CO2 in equilibrium with carbonic acid (H2CO3) and its dissociation products.
An aqueous solution, including solid electrolytes, non-volatile weak anions, and CO2, has to operate::
1-electrical neutrality
2-dissociation equilibria
3- conservation of mass —
three variables with the ability to influence, independently, the pH of biological fluids
1) the partial pressure of carbon dioxide (PCO2);
2) the concentration of non-volatile weak acids (ATOT), mainly albumin and phosphates;
3) the Strong Ion Difference (SID), defined as the difference between the sum of stable cations (mainly Na+, K+, Mg2+, Ca2+) and the sum of solid anions (mainly Cl–, lactate, and other possible unmeasured anions), according to the following formulas:
a) SID = (Na+ + K+ + Ca2+ + Mg2+) – (Cl– + other strong anions);
Abbreviated SID = (Na+ + K+) – (Cl–)
1) If SID inf is greater than the baseline concentration of plasma HCO3 –, then pH will tend toward alkalosis during the intravenous infusion;
2) If SID inf is lower than the baseline concentration of HCO3 –, then pH will tend toward acidosis during the intravenous infusion;
3) If SID inf equals the baseline concentration of HCO3 –, then pH will not change, regardless of the extent of the dilution.
ELECTROLYTE CONTENT AND BALANCED SOLUTIONS
MAGNESIUM:
Ø Hypomagnesemia, i.e., a plasmatic concentration of magnesium below 1.5 mg dL
Ø Severe hypomagnesemia may be associated with a higher incidence of cardiac arrhythmias, alterations in electrocardiographic findings, and modifications of the cerebral nervous system.
Ø “balanced” solutions (such as the crystalloid solutions Plasma-Lyte or Sterofundin ISO)
CALCIUM:
Ø Symptoms and clinical consequences of hypocalcemia are alterations in muscle contractility, peripheral and central nervous system function, and cardiac arrhythmias.
Ø treatment intravenous administration of either Ca2+-gluconate or Ca2+-chloride
POTASSIUM:
Ø Hypokalemia Symptoms include both alterations of muscle contractility and changes in cardiac rhythm.
Ø The standard route of K+ replacement is oral administration and may require intravenous administration in severe cases.
THE IMPORTANCE OF CHLORIDE CONTENT AND ITS PATHOPHYSIOLOGIC EFFECTS::
1- Chloride is the primary anion of the extracellular fluid
2-physiological features, Cl– is also the primary anion of any crystalloid solution given intravenously for fluid resuscitation and volume maintenance
3-Normal saline presents high, non-physiological content of Cl– (and Na+) and has long been known to induce, as a side-effect of its liberal administration, hyperchloremic metabolic acidosis
4- Cl– mediates vascular smooth muscle cell Ca2+-dependent contraction, may modify vascular responses to vasoconstrictor agents in the kidney and may affect plasma renin activity and systemic blood pressure.
5-Physiological mechanism maintains GFR constant and relatively independent from systemic blood pressure
6- the regulation of Na+ and water balance in the renal system, i.e., the tubule-glomerular feedback (TGF), is dependent on Cl– delivery, rather than Na+ delivery, to the distal tubule and its uptake by the macula densa
7-administration of 0.9% NaCl, as compared to balanced solutions, was associated with a lower diuresis and natriuresis and a lower renal artery blood flow velocity and cortical renal perfusion.
8-the infusion of Cl–-rich crystalloids may be fluid overload. Increased extracellular volume can cause an increase in central venous pressure and renal venous engorgement, which reduce trans-renal pressure gradient and flow, as well as interstitial edema, which increases renal interstitial pressure due to the relatively non-expansible kidney capsula]. Moreover, increased central venous pressure is commonly associated with increased intra-abdominal pressure, a situation that, in turn, can lead to fluid accumulation about reduction in venous return and cardiac output. All these mechanisms can cause kidney hypoperfusion and damage
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS:
Ø The choice of intravenous fluids in patients with renal failure (either acute or chronic) is particularly challenging,
Ø avoidance of 0.9% NaCl and other possible intravenous fluids causing metabolic acidosis in patients with acute or chronic renal failure, as well as during renal transplantation, and provide the first solid data on the safety of employing K+- containing balanced solutions for volume replacement and maintenance in this specific clinical setting
CLINICAL EVIDENCE:
Ø An important aspect related to the apparent lack of solid evidence supporting the use of particular types of crystalloids (or colloids
UNBALANCED INTRAVENOUS SOLUTIONS TO OUTCOME
Ø Firstly, is 0.9% NaCl intravenous solution more dangerous than balanced intravenous solutions
INTRAVENOUS CHLORIDE LOAD WITH OUTCOME:
Ø In a retrospective analysis of a large cohort of patients with SIRS, Shaw et al. observed a direct correlation between the total amount of Cl– intravenously received and the associated increase in serum Cl– concentration during fluid resuscitation with an increased risk of death.
BALANCED INTRAVENOUS SOLUTIONS TO SAFETY AND SURVIVAL:
Ø The administration of balanced intravenous solutions with 0.9% NaCl appeared to be associated with lower in-hospital mortality and a similar length of stay and costs per day compared to the exclusive administration of 0.9% NaCl.
THE SPLIT TRIAL:
Ø The SPLIT trial, the first large randomized controlled trial prospectively comparing the effects of a balanced solution (Plasma-Lyte 148) with those of 0.9% NaCl in critically ill patients, showed, unexpectedly, precise equipoise between the two treatments, although presenting significant limitations [9]. Whether or not balanced intravenous solutions are beneficial in high-risk patient categories (sepsis, trauma, burns), when exposed to more significant amounts of fluids, or when at higher risk of AKI still needs to be investigated.
Conclusion :
1-the type of solutions that may affect patient-centered clinical outcomes, including survival, such fluids should be considered “drugs.”
2-The type of fluid, the dose, the rate of administration, the timing, and the duration of the treatment are all equally important
3-.Intravenous balanced solutions potentially have several physiologically relevant advantages, but the actual translation of such rationale into clinically relevant outcomes still needs to be clarified.
Thank you, Nahla
Please do not copy and paste. Can you summarise the SPLIT trial, please? what is the conclusion
Balanced” solutions are commonly defined as intravenous fluids having an electrolyte composition close to that of plasma. It is well known that 0.9% saline is associated with hypercholremic metabolic acidosis so may be a balance solution is one with reduced content of chloride.
uptil now a balanced solution having low Chloride contact , no effect on acid base balance and adequate tonocity is not available.The available literature also does not support one solution upon other.
SPLIT trial
The first large randomized controlled trial comparing the effects of a balanced vs. unbalanced solutions on renal function in critically-ill patients (showed identical equipoise between the two treatments.
Among the entire balanced solutions available, either they belong to just one category (having an effect on acid- base equilibrium while having a normal Cl– content, and vice versa), or present some limitations, such as relative hypotonicity (in the case of Lactated Ringer’s, Acetated Ringer’s, or Hartmann’s solution).
Another important aspect related to the concept of “balanced” solutions concerns the content of specific electrolytes other than Na+ and Cl–, in particular of magnesium, calcium and potassium (K+).
Intravenous balanced solutions have potentially several physiologically relevant advantages, although the actual translation of such rationale into clinically relevant outcomes is still uncleared.
Whether or not the use of intravenous balanced solutions is beneficial in high-risk patient categories (sepsis, trauma, burns), when exposed to larger amounts of fluids or when at higher risk of AKI, still needs to be investigated as these questions were not answered by split trial.
Intravenous fluids should be considered as DRUGS and prescribed accordingly.
Thank you Zahid
Summary:
· “Balanced” solutions are those intravenous fluids having an electrolyte composition close to that of plasma with minimal affect on acid-base equilibrium.
· Mostly used 0.9% NaCl solution causes hyperchloremic metabolic acidosis.
· Now a days “balanced” indicates intravenous fluids with low chloride content.
· Though, the ideal balanced solution, with minimal effects on acid-base status, low chloride content, and adequate tonicity, is not yet available.
· Magnesium, Calcium, Potassium also very important to supplement in critically ill deficient patient.
· Chloride rich solution causing a vicious cycle to develop hyperchloremic metabolic acidosis as well as hyperkalemia.
· SPLIT trial, the 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy, showed identical equipoise between the two treatments.
· The type of fluid, the dose, the rate of administration, the timing and the duration of the treatment are all equally important. Intravenous balanced solutions have potentially several physiologically relevant advantages, although the actual translation of such rationale into clinically relevant outcomes is still unclear.
Hi Dr Ansary,
I liked reading your summary. Will you change your practice based on this article?
Ajay
Introduction
The colloid and crystalloid type can affect the patient’s prognosis.
It is debatable whether 0.9% normal saline could be harmful or not.
New IV balanced solutions are available.
Balanced fluids are those solutions with the closest electrolyte composition to the plasma compared to other fluids therefore will not majorly change the acid base equilibrium.
Those balance solutions have low content of chloride compared to normal saline which cause hyperchloremic metabolic acidosis.
SPLIT trial recently published no difference between the effect of use of normal saline and the use of Plasma Lyte 148 on critically ill patients.
Balanced solution definition
Roughly the amount of fluid loss from the body need to be substituted with an equal fluid intake to maintain the fluid balance.
When euvolemia is subjected to dysregulation ,IV fluid administration would be needed.
This IV fluid osmolarity need to be adjusted to be as close as possible to plasma also an oncotic molecule dissolved in the solution need to keep this fluid intravascular.
The solution electrolyte content has to be similar to plasma electrolyte content theoretically.
The solution has to be electrically neutral .
All IV solutions have included organic anions except normal saline and pure dextrose-containing solutions.
Balanced solutions with a relative above physiological
concentration of Cl– to preserve the electric neutrality.
Balanced solutions had to be done with normal (or lower than normal) Cl– content.
Having solutions with acid base balance coexisting with low CL content is difficult.
As each one can be available separately where solutions with least effect on acid base balance including Lactated Ringer’s, Acetated Ringer’s, Hart mann’s solution, Sterofundin ISO, Hextend, and Tetraspan.
Solutions with low chloride includeLactated Ringer’s, Acetated Ringer’s, Hartmann’s solution, Plasma-Lyte, Elo-Mel Isoton, Isoplex, and Gelaspan.
Stewart’s approach and the mechanisms regulating acid base balance during fluid infusion.
Includes
· water as a solvent with very low dissociation
· Electrolytes that are strong but non reactive.
· Weak non volatile acids.
· CO2 system involving dissolved molecular CO2
in equilibrium with carbonic acid (H2CO3)
Also pointed to 3 constraints that must be applied to solutions
Which are
Electric neutrality, dissociation equilibrium and conservation of mass.
He discovered 3 variables that can affect the PH of the biological fluids independently which are the partial pressure of carbon dioxide (PCO2); the concentration of non-volatile weak acids (ATOT) and the Strong Ion Difference (SID).
The SID inf and the content of weak acids intravenous fluids can change both SID and ATOT of plasma, and plasma pH .
For crystalloid solutions
If SID inf is more than plasma HCO3 then pH will tend toward alkalosis and the opposite is correct.
If SIDinf equals the baseline concentration of HCO3, then PH will be constant.
Electrically charged ionic colloids have a greater SIDinf
The effect of a specific
Specific Intravenous solution’s effect on acid-base is variable.
There is not ideal balanced solution.
Electrolytes in balanced solution
Magnesium
Hypomagnesemia can lead to cardiac arrhythmia and alteration of CNS function and it is associated with low GFR and renal blood flow.
Balance solutions include Mg opposite to older solutions.
Calcium
Hypocalcemia is the most common electrolyte disturbance in acutely ill patients presenting by cardiac arrhythmias and muscular contractility alterations .
So balanced solutions contain Ca but it can precipitate in the intravascular access, rendering the importance of having Ca free balanced solutions.
Potassium
Hypokalemia is a life threatening electrolyte disturbance in critically ill patients presented by cardiac arrhythmias and change of the muscular contractility .
Most solutions contain potassium concentration within normal range .
Therefore normal saline is the preferred solution of use in AKI and CKD cases but many trials had proofed that this tendency is not correct.
Chloride pathophysiological effects
Cl- has a significant impact on acid base equiliribium.
Supraphysiological levels of Cl-content in IV fluids have an important clinical impact.
Normal saline being the most popular fluid use can cause hyperchloremic metabolic acidosis ,it is self limited but it can superadd metabolic acidosis particularly in critically ill patients.
The critically ill patients are liable to a vicious circle of metabolic acidosis as hypoperfusion is the most common cause of metabolic acidosis in those cases leading to misdiagnosis and infusing the patient with more normal saline that is in fact could by the actual cause of hyperchloremic metabolic acidosis therefore worsening the metabolic acidosis.
Also another hazardous effect of the Cl- high concentration in normal saline is affecting the Ca in the smooth muscles of vessels leading to alteration of vasoconstriction in the renal vessels ,affecting GFR and RBF.
Tubuloglomerular feedback is dependent on Cl delivery to the distal tubule rather than Na delivery.
This feedback is responsible for maintaining the GFR regardless of systemic blood pressure changes , preserving salt and water
It was noticed that normal saline infusion is associated with less diuresis and naturesis and more fluid overload leading to kidney hypoperfusion compared to balanced solutions.
Normal saline as Cl rich fluid had a negative effect on healthy volunteers in the forum of abdominal cramps and on elderly candidates in the forum of decreasing gastric mucosa perfusion.
Hyperchloremic acidosis effect on immune system was tested on septic animals receiving HCL leading to increase of plasma nitric oxide and proinflammatory cytokines.
Another study compared normal saline effect to plasma lyte effect on septic rates ,it revealed that normal saline group experienced hyperchloremic metabolic acidosis leading to increased IL6 , AKI and higher mortality rate.
A retrospective study analysed patient’s data postoperatively concluded that those whom recived normal saline were more susceptible to postoperative infection compared to those who received plasma lyte solution.
IV fluids in Renal transplant
Renal transplant recipients are receiving large amount of fluid replacement to enhance graft function in most centers.
Normal saline is the chosen solution due to being K free thereby avoiding hyperkalemia in such risky patients .
But in fact normal saline can cause hyperkalemia through hyperchloremic acidosis.
A study compared the use of normal saline to the use of balanced solutions with plasmatic range potassium in renal transplant candidates and concluded that normal saline group had hyperchloremic acidosis in comparison to the other group and they found that there was no difference in graft function and potassium levels between the 2 groups.
This study shedded the light on the safety of using K containing balanced fluids for volume replacement in transplant candidates rather than the use of normal saline.
Clinical evidence
Recently the first large randomized controlled trial was conducted assessing the long-term clinically relevant benefit of a balanced solution over an unbalanced solution for fluid resuscitation .
Till now there is no a solid evidence to recommend the use of certain crystalloids (or colloids) due to the unclear focus of the research conducted so far.
The outcome of unbalanced solutions
A study conducted on patients undergoing major abdominal surgeries ,compared the outcome in one group that received normal saline and another group that received Ca free balanced solution , they noticed higher rate of postoperative infection and higher need for RRT and mortality in the normal saline group .
The outcome of IV Cl- load
Yunos et al compared the use of Cl restrictive strategy of fluid therapy for ICU cases versus Cl permissive strategy in a 6 months prospective study , concluding that cases on Cl restrictive fluid therapy experienced reduction of AKI as per RIFLE criteria and reduction of the need of RRT .
Shaw et al. revealed a direct association of both the total amount of Cl– given IV received and the increased risk of death.
Balanced IV solution effect on safety and survival
IV balanced solutions are safer and provide a shorter hospital stay and overall outcome particularly in patients having sepsis as proved by studies.
SPLIT trial
This trial is a large randomised controlled study conducted on 2015 on ICU patients comparing the clinical outcomes of using normal saline versus using plasma lyte , they published that there was no significant difference between the 2 studies groups regarding AKI, the need of RRT and the in hospital mortality.
This trial has limitations as including postoperative patients after elective surgeries with small comorbidity incidence and less risk APACHE II score while high risk cases were small in number.
Those cases received small volume of tested IV solutions and Cl levels effects were not evaluated.
Conclusion
The type of fluid used for fluid replacement , the amount , duration and multiple aspect can affect survival outcome of the patients.
Fluids must be considered as drugs.
The ideal balanced solution is not available yet.
The benefit of use of balanced IV fluids in large amounts for critically ill patients needs further investigations.
Hi Dr Doaa,
I liked reading your detailed summary. Will you change your practice based on this article?
Ajay
Thanks prof, Sharma
Still , the large study SPLIT not showing different between NS and balanced solution but better to deal case by case decision
Intravenous balanced solutions: from physiology to clinical evidence.
Most recent studies looking for the ideal balanced intravenous solution which is characterized by less harmful effect on acid-base equilibrium and near to physiological character of the plasma.
Simply, term of balanced solution mean low chloride solution, as hyperchloremia in 0.9 NACL has harmful effect on renal function but SPLIT trial showing no differences between the two treatments.
WHAT DOES “BALANCED” SOLUTION MEAN?
–Solution with dissolved electrolytes as close as possible to plasma osmolarity.
-Solution with an oncotic molecule dissolved which maintain volume infused intravenously.
-Most IV solution contain organic anions as precursors of HCO3– to balance the total content of positive charges.
-Intravenous solution with a normal (or lower than normal) Cl– content, equal or lower than 110 mEq L.
ELECTROLYTE CONTENT AND BALANCED SOLUTIONS.
MAGNESIUM.
Hypomagnesemia is common in both critically ill patients and patients admitted to ICU, which may be may be associated with a higher incidence of cardiac arrhythmias and other CNS manifestations, also hypomagnesemia have been reported as being associated with a worse prognosis, especially for a non-recovery renal function after development of acute kidney injury (AKI) and still no studies have ever investigated the effects of balanced solutions on the incidence of hypomagnesemia.
CALCIUM.
Hypocalcemia is corrected by Replacement of plasma Ca2+ content which is obtained generally with the intravenous administration of either Ca2+-gluconate or Ca2+-chloride and not in balanced solution due to risk of Ca2+ precipitation.
POTASSIUM.
Hypokalemia one of the common complications in ill- critical patient and the common route of K+ replacement is oral administration, intravenous administration may be required in severe cases.
THE IMPORTANCE OF CHLORIDE CONTENT AND ITS PATHOPHYSIOLOGIC EFFECTS.
Chloride has a central role in acid-base equilibrium so it is considered the main anion of any crystalloid solution given intravenously for fluid resuscitation and volume maintenance as normal saline which contain high, non-physiological content of Cl– (and Na+) that lead to hyperchloremia metabolic acidosis and we should keep it in mind to avoid mis-diagnosis .
Cl– toxicity has bad impact on small blood vessels and vasoconstriction and affect renal blood flow and affect GFR.
slower diuretic response to the infusion of Cl–-rich crystalloids may be fluid overload, increased central venous pressure is commonly associated with increased intra-abdominal pressure all these factors lead to kidney perfusion.
Hyperchloremic acidosis has also many harmful impacts on GIT, immune system and inflammatory response.
RENAL TRANSPLANTATION AND INTRAVENOUS FLUIDS.
Most common IV fluid used post KTX is 0.9 NACL, mainly because its potassium free solution in patient still has impaired renal function, correspondingly normal saline lead to Hyperchloremic acidosis which lead to hyperkalemia, but some studies shown that no difference bet balanced solution and 0.9 NACL regarding hyperkalemia.
CLINICAL EVIDENCE.
Large randomized control study e.g. SPLIT shown no differences between the two treatments , unless the physiological effect is clear so , we still need large randomized studies to focus on this issues from different aspects.
UNBALANCED INTRAVENOUS SOLUTIONS IN RELATION TO OUTCOME.
Some studies shown that patients receiving 0.9% NaCl showed a higher incidence of postoperative infections, a greater incidence of the use of renal replacement therapy and a higher unadjusted mortality rate, as compared to those receiving intravenous balanced solutions.
INTRAVENOUS CHLORIDE LOAD IN RELATION TO OUTCOME.
Restrictive CL balanced solution versus high CL solution shown reduction in the incidence of AKI, as assessed according to the Risk, Injury, Failure, Loss and End-stage kidney injury (RIFLE) criteria, especially in the injury and risk classes.
BALANCED INTRAVENOUS SOLUTIONS IN RELATION TO SAFETY AND SURVIVAL.
One large retrospective studies shown that intravenous balanced solutions in association with 0.9% NaCl appeared to be associated with a lower in-hospital mortality and a similar length of stay and costs per day as compared to the exclusive administration of 0.9% NaCl.
THE SPLIT TRIAL.
(the 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy), that compare the clinical effects of two different types of crystalloids on 2,278 ICU patients to detect the primary outcome, the proportion of patients with AKI during the first 90 days, showing the same effect in developing AKI, use of renal replacement therapy and in-hospital mortality.
Conclusion.
Balanced solution is has the least effect on acid-base, and electrolyte content equal to that of plasma, solution is a drug that also has side effects so balanced solution is considered is beneficial in high-risk patient categories (sepsis, trauma, burns), when exposed to larger amounts of fluids or when at higher risk of AKI, still needs to be investigated.
Hi Dr Saad,
I liked reading your summary. Will you change your practice based on this article?
Ajay
Thanks prof, Sharma
Still , the large study SPLIT not showing difference between NS and balanced solution but we are design our IV fluid case by case, trying to avoid NS induced hyperchloremic metabolic acidosis or hyperkalemia by ringer lactate and we prefer LR with critical cases than NS.
Hi Dr Ben,
I liked reading your summary. Will you change your practice based on this article?
Ajay
Sure prof , the trend toward balanced is solution is now the norm