Key messages
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Using buffered solutions (which contain substances that help keep acid levels in the blood stable) for critically ill adults and children makes little or no difference to the number of them who die while in hospital, when compared to using 0.9% saline (a solution of salt in water).
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Using buffered solutions rather than saline probably makes little or no difference to the number of patients who have sudden damage to the kidney that affects how it works (acute kidney injury).
What is resuscitation in critically ill patients?
Resuscitation is a set of medical procedures used to treat patients who experience a serious and urgent health problem, especially to restore their heartbeat and breathing.
What are intravenous (into a vein) fluid therapies used in resuscitation?
Fluid therapies are water-based salt solutions. They are used as a medical treatment to make sure that the body's organs and tissues receive enough blood flow, receive enough fluids, and maintain electrolyte (salts) balance. Fluid therapy is the cornerstone of treatment for many serious conditions, like sepsis (life-threatening response of the body to infection), burns, trauma (injury), or undergoing emergency surgery.
Crystalloids are a type of fluid therapy that is commonly used and include two groups of solutions.
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Buffered crystalloid solutions contain substances (buffers, like lactate, bicarbonate, or acetate) that help to maintain a constant pH (acidity) level in the blood
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0.9% saline has an osmolarity (concentration of dissolved substances) similar to blood, although its electrolyte composition is not identical. It contains only sodium and chloride, which are in a higher proportion than in blood.
What did we want to find out?
We wanted to find out the benefits of using buffered solutions in adults and children who are very seriously (critically) ill (including those with sepsis, trauma, burns, or shock) and have not had elective (planned) surgery. We also wanted to know if buffered solutions cause any unwanted effects.
What did we do?
In July 2023, we searched medical databases for relevant studies known as randomised controlled trials. We looked again in June 2025, but the studies we identified from the last two years have not yet been included in our findings.
We combined the results of the studies and rated our confidence in the evidence they provide, based on factors such as their size and the methods they used.
What did we find?
We found 34 studies that involved 37,859 adults and children with critical illness who required intravenous fluid therapy. Most of the studies were medium-sized (between 22 and 230 people), but the largest two studies together involved 26,854 people. The studies took place in 16 countries.
Main results
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Compared with 0.9% saline, buffered solutions make little or no difference to the risk of death during the hospital stay.
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Buffered solutions probably make little or no difference to the risk of acute kidney injury.
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The evidence is very uncertain about the effect of buffered solutions on the risk of organ system dysfunction (body systems failing to perform normally).
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The evidence is also very uncertain about the effect of buffered solutions on the electrolytes sodium and potassium. Buffered solutions may reduce chloride concentration, and may increase pH levels and bicarbonate concentration.
What are the limitations of the evidence?
We are confident in the evidence that compared the number of deaths when buffered solutions were used compared to when 0.9% saline was used.
We are moderately confident in the evidence for acute kidney injury. We do not have complete confidence because the assessment of kidney function (how well the kidneys work) may have been influenced by doctors knowing whether someone taking part in the study received a buffered solution or 0.9% saline. It is possible that future studies could find different results.
We are not confident in the evidence about organ system dysfunction because it is based on only a few cases, and the study that contributed most to the results did not clearly report the number of people or the results, and we could not get more information.
We are not confident in the evidence about electrolyte abnormalities because the evidence was based on too few studies to be certain about the findings.
Who paid for the studies?
Twenty of the studies were funded by governments or non-profit organisations; four received mixed funding; one was funded by a company, but it was not clear what business the company was in; and nine studies gave no details about funding.
How up to date is this review?
This review updates our previous review. The evidence in it is based on searches we did in July 2023. We conducted a further search in June 2025 and will include those results in our next update of the review.
Read the full abstract
Fluid therapy is one of the main interventions provided for critically ill patients, although there is no general consensus regarding the type of solution. Among crystalloid solutions, 0.9% saline is the most commonly administered. Buffered solutions may offer some theoretical advantages (less metabolic acidosis, less electrolyte disturbance), but the clinical relevance of these remains unknown.
Objectives
To assess the effects of buffered solutions versus 0.9% saline for resuscitation or maintenance in critically ill adults and children.
Search strategy
We searched CENTRAL, MEDLINE, Embase, CINAHL, and four trial registers in July 2023. We checked references, conducted backward and forward citation searches for relevant articles, and contacted study authors to identify additional studies. Although we updated our search in June 2025, the results have not yet been fully incorporated into the review.
Selection criteria
We included randomized controlled trials (RCTs) with parallel or cross-over design examining buffered solutions versus intravenous 0.9% saline in a critical care setting (resuscitation or maintenance). We included studies on participants with critical illness (including trauma and burns) or undergoing emergency surgery during critical illness who required intravenous fluid therapy. We included studies of adults and children. We included studies with more than two arms if they fulfilled all of our inclusion criteria. We excluded studies performed in persons undergoing elective surgery and studies with multiple interventions in the same arm.
Data collection and analysis
We used Cochrane's standard methodological procedures. We assessed our intervention effects using random-effects models, but when one or two trials contributed to 75% of randomized participants, we used fixed-effect models. We reported outcomes with 95% confidence intervals (CIs).
Main results
We included 21 RCTs (20,213 participants) and identified three ongoing studies. Three RCTs contributed 19,054 participants (94.2%). Four RCTs (402 participants) were conducted among children with severe dehydration and dengue shock syndrome. Fourteen trials reported results on mortality, and nine reported on acute renal injury. Sixteen included trials were conducted in adults, four in the paediatric population, and one trial limited neither minimum or maximum age as an inclusion criterion. Eight studies involving 19,218 participants were rated as high methodological quality (trials with overall low risk of bias according to the domains: allocation concealment, blinding of participants/assessors, incomplete outcome data, and selective reporting), and in the remaining trials, some form of bias was introduced or could not be ruled out.
We found no evidence of an effect of buffered solutions on in-hospital mortality (odds ratio (OR) 0.91, 95% CI 0.83 to 1.01; 19,664 participants; 14 studies; high-certainty evidence). Based on a mortality rate of 119 per 1000, buffered solutions could reduce mortality by 21 per 1000 or could increase mortality by 1 per 1000. Similarly, we found no evidence of an effect of buffered solutions on acute renal injury (OR 0.92, 95% CI 0.84 to 1.00; 18,701 participants; 9 studies; low-certainty evidence). Based on a rate of 121 per 1000, buffered solutions could reduce the rate of acute renal injury by 19 per 1000, or result in no difference in the rate of acute renal injury. Buffered solutions did not show an effect on organ system dysfunction (OR 0.80, 95% CI 0.40 to 1.61; 266 participants; 5 studies; very low-certainty evidence). Evidence on the effects of buffered solutions on electrolyte disturbances varied: potassium (mean difference (MD) 0.09, 95% CI -0.10 to 0.27; 158 participants; 4 studies; very low-certainty evidence); chloride (MD -3.02, 95% CI -5.24 to -0.80; 351 participants; 7 studies; very low-certainty evidence); pH (MD 0.04, 95% CI 0.02 to 0.06; 200 participants; 3 studies; very low-certainty evidence); and bicarbonate (MD 2.26, 95% CI 1.25 to 3.27; 344 participants; 6 studies; very low-certainty evidence).
Authors' conclusions
Buffered solutions do not reduce overall (in-hospital) mortality compared to 0.9% saline solution in critically ill patients, and probably do not reduce acute renal injury. Evidence for organ system dysfunction and electrolyte disturbances is of low or very low certainty.
We have high-certainty evidence about the outcome of mortality, but further trials are needed to clarify the impact of buffered solutions on acute renal injury and other outcomes. Future studies should involve underrepresented populations (paediatric, neurocritical, female) and adopt standardised, patient-centred outcome measures to broaden the evidence base.
Once the 38 relevant ongoing studies are published and the nine studies that await classification are evaluated, the inclusion of new studies in this review may alter its conclusions regarding acute renal injury, organ dysfunction, and electrolyte disturbances.
Funding
The original review and this update received no funding.
Registration
This 2026 review is an update of the 2019 review. Both versions were conducted according to the published protocol.
Protocol (2016) available at https://doi.org/10.1002/14651858.CD012247
The protocol was registered with PROSPERO (CRD42016045988).
Original review (2019) available at https://doi.org/10.1002/14651858.CD012247.pub2
