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Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit The SPLIT Randomized Clinical Trial


There have been a lot of controversies about the safety of crystalloid fluid therapy in acutely ill patients. Several observational studies have shown an increased risk of acute kidney injury (AKI) and hyperchloremic acidosis with the use of normal saline (NS). Some observational studies have shown a decreased risk of AKI when using plasmalyte solution. This trial was conducted to evaluate, which is the best fluid to give to our patients who need fluid therapy in intensive care unit (ICU)?


Young P, Bailey M, Beasley R, Henderson S, Mackle D, McArthur C, McGuinness S, Mehrtens J, Myburgh J, Psirides A, Reddy S, Bellomo R; for the SPLIT Investigators and the ANZICS CTG. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit The SPLIT Randomized Clinical Trial. JAMA. 2015;314(16):1701-1710. doi:10.1001/jama.2015.12334.



NS is the most common intravenous fluid used in fluid resuscitation in critical care unit, but it is associated with increased risks of AKI and mortality. This study was conducted to evaluate whether the use of balanced solution decreases the risk of AKI?


Prospective, multicenter, double blind, double cross over and cluster randomized.Done in 4 intensive care units in New Zealand (3 ICU general medical and surgical, 1 CTVS ).

Inclusion- All ICU patients requiring crystalloid therapy.

Exclusion- Established AKI, plans for renal replacement therapy (RRT) in the following days, or patients already receiving RRT or expected to require RRT in next 6 hours, patients admitted to ICU for organ donation.

Study period- From April 2014 to October 2014,2278 patients.

Groups- 1162 in buffered crystalloid group,1116 in saline group. Baseline character were same in both group in terms of age, comorbidities, time from ICU admission, volume of fluid administered. Rate and frequency of fluid determined are decided by treating physician. Both groups received same amount of fluid(2000ml)


Primary- Proportion of patients with AKI

Secondary-Incidence of RRT, Mechanical ventilation, ICU length of stay ,ICU readmission, all cause mortality.


Primary outcome -

102 of 1067(9.6%) in buffered crystalloid group as compared to 94 of 1025(9.2%)in saline group developed AKI within 90 days (absolute difference,0.4%,RR 1.04,P=0.77).

Secondary outcome -

RRT Requirement- 3.3% buffered crystalloid vs 3.4% in saline group(P=0.91,RR-0.96). The indication for initiation of RRT was also similar between two groups.

In-Hospital mortality- Buffered Crystalloid Group 87/1152 (7.6%),Saline group 95/1110 (8.6%) Absolute Difference -1.0% (95% CI -3.3% – 1.2%),RR 0.88 (95% CI 0.67 – 1.17; p = 0.40). ICU readmission during index stay- 6.9% vs 5.1%.

All cause mortality and cause specific mortality-

ICU (6.6%VS 7.2%), Hospital (7.6% vs 8.6%), non significant.


Among patients receiving crystalloid fluid therapy in the ICU, use of a buffered crystalloid compared with saline did not reduce the risk of AKI. Further large randomized clinical trials are needed to assess efficacy in higher-risk populations and to measure clinical outcomes such as mortality.


  1. Blinding of the study.

  2. Statistical analysis was planned before completing recruitment which helped to eliminate analysis bias.

  3. Primary end point was based on a serum creatinine measurement which helped to eliminate observer bias.

  4. Risk of selection bias was minimal because 99.3%of all eligible patients were included in the study and analysed.

  5. Intervention and controlled fluids are packed with bags 1000ml labeled fluid A or fluid B.


  1. Even though clinicians were blinded, 2/3 were able to guess the assigned treatment. The development of hypercholoremic acidosis in patients receiving saline may have un-blinded some physicians.

  2. More than 90% of patients had received fluids, mostly PL, prior to study enrollment. This fluid was not considered in the analysis.

  3. No sample size calculations performed.

  4. The purpose of fluid administration is not stated.

  5. This was a heterogenous population with a low incidence of AKI, which makes it difficult to extrapolate findings to higher-risk groups.

  6. More than half of the study population were elective post surgical cases. So the findings can not be extrapolated to unlike general ICU patients.

  7. Very low percentage of patients have sepsis (4%) and trauma (4%).




Though normal saline can cause hyperchloremic acidosis and AKI in large doses, from this study, it is clear that administration upto 2 litre normal saline in elective post surgical or less sick patients is without any significant risk of kidney injury.




                                                                                                                                                                             Dr Biswabikash Mohanty

                                                                                                                                                                                                                        MD, FNB (CCM)






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