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

Young PBailey MBeasley RHenderson SMackle DMcArthur CMcGuinness SMehrtens JMyburgh JPsirides AReddy SBellomo RSPLIT InvestigatorsANZICS CTG.

PMID: 26444692

Happy new year Nephrology Nerds. The first journal club of 2016 will be January 12th at 8pm EST and January 13th 8pm GMT.

JAMA has made the article open access for NephJC. Follow this link. JAMA is also going to offer prizes for the best tweet from the Jan 12th and Jan 13th discussions so warm up those twitter clients!


Background:  There are few interventions in the practice of Medicine more fundamental than the administration of intravenous fluids.  In recent years however, the debate between the renal safety of the use of 0.9% Sodium Chloride versus Buffered Crystalloid Solutions has become more heated.  Prospective (but not randomized) data had suggested that the use of more physiologically balanced solutions as compared with chloride-rich regimens significantly decreased the rate of Acute Kidney Injury (AKI), need for renal replacement therapy (RRT) and mortality in critically ill patients (JAMA, summary from PBFluids). This was supported by human studies demonstrating reductions in renal blood flow and cortical perfusion after saline administration (link). However a blinded, randomized controlled trial was lacking until Young published the results of the SPLIT trial.

More background from NephMadness 2014

Study Design:  This was a prospective, multicentre, blinded, cluster randomized crossover study, which was conducted in four separate ICUs in New Zealand.  All ICU patients deemed to require crystalloid fluid therapy were eligible for enrolment.  Patients already on or imminently expected to require RRT were excluded, together with patients admitted solely for organ retrieval or for palliative care purposes.  Centres were provided with 1000ml bags of Plasmalyte 148 and 0.9% NaCl.  During the 28 weeks of the study centres were randomized to alternate their use of fluid every 7 weeks, meaning that each centre used each fluid twice. The treating clinician determined the volume and rate of fluid infusion.  Primary outcome was AKI defined by the RIFLE system and secondary outcomes included incidence of RRT and in-hospital mortality.

Findings:  Of the 2278 eligible patients, 1162 received Plasmalyte 148 and 1116 received 0.9% NaCl.  Both groups had similar demographics in terms of spread of age, sex, admission reason and APACHE score, and both received similar volumes of IV fluid. 

Primary Outcome: At 90 days there was no significant difference in those who had developed AKI with 102/1067 (9.6%) of the Plasmalyte group and 94/1025 (9.2%) in the 0.9% Sodium Chloride group (absolute difference 0.4%, RR 1.04, p=0.77).

Secondary Outcomes: There was no significant difference in RRT use, 38/1152 (3.8%) in the Plasmalyte group versus 38/1110 (3.4%) in 0.9% NaCl group (RR 0.96 P=0.91) nor was there a difference in in-hospital mortality 87/1152 (7.6%) versus 95/1110 (8.6%) (RR 0.88 p=0.4). 

Discussion:  The investigators should be commended for their double blind design, and practical, real world nature of fluid administration in this heterogeneous group of critically ill patients.  This was the largest trial of its kind.  Caution however must be exercised in the study’s extrapolation outside of the ICU setting.   Given that the majority of those included were elective surgical patients there was an inherently low risk of AKI, with few fitting into the typical acidotic septic medical-ICU patient group.  The study also ignored the fact that 90% of those included had received fluid (mainly buffered crystalloid) prior to admission to ICU and that total fluid exposure in the study was only 2L. Is this enough to cause harm? Moreover, no data on serum chloride values was reported.

Take home message:  This study has shown that there is no significant difference in the renal outcome of intensive care patients receiving a buffered crystalloid versus 0.9% NaCl fluid regimens.  Given the study’s lower risk patient group, low volume fluid administration and previous evidence demonstrating risk with 0.9% NaCl, is this enough for us to turn back to ‘normal’ saline as our fluid of choice? We expect a lively debate on January 12th/13th for the next #NephJC.

Summary by Andrew McClarey & Paul Phelan, Edinburgh Royal Infirmary