SPLIT trial summary
There were no differences in any outcome (renal failure, dialysis, serum creatinine, or mortality).
Excellent internal validity
Limited external validity
- Patients included in this study were not very sick, with only a 9% rate of acute kidney injury and a 3% rate of dialysis. This may reflect the inclusion of patients transferred to the ICU following elective surgery. As the authors noted, these results may not apply to sicker patients.
- One common cause of renal failure is sepsis-associated acute kidney injury, which has a different pathogenesis compared to other types of renal injury (Gomez 2014). Given that only 4% of the patients in this study had sepsis, it is unclear whether these results apply to sepsis resuscitation.
Incorrect to make generalizations about all balanced crystalloids
- Plasmalyte contains 23 mM of sodium gluconate, which is mostly excreted unchanged in the urine and might even act as an osmotic diuretic.
- Plasmalyte contains 27 mM of sodium acetate, which the body converts into bicarbonate. Concerns have been raised about potential vasodilatory and pro-inflammatory effects of acetate (Davies 2011).
- LR contains 28 mM of sodium lactate, which the body converts into bicarbonate. Although lactate has a bad reputation due to its association with shock, lactate production is often an adaptive physiologic response to stress (e.g. sodium lactate may be used as a fuel by the heart and brain).
Normal saline is occasionally referred to as “abnormal saline” due to its physiologic abnormality, but plasmalyte is also quite abnormal. There is nothing physiologic about infusing sodium gluconate and sodium acetate. Among all of these solutions, LR is arguably the most physiologic because it is a balanced crystalloid constructed from anions normally present in the blood (chloride and lactate).
Comparison of NS vs. plasmalyte is complicated because the renal effects of gluconate and acetate are poorly understood. Therefore, a trial of NS vs. plasmalyte is simultaneously testing three unknowns: the effect of gluconate, the effect of acetate, and the effect of non-anion gap metabolic acidosis. This makes it difficult to understand the results.
- The SPLIT trial reveals that low volumes of normal saline (e.g. two liters per entire ICU stay) produce the same renal outcomes as plasmalyte.
- The SPLIT study does not reveal whether larger volumes of normal saline are equivalent to plasmalyte.
- The SPLIT study does not clarify whether hyperchloremic metabolic acidosis is safe.
- Differences between plasmalyte and LR make it incorrect to assume that results obtained with plasmalyte will apply to LR.
- Although this study is well designed with excellent internal validity, it adds little to our understanding of large-volume resuscitation.
- Plasmalyte/Normosol vs. LR
- Is correcting hyperchloremic acidosis beneficial?
- pH-guided resuscitation
- Understanding lactate & using it to our advantage