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
- JAMA: Study manuscript & editorial
- The Bottom Line
- St. Emlyn's Blog
- PulmCrit: “ARDS” is not a real thing - May 27, 2023
- IBCC – ABG, VBG, and pulse oximetry - April 27, 2023
- IBCC – CAR-T cell therapy recipient in the ICU - April 25, 2023
Thank you for this. I totally agree.
I think that patient population that would be best to check this in would be diabetic emergencies, such as DKA and HONK, as the protocols for these involve large volumes of NaCl over short periods of time. The problem with these patients is that often require extra potassium, which we’re not to add to LR.
Yep. I have encountered the same problem exact problem with added potassium when writing DKA protocols. I don’t believe KCl would be incompatible with LR, but most pharmacies may not let you add it. There are two solutions to this, neither of which is perfect: (1) Use LR-based fluids for resus and maintenance, and supplement with mini-bags of KCl (2) Use a potassium-containing fluid (e.g. NS w/ 40 mEq/L KCl, D5 1/2 NS with 40 mEq/L KCl, etc). This may generate a hyperchloremic acidosis. In some patients with marked hyperchloremic acidosis you may end up fixing it later on with… Read more »
Great assessment of the study. The low volumes received by enrolled patients and the limited number who had sepsis diagnosis really led to my essentially ignoring this study entirely and having no qualms about my LR addiction. Thanks for your thoughtful review!