Trials and guidelines in fluid and electrolyte management

This section mainly represents a place to store all those "balanced crystalloid vs saline" trials, which there would be no other place for.  Otherwise, there are few critically important ICU-relevant trials, and surprisingly few widely accepted guidelines for fluid management, electrolyte replacement or investigations. Hyponatremia seems to be a notable outlier, but otherwise good luck finding a Consensus Statement from the International Committee for Electrolyte Correction in Critical Care, as there is no such body and there is no such statement. 

Fluid and electrolyte trials

Balanced crystalloid

  • SPLIT2015 - Plasma-Lyte vs saline in the ICU; n=2278 in NZ. No difference in rate of AKI (9.6% vs 9.2%) or hospital mortality (7.6% vs 8.6%).
  • SALT-ED2018- Plasma-Lyte vs saline in the ward; n=13,347 in the US. No difference in hospital-free days, but much less composite renal badness (MAKE30 4.7% vs. 5.6%), especially in those with already crappy kidneys (creatinine > 133 mmol/L)
  • SMART2018 - Plasma-Lyte vs saline in ICU; n=15,802 in the US. Composite renal badness better with balanced crystalloid (14.3% vs 15.4%, NNT=94)
  • BaSICS (fluid type)2021 - Plasma-Lyte vs saline in ICU; n=11,052 in Brazil. No difference in mortality (26.4% vs 27.2%), except in TBI (31.3% vs 21.1% for the saline). 
  • PLUS2022 - Plasma-Lyte vs saline in ICU; n=5037 in Australia.  No difference in mortality (21.8% v 22.0%) or risk of AKI (34.2% v 34.4%)


  • BICAR-ICU2018 - isotonic (4.2%) bicarb for pH < 7.20. n=389, in France. No difference in composite outcome (71% vs 66%) except in AKI patients (82% vs 70%)

Fluid and electrolyte guidelines


Finfer, Simon, et al. "Balanced multielectrolyte solution versus saline in critically ill adults." New England Journal of Medicine 386.9 (2022): 815-826.

Zampieri, Fernando G., et al. "Effect of intravenous fluid treatment with a balanced solution vs 0.9% saline solution on mortality in critically ill patients: the BaSICS randomized clinical trial." Jama 326.9 (2021): 818-829.

Zampieri, Fernando G., et al. "Effect of slower vs faster intravenous fluid bolus rates on mortality in critically ill patients: the basics randomized clinical trial." JAMA 326.9 (2021): 830-838.

Jaber, Samir, et al. "Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial." The Lancet 392.10141 (2018): 31-40.

Self, Wesley H., et al. "Balanced crystalloids versus saline in noncritically ill adults." New England Journal of Medicine 378.9 (2018): 819-828.

Semler, Matthew W., et al. "Balanced crystalloids versus saline in critically ill adults." New England Journal of Medicine 378.9 (2018): 829-839.

Young, Paul, et al. "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 314.16 (2015): 1701-1710.

Spasovski, Goce, et al. "Clinical practice guideline on diagnosis and treatment of hyponatraemia." Nephrology Dialysis Transplantation 29.suppl_2 (2014): i1-i39.

Verbalis, Joseph G., et al. "Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations." The American journal of medicine 126.10 (2013): S1-S42.

Cohn, Jay N., et al. "New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice." Archives of internal medicine 160.16 (2000): 2429-2436.

Rossignol, Patrick, et al. "Emergency management of severe hyperkalemia: guideline for best practice and opportunities for the future." Pharmacological research 113 (2016): 585-591.