Written by Seth Walsh
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This large meta-analysis of ICU RCT subgroups found decreased mortality in patients with traumatic brain injury (TBI) treated with normal saline vs. other crystalloid and an increase in those without.
Start stocking saline again?
Hypotonicity in patients with TBI may worsen cerebral edema and cause additional neurological injury. Balanced solutions are often preferred for ICU patients, though high-level evidence of superiority is inconsistent.1,2,3 The BaSICs trial subgroup analysis found a TBI mortality benefit with normal saline (NS), perhaps because its greater tonicity lowers the risk of cerebral edema.
The analysis ultimately included 15 RCTs comparing NS to balanced solutions, with mortality data for 35,388 critically ill adults. Only five trials with 2011 patients had data for TBI patients. With these data, the odds ratio (OR) for mortality in patients with TBI receiving balanced solutions was 1.31 (95%CI 1.03-1.65; P = 0.03; I2 = 0%).
In the 33,197 patients without TBI, the OR for mortality was 0.93 (95%CI 0.87 to 0.98; P = .01, I2 = 0%). There was no significant difference in mortality when all patients were analyzed regardless of TBI status. Secondary analysis, including 90-day mortality in septic patients, lacked significant differences.
Although heterogeneity was low, there were substantial differences in the volume and type of balanced solution across studies. When excluding the BaSICs subgroup, there was no significant difference in TBI patients. Eighty percent of trials had some concern about blinding, and all but two trials were designed with mortality as a primary outcome.
How will this change my practice?
The level of evidence suffers from multiple abstractions. Ideally, we would have an RCT designed for this rather than pooling subgroups. The causes of hyponatremia and edema in TBI patients are multifactorial, so my fluid choice will reflect the overall clinical picture until NS superiority is proven.
Editor’s note: When the SALT-ED and SMART trials were done at Vanderbilt, we could opt out of balanced fluid in TBI patients in the EHR. When we used balanced fluid, it was overwhelmingly LR. BaSICs used Plasma-Lyte A, and TBI patients fared worse. Remember, 0.9% saline (NS) has 154 meq/L sodium; Plasma-Lyte A has 140; LR has 130. For now, in patients with TBI, NS is a reasonable first choice. ~Clay Smith
Source
Effect of Treatment With Balanced Crystalloids Versus Normal Saline on the Mortality of Critically Ill Patients With and Without Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Anesth Analg. 2025 Jan 20. doi: 10.1213/ANE.0000000000007368. Epub ahead of print. PMID: 39832223
Works Cited
- Semler, Matthew W et al. “Balanced Crystalloids versus Saline in Critically Ill Adults.” The New England journal of medicine vol. 378,9 (2018): 829-839. doi:10.1056/NEJMoa1711584
- 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, vol. 326,9 1–12. 10 Aug. 2021, doi:10.1001/jama.2021.11684
- Antequera Martín, Alba M et al. “Buffered solutions versus 0.9% saline for resuscitation in critically ill adults and children.” The Cochrane database of systematic reviews vol. 7,7 CD012247. 19 Jul. 2019, doi:10.1002/14651858.CD012247.pub2
