Article 1
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. Diz JC, Luna-Rojas P, Díaz-Vidal P, Fernández-Vázquez U, Gil-Casado C, Diz-Ferreira E. Anesthesia & Analgesia. 2005 July;141(1): 152-161.
Diz et al performed systematic review and meta-analysis examining patients resuscitated with balanced crystalloids (Lactated Ringer’s or Plasma-Lyte) versus 0.9% saline, and its impact on outcomes in adult critically ill patients—with prespecified subgroups for those with and without traumatic brain injury (TBI). This meta-analysis incorporated 15 randomized clinical trials with 35,207 patients included. The primary outcome was 90-day mortality, with secondary outcomes including hospital and ICU lengths of stay and renal complications. The authors found that in patients without TBI, balanced crystalloids had a lower 90-day mortality (OR 0.93; 95% CI 0.87–0.98; P = .01; I² = 0%), whereas in patients with TBI, balanced fluids were associated with increased mortality risk (OR 1.31; 95% CI 1.03–1.65; P = .03; I² = 0%). Secondary outcomes did not significantly differ by fluid type in either of subgroups.
For trauma and acute care surgeons, these findings provide additional evidence supporting the importance of tailoring intravenous fluid choice to specific patient populations. In critically ill patients without traumatic brain injury (TBI), balanced crystalloids confer a small but statistically significant survival advantage and may be preferred over saline for routine resuscitation. In contrast, in patients with TBI, balanced crystalloids are associated with worse outcomes, reinforcing the role of normal saline as the safer choice. Notably, the non-TBI cohort was heterogeneous and not limited to trauma patients, so the impact of concomitant TBI in multisystem trauma is unclear. While renal and ventilatory outcomes showed no consistent differences between fluid types, the mortality signal in TBI is strong and should inform fluid resuscitation protocols in trauma settings.
Article 2
Balanced Crystalloids versus saline for critically ill patients (BEST - Living): a sysematic review and individual patient data meta-analysis. Semler MW, Self WH, Wanderer JP, et al. Lancet Respir Med. 2024 Mar;12(3):237-246.
The BEST-Living study is a living individual patient data (IPD) meta-analysis designed to assess whether balanced crystalloid solutions (such as lactated Ringer’s or Plasma-Lyte) offer an advantage over 0.9% saline in critically ill adult patients. The investigators combined data from six randomized controlled trials—including SMART, SALT-ED, BaSICS, etc.—including a total of 34,685 ICU patients (17,407 receiving balanced fluids and 17,278 receiving saline). The primary outcome was in-hospital mortality. Overall, mortality was 16.8% in the balanced fluid group compared to 17.3% in the saline group, corresponding to an odds ratio of 0.962 (95% [CrI] 0.909–1.019). Secondary outcomes, such as the need for renal replacement therapy and hospital-free days, were found to be similar between groups.
Importantly, a pre-specified subgroup analysis of patients with traumatic brain injury (TBI) demonstrated a difference in outcomes. In this subgroup, mortality was 19.1% with balanced crystalloids compared to 14.7% with saline (OR 1.424, 95%, CrI 1.100–1.818), corresponding to a 3.2% absolute increase in mortality with balanced fluids. These findings are consistent with prior physiologic concerns about the hypotonicity of certain balanced solutions (e.g., lactated Ringer’s) in the setting of impaired cerebral autoregulation.
This study has several strengths, including the use of IPD to help ensure the findings remain up to date as new trials are published, making this an important ongoing resource in critical care fluid management. However, the study also has limitations. The absolute mortality benefit for the overall population was small, and while the posterior probability favored balanced fluids, the clinical significance of a 0.4% mortality difference is debatable. Furthermore, the included trials varied in design, fluid formulations, and populations, introducing some heterogeneity. Several of the included studies were assessed as having high risk of bias, and the generalizability of the TBI subgroup findings is limited by relatively small numbers and inconsistent fluid protocols.
In conclusion, the BEST-Living meta-analysis suggests that balanced crystalloids may provide a modest mortality benefit over saline in the general ICU population, but this benefit is likely small. In contrast, the data indicate potential harm with balanced fluids in patients with traumatic brain injury, warranting caution in this group. Given the ongoing nature of this living meta-analysis, clinicians should remain attentive to future updates. Until then, fluid choice should be individualized, with consideration for patient-specific factors, including neurologic injury, renal function, and institutional protocols.
