IMPACT OF EARLY VERSUS DELAYED FLUID RESUSCITATION ON MORTALITY AND MORBIDITY IN TRAUMA PATIENTS PRESENTING TO THE EMERGENCY DEPARTMENT: A SYSTEMATIC REVIEW AND META-ANALYSIS OF CLINICAL TRIALS AND COHORT STUDIES

Abstract

Background:

Early fluid resuscitation is an integral part of trauma management in the emergency department; however, the question of the appropriate time and amount of crystalloid administration continues to be controversial. Whilst early delivery of fluid may lead to better perfusion, excessive and/or early crystalloid resuscitation has been linked to adverse outcomes, including increased bleeding and death. The available evidence is mostly heterogeneous and is mostly observational, which requires close synthesis.

Objectives:

To systematically assess the effects of early versus delayed or restrictive fluid resuscitation and its impact on mortality and morbidity in trauma patients presenting to the emergency department and to conduct a meta-analysis, when quantitatively defensible.

Methods:

A systematic review was performed following the guidance of the PRISMA 2020. Clinical trials and cohort studies involving comparison of early or higher volume of fluid resuscitation with delayed and restrictive or no early fluid administration in trauma patients were included in the analysis. Two reviewers independently conducted the screening of studies, data extraction and risk of bias assessment using validated tools. Meta-analysis was limited to studies with comparable mortality outcome as odds ratios with 95% confidence intervals. A random effects model was used. Studies that provided time-to-event data were narratively synthesized.

Results:

Five cohort studies were included in the systematic review. Four cohort studies had similar mortality estimates and were included in the quantitative synthesis. In all these studies early or larger volume crystalloid resuscitation was consistently associated with higher mortality across cohorts. Reported adjusted odds ratios ranged from 1.87 - 2.55 with one large multicenter Asian cohort showing increased in-hospital mortality with pre-hospital crystalloid administration (OR 2.02, 95% CI 1.32 - 3.10) and an emergency room cohort showing increased mortality with high early crystalloid exposure (OR 2.55, 95% CI 1.38 - 4.72). A nationwide Japanese cohort of pre-hospital intravenous access as a proxy of early resuscitation did not have any mortality benefit (OR 0.87, 95% CI 0.55-1.38). Random-effects meta-analysis of the 4 studies showed statistically significant link between early fluid resuscitation and increased mortality with moderate heterogeneity between studies. One additional cohort reporting hazard ratios was narratively synthesized and supported the direction of increased risk with early administration of fluids. The morbidity results were unevenly reported and summarized in a narrative manner.

Conclusions:

In observational cohort evidence, early or aggressive crystalloid fluid resuscitation is linked to higher mortality in trauma patients who present to the emergency department. Whilst results were similar in all studies, the definition of exposure and time of outcome varies which is why it is not possible to draw a causal inference. These findings justify the prudent, personalized approach to fluid therapy and emphasize the importance of standardized preclinical studies to establish the optimal resuscitation time.