Evaluation and Predictors of Fluid Resuscitation in Patients With Severe Sepsis and Septic Shock

Abstract

Objectives: Rapid fluid resuscitation has become standard in sepsis care, despite "low-quality" evidence and absence of guidelines for populations "at risk" for volume overload. Our objectives include as follows: 1) identify predictors of reaching a 30 mL/kg crystalloid bolus within 3 hours of sepsis onset (30by3); 2) assess the impact of 30by3 and fluid dosing on clinical outcomes; 3) examine differences in perceived "at-risk" volume-sensitive populations, including end-stage renal disease, heart failure, obesity, advanced age, or with documentation of volume "overload" by bedside examination.

Design: Retrospective cohort study. All outcome analyses controlled for sex, end-stage renal disease, heart failure, sepsis severity (severe sepsis vs septic shock), obesity, Mortality in Emergency Department Sepsis score, and time to antibiotics.

Setting: Urban, tertiary care center between January 1, 2014, and May 31, 2017.

Patients: Emergency Department treated adults (age ≥18 yr; n = 1,032) with severe sepsis or septic shock.

Interventions: Administration of IV fluids by bolus.

Measurements and main results: In total, 509 patients received 30by3 (49.3%). Overall mortality was 17.1% (n = 176), with 20.4% mortality in the shock group. Patients who were elderly (odds ratio, 0.62; 95% CI, 0.46-0.83), male (odds ratio, 0.66; CI, 0.49-0.87), obese (odds ratio, 0.18; CI, 0.13-0.25), or with end-stage renal disease (odds ratio, 0.23; CI, 0.13-0.40), heart failure (odds ratio, 0.42; CI, 0.29-0.60), or documented volume "overload" (odds ratio, 0.30; CI, 0.20-0.45) were less likely to achieve 30by3. Failure to meet 30by3 had increased odds of mortality (odds ratio, 1.52; CI, 1.03-2.24), delayed hypotension (odds ratio, 1.42; CI, 1.02-1.99), and increased ICU stay (~2 d) (β = 2.0; CI, 0.5-3.6), without differential effects for "at-risk" groups. Higher fluid volumes administered by 3 hours correlated with decreased mortality, with a plateau effect between 35 and 45 mL/kg (p < 0.05).

Conclusions: Failure to reach 30by3 was associated with increased odds of in-hospital mortality, irrespective of comorbidities. Predictors of inadequate resuscitation can be identified, potentially leading to interventions to improve survival. These findings are retrospective and require future validation.

Figure 1:. Dose-Effect Curves

Figure 1 estimates from the multivariable logistic or negative binomial regression (ICU LOS) models including a quadratic term for volume administered by 3 hours. Gray shaded area indicate 95% CI.

Figure 2.. Comparison of the Effect of 30after3 on Mortality Across Subgroups

Figure 2 demonstrates a subgroup analysis comparing the effects of 30after3 on mortality across various subgroups of patients. An odds ratio >1 indicating increased odds of mortality for those failing to meet fluid goals when compared to those meeting fluid goals. When evaluating specific subgroups, no significant interaction effects were found.