The Effect of Body Mass Index and Weight-Adjusted Fluid Dosing on Mortality in Sepsis.

PURPOSE: The Surviving Sepsis Campaign guidelines recommend 30 mL/kg of fluids within 3 hours (30by3) of sepsis-induced hypoperfusion, but a national mandate released an allowance for dosing based on ideal instead of actual body weight (IBW/ABW) for obese patients. This study aims to determine the dose-effect of 30by3 for patients with severe sepsis or septic shock (SS/SS) with respect to body mass index (BMI) categories and secondarily, examine the clinical impact of IBW vs. ABW-based dosing. METHODS: Retrospective cohort study of adults (≥18 years; n = 1,032) with SS/SS presenting to an urban, tertiary-care emergency department. Models include MEDS score, antibiotic timing, lactate, renal and heart failure, among others. RESULTS: The cohort was 10.2% underweight and 28.7% obese. Overall mortality was 17.1% with 20.4% shock mortality. An exponential increase in mortality was observed for each 5 mL/kg under 30by3 for underweight (p = 0.02), but not obese patients. ABW vs IBW-30by3 dosing was reached in 80.0 vs 52.4% (underweight), 56.4 vs 56.9% (normal/overweight), and 23.3 vs 46.0% (obese). Across all BMI categories, there was increased mortality for not reaching ABW-based 30by3 dosing (OR 1.78, 95% CI 1.18-2.69) with no significant impact for IBW (OR 1.28, 95% CI 0.87 -1.91). The increased mortality for failing to reach ABW-dosed 30by3 remained for underweight patients ABW (OR 5.82, 95% CI 1.32-25.57) but not obese patients. Longer ICU stays were observed for not reaching 30by3 based on ABW (ß = 2.40, 95% CI 0.84-3.95) and IBW dosing (ß = 1.58, 95% CI 0.07-3.08) overall. This effect remained for obese and underweight (except IBW dosing) patients. CONCLUSIONS: An exponential, dose-effect increase in mortality was observed for underweight patients not receiving 30by3. Therefore, the mortality impact of under-dosing may be amplified using ABW for underweight patients. Fluid dosing did not impact mortality for obese patients, but we caution against deviation from guidelines without further studies.

The effect of delays in second-dose antibiotics on patients with severe sepsis and septic shock.

BACKGROUND: Early antibiotics are fundamental to sepsis management. Second-dose antibiotic delays were associated with increased mortality in a recent study. Study objectives include: 1) determine factors associated with delays in second-dose antibiotic administration; 2) evaluate if delays influence clinical outcomes. METHODS: ED-treated adults (≥18 years; n = 1075) with severe sepsis or septic shock receiving ≥2 doses of intravenous antibiotics were assessed, retrospectively, for second-dose antibiotic delays (dose time > 25% of recommended interval). Predictors of delay and impact on outcomes were determined, controlling for MEDS score, 30 mL/kg fluids and antibiotics within three hours of sepsis onset, lactate, and renal failure, among others. RESULTS: In total, 335 (31.2%) patients had delayed second-dose antibiotics. A total of 1864 second-dose antibiotics were included, with 354 (19.0%) delays identified by interval (delayed/total doses): 6-h (36/67) = 53.7%; 8-h (165/544) = 30.3%; 12-h (114/436) = 26.1%; 24-h (21/190) = 8.2%; 48-h (0/16) = 0%. In-hospital mortality in the timely group was 15.5% (shock-17.6%) and 13.7% in the delayed group (shock-16.9%). Increased odds of delay were observed for ED boarding (OR 2.54, 95% 1.81-3.55), shorter dosing intervals (6/8-h- OR 2.99, 95% CI 1.95-4.57; 12-h- OR 2.46, 95% CI 1.72-3.51), receiving 30 mL/kg fluids by three hours (OR 1.42, 95% CI 1.06-1.90), and renal failure (OR 2.57, 95% CI 1.50-4.39). Delays were not associated with increased mortality (OR 0.87, 95% CI 0.58-1.29) or other outcomes. CONCLUSIONS: Factors associated with delayed second-dose antibiotics include ED boarding, antibiotics requiring more frequent dosing, receiving 30 mL/kg fluid, and renal failure. Delays in second-dose administration were not associated with mortality or other outcomes.