Association Between Intravenous Fluid Bolus and Biomarker Trajectory During Prehospital Care

Background: Patients with acute illness who receive intravenous (IV) fluids prior to hospital arrival may have a lower in-hospital mortality. To better understand whether this is a direct treatment effect or epiphenomenon of downstream care, we tested the association between a prehospital fluid bolus and the change in inflammatory cytokines measured at prehospital and emergency department timepoints in a sample of non-trauma, non-cardiac arrest patients at risk for critical illness. Methods: In a prospective cohort study, we screened 4,013 non-trauma, non-cardiac arrest encounters transported by City of Pittsburgh Emergency Medical Services (EMS) to 2 hospitals from August 2013 to February 2014. In 345 patients, we measured prehospital biomarkers (IL-6, IL-10, and TNF) at 2 time points: the time of prehospital IV access placement by EMS and at ED arrival. We determined the relative change for marker X as: ([X_ED - X_EMS]/X_EMS). We determined the risk-adjusted association between prehospital IV fluid bolus and relative change for each marker using multivariable linear regression. Results: Among 345 patients, 88 (26%) received a prehospital IV fluid bolus and 257 (74%) did not. Compared to patients who did not receive prehospital fluids, median prehospital IL-6 was greater initially in subjects receiving a prehospital IV fluid bolus (22.3 [IQR 6.4-113] vs. 11.5 [IQR 5.5-47.6]). Prehospital IL-10 and TNF were similar in both groups (IL-10: 3.5 [IQR 2.2-25.6] vs. 3.0 [IQR 1.9-9.0]; TNF: 7.5 [IQR 6.4-10.4] vs. 6.9 [IQR 6.0-8.3]). After adjustment for demographics, illness severity, and prehospital transport time, we observed a relative decrease in IL-6 at hospital arrival in those receiving a prehospital fluid bolus (adjusted β = -10.0, 95% CI: -19.4, -0.6, p = 0.04), but we did not detect a significant change in IL-10 (p = 0.34) or TNF (p = 0.53). Conclusions: Among non-trauma, non-cardiac arrest patients at risk for critical illness, a prehospital IV fluid bolus was associated with a relative decrease in IL-6, but not IL-10 or TNF.