Impact of intra-arrest therapeutic hypothermia in outcomes of prehospital cardiac arrest: a randomized controlled trial

Abstract

Purpose: Mild therapeutic hypothermia (TH) is recommended as soon as possible after the return of spontaneous circulation to improve outcomes after out-of-hospital cardiac arrest (OHCA). Preclinical data suggest that the benefit of TH could be increased if treatment is started during cardiac arrest. We aimed to study the impact of intra-arrest therapeutic hypothermia (IATH) on neurological injury and inflammation following OHCA. Methods: We conducted a 1:1 randomized, multicenter study in three prehospital emergency medical services and four critical care units in France. OHCA patients, irrespective of the initial rhythm, received either an infusion of cold saline and external cooling during cardiac arrest (IATH group) or TH started after hospital admission (hospital-cooling group). The primary endpoint was neuron-specific enolase (NSE) serum concentrations at 24 h. Secondary endpoints included IL-6, IL-8, and IL-10 concentrations, and clinical outcome. Results: Of the 245 patients included, 123 were analyzed in the IATH group and 122 in the hospital-cooling group. IATH decreased time to reach temperature ≤34 °C by 75 min (95 % CI: 4; 269). The rate of patients admitted alive to hospital was not different between groups [IATH n = 41 (33 %) vs. hospital cooling n = 36 (30 %); p = 0.51]. Levels of NSE and inflammatory biomarkers were not different between groups [median NSE at 24 h: IATH 96.7 μg/l (IQR: 49.9–142.8) vs. hospital cooling 97.6 μg/l (IQR: 74.3–142.4), p = 0.64]. No difference in survival and cerebral performance were found at 1 month. Conclusions: IATH did not affect biological markers of inflammation or brain damage or clinical outcome.