Abstract

Introduction: Prolonged time to Return of Spontaneous Circulation (ttROSC) after Out of Hospital Cardiac Arrest (OHCA) has consistently been associated with adverse outcome by a plausible direct relation to severity of anoxic injury. Hypothesis: Target temperature management (TTM) is assumed effective against anoxic brain injury and we hypothesized that TTM at 33 degrees would be more beneficial with prolonged time to ROSC compared to 36 degrees. Methods: In a post hoc analysis of the TTM trial, which showed no overall benefit of targeting 33 °C over 36 in 939 patients (NEJM 2013), we investigated the relation of time to ROSC and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) and Modified Ranking Scale (mRS) after 180 days. Results: Prolonged ttROSC was significantly and independently associated with increased mortality, p<0.001 (figure), with Hazard Ratio (HR) of 1.02 (95% CI 1.01-1.02, p<0.001) per minute increase and level of TTM did not modify this association, p interaction =0.85. In survivors prolonged ttROSC was associated with increased odds of surviving with an unfavorable neurological outcome for CPC (p=0.008 for CPC 3-4) and a similar trend, albeit not statistically significant was observed for mRS (p=0.17, mRS 4-5). Odds for unfavorable neurological outcome (CPC>2, mRS>3) was not modified by levels of TTM overall. Conclusion: Time to ROSC remains a significant prognostic factor in comatose patients resuscitated from OHCA with regards to risk of death and risk of adverse neurological outcome in survivors. TTM at 33 degrees offers no advantage over targeting 36 degrees with regards to mortality or neurological outcome in patients with prolonged time to ROSC. Figure: Mortality rates stratified by quartiles of tome to ROSC and by TTM level. Differences tested by log rank test in between TTM in strata

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