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Timing of Induced Hypothermia

Question Type:
Intervention
Full Question:
Among patients with return of pulses after cardiac arrest in any setting  (P), does does induction of hypothermia before some time point (eg, 1 hour after ROSC or before hospital arrival)  (I), compared with compared with induction of hypothermia after that time point  (C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year (O)?
Consensus on Science:
Five RCTs(Kim 2007, 3064; Kamarainen 2009, 900; Bernard 2010, 737; Bernard 2012, 747; Kim 2014, 45) used cold IV fluids after ROSC to induce hypothermia, 1 trial used cold IV fluid during resuscitation,(Debaty 2014, 1832) and 1 trial used intra-arrest intranasal cooling.(Castren 2010, 729) The volume of cold fluid ranged from 20 to 30 mL/kg and up to 2 L, though some patients did not receive the full amount before hospital arrival. One small feasibility trial was not included.(Callaway 2002, 159) All 7 trials suffered from the unavoidable lack of blinding of the clinical team, and 3 also failed to blind the outcomes assessors. For the critical outcome of favorable neurologic outcome, 5 trials with a total of 1867 subjects with OHCA(Kamarainen 2009, 900; Bernard 2010, 737; Castren 2010, 729; Bernard 2012, 747; Kim 2014, 45) provided overall moderate-quality evidence (downgraded for risk of bias), showing that neurologic outcomes did not differ after initiation of induced hypothermia in the prehospital environment compared with later initiation (RR, 1.00; 95% CI, 0.95–1.06). For the critical outcome of mortality, 7 trials with a total of 2237 subjects provided moderate-quality evidence (downgraded for risk of bias), showing no overall difference in mortality for patients treated with prehospital cooling (RR, 0.98; 95% CI, 0.92–1.04) compared with those who did not receive prehospital cooling. No individual trial found an effect on either poor neurologic outcome or mortality. For the outcome of rearrest, 4 RCTs provided low-quality evidence (downgraded for risk of bias and inconsistency) for an increased risk among subjects who received prehospital induced hypothermia (RR, 1.22; 95% CI, 1.01–1.46).(Kim 2007, 3064; Kamarainen 2009, 900; Bernard 2012, 747; Kim 2014, 45) This result was driven by data from the largest trial.(Kim 2014, 45) For the outcome of pulmonary edema, 3 trials reported no pulmonary edema in any group. Two small pilot trials(Kim 2007, 3064; Debaty 2014, 1832) found no difference between groups, and 1 trial showed an increase in pulmonary edema in patients who received prehospital cooling (RR, 1.34; 95% CI, 1.15–1.57).(Kim 2014, 45) These trials provided overall low-quality evidence (downgraded for risk of bias and inconsistency).
Treatment Recommendation:
We recommend against routine use of prehospital cooling with rapid infusion of large volumes of cold IV fluid immediately after ROSC (strong recommendation, moderate-quality evidence). Values, Preferences, and Task Force Insights In making this recommendation, we place high value in not recommending an intervention with no proven benefit despite a large number of patients studied. We further note that the meta-analysis driven by the results from the largest study found also noted an increased risk of rearrest with prehospital induction of mild hypothermia using rapid infusion of cold IV fluid.(Kim 2014, 45) This recommendation is specific to the prehospital setting after ROSC, and we acknowledge that cold IV fluid might still be used in patients who have been further evaluated or in other settings.
CoSTR Attachments:
Temperature Management After Cardiac Arrest. Article.pdf    
Temperature Management After Cardiac Arrest. Data Supplement.pdf    

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