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Targeted Temperature Management

Question Type:
Intervention
Full Question:
Among patients with ROSC after cardiac arrest in any setting  (P), does inducing mild hypothermia (target temperature 32°C–34°C)  (I), compared with normothermia  (C), change  (O)?
Consensus on Science:
OHCA Arrest With a Shockable Rhythm For the critical outcome of survival with favorable neurologic outcome, we have identified low-quality evidence (downgraded for risk of bias and imprecision) from 1 RCT(2002, 549) and 1 quasi-randomized trial(Bernard 2002, 557) enrolling 275 and 77 patients, showing a benefit in patients with OHCA with VF or pVT as an initial rhythm. In these studies, cooling to 32°C to 34°C compared with no temperature management was associated with good neurologic outcome at 6 months (RR, 1.4; 95% CI, 1.08–1.81) and survival to hospital discharge (OR, 2.65; 95% CI, 1.02–6.88). For the critical outcome of survival, 1 study(HACA Study Group 2002, 549) showed benefit in patients treated with induced hypothermia (RR for 180-day mortality, 0.74; 95% CI, 0.58–0.95), while another study found no significant difference (51% versus 68% hospital mortality; RR, 0.76; 95% CI, 0.52–1.10).(Bernard 2002, 557) OHCA With Nonshockable Rhythms We found no RCTs comparing mild induced hypothermia (32°C–34°C) to no temperature management in patients with OHCA with pulseless electrical activity or asystole (ie, nonshockable) as the initial rhythm. For the critical outcome of survival with favorable neurologic outcome, we found 3 cohort studies including a total of 1034 patients, providing overall very-low-quality evidence (downgraded for risk of bias and imprecision) for no difference in poor neurologic outcome in patients with nonshockable OHCA (adjusted pooled OR, 0.90; 95% CI, 0.45–1.82).(Dumas 2011, 877; Testori 2011, 1162; Vaahersalo 2013, 826) One additional retrospective study that used a large registry, including 1830 patients, provided very-low-quality evidence (downgraded for risk of bias and imprecision) for an increase in poor neurologic outcome in patients with nonshockable OHCA (adjusted OR, 1.44; 95% CI, 1.039–2.006).(Mader 2014, 21) These data were not pooled with the above studies due to the lack of temperature data and limited patient information available. For the critical outcome of survival, we found very-low-quality evidence (downgraded for risk of bias and imprecision) of a benefit in mortality at 6 months (OR, 0.56; 95% CI, 0.34–0.93) from one of these studies.(Testori 2011, 1162) IHCA We found no RCTs comparing mild induced hypothermia (32°C–34°C) to no temperature management in patients with IHCA. For the critical outcome of survival to hospital discharge, we found very-low-quality evidence (downgraded for risk of bias and imprecision) in 1 retrospective cohort study including 8316 patients that showed no benefit in patients with IHCA of any initial rhythm who were treated with TTM versus no active temperature management (OR, 0.9; 95% CI, 0.65–1.23).(Nichol 2013, 620) For the critical outcome of neurologically favorable survival, we found very-low-quality evidence (downgraded for risk of bias and imprecision) from the same observational study showing no benefit (OR, 0.93; 95% CI, 0.65–1.32). Although we found numerous before-and-after studies on the implementation of temperature management, these data are extremely difficult to interpret in light of other changes in post–cardiac arrest care that accompanied implementation, making it impossible to isolate the effect of temperature on outcomes after cardiac arrest. For this reason, we excluded all before-and-after studies. Other observational studies with concurrent controls also represent low-quality evidence due to residual confounding and other factors. We, therefore, did not include these in the consensus on science, except for specific patient populations lacking higher quality (ie, RCT) evidence. Target Temperature For the critical outcomes of survival and survival with favorable neurologic outcome, we found moderate-quality evidence (downgraded for imprecision) from 1 RCT including 939 patients. This study compared cooling to 33°C compared with tight temperature control at 36°C in adult patients with OHCA of any initial rhythm except unwitnessed asystole, and found no benefit (HR for mortality at end of trial, 1.06; 95% CI, 0.89–1.28; RR for death or poor neurologic outcome at 6 months, 1.02; 95% CI, 0.88–1.16).(Nielsen 2013, 2197) For the critical outcome of survival with favorable neurologic outcome, we found low-quality evidence (downgraded for risk of bias and imprecision) in 1 additional small pilot RCT enrolling 36 patients comparing 32°C with 34°C in patients with OHCA VT/VF or asystole. This study found no benefit (neurologically intact survival 44.4% versus 11.1%; P=0.12), although with only 36 patients it was underpowered.
Treatment Recommendation:
We recommend selecting and maintaining a constant target temperature between 32°C and 36°C for those patients in whom temperature control is used (strong recommendation, moderate-quality evidence). Whether certain subpopulations of cardiac arrest patients may benefit from lower (32°C–34°C) or higher (36°C) temperatures remains unknown, and further research may help elucidate this. We recommend TTM as opposed to no TTM for adults with OHCA with an initial shockable rhythm who remain unresponsive after ROSC (strong recommendation, low-quality evidence). We suggest TTM as opposed to no TTM for adults with OHCA with an initial nonshockable rhythm who remain unresponsive after ROSC (weak recommendation, very-low-quality evidence). We suggest TTM as opposed to no TTM for adults with IHCA with any initial rhythm who remain unresponsive after ROSC (weak recommendation, very-low-quality evidence). Values, Preferences, and Task Force Insights In making these recommendations, we place a higher value on the potential for increased survival with good neurologic outcome as compared with the possible risks (which appear to be minimal) and the cost of TTM. We emphasize that the mortality after cardiac arrest is high and the treatment options are limited. Although the evidence for TTM compared with no temperature management is of low quality, it is the only post-ROSC intervention that has been found to improve survival with good neurologic outcome. We have, therefore, made our recommendation strong in spite of the low-quality evidence.
CoSTR Attachments:
Temperature Management After Cardiac Arrest. Article.pdf    
Temperature Management After Cardiac Arrest. Data Supplement.pdf    

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