1. Dallas 2015 TFQO: Michael Donnino #222 EVREV 1: Joshua Reynolds COI #265 EVREV 2: Katherine Berg COI #10 Taskforce: ALS ALS 790 : Induced Hypothermia

2. Dallas 2015 COI Disclosure (SPECIFIC to this systematic review) Joshua Reynolds COI #265 Commercial/industry List here Potential intellectual conflicts List here Katherine Berg COI #10 Commercial/industry List here Potential intellectual conflicts List here

3. Dallas 2015 2010 TR Adult patients who are comatose (not responding in a meaningful way to verbal commands) with spontaneous circulation after out-of-hospital VF cardiac arrest should be cooled to 32–34 ◦ C for 12–24 h. Induced hypothermia might also benefit comatose adult patients with spontaneous circulation after OHCA from a nonshockable rhythm or in-hospital cardiac arrest.

4. Dallas 2015 C2015 PICO Population: patients with ROSC after cardiac arrest in any setting Intervention: inducing mild hypothermia (target temperature 32- 34ºC) Comparison: compared with normothermia (36-37ºC) Outcomes: Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year (9-Critical) Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year (8-Critical)

5. Dallas 2015 Inclusion/Exclusion & Articles Found For patient populations where randomized control trials (RCT) were available (i.e., out ‐ of ‐ hospital shockable cardiac arrest), only RCTs were included. Otherwise, observational studies were included. We did not include studies without a concurrent comparator group, studies that did not report separate outcomes for shockable and non ‐ shockable rhythms, studies only reporting unadjusted outcomes. The search yielded a total of 4,391 studies. Of these, six RCTs and three observational studies were included for bias assessment.

6. Dallas 2015 2015 Proposed Treatment Recommendations We recommend targeted temperature management as opposed to no targeted temperature management for adults with OHCA with an initial shockable rhythm who remain unresponsive after ROSC (strong recommendation, low quality evidence). We suggest targeted temperature management as opposed to no targeted temperature management for adults with OHCA with an initial non ‐ shockable rhythm (weak recommendation, very low quality evidence). We suggest targeted temperature management as opposed to no targeted temperature management for adults with IHCA with any initial rhythm who remain unresponsive after ROSC (weak recommendation, very low quality evidence).

7. Dallas 2015 Risk of Bias in RCTs

8. Dallas 2015 Risk of Bias in non-RCTs

9. Dallas 2015 Evidence profile table(s)

10. Dallas 2015

12. Proposed Consensus on Science statements One RCT {HACA 2002, 549} and one pseudo-randomized trial {Bernard 2002, 557} enrolling a total of 352 patients provided overall low quality evidence for a survival benefit with good neurologic outcome in patients with OHCA with ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) as an initial rhythm that were cooled to 32-34C in comparison with no cooling. Three cohort studies {Testori 2011, 1162}{Dumas 2011, 877}{Vaahersalo 2013, 826} including a total of 1,034 patients provide overall very low quality evidence for no difference in poor neurologic outcome in patients with non- shockable OHCA (adjusted pooled odds ratio [OR] 0.90 [95% CI 0.45 – 1.82]. One of these studies reported mortality and provided overall very low quality evidence for decreased mortality at 6 months (adjusted OR 0.56 [95% CI 0.34-0.93]) {Testori 2011, 1162}. One retrospective cohort study, of 8,316 IHCA patients {Nichol 2013, 620} with any initial rhythm, provided overall very low quality evidence for no difference in mortality at hospital discharge (adjusted OR 1.11 [95% CI 0.81- 1.54]) or poor neurologic outcome (adjusted OR 1.08 [95% CI 0.76-1.54])

13. Dallas 2015 Draft Treatment Recommendations We recommend targeted temperature management as opposed to no targeted temperature management for adults with OHCA with an initial shockable rhythm who remain unresponsive after ROSC (strong recommendation, low quality evidence). We suggest targeted temperature management as opposed to no targeted temperature management for adults with OHCA with an initial non ‐ shockable rhythm (weak recommendation, very low quality evidence). We suggest targeted temperature management as opposed to no targeted temperature management for adults with IHCA with any initial rhythm who remain unresponsive after ROSC (weak recommendation, very low quality evidence).

14. Dallas 2015 Knowledge Gaps *DO NOT USE FOR PLENARY* - BREAKOUT ONLY When neurologic assessors are independent of the clinical teams (main weakness from the Bernard et al. and HACA trials), is targeted temperature management better than no targeted temperature management?