1. TFQO: Jasmeet Soar #COI 272 EVREV 1: Jasmeet Soar #COI 272 EVREV 2: Michael Donnino #COI 222 Taskforce: ALS ALS 448 OXYGEN DOSE AFTER ROSC IN ADULTS 3 January 2015

2. COI Disclosure Jasmeet Soar #COI 272 Commercial/industry None Potential intellectual conflicts None Michael Donnino COI#222 Commercial/industry None Potential intellectual conflicts None

3. 2010 Treatment Recommendation There is insufficient clinical evidence to support or refute the use of inspired oxygen concentration titrated to arterial blood oxygen saturation in the early care of cardiac arrest patients following sustained ROSC.

4. C2015 PICO P - Among adults who have ROSC after cardiac arrest in any setting I - Does an inspired oxygen concentration titrated to oxygenation (normal oxygen saturation or partial pressure) C - Compared with the use of 100% inspired oxygen O – Improve Survival with favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year (9 - critical outcome), Survival at discharge, 30 days, 60 days, 180 days AND/OR 1 year (8 - critical outcome)? ICU survival (5 - important)?

5. Inclusion/Exclusion Inc lude Human adult studies Observational, non-RCT studies Exclude Paediatric studies Animal studies Reviews, editrorials

6. Pubmed/Embase/Cochrane Search 26 November 2013 12 articles reviewed in detail + 2 further articles identified 2359 citations 8 articles in final review 1 RCT 7 non-RCTs 2347 excluded Title review/abstract review Not relevant 6 excluded (4 paediatric, 1 oxygen during CPR, 1 no PaO2 data) Search details As of 5 December 2014 2 further non-RCT identified by authors Vaahersalo et al. Crit Care Med 2014; 42:1463–1470) Elmer et al. Intensive care Medicine. Dec 2014. 10 studies in updated review 1 RCT, 9 non-RCT

7. 2015 Proposed Treatment Recommendations We recommend the avoidance of hypoxia in adults with ROSC after cardiac arrest in any setting (strong recommendation, very low quality evidence). We suggest the avoidance of hyperoxia in adults with ROSC after cardiac arrest in any setting (weak recommendation, very low quality evidence). We suggest the use of 100% inspired oxygen until the arterial oxygen saturation or the partial pressure of arterial oxygen can be measured reliably in adults with ROSC after cardiac arrest in any setting (weak recommendation, very low quality evidence).

8. Risk of Bias in RCTs

9. Risk of Bias in non-RCTs

13. Proposed Consensus on Science statements 30% inspired oxygen for 60 minutes after ROSC vs. 100% inspired oxygen for 60 minutes after ROSC For the critical outcome of survival to hospital discharge with favourable neurological outcome (CPC 1 or 2) we identified very low quality evidence from one RCT [Kuisma 2006 199] that showed no difference between 30% inspired oxygen for 60 minutes after ROSC vs.100% inspired oxygen for 60 minutes after ROSC. For the critical outcome of survival to hospital discharge we identified very low quality evidence from one RCT [Kuisma 2006 199] that showed no difference between 30% inspired oxygen for 60 minutes after ROSC and 100% inspired oxygen for 60 minutes of after ROSC

14. Consensus on Science statements Hyperoxia vs. Normoxia (1) For the critical outcome of survival with favourable neurological outcome (CPC 1 or 2) at 12 months we identified very low quality evidence from 1 study [Vaahersalo 2014 1463] that showed no harmful effect from hyperoxia during the first 24 hours of ICU care. For the critical outcome of survival to hospital discharge with favourable neurological outcome (CPC 1 or 2) we have identified very low quality evidence from 5 observational studies [Janz 2012 3135, Roberts 2013 2107, Elmer 2014, Kilgannon 2010 2165, Bellomo 2011 R90] with conflicting results [2 showed hyperoxia worse than normoxia].

15. Consensus on Science statements Hyperoxia vs. Normoxia (2) For the critical outcome of survival to discharge (or survival to 30 days) we have identified very low quality evidence from 7 observational studies [Kilgannon 2010 2165, Kilgannon 2011 2717, Bellomo 2011 R90, Janz 2012 3135, Ihle 2013 186, Nelskyla 2013, Elmer 2014] with conflicting results [4 showed hyperoxia worse than normoxia]. For the important outcome of survival to ICU discharge we have identified very low quality evidence from 2 observational studies [Ihle 2013 186, Nelskyla 2013] that showed no harm from hyperoxia.

16. Consensus on Science statements Hypoxia vs. Normoxia () For the critical outcome of survival to discharge (or survival to 30 days) we have identified very low quality evidence from 3 observational studies [Kilgannon 2010 2165, Bellomo 2011 R90, Ihle 2013 186] - 2 showed harm from hypoxia For the important outcome of survival to ICU discharge we have identified very low quality evidence from 1 observational studies [Ihle 2013 186] that showed harm from hypoxia.

17. Draft 2015 Treatment Recommendations We recommend the avoidance of hypoxia in adults with ROSC after cardiac arrest in any setting (strong recommendation, very low quality evidence). We suggest the avoidance of hyperoxia in adults with ROSC after cardiac arrest in any setting (weak recommendation, very low quality evidence). We suggest the use of 100% inspired oxygen until the arterial oxygen saturation or the partial pressure of arterial oxygen can be measured reliably in adults with ROSC after cardiac arrest in any setting (weak recommendation, very low quality evidence).

18. Knowledge Gaps Is it feasible to assess arterial oxygenation after ROSC? Can inspired oxygen be titrated immediately after ROSC? What is the optimum arterial oxygenation Immediately after ROSC? In first 24, 48 or 72 h after ROSC? How is arterial oxygenation assessed in studies SaO2 vs. PaO2? Serial readings of SaO2? Highest lowest readings?