1. 1 Cooling after cardiac arrest From evidence to clinical practice Jan Martner SIR Presenterat vid SFAI-mötet september 2011

2. 2 Out-of hospital cardiac arrest Hospital ER ICU CCU/Ward Survivors In-hospital cardiac arrest 10 000/year

3. 3 Out-of hospital cardiac arrest Hospital ER ICU CCU/Ward Survivors In-hospital cardiac arrest Year 2010 n=1222 SIR 2011

4. 4 ICU Out-of hospital admission In-hospital admission Year 2010 40% 60% SIR 2011

5. 5 Out-of hospital cardiac arrest Hospital ER ICU CCU/Ward 404 (33%) Survivors In-hospital cardiac arrest Longterm (180 days) Outcome 2010 n=1222 818 (67%) SIR 2011

6. 6 N=275

7. 7

8. 8

9. 9

10. 10 N Engl J Med 2002 346 557 N=77

11. 11 Results  Improved neurological outcome  Mortality: TH 51% vs no-TH 68% (ns.)

12. 12 ILCOR recommendation: Resuscitation 2003 57 231-5 Unconscious adult patients with spontanous circula- tion after out-of-hospital cardiac arrest should be cooled to 32-34 o C for 12-24 h when the initial rythm was ventricular fibrillation (VF). Such cooling may also be beneficial for other rythms or in-hospital arrest.

13. 13 SBU's appraisal of the evidence The scientific evidence is insufficient* to show that treatment with induced hypothermia after resuscitation from cardiac arrest improves survival or lowers the risk for permanent functional impairment. Although the scientific evidence is too weak to support reliable conclusions, the method appears to be promising and potentially may be of clinical importance. However, it is essential to continue testing this method in Sweden under scientifically acceptable conditions so that its benefits, risks, and cost effectiveness can be assessed. Until adequate scientific evidence is available, therapeutic hypothermia should be used only within the framework of well-designed, prospective, and controlled trials. Alert report from SBU 2006

14. 14 2002 2004 2006 2008 2010 2012 Original publications in N Engl J M Start of Hypothermia Network Registry Recommended use by ILCOR Alert report From SBU Report from Hypothermia Network Registry published

15. 15

16. 16 Results  From 2004 until 2008 986 patients were reported the Hypothermia Network  50 % of the patients had a longterm survival  > 90 % had good neurological function

17. 17 2002 2004 2006 2008 2010 2012 Original publications in N Engl J M Widespread use of TH in Sweden Start of Hypothermia Network Registry Recommended use by ILCOR Alert report From SBU Report published from HNR SIR 10 year anniversery SIR was born 2001 2011

18. 18 Proportion of ICU patients with cardiac arrest receiving hypothermia treatment 2003-2010:

19. 19 Proportion of hypothermia treatment according to hospital type

20. 20 Proportion of patient recieving hypothermia treatment according to region 2004-2010

21. 21 Proportion of patient recieving hypothermia treatment vs total number of cardiac arrest patients per ICU

22. 22 Active cooling after cardiac arrest Out-of-hospital 2010 (N=791)

23. 23 Why was the introduction of TH after cardiac arrest so rapid ?  Contrary to drugs no official approval was required  No substantial extra costs except increased LOS in the ICU  An effective tool to improve outcome after cardiac arrest was much desired  ILCOR recommended TH  Group pressure ??  Perhaps intensivists are more bold and impatient regarding introduction of new methods than other doctors ????

24. 24 Can the results from the RCTs  with a very high degree of patient selection  with strict protocols  and performed in dedicated ICUs be replicatet in a widespread ”real life” use with broader inclusion criteria ?

25. 25 Tabell 1 - Jämförelse av patienter med och utan aktiv hypotermi Activ hypothermiaNo aktiv hypothermia P-value Number of patients1398 (36.1 %)2520 (64.3 %) Age, mean (SD)64.1 (15.6) år67.2 (16.8) år<0.001 (t-test) Gender (Male/Female) 70.4 / 29.6 %62.8 / 37.2 %<0.001 (Chi 2 -test) Risk of death (Apache), mean (SD). 74.5 (16.7) % N=762 71.3 (22.9) % N=1294 <0.001 (t-test) LOS ICU, median (IQR) 88 (55-141) tim30 (9-74) tim<0.001 (t-test) Surviving patients 30 days after ICU admission 41.3 % 30.7 % <0.001 (Chi 2 -test) a bedömt enligt APACHE-systemet (8) Comparison of patients with or without activ hypothermia

26. 26 Case study II: Active cooling after out-of-hospital cardiac arrest SIR data from 2005-2010

27. 27 Registry studies vs RCT  Data quickly available  Reflects ”real life” conditions  Can easily be combined with other registry data

28. 28 2002 2004 2006 2008 2010 2012 Original publications in N Engl J M Start of Hypothermia Network Registry Recommended use by ILCOR Alert report From SBU Report from Hypothermia Network Registry published Start of TTM trail The use of TH is based on more solid data ?

29. 29 Conclusions  TH was rapidly introduced in Swedish ICUs in spite of effects not being fully scientifically proven  There are no differences between different types of hospitals regarding introduction and use of TH although there are large differences between individual ICUs  There are minor regional differences regarding the use of TH  ICUs admitting many patients after cardiac arrest show more conformity in the use of TH  A national quality registry with good cover is a valuable tool to monitor introduction of new therapeutic strategies  Survival (30 days) ”in real life” was higher after TH perhaps indicating a positive effect of TH