Targeted temperature management after post-anoxic brain insult: where do we stand?

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1 Targeted temperature management after post-anoxic brain insult: where do we stand? Alain Cariou Intensive Care Unit Cochin University Hospital Paris Descartes University INSERM U970 (France)

2 COI Disclosure Bard France Pulsion

3 Outcome of cardiac arrest victims Sudden cardiac arrest 60% CPR 15-20% ROSC Pre-hospital period and ICU admission 3-5% survivors 3% no or minor sequel Post-resuscitation: Post-cardiac arrest shock Brain damages Long-term?

4 ICU mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort Lemiale V, Dumas F, Mongardon N, Giovanetti O, Charpentier J, Chiche JD, Carli P, Mira JP, Nolan J, Cariou A Intensive Care Med 2014 n=768 n=499 n=269

5 PCI + / MTH + PCI + / MTH - PCI - / MTH + PCI - / MTH -

6 European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support Deakin CD, Nolan JP, Soar J, Sunde K, Kostere RW, Smith GB, Perkins GD Resuscitation 2010

7 Reasons given for not cooling

8 The jury RECOMMENDS STRONGLY FOR TTM to a target of c as preferred treatment (versus unstructured temperature management) of out of hospital adult cardiac arrest victims with a first registered rhythm of VF or pulseless VT and still unconscious after restoration of spontaneous circulation.

9 WHAT LEVEL? 33 C: the dogma

10 Bladder Temperature in the Normothermia and Hypothermia Groups? The Hypothermia after Cardiac Arrest Study Group, N Engl J Med 2002;346:

11 WHAT LEVEL? 36 C: the future? 33 C: the dogma

12 Nielsen N. NEJM 2013

13 Nielsen N. NEJM 2013 Nielsen N et al. NEJM 2013

14 FOR EVERYONE?

15 VF studies

16 To cool or not to cool

17 Cobb LA. JAMA 2002 Annual cases of VF in Seattle, WA

18 Resuscitation 2011

19 Independent predictors of good outcome after cardiac arrest PEA/ asystolia(n=437) X Time Low between flow > 15 BLS minand ROSC > 15 minutes Post-CA resuscitation shock shock Time No flow between 4 min collapse and BLS 4minutes Blood Lactate Lactate (per quartile) (by quartile increase ) Therapeutic Hypothermiahypothermia 0 0,5 1 1,5 2 2,5 3 3,5 Bad outcome Good outcome Dumas F et al. Circulation 2011

20 Use of therapeutic hypothermia p<0.001 Use of therapeutic hypothermia 68% 75% 49% 50% Shockable N=876 Non shockable N=1492

21 «Different mechanisms of cardiac arrest, which cause different morphologic patterns of brain damage, may need different cerebral resuscitation treatments.»

22 Control group T Control 72 hours - 37 C D90 Non shockable OHCA ROSC First 72 hours after CA Proportion of CPC 1-2 in each group TH 24 hours C Rewarming T control - 37 C Intervention group

23 HOW EARLY?

24 The sooner, the better! Crit Care Med 2011

25 MJ Foedisch, M Fischer - Bonn / FRG 33.8 C on admission

26 Is soonerreallybetter?

27 Prehospital therapeutic hypothermia after cardiac arrest: A systematic review and meta-analysis of randomized controlled trials Diao M et al. Resuscitation 2014 Regarding the survival to hospital discharge, favorable neurological outcome at hospital discharge, and rearrest, our meta-analysis and review produces non-significant results. Using the GRADE methodology, we conclude that the quality of evidence is very low.

28 Rearrest post-randomization Intervention (n=686) Control (n=671) P value 176 (26) 138 (21).008

29 Eighteen device-related adverse events (1 periorbital emphysema, 3 epistaxis, 1 perioral bleed, and 13 nasal discolorations) were reported. Circulation 2010

30 WHAT COMPLICATIONS?

31 Hypothermia for neuroprotection in adults after CPR Arrich J, Holzer M, Havel C, Mu llner M, Herkner H. Cochrane Library 2012 Studies Nb Pts RR (95% CI) Bleeding ( ) Platelet transfusion ( ) Pneumonia ( ) Sepsis ( ) Pancreatitis ( ) Renal failure or oliguria ( ) Across all Haemodialysis studies, there was no 2significant 350difference 1.11 in ( ) reported adverse events between hypothermia and control. Pulmonary edema ( ) Seizures ( ) Severe arrhythmia ( ) Significant haemorrhage 1???? Cardiac complication ( ) Hypokalaemia ( ) Hypophosphataemia 1

32 Infectious complications in out-of-hospital cardiac arrest patients in the therapeutic hypothermia era Mongardon N, Perbet S, Lemiale V, Dumas F, Poupet H, Charpentier J, Péne F, Chiche JD, Mira JP, Cariou A Crit Care Med /421 patients (67%) developed 373 infections: 3% 1% 1% 1% Pneumonie n=318 9% Pneumonia n=318 Bacteriemia n=35 Bactériémie n=35 Catheter-related infection n=11 Infection liée au cathéter n=11 Intra-abdominal infection n=5 Infection intra-abdominale n=5 Urinary Infection tract urinaire infectionn=4 n=4 85% Sinusite n=3 Sinusitis n=3

33

34 Should we add antibiotic prophylaxis after cardiac arrest? If yes, in which patients?????

35

36 Braintoxicity of glucose Stress Glut 1 + Hypoxia IL-1,IL-6,TNFa Intracellular glucose Glucose use Apoptosis Oxydantsreactives pecies glycolysis

37 Increased BG variability during TH is an independent risk factor of in-hospital mortality, irrespective of mean BG levels and of the severity of injury. These data suggest that increased BG variability during TH is more important than BG levels per se in predicting prognosis of coma after CA.

38 Therapeutic hypothermia after cardiac arrest : safety concerns Unintentional overcooling Electrolyte abnormalities Worsening of haemodynamic status Exacerbation of the inflammatory response Use of muscle relaxants Reduced cytochrome P450 activity Increase of the infection rate Decreased risk-benefit ratio in certain subgroups?

39 71 studies found for: Therapeutic hypothermia Open Studies Studies Without Results

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