Hypothermie thérapeutique post-arrêt cardiaque

Transcription

1 Hypothermie thérapeutique post-arrêt cardiaque Alain Cariou Intensive Care Unit Cochin University Hospital Paris Descartes University INSERM U970 (France)

2 Cardiac arrest management: hope and fears Comparison of published VF OHCA survival percentages in various US cities before (white bars) and after (black bars) an EMS based early defibrillation program was instituted

3 Cardiac arrest management: hope and fears New cases/yr in the US Persistent Vegetative State Minimally Conscious State Traumatic Brain Injury Cardiac Arrest Survivors Comparison of published VF OHCA survival percentages in various US cities before (white bars) and after (black bars) an EMS based early defibrillation program was instituted Thurman D et al. JAMA 1999 Engdahl et al. Resuscitation 2002

4 Outcome of sudden cardiac arrest (SCA) victims SCA/yrs 60% CPR 15-20% ROSC Pre-hospital period and ICU admission 3-5% survivors 3% no or minor sequel Long-term? Post-resuscitation: Post-cardiac arrest shock Brain damages Cardiovascular diseases

5 Post-cardiac arrest disease ILCOR Consensus Statement ROSC 20 min 6-12 hours Phase Immediate Early Intermediate Persistent precipitating pathology Systemic ischemiareperfusion 72 hours Recovery Post-cardiac Treatment targets arrest disease Discharge Rehabilitation Post-CA cardiocirculatory dysfunction Post-anoxic brain injury

6 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. n=768 n=499 n=269 Submitted

7 Time-course of brain injury caused by transient cardiac arrest Stop cerebral circulation 20 secondes No Flow Low Flow ROSC Depletion in neuronal O 2 stores 4-6 minutes Complete loss of in brain glucose and ATP stores Reperfusion Reoxygenation-induced reactions Loss of consciousness Neuronal membrane and pumps dysfunction: influx of calcium lactate acidosis glutamate release free fatty acids occurrence oxydative stress inflammatory response Free radical trigerred injury & excito-toxicity: lipid peroxydation primary necrosis apoptosis

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9 Hypothermia and cardiac arrest: preliminary clinical studies Benson DW, Williams GR, Spencer FC. The use of hypothermia after cardiac arrest. Anesth Analg. 1958; 38:423 4 Williams GR Jr, Spencer FC. Clinical use of hypothermia following cardiac arrest. Ann Surg. 1959; 148: Stroke 2000; 31:86-94 Circulation. 2001;104:

10 P. Safar & PM Kochanek.

11 Hypothermia after cardiac arrest: pivotal studies N Engl J Med 346, 2002 European study Out-of-hospital CA First rhythm= VF Coma CGS < 7 Cardiac origin Australian study Out-of-hospital CA First rhythm= VF Coma CGS < 7 Cardiac origin Target temperature: C Duration 24 hrs, in-hospital Sedation + NM blockade HACA study group Target temperature: 33 C 12 hrs, pre- and in-hospital Sedation + NM blockade Bernard et al.

12 Hypothermia after cardiac arrest: pivotal studies N Engl J Med 346, 2002 CPC 1 or 2 (at 6 months) Favorable outcome % RR= 1.44 IC 95 [ ] p= RR= 5.25 IC 95 [ ] p= HT NT HT NT 0 Normothermie (NT) Hypothermie (HT) European study HACA study group N Engl J Med 346, 2002 Australian study Bernard et al.

13 VF studies

14 Should all patients be treated with hypothermia following cardiac arrest? Deem S & Hurford B. Respiratory Care 2007 Condition Therapy NNT Cardiac arrest VF Hypothermia 6 ALI / ARDS Stroke Lung protective ventilation Aspirin AMI Thrombolytics 37-91

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16 Survie angioplastie+/ht+ PCI + / MTH + angioplastie+/htangioplastie-/ht+ PCI - / MTH + PCI + / MTH - angioplastie-/ht- PCI - / MTH Années

17 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.

18 Reasons given for not cooling

19 Critical Knowledge Gaps Related to Post Cardiac Arrest Syndrome Therapy 1. What is the optimal application of therapeutic hypothermia in the post-cardiac arrest patient? a. Which patients benefit? b. What are the optimal target temperature, initiation time, duration, and rewarming rate? c. What is the most effective cooling technique (external vs internal)? d. What are the complications?

20 To cool or not to cool

21 Out-of-hospital cardiac arrest outside home in Sweden, change in characteristics, outcome and availability for public access defibrillation Ringh M, Herlitz J, Hollenberg J, Rosenqvist M, Svensson L Scand J Trauma Resuscitation Emerg Med 2009, 17:18 «The proportion of patients found in ventricular fibrillation (VF) declined from 56% to 50% among witnessed cases (p for trend < ) and a significant (p < ) decline was also seen among non witnessed cases»

22 Resuscitation 2011

23 1145 patients admitted survivors of OHCA 708 patients (62%) VF/ pulseless VT 437 patients (38%) Asystole / PEA Hypothermia Group:457 Pts (65%) No Hypothermia Group: 251 Pts (35%) Hypothermia Group: 261 Pts (35%) No Hypothermia Group: 176 Pts (65%) Good Outcome 201 Pts (44%) Good Outcome 73 Pts (29%) Good Outcome 38 Pts ( 15%) Good Outcome: 30 Pts (17%) X

24 Independent predictors of good outcome after cardiac arrest VF/ VT (n=708) Time A"%#$"%#C#EF#(*# between BLS and ROSC > 15 minutes Epinephrine B7)*5718)*5#C#D#(4# > 3 milligrames Time!"#$"%#&#'#()*# between collapse and BLS! 4minutes Post +",-./0#,1"23# resuscitation shock Blood A;2-;-5#6758#9:;8<=5># Lactate (by quartile increase) Age 045#6758#9:;8<=5># (by quartile increase) Hypothermia?158;75:<2#1@7"-158();# 0 0,5 1 1,5 2 2,5 3 3,5!"#$%&'(%)*$ +%%#$%&'(%)*$ Dumas F et al. Circulation 2011

25 Independent predictors of good outcome after cardiac arrest PEA/ asystolia (n=437) X Time A"%#$"%#C#EF#()*# between BLS and ROSC > 15 minutes Post +",-./0#,1"23# resuscitation shock Time!"#$"%#&#'#()*# between collapse and BLS! 4minutes Blood A;2-;-5#6758#9:;8<=5># Lactate (by quartile increase )?158;75:<2#1@7"-158();# Hypothermia 0 0,5 1 1,5 2 2,5 3 3,5!"#$%&'(%)*$ +%%#$%&'(%)*$ Dumas F et al. Circulation 2011

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

27 Shockable Non shockable More severe brain damages? Dumas F et al. Circulation 2011

28 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

29 Crit Care Med 2011

30 The sooner, the better! Crit Care Med 2011

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32 Cooling methods Methods Speed ( C/h) Maintenance Rewarming Cost Cool air shelter Lent +/ Iced packs Lent «Iced tunnel» Cooled helmet Cooled fluid bed Iced bath ? Cooled air bed ? Iced fluids Cooling catheter Extra-corp. circuit > Lemiale V, Deye N, Cariou A. Traité de Réanimation Médicale 2009

33 «Home made» hypothermia

34 Predictors of external cooling failure after cardiac arrest Ricome S, Dumas F, Mongardon N, Varenne O, Fichet J, Pène F, Zuber B, Vivien B, Charpentier J, Chiche JD, Mira JP, Cariou A Intensive Care Med 2013 (in press)

35 Predictors of external cooling failure after cardiac arrest Ricome S, Dumas F, Mongardon N, Varenne O, Fichet J, Pène F, Zuber B, Vivien B, Charpentier J, Chiche JD, Mira JP, Cariou A Intensive Care Med 2013 (in press)

36 Cooling surfaces Medivance Arctic Sun System n Circulating cooled air or water Criticool

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

38 281/421 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 infection n=4 n=4 85% Sinusite n=3 Sinusitis n=3

39 Pneumonia in post-cardiac arrest patients: mechanisms Coma Emergency airway access Loss of airway protection Mechanical ventilation Pulmonary contusion Post CA pulmonary complications Hypothermia?

40 Incidence of pneumonia in postcardiac arrest patients n=641 Hypothermia era n=765 n=421 n=117 Before hypothermia era n=96 n=56

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43 Therapeutic hypothermia: 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?

44 Sedation Confounds Outcome Prediction in Cardiac Arrest Survivors Treated with Hypothermia Samaniego AS, Mlynash M, Finley Caulfield A, Eyngorn I, Wijman CAC. Neurocritical Care 2011

45 Sedation Confounds Outcome Prediction in Cardiac Arrest Survivors Treated with Hypothermia Samaniego AS, Mlynash M, Finley Caulfield A, Eyngorn I, Wijman CAC. Neurocritical Care 2011 PPV for prediction of 3-month bad outcome (death or vegetative state)

46 Conclusion n Therapeutic hypothermia is indicated in all post- VF comatose patients, and its use should be at least discussed in all others n No device / method demonstrated superiority n Infectious complications (pneumonia) are more frequent in cooled patients n Neurological assessment should be differed in cooled patients