Hypothermie thérapeutique post-arrêt cardiaque

Alain Cariou Intensive Care Unit – Cochin University Hospital Paris Descartes University – INSERM U970 (France)

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

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

0 50 000 100 000 150 000 200 000

Cardiac Arrest Survivors

Traumatic Brain Injury

Minimally Conscious State

Persistent Vegetative State

New cases/yr in the US

Thurman D et al. JAMA 1999 Engdahl et al. Resuscitation 2002

Pre-hospital period

Post-resuscitation:

§  Post-cardiac arrest shock

§  Brain damages

§  Cardiovascular diseases

≈ 30.000 SCA/yrs

60% CPR

15-20% ROSC…

…and ICU admission

3-5% survivors

3% no or minor sequel

Outcome of sudden cardiac arrest (SCA) victims

Long-term ?

Immediate

Early

Intermediate

Recovery

Rehabilitation

Phase ROSC

20 min

6-12 hours

72 hours

Discharge

Post-cardiac arrest disease ILCOR Consensus Statement

Post-cardiac arrest disease

Post-CA cardiocirculatory

dysfunction

Systemic ischemia-

reperfusion

Treatment targets

Post-anoxic brain injury

Persistent precipitating

pathology

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.

Submitted

n=499

n=269 n=768

Time-course of brain injury caused by transient cardiac arrest

Stop cerebral circulation

Depletion in neuronal O2 stores Loss of consciousness

20 secondes

No Flow

Low Flow

ROSC Reoxygenation-induced reactions

Reperfusion

Free radical trigerred injury & excito-toxicity: •  lipid peroxydation •  primary necrosis •  apoptosis

4-6 minutes

Complete loss of in brain glucose and ATP stores

Neuronal membrane and pumps dysfunction: •  influx of calcium •  lactate acidosis •  glutamate release •  free fatty acids occurrence •  oxydative stress •  inflammatory response

Hypothermia and cardiac arrest: preliminary clinical studies

Circulation. 2001;104:1799-1804

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; 148:462–468

Stroke 2000; 31:86-94

P. Safar & PM Kochanek.

European study Australian study

•  Out-of-hospital CA •  First rhythm= VF •  Coma CGS < 7 •  Cardiac origin

•  Out-of-hospital CA •  First rhythm= VF •  Coma CGS < 7 •  Cardiac origin

•  Target temperature: 32-34°C •  Duration 24 hrs, in-hospital •  Sedation + NM blockade

•  Target temperature: 33°C •  12 hrs, pre- and in-hospital •  Sedation + NM blockade

Hypothermia after cardiac arrest: pivotal studies

HACA study group Bernard et al.

N Engl J Med 346, 2002

0

20

40

60

European study Australian study

% RR= 1.44 IC95 [ 1.08-1.81]

p= 0.009

RR= 5.25 IC95 [ 1.47-18.76]

p= 0.011

CPC 1 or 2 (at 6 months) Favorable outcome

Hypothermie (HT)

Normothermie (NT) N Engl J Med 346, 2002

HACA study group Bernard et al.

HT HT NT NT

Hypothermia after cardiac arrest: pivotal studies N Engl J Med 346, 2002

VF studies

Condition

Cardiac arrest VF

ALI / ARDS

Stroke

AMI

Hypothermia

Lung protective ventilation

Aspirin

Thrombolytics

Therapy NNT

6

11

33

37-91

Deem S & Hurford B. Respiratory Care 2007

Should all patients be treated with hypothermia following cardiac arrest?

0.00

0.25

0.50

0.75

1.00

Survie

0 1 2 3 4 5Années

angioplastie-/HT-

angioplastie+/HT+angioplastie+/HT-angioplastie-/HT+

PCI + / MTH +

PCI + / MTH -

PCI - / MTH +

PCI - / MTH -

“The jury RECOMMENDS STRONGLY FOR TTM to a target of 32-34°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.”

Reasons given for not cooling

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?

To cool or not to cool…

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 < 0.0001) and a significant (p < 0.0001) decline was also seen among non witnessed cases »

Resuscitation 2011

1145 patients admitted survivors

of OHCA

708 patients (62%) VF/

pulseless VT

Hypothermia Group:457 Pts

(65%)

Good Outcome 201 Pts (44%)

No Hypothermia Group: 251 Pts

(35%)

Good Outcome 73 Pts (29%)

437 patients (38%) Asystole / PEA

Hypothermia Group: 261 Pts

(35%)

Good Outcome 38 Pts ( 15%)

No Hypothermia Group: 176 Pts

(65%)

Good Outcome: 30 Pts (17%) X

0 0,5 1 1,5 2 2,5 3 3,5

Time between BLS and ROSC > 15 minutes

Epinephrine > 3 milligrames

Time between collapse and BLS ! 4minutes

Post resuscitation shock

Blood Lactate (by quartile increase)

Age (by quartile increase)

Hypothermia

!"#$%&'(%)*$ +%%#$%&'(%)*$

VF/ VT (n=708)

Independent predictors of good outcome after cardiac arrest

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Dumas F et al. Circulation 2011

0 0,5 1 1,5 2 2,5 3 3,5

Time between BLS and ROSC > 15 minutes

Post resuscitation shock

Time between collapse and BLS ! 4minutes

Blood Lactate (by quartile increase )

Hypothermia

!"#$%&'(%)*$ +%%#$%&'(%)*$

PEA/ asystolia (n=437)

X !"#$"%#&#'#()*#

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Dumas F et al. Circulation 2011

Independent predictors of good outcome after cardiac arrest

Different mechanisms of cardiac arrest, which cause different morphologic patterns of brain

damage, may need different cerebral resuscitation treatments.

Dumas F et al. Circulation 2011

Shockable Non shockable

More severe brain damages?

Non shockable

OHCA

TH 24 hours –

32-34°C

ROSC

Rewarming T° control - 37°C

T° Control 72 hours - 37°C

First 72 hours after CA

Proportion of CPC 1-2

in each group

D90

Intervention group

Control group

Crit Care Med 2011

Crit Care Med 2011

The sooner, the better!

Cooling methods

Methods Speed (°C/h) Maintenance Rewarming Cost Cool air shelter Lent +/- +++ + Iced packs Lent ++ 0 0 « Iced tunnel » 1.1 ++ 0 0 Cooled helmet 1.5 + 0 ++ Cooled fluid bed 1.5-3 +++ +++ ++ Iced bath 9.3 +++ 0 ? Cooled air bed - ++ +++ ? Iced fluids 0.6-2.5 0 0 + Cooling catheter 2 +++ +++ +++ Extra-corp. circuit >4 +++ +++ +++

Lemiale V, Deye N, Cariou A. Traité de Réanimation Médicale 2009

« Home made » hypothermia

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)

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)

Cooling surfaces

n  Circulating cooled air or water

Criticool®

Medivance Arctic Sun System™

33.8°C on admission

MJ Foedisch, M Fischer - Bonn / FRG

85%

9%

3% 1% 1% 1%

Pneumonie n=318

Bactériémie n=35

Infection liée au cathéter n=11

Infection intra-abdominale n=5

Infection urinaire n=4

Sinusite n=3

281/421 patients (67%) developed 373 infections:

Pneumonia n=318

Bacteriemia n=35

Catheter-related infection n=11

Intra-abdominal infection n=5

Urinary tract infection n=4

Sinusitis n=3

Post CA pulmonary

complications

Pulmonary contusion

Loss of airway

protection

Coma Emergency airway access

Mechanical ventilation

Hypothermia?

Pneumonia in post-cardiac arrest patients: mechanisms

n=421

n=117

n=56

n=96

Incidence of pneumonia in post-cardiac arrest patients

n=765

n=641

Hypothermia era

Before hypothermia

era

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?

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

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)

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