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Therapeutic Hypothermia,
Göran Olivecrona, MD PhD
Vienna, October 18, 2015
Department of CardiologyLund University
Skåne University Hospital-LundLund, Sweden
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For whom?
Hypothermia • Successfully Resuscitated patients still in coma
following cardiac arrest due to cardiac causes and with reasonable chances of a good neurologic outcome
Why & When • As soon as possible after hospital arrival to increase survival.
• Targeted temperature managements (TTM) with intravascular or topical cooling devices to target temperature ≤ 36°C for 24 hrs.
How?
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What is the mechanism by which hypothermia reduces Cell death ???
• Reduction of metabolism
• Reduction of oxygen consumption
• Multifactorial chemical and physical mechanisms- Retardation of destructive enzymatic reactions, - Suppression of free-radical reactions, - Protection of the fluidity of lipoprotein membranes, - reduction of the oxygen demand in low flow regions, - Reduction of intracellular acidosis,- Inhibition of the biosynthesis, release, and uptake of excitatory neurotransmitters.
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Hypothermia after Cardiac ArrestLandmark trials
2002
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Hypothermia Registry • 986 patients from 34 hospitals• 975 patients with 6 months follow-up• 50 % survival rate at 6 months
– 46% good outcome• Few vegetative patients (n=4)• Time from arrest to hypothermia and time
from arrest to target temperature were not related to outcome
Nielsen et al. Acta Anesth Scand 2009;53:926
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• ERC• AHA• Cochrane• Multiple national guidelines
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2010 Guidelines based on
• Randomised clinical trials: 2
• Observational studies: More
• Expert opinions: Even more
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Update needed on optimal temperature and Timing of Hypothermia
TTM StudyNEJM 2013
Kim et al.JAMA 2014
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• 950 patients randomized• 36 hospitals• 10 countries• Europe and Australia
Funded by:
Swedish Heart Lung Foundation
AFA-insurance Foundation, Sweden
Swedish Research Council
Governmental and Regional funding within the Swedish National Health System
TrygFoundation, Denmark
Zoega, Krapperup, Thure Carlsson, Trolle-Wachtmeister foundations, Sweden
TTM-trial 2010-2013Targeted Temperature Management
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• To assess the benefits and harms of a targeted temperature management at 33°C versus 36°C in a prospective randomized trial
• Avoiding fever in post-cardiac arrest patients in both groups
Main Objectives TTM study
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• Out-of-hospital cardiac arrest
• Adult (18 years and over)
• Presumed cardiac cause
• All initial rhythms
• Unconscious (Glasgow Coma Scale < 8)
• Stable Return of Spontaneous Circulation
Inclusion Criteria
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Nielsen et al HACA study
~37.6oC
~36.0oC
Bernard et al: ~37.3oC
Large difference in maintenance temperatures
Active TTM
Difference compared to previous trials
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P=0.51
No difference in survival
Survival
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Cerebral Performance Category
No difference in CPC
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Seattle & King CountyCardiac arrest study
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Field Cardiac Arrest
1364
N=583VF
Intervention292
Control291
5696
Eligible
Enrolled
2377
N=776Non-VF
Intervention396
Control380
Not Eligible (3319)
Not Enrolled (1013)
Outcomes: Survival at discharge/neurologic status
Trial Flow
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Outcomes-Survival
VF intervention n=292control n=291
Non-VF intervention n=396
control n=380
No difference in survival
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Outcomes-neurologic status at discharge
No difference in Neurologic Outcome
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30275
950
1364
77
Landmark Trials
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2015 Updated AHA GuidelinesClass I, (LOE B-R)• Treating comatose adult patients with ROSC after out-of-hospital VF/VT
cardiac arrest should be cooled to 32°C to 36°C.
Class I, (LOE C-EO)• Treating comatose adult patients with ROSC after out-of-hospital with non
VF/VT (non shockable) cardiac arrest or in hospital cardiac arrest should be cooled to 32°C to 36°C.
Class IIa, (LOE C-EO)• Hypothermia (TTM) post cardiac arrest should be maintained for at least 24
hours after achieving target temperature. R= based on randomized studiesEO= based on consensus of expert opinions
Callaway et al. Circulation. 2015;132[suppl 1]:S465–S482
TTM= Targeted Temperature Managment
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2015 Updated AHA Guidelines
Class III: No Benefit, (LOE A)• Recommendation against the routine pre hospital administration of cold
intravenous fluids in patients with ROSC.
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Conclusions: Who to cool
ü HACA criteria: good outcome 49% - 70%ü All VT/VF: good outcome 45% - 66%ü Asystole: good outcome 19% - 50%
Ø All “reasonable” Patients with VT/VF and Non-VF/VT cardiac arrest both out-of-hospital and in-hospital
(level I evidence)
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Conclusions: Why to Cool
Ø To reduce MortalityØ To Increase Neurologic functionØ To decrease Myocardial infarct size ?
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Conclusions: How & When to Cool
Following ROSC and arrival in the ERØ Initiate cooling with a topical or intra vascular device.Ø Continue to target temperature of 32°-36°C.Ø Maintain mild hypothermia (32°-36°C) for at least 24
hrs.Ø Liberal use of angiography/PCI in VF patients even
without STE-Elevation
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Cardiac Arrest• The optimal target temperature is now 32°-36°C• Pre hospital cooling has no benefit• Follow guidelines until more data is available• Patient selection is important
Take-home message
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Remaining questions for post Cardiac arrest patients?
• Hypothermia – what temperature(<37°C)?
• Hypothermia – duration?• Rewarming phase – importance of?
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Conclusions1. Hypothermia post cardiac arrest is standard of care for All correctly selected patients with ROSC.2. Cooling should be initiated as soon as possible but can be delayed until arrival in hospital.
3. Target Temperature is now 32°-36°C. -Duration is currentlly 24 hours but needs to be evaluated
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