therapeutic hypothermia in out of hospital cardiac arrest towards
DESCRIPTION
Therapeutic Hypothermia in Out of Hospital Cardiac Arrest towards. ?. Cara Jager Aios Spoed Eisende Geneeskunde AMC Regionale Refereeravond Juli 2013. Therapeutic Hypothermia in OHCA: Background. Europe: ± 10 - 20% survives OHCA Mortality and morbidity largely due to anoxic brain injury - PowerPoint PPT PresentationTRANSCRIPT
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Therapeutic Hypothermiain Out of Hospital Cardiac Arresttowards
Cara JagerAios Spoed Eisende Geneeskunde AMCRegionale RefereeravondJuli 2013
?
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◦ Europe: ± 10 - 20% survives OHCA
◦ Mortality and morbidity largely due to anoxic brain injury◦ 7-30% good neurological outcome
Therapeutic hypothermia (TH)/ Mild Induced Hypothermia (MIH) recommended current guidelines
◦ Bernard et al. N Engl J Med 2002◦ HACA study group. N Engl J Med 2002
Therapeutic Hypothermia in OHCA: Background
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Where?- Inhospital
Therapeutic HypothermiaCurrent Practice
When?- Post cardiac arrest
How?- External cooling techniques- Internal cooling techniques
Which population?- Post cardiac arrest/ ROSC- No recent trauma- GCS ≤ 8
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Induction Sedation Cold fluids 4°C Cool Mattress
Maintenance Target temperature 32°- 34° within 4 hours 24 hrs
Rewarming Slow, 0.25- 0.5 °C/h within 8 hours Stop sedation at 36°C
Awake/ Postanoxic coma?
Therapeutic Hypothermia:Current Practice the Netherlands
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Therapeutic HypothermiaReally Effective?
PRONolan J and Soar J.BMJ 2011
CONWalden AP, Nielsen et al.BMJ 2011
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ProNeurological Outcome
Arrich et al. Cochrane 2010
NNT = 5
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Evidence good enough to support mild induced hypothermia in OHCA◦ Patients with VF◦ In other circumstances evidence weaker
(neurological outcome generally worse)
Package of care in resuscitation protocol
By no means perfect trials
Therapeutic HypothermiaPRO
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Bernard 2002:◦ Quasi randomization with odd and even dates◦ Unplanned adaptive design:
nonscheduled interim analysis after inclusion of 80% of the patients (no adjustment of P-value)
Therapeutic HypothermiaCON
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ConNeurological Outcome
Nielsen et al. Int J Cardiology 2011
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Majority of the trials compared therapeutic hypothermia with no temperature control in the control groups◦ Control groups: majority not treated for fever, median temp: 37°C - 38°C
Intervention effect due to:◦ Increased temperature in control group?◦ Beneficial induced hypothermia?◦ Both?
Observational data poor outcome with higher temperatures:◦ OR 2.26 (1.24–4.12) for every degree higher than 37 °C◦ Clear association, how about causality?
Con
Nielsen et al. Int J Cardiology 2011
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Targeted Temperature Management = TTM trial
Nielsen et al. Am Heart J 2012
Targeted Temperature Management = TTM trial
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International, multicenter RCT Assessor blinded
Inclusion: ≥ 850 patients
Controlled hypothermia 33° versus controlled 36°
Standardized treatment decisions
Outcome:◦ All cause mortality◦ Poor neurological function◦ Adverse events
Presented at American Heart Association meetingNovember 2013 Dallas
TTM-trial: protocol
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Current practice: ICU
Timing of Therapeutic hypothermia◦ Animal models: as early as possible
◦ When?
Therapeutic HypothermiaReally effective?
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Emergency Department?
Therapeutic HypothermiaWhen?
Egmond 2013
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Regression-analysis For every 5 minute delay in initiating TH:
increased chance of having a poor neurological outcomeOR 1.06 (95% CI 1.02-1.10)
Retrospective observational study◦ Clear association, how about causality?
Optimal timing of TH?
Time Intervals N mean SDArrest to ROSC (min) 172 24 14.6Arrest to initiation TH (min) 172 94.4 81.6Arrest to target temperature (min) 172 309 151Target temperature maintained (h) 172 23.1 5.4
Sendelbach et al. Resuscitation 2012
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Pre-hospital setting?
Therapeutic HypothermiaWhen?
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40 relevant:
8 RCT
8 Review
Therapeutic HypothermiaPre-Hospitalinduced hypothermia [MESH]hypothermia [MESH]hypothermia, induced [MESH]induced mild hypothermia [MESH]induced moderate hypothermia [MESH]cooling [T/A]therapeutic [T/A] AND hypothermia [T/A]therapeutic [T/A] AND cooling [T/A]
50952
prehospital [T/A]pre-hospital [T/A]paramedic*[T/A] 12942
intra-arrest [T/A]intra arrest [T/A]intraarrest [T/A]post-arrest [T/A]post arrest [T/A]postarrest [T/A] 13259
Medline 1966 – 06-2013
AND
arrest [T/A]cardiac arrest [T/A]OHCA [T/A]out of hospital cardiac arrest [T/A]out-of-hospital cardiac arrest T/A]out of hospital cardiac arrest [MESH] 83480
AND
187 hits
Limits English
Total 173 hits
Pre hospital/ Emergency Department:
Post-arrest/ post-ROSC
Intra-arrest
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Therapeutic HypothermiaPre- Hospital
Diao et al. Resuscitation 2013
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RCT, n= 37 Ice cold saline infusion versus normal treatment
Bottom line: Prehospital induction of mild hypothermia is feasible Cooling rate 2°C/h (95% CI 1.5-2.7) Not to the level of therapeutic hypothermia
Acta Anaesthesiol Scand 2009
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RCT, n= 125 Ice cold saline infusion versus normal treatment
Bottom line: Significant lower temperature at hospital arrival with ice cold
saline◦ volume dependent
Not associated with adverse events(i.e. pulmonary edema, rearrest)
Kim et al. Circulation 2007
*P0.0001 by ANOVA
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Therapeutic HypothermiaPre- Hospital: Improving Outcome?
Bernard et al. Circulation 2010
Bernard et al. Crit Care Med 2012
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6730=Total cardiac arrests during trial period
6436 =Adults ≥ 15y with cardiac arrest during trial period
4763=Cardiac arrest of presumed cardiac cause
2268=Resuscitation attempted by paramedics
842=Initial rhythm ventricular fibrillation
1426= Initial rhythm asystole/ PEA
398=ROSC and transport to hospital
234=Eligible and enrolled
164=Eligible/
Not enrolled
118=Paramedic cooling
100 ml/min cold salineup to 2l
116=Hospital cooling
118=Assessed for 1° endpoint
116=Assessed for 1° endpoint
309=ROSC and transport to hospital
146=Eligible/
Not enrolled
163=Eligible and enrolled
82=Paramedic cooling
100 ml/min cold salineup to 2l
82=Hospital cooling
82=Assessed for 1° endpoint
81=Assessed for 1° endpoint
Bernard et al 2010 Bernard et al 2012
Prospectivemulticenter RCT
AustraliaOct 2005- Nov 2007
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Bottom line:In pre-hospital cooled group Significant decrease in temperature at hospital arrival Less time to reach therapeutic hypothermia (<34°C)
No benefit cooling in the field in patients with OHCA◦ either VF or nonVF
Postarrest Prehospital Cooling:Improving Outcome?
WHY?
Bernard et al. 2010 and 2012
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Rewarming?
Bernard et al. 2010
Cooling in field or ED same temperature 1h after arrival
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Feasible lowering temperatures No outcome differences
Therapeutic HypothermiaPrehospital setting
Diao et al. Resuscitation 2013
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Current practice◦ To believe or not to believe
Towards The Cold Chain Prehospital cooling:
◦ Post-arrest, feasible◦ Intra-arrest, the future?
Package of care?
Therapeutic Hypothermia:Summary
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Intra-Arrest? Package of Care?
BMC Emergency Medicine 2011
J Translational Medicine 2012
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Baseline CharacteristicsBernard 2010 VF/ VT Bernard 2012 non- VF
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Diao et al. Resuscitation 2013
Baseline Characteristics