Cara Jager Aios Spoed Eisende Geneeskunde AMC Regionale Refereeravond Juli 2013 ?
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Transcript of Cara Jager Aios Spoed Eisende Geneeskunde AMC Regionale Refereeravond Juli 2013 ?
Therapeutic Hypothermiain Out of Hospital Cardiac Arresttowards
Cara JagerAios Spoed Eisende Geneeskunde AMCRegionale RefereeravondJuli 2013
?
◦ 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
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
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
Therapeutic HypothermiaReally Effective?
PRONolan J and Soar J.BMJ 2011
CONWalden AP, Nielsen et al.BMJ 2011
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
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
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
Targeted Temperature Management = TTM trial
Nielsen et al. Am Heart J 2012
Targeted Temperature Management = TTM trial
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
Current practice: ICU
Timing of Therapeutic hypothermia◦ Animal models: as early as possible
◦ When?
Therapeutic HypothermiaReally effective?
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 SD
Arrest to ROSC (min) 172 24 14.6
Arrest to initiation TH (min) 172 94.4 81.6
Arrest to target temperature (min) 172 309 151
Target temperature maintained (h) 172 23.1 5.4
Sendelbach et al. Resuscitation 2012
40 relevant:
8 RCT
8 Review
Therapeutic HypothermiaPre-Hospital
induced 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
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
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
Therapeutic HypothermiaPre- Hospital: Improving Outcome?
Bernard et al. Circulation 2010
Bernard et al. Crit Care Med 2012
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
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
Feasible lowering temperatures No outcome differences
Therapeutic HypothermiaPrehospital setting
Diao et al. Resuscitation 2013
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