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WAWA--ACEP Journal ClubACEP Journal Club

Value of Therapeutic Hypothermia Value of Therapeutic Hypothermia as a Treatment Modalityas a Treatment Modality(May 18, 2011)(May 18, 2011)

Today’s OutlineToday’s Outline

Review History and Objectives of JCReview History and Objectives of JC Summary of November JCSummary of November JC Therapeutic HypothermiaTherapeutic Hypothermia Therapeutic HypothermiaTherapeutic Hypothermia

–– Current status as treatment modalityCurrent status as treatment modality–– Literature on TH in cardiac arrestLiterature on TH in cardiac arrest–– “Cutting Edge” uses“Cutting Edge” uses–– Sample Protocols in current useSample Protocols in current use

Open ForumOpen Forum

Background on WABackground on WA--ACEP ACEP Journal ClubJournal Club Proposed by WAProposed by WA--ACEP Board in 2009ACEP Board in 2009 Funded by National ACEP Grant in Funded by National ACEP Grant in

2010201020102010 Coordinated by WACoordinated by WA--ACEP Board ACEP Board

Education SubcommitteeEducation Subcommittee This is our second sessionThis is our second session

Strategic Goals for JCStrategic Goals for JC

BiBi--annual Webinarsannual Webinars Open to all WAOpen to all WA--ACEP members ACEP members CMECME CMECME Active participation of WA EM Active participation of WA EM

ResidentsResidents

Review of WAReview of WA--ACEP ACEP Journal Club ObjectivesJournal Club Objectives To the extent possible, standardize To the extent possible, standardize

medical care on controversial topicsmedical care on controversial topics Improve communication amongstImprove communication amongst Improve communication amongst Improve communication amongst

state providersstate providers Stimulate literature discussionStimulate literature discussion Promote skills in the critical evaluation Promote skills in the critical evaluation

of the literature.of the literature.

Today’s Topic Today’s Topic ––Therapeutic HypothermiaTherapeutic Hypothermia Current status as treatment modalityCurrent status as treatment modality Literature on TH in cardiac arrestLiterature on TH in cardiac arrest

–– Should we expand beyond post VShould we expand beyond post V--fibfib–– Should we expand beyond post VShould we expand beyond post V--fib fib arrest?arrest?

–– Pro/Con arguementPro/Con arguement

“Cutting Edge” uses“Cutting Edge” uses Sample Protocols in current useSample Protocols in current use

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Common Template for Common Template for article presentationsarticle presentations TitleTitle Objective of StudyObjective of Study Methodology/Study DesignMethodology/Study Design ResultsResults

–– Statistical AnalysisStatistical Analysis–– Variables InvolvedVariables Involved

Panel DiscussionPanel Discussion–– Was the Objective of the study met?Was the Objective of the study met?–– Biases/Flaws/ExtrapolationsBiases/Flaws/Extrapolations

Key ReferencesKey References Short Open Discussion on each paperShort Open Discussion on each paper

Therapeutic Hypothermia Therapeutic Hypothermia –– Where are we today?Where are we today? Consensus PaperConsensus Paper

–– Circulation 2008: 118; 2452Circulation 2008: 118; 2452--24832483–– International Liason Committee on ResuscitationInternational Liason Committee on ResuscitationAmerican Heart AssociationAmerican Heart AssociationAustralian & New Zealand Council on ResuscitationAustralian & New Zealand Council on ResuscitationEuropean Resuscitation CouncilEuropean Resuscitation CouncilHeart & Stroke Foundation of CanadaHeart & Stroke Foundation of CanadaInterAmerican Heart FoundationInterAmerican Heart FoundationResuscitation Council of AsiaResuscitation Council of AsiaResuscitation Council of Southern AfricaResuscitation Council of Southern Africa

ILCOR ObjectiveILCOR Objective

Review all literature pertaining to the unique Review all literature pertaining to the unique pathophysiologic state of pathophysiologic state of Post Cardiac Arrest SyndromePost Cardiac Arrest Syndrome––PostPost--arrest Brain Injuryarrest Brain InjuryPostPost arrest Brain Injuryarrest Brain Injury––PostPost--arrest Myocardial Dysfunctionarrest Myocardial Dysfunction––Systemic Ischemia/ Reperfusion ResponseSystemic Ischemia/ Reperfusion Response––All complicated by the unresolved process All complicated by the unresolved process

that caused the initial arrest.that caused the initial arrest.

ILCOR MethodologyILCOR Methodology

EpidemiologyEpidemiologyPathophysiologyPathophysiologyTherapeutic StrategiesTherapeutic StrategiesTherapeutic StrategiesTherapeutic StrategiesPost Cardiac Arrest PrognosticationPost Cardiac Arrest PrognosticationPediatric ConsiderationsPediatric ConsiderationsChallenges to ImplementationChallenges to ImplementationBibliography Bibliography ( 374 key references)( 374 key references)

EpidemiologyEpidemiology

Early Post arrest PhaseEarly Post arrest Phase: 20 minutes to 6: 20 minutes to 6--12 hours12 hours Intermediate Phase:Intermediate Phase: 12 to 72 hours12 to 72 hours Recovery PhaseRecovery Phase: Beyond 3 days: Beyond 3 days Cerebral Performance Categories: 1 & 2 goodCerebral Performance Categories: 1 & 2 good-- 5 5

dead dead One Canadian Study; 71% ICU admits after ROSC One Canadian Study; 71% ICU admits after ROSC

still died before discharge.still died before discharge.

PathophysiologyPathophysiology

Post Arrest Brain InjuryPost Arrest Brain Injury: Increased with pyrexia, : Increased with pyrexia, hyperglycemia, & seizures. 68% of in house hyperglycemia, & seizures. 68% of in house deaths attributable to brain death.deaths attributable to brain death.

Post Arrest Myocardial DysfunctionPost Arrest Myocardial Dysfunction: EF : EF y yy ydecreases from 55% to 20% even with normal decreases from 55% to 20% even with normal coronary perfusion. “Stunning”. Peaks at 8 coronary perfusion. “Stunning”. Peaks at 8 hours, resolved by 72 hours.hours, resolved by 72 hours.

Systemic Ischemia/ ReperfusionSystemic Ischemia/ Reperfusion: Similar to : Similar to Sepsis.Sepsis.

Precipitating PathologyPrecipitating Pathology: OOH Arrest, 50% due : OOH Arrest, 50% due to MI. InH Arrest, 11% due to MI. to MI. InH Arrest, 11% due to MI.

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Therapeutic StrategiesTherapeutic Strategies MonitoringMonitoring: Hemodynamically is EGDT. MAP : Hemodynamically is EGDT. MAP

6565--100. CVP 8100. CVP 8--12.12. OxygenationOxygenation: O2 sats 94: O2 sats 94--96%, avoid free 96%, avoid free

radicals/ hyperoxia.radicals/ hyperoxia. Circulatory SupportCirculatory Support: Preload first Inotropes: Preload first Inotropes Circulatory SupportCirculatory Support: Preload first, Inotropes : Preload first, Inotropes

second, IABP third.second, IABP third. Management ACSManagement ACS: PCI!: PCI! Sedation & Neuromuscular BlockadeSedation & Neuromuscular Blockade: Control : Control

Seizures & myoclonus. Up to 15% after ROSC Seizures & myoclonus. Up to 15% after ROSC have seizures, and up to 40% of those remain have seizures, and up to 40% of those remain comatose.comatose.

Glucose ControlGlucose Control: Target 80: Target 80--144.144.

Therapeutic Strategies:Therapeutic Strategies:Mild HypothermiaMild HypothermiaONLY therapy postONLY therapy post--arrest to be arrest to be

proven to increase both survival proven to increase both survival & Cerebral Performance& Cerebral Performance& Cerebral Performance & Cerebral Performance CategoryCategory!!Pyrexia MUST be avoided!Pyrexia MUST be avoided!3 Phases: Induction, Maintenance & 3 Phases: Induction, Maintenance &

RewarmingRewarming

Therapeutic Mild Therapeutic Mild HypothermiaHypothermia

Induction:Induction: Iced Crystalloid vs. Ice Iced Crystalloid vs. Ice Packs without delay.Packs without delay.MaintenanceMaintenance: 12: 12 24 hours at 3224 hours at 32 3434MaintenanceMaintenance: 12: 12--24 hours at 3224 hours at 32--34 34

degrees C. External vs. Internal degrees C. External vs. Internal devices to avoid fluctuations.devices to avoid fluctuations.Rewarming:Rewarming: 0.250.25--0.5 degrees C per 0.5 degrees C per

hour.hour.

Complications Associated With Complications Associated With Therapeutic Mild HypothermiaTherapeutic Mild HypothermiaShiveringShivering Increases SVR & reduces COIncreases SVR & reduces CO Induces ArrhythmiaInduces ArrhythmiaDiuresis: Associated hypophosphatemia, Diuresis: Associated hypophosphatemia,

hypokalemia, hypomagnesemia, hypokalemia, hypomagnesemia, hypocalcemia.hypocalcemia. Impair Immune ResponseImpair Immune ResponseHyperglycemiaHyperglycemiaDelays Drug MetbolismDelays Drug Metbolism

Think Magnesium!

Mild Therapeutic Hypothermia to Improve the Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac ArrestNeurologic Outcome after Cardiac ArrestANDANDTreatment of Comatose Survivors of Out of Hospital Treatment of Comatose Survivors of Out of Hospital Cardiac Arrest with Induced HypothermiaCardiac Arrest with Induced HypothermiaStephen Bernard MB, et al, Stephen Bernard MB, et al, NEJM Feb. 21, 2002; 346: 549NEJM Feb. 21, 2002; 346: 549--556 & 557556 & 557--563563

Back to back papers (European data vs. Melbourne data)Back to back papers (European data vs. Melbourne data) Compare Survival & Neurologic outcomes of TMH vs. Normothermic Compare Survival & Neurologic outcomes of TMH vs. Normothermic

patients s/p ROSC from VF or PVT.patients s/p ROSC from VF or PVT. Similar designs (more excluded from European data). Good Similar designs (more excluded from European data). Good

outcome defined as class 1 or 2 CPC.outcome defined as class 1 or 2 CPC. Study 1: Death rate 14% lower in hypothermia group. Favorable Study 1: Death rate 14% lower in hypothermia group. Favorable

Neurologic outcome 54% in Hypothermia group vs. 39% in Neurologic outcome 54% in Hypothermia group vs. 39% in Normothermia group.Normothermia group.

Study 2: Good neuro outcome in 49% or Hypothermia group vs. Study 2: Good neuro outcome in 49% or Hypothermia group vs. 26% in Normothermia group.26% in Normothermia group.

Prognostication Prognostication Post ArrestPost Arrest

Multifactoral. Best remains bedside Multifactoral. Best remains bedside neurological exam with focus on neurological exam with focus on ggcranial nerves at day 3 to predict cranial nerves at day 3 to predict poor outcome.poor outcome.Hypothermia protocol may delay Hypothermia protocol may delay

this.this.

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Implementation Implementation ChallengesChallenges

??Pertinent ReferencesPertinent References

Bernard SA, Gray TW, et al. Treatment of comatose survivors ofBernard SA, Gray TW, et al. Treatment of comatose survivors ofBernard SA, Gray TW, et al. Treatment of comatose survivors of Bernard SA, Gray TW, et al. Treatment of comatose survivors of out of hospital cardiac arrest with induced hypothermia. NEJM. out of hospital cardiac arrest with induced hypothermia. NEJM. 2002; 346: 5572002; 346: 557--563.563.

Sunde K, Pytte M, et al. Implementation of a standardized Sunde K, Pytte M, et al. Implementation of a standardized treatment protocol for post resuscitation care after out of hospital treatment protocol for post resuscitation care after out of hospital cardiac arrest. Resuscitation. 2007; 73: 29cardiac arrest. Resuscitation. 2007; 73: 29--39.39.

Pro ArticlePro Article Early predictors of outcome in Early predictors of outcome in comatose survivors of ventricular comatose survivors of ventricular fibrillation and nonfibrillation and non--ventricular ventricular fibrillation cardiac arrest treated fibrillation cardiac arrest treated with hypothermia: a prospective with hypothermia: a prospective studystudystudy.study.

Mauro Oddo, et al.Mauro Oddo, et al.Department of Critical Care MedicineDepartment of Critical Care MedicineLausanne University Medical Center and Faculty of Biology Lausanne University Medical Center and Faculty of Biology

and Medicine, Lausanne, Switzerlandand Medicine, Lausanne, SwitzerlandCrit Care Med 2008; 36:2296 Crit Care Med 2008; 36:2296 ––23012301

Study ObjectivesStudy Objectives

Better define the role of therapeutic Better define the role of therapeutic hypothermia in the general clinical hypothermia in the general clinical setting setting gg

Identify early predictors of good Identify early predictors of good outcome. outcome.

Study ParametersStudy Parameters

DesignDesign–– Prospective Cohort Prospective Cohort –– Inclusion CriteriaInclusion Criteria

Consecutive subjects, aged < 80 yrs Consecutive subjects, aged < 80 yrs admitted for persistent coma following admitted for persistent coma following outout--ofof--hospital cardiac arrest.hospital cardiac arrest.

–– Single center (tertiary, academic)Single center (tertiary, academic)

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VariablesVariables Predictors: Predefined clinical variables obtained at Predictors: Predefined clinical variables obtained at

admissionadmissionD i f CA (d fi d h i fD i f CA (d fi d h i f

Study ParametersStudy Parameters

–– Duration of CA (defined as the time from Duration of CA (defined as the time from collapse to ROSC)collapse to ROSC)

–– Initial arrest rhythm (VF or nonInitial arrest rhythm (VF or non--VF) VF) –– Hemodynamic status (presence or absence of Hemodynamic status (presence or absence of

postresuscitation circulatory shock)postresuscitation circulatory shock) Outcomes:Outcomes:

–– SurvivalSurvival–– Neurologic status at discharge (Good = CPC 1Neurologic status at discharge (Good = CPC 1--2)2)

Study Parameters (con’t)Study Parameters (con’t)

Statistical AnalysisStatistical Analysis–– Multivariable logistic regression Multivariable logistic regression –– Time from collapse to ROSC was not linearTime from collapse to ROSC was not linear–– CovariatesCovariatesCovariatesCovariates

ageage SexSex initial arrest rhythm (VF or noninitial arrest rhythm (VF or non--VF)VF) arterial lactate on admission to the emergency roomarterial lactate on admission to the emergency room presence of circulatory shock on admission to the ICU. presence of circulatory shock on admission to the ICU.

ResultsResults

88 Eligible patients88 Eligible patients–– 11 excluded for Age > 8011 excluded for Age > 80–– 3 excluded for underlying terminal disease3 excluded for underlying terminal disease

74 patients included in study74 patients included in study–– 46% had post arrest circulatory shock46% had post arrest circulatory shock–– 51% VF initial rhythm51% VF initial rhythm–– 39% survival39% survival–– Of survivors, 32% good neurologic outcome.Of survivors, 32% good neurologic outcome.

ResultsResults

ResultsResults ResultsResults

ROC: Area Under Curve = 0.93

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ResultsResults

Previous retrospective study reassessed using collapseROSC interval.

ConclusionsConclusions

Were the objectives met?Were the objectives met?–– Two strong predictors of good Two strong predictors of good

outcome with therapeuticoutcome with therapeuticoutcome with therapeutic outcome with therapeutic hypothermia were identified (Time hypothermia were identified (Time to ROSC and Lactate) to ROSC and Lactate)

–– Initial Rhythm failed to predict Initial Rhythm failed to predict survival in multivariable analysis.survival in multivariable analysis.

Pros/ConsPros/Cons

ProsPros–– Directly compares predictors using multivariable logistic Directly compares predictors using multivariable logistic

regression.regression.–– Strong predictors identifiedStrong predictors identified

ConsCons ConsCons–– No interactions or higher order models examined.No interactions or higher order models examined.–– Selection Bias?Selection Bias?

Single Tertiary Academic CenterSingle Tertiary Academic Center–– Small #’sSmall #’s–– Doubtful power Doubtful power –– Generalizable? Generalizable?

PhysicianPhysician--led EMS resuscitation teamled EMS resuscitation team Multifaceted postMultifaceted post--arrest care provided. arrest care provided.

Take Home PointsTake Home Points

All cardiac arrest rhythms eventually All cardiac arrest rhythms eventually lead to lead to asystoleasystole..

“Absence of evidence is not evidence “Absence of evidence is not evidence of absence”. of absence”. --D Altman D Altman BMJBMJ

Identification of initial rhythm is not Identification of initial rhythm is not exact exact ((PokornaPokorna et al, et al, ResuscitationResuscitation 2011)2011)

Initial rhythm is not an adequate Initial rhythm is not an adequate predictive marker on which to base predictive marker on which to base the decision to cool. the decision to cool.

Late BreakerLate Breaker•J-STAGE Hypo Investigators. Registry of 14 Japanese centers (N=452).•80% Survival, 55% with favorable neurologic outcome.

Yokohama, et al. Circ J. 2011 Apr 7. [Epub ahead of print]

ReferencesReferences

Yokoyama H, and The JYokoyama H, and The J--PULSEPULSE--Hypo Investigators. Hypo Investigators. Impact of Impact of Therapeutic Hypothermia in the Treatment of Patients With Therapeutic Hypothermia in the Treatment of Patients With OutOut--ofof--Hospital Cardiac Arrest From the JHospital Cardiac Arrest From the J--PULSEPULSE--HYPO HYPO Study RegistryStudy Registry. Circ J. 2011 Apr 7. [Epub ahead of print]. Circ J. 2011 Apr 7. [Epub ahead of print]

Pokorna M, et al. Pokorna M, et al. How accurately can the aetiology of cardiac How accurately can the aetiology of cardiac arrest be established in an outarrest be established in an out--ofof--hospital setting? Analysis hospital setting? Analysis by "Concordance in Diagnosis Crosscheck Tables".by "Concordance in Diagnosis Crosscheck Tables".Resuscitation. 2011 Apr;82(4):391Resuscitation. 2011 Apr;82(4):391--7. Epub 2011 Jan 13.7. Epub 2011 Jan 13.

Engdahl J, Bång A, Karlson BW, Lindqvist J, Herlitz J. Engdahl J, Bång A, Karlson BW, Lindqvist J, Herlitz J. Characteristics and outcome among patients suffering from Characteristics and outcome among patients suffering from out of hospital cardiac arrest of nonout of hospital cardiac arrest of non--cardiac aetiology.cardiac aetiology.Resuscitation. 2003 Apr;57(1):33Resuscitation. 2003 Apr;57(1):33--41.41.

–– 75% of Cardiac etiology of arrest were witnessed vs. 58% of non75% of Cardiac etiology of arrest were witnessed vs. 58% of non--cardiac cardiac etiology (p<0.0001).etiology (p<0.0001).

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Con ArticleCon ArticleIs Hypothermia After Cardiac Is Hypothermia After Cardiac

Arrest Effective in Both Shockable Arrest Effective in Both Shockable and Nonshockable Patients?and Nonshockable Patients?and Nonshockable Patients? and Nonshockable Patients?

Dumas F, Grimaldi D, Zuber B, et al.Dumas F, Grimaldi D, Zuber B, et al.Circulation.Circulation. 2011;123:8772011;123:877--886886

BackgroundBackground

Origin for the use of TMH for postOrigin for the use of TMH for post--ventricular fibrillation ventricular fibrillation (VF)/ventricular tachycardia (VT) cardiac arrest (CA)(VF)/ventricular tachycardia (VT) cardiac arrest (CA)–– Improved neurologic and survival outcomes for postImproved neurologic and survival outcomes for post--

VF/VT CA patients (“Works for some patients”) VF/VT CA patients (“Works for some patients”)

Extension of concept to nonExtension of concept to non--VF/VT CA patients (PostVF/VT CA patients (Post--Cardiac Arrest Syndrome)Cardiac Arrest Syndrome)–– Several small studies with equivocal results (“May not Several small studies with equivocal results (“May not

help much, but does not appear to ‘harm’ either”)help much, but does not appear to ‘harm’ either”)

In 2011, the American Heart Association now recommends In 2011, the American Heart Association now recommends TMH for PEA/asystole CA patients TMH for PEA/asystole CA patients

Pretty convincing, right?

Study ObjectiveStudy Objective

Assess the influence of therapeutic Assess the influence of therapeutic hypothermia on hospital outcome in outhypothermia on hospital outcome in out--

ofof--hospital cardiac arrest (OHCA) patients, hospital cardiac arrest (OHCA) patients, separately in those with VF/VT and in separately in those with VF/VT and in

those with PEA/asystole as initial those with PEA/asystole as initial presenting rhythm presenting rhythm

Study ParametersStudy Parameters

Overall Study DesignOverall Study Design–– Type: Observational prospective registry of 1145 patientsType: Observational prospective registry of 1145 patients

–– Setting: Tertiary care center, Paris, FranceSetting: Tertiary care center, Paris, France

–– Time: January 2000 Time: January 2000 –– June 2009June 2009

–– Inclusion Criteria: Nontraumatic OHCA patients admitted Inclusion Criteria: Nontraumatic OHCA patients admitted consecutively after successful return of spontaneous consecutively after successful return of spontaneous circulation (ROSC)circulation (ROSC)

–– Exclusion Criteria: None specifiedExclusion Criteria: None specified

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Data Collection Data Collection –– Primary Data PointPrimary Data Point–– Neurologic outcome upon hospital discharge as Neurologic outcome upon hospital discharge as

defined by the Cerebral Performance Category (CPC) defined by the Cerebral Performance Category (CPC) Scale Scale

MethodsMethods

Study GroupsStudy Groups 20002000--2003 (“Pre2003 (“Pre--TMH”)TMH”)

–– VF/VT without TMHVF/VT without TMH–– VF/VT with TMHVF/VT with TMH

MethodsMethods

20002000--2003 (“Pre2003 (“Pre--TMH”)TMH”)–– NonNon--VF/VT without TMHVF/VT without TMH–– NonNon--VF/VT with TMHVF/VT with TMHVF/VT with TMHVF/VT with TMH

20042004--2006 (Adoption)2006 (Adoption)–– VF/VT without TMHVF/VT without TMH–– VF/VT with TMHVF/VT with TMH

20072007--2009 (Routine)2009 (Routine)–– VF/VT without TMHVF/VT without TMH–– VF/VT with TMHVF/VT with TMH

NonNon VF/VT with TMHVF/VT with TMH

20042004--2006 (Adoption)2006 (Adoption)–– NonNon--VF/VT without TMHVF/VT without TMH–– NonNon--VF/VT with TMHVF/VT with TMH

20072007--2009 (Routine)2009 (Routine)–– NonNon--VF/VT without TMHVF/VT without TMH–– NonNon--VF/VT with TMHVF/VT with TMH

MethodsMethods

Statistical AnalysesStatistical Analyses–– Chi SquareChi Square

–– Student t TestStudent t Test

–– Single Multivariable Logistic Regression AnalysisSingle Multivariable Logistic Regression Analysis

–– Odds Ratio with 95% Confidence Intervals (CI)Odds Ratio with 95% Confidence Intervals (CI)

–– Wald TestWald Test

ResultsResults

Main Points of InterestMain Points of Interest–– Nonadjusted Odds Ratio for Use of TMH Nonadjusted Odds Ratio for Use of TMH

VF/VT VF/VT –– 1.91 (95% CI, 1.381.91 (95% CI, 1.38--2.66)2.66) NonNon--VF/VTVF/VT –– 0 83 (95% CI 0 490 83 (95% CI 0 49--1 40)*1 40)* NonNon VF/VT VF/VT 0.83 (95% CI, 0.490.83 (95% CI, 0.49 1.40)1.40)

–– Adjusted Odds Ratio for Use of TMHAdjusted Odds Ratio for Use of TMH VF/VT VF/VT -- 1.90 (95% CI, 1.181.90 (95% CI, 1.18--3.06)3.06) NonNon--VF/VT VF/VT -- 0.71 (95% CI, 0.370.71 (95% CI, 0.37--1.36)*1.36)*

*Did not achieve statistical significance*Did not achieve statistical significance

InterludeInterlude

Odds Ratio (OR)Odds Ratio (OR)–– A method of comparing whether the probability of a A method of comparing whether the probability of a

certain event is the same for two groupscertain event is the same for two groups

–– An OR of 1 = the event is equally likely in both groupsAn OR of 1 = the event is equally likely in both groups OR > 1 = the event is more likely in the first groupOR > 1 = the event is more likely in the first group OR < 1 = the event is less likely in the first groupOR < 1 = the event is less likely in the first group

–– Several caveats:Several caveats: OR can exaggerate the size of effectOR can exaggerate the size of effect Assumes disease is uncommonAssumes disease is uncommon Assumes study population was randomly selectedAssumes study population was randomly selected

ResultsResults

Main Points of InterestMain Points of Interest–– Nonadjusted Odds Ratio for Use of TMH Nonadjusted Odds Ratio for Use of TMH

VF/VT VF/VT –– 1.91 (95% CI, 1.381.91 (95% CI, 1.38--2.66)2.66) NonNon--VF/VTVF/VT –– 0 83 (95% CI 0 490 83 (95% CI 0 49--1 40)*1 40)* NonNon VF/VT VF/VT 0.83 (95% CI, 0.490.83 (95% CI, 0.49 1.40)1.40)

–– Adjusted Odds Ratio for Use of TMHAdjusted Odds Ratio for Use of TMH VF/VT VF/VT -- 1.90 (95% CI, 1.181.90 (95% CI, 1.18--3.06)3.06) NonNon--VF/VT VF/VT -- 0.71 (95% CI, 0.370.71 (95% CI, 0.37--1.36)*1.36)*

*Did not achieve statistical significance*Did not achieve statistical significance

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ResultsResults

StrengthsStrengths

Large sample size, one of the largest studies evaluating Large sample size, one of the largest studies evaluating the use of TMH for nonthe use of TMH for non--VF/VT cardiac arrest patientsVF/VT cardiac arrest patients

Used patients before, during, & after routine use of TMHUsed patients before, during, & after routine use of TMHp , g,p , g,

Used resuscitation guidelines, TMH protocols, and CPC Used resuscitation guidelines, TMH protocols, and CPC scale similar to other referenced studiesscale similar to other referenced studies

Collected and analyzed numerous other data pointsCollected and analyzed numerous other data points

Findings for VF/VT group correlates with other studiesFindings for VF/VT group correlates with other studies

LimitationsLimitations Applicability? Are populations & times comparable to Applicability? Are populations & times comparable to

U.S.?U.S.?

Patients admitted directly to ICUPatients admitted directly to ICU

Patients not randomizedPatients not randomized

Use of specific cooling techniqueUse of specific cooling technique

Multiple statistical tools Multiple statistical tools

Suggestion that TMH for nonSuggestion that TMH for non--VF/VT is “harmful” did not VF/VT is “harmful” did not achieve statistical significanceachieve statistical significance

SummarySummary

Pertinent OutcomePertinent Outcome–– Longer delays to resuscitation were inversely Longer delays to resuscitation were inversely

associated with a better neurologic outcome associated with a better neurologic outcome

Primary OutcomesPrimary Outcomes–– TMH nearly doubled the probability of being discharged TMH nearly doubled the probability of being discharged

with a favorable neurologic outcome in patients with a favorable neurologic outcome in patients resuscitated from VT/VT cardiac arrestresuscitated from VT/VT cardiac arrest

–– TMH tended to decrease the probability of being TMH tended to decrease the probability of being discharged with a favorable neurologic outcome in discharged with a favorable neurologic outcome in patients resuscitated from nonpatients resuscitated from non--VF/VT cardiac arrestVF/VT cardiac arrest

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Discussion PointsDiscussion Points

Do the results pass the “sniff test”?Do the results pass the “sniff test”?

Are the results applicable to your practice?Are the results applicable to your practice?

Will the results affect your practice?Will the results affect your practice?

–– If not, why not? “Will not hurt”?If not, why not? “Will not hurt”?

–– If yes, how? Can application be “selective”? InIf yes, how? Can application be “selective”? In--hospital cardiac arrest? Known short delay before hospital cardiac arrest? Known short delay before ROSC?ROSC?

ConclusionConclusion

Cutting Edge UsesCutting Edge Uses

Very early hypothermia induced in Very early hypothermia induced in patients with severe brain injury patients with severe brain injury (the National Acute Brain Injury Study: (the National Acute Brain Injury Study: ( j y y( j y yHyperthermia II)Hyperthermia II)

Why Do the Study?Why Do the Study?

Previous study, NABIS I, looked at Previous study, NABIS I, looked at hypothermia induce within first 10 hypothermia induce within first 10 hours.hours.

Hypothermic group had increased Hypothermic group had increased mortalitymortality

BUT subgroup analysis indicated that BUT subgroup analysis indicated that very early hypothermia might improve very early hypothermia might improve mortalitymortality

Study overviewStudy overview Randomized multicenter trialRandomized multicenter trial

2 treatment groups: normothermia and 2 treatment groups: normothermia and hypothymia to 33hypothymia to 33°°C for 48 hours.C for 48 hours.

Hypothermia treatment was induced within 2Hypothermia treatment was induced within 2--1/2 hours from trauma1/2 hours from trauma1/2 hours from trauma1/2 hours from trauma

Hypothermia was induced immediately upon Hypothermia was induced immediately upon arrival by either EMS or the emergency arrival by either EMS or the emergency departmentdepartment

Inclusion criteria: 16Inclusion criteria: 16--45 years, none penetrating 45 years, none penetrating brain injury, not responsive to instructionsbrain injury, not responsive to instructions

Hypothermia Induced ByHypothermia Induced By

Using Artic Sun surface cooling matUsing Artic Sun surface cooling mat

Room temperature ventilated airRoom temperature ventilated air Room temperature ventilated airRoom temperature ventilated air

Chilled IV crystalloidChilled IV crystalloid

Gastric lavage with cold H2OGastric lavage with cold H2O

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Exclusion Criteria: Exclusion Criteria: complexcomplex 2 sets of exclusion criteria.2 sets of exclusion criteria. At randomizationAt randomization

–– hypotensive (SBP <110; DBP<60)hypotensive (SBP <110; DBP<60)–– HR>120HR>120HR>120 HR>120 –– injury was greater than 2.5 hrs agoinjury was greater than 2.5 hrs ago

After complete assessment & resuscitation: After complete assessment & resuscitation: –– GCS 3 and NR pupilsGCS 3 and NR pupils–– GCS 7GCS 7--8 w nl brain CT8 w nl brain CT–– Decreased BP (see above)Decreased BP (see above)–– Abrev Injury score 4 or more (excluding brain)Abrev Injury score 4 or more (excluding brain)–– Hypoxia (O2 sat <94%)Hypoxia (O2 sat <94%)

ResultsResults

Large number patients screened to get Large number patients screened to get reasonable sample sizereasonable sample size

Groups were reasonably matchedGroups were reasonably matched–– Normothermic slightly older 31 vs 26Normothermic slightly older 31 vs 26–– Normothermic slightly sicker Normothermic slightly sicker

Table 1 -- Demographics and baseline characteristics

Hypothermia (n=52)

Normothermia (n=45)

Age (years) 26 (9) 31 (11)

GCS score 5–8 33 (63%) 22 (49%)

GCS score 3–4 19 (37%) 23 (51%)

Non-reactive pupils[*] 6 (12%) 5 (11%)

Surgical lesion removed in first 24 h after injury

15 (29%) 15 (33%)j y

Prehospital hypotension[‡] 7 (15%) 7 (16%)

Prehospital hypoxia[‡] 11 (23%) 4 (9%)

Injury severity score 30 (6) 30 (9)

Abbreviated injury severity score for head 4·56 (0·61) 4·47 (0·63)

Positive blood alcohol[§] 17 (59%) 17 (59%)

First temperature (°C)[¶] 36·1 (0·8) 36·0 (0·9)

Data are mean (SD) or number (%). GCS=Glasgow coma scale.

Hypothermia Did Hypothermia Did NotNot Improve Improve Mortality or Neuro OutcomeMortality or Neuro Outcome

Table 2 -- Outcome and mortality rates

Poor outcome Died

n (%) RR (95% CI)

p value

n (%) RR (95% CI)

p value

Primary analysis

All patients (n=97)

56 (58%)

.. .. 20 (21%)

.. ..

Hypothermia (n=52)

31 (60%)

1·08 (0·76–1·53)

0·67 12 (23%)

1·30 (0·58–2·89)

0·52

Normothermia ( 45)

25 (56%

.. .. 8 (18%

..

Subgroup Analysis: Subgroup Analysis: Hypothermia Didn’t Hypothermia Didn’t Help In Any Help In Any SubgroupSubgroupSubgroupSubgroup

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Subgroup analysis

Diffuse brain injury (n=69) 42 (61%)

.. .. 13 (19%)

.. ..

Hypothermia (n=37) 26 (70%)

1·44 (0·95–2·17)

0·09

10 (27%)

2·88 (0·87–9·57)

0·08

Poor outcome Died

n (%)

RR (95% CI)

p value

n (%)

RR (95% CI)

p value

Normothermia (n=32) 16 (50%)

.. .. 3 (9%)

.. ..

Surgically removed haematomas (n=28)

14 (50%)

.. .. 7 (25%)

.. ..

Hypothermia (n=15) 5 (33%)

0·44 (0·22–0·88)

0·02

2 (13%)

0·35 (0·08–1·50)

0·16

Normothermia (n=13) 9 (69%)

.. .. 5 (39%)

.. ..

Bottom lineBottom line

Hypothermia does not help in blunt Hypothermia does not help in blunt trauma to the brain trauma to the brain

Hypothermia does not improve Hypothermia does not improve outcome wither due to diffuse brain outcome wither due to diffuse brain injury or hemorrhageinjury or hemorrhage

Cooling Methods for Cooling Methods for Inducing HypothermiaInducing Hypothermia

What is the best way?What is the best way?

Many Ways to Be CoolMany Ways to Be Cool

Simplest:Simplest: 30 ml/ kg cold (4 C) lactated Ringer’s 30 ml/ kg cold (4 C) lactated Ringer’s over 30 minutesover 30 minutes

SimpleSimple: pack head, neck, torso and limbs and ice: pack head, neck, torso and limbs and iceSimpleSimple: pack head, neck, torso and limbs and ice : pack head, neck, torso and limbs and ice packspacks

Used in seminal Australian study on hypothermia and V. fib Used in seminal Australian study on hypothermia and V. fib arrest (NEJM 346:557, 2002)arrest (NEJM 346:557, 2002)

Low techLow tech: Cooling mattress that covers the body: Cooling mattress that covers the body Used in seminal European study on hypothermia and V. Fib Used in seminal European study on hypothermia and V. Fib

arrest (NEJM 236:549, 2002)arrest (NEJM 236:549, 2002)

Hi TechHi Tech: Intravascular cooling systems: Intravascular cooling systems

Which Way is Best?Which Way is Best?

No studies comparing methods in No studies comparing methods in EDED

Two Recent Studies in ICU Two Recent Studies in ICU PatientsPatients

Crit Care 11 R91, 2007Crit Care 11 R91, 2007–– Water circulating blankets/gelWater circulating blankets/gel--pads/intravascular pads/intravascular

cooling cooling cool fastercool faster than IV cold saline and ice packs than IV cold saline and ice packs or air blanket cooling.or air blanket cooling.

–– With Intravascular cooling temperature more constantWith Intravascular cooling temperature more constant–– But do these cooling methods give a better clinical But do these cooling methods give a better clinical

outcome? Study did not answeroutcome? Study did not answeroutcome? Study did not answeroutcome? Study did not answer

Crit Care 39: 443, 2011Crit Care 39: 443, 2011–– Surface cooling with blanket (Artic Sun) vs Surface cooling with blanket (Artic Sun) vs

Intravascular cooling (Coolgard)Intravascular cooling (Coolgard)–– No difference in survival to D/C, neurological No difference in survival to D/C, neurological

outcomes at D/C and at 6 mosoutcomes at D/C and at 6 mos

5/16/2011

13

Bottom LineBottom Line

Most likely any cooling methods will do Most likely any cooling methods will do in ED.in ED.

Cooling blanket makes most sense in a Cooling blanket makes most sense in a patient who will be in ED for awhile patient who will be in ED for awhile and/or no significant money issuesand/or no significant money issues–– Needs less nursing involvementNeeds less nursing involvement–– Keeps temperature constantKeeps temperature constant–– Less messyLess messy

PRMCE ProtocolPRMCE Protocol

Indications Indications –––– VV--fib/Pulseless VTachfib/Pulseless VTach–– Spontaneous Return of CirculationSpontaneous Return of Circulation

ComatoseComatose–– ComatoseComatose GoalsGoals

–– Temp 33 C for 24 hours after SROCTemp 33 C for 24 hours after SROC–– Passive rePassive re--warming if pt awakenswarming if pt awakens–– Diazepam/Meperidine for shivering (q30 min)Diazepam/Meperidine for shivering (q30 min)

Cinncinatti Sub Zero cooling machineCinncinatti Sub Zero cooling machine

HMC ProtocolHMC Protocol

IndicationsIndications–– VV--fib, Pulseless V Tach, PEA, Asystolefib, Pulseless V Tach, PEA, Asystole–– SROC w/in 1 hourSROC w/in 1 hour–– UnresponseiveUnresponseive–– > 18 y/o> 18 y/o

GoalsGoals–– Temp of 33 C w/in 4 hoursTemp of 33 C w/in 4 hours–– Continue for 24 hour after SROCContinue for 24 hour after SROC

After 24 hours passive rewarm to 37 C over 4 hoursAfter 24 hours passive rewarm to 37 C over 4 hours–– Fentanyl/Midazolan/VecuroniumFentanyl/Midazolan/Vecuronium

Artic Sun Temperature Management SystemArtic Sun Temperature Management System

Open ForumOpen Forum

Who else has protocols currently in Who else has protocols currently in place?place?–– Do they differ significantlyDo they differ significantlyDo they differ significantlyDo they differ significantly

Moving forwardMoving forward

Monkey Survey for input coming out Monkey Survey for input coming out soon.soon.

Suggestions on future JC’sSuggestions on future JC’s Suggestions on future JC sSuggestions on future JC s–– TopicsTopics–– Format changesFormat changes