Targeted Temperature Targeted Temperature Management:Management:

An Evolving Therapy for Cardiac An Evolving Therapy for Cardiac

ArrestArrest

By Meagan Dunn, By Meagan Dunn, BScNBScN, , MScMSc, RN, CNE, RN, CNE

NP Forum NP Forum

April 8, 2016April 8, 2016

ObjectivesObjectives

To understand:To understand:

�� What Therapeutic Temperature What Therapeutic Temperature Management (TTM) isManagement (TTM) is

�� The goals of TTMThe goals of TTM

�� How we apply the treatment in CCUHow we apply the treatment in CCU

�� PrognosticationPrognostication

�� Long term implicationsLong term implications

HistoryHistory

�� Hippocrates recommended packing of Hippocrates recommended packing of severe wounds in snow to stop bleeding.severe wounds in snow to stop bleeding.

�� In Napoleonic wars of 1800s, noted that In Napoleonic wars of 1800s, noted that injured soldiers who were farther from the injured soldiers who were farther from the fire fared better than officers who were fire fared better than officers who were rere--warmed.warmed.

�� Used to treat Typhoid Fever.Used to treat Typhoid Fever.

HistoryHistory

�� 1938 1938 –– generalized refrigeration of the generalized refrigeration of the human brain.human brain.

�� 19451945--1964 1964 –– first studies on induced first studies on induced hypothermia for traumatic brain injury.hypothermia for traumatic brain injury.

�� 1950s 1950s –– induced hypothermia used induced hypothermia used intraoperativelyintraoperatively during cardiac surgery.during cardiac surgery.

�� 20022002 –– landmark studies published on landmark studies published on hypothermia after cardiac arrest.hypothermia after cardiac arrest.

What is Targeted Temperature What is Targeted Temperature Management (TTM)?Management (TTM)?

�� Also known as Therapeutic Hypothermia, Also known as Therapeutic Hypothermia, Induced Hypothermia, or Induced Hypothermia, or ““Brain CoolingBrain Cooling””

�� Therapeutic treatment where a patientTherapeutic treatment where a patient’’s body s body temperature is lowered in a controlled manner temperature is lowered in a controlled manner for a predetermined amount of timefor a predetermined amount of time

�� Helps reduce the risk of ischemic injury to tissue Helps reduce the risk of ischemic injury to tissue following a period of insufficient blood flowfollowing a period of insufficient blood flow

Insufficient Blood FlowInsufficient Blood Flow

May be due to:May be due to:�� Cardiac arrestCardiac arrest

�� The occlusion of an artery by an embolism, as The occlusion of an artery by an embolism, as occurs in the case of strokesoccurs in the case of strokes

�� Neonates suffering from hypoxicNeonates suffering from hypoxic--ischemic ischemic encephalopathyencephalopathy

�� Traumatic brain or spinal cord injury without Traumatic brain or spinal cord injury without feverfever

�� NeurogenicNeurogenic fever following brain traumafever following brain trauma

Cardiac ArrestCardiac Arrest

�� 40,000 people arrest annually in Canada 40,000 people arrest annually in Canada

�� 85% of arrests occur out of hospital, 85% of arrests occur out of hospital, �� 5% survival to hospital admission5% survival to hospital admission

�� Many remain comatose after arrestMany remain comatose after arrest

�� Poor survival rate with intact neurologic Poor survival rate with intact neurologic functionfunction�� Dysfunction ranges from mild cognitive Dysfunction ranges from mild cognitive

impairment through to vegetative stateimpairment through to vegetative state

NeuroNeuro -- MechanismMechanism

Mechanism of neurological injury Mechanism of neurological injury associated with cardiac arrest:associated with cardiac arrest:

�� ischemic injury to tissue following a ischemic injury to tissue following a period of insufficient blood flowperiod of insufficient blood flow

�� reperfusion injury following rereperfusion injury following re--establishment of blood flowestablishment of blood flow

NeuroNeuro -- MechanismMechanism

�� Cardiac arrest presents global ischemic Cardiac arrest presents global ischemic insult to the brain, largely influenced by insult to the brain, largely influenced by duration of interrupted cerebral blood flowduration of interrupted cerebral blood flow

�� Cerebral Cerebral hyperemiahyperemia, followed by , followed by vasospasm and multifocal and global vasospasm and multifocal and global hypoperfusionhypoperfusion

�� Cerebral O2 stores gone in 20 seconds, Cerebral O2 stores gone in 20 seconds, glucose and ATP in 5 minutesglucose and ATP in 5 minutes

�� Leads to neuronal deathLeads to neuronal death

Mongardon N, D. F. (2011). Postcardiac arrest syndrome from immediate resuscitation to long-term outcome. Ann Intensive Care, 1:45.

How Cooling HelpsHow Cooling Helps

�� Counteracts Counteracts neuroexcitationneuroexcitation of brain cells, of brain cells, reducing the degree of cell death.reducing the degree of cell death.

�� Stabilizes bloodStabilizes blood--brain barrier.brain barrier.

�� Suppresses inflammatory process.Suppresses inflammatory process.

�� Decreases cerebral metabolism (6Decreases cerebral metabolism (6--10% for 10% for every degree Celsius the body every degree Celsius the body temperature drops).temperature drops).

Decreases death and neurological Decreases death and neurological damage!!damage!!

2015 AHA Guidelines2015 AHA Guidelines

�� American Heart Association 2015 guidelines for American Heart Association 2015 guidelines for post cardiac arrest care includes class 1 post cardiac arrest care includes class 1 (strong) recommendations for TTM.(strong) recommendations for TTM.�� For all patients remaining comatose following For all patients remaining comatose following

resuscitation from cardiac arrestresuscitation from cardiac arrest

�� ShockableShockable, out, out--ofof--hospital arrest (LOE B)hospital arrest (LOE B)

�� NonNon--shockableshockable, in, in--hospital arrest (LOE C)hospital arrest (LOE C)

�� Target temperature 32Target temperature 32--3636˚̊C (LOE B)C (LOE B)

2015 Canadian Guidelines for the use of TTM: target temperature 2015 Canadian Guidelines for the use of TTM: target temperature 3232--3434˚̊CC

Inclusion ConsiderationsInclusion Considerations

�� Initial rhythmInitial rhythm�� Witnessed vs. Witnessed vs. unwitnessedunwitnessed

�� DowntimeDowntime

�� GlascowGlascow Coma ScaleComa Scale

�� PrePre--arrest quality of lifearrest quality of life

Temperature ManagementTemperature Management

�� InductionInduction�� Getting to desired goalGetting to desired goal

�� MaintenanceMaintenance�� Keeping the patient at the desired temp for a Keeping the patient at the desired temp for a

predefined period of timepredefined period of time

�� RewarmingRewarming�� Returning to Returning to normothermianormothermia

Induction PhaseInduction Phase

�� SedationSedation

�� ParalyticsParalytics

�� VentilatorVentilator�� Assist ControlAssist Control

�� Iced IV fluidsIced IV fluids

�� Normal Saline or RingerNormal Saline or Ringer’’s Lactates Lactate

�� Target 32Target 32--3434°°C (36C (36°°C?)C?)

Cooling MethodsCooling Methods

MethodMethod AdvantagesAdvantages DisadvantagesDisadvantages

Surface Cooling Surface Cooling

(blankets, gel (blankets, gel pads, ice packs pads, ice packs and fans)and fans)

NonNon--invasive,invasive,

Cheap,Cheap,

Minimal training.Minimal training.

Slow,Slow,

Less thermal Less thermal control,control,

Messy.Messy.

IntraIntra--vascular vascular CoolingCooling

(ICY catheter)(ICY catheter)

More thermal More thermal control,control,

No skin issues.No skin issues.

Invasive,Invasive,

More expensive,More expensive,

Requires special Requires special training to insert.training to insert.

Temperature MonitoringTemperature Monitoring

�� PA catheterPA catheter

�� EsophagealEsophageal

�� BladderBladder�� If patient has adequate U/O 0 If patient has adequate U/O 0 –– 30 cc/hr 30 cc/hr ––

varies per manufacturervaries per manufacturer

�� Rectal/skin/tympanic less accurateRectal/skin/tympanic less accurate

Maintenance PhaseMaintenance Phase

�� Sedation and Paralytics continueSedation and Paralytics continue

�� Rhythm and Blood Pressure controlRhythm and Blood Pressure control

�� AmiodaroneAmiodarone, , InotropesInotropes, , VasopressorsVasopressors, Fluid, Fluid

�� Continuous MonitoringContinuous Monitoring

�� End Tidal CO2, TemperatureEnd Tidal CO2, Temperature

�� Hourly pupil assessmentsHourly pupil assessments

�� LaboratoryLaboratory

�� ABG, electrolytes, PT/PTT, cultures, blood ABG, electrolytes, PT/PTT, cultures, blood glucoseglucose

SedationSedation

�� Reduces oxygen consumptionReduces oxygen consumption

�� Can prevent shiveringCan prevent shivering

�� More rapid coolingMore rapid cooling

�� May delay prognosticationMay delay prognostication

�� May contribute to hypotensionMay contribute to hypotension

ParalysisParalysis

�� Eliminates shiveringEliminates shivering�� Decrease MVO2Decrease MVO2

�� MUST sedate prior to paralyzingMUST sedate prior to paralyzing

�� Seizures may be concealedSeizures may be concealed

Ventilator ManagementVentilator Management

�� Avoid high FiO2 (PO2>300)Avoid high FiO2 (PO2>300)�� Titrate FiO2 to keep PaO2 85Titrate FiO2 to keep PaO2 85--100mmhg100mmhg

�� Adjust vent for normal acidAdjust vent for normal acid--base balancebase balance�� Hyperventilation may produce cerebral Hyperventilation may produce cerebral

ischemiaischemia

�� Hypoventilation may increase ICPHypoventilation may increase ICP

�� TargetTarget normocarbianormocarbia

�� Vigilance for early signs of pneumonia!Vigilance for early signs of pneumonia!

Fluid and ElectrolytesFluid and Electrolytes

�� Cold Cold diuresisdiuresis

�� VenoconstrictionVenoconstriction,,

�� If uncorrectedIf uncorrected�� HypovolemiaHypovolemia ��hypoperfusionhypoperfusion

�� HemoconcentrationHemoconcentration ��hyperviscosityhyperviscosity

�� RewarmingRewarming may unmask may unmask hypovolemiahypovolemia

Fluid and ElectrolytesFluid and Electrolytes

�� Decreased electrolytesDecreased electrolytes�� K+, Mg, K+, Mg, PhosPhos

�� DiuresisDiuresis induced renal excretioninduced renal excretion

�� Intracellular electrolyte shiftsIntracellular electrolyte shifts

�� Shift extracellular with Shift extracellular with rewarmingrewarming

�� Prevented with slow controlled Prevented with slow controlled rewarmingrewarming

�� Replace to low normal during coolingReplace to low normal during cooling

�� If increased, treat before If increased, treat before rewarmingrewarming

InfectionInfection

�� Must be vigilantMust be vigilant

�� Signs/symptoms not availableSigns/symptoms not available

�� Inspect lines/tubes, skin, routine Inspect lines/tubes, skin, routine CXRsCXRs

�� Suspect if sudden increase in work of Suspect if sudden increase in work of cooling device (cooling device (�� water temp)water temp)�� Indicates increased heat productionIndicates increased heat production

�� Have low threshold to start antibioticsHave low threshold to start antibiotics

PharmacyPharmacy

�� Many medications are required during THMany medications are required during TH

sedatives, analgesia, antisedatives, analgesia, anti--epileptics, epileptics, paralytics, etcparalytics, etc

�� None have specific dose recommendations None have specific dose recommendations during THduring TH

�� Majority of pts require decreased doses Majority of pts require decreased doses during TH or at standard doses experience during TH or at standard doses experience prolonged effectsprolonged effects

RewarmingRewarming PhasePhase

�� Stop all active coolingStop all active cooling

�� RewarmRewarm slowly slowly (0.1(0.1--0.50.5°°C/hr)C/hr)

�� Discontinue Neuromuscular Blocking Discontinue Neuromuscular Blocking AgentsAgents

�� Titrate sedationTitrate sedation

�� Monitor for rebound Monitor for rebound hyperhyperthermiathermia

Central Nervous SystemCentral Nervous System

�� DecisionDecision--making is not as easy as it making is not as easy as it

soundssounds

�� DonDon’’t t neuroprognosticateneuroprognosticate during THduring TH

�� Wait until TH reversed Wait until TH reversed at leastat least 72 hours72 hours

�� Deeply sedate and paralyze during coolingDeeply sedate and paralyze during cooling

�� Use of NSE as a biomarkerUse of NSE as a biomarker

SeizuresSeizures

�� Seizures may be concealed by NMBASeizures may be concealed by NMBA�� Occur in 5 Occur in 5 –– 15% who achieve ROSC15% who achieve ROSC

�� 10 10 –– 40% of those who remain comatose40% of those who remain comatose

�� Increase cerebral metabolism 3Increase cerebral metabolism 3--foldfold

�� *EEG monitoring*EEG monitoring

�� Good Good neuroneuro outcomes reported in outcomes reported in patients initially with status patients initially with status epilepticusepilepticus

Tips and Tricks for ShiveringTips and Tricks for Shivering

�� Decrease pt temperature by 1Decrease pt temperature by 1̊̊ CC

�� Apply warm blankets to hands and feetApply warm blankets to hands and feet

-- this may trick pt brain, although pt core temp this may trick pt brain, although pt core temp remains coolremains cool

�� Keep Mg over 1.0 Keep Mg over 1.0

Adverse EffectsAdverse Effects

�� 3 most frequent Adverse Effects3 most frequent Adverse Effects�� ArrhythmiaArrhythmia�� PneumoniaPneumonia�� BleedingBleeding

�� Adverse effects in TH ptsAdverse effects in TH pts(74%)(74%)

�� Adverse effects in standard careAdverse effects in standard care(71%)(71%)

�� No significant difference in any AE No significant difference in any AE measured!measured!

HolzerHolzer, NEJM 2010, NEJM 2010 Combined results from 4 comparative clinical trialsCombined results from 4 comparative clinical trials

Therapeutic Hypothermia and Therapeutic Hypothermia and PCIPCI

�� Immediate 12 lead ECG to determine Immediate 12 lead ECG to determine cathcathor not or not �� do not delay do not delay cathcath for cooling. for cooling.

�� May do in conjunctionMay do in conjunction

�� Timing:Timing:

--STEMI: minimize delay to STEMI: minimize delay to cathcath lablab

Therapeutic Hypothermia and Therapeutic Hypothermia and PCIPCI

�� Initiate moderate hypothermia with ice packs, Initiate moderate hypothermia with ice packs, cool infusions, add cooling device if timecool infusions, add cooling device if time

�� Cooling devices Cooling devices cancan be used during be used during angiography angiography

�� Continue cooling post Continue cooling post cathcath/PCI per protocol/PCI per protocol

�� Standard medications (ASA, heparin, Standard medications (ASA, heparin, IIb/IIIaIIb/IIIainhibitors, inhibitors, clopidogrelclopidogrel) can be used) can be used

�� No apparent increased risks of bleedingNo apparent increased risks of bleeding

PostPost--Resuscitation Care Resuscitation Care BundleBundle

�� STEMISTEMI�� Early PCIEarly PCI

�� Therapeutic HypothermiaTherapeutic Hypothermia

�� Early Hemodynamic OptimizationEarly Hemodynamic Optimization

�� HyperglycemiaHyperglycemia�� Glucose Management Glucose Management –– b.gb.g.<10.<10

�� ALI/ARDSALI/ARDS

�� Antibiotic, GI, DVT ProphylaxisAntibiotic, GI, DVT Prophylaxis

Evidence to date:Evidence to date:

�� HACA 2002 HACA 2002 -- RCTRCT

�� Bernard 2002 Bernard 2002 -- RCTRCT

�� ArrichArrich 2016 2016 –– Systematic ReviewSystematic Review

Support the use of TTM for cardiac arrestSupport the use of TTM for cardiac arrest

‘‘CoolCool’’ RegistryRegistry

�� Enrolled patients resuscitated from cardiac Enrolled patients resuscitated from cardiac arrest March 2014 to August 2015 who:arrest March 2014 to August 2015 who:�� Were admitted to the CCU (n=65) or ICU Were admitted to the CCU (n=65) or ICU

(n=45) at the Royal Alexandra Hospital(n=45) at the Royal Alexandra Hospital

�� remained unresponsive remained unresponsive

TH (n=56)TH (n=56)

n (%)n (%)

No TH (n=44)No TH (n=44)

n (%)n (%)

TTM (n=10)TTM (n=10)

n (%)n (%)

GenderGender

MaleMale 40 (71.43)40 (71.43) 30 (68.18)30 (68.18) 7 (70.00)7 (70.00)

FemaleFemale 16 (28.57)16 (28.57) 14 (31.82)14 (31.82) 3 (30.00)3 (30.00)

AgeAge

Mean(SDMean(SD))61.23214 61.23214

(SD=12.84734)(SD=12.84734)57.97727 57.97727

(SD=15.7384)(SD=15.7384)48.1 48.1

(SD=18.788)(SD=18.788)

Location of arrestLocation of arrest

IHCAIHCA 4 (7.14)4 (7.14) 12 (27.27)12 (27.27) 2 (20.00)2 (20.00)

OHCAOHCA 52 (92.86)52 (92.86) 32 (72.73)32 (72.73) 8 (80.00)8 (80.00)

Initial RhythmInitial Rhythm

ShockableShockable 48 (85.71)48 (85.71) 5 (11.36)5 (11.36) 1 (10.00)1 (10.00)

VfibVfib 35 (72.92)35 (72.92) 4 (80.00)4 (80.00) 1 (100.00)1 (100.00)

Pulseless VtachPulseless Vtach 3 ( 6.25)3 ( 6.25) 1 (20.00)1 (20.00) 00

UnknownUnknown 10 (20.83)10 (20.83) 00 00

NonNon--shockableshockable 8 (14.29)8 (14.29) 39 (88.64)39 (88.64) 9 (90.00)9 (90.00)

PEAPEA 6 (75.00)6 (75.00) 16 (41.03)16 (41.03) 2 (22.22)2 (22.22)

AsystoleAsystole 2 (25.00)2 (25.00) 22 (56.41)22 (56.41) 7 (77.78)7 (77.78)

UnknownUnknown 00 1 (2.56)1 (2.56) 00

WitnessedWitnessed 43 (76.79)43 (76.79) 31 (70.45)31 (70.45) 8 (80.00) 8 (80.00)

UnwitnessedUnwitnessed 13 (23.21)13 (23.21) 13 (29.55)13 (29.55) 2 (20.00)2 (20.00)

Bystander CPRBystander CPR

YesYes 40 (71.43)40 (71.43) 25 (56.82) 25 (56.82) 6 (60.00)6 (60.00)

NoNo 14 (25.00)14 (25.00) 16 (36.36)16 (36.36) 2 (20.00)2 (20.00)

UnknownUnknown 2 (3.57)2 (3.57) 3 (6.82)3 (6.82) 2 (20.00)2 (20.00)

Total downtimeTotal downtime

Mean(SD)Mean(SD)Observations: 52Observations: 52

26.53846 26.53846

(SD=14.05237)(SD=14.05237)

Observations: 37Observations: 37

26.05405 26.05405

(SD=14.1597) (SD=14.1597)

Observations: 10Observations: 10

26.426.4

(SD=22.50037)(SD=22.50037)

MI Cause of ArrestMI Cause of Arrest

YesYes 36 (64.29)36 (64.29) 5 (11.36)5 (11.36) 3 (30.00)3 (30.00)

NoNo 20 (35.71)20 (35.71) 39 (88.64)39 (88.64) 7 (70.00)7 (70.00)

DeceasedDeceased 31 (55.36)31 (55.36) 38 (86.36)38 (86.36) 9 (90.00)9 (90.00)

‘‘CoolCool’’ Registry: ResultsRegistry: Results

�� TH was associated with continuing TH was associated with continuing improvements in neurological functioningimprovements in neurological functioning

Primary OutcomePrimary Outcome

�� MoCAMoCA--3 months: mean improvement of 3 months: mean improvement of 3.3 points (SD 2.60) for TH patients (n=8)3.3 points (SD 2.60) for TH patients (n=8)

RT6

Slide 39

RT6 this slide should come bRoss Tsuyuki, 2/21/2016

‘‘CoolCool’’ Registry: ResultsRegistry: Results

Secondary Outcomes:Secondary Outcomes:

��MoCAMoCA--6 months: mean improvement of 6 months: mean improvement of 4.3 points (SD 4.72) for TH patients (n=7) 4.3 points (SD 4.72) for TH patients (n=7)

��CPCCPC--3 & 6 months: mean improvement of 3 & 6 months: mean improvement of 0.7 points (SD .72) and 0.7 points (SD 0.8) 0.7 points (SD .72) and 0.7 points (SD 0.8) for TH patients (n=15)for TH patients (n=15)

��mRSmRS--3 & 6 months: mean improvement of 3 & 6 months: mean improvement of 1.5 points (SD 1.13) and 1.9 points (SD 1.5 points (SD 1.13) and 1.9 points (SD 1.36) for TH patients (n=15)1.36) for TH patients (n=15)

‘‘CoolCool’’ Registry: ResultsRegistry: Results

Secondary Outcomes contSecondary Outcomes cont’’d:d:

��SurvivalSurvival: TH patients (n=56) also had a : TH patients (n=56) also had a decreased hazard of death compared to the decreased hazard of death compared to the no TH group (n=44), HR 0.39 (95% CI no TH group (n=44), HR 0.39 (95% CI 0.24, 0.64; p=0.0006).0.24, 0.64; p=0.0006).

‘‘CoolCool’’ Registry: ConclusionsRegistry: Conclusions

�� Supports the use of TH in the treatment of Supports the use of TH in the treatment of patients resuscitated from cardiac arrest. patients resuscitated from cardiac arrest.

Overall ConclusionsOverall Conclusions

�� Confirmed efficacy of TH for on mortality Confirmed efficacy of TH for on mortality and neurological functionand neurological function

�� Neurological improvement continues over Neurological improvement continues over timetime

�� Cannot accurately assess outcomes at Cannot accurately assess outcomes at short followshort follow--up timesup times

�� Variety of tools should be used to assess Variety of tools should be used to assess neurological outcomes in future studiesneurological outcomes in future studies

ReferencesReferences

�� Hypothermia and Resuscitation Training Institute At Penn Hypothermia and Resuscitation Training Institute At Penn Therapeutic Hypothermia After Cardiac Arrest and in Critical CarTherapeutic Hypothermia After Cardiac Arrest and in Critical Care.e.Benjamin Abella. January 2010. Benjamin Abella. January 2010. Hypothermia and Resuscitation Hypothermia and Resuscitation Training Institute At Penn.Training Institute At Penn.

�� Therapeutic Hypothermia: ICU Management of the PostTherapeutic Hypothermia: ICU Management of the Post--Cardiac Cardiac Arrest Patient. David Gaieski. April 2010. Arrest Patient. David Gaieski. April 2010. Hypothermia and Hypothermia and Resuscitation Training Institute At Penn.Resuscitation Training Institute At Penn.

�� Holzer M. Targeted Temperature Management for Comatose Holzer M. Targeted Temperature Management for Comatose Survivors of Cardiac Arrest. New England Journal of Medicine 201Survivors of Cardiac Arrest. New England Journal of Medicine 2010; 0; 363:1256363:1256--1264 1264

ReferencesReferences

�� Howes D, et al. Canadian Guidelines for the use of targeted Howes D, et al. Canadian Guidelines for the use of targeted temperature management (therapeutic hypothermia) after cardiac temperature management (therapeutic hypothermia) after cardiac arrest: A joint statement from The Canadian Association of arrest: A joint statement from The Canadian Association of Emergency Physicians (CAEP), the Canadian Critical Care Society Emergency Physicians (CAEP), the Canadian Critical Care Society (CCCS), Canadian Neurocritical Care Society (CNCCS), and the (CCCS), Canadian Neurocritical Care Society (CNCCS), and the Canadian Critical Care Trials Group (CCCTG). Resuscitation (2015Canadian Critical Care Trials Group (CCCTG). Resuscitation (2015), ), http://dx.doi.org/10.1016/j.resuscitation.2015.07.052 http://dx.doi.org/10.1016/j.resuscitation.2015.07.052

�� Peberdy M, et al. Part 9: PostPeberdy M, et al. Part 9: Post––Cardiac Arrest Care 2010 American Cardiac Arrest Care 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation aHeart Association Guidelines for Cardiopulmonary Resuscitation and nd Emergency Cardiovascular Care. Emergency Cardiovascular Care. CirculationCirculation. 2010;122:S768. 2010;122:S768--86. 86.

�� Mongardon N, D. F. (2011). Postcardiac arrest syndrome from Mongardon N, D. F. (2011). Postcardiac arrest syndrome from immediate resuscitation to longimmediate resuscitation to long--term outcome. Ann Intensive Care, term outcome. Ann Intensive Care, 1:45.1:45.