Hypothermic Resuscitation

Sombat Muengtaweepongsa M DSombat Muengtaweepongsa, M.D.Division of NeurologyFaculty of Medicine

Thammasat UniversityThammasat University

ScopeScope• Therapeutic hypothermia after cardiac arrest• Therapeutic hypothermia in ischemic strokeTherapeutic hypothermia in ischemic stroke• Fever control in critical care neurology

2005 ILCOR2005 ILCOR

• There seems to be good evidence (level 1) to recommend the use of induced )mild hypothermia in comatose survivors of-out-hospital cardiac arrestsurvivors of out hospital cardiac arrest caused by VF.

Level 1 evidence indicates one or more randomized clinical trials in which benefit was shown

Therapeutic Hypothermia after CardiacTherapeutic Hypothermia after Cardiac

Arrest

(N Engl J Med 2002;346:557-63.)

Th RCT f TH ft di tThe RCT of TH after cardiac arrest

HACA (European) Bernard trial (Australia)

Sample N=275 N=77Cooled verses normothermia

137 cooled138 normothermia

43 cooled34 normothermia

Intervention Cooling blankets and ice packs

Ice packs

Target temperature 32-34 degrees 33 degreesInitiation Prehospital ERpDuration 24 hours 12 hoursFollow up 6 months 30 daysFollow up 6 months 30 days

BenefitBenefit

• NNT of 7 to prevent 1 death with TH• NNT of 6 to reduce neurologicNNT of 6 to reduce neurologic

impairment with TH

The NNT is the number of patients who need to be treated in order to prevent one additional bad outcome

Ad E tHACA study group, 2002. New England Journal of

Medicine 346(8).

Adverse Events• Bleeding, pneumonia, sepsis, pancreatitis,

renal failure, pulmonary edema, seizures, , p y , ,arrhythmias and pressure sores were recorded in both trials with no significant gadverse events.

“ Sepsis was more likely to develop in the patients ith h pothermia than those in normothermiawith hypothermia than those in normothermia,

although this difference was not statistically significant” (HACA study group 2002)significant (HACA study group, 2002)

Sid ff t f d t h th iSide effects of moderate hypothermia on various organ systems

Variable Normothermia Hypothermia After-rewarming

Plt tPlt count 183 (145-310) 110 (20-180) 160 (50-210)

aPTT 27 (20-45) 34 (25-50) 30 (20-55)

lipase 140 (60-190) 250 (140-1200) 200 (135-1000)

K+ 4.1 (3.5-4.7) 3.4 (3.1-3.9) 4.4 (4.0-5.2)K+ 4.1 (3.5 4.7) 3.4 (3.1 3.9) 4.4 (4.0 5.2)

Na+ 139 (134-145) 140 (138-150) 145 (139-155)

C ClCr Clearance 81 (60-100) 65 (45-90) 70 (45-95)

Norepinephrine 0 0.32 (0.0-0.45) 0.08 (0.0-0.24)

What is the purpose of TH?What is the purpose of TH?• Aimed at minimizing the effects of

anoxic neurologic injury following g j y gcardiac arrest

• Other than supportive care TH it is the• Other than supportive care TH it is the only identified measure to improve

f fquality of life post resuscitation

So why is TH notSo why is TH not done more often?

Both of these studies involved a highly selected group ofpatients, excluding up to 92% of patients with out-of-hospitalcardiac arrest initially assessed for eligibility

Suggested Inclusion Criteriagg• TH is indicated if the patient meets all of the

following criteria:following criteria:1. Witnessed arrest2. Initial rhythm VF or pulseless VT…. But3. Time to ACLS was less than 15 minutes and total

of ACLS time less than 60 minutes4. GCS of 8 or below4. GCS of 8 or below5. SBP of > 90 with or without vasopressors6 Less than 8 hours have elapsed since return of6. Less than 8 hours have elapsed since return of

spontaneous circulation (ROSC)

Suggested Exclusion Criteriagg1. Pregnancy2. GCS 10 and improving3. Down time of > 30 minutes4. ACLS preformed for > 60 minutes5 Known terminal illness5. Known terminal illness6. Comatose state prior to cardiac arrest7 P l d h t i (i MAP 60 f 307. Prolonged hypotension (ie MAP < 60 for >30

minutes)8. Evidence of hypoxemia for > 15 min following

ROSC9. Known coagulopathy that cannot be reversed

M h i f t ti bMechanisms of neuroprotection by hypothermia

• counteract ischemic brain damage by several mechanisms– prevention of the blood–brain-barrier

disruptiondisruption– oxygen-based free-radical production excitotoxicneurotransmitter release– excitotoxicneurotransmitter release

– anti-inflammatory action– delayed apoptosis

Historical ObservationsHistorical Observations

• Not Dead till Warm and Dead– Cold patients would wake up in the Morguep p g

• Kids / Hockey Players- fall through ice, long rescue times but good recoverylong rescue times, but good recovery

• Hibernation: state of low oxygen, acidosis, yglow energy supply

Ideal temperature curve

Induction

erat

ure

Rewarming

Tem

pe Sustainment Rewarming

Timee

Methods to Control Brain Temperature in Stroke

PatientsPatients

Methods of CoolingMethods of Cooling

• Selective head cooling– Cooling helmet: ineffective in adultg

• Internal cooling by intravenous and intraarterial ice cold salineintraarterial ice-cold saline– Need large volume

• Surface cooling• Endovascular cooling• Endovascular cooling

Surface blanketSurface blanket

Surface coolingSurface cooling

Surface coolingSurface cooling

Figure 1. The Reprieve Endovascular Temperature Management System

De Georgia, M. A. et al. Neurology 2004;63:312-317

Endovascular catheterEndovascular catheter

Intravascular Hypothermic Machine

Intravascular Hypothermic Catheter

Thermoregulatory Defenses Against Hypothermia

• Vasoconstriction– Primary autonomic defensesy– Threshold: 36.5o C

• Shivering• Shivering– “last resort” response– Threshold: 35.5o C

Introduction of thermoregulatory tolerance

• Nonpharmacological treatments– Whole body surface warmingy g

• Pharmacological treatmentsA th ti d M l l t– Anesthetics and Muscle relaxants

– Meperidine– Drug combination

• Meperidine and Buspironep p• Meperidine and Dexmedetomidine

Reductions in the shivering threshold (compared with the control day) for the dexmedetomidine (Dex), meperidine (Mep), and 2-drug combination (Combo) days

Copyright ©2003 American Heart Association

Doufas, A. G. et al. Stroke 2003;34:1218-1223

RewarmingRewarming

Th t iti l i d f i k l t d t• The most critical period of risk related to therapeutic hypothermia

• Vasodilation• Hypermetabolic responseHypermetabolic response

– Systemic inflammatory response syndrome (SIRS)(SIRS)

• Passive controlled rewarmingSt i i t 0 1 0 5 oC h– Stepwise rewarming rate: 0.1-0.5 oC per hr

RewarmingRewarming

C b l id ff t• Cerebral side effects– Rebound edema and ICP elevation

E b l id ff• Extracerebral side effects– Infection

P i• Pneumonia• Sepsis

– CardiopulmonaryCardiopulmonary• Elevation of catecholamines: arrhythmia

– Hematologic• Induced thrombosis

Therapeutic Hypothermia for

Ischemic StrokeIschemic Stroke

A case scenarioA case scenario

69 y/o woman presented to an outside h it l ith dd t f i ht id dhospital with sudden onset of right sided weakness and speech impairment. She arrived at the OSH at 20 minutes after onset. CT-brain was negative. TPA wasonset. CT brain was negative. TPA was started at 90 minutes after the onset before she was transferred to SLUHbefore she was transferred to SLUH.

A case scenario (cont )A case scenario (cont.)

Sh l t d k b t h iShe was alert and awake, but aphasic. NIHSS was 8 with:

LOCb 2, partial hemianopiapartial hemianopia, right arm drifting, some effort against gravity on right legsome effort against gravity on right leg, partial sensory loss on the left sidemoderate aphasiamoderate aphasia.

A case scenario (cont )

With t ith i t b ti d ti

A case scenario (cont.)

Without either intubation or sedation, therapeutic hypothermia with endovascular cooling technique was started at 5 hours after onset. Target core temperature of 33oC was reached within 3 hrs. Shivering was under control with combination of surface warming and meperidine plus buspirone. Gradual p p prewarming was applied after target temperature was maintained for 24 hrs.

Temperature and stroke

For each 1 degrees C increase in body temperature the relative risk of poor outcome rose by 2.2 (95of poor outcome rose by 2.2 (95 percent CI 1.4-3.5) (p less than 0.002).

She was discharged to a rehab after 5 days of admission with NIHSS of 5 and mRS of 3.

At day 30 She walked by herself to followAt day 30, She walked by herself to follow up at DOB. NIHSS was only 3 including

Shemianopia and partial sensory loss. mRS was 2.

Hypothermia for MalignantHypothermia for Malignant MCA Infarction

Fever-related Brain Injury in the

C b l I f tiNeuro-ICU

• Cerebral Infarction• Elevated temperature is associated with

t ft t kpoor outcome after strokeHajat et al, Stroke 2000;31:410

• Subarachnoid Hemorrhage• Subarachnoid Hemorrhage• Fever burden independently associated with

mortality & poor functional outcome.y pMayer et al, Crit Care Med 2003 (Suppl);30:A5

• Intracerebral HemorrhageD ti f f ( 37 5° C) ithi th fi t• Duration of fever (>37.5° C) within the first 72 hours is independently associated with poor outcomeSchwarz et al, Neurology 2000;54:354

Treatment of fever in the neurologic intensive care unit with a th t b d h t h tcatheter-based heat exchange system

Diringer MN, CCM 2204;32:559

• 296 patients with T ≥38° C for at least 2 ioccasions

– SAH, TBI, ICH and cerebral infarction• Alsius Cool Line endovascular heat exchange• Alsius Cool Line endovascular heat exchange

catheter plus standard surface cooling• Fever Burden >38 °CFever Burden 38 C

– 7.92 °C-hours – 2.87 °C-hours

64% relative reduction (P<0.01)

• Shivering “of concern” in four patients (3.7%)

Clinical Trial of a Novel Surface Cooling System for Fever Control in Neurocritical Care Patientsfor Fever Control in Neurocritical Care PatientsMayer, et al, Crit Care Med 2004

• 47 patients with T ≥38.3° C for >2 consecutive hours after receiving acetaminophen

Median GCS 8 0– Median GCS 8.0– SAH, ICH, infarction, TBI– Mean 42 hours >38 3° C prior to– Mean 42 hours >38.3 C prior to

randomization• Interventions

– Standard SubZero cooling blanket– Medivance Artcic Sun surface cooling

system• Main outcome measure

24 h f b d– 24 hour fever burden

Clinical Trial of a Novel Surface Cooling System for Fever Control in Neurocritical Care Patients

P=0.001

Change in Glasgow Coma ScaleChange in Glasgow Coma Scale

P=.038, GEE model

ConclusionConclusion

• TH is a standard treatment in selected patients after cardiac arrest.p

• TH should be benefit for penumbra salvaging in acute ischemic strokesalvaging in acute ischemic stroke.

• TH is one of treatments for increase ICP.• Fever control is essential, particularly in

such a bad neurological conditionssuch a bad neurological conditions.

Take home messageTake home message

“ No evidence” doesn’t meandoesn t mean

“Evidence does not exist”.

Thank you for your attentionThank you for your attention