Hypothermia Post Cardiac Arrest Mazen Kherallah, MD, FCCP

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HypothermiaPost Cardiac Arrest

• Mazen Kherallah, MD, FCCP
• Infectious Disease and Critical Care Medicine

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Magnitude of Sudden Cardiac Arrest in the US
167,366
Stroke
450,000
Sudden cardiac arrest claims more lives each year
than these other diseases combined
Sudden Cardiac Arrests
Lung Cancer
157,400
1 Killer in the U.S.
Breast Cancer
40,600
AIDS
42,156
1 U.S. Census Bureau, Statistical Abstract of
the United States 2001. 2 American Cancer
Society, Inc., Surveillance Research, Cancer
Facts and Figures 2001. 3 2002 Heart and Stroke
Statistical Update, American Heart Association. 4
Zheng Z. Circulation. 20011042158-2163.
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EMS systems have improved outcome of cardiac
arrests
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Survival Rates of Different Setting Cardiac
Arrests
Internal Medicine Journal 34  398  - July
2004 Critical care, 2001 Acta Anesthesiologica
,Aug 2006
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Survival According to Initial Rhythm
Critical care medicine 1999
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Outcome of cardiac arrest improved slowly over
the years
Critical Care Medicine, 1999
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Cerebral Energy Requirements

• CMRO2 3.5 cc O2/min/100 g
• CMR glucose 5.5 mg/min/100 g
• Activation Metabolism
• 55-60
• Residual Metabolism
• 40-45

60
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Barash, Cullen, Stoelting. Clinical Anethesia,
5th Ed. Lippincott Williams Wilkins, 2006 p
751.
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Global Ischemia
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Ischemic
Cascade
Cucchiara, Black, Michenfelder. Clinical
Neuroanesthesia, 2nd Ed. Churchill Livingstone,
1998 p 184.
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Neuro-Protection?

• Maintain blood flow
• Maintain ATP levels by reducing CMR
• Blocking Na and Ca influx
• Scavenge free radicals
• Block release/receptors for excitatory amino
  acids
• Delay membrane failure apoptotic processes
• Inhibiting proteins that activate or contribute
  to damage (proteases, phospholipases, certain
  kinases)
• Activating proteins that induce repair or rescue

Barash, Cullen, Stoelting. Clinical Anethesia,
5th Ed. Lippincott Williams Wilkins, 2006 p
751.
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Hypothermia
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Beneficial Effects of Hypothermia

• Decrease in cerebral metabolism
• Maintains integrity of membranes
• Preserves ion homeostasis
• Decreases excitatory AA release
• Decrease Ca influx
• Decrease lipid peroxidation
• Decrease free radical formation
• Decrease nitric oxide synthase activity

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CMRO2 Temperature
Miller. Millers Anesthesia, 6th Ed, Vol 1.
Elsevier Churchill Livingstone, 2005 p 816.
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Therapeutic Hypothermia Post Resuscitation
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Therapeutic Hypothermia

• 1st reported use of therapeutic hypothermia in
  TBI in 1943.
• 1st reported use as a protective adjunct to
  neurosurgery in 1955.

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Benson DW, Williams GR Jr, Spencer FC, Yates AJ.
Anesth Analg 1959 38 423-8.
The Use of Hypothermia After Cardiac Arrest

• Comatose survivors
• Asystole or VF
• 31-32C
• Cooling until neurologic recovery(3 hours to 8
  days)
• Water-filled blanket

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• Michael Holzer N Engl J Med 2002346549-56

Vienna, Austria
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Mild Therapeutic Hypothermia to Improve the
Neurologic Outcome After Cardiac Arrest (HACA)
Inclusions
Exclusion

• Tympanic-membrane temperature below 30C
• Comatose state before the cardiac arrest
• pregnancy
• Response to verbal commands after ROSC
• Evidence of hypotension MAPlt 60 mm Hg for more
  than 30 minutes after ROSC
• Evidence of hypoxemia O2 Sat lt85 for more than
  15 minutes after ROSC
• Terminal illness that preceded the arrest
• Preexisting coagulopathy.

• Witnessed cardiac arrest,
• Ventricular fibrillation or nonperfusing
  ventricular tachycardia
• Presumed cardiac origin of the arrest
• Age of 18 to 75 years
• Estimated interval of 5 to 15 minutes from the
  patients collapse to the first attempt at
  resuscitation
• Interval of no more than 60 minutes from
  collapse to restoration of spontaneous
  circulation.

The Hypothermia after Cardiac Arrest Study Group,
. N Engl J Med 2002346549-556
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Mild Therapeutic Hypothermia to Improve the
Neurologic Outcome After Cardiac Arrest (HACA)
275/3,551 (8) Pts s/p Witnessed V-fib Arrest
Multicenter RCT, Blinded assessment outcome.
Hypothermia (32-34 oC) x 24 hrs 137 Patients
normothermia (37-38 oC) 138 Patients
Primary endpoint favorable neuro outcome w/in 6
mo
Secondary 6 mo mortality 7 day complication
rate.
Pittsburgh cerebral-performance category, 1
good recovery or 2 moderate disability
The Hypothermia after Cardiac Arrest Study Group,
. N Engl J Med 2002346549-556
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Bladder Temperature in the Normothermia and
Hypothermia Groups
The Hypothermia after Cardiac Arrest Study Group,
. N Engl J Med 2002346549-556
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Neurologic Outcome and Mortality at Six Months
The Hypothermia after Cardiac Arrest Study Group,
. N Engl J Med 2002346549-556
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Mild Therapeutic Hypothermia to Improve the
Neurologic Outcome After Cardiac Arrest (HACA)
The Hypothermia after Cardiac Arrest Study Group,
. N Engl J Med 2002346549-556
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Cumulative Survival in the Normothermia and
Hypothermia Groups
The Hypothermia after Cardiac Arrest Study Group,
. N Engl J Med 2002346549-556
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• Bernard et al. N Engl J Med 2002 346557-563

Melbourne, Australia
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Treatment of Comatose Survivors of OOH Cardiac
Arrest with Induced Hypothermia

• Multicenter rCT 77 Pts who remained unconscious
  s/p out of hospital cardiac arrest (V-fib _at_
  scene).
• Randomized (by day) to hypothermia group (33 oC 2
  hrs after return of spont circulation maintained
  for 12 hours) or normothermia.

Bernard, S. et al. N Engl J Med 2002346557-563
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Treatment of Comatose Survivors of OOH Cardiac
Arrest with Induced Hypothermia
P0.046
P0.145
Bernard, S. et al. N Engl J Med 2002346557-563
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Favorable Neuro Outcome Three Studies
Chi SquareTesting p lt 0.0005
308 Patients
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Conclusion

• In patients who have been successfully
  resuscitated after cardiac arrest due to
  ventricular fibrillation, therapeutic mild
  hypothermia increased the rate of a favorable
  neurologic outcome and reduced mortality.

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ILCOR Advisory Statement

• Unconscious adult patients with ROSC after
  out-of-hospital VF cardiac arrest should be
  cooled to 32C - 34C for 12 - 24 hours
• Possible benefit for other rhythms or in-hospital
  cardiac arrest

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2005 AHA guidelines for ACLS and post CPR care

• In a select subset of patients who were initially
  comatose but hemodynamicaly stable after a
  witnessed VF arrest of presumed cardiac etiology,
  active induction of hypothermia was beneficial.
  Thus, unconscious adult patients with ROSC after
  out-of-hospital cardiac arrest should be cooled
  to 32C to 34C for 12 to 24 hours when the
  initial rhythm was VF (Class IIa). Similar
  therapy may be beneficial for patients with
  non-VF arrest out of hospital or for in-hospital
  arrest (Class IIb).

2005 AHA guidelines, Circulation, 2005
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How to apply hypothermia
It is not that complicated!!
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Hypothermia Protocol

• Indications
• Only comatose adults after ROSC who are
  hemodynamically stable
• Initiation
• ASAP, but at least within 6 hours of event
• Degree of Hypothermia
• 32-35oC core temperature
• Duration
• At least 12 hours 24 hours probably better

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How to Cool Four Modes of Heat Transfer

• Conduction
• Cold water immersion
• Radiation
• Cold room
• Convection
• Fans (do not use for infection control purposes)
• Evaporation
• Sweating

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How to Cool Hypothermia Protocol

• Blanket cooling not effective in adults
• Intravascular cooling with bolus of iced RL or NS
  is effective
• Surface SURFACE COOLING
• SubZero, Aquamatic (conventional
  water-circulating)
• Polar Air (forced air convection cooling)
• Arctic Sun (adhesive hyrogel, water
  circulating)
• MTRE (tight wrap water circulating)

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HOW TO COOL Hypothermia Protocol

• ENDOVASCULAR CATHETER COOLING
• Radiant
• Alsius
• Innercool (metallic)

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Monitoring Mild/Moderate Hypothermia Protocol
(33 C)

• Endotracheal intubation
• Sedation fentanyl midazolam
• Paralysis vecuronium 0.1 mg/kg PRN
• Thermistors bladder, rectal, esophageal, or
  blood temperature, ? Brain temperature
• Radial artery and internal jugular lines
• Intraparenchymal ICP temperature monitor
• Insulin drip for BS gt180 mg/dl
• Hypokalemia lt3.4 mEq/l replaced

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Monitoring Mild/Moderate Hypothermia Protocol

• ABGs at room temp (alpha-stat)
• Vasopressors to keep CPP gt70 mm Hg
• ICP gt20 mm Hg treated per protocol
• Feedings held x 48 hours
• Cultures/antibiotics as indicated
• Passive controlled rewarming (0.5 / hr)
• Active cooling is maintained at 36.5C thereafter
  for 24 hrs to avoid overshoot
• Need to adjust medications during hypothermia?

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Example of Anti-Shivering Protocol

• Focal Counterwarming
• Feet and hands
• Face
• Body (Bear Hugger)
• Buspirone 20 q8H
• Meperidine 25-100 mg q4H
• Alt dexmendetomidine, fentanyl, propofol
• If use NMB, need to monitor EEG
• Sub-clinical seizures may be more common than
  clinically recognized should we load with
  anticonvulsants?

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Detrimental Effects of Hypothermia

• Circulatory afterload, 3rd spacing,
  viscosity, diuresis, hypovolemia, hypotension
• Cardiac shivering, cardiac output, arrhythmias
• Pulmonary pulm edema
• Neurologic ICP w/ rewarming, affects
  neuromonitoring
• Coagulation plt dysfxn, fibrinolysis, bleeding
• Metabolic shifts O2 dissociation curve left,
  metabolic acidosis, respiratory alkalosis,
  Hypokalemia, hyperglycemia, ileus, drug metab
• Immunologic leuk mobility phagocytosis

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Use of Therapeutic Hypothermia by Clinical
Specialty
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Reasons Against Use of Hypothermia as a
Therapeutic Tool
Reason for nonuse
-
Percentage of respondents
0 10 20 30 40
50
Not enough data
49
Havent considered it
32
Not in ACLS guidelines
32
Too technically difficult
19
Current methods cool too slow
9
Unsatisfactory initial attempts
4
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Cooling Technique
Cooling technique Percentage
of respondents
0 10 20 30 40
50
Cooling blankets
50
15
Ice / cold liquid packing
13
Ice / cold liquid gastric lavage
2
IV cooling catheter
2
Cooling mist
17
Other method
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Take home messages

• Strong evidence that mild hypothermia is
  neuro-protective after return of spontaneous
  circulation.
• Fever is detrimental post resuscitation (and for
  any neuro patient)
• Hypothermia is underutilized so far but should be
  included in post resuscitaion care of cardiac
  arrest victims

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Critical Care is A Promise
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If you are admitted to our ICU after cardiac
arrest

• You will get cooled

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Thank You
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