Shah + Badjatia: Therapeutic Hypothermia 2014

Today we are fortunate to have the combined mental powers of two of the greatest minds in the field of therapeutic hypothermia. First you will hear from Nirav Shah, Assistant Professor of Medicine and current Program Director for the Pulmonary and Critical Care Fellowship at the University of Maryland. Using a vast knowledge base on the topic as well as years of scientific research, Dr Shah has combed through thousands of articles to give you only the most relevant and up to date look at hypothermia for cardiac arrests.

In addition, you will then hear from Neeraj Badjatia, Associate Professor of Neurology at the University of Maryland, Director of the Neurosurgery Critical Care Unit, Program Director for the Neurocritical Care Fellowship AND one of the world’s leading experts in the field of hypothermia. Dr. Badjatia is a recent addition from Columbia University and he shares over a decade of groundbreaking research and knowledge on the use of hypothermia for neurological disasters.

You would have to travel the globe to find a more concise and useful guide to Hypothermia all in one hour. This is one talk you CANNOT afford to miss!

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Review and summary by Dr. Rabin Shrestha 

Dr. Shah’s contribution:

Hypothermia is classified as:

• Mild (32-35°C)
• Moderate (28-32°C)
• Severe (20-28°C)
• Profound (<20°C)

Therapeutic hypothermia Indications

• Evidence proven:
  • Out of hospital cardiac arrest
  • Neonatal Hypoxia-ischemia
• Controversial:
  • Traumatic brain injury
  • Hemorrhagic shock
  • Ischemic stroke
  • Septic shock
  • Acute lung injury

Three phases of treatment:

• Induction – rapidly cooling; sedate and possibly paralyze
• Maintenance – standard 12-24 hours
• Rewarming – rewarm slowly – most dangerous period: hypotension, cerebral edema, seizures

Important studies for therapeutic hypothermia:

• Bernard et al. NEJM 2002
  • Randomized non-blinded Australian study N= 43 hypothermia; N=34 normothermia
  • Population V-fib or pulseless V-tach, comatose
  • Primary outcome: survival with good neurologic function
  • Maintained at 33⁰C for 12 hours and rewarmed after 6 hours
  • 49% vs 26% had moderate to good neurologic outcomes in favor of hypothermia
• Hypothermia after Cardiac Arrest Study Group. NEJM 2002
  • Randomized control trial in Europe N = 137 hypothermia, N= 138 normothermia
  • Population V-fib or pulseless V-tach, comatose
  • Primary outcome – favorable neurologic outcome in 6 months
  • 32 ⁰C– 34⁰ C for 24h and rewarmed over 8 hours
  • 55% vs 39% in favor of hypothermia
• Neilsen et al. NEJM 2013
  • Prospective study in 36 ICUs in Europe and Australia
  • Inclusion – Out of hospital cardiac arrest irrespective of rhythm
  • 33⁰C vs 36⁰C, multiple cooling methods; rewarmed after 28h
  • Primary outcome – All cause mortality at end of trial
  • No difference in all-cause mortality (approx. 50%) or combined end point of mortality + neurologic outcome at 6 months
• Kim et al. JAMA 2014
  • Randomized trial in USA
  • Prehospital cardiac arrest cooled with 2 L of 4⁰C normal saline
  • Temperature goal <34⁰C, stratified to with and w/o V-fib
  • No difference in survival or neurologic outcome
  • Increased rearrest and pulmonary edema in hypothermia group

Take home points:

• Not all black and white
• Hypothermia still is an important tool in neurologic preservation post arrest
• Keeping patient afebrile post arrest may be more important that hypothermia

Dr. Badjatia’s contribution:

• Neurologic outcomes in key studies on therapeutic hypothermia have not been well defined in most studies
• Studies are complicated by high rates of withdrawal of care

Prognostication:

• Neurologic exam
  • Best predictor of brain injury
  • Day 3 exam traditionally considered best
  • Hypothermia has changed timing due to effect of temperature on sedatives/physiologic response
• Electrophysiological tests
  • EEG – provides pattern of injury, impacted by sedation and motor activity
  • SSEP (somatosensory evoked potential) – provides information about the reticular activating system
• Biomarkers – neuron specific enolase being the most reliable predictor
• Neuroimaging – CT scan and MRI

Take home points:

• Hypothermia complicates interpretation of neurologic prognosis typically done at 72 hours
• Multimodality approach that includes exam, electrophysiological tests, biomarkers and imaging will likely provide the best assessment
• Overall prognosis needs to be tailored to patent specific factors