Critically evaluate the use of therapeutic hypothermia in intensive care practice.
Answer and interpretation
Maintenance of a target temperature to provide neuroprotection. A range of different temperatures employed with ‘mild hypothermia’ traditionally 32-34oC; more recently 36oC post TTM trial.
Hypothermia may lessen the brain injury through a number of mechanisms:
- Cerebral metabolic rate decreases by ~6-10% per degree Celcius drop in temperature
- Reduced release of excitatory amino acids / glutamate which mediate neuronal injury
- Reduced ischaemia reperfusion induced reactive oxygen species release
- Reduced inflammation – both cellular response and cytokine expression
- Reduced apoptosis
- Preservation of blood brain barrier (reduced NO, aquaporin 4, metallo-proteinases)
Clinical utility and evidence:
Post cardiac arrest:
- Standard of care
- HACA and Bernard studies in 2002 cooled VF/VT patients to 32-34 for 12-24 hrs.
- TTM trial 2013 showed no difference between target 33 and 36 in patients with out of hospital arrest of presumed cardiac cause. Fever avoided for 72 hrs in TTM.
- Current ARC/ILCOR guideline remains 32-34 but either approach reasonable.
- Avoidance of hyperthermia may be more important than hypothermia.
- ILCOR draft guidelines for 2015 recommend 32-36 for all arrests with unresponsiveness post ROSC for 24 hours (weak recommendation, very low quality evidence.)
- Prehospital cooling with crystalloid confers no benefit with increased APO
- Studies that suggest benefit of TTM in patients with cardiac arrest post hanging
- HYPERION trial underway to evaluate TTM 32.5 – 33.5 in non-shockable cardiac arrest survivors
Traumatic brain injury:
- Multiple studies have looked at TH to treat severe TBI i.e. prophylaxis.
- Meta-analysis of trials spanning over 20 yrs suggests a beneficial effect on mortality and favourable outcome.
- When limited to higher quality trials no significant mortality benefit.
- BTF guidelines level III recommendation for prophylactic hypothermia with no significant decrease in mortality but association with higher GOS
- Cooling associated with lower ICP and higher incidence of pneumonia
- Most trials using 32-35 degrees for at least 48 hrs
- POLAR awaited – TH for severe TBI
- Eurotherm 3235 awaited – TH for Intracranial hypertension
- TH commonly used to treat intracranial hypertension rather than as prophylaxis.
- Contemporary data evaluating this practice is lacking
Other potential uses
- Intracranial hypertension common in grade III/IV encephalopathy related to ALF
- Some advocate cooling as a treatment of strategy to manage intracranial HT
- No RCTs
- Evidence of potential harm
- Fever associated with two-fold risk of death after haemorrhagic or ischaemic stroke
- Pharmacologic methods of fever control have not shown improved outcome
- NINDS and European (EuroHYP-1) funded trials looking at induced hypothermia underway
- Case reports with HYBERNATUS trial underway evaluating TH for refractory SE
- No good data to support the use of TH in SAH.
- Small studies have looked at TH in patients with intracranial HT
- Fever associated with worse outcomes
- Results of RCTs recommend cooling 33-34 for 72hr
- Bradycardia / Arrhythmias
- Increased SVR and venous return with cold diuresis
- Hypokalaemia during cooling and rebound hyperkalaemia during rewarming
- Immunosuppression / infectious Complications
- Altered drug metabolism / reduced clearance sedative drugs
- Requirement for sedation +/- paralysis
- Concern regarding rebound intracranial hypertension during warming phase
- Challenge of achieving and maintaining target temperature
- Reasonable statement of candidates practice re TH
- Pass rate: 51%
- Highest mark: 7.5
- Candidates mentioned detail that was not requested, such as methods of cooling. Candidates also showed poor breadth of knowledge related to the potential use of hypothermia in conditions such as TBI / SAH / CVA.
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.
After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.
He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE. He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.
His one great achievement is being the father of three amazing children.
On Twitter, he is @precordialthump.