CICM SAQ 2015.1 Q9

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.

Rationale:

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

Hepatic encephalopathy

• Intracranial hypertension common in grade III/IV encephalopathy related to ALF
• Some advocate cooling as a treatment of strategy to manage intracranial HT
• Controversial
• No RCTs

Meningitis

• Evidence of potential harm

Stroke

• 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

Seizures

• Case reports with HYBERNATUS trial underway evaluating TH for refractory SE

SAH

• 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

Neonatal encephalopathy

• Results of RCTs recommend cooling 33-34 for 72hr

Adverse effects:

• Bradycardia / Arrhythmias
• Increased SVR and venous return with cold diuresis
• Hypokalaemia during cooling and rebound hyperkalaemia during rewarming
• Immunosuppression / infectious Complications
• Coagulopathy
• 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

Practice:

• Reasonable statement of candidates practice re TH