Question 21

College answer

Not available.

Discussion

Rationale:

• Therapeutic hypothermia has been advanced as a means of improving survival and good neurological outcome following cardiac arrest.
• Therapeutic hypothermia modulates the activity of body proteins and electrolytes.
• This modulation is thought to have some beneficial effects in scenarios where inflammatory damage is anticipated.
• This also involves the down-modulation of the overall metabolic rate, which decreases the metabolic demands of the organism in poor cardiac output states
• Decrease in oxygen consumption matches decreased demand with decreased supply in "penumbra" areas, at the watersheds, where hypoxic injury has caused oedema

Advantages:

• Decreased granulocyte migration into the brain tissue.
• Decreased cerebral oedema
• Intrinsic anticonvulsant effects of hypothermia

Disadvantages:

• Decreased rate of drug metabolism
• Impaired immunity
• Decreased cardiac output and bradycardia
• Prolongation of QT
• Risk of arrhythmias
• Increased haematocrit and blood viscosity
• Hyperglycaemia
• Counterproductive energy expenditure via shivering

Evidence:

• Pseudorandomised unblinded trial in 1996 showed promising results
• Bernard et al (2002), in a small study (n=77) demonstrated a marked difference in survival (26% vs 49%) in out of hospital VF arrest survivors using 33°C.
• HACA trial (2002) in a small study (n=134) demonstrated good neurological outcomes in 55% of cooled patients, vs. 39% of non-cooled patients.
• TTM trial (2013) in a larger and more methodologically robust study (n=950) had demonstrated non-inferiority of a more conservative hypothermia (36°C), in terms of mortality.
• HYPERION trial (2019), specifically among patients with nonshockable rhythm (n=584) , found a benefit to good neurological outcome (10.2% vs 5.7%) using 33°C.
• TTM2 trial (2021), the largest so far (n=1861) had further demonstrated that merely maintaining normothermia (under 37.8°C) was also non-inferior to using  33°C (54% vs 54% mortality).

Society recommendations

• ESC (2021) recommend 32 and 36 °C for at least 24 hours
• AHA (2020) recommend TTM 
• AHA (2015) had specifically recommended 32-36° C
• ARC recommended 32-36° C in 2016 (and that was their last update)

Own practice:

• Any reasonable response, so long as it incorporates the avoidance of fever, eg. "In my practice, I cool patients to keep their temperature in the normal range, under 37.8° C"