Clinical meaning
Targeted temperature management (TTM, formerly 'therapeutic hypothermia') is a neuroprotective strategy used primarily after cardiac arrest to reduce brain injury. After return of spontaneous circulation (ROSC), the brain undergoes a cascade of secondary injury: reperfusion injury (paradoxical damage from re-oxygenation — reactive oxygen species generation, calcium influx, mitochondrial dysfunction, apoptosis activation, excitotoxic glutamate release, and inflammatory cascade activation). This secondary injury occurs over hours to days and is potentially modifiable. TTM slows metabolic rate (~6-7% reduction per 1°C decrease), reduces oxygen consumption and CO₂ production, decreases excitotory neurotransmitter release (glutamate), reduces free radical generation, suppresses inflammatory cascades (TNF-α, IL-1, IL-6), inhibits apoptotic pathways (caspase activation), reduces cerebral edema, and stabilizes the blood-brain barrier. The TTM2 trial (2021) compared 33°C vs. 36°C targeting and found no difference in mortality or neurological outcome, shifting practice from mandatory deep cooling to targeted normothermia with active fever prevention (≤37.5°C). Current AHA guidelines (2020/2022) recommend: selecting and maintaining a constant target temperature between 32-37.5°C for at least 24 hours in comatose adult survivors of cardiac arrest, with ACTIVE FEVER PREVENTION (avoiding temperature >37.5°C) for at least 72 hours. The key takeaway is that preventing FEVER is critical — hyperthermia after cardiac arrest worsens neurological outcomes and should be aggressively treated.