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In targeted temperature management of comatose patients post-cardiac arrest, the question of how cold to keep them could depend on the extent of brain and cardiopulmonary injury, a single-center study suggested.

Among patients at the University of Pittsburgh Medical Center (UPMC) believed to have salvageable brain function, chances of survival differed according to the interaction between Pittsburgh Cardiac Arrest Category (PCAC) and target temperature (33°C, 91.4°F vs 36°C, 96.8°F):

• Lower survival at 33 °C in people with mild to moderate coma and no shock (PCAC 2): 64.2% vs 78.0% (risk difference -13.8%, 95% CI -24.4% to -3.2%)
• Higher survival at 33 °C in people with mild to moderate coma and cardiopulmonary failure (PCAC 3): 55.1% vs 33.3% (risk difference +21.8%, 95% CI 5.4-38.2%)
• Higher survival at 33 °C in people with severe coma and missing some brainstem reflexes (PCAC 4): 15.1% vs 5.4% (risk difference +9.7%, 95% CI 4.0-15.3%)

"The present analysis confirms how strongly illness severity is associated with expected survival and outcomes and how illness severity can interact with response to TTM [targeted temperature management]," wrote UPMC's Clifton Callaway, MD, PhD, and colleagues .

Callaway and colleagues developed the PCAC as one way to measure initial illness severity in people resuscitated from cardiac arrest. Assessed within 6 hours of restoration of pulses, the score comprises a neurologic examination (FOUR score) plus a test of cardiopulmonary failure (SOFA score).

"While it is apparent that the one-size-fits-all approach to any therapy is imprecise, there has been little attempt to surmount this problem in post-cardiac arrest care. It may appear evident that patients with different severities of brain injury require different types of therapy," according to by Romergryko Geocadin, MD, of Johns Hopkins Hospital in Baltimore.

Geocadin advocated looking "beyond injury detection and clinical stratification" to develop "brain-specific biomarkers that can detect not only ongoing brain injury, but also its recovery."

"With the ability of TTM to improve survival and outcome, we need to identify biomarkers to help us use TTM to its fullest. We need to develop reliable brain and systemic biomarkers that are capable of early detection and stratification of injury. With these biomarkers, we can match the 'dose' of TTM, either the depth of cooling or the duration of cooling," according to the editorialist.

Callaway's team suggested that lower body temperatures may help in severe illness by reducing seizure risk, cerebral edema, intracranial pressure, and metabolic demand during marginal perfusion.

Their retrospective study included 1,319 consecutive TTM patients in 2010-2018 as identified by an institutional quality improvement database. Eligible participants were eligible for aggressive critical care at Callaway's institution, a regional referral center for post-cardiac arrest care.

It is routine to keep all comatose patients in a mild hypothermia range for 24 hours -- using surface cooling with gel-adhesive pads or water-filled blankets and endovascular cooling devices -- followed by rewarming at 0.25 °C/h, according to Callaway's group.

Over half of the people in the study had 36°C as the target temperature (55.2%; 62.0% men, median age 61 years). Their rate of survival to discharge was 24.5%. The remainder was targeted to 33°C (44.8%; 59.7% men, median age 59 years), with 29.3% surviving to discharge.

Nearly two-thirds of deaths resulted after withdrawal of life-sustaining therapies. Mortality was almost universal for those with severe cerebral edema or EEG readings suggestive of irrecoverable primary brain injury, regardless of target temperature.

The observational nature of the study made it inherently subject to various biases, the study authors acknowledged.

"TTM at 33°C was the routine treatment for all comatose patients after cardiac arrest from 2010 to 2013. From 2014 to 2018, our clinicians selected TTM at 33°C or 36°C based on individual preference, anecdotally reporting that their choices were influenced by illness severity," they noted.

"Despite these limitations, the study by Callaway and colleagues is an encouraging step forward from the status quo. It provides supporting evidence that brain injury in patients who experience cardiac arrest is a significant target and beneficiary of TTM," Geocadin said.

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