Is there an ideal core body temperature to improve survival in patients who are comatose following cardiac arrest? A study by University of Pittsburgh researchers suggests that severity of illness is the key to determining optimal targeted temperature management (TTM).
Clifton W. Callaway, MD, PhD, of the Pittsburgh Post-Cardiac Arrest Service, Department of Emergency Medicine, University of Pittsburgh, and colleagues reported in JAMA Network Open that TTM at 33°C “was associated with better survival than TTM at 36 °C among patients with the most severe post–cardiac arrest illness but without severe cerebral edema or malignant EEG. However, TTM at 36 °C was associated with better survival among patients with mild- to moderate-severity illness.”
Romergryko G. Geocadin, MD, Johns Hopkins Hospital, writing an invited commentary in the journal, said Calloway’s study was “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. The study demonstrates a potential direction that may transform much of the current neurologic assessment of patients after cardiac arrest that is mostly focused neurologic prognostication.”
The retrospective cohort study compared outcomes in 1,319 patients at a single institution from January 2010 through December 2018. All were comatose following cardiac arrest. Severity of illness was determined by “coma and organ failure scores, presence of severe cerebral edema, and presence of highly malignant electroencephalogram (EEG) after resuscitation,” the authors explained. Patients had TTM at 36 °C or 33 °C.
Among the findings:
- 728 patients (median age 61, 62% men) had TTM at 33 °C.
- 591 patients (median age 59, 59.7% men) had TTM at 36 °C.
- 187 of the patients had severe cerebral edema.
- 184 of the severe cerebral edema patients died.
- 243 patients had highly malignant EEG.
- 234 of the patients with highly malignant EEG died.
- The mortality among patients with highly malignant EEG and severe cerebral edema as not affected by TTM.
“Among 911 patients (69.1%) with neither severe cerebral edema nor highly malignant EEG, we treated 489 (53.7%) with TTM at 33°C and 422 (46.3%) with TTM at 36°,” Callaway and colleagues wrote. “In this cohort, multiple organ failure was the reason for 100 deaths (39.5%) in the TTM at 36 °C cohort and 87 deaths (27.3%) in the TTM at 33 °C cohort; [withdrawal of life-sustaining therapy (WLST)] for non-neurologic reasons, 64 deaths (25.3%) and 35 deaths (11.0%), respectively.”
Likewise, there were interactions between PCAC level and choice of TTM at 33°C for mRS (TTM × PCAC 3: RR, 4.89; 95% CI, 1.73-13.8) and CPC outcomes (TTM × PCAC 3: RR, 1.76; 95% CI, 1.14-2.74; TTM × PCAC 4: RR, 3.35; 95% CI, 1.50-7.49). Callaway and colleagues wrote. “Interactions were similar for functional outcomes. Most deaths (633 of 968 [65.4%]) resulted after withdrawal of life-sustaining therapies.”
Pittsburgh Cardiac Arrest Category (PCAC) was predictive of survival to discharge: “(PCAC 2, 196 of 275 [71.3%]; PCAC 3, 59 of 139 [42.5%]; PCAC 4, 47 of 407 [11.6%]; unknown PCAC, 37 of 90 [41.1%]) and there were robust interactions between PCAC level and effect of TTM at 33 °C ,” For example, patients in PCAC 2 with TTM at 36°C had improved survival compared to PCAC 2 patients at TTM 33°C. But for patients in PCAC 3, TTM 33°C was associated with better survival to discharge.
In the commentary Geocadin wrote that the “key finding was that in patients without severe cerebral edema or highly malignant EEG, TTM at 33 °C was associated with better survival than TTM at 36°C for patients with the most severe post–cardiac arrest illness. TTM at 36°C was associated with better survival in mild to moderate severity of illness. Patients with severe cerebral edema or highly malignant EEG had poor outcomes regardless of the TTM strategy. “
Calloway and colleagues noted that the study was limited by its retrospective design and they said caution should be used when applying the findings to clinical practice. “Observational data are prone to unmeasured biases, and we documented that physicians are consciously using clinical gestalt to select TTM strategies. Adjusted analyses using measured variables can never completely remove this type of bias.”
In the commentary Geocadin wrote that regardless of those limitations, the study presents an opportunity 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.
“After the studies by Callaway and colleagues are prospectively validated, we need to look beyond injury detection and clinical stratification to guide therapies. We need to encourage the development of brain-specific biomarkers that can detect not only ongoing brain injury, but also its recovery. It should provide actionable information to clinicians about treatment response of the brain in real time. These brain-specific biomarkers should allow clinicians not only to define the appropriate initial therapy but also to titrate ongoing therapies or modify treatments based on the response of the brain. This dynamic interaction of real-time brain injury detection and treatment titration will be undertaken with the ultimate goal to improve long-term outcomes in this very challenging population.”
Be aware that findings from this cohort study suggest that in patients without severe cerebral edema or highly malignant EEG, TTM at 33°C was associated with better survival than TTM at 36°C for patients with the most severe post–cardiac arrest illness. TTM at 36°C was associated with better survival in mild to moderate severity of illness.
Note that patients with severe cerebral edema or highly malignant electroencephalogram had poor outcomes regardless of TTM strategy; the findings suggest that measuring initial illness severity in resuscitated patients may guide selection of the optimal TTM strategy.
Peggy Peck, Editor-in-Chief, BreakingMED™
Callaway reported receiving grants from the National Institutes of Health outside the submitted work and working on American Heart Association and International Guidelines committees for resuscitation guidelines.
Geocadin is supported in part by NIH Grants UG3HL145269 and HL071568 and a nonrestricted grant from the Wenzel Family Foundation.
Cat ID: 358
Topic ID: 74,358,254,791,730,358,914,192,925