Prolonged Targeted Temperature Management Reduces Memory Retrieval Deficits Six Months Post-cardiac Arrest: A Randomised Controlled Trial

Background: Cognitive sequelae, most frequently memory, attention, and executive dysfunctions, occur commonly in out-of-hospital cardiac arrest (OHCA) survivors. Targeted temperature management (TTM) following OHCA is associated with improved cognitive function. However, the relationship between the duration of TTM and cognitive outcome remains unclear. We hypothesised that OHCA survivors that were subjected to prolonged TTM of 48 h (TTM48) would exhibit better cognitive functions compared to those subjected to standard TTM of 24 h (TTM24) six months post-OHCA.

Methods: A predefined, cognitive post-hoc sub-study was conducted on the multicentre clinical trial: "Target Temperature Management for 48 vs. 24 h and Neurologic Outcome after out-of-hospital cardiac arrest: A Randomised Clinical Trial" (the TTH48 trial). OHCA survivors with perceived good cognitive outcome (CPC score ≤ 2) were invited to a neuropsychological assessment of memory, attention, and executive functions six months post-OHCA.

Results: In total, 79 patients were included in the study. Multivariate regression analysis revealed that TTM48 was associated with a significant better performance on three of 13 cognitive tests specific to memory retrieval after adjusting for age at follow-up and time to return of spontaneous circulation. Overall, patients in the TTM24 group were almost three times more likely (RR = 2.9 (95% CI 1.1-7.4)), p = 0.02) to be cognitively impaired.

Conclusions: This study reports an association between the duration of TTM and cognitive outcome. In OHCA survivors with perceived good cognitive outcome (CPC ≤ 2), TTM48 was associated with reduced memory retrieval deficits and lower relative risk of cognitive impairment six months after OHCA compared to standard TTM24. ClinicalTrials.gov (identifier: NCT01689077).