The benefit of hypothermic targeted temperature management decreases when post-arrest care improves

Background: Several clinical trials and cohort studies in the past two decades have demonstrated inconsistent results regarding survival and neurologic recovery benefits for patients undergoing targeted temperature management (TTM) at 33°C as compared to those undergoing TTM at 36°C or normothermia. Whether the improved quality of post-arrest care over time contributes to diminishing benefit of TTM at 33°C remains un-investigated. Methods: There were 1,809 adult non-traumatic cardiac arrest survivors during 2011-2020. After excluding patients with pre-arrest poor conscious level defined as Glasgow-Pittsburgh Cerebral Performance Category (CPC) >2 (n=258), patients who regained clear consciousness after return of spontaneous circulation (ROSC) (n=300), patients with active bleeding or intracranial hemorrhage (n=48) and patients who underwent TTM of 36°C due to unstable hemodynamic (n=11), a total of 1,192 eligible candidates for TTM of 33°C were finally enrolled and classified into Period 1 (during 2011-2015, n = 449) and Period 2 (during 2016-2020, n = 693). Results: Patients in Period 2 received more diagnostics procedures and specific therapies than those in Period 1. The proportion of patients with good neurological recovery at hospital discharge in Period 2 is significantly higher than that in Period 1 (21.4% vs.14.0%, adjusted odds ratio [aOR] 1.60, 95% confidence interval [CI] 1.14-2.26). TTM was beneficial for the outcomes in both Period 1 and 2, with patients in Period 1 having higher chances of survival and good neurological outcome than those in Period 2 (survival: aOR 5.66, 95% CI 3.49-9.18 vs. aOR 2.91, 95% CI 1.98-4.28; good neurological recovery: aOR 3.92, 95% CI 2.12-7.25 vs. aOR 2.19, 95% CI 1.43-3.34). Among patients with low-risk and medium-risk severity of illness, TTM benefited survival and neurological outcomes, regardless of time period. But the chance of beneficial outcomes decreased consistently from Period 1 to Period 2. Conclusion Among cardiac arrest survivors, improvement in the quality of post-cardiac arrest care over time is associated with better neurological recovery. TTM remains beneficial for survival and neurological outcomes following cardiac arrest, regardless of the time period. However, the benefit of TTM may diminish when post-cardiac arrest care improves. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial not applicable ### Funding Statement No funding applicable ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This retrospective cohort study was approved by the Institutional Review Board of NTUH (202111079RINA) and waived participant consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data are available in the manuscript.