therapeutic hypothermia | The Journal of Critical Care Medicine

Therapeutic Hypothermia Following Cardiopulmonary Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis

Robert Maclaren¹, Sterling Torian², Tyree Kiser¹, Scott Mueller³, Paul Reynolds⁴

1 Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA
2 Department of Pharmacy, TriStar Centennial Medical Center, Nashville, Tennessee, USA
3 Department of Pharmacy, University of Colorado Hospital, Aurora, Colorado, USA
4 Department of Pharmacy, VA Eastern Colorado Health Care System, Aurora, Colorado, USA

DOI: 10.2478/jccm-2023-0015

Introduction: The risk-benefit profile of therapeutic hypothermia is controversial with several randomized controlled trials providing conflicting results. Aim of Study: The purpose of this systematic review and meta-analysis was to determine if therapeutic hypothermia provides beneficial neurologic outcomes relative to adverse effects.
Material and Methods: MEDLINE and EMBASE databases were searched for randomized controlled trials of post-cardiac arrest patients comparing therapeutic hypothermia (~33 degrees Celsius) to normothermia or the standard of care (36 – 38 degrees Celsius). Data were collected using the Covidence systematic review software. Statistical analysis was performed by Review Manager software. Risk of bias, sensitivity, and heterogeneity were analyzed using the Cochran’s Collaboration tool, trial sequential analysis (TSA) software, and I2 statistic respectively.
Results: A total of 1825 studies were screened and 5 studies (n=3614) were included. No significant differences existed between the hypothermia group and normothermia for favorable neurologic outcome (risk ratio [RR] 1.17, 95% confidence interval [CI] 0.97 to 1.41) or all-cause mortality (RR 0.97, 95% CI 0.89 to 1.05). When compared to normothermia, the hypothermia group had greater risk of adverse effects (RR 1.16, 95% CI 1.04 to 1.28), which was driven by the onset of arrhythmias. Subgroup analyses revealed that therapeutic hypothermia provided greater neurologic benefit in trials with a higher percentage of subjects with shockable rhythms (RR 0.73, 95% CI 0.6 to 0.88). Trial sequential analysis revealed statistical futility for therapeutic hypothermia and favorable neurologic outcome, mortality, and adverse effects.
Conclusions: Therapeutic hypothermia does not provide consistent benefit in neurologic outcome or mortality in the general cardiac arrest population. Patients with shockable rhythms may show favorable neurologic outcome with therapeutic hypothermia and further investigation in this population is warranted. Any potential benefit associated with therapeutic hypothermia must be weighed against the increased risk of adverse effects, particularly the onset of arrhythmias.

A satisfactory neurologic outcome is the key factor for survival in patients with sudden cardiac death (SCD), however this is highly dependent on the haemodynamic status. Short term cardiopulmonary resuscitation and regained consciousness on the return of spontaneous circulation (ROSC) is indicative of a better prognosis. The evaluation and treatment of SCD triggering factors and of underlying acute and chronic diseases will facilitate prevention and lower the risk of cardiac arrest. Long term CPR and a prolonged unconscious status after ROSC, in the Intensive Care Units or Coronary Care Units, indicates the need for specific treatment and supportive therapy including efforts to prevent hyperthermia. The prognosis of these patients is unpredictable within the first seventy two hours, due to unknown responses to therapeutic management and the lack of specific prognostic factors. Patients in these circumstances require the highest level of intensive care and aetiology driven treatment without any delay, independently of their coma state. Current guidelines sugest the use of multiple procedures in arriving at a diagnosis and prognosis of these critical cases.