Source: Abdalla M, Mohamed A, Mohamed W, Khtab K, Cattoni H, Salih M. Targeted temperature management after cardiac arrest: Updated meta-analysis of all-cause mortality and neurological outcomes. Int J Cardiol Heart Vasc. 2019;24:100400.
Study Population: 9 trials of 1592 adult patients with cardiac arrest (1505 out-of-hospital cardiac arrest patients)
Efficacy Endpoints: Death from any cause and poor neurologic outcomes
Harm Endpoints: Not reported
Narrative: Cardiac arrest occurs in over 550,000 patients every year in the United States.1, 2 Survival to hospital discharge occurs in only 12% of arrests, regardless of rhythm, and many survivors experience complications such as anoxic brain injury and poor neurologic function after cardiac arrest.2, 3 Post cardiac arrest hyperthermia is associated with poor outcomes, including increased mortality and rates of neurologic injury.4 In the first 48 hours after cardiac arrest, each degree above 37°C is associated with elevated risk of mortality.4 Lowering the body temperature, or targeted temperature management (TTM), in a comatose patient after return of spontaneous circulation (ROSC) is an intervention that may improve neurologic outcome and reduce mortality in post-arrest patients.5, 6 Two studies by Bernard et al. in 1997 and 2002 found improved survival and neurologic outcome in patients with out-of-hospital cardiac arrest (OHCA) cooled to 33°C.7, 8 More recently, the targeted temperature range is 32°C to 36°C, with focus on avoiding hyperthermia.5,6 However, there is significant variation concerning use of TTM in witnessed or unwitnessed cardiac arrests, the specific device used for cooling, temperature target, duration of TTM, post-hypothermia temperature management, and neuroprognostication protocols. While TTM is included as a component of the 2015 American Heart Association guidelines,6 there is currently a variation in data regarding the efficacy of TTM in individual studies, prompting the need for this meta-analysis.
The systematic review and meta-analysis summarized here evaluated all-cause mortality and neurologic outcomes among randomized controlled trials of adults receiving TTM after inhospital cardiac arrest (IHCA) or OHCA, irrespective of initial cardiac arrest rhythm.9 A subgroup analysis was performed for patients suffering from OHCA. This meta-analysis included more patients, different outcomes, and subgroup analyses by OHCA versus IHCA which differed when compared with prior meta-analyses.10
Eight studies evaluated TTM after OHCA, while 1 study included both IHCA and OHCA. The analysis showed that TTM reduced mortality (in-hospital or long-term) (odds ratio [OR] 0.637, 95% confidence interval [CI] 0.436-0.930; absolute risk reduction [ARR] 5.3%; number needed to treat [NNT] 19), as well as the risk of poor neurologic outcomes (in-hospital or long-term) (OR 0.582, 95% CI 0.363-0.931; ARR 5.5%; NNT 19). Subgroup analysis for OHCA found similar results, with reduced mortality (OR 0.562, 95% CI 0.331–0.955; ARR 5.4%; NNT 19) and risk of poor neurologic outcomes (OR 0.674, 95% CI 0.454–0.999; ARR 4.55%; NNT 22).
Caveats: This meta-analysis has several limitations. While the inclusion criteria were appropriate, there were significant variations on whether the arrest was witnessed or unwitnessed, the specific device used for cooling, temperature target, duration of TTM, post-hypothermia temperature management, and neuroprognostication protocols. There was significant variation in duration of outcome assessment, with some studies evaluating survival and neurologic function at time of discharge, while others assessed these outcomes at 3 and/or 6 months after discharge. Studies also utilized a variety of tools to assess neurologic outcome. Only 1 study evaluated both IHCA and OHCA; all other studies evaluated OHCA only.11 With this limited data from 1 trial regarding IHCA,11 further data evaluating TTM for IHCA are needed. Most of the data came from two studies,12, 13 and other studies were comprised of small sample sizes. This limited the evaluation of publication bias and the ability to perform a sensitivity analysis. It also contributed to the moderate heterogeneity that was present in meta-analysis. One of these larger studies compared 33°C with 36°C in 939 patients, finding no survival benefit between these two TTM targets.13 Study authors sought to avoid hyperthermia in all included patients by using 36°C as the control group.13 However, as both groups received variations on TTM, this may have confounded the overall results. This meta-analysis did not include a standardized quality assessment of the included trials, further limiting the interpretation of these findings. Finally, many of the included studies did not possess comprehensive patient data, which limits evaluation of other factors in cardiac arrest that may impact mortality and neurologic outcome.
Of note, a 2019 randomized controlled trial including 581 patients with IHCA or OHCA and nonshockable rhythm found TTM at 33°C was associated with favorable neurologic outcomes at 90 days,14 similar to the results of the discussed meta-analysis. However, the study did not find improved survival with TTM.14
In summary, TTM reduces mortality and risk of poor neurologic outcome after cardiac arrest.6 Further data regarding the specific device used for cooling, temperature target, duration of TTM, post-hypothermia temperature management, and neuroprognostication protocols are required. Due to heterogeneity and variation in study quality, we have assigned a color recommendation of Yellow (Unclear if benefits) for use of TTM in post cardiac arrest patients.
The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.
Author: Brit Long, MD; Alex Koyfman, MD; Michael Gottlieb, MD, RDMS
Supervising Editor: Shahriar Zehtabchi, MD
Published/Updated: December 16, 2019
The title bar is color-coded with our overall recommendation.