ALiEM-Annals of EM Journal Club: Targeted Temperature Management

We are very excited this month to bring you our third Global Journal Club. We hope you will participate in an online discussion based on the clinical vignette and questions below from now until March 27th. Respond by commenting below or tweeting (#ALiEMJC).

On Tuesday, March 25, 2014 at 1630 EST, we will be hosting a 30-minute live Google Hangout with Dr. Niklas Nielsen, the lead author of the Targeted Temperature Management (TTM) study, that is informed by the discussion. Later this year a summary of this journal club will be published in Annals of Emergency Medicine.

Google Hangout with Dr. Nielsen

Journal Club Paper

Nielsen, Niklas, et al. “Targeted temperature management at 33 C versus 36 C after cardiac arrest.” New England Journal of Medicine 369.23 (2013): 2197-2206. PMID: 24237006; Altmetric

Abstract

BACKGROUND: Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever.

METHODS: In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale.

RESULTS: In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar.

CONCLUSIONS: In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916).

FOAM Discussion to Date

Nielsen’s TTM study has been one of the most, if not the most, discussed papers online since its publication in November 2013. A brief Google search returned 17 blog posts and 7 podcasts discussing the study, most of which were published within a week following the paper’s release. For a FOAM primer on the paper, check out any of the resources listed on the table below. Chris Nickson of Life in the Fast Lane has also compiled an exceptional summary of the cardiac arrest literature. Now that about four months have passed, we would love to hear your thoughts about how you have thought about your cardiac arrest protocol and whether the study has changed (if at all) your practice.

Featured Questions

Two questions were selected from those published in this month’s Journal Club questions published in Annals of EM [free PDF] and two questions posed by the ALiEM team to address more issues of how HOW and WHETHER these results change practice. If you have additional questions, feel free to pose them!

• Q1: If you were creating a cardiac arrest protocol in your hospital, what would you set for the target temperature? Do you think the temperature or the protocol is more important for survival?
• Q2: The authors note the inability to blind the critical care practitioners; however, they were able to blind the assessors providing follow-up neurologic examination. Were the methods used to eliminate the risk of critical care provider bias sufficient?
• Q3: Do you think there is a subgroup of patients that will benefit from cooling to lower temperatures (ie 32-34 C)?
• Q4: The authors examined the primary outcome of survival time and followed patients up to the end of the trial (i.e. 180 days after the enrollment of the last patient) and powered the study to this outcome. The trial was designed as a superiority trial to detect a 20% reduction in the hazard ratio for death with hypothermia at 33C (91.4F) versus a control group at 36C (96.8F). Was the study appropriately powered for this outcome? How would the power calculations change if the study design were a noninferiority trial of relative normothermia at 36C (96.8F) versus hypothermia at 33C (91.4F)?

Please participate in the journal club by answering either on the ALiEM blog comments below or by tweeting us using the hashtag #ALiEMJC. Please denote the question you are responding to by starting your reply with Q1, Q2, Q3, or Q4.

We reserve the right to use any and all tweets to #ALiEMJC and comments below in a commentary piece for an Annals of Emergency Medicine publication as a curated conclusion piece for this global journal club. Your comments will be attributed, and we thank-you in advance for your contributions.

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