• Targeted temperature management at 33°C versus 36°C after cardiac arrest

    by Alan Batt. Last modified: 24/02/14

    thypotherm

    Summary

    • Randomized, controlled, multi-centre trial
    • 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause randomized.
    • Targeted temperature management at either 33°C or 36°C
      • 939 included in the primary analysis (neuroprognostication at 72 hours)
      • During the first 7 days of hospitalization, life-sustaining therapy was withdrawn in 247 patients (132 in 33°C group and 115 in 36°C group) due to brain death, multiorgan failure, ethical concerns
      • No difference in mortality rate: 33°C group (n=473) had 50% mortality rate v 48% in 36°C group (n=466)
      • No difference in neurological outcome as per CPC: 33°C group 54% v 52% in 36°C group
      • Shorter duration of mechanical ventilation in the 36°C group
    • No difference in inducing hypothermia at a targeted temperature of 33°C compared with a targeted temperature of 36°C.

    An extremely robustly designed and executed study, results from this can be taken to be accurate for the patient population studied. Some limitations of this study include:

    • Witnessed arrests accounted for around 90% of the study population in both groups.
    • Rates of bystander CPR in this study were approx 75%, with shockable rhythms accounting for 80% of presentations on first analysis – these figures are not comparable to every other EMS systems, where rates of bystander CPR are far lower.
    • Median time to BLS provision was 1 minute, and ALS provision was 9 minutes – again, these figures are not comparable for EMS systems worldwide.
    • Unknown data on dose and type of sedation or the use of neuromuscular blocking agents.

    cpcscale

     
    Nielsen N1, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Åneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Køber L, Langørgen J, Lilja G, Møller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H; TTM Trial Investigators. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013 Dec 5;369(23):2197-206. PMID: 24237006.

    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.

    Trial Registration

    ClinicalTrials.gov number, NCT01020916

    References

     
    1.

    Nielsen N1, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Åneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Køber L, Langørgen J, Lilja G, Møller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H; TTM Trial Investigators. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013 Dec 5;369(23):2197-206. PMID: 24237006.

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    Alan Batt

    Alan Batt

    Paramedic, educator, researcher
    Alan is a critical care paramedic, paramedic educator and prehospital researcher, currently working around the world as an educator and researcher. He has previously worked and studied across Europe, North America and the Middle East. He holds a Graduate Certificate in Intensive Care Paramedic Studies, and an MSc in Critical Care. His main interests are in care of the elderly, end-of-life care, patient safety, professionalism (including role and identity), and paramedic education.

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