Speed of cooling after cardiac arrest in relation to the intervention effect: a sub-study from the TTM2-trial. Simpson, R. F. G., Dankiewicz, J., Karamasis, G. V., Pelosi, P., Haenggi, M., Young, P. J., Jakobsen, J. C., Bannard-Smith, J., Wendel-Garcia, P. D., Taccone, F. S., Nordberg, P., Wise, M. P., Grejs, A. M., Lilja, G., Olsen, R. B., Cariou, A., Lascarrou, J. B., Saxena, M., Hovdenes, J., Thomas, M., Friberg, H., Davies, J. R., Nielsen, N., & Keeble, T. R. Critical Care (London, England), 26(1):356, November, 2022.
doi  abstract   bibtex   
BACKGROUND: Targeted temperature management (TTM) is recommended following cardiac arrest; however, time to target temperature varies in clinical practice. We hypothesised the effects of a target temperature of 33 °C when compared to normothermia would differ based on average time to hypothermia and those patients achieving hypothermia fastest would have more favorable outcomes. METHODS: In this post-hoc analysis of the TTM-2 trial, patients after out of hospital cardiac arrest were randomized to targeted hypothermia (33 °C), followed by controlled re-warming, or normothermia with early treatment of fever (body temperature, ≥ 37.8 °C). The average temperature at 4 h (240 min) after return of spontaneous circulation (ROSC) was calculated for participating sites. Primary outcome was death from any cause at 6 months. Secondary outcome was poor functional outcome at 6 months (score of 4-6 on modified Rankin scale). RESULTS: A total of 1592 participants were evaluated for the primary outcome. We found no evidence of heterogeneity of intervention effect based on the average time to target temperature on mortality (p = 0.17). Of patients allocated to hypothermia at the fastest sites, 71 of 145 (49%) had died compared to 68 of 148 (46%) of the normothermia group (relative risk with hypothermia, 1.07; 95% confidence interval 0.84-1.36). Poor functional outcome was reported in 74/144 (51%) patients in the hypothermia group, and 75/147 (51%) patients in the normothermia group (relative risk with hypothermia 1.01 (95% CI 0.80-1.26). CONCLUSIONS: Using a hospital's average time to hypothermia did not significantly alter the effect of TTM of 33 °C compared to normothermia and early treatment of fever.
@article{simpson_speed_2022,
	title = {Speed of cooling after cardiac arrest in relation to the intervention effect: a sub-study from the {TTM2}-trial},
	volume = {26},
	issn = {1466-609X},
	shorttitle = {Speed of cooling after cardiac arrest in relation to the intervention effect},
	doi = {10.1186/s13054-022-04231-6},
	abstract = {BACKGROUND: Targeted temperature management (TTM) is recommended following cardiac arrest; however, time to target temperature varies in clinical practice. We hypothesised the effects of a target temperature of 33 °C when compared to normothermia would differ based on average time to hypothermia and those patients achieving hypothermia fastest would have more favorable outcomes.
METHODS: In this post-hoc analysis of the TTM-2 trial, patients after out of hospital cardiac arrest were randomized to targeted hypothermia (33 °C), followed by controlled re-warming, or normothermia with early treatment of fever (body temperature, ≥ 37.8 °C). The average temperature at 4 h (240 min) after return of spontaneous circulation (ROSC) was calculated for participating sites. Primary outcome was death from any cause at 6 months. Secondary outcome was poor functional outcome at 6 months (score of 4-6 on modified Rankin scale).
RESULTS: A total of 1592 participants were evaluated for the primary outcome. We found no evidence of heterogeneity of intervention effect based on the average time to target temperature on mortality (p = 0.17). Of patients allocated to hypothermia at the fastest sites, 71 of 145 (49\%) had died compared to 68 of 148 (46\%) of the normothermia group (relative risk with hypothermia, 1.07; 95\% confidence interval 0.84-1.36). Poor functional outcome was reported in 74/144 (51\%) patients in the hypothermia group, and 75/147 (51\%) patients in the normothermia group (relative risk with hypothermia 1.01 (95\% CI 0.80-1.26).
CONCLUSIONS: Using a hospital's average time to hypothermia did not significantly alter the effect of TTM of 33 °C compared to normothermia and early treatment of fever.},
	language = {eng},
	number = {1},
	journal = {Critical Care (London, England)},
	author = {Simpson, Rupert F. G. and Dankiewicz, Josef and Karamasis, Grigoris V. and Pelosi, Paolo and Haenggi, Matthias and Young, Paul J. and Jakobsen, Janus Christian and Bannard-Smith, Jonathan and Wendel-Garcia, Pedro D. and Taccone, Fabio Silvio and Nordberg, Per and Wise, Matt P. and Grejs, Anders M. and Lilja, Gisela and Olsen, Roy Bjørkholt and Cariou, Alain and Lascarrou, Jean Baptiste and Saxena, Manoj and Hovdenes, Jan and Thomas, Matthew and Friberg, Hans and Davies, John R. and Nielsen, Niklas and Keeble, Thomas R.},
	month = nov,
	year = {2022},
	pmid = {36380332},
	pmcid = {PMC9667681},
	keywords = {Cardiopulmonary Resuscitation, Cold Temperature, Fever, Humans, Hypothermia, Hypothermia, Induced, Out of hospital cardiac arrest, Out-of-Hospital Cardiac Arrest, Temperature management, Time to target temperature, Treatment Outcome},
	pages = {356},
}
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