Targeted temperature management at 33°C versus 36°C after cardiac arrest.
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.).
The authors' affiliations are listed in the Appendix.
Niklas
N
Nielsen
Jørn
J
Wetterslev
Tobias
T
Cronberg
David
D
Erlinge
Yvan
Y
Gasche
Christian
C
Hassager
Janneke
J
Horn
Jan
J
Hovdenes
Jesper
J
Kjaergaard
Michael
M
Kuiper
Tommaso
T
Pellis
Pascal
P
Stammet
Michael
M
Wanscher
Matt P
MP
Wise
Anders
A
Åneman
Nawaf
N
Al-Subaie
Søren
S
Boesgaard
John
J
Bro-Jeppesen
Iole
I
Brunetti
Jan Frederik
JF
Bugge
Christopher D
CD
Hingston
Nicole P
NP
Juffermans
Matty
M
Koopmans
Lars
L
Køber
Jørund
J
Langørgen
Gisela
G
Lilja
Jacob Eifer
JE
Møller
Malin
M
Rundgren
Christian
C
Rylander
Ondrej
O
Smid
Christophe
C
Werer
Per
P
Winkel
Hans
H
Friberg
D000328:Adult; D000368:Aged; D001831:Body Temperature; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007036:Hypothermia, Induced; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D058687:Out-of-Hospital Cardiac Arrest / Q000150:complications / Q000401:mortality / Q000628:therapy*; D017211:Treatment Failure; D014474:Unconsciousness / Q000209:etiology; D028761:Withholding Treatment