Editor’s note: This is a series based on work done by three physicians (Patrick Archambault, Tim Chaplin, and our BoringEM Managing editor Teresa Chan) for the Canadian National Review Course (NRC). You can read a description of this course here.
The NRC brings EM residents from across the Canada together in their final year for a crash course on everything emergency medicine. Since we are a specialty with heavy allegiance to the tenets of Evidence-Based Medicine, we thought we would serially release the biggest, baddest papers in EM to help the PGY5s in their studying via a spaced-repetition technique. And, since we’re giving this to them, we figured we might as well share those appraisals with the #FOAMed community! We have kept much of the material as drop downs so that you can quiz yourself on the studies.
Paper: Targeted temperature management at 33°C versus 36°C after cardiac arrest
Citation:
Nielsen N, Wettersley J, Cronberg T, Erlinge D, Gasche Y, Hassager C et al.. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013 Dec 5;369(23):2197-206. Epub 2013 Nov 17. doi: 10.1056/NEJMoa1310519.
Nickname of study:
TTM
Summarized by: Teresa Chan
Reviewed by: Patrick Archambault & Tim Chaplin
[bg_faq_start]Clinical Question
Does cooling people to 33 degrees after cardiac arrest result in better outcomes (mortality and neurological) than 36 degrees?
Population | Unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause |
Intervention | Targeted temperature of 33 degrees C |
Control | Targeted temperature of 36 degrees C |
Outcome | 1) All Cause Mortality 2) Composite of poor neurologic outcome and death using cerebral performance score (CPC) and modified Rankin Score (mRS) |
Methods
RCT: Multicentre Randomized Controlled trial, 939 patients included in analysis
Results
ALL CAUSE MORTALITY
- 50% of pts in 33 degree group died vs. 48% of pts in 36 degree group
- Hazard ratio 1.06 (95% CI 0.89-1.28); P=0.51
POOR NEUROLOGIC FUNCTION OR DEATH
- CPC: 54% of pts in 33 degree group died or had poor neurologic outcome per the CPC vs. 52% of pts in 36 degree group
- Risk ratio 1.02 (95% CI 0.88-1.16); P=0.78
- Modified Rankin: 52% of pts died or had poor neurologic per the mRS
- Risk Ratio 1.01 (95% CI 0.89-1.14; P=0.87)
Conclusions
The study states that: “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.” However, this is a slight overreach because the superiority design only powered the study to find an 11% absolute reduction in mortality.
[bg_faq_end]Take Home Point
Cooling post-arrest patients (of cardiac cause) to temperatures of 33 degrees was not found to be superior to cooling them to 36 degrees.
[bg_faq_start]EBM Considerations
Some clinicians are interpreting the results of the targeted temperature management trial by concluding that the ‘absence of fever’ is the key concept that results in benefit for post-arrest patients. That said, this paper did not show that inference, but showed that there are not a large differences in mortality and/or neurologic outcomes between patients ‘controlled’ to a target temperature of 33 vs. 36 degrees. Notably, invasive cooling devises were still used in the 36°C group and if a patient was cooler than the target temperatures upon randomization the team did not actively warm them.
[bg_faq_end]To download a copy of this summary click here (NRC – BoringEM – TTM summary download).
Note: This post was amended on November 27th to clarify that the study showed a lack of superiority between the two arms of the TTM study.