Case Scenario: A 72 year old man has witnessed arrest at the Goderich beach. By-standard CPR is started and he shocked out of ventricular fibrillation by emergency medical services but does not regain consciousness. We know from SGEM#54 that cooling in the field does not improve survival. His temperature on arrival to the emergency department is 36°C.
Question: Does cooling to a target temperature of 33°C improve survival to hospital discharge and neurological outcome in unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause?
Background: Therapeutic hypothermia post cardiac arrest has received a great deal of attention over the last decade. Two randomized control trials showed that hypothermia post cardiac arrest resuscitation was neuroprotective. One trial (n=273) in NEJM 2002 used cooled air mattress to demonstrate good outcome at 6 months (55% vs. 39%). The smaller Australian study (n=77) also published in NEJM 2002 showed good neurologic outcome at time of hospital discharge (49% vs. 26%).
Dr. David Newman has calculated the NNT=6 for mild therapeutic hypothermia for neuroprotection following cardiopulmonary resuscitation. The Cochrane Collaboration updated their review on hypothermia for neurporotection in adults after CPR in 2012. They concluded:
“Conventional cooling methods to induce mild therapeutic hypothermia seem to improve survival and neurologic outcome after cardiac arrest. Our review supports the current best medical practice as recommended by the International Resuscitation Guidelines.”
The SGEM was skeptical after it covered the issue in Episode#21: Ice, Ice Baby. We looked at the paper by Bernard SA et al. called Induction of therapeutic hypothermia by paramedics after resuscitation from out-of-hospital ventricular fibrillation cardiac arrest: a randomized controlled trial, Circulation. 2010;122:737-742. The question was whether pre-hospital therapeutic hypothermia improve patient outcomes after successful resuscitation? The study had 234 patients and used large volumes of ice-cold lactated Ringer’s. The primary outcome was about 50% of patients survived to functional hospital discharge and there was not benefit to cooling.
The SGEM covered the larger pre-hopsital cooling paper by Kim F et al. in JAMA earlier this year. The bottom line was: Scoop and run after cardiac arrest with no cooling required in the field.
Reference: Nielsen N et al. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest. NEJM 2013
Population: 939 patients from36 intensive care units (ICUs) in Europe and Australia with OHCA with more than 20 consecutive minutes of spontaneous circulation after resuscitation.
Intervention: Cooling to 36 degrees celsius for 36 hours, <37.5 for 72 hs post-arrest
Authors’ Conclusions: In conclusion, our trial does not provide evidence that targeting a body temperature of 33°C confers any benefit for unconscious patients admitted to the hospital after out-of-hospital cardiac arrest, as compared with targeting a body temperature of 36°C.
Quality Check List:
The study population included or focused on those in the ED. Unsure
Comment: These were all out of hospital cardiac arrests. The emergency department was not mentioned. Some countries such as Sweden patients bypass the emergency department and are admitted directly to the hospital. However, it is reasonable to believe that many patients were admitted through the emergency department.
The patients were adequately randomized. Yes
The randomization process was concealed. Yes
The patients were analyzed in the groups to which they were randomized. Yes
The study patients were recruited consecutively (i.e. no selection bias). Yes
The patients in both groups were similar with respect to prognostic factors. Yes
All participants (patients, clinicians, outcome assessors) were unaware of group allocation.
Health care professionals caring for the trial patients were aware of the intervention assignments because of inherent problems with blinding of body temperature. Physicians performing neurologic prognostication, assessors of neurologic follow-up and final outcome, study administrators, statisticians, and the authors were unaware of the intervention assignments and so were the patients and their families. Manuscript written before randomization code was broken.
All groups were treated equally except for the intervention. Yes
Follow-up was complete (i.e. at least 80% for both groups). Yes, 100%
All patient-important outcomes were considered. Unsure
Little focus on disability. Modified Ranking Scale 0-3 slumped together
The treatment effect was large enough and precise enough to be clinically significant. No
Results: No difference in mortality. No difference in Cerebral Performance Category (CPC), modified Rankin Score (mRS) or mortality at 180 days.
Dr. Katrin Hruska
Commentary: This is a well conducted multisite randomized controlled trial on targeted temperature management after out-of-hospital cardiac arrest. They excluded very few patients from the trial. The main reasons for exclusion:
Interval from return of spontaneous circulation to screening of >4 hours
Unwitnessed arrest with asystole as the initial rhythm
Suspected or know acute intracranial hemorrhage or stroke
Body temperature of <30°C
A strength of the study was the multiple sites where the trial was conducted and the various sizes of hospitals.
Another strong feature of this study was that temperature was managed in different ways depending on the site’s preferences. The different methods of cooling did not seem to influence the results. This makes the result applicable to different practice settings depending on local protocols.
There was a risk of bias because of the inherent difficulty of blinding the treating physician to the intervention, but this is unlikely to affect mortality.
Three were lots of bubbles in the FOAMed world as a result of the TTM trial. It is not necessary to go into all the details but you can read more about this issue by clicking on the links:
Comment on Author’s Conclusions: Agree with author’s conclusions.
Bottom Line: This study did not demonstrate a benefit of a targeted temperature 33C vs. 36C for survival of out-of-hospital cardiac arrest.
Case Resolution: The 72 year old man with the out-of-hospital cardiac arrest who arrived at 36°C. He was actively cooled to maintain this temperature but was not cooled further to 33°C. You plan to check in on him in the intensive care unit on your next shift.
Clinical Application: I will start cooling patients to 36°C and admit them to the intensive care unit for further management based on our own local protocols.
What Do I Tell the Patient: I will tell the patient’s wife that her husband had a cardiac arrest. We were able to bring him back but he is still unconscious. We are going to cool him to improve his chances of survival and a good neurological outcome.
KEENER KONTEST: Last weeks winner was Dr. Neil Dattani from Toronto. He knew cocaine was the first local anesthetic isolated from a plant source?
If you want to play the Keener Kontest this week then listen to the podcast for the question. Email me your answer at TheSGEM@gmail.com with “keener” in the subject line. The first person to correctly answer the question will receive a cool skeptical prize.