Targeted Temperature Management Trial: Is it Time to Stop Cooling Patients after Cardiac Arrest?6/1/2014
 In 2002 two published articles in the New England Journal of Medicine changed ICU management of out of hospital arrests profoundly. According to these two articles (cited below) the American Heart Association labeled this to be good evidence (Level1) to recommend induced hypothermia in comatose survivors of out of hospital cardia arrest caused by VF. The target temperature was recommended to be between 32-34°C and to be maintained for 12-24 hours.
And now this... Nielsen et al. present the Targeted Temperature Management Trial showing, that there is NO difference between patients cooled to 33°C and patients kept at 36°C. Is this the end of the cooling era, should we change our management? I personally think think that this trial basically adds up to our knowledge in the field of post cardiac arrest care, but not necessarily contradicts the previous two trials. We now have one trial showing that there seems to be no difference between 33°C and 36°C but we also know, that hyperthermia (pyrexia) is troublesome and associated with worse neurological outcome. So, as pronounced hypothermia (33°C) makes no difference to ‘mild’ hypothermia (36°C) and pyrexia is proven to be harmful... the question is: What is the right temperature? We seem to head towards normothermia or mild hypothermia in order to provide best management for our patients. It’s going to be interesting to see how recommendations will change in the near future. The Targeted Temperature Management Trial: Nielsen N, et al. New Engl J Med. 2013 Dec;369(23):2197-206 The 2 trials that introduced therapeutic hypothermia into ICU practice: The Hypothermia After Cardiac Arrest Study Group, Holzer at al. New Engl J Med. 2002 Feb;346(8):549-556 Bernard S.A. et al. New Engl J Med. 2002 Feb;346(8):557-563 Review article on therapeutic hypothermia for non-VF/VT cardiac arrest: Sandroni S. et al. Crit Care Med; 2013;17:215 Pyrexia and neurological outcome: Leary M. et al. Resuscitation. 2013 Aug;84(8):1056-61  Therapeutic hypothermia - Here we go again. Another quite invasive therapy we offered to patients in the last couple of years might actually not help as we thought it would. This seems to become another deja-vu and might just show the saying which is so true for intensive care: ‘Less is more’.
Just last month the New England Journal of Medicine published this international multi-center trial where 950 patient initially were enrolled to receive hypothermic treatment at 33°C or 36°C. 939 patients finally where followed up for neurologic function (CPC scale and Rankin scale) and death. And guess what... There is no difference what so ever! The evidence of this study implicates that therapeutic hypothermia might not be of any benefit. So what do we do now? Is this the end of the hypothermic era? Nielsen N, et al. New Engl J Med. 2013 Dec;369(23):2197-206  Hypothermia is back in the focus of discussions and was not only used for treatment after cardiac arrest. If hypothermia would protect after cerebral ischemia after an arrest it might be also useful after other impacts like stroke or meningitis.
To answer this question a french multi-center study was started involving 49 intensive care units. Patients with communitiy acquired bacterial meningitis and a GCS of less than 8 for less than 12 hours were enroled. The hypothermia group was cooled to 32-34°C for 48 hours and then passively rewarmed. Primary outcome was GCS at three months. After including 98 patients the study had to be stopped on the request of the data ans safety monitoring board due to concerns over excess mortality in the hypothermia group. Analysis showed no improve of outcome but might actually be harmful to patients. Hypothermia doesn’t seem to be the magic bullet here either. Mourvillier B, et al. JAMA. 2013 Nov;310(20):2174-83 |
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