SGEM#391: Is it Time for a Cool Change (Hypothermia After In-Hospital Cardiac Arrest)?

Date: February 1, 2023 Reference: Wolfrum et al. Temperature Control After In-Hospital Cardiac Arrest: A Randomized Clinical Trial. Circulation. September 2022 Guest Skeptic: Dr. Justin Morgenstern is an emergency physician and the creator of the #FOAMed project called www.First10EM.com Case: You are working an overnight shift at a small rural hospital. You are tidying your things in anticipation of the arrival of the dayshift when a code blue is called. A 50-year-old man who was admitted to the hospital with a non-ST elevated myocardial infarction (NSTEMI) overnight was found unconscious and without a pulse. The nurses started CPR immediately and place pads before you even arrived. The patient is in ventricular fibrillation, and you achieve return of spontaneous circulation (ROSC) on the second shock. The patient is still unconscious. A post-arrest ECG doesn’t show any signs of STEMI. At this point, the dayshift doc walks into the room and asks, “I can’t keep up with all the evidence. Are we supposed to be starting hypothermia?” Background: “Therapeutic” hypothermia took the critical care world by storm in 2002, with the simultaneous publication of two randomized control trials (RCTs) in the same issue of the New England Journal of Medicine – the Hypothermia after Cardiac Arrest (HACA) study and the Bernard study. As a very brief recap, the HACA study randomized 275 comatose adult patients with ROSC after a witnessed cardiac arrest with a shockable rhythm, a presumed cardiac origin of arrest, and a short downtime. The hypothermia group was cooled using an external device to a target temperature between 32 and 34 degrees Celsius and maintained there for 24 hours. The primary outcome was a good neurologic outcome within six months and occurred in 55% of the hypothermia group and 39% of the normothermia group (p=0.009, RR 1.40, 95% CI 1.08-1.81). This translated into an impressive NNT of 6. The six-month mortality was also improved in the hypothermia group (41% vs 55%, p=0.02) NNT 7. Key issues with this study were possible selection bias, early stopping without a clear endpoint, and a subjective outcome in a trial that was only partially blinded. The Bernard study included 77 patients with an initial cardiac rhythm of ventricular fibrillation who had achieved ROSC but were persistently comatose. It was not randomized to individual patients, but rather based on the day of the week. It was also not blinded. The primary outcome, patients with neurologic function good enough to be sent home or to a rehabilitation facility, occurred in 49% of the hypothermia group and 26% of the normothermia group (p=0.046, although when you plug the numbers into a fragility index calculator, you get a fragility index of 0 and a p value of 0.06). This give a very impressive NNT of 4. There was an NNT of 6 for mortality (51% vs 68%, p=0.16) but it was not statistically significant. For more information on the fragility index (FI) click on this LINK. Therefore, therapeutic hypothermia was introduced into clinical practice based on two small trials with multiple sources of bias. Since 2002, we have seen several larger trials that have raised questions about the value of hypothermia. We have covered the issue of cooling patients post OHCA sever times on the SGEM including the original Targeted Temperature Management (TTM) trial (SGEM#82). TTM was a multicentre RCT from 36 intensive care units (ICUs) in Europe and Australia, which enrolled 950 comatose adult patients on arrival to hospital after out of hospital cardiac arrest, regardless of the presenting rhythm. Patients all had their temperatures controlled, but they were randomized to a target of either 33 or 36 degrees Celsius. There were no statistical differences between the groups in mortality, Cerebral Performance Category (CPC), modified Rankin Score (mRS) or mortality at 180 days. The TTM2 trial was covered on SGEM#336. It was another multicenter RCT,