Therapeutic hypothermia became the standard of care quickly when advance life support (ALS) task force issued the statement “Unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32°C to 34°C for 12 to 24 hours when the initial rhythm was ventricular fibrillation (VF).” This was based off of two studies published in 2002 and was recommended internationally in 2010 although some said the evidence was weak. Therefore, researchers in Europe looked to gather more data.
This is an international randomized trial of 950 patients that had out of hospital cardiac arrest with ROSC regardless of rhythm. The study aimed to evaluate if there was a difference in patients cooled to 33°C versus patients strictly kept at 36°C with a goal of preventing fever in both subgroups.
Primary outcome: mortality by the end of the trial
Secondary outcome: neurologic outcome at 180 days using the CPC scale and modified Rankin scale
0-7 days
- Life sustaining therapy had been withdrawn from 133 pts in the 33°C group
- Life sustaining therapy had been withdrawn from 115 pts in the 36°C group
0-Trial end date
- 33°C group- 235/473 (50%) of patients died
- 36°C group- 225/466 (48%) of patients died
180 day follow up
- 33°C group- 54% had died (235 pts) or had poor neurologic outcome (20 pts) using the CPC scale or 52% using the modified Rankin scale (11 pts)
- 36°C group- 52% had died (225 pts) or had poor neurologic outcome (13 pts) using the CPC scale or 52% using the modified Rankin scale (13 pts)
Conclusions:
This study is different from prior trials because it strictly controlled the temperature in each study group and they aggressively prevented fever during the first 3 days. They also evaluated all cardiac arrest patients with ROSC and 20% of their study population had a non-shockable rhythm on arrival.
The Continued Debate:
Should therapeutic hypothermia be extended to non-shockable rhythms?
- It is difficult to use this data to compare the previous hypothermia protocol studies since the inclusion criteria is different and there have been dramatic changes in pre-hospital care in the last 10 years.
What is the target temperature we should cool to in therapeutic hypothermia?
- This study said “In patients with out of hospital cardiac arrest who achieved ROSC regardless of rhythm, they conclude that their trial does not show any difference in patients who are cooled to 33°C when compared to patients that are kept at 36°C.”
Where there any differences in neurologic status in the other 50% patients that did not die or have poor neurologic outcome?
- Further study is required to determine the factors that influence long term neurologic outcomes in patients who survive to 180 days status post therapeutic hypothermia. This study was not designed or sufficiently powered to evaluate this issue.
This study challenges the current practice of therapeutic hypothermia and has made some very big findings and bold statements. This could be a game changer! Let us know your thoughts.
See the full article here:
FOAM sources discussing targeted temperature management in therapeutic hypothermia:
- Life in the Fast Lane: “Targeted temperature management (TTM) after cardiac arrest” and “Reports of therapeutic hypothermia’s death are greatly exaggerated"
- Emergency Medicine Literature of Note: “Giving Hypothermia the Cold Shoulder”
- Intensive Care Network: “Cooling post OOHCA: The world has just changed"
- St. Emlyn’s Blog: “JC: What’s the target temperature for OOHCA cooling. St.Emlyn’s”
- EMCrit: “Five Minutes with Jon Rittenberger on the TTM Trial"
Sources
- Nielsen, N. et al: Targeted Temperature Management at 33°C vs 36°C after Cardiac Arrest. N Engl J Med (17 November 2013), doi:10.1056/nejmoa1310519
- http://circ.ahajournals.org/content/108/1/118.full
- Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002; 346: 557–563.
The Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002; 346: 549–556. - http://circ.ahajournals.org/content/122/18_suppl_3/S768.full?sid=d5eb1f7b-ea08-48c2-b8f0-7e74a38d6806
- http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4100b1_03_CPC%20Scale.pdf
- http://www.rankinscale.org