HYPERION trial "will force us to consider more use"
Moderate therapeutic hypothermia improved outcomes for patients in a coma after cardiac arrest with nonshockable rhythm, a French randomized trial showed.
Keeping such patients at 33°C (91°F) for 24 hours boosted the number who survived with a favorable neurologic outcome (Cerebral Performance Category [CPC] score of 1 or 2 on the 5-point scale) at day 90 compared with targeted normothermia.
The difference -- 10.2% vs 5.7% (P=0.04), driven by significantly more patients with good neurologic status at 90 days -- was of "clinical importance," reported Jean-Baptiste Lascarrou, MD, of the University Hospital Center in Nantes, France, and colleagues in the HYPERION trial.
Mortality was statistically similar at 90 days (81.3% vs 83.2%), the group reported online in the New England Journal of Medicine to coincide with the presentation at the European Society of Intensive Care Medicine meeting in Berlin.
"The number needed to treat for one additional patient to survive with a CPC score of 1 or 2 is 22 with hypothermia, as compared with a number needed to treat to prevent one death of 15 with bystander CPR and 112 with epinephrine," they noted.
While moderate hypothermia had been widely used in such patients based on extrapolation of data from patients with shockable rhythms, the Targeted Temperature Management (TTM) trial threw the field into confusion in 2013 by finding no advantage to moderate versus minimal hypothermia for patients with shockable or non-shockable rhythms, noted Clifton Callaway, MD, PhD, of the University of Pittsburgh.
The HYPERION trial was thus eagerly anticipated, Callaway, who was not involved with the trial, told MedPage Today.
"These are patients who are much more on the edge of survival, and who thus have much more to gain from aggressive treatments," he said. "It is exciting that the investigators have found an increase in good neurological recovery in such a sick population. I think that this result will force us to consider more use of hypothermia for the more-injured patients. I also think we will be pondering all the nuances and details of the trial over the next few months to see if the enrolled patients are representative of the patients we all treat."
The open-label trial randomized 584 patients in a coma after cardiac arrest with nonshockable rhythms for which CPR had been started within 10 minutes of collapse and spontaneous circulation returned within 60 minutes.
Cardiac arrest occurred outside the hospital in 73% of the patients, with a non-cardiac presumed cause of cardiac arrest in two-thirds and circulatory shock in 58%.
For the hypothermia group, patients were kept at 33°C for 24 hours using standardized protocols for active internal or external cooling devices or active external cooling without a specific device. They were slowly rewarmed from 36.5 to 37.5°C for the next 24 hours. Sedation was protocolized to keep patients unresponsive, and then tapered when patients got back above 36°C.
The normothermia group was kept at 36.5 to 37.5°C for 48 hours, according to the ICU's standard protocol, with routine sedation only for the first 12 hours.
While there was blinded outcome assessment, the researchers noted that use of phone, rather than in-person, interviews for the primary endpoint was a limitation.
Also, "an outcome change in a single patient would make the difference in the primary outcome nonsignificant," they noted, although the three patients who withdrew consent were all in the hypothermia group.
The trial was supported by the French Ministry of Health, Centre Hospitalier Départemental Vendée, and the Laerdal Foundation.
Lascarrou reported grants from the French Ministry of Health, Laerdal Foundation, and District Hospital Center in La Roche sur Yon, France.
New England Journal of Medicine
Source Reference: Lascarrou J-B, et al "Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm" N Engl J Med 2019; DOI: 10.1056/NEJMoa1906661.
Read the original article on Medpage Today: Hypothermia Helps After Cardiac Arrest With Nonshockable Rhythm