Supplementation With Lower Oxygen May Not Worsen Mortality Risk In Patients With Hypoxic-Ischemic Brain Injury

In patients with hypoxic-ischemic brain injury, researchers observed no significant difference between liberal and restrictive oxygenation on any-cause death.

Mechanical ventilation that supplements oxygenation could be a lifesaving tool for comatose patients who were resuscitated after out-of-hospital cardiac arrest. However, new data suggest that risk of death from any cause or poor neurological state are not significantly worse when supplemented with different oxygenation levels, according to the authors of a study published in the New England Journal of Medicine.

Among restrictive-target participants, 32% experienced a primary outcome event, with 33.9% among liberal-target participants. At day 90, 113 patients in the restrictive-target group died, with death also occurring in 123 liberal-target group patients as well.

“Targeting of a restrictive or liberal oxygenation strategy in comatose patients after resuscitation for cardiac arrest resulted in a similar incidence of death or severe disability or coma,” the study authors wrote .

When a patient dies after being resuscitated from cardiac arrest, the most common cause is hypoxic–ischemic brain injury—this occurs when the hypoxic brain regains circulation, but the patient experiences reperfusion. This can cause the patient to become comatose, where they will require oxygen using mechanical ventilation. However, too much oxygen can lead to death, but too little oxygen can increase risk of tissue hypoxia.

In the Blood Pressure and Oxygenation Targets in Postresuscitation Care trial, researchers analyzed the superiority of restrictive versus liberal supplemental oxygen on risks of any-cause death and/or a poor neurologic state for comatose patients following being discharged from the hospital.

The primary outcome was a composite of any-cause death or hospital discharge with coma or severe disability—whichever was first within 90 days of randomization. Secondary key endpoints were neuron-specific enolase levels at 48 hours, any-cause death, a score of 0 to 30 on the Montreal Cognitive Assessment, a score on the Rankin scale for disability, and a scire on the Cerebral Performance Category (CPC) at 90 days.

In the investigator-initiated, open label, randomized 2-by-2 factorial designed trial, researchers included 789 patients who were at high risk for hypoxic-ischemic encephalopathy. The team compared restrictive oxygenation of 9 to 10 kPa with liberal oxygenation of 13 to 14 kPa in comatose patients that were resuscitated following an out-of-hospital cardiac arrest event.

“At 48 hours, the median neuron-specific enolase level was 17 μg per liter in the restrictive-target group and 18 μg per liter in the liberal target group,” study authors wrote in the report. Additionally, CPC results showed a median score of 1 in both groups—a lower value indicated milder disability.

Further, the average score of the modified Rankin scale was 2 in the restrictive-target group and 1 for the liberal-target, suggesting lower disability, and 27 on the Montreal Cognitive Assessment (MCA)--the study authors noted that high scores on the MCA indicate greater cognitive abilities.

The researchers noted that the study included several limitations. First, the patient population had a predisposed tendency of acute coronary syndrome, but they could also be “too healthy” for observable benefits. The number of in-person patient evaluations was lower than expected because of pandemic restrictions, and the trial design may contain choice-biases for this life-sustaining therapy.


Schmidt H, Kjaergaard J, Hassager C, et al. Oxygen Targets in Comatose Survivors of Cardiac Arrest. N Engl J Med. 2022;387:1467-76. doi:10.1056/NEJMoa2208686