Conservative oxygen therapy for mechanically ventilated adults with suspected hypoxic ischaemic encephalopathy

Abstract

Purpose: Liberal use of oxygen may contribute to secondary brain injury in patients with hypoxic-ischaemic encephalopathy (HIE). However, there are limited data on the effect of different oxygen regimens on survival and neurological disability in HIE patients.

Methods: We undertook a post-hoc analysis of the 166 patients with suspected HIE enrolled in a trial comparing conservative oxygen therapy with usual oxygen therapy in 1000 mechanically ventilated ICU patients. The primary endpoint for the current analysis was death or unfavourable neurological outcome at day 180. Key secondary outcomes were day 180 mortality, and cause-specific mortality.

Results: Patients with HIE allocated to conservative oxygen spent less time in the ICU with an SpO₂ ≥ 97% (26 h [interquartile range (IQR) 13-45 vs. 35 h [IQR 19-70], absolute difference, 9 h; 95% CI - 21.4 to 3.4). A total of 43 of 78 patients (55.1%) assigned to conservative oxygen and 49 of 72 patients (68.1%) assigned to usual oxygen died or had an unfavourable neurological outcome at day 180; odds ratio 0.58; 95% CI 0.3-1.12; P = 0.1 adjusted odds ratio 0.54; 95% CI 0.23-1.26; P = 0.15. A total of 37 of 86 patients (43%) assigned to conservative oxygen and 46 of 78 (59%) assigned to usual oxygen had died by day 180; odds ratio 0.53; 95% CI 0.28-0.98; P = 0.04; adjusted odds ratio 0.56; 95% CI 0.25-1.23; P = 0.15. Cause-specific mortality was similar by treatment group.

Conclusions: Conservative oxygen therapy was not associated with a statistically significant reduction in death or unfavourable neurological outcomes at day 180. The potential for important benefit or harm from conservative oxygen therapy in HIE patients is not excluded by these data.

Keywords: Cardiac arrest; Critical care; Hypoxic ischemic encephalopathy; Intensive care medicine; Oxygen therapy; Randomized controlled trial.

Fig. 1

Participant flow. GOS-E Glasgow Outcome Scale—Extended, ICU intensive care unit, ICU-ROX intensive care unit randomized trial comparing two approaches to oxygen therapy

Fig. 2

PaO₂ by treatment group while ventilated in ICU* (a time-weighted mean; b highest; c lowest). * The number of observations by group on each day is shown on the horizontal axis. The time-weighted mean daily PaO₂ was calculated from recordings of PaO₂ taken 6 h while the patient was invasively ventilated in the ICU up until day 10. The highest and lowest PaO₂ were recorded daily while the patient was invasively ventilated in ICU up until day 28. Data are presented as mean with error bars showing standard error mean. PaO₂ arterial oxygen partial pressure, C conservative oxygen group, S standard (usual) oxygen group

Fig. 3

Kaplan–Meier estimates of the probability of survival and Glasgow Outcome Scale Extended (GOS-E) categories for patients with suspected hypoxic ischemic encephalopathy*. *Adapted from N Engl J Med, ICU-ROX investigators, Conservative Oxygen Therapy During Mechanical Ventilation in the ICU, 382: 989–998 Copyright © 2020 Massachusetts Medical Society. Reprinted with permission. The number of observations in the Kaplan–Meier analysis is shown by treatment group on the horizontal axis. Adjusted hazard ratio, 0.67 (95% CI 0.43–1.03), P = 0.20. Adjusted for age, cardiac arrest location outside hospital, shockable first monitored rhythm, time to ROSC, whether there was a medical cause for arrest, and whether the patient had a STEMI. Analysis was undertaken with patients nested in site and site treated as a random variable. GOS-E Glasgow Outcome Scale, ROSC return of spontaneous circulation, STEMI ST elevation acute myocardial infarction