Effect of targeting normoxemia on supplemental oxygen-free days for adults with acute thermal burns: A stepped wedge cluster randomized clinical trial

Abstract

Background: Supplemental oxygen is essential in caring for adults with acute thermal burns but can expose patients to excess inspired oxygen. We sought to determine the safety and effectiveness of targeting normoxemia (peripheral oxygen saturation [SpO 2 ] 90-96%) in adults with acute thermal burns admitted to a specialized burn unit. We hypothesized that targeting normoxemia would increase the number of supplemental oxygen-free days (SOFDs) and safely reduce exposure to hyperoxemia.

Methods: In this multicenter cluster-randomized, stepped-wedge trial, we randomized six US burn centers to cross over from usual care to targeted normoxemia at three-month intervals between January 15, 2021, and October 15, 2022. In usual care, supplemental oxygen was determined by treating clinicians. In targeted normoxemia, we specified decreasing administered supplemental oxygen whenever SpO 2 was >96%. The primary outcome was SOFD, defined as the number of days alive and not receiving supplemental oxygen through Day 28. Safety outcomes included hypoxemia (SpO 2 < 88%), in-hospital mortality, and adverse events.

Results: The 1,437 enrolled patients were mean age 48 years, 26% female, 38% with full-thickness burns, and 11% mean total body surface area burned. The proportion of time spent in normoxemia increased from 77% in the usual care group to 81% in the targeted normoxemia group. Time spent with hyperoxemia (SpO 2 > 96%) decreased from 22% to 17%, and hypoxemia was similar between groups (0.7% vs. 0.8%). The raw mean number of SOFD was 18.8 days for targeted normoxemia and 17.2 days for usual care (adjusted mean difference [aMD], 0.90 days; 95% confidence interval [CI], -0.77 to 2.57; p = 0.29). Hospital-free days through Day 90 were greater among the targeted normoxemia group (71 days) than the usual care group (70 days) (aMD, 3.47 days; 95% CI, 0.19-6.76). In-hospital mortality to Day 90 occurred in 36 (5.7%) targeted normoxemia patients and 65 (8.1%) usual care patients (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.31-1.42).

Conclusion: Targeting normoxemia did not increase supplemental oxygen-free days among adults with acute thermal burns, but safely maintained clinical outcomes.

Level of evidence: Therapeutic Care/Management; Level I.

Trial registration: ClinicalTrials.gov Identifier: NCT04534972.

Keywords: Oxygen; critical illness; hyperoxemia; injury; military; thermal burn; wound healing.

Figure 1.

CONSORT flow diagram.

Figure 2.

Top panel—mean values of oxygen saturation (SpO₂) and fraction of inspired oxygen (FIO₂) by group (targeted normoxemia vs. usual care) for modifiable patient time. Shaded areas represent the 95% confidence interval of the mean at a given time.Bottom panel—difference in mean (targeted normoxemia minus usual care) SpO₂ and FIO₂ for modifiable patient time. A negative mean difference indicates that targeted normoxemia was lower than usual care.Patient time was considered “nonmodifiable” if the patient was receiving room air or 21% FIO₂ but had an oxygen saturation (SpO₂) >96% (i.e., was in the hyperoxemia range). All other patient time is included in this figure.

Figure 3.

A, Proportion of patients alive and not receiving supplemental oxygen through Day 28. (B) Proportion of patients by quartile of supplemental oxygen-free days. The top curve is a Kaplan-Meier plot of mortality, and the bottom curve is the time to liberation from supplemental oxygen (time to room air). Shaded areas represent 95% confidence intervals. CI, confidence interval. (B) Each color represents the proportion of patients in one quartile of supplemental oxygen-free days through Day 28. Each shade within each color represents the proportion of patients who achieved the exact number of supplemental oxygen-free days. Patients who experienced in-hospital mortality within 28 days of admission received a supplemental oxygen-free day value of −1 and are represented in black.

Figure 3.

A, Proportion of patients alive and not receiving supplemental oxygen through Day 28. (B) Proportion of patients by quartile of supplemental oxygen-free days. The top curve is a Kaplan-Meier plot of mortality, and the bottom curve is the time to liberation from supplemental oxygen (time to room air). Shaded areas represent 95% confidence intervals. CI, confidence interval. (B) Each color represents the proportion of patients in one quartile of supplemental oxygen-free days through Day 28. Each shade within each color represents the proportion of patients who achieved the exact number of supplemental oxygen-free days. Patients who experienced in-hospital mortality within 28 days of admission received a supplemental oxygen-free day value of −1 and are represented in black.

Figure 4.

Heterogeneity of Treatment Effect for SOFDs.