Conservative Oxygenation Outperforms Liberal Targets for Critically Ill Kids

Conservative oxygenation targets in the pediatric intensive care unit (PICU) improved outcomes and reduced costs for ventilated patients, a randomized clinical trial found.

The rank-based endpoint of duration of organ support or death before day 30 was significantly lower among children randomized to conservative oxygenation as opposed to liberal targets (probabilistic index 0.53, 95% CI 0.50-0.55), reported Mark Peters, PhD, of the University College London Great Ormond Street Institute of Child Health, and colleagues.

Compared with a liberal oxygenation peripheral oxygen saturation (SpO₂) target above 94%, a conservative target of 88-92% therefore provided a “small, but significant, greater probability for a better outcome” for invasively ventilated children (adjusted OR 0.84, 95% CI 0.72-0.99), according to the multicenter Oxy-PICU trial published in The Lancet.

“While the observed effect between groups was small, given the number of critically ill children treated with oxygen each year, a small effect might result in larger clinical effect,” the study authors wrote. “To put these findings into context, acknowledging the uncertainty around the point estimates, if the observed change in the distribution of the primary outcome is true then for every 200 patients treated with a conservative oxygenation target this would equate to one fewer death and 123 fewer days of organ support, corresponding to approximately 0.6 days per patient.”

Oxy-PICU represents the first large randomized trial of different oxygenation targets for critically ill children. Although previous research had not strongly favored any single oxygenation strategy, current practice is an SpO₂ target of 95-100%.

It is believed that more liberal strategies featuring high fractions of inspired oxygen (FiO₂) “might contribute to oxidative stress,” while conservative approaches “might reduce the risk of harm from higher FiO₂ but could increase exposure to potentially harmful hypoxia,” noted Peters and colleagues.

They reported that in Oxy-PICU, adverse events were similar between the treatment groups, reaching 3% of conservative oxygenation patients and 4% of liberal oxygenation patients. Events included lactic acidosis, cardiac ischaemia, acute kidney injury, seizures, and critical hypotension and hypoxia.

Steven Shein, MD, of Rainbow Babies and Children’s Hospital in Cleveland, and Todd Karsies, MD, of Nationwide Children’s Hospital in Columbus, Ohio, urged caution in applying the study’s findings to practice.

“Overall, meta-analysis of 17 studies including more than 10,000 critically ill adults shows no effect of oxygenation targets on mortality, serious adverse events, or quality of life. While critically ill children should not be considered either small adults or overgrown neonates, the lack of consistent benefit across trials limits enthusiasm for declaring SpO₂ of 88-92% the new standard of PICU care based on one trial,” the pair wrote in a linked commentary.

“At the bedside, we believe this study can justify generally titrating ventilator settings to maintain SpO₂ around 93-95%, hoping to decrease oxidative injury in very ill children, and remove unnecessary respiratory support in more mild illness. But before permissive hypoxemia can be adopted as standard care, additional trials with optimised achievement of putative targets are needed, as are data on long-term outcomes,” Shein and Karsies stressed.

Karsies told MedPage Today via email that the median mean oxygen saturation of 94% achieved in the conservative oxygenation arm of Oxy-PICU aligns with his current practice. “I wouldn’t currently routinely target an oxygen saturation lower than this, and I suspect that most other pediatric intensivists that I have worked with have similar practice.”

The Oxy-PICU trial was conducted in 15 PICUs within the National Health Service in England and Scotland from 2020 to 2022. Eligible participants were children from 38 weeks corrected gestational age and 16 years of age who had been accepted for admission to a participating PICU as an emergency and were receiving invasive mechanical ventilation with supplemental oxygen.

The 1,872 children enrolled were randomly assigned 1:1 to either conservative or liberal oxygenation groups. Girls comprised over 55% of the population, and the average patient age was 2.6 years. Nearly 70% of patients were white. Bronchiolitis was the most common reason for admission to PICU, accounting for nearly 37% of cases.

The editorialists pointed out that the conservative oxygenation group was often above-range, with only a quarter of SpO₂ values in goal range.

Patients in each group had a median 5 days of organ support up to day 30, with deaths in 2.4% of the conservative group at this point versus 3% in the liberal group (P=0.48). Length of PICU and hospital stays were also similar.

There was a cost difference of £2,143 (approximately $2,699, P=0.05) making conservative treatment the more economical strategy by 30 days.

Researchers noted their “somewhat atypical case-mix,” as there were fewer than expected Oxy-PICU participants with respiratory tract infections, potentially due to the COVID-19 pandemic.

Other possible study limitations included the exclusion of patients admitted with a primary diagnosis of congenital cardiac disease or acute encephalopathy, as well as the exclusion of some patients due to missing consent from a parent or guardian.