Critical care
years,” says associate professor of medicine and critical care physician at Vanderbilt University Medical Centre, Matthew Semler. These trials represent a new wave of research that’s challenging conventional wisdom about oxygen: it’s a highly reactive molecule, so would very ill people be better off receiving a little less of it? The results we have so far offer something of an
answer, but there’s still a lot we don’t know. Adult studies have had conflicting findings and it’s not yet clear which patients might benefit most from being given conservative versus the standard liberal levels of oxygen. In children, however, lower targets do seem to be preferable. “We now have a pretty good certainty that there’s not a huge treatment effect for conservative oxygen targets for everyone. But [oxygen therapy is] so common that it’s worth knowing: is there even a small treatment effect?” says Semler. This poses two follow-up questions he adds: can conservative oxygen therapy help most people in a small way? And can it help some patients in a big way?
“We now have a pretty good certainty that there’s not a huge treatment effect for conservative oxygen targets for everyone. But [oxygen therapy is] so common that it’s worth knowing: is there even a small treatment effect?” Matthew Semler
6% The Lancet 50
The percentage of patients more likely to survive or spend less time on machines when receiving a conservative amount of oxygen.
A small improvement for most? In theory, it makes sense that the bulk of critical care patients would see at least a small benefit from receiving less oxygen. “Oxygen is a horribly reactive thing that pulls electrons out of other molecules,” says Professor of Paediatric Intensive Care at University College London Great Ormond Street Institute of Child Health, Mark Peters. “If you’re exposed to a lot of supplemental oxygen for a long time, that may contribute to the severity of the biological injury you’re suffering.” When too much oxygen is taken in, it can break down into free radicals – very reactive molecules that can cause cell damage. This can bring on inflammation that may be harmful to the body and brain. Being more conservative with oxygen also follows the principle of minimum safe care: doing the least amount of intervention possible while ensuring patient safety. This can help minimise the risks that come with additional treatment while helping short- stay patients get out of hospital quicker, says Peters. For instance, turning up oxygen may then mean that the patient needs more sedation – but if they are still on sedation, they can’t come off the ventilator. “A lot of trials have shown that the more aggressive
[treatment] arm is harmful… nearly always, the less interventional group is better,” says Peters. But in practice, evidence in favour of more conservative targets for adults isn’t decisive – although this approach wasn’t found to be harmful, either. In a review and meta-analysis of 25 trials including a range of critical care patients, there were more deaths in the hospital and at least 30 days later for those receiving liberal (94–99%) rather than conservative levels of oxygen. Yet there was no difference in illness between the groups at any of these points.
Other trials, including the ICU-ROX trial of 1,000 ICU patients, have found no difference in outcomes between conservative and liberal approaches. However, because there’s no standard definition for a conservative target, many studies report differing lower ranges of oxygen. Sometimes, these overlap with what would be given routinely. To really understand the treatment effect for entire groups of people, we need huge trials, says Semler. And a few are under way, such as the UK-ROX trial that will enrol 16,500 patients.
Evidence for lower targets is more convincing when it comes to children. A new, landmark study of 2,040 children – the Oxy-PICU trial – found that those receiving a conservative amount of oxygen (88–92%) versus a standard level (higher than 94%) were 6% more likely to either survive or spend less time on machines.
The researchers estimated that if this approach were rolled out across the country’s National Health Service, it could save 50 lives, 6,000 days spent in ICU beds, and save £20m per year in the UK alone. Peters, who was the lead author on the study, says that the results are generalisable as the patients recruited were representative of the UK critical care population. They also align with other research, he adds. “There are three trials in kids, they all show a small signal in favour of the lower target… that adds to the credibility of our result.”
Bigger benefits for some
“There are a lot of conditions, especially for patients at the hospital, for which the administration of too much oxygen could cause that oxygen to break down into free radicals,” says Semler. And presently, we do have some idea of who those patients might be. “Cardiac arrest is one of those groups where there’s real interest,” Semler explains. During cardiac arrest, the brain is starved of oxygen – but if that patient then receives a flood of oxygen, could that cause further damage to the brain? “The answer is that we’re still less certain than we would want to be,” he adds. There have been some trials looking at conservative oxygen therapy in cardiac arrest patients, but again, the results are unclear. The BOX trial, which included 789 comatose patients following
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