Updated: Apr 9
Patients in the critical care unit (ICU) can be exposed unnecessarily to hyperoxia with the lack of attentive oxygen management, which could result in harmful consequences. In humans, one potential direct harm from hyperoxia is toxicity to the lungs, causing side effects such as interstitial fibrosis, atelectasis, and tracheobronchitis. Hyperoxia also has systemic effects by constricting peripheral vessels and increasing reactive oxygen species production as shown in animal models.
Although there are many warnings about the potential damage from hyperoxia, medical guidelines and clinicians' practices continue to promote prompt, uncontrolled administration of oxygen. This subject has been addressed in the literature through multiple clinical trials that failed to show a benefit of a conservative oxygen strategy in terms of patient-centered outcomes as compared to a liberal oxygen management strategy. More recently, the PILOT trial was published in NEJM and added another negative trial to the plethora of evidence that is available.
A conservative oxygen supplementation protocol was compared to conventional oxygen therapy in 434 adults admitted to the ICU with an expected length of stay of 72 hours or longer. The study was stopped early due to difficulties in enrollment, but the results showed that the conservative oxygen therapy group had a lower ICU mortality rate. The secondary outcomes of new shock episodes, liver failure, and bloodstream infections were also lower in the conservative oxygen therapy group. These preliminary findings suggested that a conservative oxygen supplementation protocol may be beneficial for critically ill patients .
A total 201 patients with acute respiratory distress syndrome were randomized to receive either conservative oxygen therapy (target Spo2: 88 to 92%) or liberal oxygen therapy (target Spo2, ≥96%) for 7 days. The primary outcome was death from any cause at 28 days. At day 28, a total of 34 of 99 patients (34.3%) in the conservative-oxygen group and 27 of 102 patients (26.5%) in the liberal-oxygen group had died. At day 90, 44.4% of the patients in the conservative-oxygen group and 30.4% of the patients in the liberal-oxygen group had died. Five mesenteric ischemic events occurred in the conservative-oxygen group. These results suggest that, among patients with ARDS, early exposure to a conservative-oxygenation strategy with a Pao2 between 55 and 70 mm Hg did not increase survival at 28 days, and there was a worrisome but not established signal of increased mortality at 90 days and mesenteric ischemia.
The ICU ROX trial was conducted to compare the effects of conservative oxygen therapy with usual oxygen therapy in ICU patients receiving mechanical ventilation. The primary outcome of the trial was the number of ventilator free days from randomization to day 28. At day 28, there was no difference between the two groups in ventilator free days. There was also no difference in deaths at day 180 or recorded adverse events. The authors concluded that there was no benefit to using conservative oxygen therapy in ICU patients receiving mechanical ventilation .
In the HOT-ICU multicenter trial, 2888 adult patients who were requiring oxygenation support were randomly assigned to receive oxygen therapy targeting a Pao2 of either 60 mm Hg or 90 mm Hg. There was no significant difference in 90-day mortality between the two groups (42.9% in the lower-oxygenation group vs. 42.4% in the higher-oxygenation group, p=0.64). There was also no significant difference in the percentage of days that patients were alive without life support, days alive after hospital discharge, and adverse events, including intestinal ischemia .
A total of 789 comatose adults who had been resuscitated after an out-of-hospital cardiac arrest were randomized to receive a restrictive oxygen target of partial pressure of arterial oxygen of 68 to 75 mm Hg, or a liberal oxygen target of 98 to 105 mm Hg. The composite of death from any cause or hospital discharge with a severe disability or coma within 90 days was not significantly different between the two groups .
A pragmatic, unblinded, cluster-randomized, cluster-crossover trial was conducted in the emergency department and medical intensive care unit at Vanderbilt University Medical Center in the US. 2541 adult patients who were receiving mechanical ventilation were randomized to receive a lower target for oxygen saturation (90%; goal range, 88 to 92%), an intermediate target (94%; goal range, 92 to 96%), or a higher target (98%; goal range, 96 to 100%). The primary outcome of ventilator-free days through day 28 was not significantly different among the three groups. Additionally, there were no differences in the secondary outcomes including 28-day mortality .
It appears that there is no significant difference in mortality or other outcomes when critically ill patients are given a conservative oxygen therapy protocol as opposed to a liberal oxygen therapy protocol. There may be some benefits to using a conservative oxygen therapy approach in certain populations of ICU patients, but more research is needed to make any definitive conclusions.
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