' Turn the Oxygen down' - you don't want Oxygen Toxicity. Was a common reminder, during Training. The issue really would come to head while treating ARDS patients with severe hypoxia - when FiO2 slowly creeped up to 100%- How - nobody would know. Pulmonary Complications like- Atelectasis, Tracheo - Bronchitis, Diffuse Alveolar Damage (DAD), worsening hypercarbia & even increased Mortality were cited. Fancy Terms like Haldane Effect - were quoted; mechanism's like- oxygen free radicals, inflammatory mediators release were blamed.





While Intensivist's were trying to Dial down the FiO2, the Surgeons were touting the benefits of High FiO2 in preventing Surgical Site Infections (SSI) and were dialing it up! Beneficial effects of oxygen in enhancing bacterial killing by antibiotics, potentiating neutrophil killing were cited. Increased PaO2 was also needed to promote surgical wound healing.





Even Michael Jackson was using Oxygen - so there has to be some truth to it. Haven't we seen high performance athlete's breathing oxygen on sideline's...





Hopefully we have some studies with fanciful names addressing these issues -





PROXI -Trial: JAMA Oct 14th 2009, 302 (14).

Multi center Randomized Trial across Denmark involving 1400 Pt's, looked at effect of Peri-Operative Oxygen on Surgical Site Infection (SSI). 80% FiO2 was compared with 30% FiO2, in patients undergoing exploratory laparotomy (scheduled or urgent).

The trial did not find any difference in the primary outcome of SSI. There was also no difference in secondary outcomes of atelectasis, pneumonia, respiratory failure & mortality.





The trial did suggest a trend towards increased respiratory failure & increased mortality in the high FiO2 arm leading to the next trial.





OXYGEN-ICU Trial: JAMA Oct 18th 2016; 316 (15).

A Singe Center Randomized trial, randomized 434 Pt's - 216 (Conservative Arm - PaO2 goal 70-100 mm Hg; SaO2 goal 94-98%) vs 218 (Conventional Arm - PaO2 up to 150 mm Hg; SaO2 97-100%). Approximately 66% Pt's were on Mechanical Ventilation.

The trial found - significantly lower Mortality in Conservative Arm 11.6% vs 20.2% (p=0.01). Even secondary outcomes like Shock, Liver Failure & Bacteremia were significantly lower in Conservative Arm.





Unfortunately, the trial had stopped early before full recruitment, due to poor recruitment & an earthquake, plus Pt's in Conventional Arm were sicker despite randomization.





ICU-ROX Study was published online on Oct 14th 2019 in NEJM.

A multi-center randomized trial across Australia/NZ involving almost 1000 Pt's on Mechanical Ventilation. In the conservative arm FiO2 was lowered for Sao2 > 97%, lowest FiO2 of 21% was used if SaO2 was > 90%. In Conventional Arm, lowest FiO2 allowed was 30%.

The trial found no difference in its primary outcome of Mechanical Ventilation free days. Secondary outcomes of death, Employment & Cognitive functions were also similar.





Not to be left out of the Surgeon vs Intensivist Debate - Cardiologist's decided to chip in with their own AVOID Trial in Circulation June 16th, 2015, involving almost 450 STEMI Pt's.The found higher peak CK levels but not Troponin levels in high FiO2 arm. Few Pt's who underwent CMR at 6 months showed larger Infarct area in High Oxygen arm.





So, what do we do: at least we have data to stop high FiO2 use perioperatively in Surgical Patients. Just keep them Normothermic (avoid hypothermia) & adequately Fluid Resuscitated. In Medical ICU, no need to go all the way down to 21%, can stop at 30% & avoid > 150 PaO2. If Sao2 shows 100% - Dial it down! Only reason I avoid 21% is, agitation while awakening from sedation; fluid shifts in Pt's with poor EF & partial atelectasis due to secretions can result in decompensation, which is enough to raise Fio2 from 21% --> 30% & trigger a VAP evaluation. Plus, now I have studies to support keeping Fio2 at 30%.







