Supplementation of high levels of oxygen increases mortality risk

Prompt oxygen supplementation has become a routine practice in critically ill patients primarily to correct tissue hypoxia and maintain adequate oxygenation due to arterial hypoxemia in acute illnesses such as respiratory distress, cardiac arrest, myocardial infarction. Oxygen therapy in these situations is life saving (J Intern Med. 2013;274(6):505-28). Tissue hypoxia occurs within 4 minutes of failure of any of these systems because the oxygen reserves in tissue and lung are relatively small (BMJ. 1998;317(7161):798-801).

Recently, however, focus has been on the harmful effects of high levels of oxygen or ‘oxygen toxicity’ because of the vasoconstrictor effect of hyperoxemia and the risk of significant blood flow reduction to the at-risk tissue, especially on normal, nondiseased vasculature (J Intern Med. 2013;274(6):505-28).

While acute critical illnesses merit early supplementation of high levels of oxygen, evidence is accumulating that while hyperoxemia is probably prudent during resuscitation, avoiding hyperoxemia is probably desirable in the post-resuscitation phase (Crit Care. 2014;18(5):555). But, most patients on mechanical ventilation continue to be on high levels of oxygen supplementation all through intensive care (Crit Care. 2014;18(5):556). And the adverse effects of too much oxygen are often ill-understood.

A statement from the International Liaison Committee on Resuscitation published in December 1, 2008 in Circulation says “post–cardiac arrest care, ventilation with 100% oxygen for the first hour after resumption of spontaneous circulation resulted in worse neurological outcome than immediate adjustment of the FIO2 to produce an arterial oxygen saturation of 94% to 96%”.

Following this, in 2010, the AHA recommended that providers should titrate inspired oxygen to the lowest level required to achieve an arterial oxygen saturation of ≥94%, so as to avoid potential oxygen toxicity.

The Improving Oxygen Therapy in Acute-illness (IOTA) systematic review and meta-analysis of 25 trials published very recently April 28, 2018 in The Lancet shows that liberal oxygen therapy in acutely ill adults increases mortality without improving other patient-important outcomes. Supplemental oxygen might become unfavorable above an SpO2 range of 94–96%. These results support the conservative administration of oxygen therapy.

The meta-analysis included patients with sepsis, critical illness, stroke, trauma, MI or cardiac arrest, and patients who had emergency surgery. Patients with chronic respiratory diseases or psychiatric disease, patients on extracorporeal life support, or patients treated with hyperbaric oxygen therapy or elective surgery were excluded.

Compared with a conservative oxygen strategy, a liberal oxygen strategy (median baseline saturation of peripheral oxygen [SpO₂] across trials, 96% [range 94–99%, IQR 96–98]) increased mortality in-hospital (relative risk [RR] 1·21, 95% CI 1·03–1·43, I²=0%, high quality), at 30 days (RR 1·14, 95% CI 1·01–1·29, I²=0%, high quality), and at longest follow-up (RR 1·10, 95% CI 1·00–1·20, I²=0%, high quality). The mortality rates increased as the oxygen saturation levels crossed the threshold of 94% to 96%. A 20% increase in hospital mortality was seen when oxygen was given to critically ill patients who were nonhypoxic.

A systematic review and meta-analysis is regarded as the highest level of evidence (level 1). Hence, there is a need to exercise caution with oxygen therapy and incorporate the findings of this trial in day to day clinical practice.

The clinical implications of these findings were best summed up by Lisa H.-Y. Kim, MD, from McMaster University, Hamilton, Ontario, Canada and a coauthor of the study, “"Oxygen shouldnt be treated as a harmless intervention. Now that we have high-quality data that too much oxygen is harmful, we should be really cautious in administering supplemental oxygen. We should really be, frankly, treating it as any prescribed drug, recognizing that it has both benefits and adverse effects." (Source: Medscape)

Dr KK Aggarwal

Padma Shri AwardeeVice President CMAAOGroup Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Immediate Past National President IMA