Oxygen Supplementation in COVID-19—How Much Is Enough?

Abstract

Humans are aerobic animals; we need oxygen to support metabolism and generate energy. Simply put, breathing oxygen is necessary for life. Consequently, it would make sense that diseases that inhibit the transfer of oxygen from the lung to the blood should be treated with supplementary oxygen to overcome problems associated with hypoxemia, and one should strive to achieve "normal" levels of arterial oxygen (PaO 2 ). But is that reasoning supported by the understanding of physiology and the weight of clinical evidence?Stating that human tissues are dependent on oxygen refers to the need for oxygen delivery to vital organs; oxygen delivery encompasses the oxygen content of the blood as well as cardiac output. Because total oxygen content consists of oxygen bound to hemoglobin as well as oxygen dissolved in plasma, with the former far exceeding the latter, one might reason that transfusing patients with anemia to a normal level of hemoglobin would result in better outcomes. The evidence suggests otherwise, however, and the threshold for transfusion of red blood cells is well below "normal" values of hemoglobin. [1][2][3] From an evolutionary perspective, it might be argued that humans are built to tolerate mild degrees of hypoxemia. The oxygen-hemoglobin saturation curve has a characteristic sigmoid shape. A decrease in PaO 2 from 90 mm Hg to 60 mm Hg still leaves one with near-normal oxygen saturation and oxygen content of the blood; long before supplemental oxygen was available, humans had pneumonia, asthma, or heart failure and tolerated mild to moderate decrements in PaO 2 . Nevertheless, the sickest patients, those with acute hypoxemic respiratory failure, must benefit from restoring oxygen saturation to normal values, or at least that is what clinical intuition might tell us.The study by Nielsen et al 4 reported in this issue of JAMA builds on prior work of the HOT-COVID trial 5 to assess the impact of targeting PaO 2 to 90 mm Hg vs 60 mm Hg in patients with COVID-19 pneumonia and hypoxemic respiratory failure. This study was a large multicenter trial involving medical intensive care units (ICUs) in 5 European countries. Acute hypoxemic respiratory failure was defined as necessitating supplemental oxygen of at least 10 L/min in an open system or mechanical ventilatory support (either invasive or noninvasive). The protocol required randomization of participants to supplemental oxygen to achieve high PaO 2 (90 mm Hg) or low PaO 2 (60 mm Hg) targets. Arterial lines were placed in all patients; this is one of the strengths of the study given the technical issues that often confound interpretation of pulse oximetry (eg, inadequate waveforms; erroneous measurements 15.