Hooray for Hypoxia?

Hypoxaemia kills. Recently we have shown, in a study of over 50 000 critically ill patients, that mortality rises steadily as the partial pressure of arterial oxygen (PaO2) falls below about 11 kPa (80 mm Hg) (Figure 1) [1]. Rats exposed to hypoxic conditions develop a mild infl ammatory response with increased capillary leak and proinfl ammatory cytokine release [2]. Hypoxia increases leukocyte adhesion, prolongs neutrophil survival, enhances pro-infl ammatory responses (in particular, increasing leukocyte IL-8 expression), and reduces lung fl uid transport [3,4]. A new study by Thiel et al. in PLoS Biology that shows a potential benefi t for hypoxia is therefore a challenge to current thinking [5]. To put this fi nding into context we must acknowledge the equally accepted fact that hyperoxia is toxic. Experiments in primates show that 100% oxygen results in progressive damage to the pulmonary endothelium and epithelium. It causes free radical release, capillary leak, and impaired surfactant function in addition to arteriolar vasoconstriction and maldistribution of microcirculatory perfusion [6,7]. What, then, is the clinical balance we should strike between these extremes? Oxygenation of patients with acutely impaired lung function saves lives, but what is the right amount of oxygen? Many clinicians use the oxygen dissociation curve, aiming for saturations of above 92%. Others highlight the fact that patients with severe respiratory failure can survive despite being mechanically ventilated for days on 100% oxygen. In other words, a high percentage of inspired oxygen itself may not be harmful. (In animal studies showing harm from giving 100% oxygen, the lungs are usually normal at the beginning of the study, so the arterial oxygen is correspondingly high— typically a PaO2 of 40 kPa (300 mm Hg); thus, it may be the high PaO2 rather than the high percentage of inspired oxygen that causes lung damage.) Some researchers question the importance of oxygen toxicity at all—for example, Meier et al., using a haemorrhagic shock model, found a signifi cant improvement in outcome from the addition of 100% oxygen to the resuscitation [8].