Biological effects of the oxygen molecule in critically ill patients

Abstract

The medical use of oxygen has been widely and frequently proposed for patients, especially those under critical care; however, its benefit and drawbacks remain controversial for certain conditions. The induction of oxygen therapy is commonly considered for either treating or preventing hypoxia. Therefore, the concept of different types of hypoxia should be understood, particularly in terms of their mechanism, as the effect of oxygen therapy principally varies by the physiological characteristics of hypoxia. Oxygen molecules must be constantly delivered to all cells throughout the human body and utilized effectively in the process of mitochondrial oxidative phosphorylation, which is necessary for generating energy through the formation of adenosine triphosphate. If the oxygen availability at the cellular level is inadequate for sustaining the metabolism, the condition of hypoxia which is characterized as heterogeneity in tissue oxygen tension may develop, which is called dysoxia, a more physiological concept that is related to hypoxia. In such hypoxic patients, repetitive measurements of the lactate level in blood are generally recommended in order to select the adequate therapeutic strategy targeting a reduction in lactate production. Excessive oxygen, however, may actually induce a hyperoxic condition which thus can lead to harmful oxidative stress by increasing the production of reactive oxygen species, possibly resulting in cellular dysfunction or death. In contrast, the human body has several oxygen-sensing mechanisms for preventing both hypoxia and hyperoxia that are employed to ensure a proper balance between the oxygen supply and demand and prevent organs and cells from suffering hyperoxia-induced oxidative stress. Thus, while the concept of hyperoxia is known to have possible adverse effects on the lung, the heart, the brain, or other organs in various pathological conditions of critically ill patients, and no obvious evidence has yet been proposed to totally support liberal oxygen supplementation in any subset of critically ill patients, relatively conservative oxygen therapy with cautious monitoring appears to be safe and may improve the outcome by preventing harmful oxidative stress resulting from excessive oxygen administration. Given the biological effects of oxygen molecules, although the optimal target levels remain controversial, unnecessary oxygen administration should be avoided, and exposure to hyperoxemia should be minimized in critically ill patients.

Upregulation of oxidative stress gene markers during SARS-COV-2 viral infection

“…Similar to other viral infections, it is difficult to differentiate between association and causation effects of SARS-COV-2 infection on oxidative stress mediated cellular injury [ 59 ]. Viral induced hypoxemia requires increasing the levels of inspired concentration of oxygen to maintain the systemic oxygen delivery [ 60 ]. A level of lung oxidative stress could then be induced corresponding to this increase in the level of inspired oxygen [ 60 ].…”

“…Viral induced hypoxemia requires increasing the levels of inspired concentration of oxygen to maintain the systemic oxygen delivery [ 60 ]. A level of lung oxidative stress could then be induced corresponding to this increase in the level of inspired oxygen [ 60 ]. This may contribute to the observed increase in oxidative stress gene markers.…”

Hypoxemia During One-Lung Ventilation: Does It Really Matter?

“…Hypoxia is medically classified into five pathophysiologic conditions, comprehensively reviewed elsewhere [ 8 •]. Hypoxemia as it pertains to OLV is largely attributable to shunt which improves with time so long as HPV is not impaired and remains fixed unless ancillary measures are taken or two-lung ventilation is resumed.…”

“…A reduction in any of these will decrease oxygen delivery (DO 2 ) and may lead to target organ dysfunction. Regional variations in microvascular tone, tissue edema, and to a much lesser degree dissolved oxygen content (PaO 2 ) are also variables that influence whether transported oxygen is able to reach the mitochondria of target organs [ 8 •]. While the above mentioned all contribute to oxygen transport, in examining the oxygen delivery (DO 2 ) equation, it becomes clear that cardiac output is of particular importance.…”

“…Healthy individuals exposed to hypoxic environments have been explored at length, particularly through studies on mountain climbers and high-altitude populations [ 26 ••]. With respect to the former where hypoxia progresses slowly over weeks, oxygen saturations in the sixties are observed without detrimental effects as a result of physiologic adaptations triggered by hypoxia-inducible factors including transcription of genes responsible for erythropoiesis and metabolic conditioning [ 8 •], shifting of the oxygen dissociation curve, increase in cardiac output through tachycardia, and increased ventilation [ 27 ]. A more acute hypoxemia scenario is that of breath-hold divers who can experience saturation nadirs around 50% without appreciable consequence but again likely have some preconditioning [ 26 ••].…”