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.

Keywords: Critical care; Hyperoxia; Hypoxia; Lactate; Oxidative stress; Oxygen; Reactive oxygen species.

Fig. 1

Chemiosmotic mechanism of oxidative phosphorylation in mitochondria to form adenosine triphosphate (ATP). ADP: adenosine diphosphate, FeS: iron sulfide protein, FMN: flavin mononucleotide, NAD⁺: nicotinamide adenine dinucleotide, NADH: reduced nicotinamide adenine dinucleotide, Q: ubiquinone. (Reuse from Guyton and Hall Textbook of Medical Physiology 14th ed. with permission from Elsevier B.V.)

Fig. 2

Diffusion of an oxygen molecule from the arterial end of a capillary to tissue cells. PO₂ in the interstitial fluid averaged 40 mmHg, and that in the cells was 23 mmHg, ranging from 5 to 40 mmHg. (Reuse from Guyton and Hall Textbook of Medical Physiology 14th ed. with permission from Elsevier B.V.)

Fig. 3

Effect of the blood flow and rate of oxygen consumption on tissue PO₂. An increase in blood flow to 400% from point A to B increases the tissue PO₂ from 40 to 66 mmHg, limited to 95 mmHg, just as with the arterial PO₂, even with maximal blood flow. Conversely, if the blood flow decreases from point A to C, the tissue PO₂ also decreases. (Reuse from Guyton and Hall Textbook of Medical Physiology 14th ed. with permission from Elsevier B.V.)

Fig. 4

Relationship between PO₂ and the rate of oxygen usage by the cells at different concentrations of intracellular adenosine diphosphate (ADP). As long as intracellular PO₂ remains above 1 mmHg, the rate of oxygen usage remains constant, depending on the ADP concentration. (Reuse from Guyton and Hall Textbook of Medical Physiology 14th ed. with permission from Elsevier B.V.)

Fig. 5

In the process of the stepwise reduction from oxygen to water, reactive oxygen species (ROS) are produced. Both hydroxy radical and peroxynitrite are the most reactive agents among the species