MEDICAL 99.5% V/V OF OXYGEN GAS

Indications

• Hypoxemia
• Chronic obstructive pulmonary disease (COPD)
• Acute respiratory distress syndrome (ARDS)
• Pneumonia
• Asthma exacerbations
• Postoperative recovery
• Carbon monoxide poisoning
• Cyanide poisoning

Dosage

Children: Oxygen therapy in children should be similarly guided by clinical assessment of oxygen saturation and respiratory status. Specific pediatric dosing and administration routes are outlined in the BNF for

Adults: Oxygen should be administered in a controlled manner, typically using nasal cannula, face masks, or mechanical ventilation, with the exact dosage tailored to the patient's oxygen saturation levels and clinical condition. Refer to local guidelines for specific protocols.

Mechanism of action

Oxygen therapy increases the arterial pressure of oxygen and enhances gas exchange, provided functional alveolar units are intact. It acts as an electron acceptor during oxidative phosphorylation in the electron transport chain, activating cytochrome c oxidase, which is crucial for aerobic respiration and ATP production. Oxygen also interacts with voltage-gated potassium channels in glomus cells, causing hyperpolarization of the mitochondrial membrane and modulating hypoxic pulmonary vasoconstriction.

Pharmacodynamics

Oxygen therapy improves cellular oxygenation even at low tissue perfusion rates. It adjusts the hypoxic ventilatory drive by acting on carotid body chemoreceptors, reducing mitochondrial depolarization that can lead to reactive oxygen species generation and apoptosis. Hyperbaric oxygen therapy has shown potential in promoting neural stem cell proliferation and accelerating recovery at peripheral sites through the mobilization of specific leukocyte subsets.

Pharmacokinetics

Oxygen is inhaled and absorbed through the alveoli into the bloodstream, where it binds to hemoglobin in red blood cells for transport to tissues. The distribution and elimination of oxygen from the body are primarily determined by ventilation and perfusion dynamics, with the half-life being influenced by the concentration of oxygen and the presence of underlying pulmonary conditions.

Adverse effects

• Hyperoxia
• Oxygen toxicity
• Respiratory depression
• Pulmonary oxygen toxicity
• Retinopathy of prematurity in neonates

Precautions

• Use with caution in patients with chronic obstructive pulmonary disease (COPD) to prevent carbon dioxide retention
• Ensure proper monitoring of oxygen saturation levels
• Avoid high concentrations of oxygen in premature infants to prevent retinopathy

Pregnancy

Oxygen is generally considered safe during pregnancy when used for medical indications, but should be administered under medical supervision.

Breast-feeding

Oxygen is safe to use during breastfeeding, as it does not affect breast milk production or composition.

Storage

Store oxygen cylinders in a cool, dry place away from heat sources and flammable materials. Ensure proper handling according to local regulations.

Formulations

• Oxygen gas (medical grade) in cylinders
• Oxygen concentrators
• Liquid oxygen systems

Mechanism of action

Oxygen therapy increases the arterial pressure of oxygen and is effective in improving gas exchange and oxygen delivery to tissues, provided that there are functional alveolar units. Oxygen plays a critical role as an electron acceptor during oxidative phosphorylation in the electron transport chain through activation of cytochrome c oxidase (terminal enzyme of the electron transport chain). This process achieves successful aerobic respiration in organisms to generate ATP molecules as an energy source in many tissues. Oxygen supplementation acts to restore normal cellular activity at the mitochondrial level and reduce metabolic acidosis. There is also evidence that oxygen may interact with O2-sensitive voltage-gated potassium channels in glomus cells and cause hyperpolarization of mitochondrial membrane. The exact mechanism whereby hypoxic pulmonary vasoconstriction is elicited is still unsettled. A possible role for toxic oxygen metabolites was evaluated, employing a set-up of blood-perfused isolated rat lungs. Hypoxic pulmonary vasoconstriction reflected as pulmonary arterial pressor responses, was evoked by alternately challenging the airways with a hypoxic- and a normoxic gas mixture, resulting in gradually increasing responses until a maximum was obtained. In a sequence of responses (mean +/- s.e. mean) increasing from 2.5 +/ - 0.2 kPa to 3.2 +/ - 0.1 kPa, administration to the perfusate of the inhibitor of xanthine oxidase, allopurinol reduced the subsequent response to 2.5 +/- 0.2 kPa (P < 0.001). By contrast, allopurinol did not affect vasoconstriction induced by serotonin or bradykinin. In control experiments responses continued to increase after administration of hypoxanthine (substrate of xanthine oxidase). Neither pretreatment with daily injections of the antioxidant vitamin E for 3 days in advance, nor addition to the perfusate of the scavenger enzymes superoxide dismutase and catalase, or dimethylsulfoxide had any impact on hypoxic pulmonary vasoconstriction; the subsequent responses rose at the same rate and in the same way as before. Thus, the present study has shown that allopurinol inhibition of xanthine oxidase depresses hypoxic pulmonary vasoconstriction. This could be due either to reduced production of toxic oxygen metabolites or to accumulation of purine metabolites. The absence of inhibitory effects of quenchers of toxic oxygen metabolites refutes a role for these metabolites in the elicitation of hypoxic pulmonary vasoconstriction. More likely, allopurinol inhibits hypoxic pulmonary vasoconstriction by interfering with the purine metabolism. Exposure to hyperoxia results in endothelial necrosis followed by type II cell proliferation. This suggests that type II cells are resistant to hyperoxia. Oxygen-induced lung injury may result from an overproduction of oxygen metabolites normally scavenged by antioxidants such as superoxide dismutase, glutathione peroxidase, catalase and reduced glutathione. Therefore, resistance of type II cells to hyperoxia may be linked to high antioxidant activities. To test this hypothesis /the authors/ compared in vitro the effects of a 24 hr exposure period to 95% O2 on cultured type II cells, lung fibroblasts and alveolar macrophages isolated from rats. We show that type II cells, when compared with other cell types, are highly sensitive to hyperoxia as shown by increased lactate dehydrogenase release, decreased deoxyribose nucleic acid and protein content of Petri dishes and decreased thymidine incorporation into DNA. Synthesis of dipalmitoylphosphatidylcholine was also significantly reduced. Antioxidant enzyme activities as well as glutathione content were not higher in type II cells than in other cell types. However, hyperoxia results in a decreased superoxide dismutase activity and glutathione content in type II cells which was not observed in fibroblasts. /It was concluded/ that adaptative changes in superoxide dismutase and glutathione metabolism could be important de

Pharmacodynamics

Oxygen therapy improves effective cellular oxygenation, even at a low rate of tissue perfusion. Oxygen molecules adjust hypoxic ventilatory drive by acting on chemoreceptors on carotid bodies that sequentially relay sensory information to the higher processing centers in brainstem. It also attenuates hypoxia-induced mitochondrial depolarization that generates reactive oxygen species and/or apoptosis. Studies investigating on hyperbaric oxygen therapy has shown that oxygen supplementation can induce neural stem cell proliferation in neonatal rats thus promoting neurological regeneration after injuries. CD34+, CD45-dim leukocytes are also potential targets for hyperbaric oxygen therapy benefit as their mobilization was increased in vitro which could facilitate the acceleration of recovery at peripheral sites.