Mechanism and Prevention of Hyperbaric Oxygen Convulsions

Hyperbaric oxygen therapy (HBOT) proves vital in saving lives by elevating the partial pressure of oxygen (pO2). However, HBOT may also have toxic effects, including lung and retinal damage (peripheral HBOT toxicity), muscle spasms and violent myoclonic convulsions (CNS HBOT toxicity), which may even lead to death if left untreated. Despite the severity of the toxic effects of HBOT, their mechanism is only poorly understood to date. This lack of understanding the underlying mechanism hinders the development of new, effective therapies and preventive strategies to supress HBOT toxicity. Herein, we provide evidence that (1) increased pO2 increases the content of reactive oxygen species (ROS) in tissues, which causes peripheral HBOT toxicity and contributes to CNS toxicity by irreversibly altering cell receptors. Moreover, (2) increased ROS concentration in brain lowers activity of glutamic decarboxylase (GD), which lowers concentrations of inhibitory neurotransmitter gamma-aminobutyric acid (GABA), thereby contributing to the onset of HBOT-derived convulsions. At last, we provide long overlooked evidence that (3) elevated ambient pressure directly inhibits GABA(A) and glycine receptors, thereby leading to the rapid onset of HBOT-derived convulsions. We show that only a combination of these three mechanisms (1 + 2 + 3) are needed to explain most phenomena seen in HBOT toxicity (especially in CNS toxicity). Based on these proposed intertwined mechanisms, we propose administering antioxidants (lowering ROS concentrations), pyridoxine (restoring GD activity), and low doses of sedatives/ anaesthetics (reversing inhibitory effects of pressure on GABA(A) and glycine receptors) before routine hyperbaric oxygen therapies and deep-sea diving to prevent the HBOT toxicity.