Oxygen Toxicity: Other Manifestations of Toxicity

It has been suggested that oxygen, although essential for survival of aerobic cells, should be regarded as a universal cellular poison. All organs and tissues of the body are susceptible to damage from oxygen free radical production. Nevertheless, in other organs receiving a high blood flow such as heart, kidney and liver, no toxicity has yet been detected in humans. It may be that CNS and pulmonary toxicity pre-empt its development in other organs.

Haematopoietic system

Oxygen, in space flight exposures, has been shown to have a deleterious effect on red blood cells that is manifested by abnormal cell morphology and/or a decrease in circulating red blood cell mass. This may be caused by depression of erythropoiesis, inactivation of essential glycolytic enzymes or damage to red blood cell membranes resulting from peroxidation of membrane lipid. Mice studies show irreversible damage to haematopoietic stem cells after 24 hours of exposure to 100 per cent oxygen.

There have also been occasional reports of haemolytic episodes following hyperbaric oxygen exposure, but these seem to be related to individual idiosyncrasies such as specific enzyme defects.

Eye

In 1935 Behnke reported a reversible decrease in peripheral vision after oxygen breathing at 3.0 ATA. Lambertsen and Clarke demonstrated a progressive reduction in peripheral vision after 2.5 hours of breathing oxygen at 3.0 ATA that reached about 50 per cent after 3.5 hours. Recovery was complete after 45 minutes of air breathing.

Progressive myopic changes have been well documented during hyperbaric therapy, and they have also been noted in divers. Reversal of this myopic shift usually occurs within a few weeks, but could take many months. Changes are probably related to an effect on the crystalline structure of the lens. Butler and colleagues demonstrated a myopic shift after 15 days of hyperbaric oxygen therapy and approximately 45 hours of diving exposure to 1.3 ATA oxygen14.

Cataract formation has also been reported after extreme hyperbaric exposure (more than 100 treatment sessions), with lens opacities not completely reversible.

A reduction of the intraocular pressure may represent a toxic effect on the ciliary process. Retinal detachments, retinal micro-infarcts, changes in dark adaptation, photoreceptor damage and a decrease in the amplitude of the electroretinogram have all been recorded.

Other ocular effects of oxygen toxicity include retinopathy of prematurity in infants breathing supplemental oxygen. Initial retinal blanching resulting from vasoconstriction is followed by vessel obliteration and fibro-vascular proliferation, which may lead to retinal fibrosis and traction retinal detachments. Animal studies have demonstrated death of visual cells and retinal detachments on exposure to 0.9 to 3 ATA oxygen. Irreversible changes in the cornea and lens of guinea pigs develop after exposure to 3 ATA oxygen for between 4 and 16 hours.

Vasoconstriction

Other disorders that may be affected by the hyperoxic-induced vasoconstriction include Raynaud’s phenomenon, Buerger’s disease and migraine. Risk of closure of the ductus arteriosus has been proposed in the foetus exposed to increased oxygen.

Ear

Serous otitis media has been noted in aviators exposed to high concentrations of oxygen. It results from absorption of oxygen from the middle ear. A syndrome related to the middle ear was described in US Navy divers breathing 100 per cent oxygen from semi-closed-circuit and closed-circuit diving equipment. The symptoms were fullness, popping or crackling sensation in the ear and a mild conductive hearing loss. On examination the most common finding was fluid in the middle ear. The syndrome was first noted after rising from a night’s sleep, not immediately after the dive itself, and it disappeared rapidly. There was no suggestion of barotrauma.

Cancer

Repeated or long-term exposure to high levels of oxygen free radicals could be expected to enhance tumour development. A literature review including human and animal studies failed to support a possible cancer-causing effect of hyperbaric oxygen15.

It is likely that, as more sensitive methods of detection are used, evidence of oxygen toxicity in many other cells and organs will be observed.