Central Nervous System Oxygen Toxicity and Hyperbaric Oxygen Seizures

Abstract

Introduction: The use of hyperbaric oxygen (O2) as a therapeutic agent carries with it the risk of central nervous system (CNS) O2 toxicity.

Methods: To further the understanding of this risk and the nature of its molecular mechanism, a review was conducted on the literature from various fields.

Results: Numerous physiological changes are produced by increased partial pressures of oxygen (Po2), which may ultimately result in CNS O2 toxicity. The human body has several equilibrated safeguards that minimize effects of reactive species on neural networks, believed to play a primary role in CNS O2 toxicity. Increased partial pressure of oxygen (Po2) appears to saturate protective enzymes and unfavorably shift protective reactions in the direction of neural network overstimulation. Certain regions of the CNS appear more susceptible than others to these effects. Failure to decrease the elevated Po2 can result in a tonic-clonic seizure and death. Randomized, controlled studies in human populations would require a multicenter trial over a long period of time with numerous endpoints used to identify O2 toxicity.

Conclusions: The mounting scientific evidence and apparent increase in the number of hyperbaric O2 treatments demonstrate a need for further study in the near future.

Fig. 1.

Schematic of extracellular interactions produced by increased Po₂ that result in CNS HBO₂ seizures. Increased cerebral blood flow (CBF) results in decreased time to onset of HBO₂ seizures (tHBO₂S). Extracellular substances such as phosphodiesterase-5 inhibitors (PDE-5i), 7-NI, N-nitro-L-arginine (NNA, a NOS inhibitor), and daurisoline (DSL, a calcium channel blocker) affect CBF. Dotted line = lessened action (−). Bold line = increased action (+). Large arrow = correlation.

Fig. 2.

Schematic of some synaptic changes produced by increased Po₂ and resulting in CNS HBO₂ seizures. The human body has several equilibrated safeguards that minimize effects of ROS on neural networks. Increased Po₂ appears to saturate protective enzymes and unfavorably shift protective reactions in the direction of neural network overstimulation, resulting in HBO₂ seizures. NT = neurotransmitter; AP = action potential. Dotted line = lessened action. Bold line = increased action.

Fig. 3.

Brain regions most likely involved in HBO₂-induced seizures. Certain regions of the CNS (including the solitary complex in the dorsal medulla, hippocampus, globus pallidus, substantia nigra, superior olivary nucleus, ventral cochlear nucleus, and spinal cord gray matter) appear more susceptible than others to these effects. Note the central nature of these regions, anatomically similar to CO susceptible regions.