High doses of pseudoephedrine hydrochloride accelerate onset of CNS oxygen toxicity seizures in unanesthetized rats

• Hypothesis – does psedoephedrine, a sympathomimetic agent, increase risk for CNS-OT?
• High doses of pseudoephedrine (>100 mg/kg) accelerate the onset of CNS-OT in rat.
• Lower doses (40–80 mg/kg) of pseudoephedrine do not increase the risk of CNS-OT in rat.
• Pseudoephedrine should not be abused in divers breathing high-dose oxygen.

Pseudoephedrine (PSE) salts (hydrochloride and sulfate) are commonly used as nasal and paranasal decongestants by scuba divers. Anecdotal reports from the Divers Alert Network suggest that taking PSE prior to diving while breathing pure O2 increases the risk for CNS oxygen toxicity (CNS-OT), which manifests as seizures. We hypothesized that high doses of PSE reduce the latency time to seizure (LS) in unanesthetized rats breathing 5 atmospheres absolute (ATA) of hyperbaric oxygen. Sixty-three male rats were implanted with radio-transmitters that recorded electroencephalogram activity and body temperature. After ⩾7-day recovery, and 2 h before “diving”, each rat was administered either saline solution (control) or PSE hydrochloride intragastrically at the following doses (mg PSE/kg): 0, 40, 80, 100, 120, 160, and 320. Rats breathed pure O2 and were dived to 5 ATA until the onset of behavioral seizures coincident with neurological seizures. LS was the time elapsed between reaching 5 ATA and exhibiting seizures. We observed a significant dose-dependent decrease in the LS at doses of 100–320 mg/kg, whereas no significant differences in LS from control value were observed at doses ⩽80 mg/kg. Our findings showed that high doses of PSE accelerate the onset of CNS-OT seizures in unanesthetized rats breathing 5 ATA of poikilocapnic hyperoxia. Extrapolating our findings to humans, we conclude that the recommended daily dose of PSE should not be abused prior to diving with oxygen-enriched gas mixes or pure O2.