Hypoxia continues to be a significant source of peril in military aviation. Over three dozen hypoxia-related incidents were reported in the past decade with three resulting in fatalities (Clark & Megown, 2005;Ostrander, 2008). Previous work has addressed loss of consciousness resulting from extreme levels of hypoxia (Carlyle, 1963); however, most mishaps are related to moderate hypoxia exposure. More work is required to establish the cognitive effects of moderate hypoxia and the time required, post-exposure, to fully recover. The present study examined the effect of a ten minute exposure to an air mixture equivalent to 20,000 ft on two-choice reaction time. Carryover effects were assessed over a ten minute recovery period. Hypoxia exposure resulted in significant delays in two-choice reaction time. Significant carry-over effects continued to be detected throughout the recovery period. This information is essential to military aviation, where high levels of cognitive performance are required after moderate hypoxia exposure.

Results of the current study strongly suggest that intranasal scopolamine is efficacious for the treatment of motion sickness in susceptible individuals with no significant cognitive or sedative effects. Intranasal delivery offers a promising alternative for use in dynamic operational environments without cognitive detriment or increased side effects.

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INTRODUCTION: Rapid onset, noninjection methods are required to provide “as needed” therapy for motion sickness. Intranasal scopolamine (IN SCOP) is attractive because it can be fast acting and work when gastric motility is slowed. Intranasal administration can provide a time to maximal concentration (Tmax) of drugs (e.g., naloxone and midazolam) of 30 min or less. We evaluated the efficacy, pharmacodynamics, and pharmacokinetics of IN SCOP in a placebo-controlled, randomized, double-blind, dose-ranging study, and compared pharmacokinetic outcomes against other published results.METHODS: There were 18 healthy adult volunteers (10 M, 8F) who received placebo, low dose (0.2 mg), and high dose (0.4 mg) IN SCOP intranasally using a pump device and a gel formulation. Participants rode in an off-vertical axis rotation (OVAR) chair 1.25 h after dose administration and completed neurocognitive tests to evaluate secondary drug impacts. Pharmacokinetics (PK) and pharmacodynamics (PD) were assessed in eight subjects. PK data were compared to results from previously published studies.RESULTS: Low and high dose IN SCOP increased chair time significantly compared to placebo. No significant sleepiness or cognitive impairment was seen, likely due to the small sample size. Tmax was long for both dosages (High dose 75.0 ± 49.4 min, Low dose 61.9 ± 37.1 min), compared to other intranasally administered drugs and some previous studies with IN SCOP. Average Tmax was not superior to previously published values for dose-matched (0.4–0.5 mg), orally-delivered SCOP.DISCUSSION: IN SCOP has potential as a rapid administration route for relieving MS symptoms, but more work is needed to identify optimal intranasal formulation and dispensing methods.KEYWORDS: Motion sickness, pharmacokinetics, scopolamine, intranasal administration.Stankovic AS, Alvarenga DL, Daniels VRC, Simmons RG, Buckey JC, Putcha L. Intranasal scopolamine for motion sickness. Aerosp Med Hum Perform. 2019; 90(11):917–924.

These results justify additional investigation into the efficacy of armodafinil to promote sustained vigilance in military operational settings where fatigue-related performance decrements are especially problematic.