Modafinil Subjectively Does Not Impair Sleep in Aviators After a Period of Extended Wakefulness.

INTRODUCTION: Modafinil is used as a countermeasure to limit the effects of fatigue in military aviation. However, literature is conflicting about its negative effects on subsequent sleep.METHODS: This randomized placebo-controlled trial conducted by the Center of Man in Aviation of the Royal Netherlands Airforce is part of a larger study. It included 32 subjects (mean age 35 yr old, 84% male) who followed a normal daily routine and stayed awake the subsequent night. At midnight, all subjects received either 300 mg caffeine, 200 mg modafinil, or placebo. At the end of the test night, subjects were awake for a median period of 26 h. Afterwards, sleep questionnaires containing qualitative (Groningen Sleep Quality Scale) and quantitative parameters of sleep for the subsequent day (recovery sleep) and consecutive night (post-test sleep) were completed and statistically analyzed using Friedman and Wilcoxon signed rank tests.RESULTS: A statistically significant difference in the reported recovery sleep was observed. The modafinil group slept 30% shorter than placebo, but sleep efficiency was not statistically different. Quantitatively post-test sleep did not vary statistically significantly between the three groups. However, Groningen Sleep Quality Scale scores were lower post-test than pre-test in the modafinil group, while this was not the case in the caffeine and placebo group.DISCUSSION:This study found that modafinil subjectively does not negatively impact recovery sleep or subsequent nighttime sleep after an extended period of wakefulness and suggests it may decrease the need for recovery sleep compared to placebo or caffeine.Wingelaar-Jagt YQ, Wingelaar TT, Riedel WJ, Ramaekers JG. Modafinil subjectively does not impair sleep in aviators after a period of extended wakefulness. Aerosp Med Hum Perform. 2024; 95(6):290-296.

Daily Caffeine Intake and the Effect of Caffeine on Pilots' Performance After Extended Wakefulness.

INTRODUCTION: Fatigue is a major contributor to aviation accidents. Sufficient sleep may be difficult to achieve under operational conditions in military aviation. Countermeasures include caffeine, however, studies evaluating its effects often do not represent daily practice with regular caffeine consumption. This study aims to establish the effect of caffeine on psychomotor performance in a realistic scenario (i.e., after a limited period of extended wakefulness).METHODS: This randomized, double-blind, crossover, placebo-controlled trial included 30 aeromedically fit subjects. On trial days, subjects followed their normal routine till 17:00, after which caffeine intake was stopped. At midnight, subjects were given 300 mg of caffeine or placebo and performed the Psychomotor Vigilance Test, Vigilance and Tracking Test, and the Stanford Sleepiness Scale hourly up to 04:00 and again at 06:00 and 08:00. Four blood samples were collected. Statistical analyses included repeated-measures ANOVA or Friedman tests, marginal models, and Wilcoxon Signed Rank tests.RESULTS: Median time awake at midnight was 17 h (IQR 16.5-17.5 h). Performance decreased significantly less during the night in the caffeine condition versus placebo. Neither habitual intake nor daytime caffeine consumption affected this. No statistically significant correlation was identified between blood concentrations of caffeine and performance.DISCUSSION: A single dose of 300 mg of caffeine has beneficial effects on performance during the night in a realistic scenario for military aviation. Daytime caffeine consumption does not affect the effects of caffeine at night. These findings could be relevant for all industries in which optimal performance is required during nighttime after a limited period of extended wakefulness.Wingelaar-Jagt YQ, Wingelaar TT, de Vrijer L, Riedel WJ, Ramaekers JG. Daily caffeine intake and the effect of caffeine on pilots' performance after extended wakefulness. Aerosp Med Hum Perform. 2023; 94(10):750-760.

Effects of modafinil and caffeine on night-time vigilance of air force crewmembers: A randomized controlled trial.

BACKGROUND: Fatigue remains an important factor in major aviation accidents. Stimulants may counteract fatigue's adverse effects, with modafinil as a promising alternative to caffeine. However, the effect of a single dose of modafinil after a limited period of sleep deprivation remains unknown. AIMS: This study aims to determine the effect of 200 mg modafinil on vigilance during a limited period of sleep deprivation compared to 300 mg caffeine and placebo. METHODS: Thirty-two volunteers of the Royal Netherlands Air Force (RNLAF) were double-blindly administered modafinil, caffeine, and placebo on three non-consecutive trial days after being awake for median 17 h. Afterwards, subjects completed six series of the Vigilance and Tracking test (VigTrack), psychomotor vigilance task (PVT), and Stanford Sleepiness Scale (SSS), yielding six primary endpoints. RESULTS: This study revealed statistically significant effects of caffeine and modafinil compared with placebo on all endpoints, except for VigTrack mean tracking error. PVT results were less impaired 2 h after administration, followed by VigTrack parameters and SSS scores 2 h thereafter. Compared with caffeine, modafinil significantly improved PVT and SSS scores at 8 h after administration. CONCLUSIONS: The present study demonstrates that 200 mg modafinil and 300 mg caffeine significantly decrease the effects of a limited period of sleep deprivation on vigilance compared with placebo. Although PVT parameters already improved 2 h after administration, the most notable effects occurred 2-4 h later. Modafinil seems to be effective longer than caffeine, which is consistent with its longer half-life.

Comparison of effects of modafinil and caffeine on fatigue-vulnerable and fatigue-resistant aircrew after a limited period of sleep deprivation.

Introduction: Literature suggests pilots experience fatigue differently. So-called fatigue-resistant or -vulnerable individuals might also respond differently to countermeasures or stimulants. This study, which is part of a larger randomized controlled clinical trial, aims to investigate the effect of caffeine and modafinil on fatigue-resistant and -vulnerable pilots. Methods: This study included 32 healthy employees of the Royal Netherlands Air Force, who completed three test days, separated by at least 7 days. After a regular work day, the subjects were randomly administered either 300 mg caffeine, 200 mg modafinil or placebo at midnight. Hereafter the subjects performed the psychomotor vigilance test (PVT), vigilance and tracking test (VigTrack) and Stanford sleepiness scale (SSS) six times until 8 a.m. the next day. Subjects were ranked on the average number of lapses on the PVT during the placebo night and divided into three groups: fatigue-vulnerable (FVUL), -intermediate (FINT) and -resistant (FRES), with 11, 10 and 11 subjects in each group, respectively. Area under the curve (AUC) of the PVT, VigTrack and SSS during the test nights were calculated, which were used in univariate factorial analysis of variance (ANOVA). Tukey's HSD post hoc tests were used to differentiate between the groups. Results: A significant effect of treatment was found in the ANOVA of both PVT parameters, VigTrack mean reaction time and SSS. There was a statistically significant effect of fatigue group on all PVT parameters and VigTrack mean percentage omissions, where FINT and FRES scored better than FVUL. There was a significant interaction effect between treatment and fatigue group for PVT number of lapses. This is congruent for the AUC analyses in which for all parameters (except for the SSS) the performance of the FVUL group was consistently worse than that of the FINT and FRES groups. Discussion: This study demonstrates that the performance of individuals with different fatigue tolerances are differently affected by simulants after a limited period of sleep deprivation. The classification of fatigue tolerance through PVT lapses when sleep deprived seems to be able to predict this.

Fatigue in Aviation: Safety Risks, Preventive Strategies and Pharmacological Interventions.

Fatigue poses an important safety risk to civil and military aviation. In addition to decreasing performance in-flight (chronic) fatigue has negative long-term health effects. Possible causes of fatigue include sleep loss, extended time awake, circadian phase irregularities and work load. Despite regulations limiting flight time and enabling optimal rostering, fatigue cannot be prevented completely. Especially in military operations, where limits may be extended due to operational necessities, it is impossible to rely solely on regulations to prevent fatigue. Fatigue management, consisting of preventive strategies and operational countermeasures, such as pre-flight naps and pharmaceuticals that either promote adequate sleep (hypnotics or chronobiotics) or enhance performance (stimulants), may be required to mitigate fatigue in challenging (military) aviation operations. This review describes the pathophysiology, epidemiology and effects of fatigue and its impact on aviation, as well as several aspects of fatigue management and recommendations for future research in this field.

The Effect of Using the Lower Limit of Normal 2.5 in Pulmonary Aeromedical Assessments.

INTRODUCTION: Many regulations for aeromedical assessments state that a ratio between forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of < 0.7 should be evaluated by a pulmonary specialist. The Global Lung Initiative (GLI) reference values introduced the lower limit of normal (LLN 2.5), in which the lowest 2.5% of the population is regarded as abnormal, instead of a fixed ratio. This study assesses the impact of adopting GLI reference values on aeromedical evaluation and referrals.METHODS: The Royal Netherlands Air Force performed 7492 aeromedical assessments between February 2012 and April 2017. Cases with FEV1/FVC < 0.7 from three groups were selected: 1) men < 25 yr; 2) men > 40 yr; and 3) women, with twice as many matched controls. Pearson's Chi-squared and Fisher's exact tests were used to analyze the data.RESULTS: From the database, 23 (group 1), 62 (group 2), and 7 (group 3) cases were selected, with 184 controls. Respectively, 17%, 84%, and 29% would not be referred using the GLI. In the controls, this would lead to one additional referral (group 1). Qualitative analysis of the cases who would not be referred using the GLI showed that no significant diagnoses would have been missed.DISCUSSION: Using the GLI LLN 2.5 reference values for pulmonary function tests leads to significantly fewer referrals to a pulmonary specialist without missing relevant pulmonary pathology in our aircrew. This would reduce resources spent on the assessment of aircrew without compromising flight safety.Wingelaar-Jagt YQ, Wingelaar TT, Bülbül M, vd Bergh PP, Frijters E, Staudt E. The effect of using the lower limit of normal 2.5 in pulmonary aeromedical assessments. Aerosp Med Hum Perform. 2020; 91(8):636-640.