Simulated Sustained Flight Operations and Performance, Part 1: Effects of Fatigue

Sustained flight operations are likely to produce fatigue and performance decrement in aviators. We assessed changes in cognitive performance using a work/rest schedule modeled on successive long-range attack missions. Twelve subjects performed several subtests of the Unified Tri-Service Cognitive Performance Assessment Battery and the Walter Reed Performance Assessment Battery 18 times during a simulated sustained operation. The scenario consisted of a 9-hr planning session followed by a 4-hr rest period and a 14-hr daytime mission. After 6 hr of rest, subjects repeated this schedule with a nighttime mission. For two spatial tests, subjects showed linear increases in response rate and one of its components, error rate. Subjects appeared to change strategy as the study progressed, possibly exchanging a higher failure rate for a savings in time. Any tendency to take chances when fatigued may have serious implications for aircrew in sustained operations

Chronopharmacokinetics and Chronopharmacodynamics of Dextromethamphetamine in Man

Stimulants, in particular the amphetamines, have been studied as countermeasures to fatigue induced by circadian desynchronosis and extended flight operations. To make recommendations concerning the use of dextromethamphetamine for operational tasks, its chronopharmacokinetic and chronopharmacodynamic profiles and influence on circadian rhythms as a countermeasure to performance deficits and fatigue were studied. Ten male volunteers, divided into two groups of five each, were given 30 mg/70 kg of oral dextromethamphetamine during two test sessions one week apart and were evaluated with cognitive (dichotic listening, pattern recognition, and compensatory tracking), subjective (fatigue scale), and physiologic (blood pressure) testing. Session order was counterbalanced with dextromethamphetamine administration at either 8:40 AM or 8:40 PM during session one and a crossover to the other time during session two. Subjective and cognitive testing was begun 1.5 hours before dextromethamphetamine administration and continued every half hour until 12.5 hours after administration. Blood pressure was measured immediately before behavioral testing. Serum and urine were collected at regular intervals for gas chromatography/mass spectrometer analysis of methamphetamine and one of its metabolites, amphetamine. No differences were found in the day-versus-night pharmacokinetic profile of dextromethamphetamine. Cognitive performance and subjective fatigue improved after daytime administration of dextromethamphetamine in comparison to performance before drug administration. This effect was suppressed during the circadian trough, which occurred approximately 8 hours into the night sessions (4:30 AM). No correlations were seen between serum concentration of methamphetamine and measured behavioral parameters

GC-MS Determination of Amphetamine and Methamphetamine in Human Urine for 12 Hours Following Oral Administration of Dextro-Methamphetamine: Lack of Evidence Supporting the Established Forensic Guidelines for Methamphetamine Confirmation

Ten human volunteers, naive to amphetamines and divided into two groups of five each, were given an oral dose of 30 mg/70 kg D-methamphetamine in one of two different paradigms: the initial dose at 0930 h or the initial dose at 2130 h. One week later, each subject was crossed over with regard to time but given the same dose. A total of 214 urine specimens were collected either prior to dosing or at each micturition for a 12-h period post dose. Specimens were analyzed on a blind basis for methamphetamine and one of its metabolites, amphetamine, by gas chromatography-mass spectrometry (GC-MS) using coinjection of extracted sample and pentafluoropropionic anhydride and selected-ion monitoring. Approximately 20% of the D-methamphetamine was recovered unchanged from the urine specimens, and 2% was recovered as amphetamine. The mean urine methamphetamine concentration in both groups reached a maximum within 4-6 h and declined thereafter. A residual amount of methamphetamine was found in some predose specimens at the crossover evaluation, reflecting that methamphetamine may be detected in urine for up to 7 days. The amphetamine concentration reached a plateau by 4-6 h. This observation coupled with the finding that all subjects excreted approximately 2% of the methamphetamine dose as amphetamine suggested a saturable process for its biotransformation. Concentrations of both methamphetamine and amphetamine tended to be higher, but were not significantly different, for night administration. Methamphetamine concentrations were consistently greater than the 500-ng/mL cutoff in most post-dosing specimens, whereas amphetamine concentrations generally did not achieve the 200-ng/mL cutoff specified by the Substance Abuse and Mental Health Services Administration (SAMHSA) guidelines for GC-MS confirmation of methamphetamine. Some specimens containing methamphetamine had no amphetamine metabolite. The current guidelines would have resulted in 90.2% of the specimens containing methamphetamine being ruled negative by confirmation following either night or day administration, whereas one subject following the initial day administration and another following night crossover administration would have been judged positive at most time intervals. These findings suggest that the current SAMHSA guidelines select for individual metabolic variations and that GC-MS confirmation of methamphetamine will result in most occasional users being ruled negative following an oral dose of methamphetamine while some will be ruled positive

Simulated Sustained Flight Operations and Performance, Part 2: Effects of Dextro-Methamphetamine

As aircrew performance declines during periods of sustained flight operations (SUSOPs), countermeasures become more important. This study examined the ability of the central nervous system stimulant d-methamphetamine to ameliorate the detrimental effects of a simulated SUSOP on subjective fatigue and cognitive performance. Subjects (N = 25) repeatedly completed three subjective questionnaires and several subtests of the Unified Tri-Service Cognitive Performance Assessment Battery (UTC-PAB) and the Walter Reed Performance Assessment Battery (WR-PAB) during a simulated SUSOP. The scenario consisted of a 9-hr planning session followed by 4 hr of rest and a 14-hr mission. After 6 hr of rest, the 9 hr-4 hr-14 hr work-rest-work pattern was repeated. In a double-blind procedure, 13 subjects were administered 10mg/70kg body weight of d-methamphetamine 4 hr 20 min into the second mission, whereas the other 12 subjects received a placebo. Consistent with our preceding article in this series (Neri, Shappell, & DeJohn, 1992), the aircrew appeared to shift from a conservative to a more risky response strategy as the simulated SUSOP progressed. Administration of d-methamphetamine reduced subjective fatigue, improved performance, and lessened the apparent risky behavior on two spatial memory tasks