Evaluation of the effect of modafinil in conditions of sleep deprivation and fatigue in the medical profession
Creators: name: Sugden, Colin Alisdair
Publisher: name: Imperial College London
Year: 2014

description: Aims and objectives This thesis aimed to investigate the use of modafinil to reverse the effects of sleep deprivation and fatigue in the medical profession. The objectives were to: (1) determine the pattern of expected cognitive and clinical psychomotor effects of sleep deprivation and fatigue in the context of the medical profession, (2) investigate the subjective and objective effects of modafinil on the performance of sleep deprived participants using a battery of carefully selected cognitive and clinical tasks, (3) investigate the subjective and objective effects of modafinil on the performance of acutely fatigued subjects using a battery of carefully selected tasks. Methods Objective 1: A systematic review of the sleep deprivation and fatigue literature was performed Objective 2: Two double blind, placebo controlled, randomised trials were performed. In the first study participants were randomised to receive either modafinil or placebo following extended wakefulness. Cognitive tasks and a virtual reality laparoscopic skill simulator were used to assess performance. In the second study, participants took part in a counterbalanced crossover study in which they were allocated to all three study conditions (rest, sleep deprivation, sleep deprivation and modafinil) in a randomised order. A surgical performance monitoring task and a matched neurobehavioural task were used to assess performance and Near Infrared Spectroscopy was used to record cortical haemodynamics. Objective 3: (i) Two studies were carried out with the aim of developing and validating a series of virtual reality intubation and extubation tasks. In the first study a battery of intubation assessment tasks was identified. Comparisons between novice and experienced colonoscopists led to the isolation of tasks that possessed construct validity. In the second study, a series of colonoscopy extubation tasks was developed and validated by comparing the performance of cohorts of experienced and novice colonoscopists. (ii) An experimentally induced acute mental fatigue protocol was developed and a single blind randomised controlled trial was performed to investigate the effect of acute mental fatigue on colonoscopy performance. (iii) Two studies were carried out to investigate strategies to ameliorate the effects of acute mental fatigue on colonoscopy performance. In the first study the acute mental fatigue protocol was administered to all participants following which they were randomly allocated to either receive no intervention or a “goal setting” psychological intervention. Performance was assessed using the colonoscopy task battery. In the second study a double blind, placebo controlled randomised trial was performed to investigate the effect of modafinil on the performance of participants following administration of the acute mental fatigue protocol. Again, performance was assessed using the colonoscopy task battery. (iv) One study was carried out to determine the pattern of effects of modafinil on sustained attention, visual perception, metacognition and working memory. In this randomised, placebo controlled, double blind study, rested participants were allocated to receive modafinil or lactose placebo and interrelated cognitive domains were assessed using a sophisticated neurocognitive task battery. Results Objective 1: Sleep loss was consistently associated with impaired attention, memory higher-order cognitive function and the performance of virtual reality laparoscopic skills tasks. No studies investigated the effect of acute mental fatigue. Objective 2: In the first study, modafinil was found to improve the performance of sleep deprived participants on tests of attention, impulsivity and working memory but did not improve the performance of a laparoscopic psychomotor skills task. In the second study, modafinil administration was again associated with a pronounced improvement in attention using a classical vigilance paradigm but was only associated with a small improvement in the performance of a matched surgical clinical performance monitoring task. Improved performance on the classical vigilance paradigm in the modafinil condition was associated with activation in the right Dorsolateral Prefrontal Cortex. Modafinil also improved performance and attenuated task disengagement following a high cognitive load divided attention and working memory task. Objective 3: (i) A comprehensive battery of valid intubation and extubation tasks was developed. (ii) An experimentally induced acute mental fatigue protocol was effective in inducing subjective feelings of fatigue. Acute mental fatigue was associated with impaired colonoscopy intubation performance but was not associated with impaired abnormality detection. (iii) The psychological “goal setting” intervention was not effective in improving intubation or extubation colonoscopy performance. Modafinil was found to be effective in improving both intubation and extubation colonoscopy performance. Participants in the modafinil group identified more abnormalities than those in the placebo group in all task conditions and this effect was predicted by Psychomotor Vigilance Task performance. (iv) Modafinil was found to improve vigilant attention and working memory in rested subjects and, in a visual perception and metacognition task, was found to improve performance without promoting over or underconfidence. Conclusions Sleep deprivation and fatigue impair cognitive and simulated clinical performance. Modafinil is effective in improving sustained attention, resilience to cognitive load, impulsivity and working memory in conditions of sleep deprivation but less effective in improving simulated laparoscopic performance monitoring and ineffective in improving simulated laparoscopic psychomotor skill. Simulated colonoscopy intubation performance is degraded by acute mental fatigue and impaired extubation performance is associated with subjective feelings of fatigue. Psychological “goal setting strategies are ineffective in reversing these effects. However, modafinil is effective in improving intubation and extubation performance by promoting resilience to demanding mental work by improving sustained attention and visual perception without compromising introspective accuracy.