Midazolam-Induced Cognitive Function Impairments and Treatment Effects of Flumazenil in Day-Case Colonoscopy Patients

• Main Authors: Yen-Hsuan Jsu, 徐晏萱
• Other Authors: Mau-Sun Hua
• Format: Others
• Language: en_US
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/98735426425300732876

碩士 === 國立臺灣大學 === 心理學研究所 === 96 === BACKGROUND AND AIMS: Midazolam is a widely used benzodiazepine sedative agent in endoscopy. Flumazenil is a benzodiazepine antagonist capable of reversing midazolam-induced state. The present study aimed to investigate the midazolam-induced cognitive vulnerability profile, the reversal effects and dose-dependent effect of flumazenil, and statistical feasibility of intrapersonal analysis adopting modified Reliable Change Index procedure. METHOD: Prospective, double-blinded and randomized studies were conducted. In study one, thirty patients undergoing sedative colonoscopy and twenty-five non-sedative, non-operated controls were recruited. A battery of neuropsychological tests was given at the entry of study, 15 and 120 minutes after midazolam infusion. Orientation, sustained attention, psychomotor speed, memory, working memory, and executive functions were assessed. In study two, 14, 18, and 19 patients were randomly assigned to receive three different amounts of flumazenil as follows: (i) midazolam only; (ii) midazolam and 0.1mg flumazenil; (iii) midazolam and 0.4mg flumazenil. Control group was the same as in study 1. Psychomotor speed and memory function were assessed before treatment and 15 minutes after drug infusion. RESULTS: Our results revealed that midazolam affected sustained attention (11%), psychomotor speed (48%), memory functions (up to 37%), and working memory (17%), whilst there was no effect on orientation and executive function. Midazolam-induced cognitive impairments generally spontaneously recovered in 2 hours, whereas residual memory impairments were still evident in 10% of the patients. Flumazenil largely reversed psychomotor and memory impairments, particularly the former at 15 minutes. High- rather than low- dosed flumazenil reversed psychomotor function completely. However, flumazenil regardless of the dose level failed to fully reversed memory impairments, but low dose seemed to act better in partially reversing memory impairment. CONCLUSIONS: Midazolam selectively affected sustained attention, psychomotor, and memory functions but these effects generally subsided in 2 hours. Flumazenil improved impaired performance on psychomotor better than memory functions. These reversal effects were dose-dependent, thereby degree of reversal seemed to depend on dosage. Intrapersonal analysis was more sensitive to drug-induced cognitive impairments since individuals’ cognitive changes were liable to be obscured by group mean data analysis. Strength and limitation of this procedure are discussed.