Benzodiazepine receptor antagonist (flumazenil) does not affect sleep-related breathing disorders

Abstract

B Be en nz zo od di ia az ze ep pi in ne e r re ec ce ep pt to or r a an nt ta ag go on ni is st t ( (f fl lu um ma az ze en ni il l) ) d do oe es s n no ot t a af ff fe ec ct t s sl le ee ep p--r re el la at te ed d b br re ea at th hi in ng g d di is so or rd de er rs s ABSTRACT: Benzodiazepine drugs may impair breathing during sleep, leading to the development of sleep-disordered breathing or, in subjects with sleep apnoea, an increase in the severity of pre-existing apnoeas. Flumazenil is a selective benzodiazepine-antagonist. We hypothesized that endogenous ligands of benzodiazepine receptors might contribute to the pathogenesis of obstructive sleep apnoea syndrome (OSAS) and that the intensity of OSAS could, therefore, be reduced by flumazenil.Ten male patients (mean age 55 yrs, mean body mass index 42.4 kg·m -2 , mean apnoea index (AI) 53.5 and mean respiratory disturbance index (RDI) 74.2) were investigated. None of the patients had been treated for OSAS prior to the study. The study design was randomized, single-blind, placebo-controlled and cross-over. On the first or second study night, patients were randomly assigned to receive i.v. flumazenil (2 mg) or placebo (0.9% NaCl) between 01:00 and 01:30 h.Comparing the polysomnographic results of the placebo night and the flumazenil night in all 10 patients, no significant differences were found regarding obstructive events or sleep architecture. Accordingly, the data concerning sleep-disordered breathing and sleep stages during the 30 min period prior to and the 30 min period following the administration of flumazenil did not differ.It is concluded that endogenous ligands of the benzodiazepine receptor play no role in the pathogenesis of obstructive sleep apnoea syndrome, since respiratory and sleep data are not altered by flumazenil. Therefore, attempts to treat obstructive sleep apnoea syndrome with flumazenil do not seem to be warranted.

Sleep and Anesthesia

“…However, for the sleep deprived patients, it rather lengthens sleep onset latency and disturbs SWS [77]. Moreover, according to the study conducted by Schönhofer and Kohler [78], it has no effect on respiratory pathway thus can be applied to the patients with OSAS.…”