Naltrexone improves blood gas patterns in obstructive sleep apnoea syndrome through its influence on sleep

Endogenous opiates have been shown to depress ventilation, and could therefore play a role in sleep apnoea syndrome (SAS). Hence, opiate antagonists have been used to treat SAS. The improvement they seem to give in blood-gas monitoring could derive either from a direct blocking of endorphins that inhibit respiration or else, indirectly, through an influence on sleep patterns. The present study used a double blind cross-over protocol to investigate the relationships between the effects on blood-gas and on sleep patterns of the oral opiate antagonist naltrexone in obstructive SAS. Sleep patterns and transcutaneous blood gas (tcPO2 and tcPCO2) were recorded in parallel. Control recordings, without treatment, were carried out over two nights, followed by two nights of recording after administration either of naltrexone followed by a placebo or of a placebo followed by naltrexone. The number of obstructive apnoea and hypopnoea events per hour of sleep (Apnoea-Hypopnoea Index: AHI), of hypoxic events (defined as a tcPO2 fall of at least 10, 15 or 20 mm Hg) and of hypercapnic events (defined as a tcPCO2 increase of at least 5 mm Hg) were counted. A Metabolic Suffering Index (MSI) was calculated, defined as the product of the number, duration and magnitude of hypoxic and hypercapnic events. Compared to placebo, naltrexone resulted in significant improvements in blood-gas patterns for the duration and MSI of hypoxic events and for the number, duration and MSI of hypercapnic events. Likewise, compared to placebo, naltrexone induced significant decreases in total sleep time, slow-wave sleep and rapid eye movement (REM) sleep, and, on the other hand, significant increases in total wake time and in the number of wakenings per hour of sleep (Nw h-1). Certain naltrexone-linked blood-gas improvements were closely correlated with certain of the sleep pattern changes: the decrease in number and duration of hypoxic events correlated with REM-time decrease and the decrease in number and duration of hypercapnic events correlated with the increase in Nwh-1. These findings suggest that the improvement in blood-gas patterns induced by naltrexone in SAS may be mediated by sleep pattern effects: i.e. a decrease in REM-time and an increase in intra-sleep wakening.