piperidines and Sleep-Apnea--Central

There are no pharmacological treatments for obstructive sleep apnea syndrome, but dronabinol showed promise in a small pilot study. In anesthetized rats, dronabinol attenuates reflex apnea via activation of cannabinoid (CB) receptors located on vagal afferents; an effect blocked by cannabinoid type 1 (CB1) and/or type 2 (CB2) receptor antagonists. Here, using a natural model of central sleep apnea, we examine the effects of dronabinol, alone and in combination with selective antagonists in conscious rats chronically instrumented to stage sleep and measure cessation of breathing.. Adult male Sprague-Dawley rats were anesthetized and implanted with bilateral stainless steel screws into the skull for electroencephalogram recording and bilateral wire electrodes into the nuchal muscles for electromyogram recording. Each animal was recorded by polysomnography on multiple occasions separated by at least 3 days. The study was a fully nested, repeated measures crossover design, such that each rat was recorded following each of 8 intraperitoneal injections: vehicle; vehicle and CB1 antagonist (AM 251); vehicle and CB2 antagonist (AM 630); vehicle and CB1/CB2 antagonist; dronabinol; dronabinol and CB1 antagonist; dronabinol and CB2 antagonist; and dronabinol and CB1/CB2 antagonist.. Dronabinol decreased the percent time spent in rapid eye movement (REM) sleep. CB receptor antagonists did not reverse this effect. Dronabinol also decreased apneas during sleep, and this apnea suppression was reversed by CB1 or CB1/CB2 receptor antagonism.. Dronabinol's effects on apneas were dependent on CB1 receptor activation, while dronabinol's effects on REM sleep were CB receptor-independent.

Topics: Animals; Cannabinoid Receptor Agonists; Cannabinoid Receptor Antagonists; Disease Models, Animal; Dronabinol; Electroencephalography; Electromyography; Indoles; Male; Piperidines; Polysomnography; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Respiration; Sleep; Sleep Apnea, Central; Sleep, REM; Vagus Nerve

The authors report the case of a patient suffering from central sleep apnea (CSA) who underwent neurosurgery for ventriculo-peritoneal derivation under general anesthesia. Given the risk of postoperative hypoventilation in CSA, intraoperative anesthesia was induced using remifentanyl, an opiate with a plasma half-life of less than 5 minutes. Propofol (2 mg/kg) and remifentanyl at a dose of 0.5 microgram/kg was used during induction. The patient was curarised with vecuronium bromide, intubated and ventilated with a mixture of O2/N2O. During the operation, remifentanyl was administered as a continuous infusion at a starting dose of 0.2 microgram/kg/min, subsequently modified according to changes in arterial pressure and heart rate. At the end of surgery, which lasted approximately 120", decurarisation was carried out using prostigmin, and the infusion of remifentanyl was suspended, together with N2O. Reawakening times were recorded. Extubation took place 8' and 30" after the suspension of remifentanyl. Postoperative monitoring of SpO2 continued for 1 h and blood-gas analysis was satisfactory. No hypoventilation episodes were reported throughout the postoperative period and the patient was discharged from hospital after 7 days. The authors consider that remifentanyl should be the drug of choice to guarantee intraoperative analgesia in patients suffering from CSA requiring general anesthesia.

Topics: Aged; Anesthesia, General; Anesthetics, Intravenous; Humans; Hydrocephalus; Male; Piperidines; Remifentanil; Sleep Apnea, Central; Ventriculoperitoneal Shunt