Background -Tiredness and daytime respiratory failure occur frequently in myotonic dystrophy. Sleep hypoxaemia was studied in 12 patients with myotonic dystrophy and correlations were sought with their daytime lung and respiratory muscle function. Methods -All patients underwent overnight sleep studies, clinical assessment, measurement of flow-volume loops and carbon monoxide transfer factor, arterial blood gas analysis, and physiological assessment of both thoracic muscle function and upper airways obstruction. Results -The mean nadir of oxygen saturation during sleep was 75% (95% confidence interval 69% to 81%). A mean of 3-4% of total sleep duration was spent at an oxygen saturation level below 85%.

We therefore conducted a double-blind, placebo-controlled, cross-over study of baclofen 25 mg, administered before sleep in 10 snorers with mild sleep-disordered breathing (respiratory disturbance index <30 events per sleep hour). Each subject underwent two standard polysomnographic assessments, one week apart.Total sleep time was significantly prolonged by baclofen (placebo 356±9.9 SEM min; baclofen 386±9.9 min). Both nonrapid eye movement(REM) and REM sleep duration were increased (nonREM: placebo 295±6.8 min; baclofen 311±8.9 min; REM: placebo 61±7.5 min; baclofen 76±9.0 min). Time spent awake after sleep onset was reduced after baclofen (placebo 71±10.3 min; baclofen 51±9.7 min). There was a slight reduction in mean overnight oxygen saturation (placebo 95.2±0.5%; baclofen 94.4±0.7%). The frequency of apnoeas plus hypopnoeas (respiratory disturbance index (RDI)) did not change significantly (placebo 9±1.8 events·h· -1 ; baclofen 13±3.4 events·h· -1 ).We conclude that a single, therapeutic dose of baclofen alters sleep architecture and produces a small reduction in mean sleep oxygen saturation, but does not significantly increase sleep-disordered breathing. Eur Respir J., 1995, 8, 230-234 Baclofen is a centrally-acting gamma aminobutyric acid (GABA)-B agonist with muscle relaxant and antispasmodic properties. It is widely used in the treatment of painful spasms in patients with spinal cord lesions, multiple sclerosis and other neurological disorders [1]. It has also been used experimentally to treat periodic limb movements during sleep [2]. GABA is a neurotransmitter with mainly inhibitory effects in the central nervous system and appears to decrease central ventilatory drive. It has been shown to decrease ventilation and ventilatory responsiveness to hypercapnia in experimental animals [3][4][5], and is a putative mediator of hypoxic ventilatory depression [6].In a preliminary study, we found a high prevalence of significant nocturnal hypoxia in quadriplegic patients [7]. Subsequent polysomnographic studies of 40 quadriplegics from the same population (unpublished data) have shown a high prevalence of obstructive sleep apnoea (OSA); which concurs with the results of preliminary studies reported by other groups [8][9][10]. We conducted a survey of quadriplegic patients in South Australia, and found that 75% were treated with baclofen at an average evening dose of 30 mg (range 10-50 mg); whereas, other anti-spasmodic agents were used less frequently (diazepam, 5-10 mg nocte in 58%, and dantrolene in 28%). It seemed important, therefore, to objectively assess the effects of baclofen on breathing during sleep.We hypothesized that the adverse effects of baclofen on respiratory control would be most evident during sleep, especially in patients with a pre-existing tendency to sleep-disordered breathing. Because of its muscle relaxant properties, baclofen could increase the tendency to upper airway collapse during sleep and increase obstructive apnoeas (e.g. in snorers); whilst its depressant effect on respiratory dr...

This study was designed to determine the effect of inhaled N-formyl-methionyl-leucyl-phenylalanine (FMLP) on microvascular permeability in the rabbit trachea and to determine if the effect could be modified by cholinergic antagonism, neutral endopeptidase (NEP) inhibition, opioid receptor antagonism, or an opioid agonist. New Zealand White rabbits were anesthetized and pretreated intravenously with one of the following: saline, dimethyl sulfoxide (DMSO) (both controls), thiorphan, phosphoramidon (both NEP inhibitors), thiorphan and naloxone, morphine, or atropine. All rabbits were then given intravenous Evans blue before inhalation of nebulized DMSO (control) or FMLP. Extravascular tracheal Evans blue concentration was subsequently determined spectrophotometrically. FMLP caused a highly significant increase in microvascular permeability (92.6 +/- 7.1 micrograms/g of trachea, control 20.4' +/- 3.4). The effect of FMLP was significantly modified by cholinergic blockade (61.1 +/- 6.9) and by NEP inhibition (thiorphan 38.8 +/- 5.6, phosphoramidon 52.6 +/- 4.2). This effect of NEP inhibition could be reversed by concurrent treatment with the opioid receptor antagonist naloxone (95.9 +/- 34.6). Morphine had no significant effect. We concluded that FMLP increases microvascular permeability, which may in part explain the effect of FMLP on airway resistance in the rabbit. Inhibiting NEP decreases the response possibly through an effect on endogenous opioids. The response appears to be partially vagally mediated.