sodium-oxybate and Apnea

Sodium oxybate (SXB) was administered for the first time in 1979 in 16 patients with narcolepsy with cataplexy (NT1) that improved up to 20 months.. To evaluate the effect of SXB on daytime sleepiness and sleep architecture by video-polysomnography in a sample of 23 NT1 adult patients (13 men, 10 females) treated up to three years. Additional goal was to study the presence of sleep comorbidities.. NT1 patients were diagnosed according to International Classification of Sleep Disorders, third edition. We conducted a longitudinal observational study and a video-polysomnography comparing the sleep parameters of patients treated with an initial nocturnal dose of 4.5 g of SXB after six months (FU-1), one year (FU-2) and three years (FU-3) of uninterrupted treatment. Video-polysomnography parameters were analyzed including apnea-hypopnea and periodic leg movements indexes.. Patients were HLA-DQB1*06:02 positive except a familial case. Thirteen patients (56%) discontinued SXB treatment over the three-year of the study. The two-nightly doses has been one of the reason for discontinuing treatment as well as insufficient compliance, mild or severe side effects, comorbidities and pregnancy. We found significant differences at FU-2 in sleep structure with an increased in stage N2 (p < 0.03) and a higher periodic leg movements index (p < 0.01). At FU-3 we found significant differences in sleep structure with an increase in stage N1 (p = 0.03) and in comorbidities (periodic leg movements and apnea-hypopnea indexes). There was not significant change on daytime sleepiness during the study.. SXB was administered in low-medium doses. Two-nightly doses and sleep fragmentation linked to sleep comorbidities at long-term lead to drug withdrawal.. Efecto a largo plazo del oxibato de sodio en la somnolencia diurna y en la estructura del sueño en pacientes con narcolepsia de tipo 1.. Introducción. El oxibato de sodio (SXB) se utilizó en 1979 en 16 enfermos con narcolepsia-cataplejía (NT1) que mejoraron tras 20 meses de tratamiento. Objetivos. Evaluar el efecto del SXB en la somnolencia diurna y en la estructura del sueño mediante videopolisomnografía en una muestra de 23 enfermos de NT1 (13 hombres y 10 mujeres) tratados durante tres años. Investigamos adicionalmente la presencia de comorbilidad. Pacientes y métodos. Diagnosticamos a los enfermos de acuerdo con la Clasificación Internacional de Trastornos del Sueño, tercera edición. Realizamos un estudio longitudinal, observacional y de videopolisomnografía, comparando los parámetros de sueño y los índices de apnea-hipopnea y de movimientos periódicos de las piernas de los enfermos, tratados con una dosis nocturna inicial de 4,5 g de SXB al cabo de seis meses (C-1), un año (C-2) y tres años (C-3) de tratamiento ininterrumpido. Resultados. Todos los enfermos eran HLA-DQB1*06:02 positivos, excepto un caso familiar. Trece enfermos (56%) interrumpieron el tratamiento debido a las dos tomas nocturnas, así como a la presencia de efectos secundarios, comorbilidad y embarazo. Encontramos diferencias significativas en C-2 en la estructura del sueño con aumento del estadio N2 (p < 0,03) y del índice de movimientos periódicos de las piernas (p < 0,01). En el control C-3 encontramos diferencias significativas en la estructura del sueño con aumento del estadio N1 (p = 0,03), y de los índices de movimientos periódicos de las piernas y de apnea-hipopnea. Conclusiones. El SXB se administró en dos dosis nocturnas, lo que, unido a la fragmentación del sueño y a la aparición de comorbilidades, condujo a la interrupción del tratamiento a largo plazo.

Topics: Adult; Apnea; Female; Follow-Up Studies; Humans; Male; Narcolepsy; Sleep; Sodium Oxybate

I.v. administration of sodium hydroxybutyrate induced periodic apneustic breathing with inspiratory arrests in anesthetised cats. Bilateral vagotomy did not change respiratory or circulatory parameters under these conditions. Administration of the same agent into both nuclei tractus solitarii induced similar effects, as well as administration of the GABA agonist baclofen. The data obtained suggest that the medullary GABA-ergic system takes an active part in generation of the respiration rhythm.

Topics: Animals; Apnea; Baclofen; Cats; Electromyography; Female; gamma-Aminobutyric Acid; Male; Medulla Oblongata; Periodicity; Receptors, GABA; Respiration; Respiratory Muscles; Sodium Oxybate

Experiments on sodium pentobarbital (40 mg/kg i.p.) anesthetized mongrel cats of either sex weighing from 2.25 to 4.25 kg showed that administration of sodium hydroxybutyrate (200 mg/kg, i.v.) resulted in periodic apneic breathing with inspiratory arrests in more than 80%. An abrupt decrease of respiratory rate and thus ventilation was conditioned by a prolonged activation of inspiratory muscles (diaphragm and external intercostals). Under these conditions, the activity of expiratory muscles (internal intercostals and abdominal muscles) was not depressed. The changes in the respiratory pattern were not due to alterations in systemic hemodynamics. The periodic breathing affected the arterial blood components as follows: the most pronounced variations were in pO2 less pronounced ones in pCO2 and the smallest ones in pH. After the periodic apneic breathing formation, vagotomy either produced no marked alterations in the respiratory pattern or even promoted restoration of more regular breathing. It is assumed that the activation of GABA-ergic system of the brain can interfere with the generation of the respiratory rhythm depressing the "switch-off" mechanism and breaking the vagal afferent transmission to the neurons of respiratory centre.

Topics: Afferent Pathways; Animals; Apnea; Brain; Cats; Electromyography; Female; Hemodynamics; Lung; Male; Periodicity; Receptors, GABA-A; Sodium Oxybate; Time Factors; Vagotomy