title: Exacerbation of obstructive sleep apnea by oral indomethacin.
abstract: Patients with obstructive sleep apnea (OSA) are predisposed to instability in central ventilatory control during sleep. Increased instability, as reflected in an enhanced expired volume in per unit time loop gain, has been associated with a greater predisposition to upper airway collapse. Here, in an otherwise healthy patient with untreated mild OSA, we describe the further exacerbation of OSA after oral indomethacin administration. The subject was a control subject in part of a study to investigate the effects of altering cerebral blood flow (CBF) on ventilatory responses and sleep. He was administered either placebo or 100 mg of indomethacin orally with 20 mL of antacid 2.5 h before sleep on different days. He was studied overnight by polysomnography, arterial blood gases, and transcranial Doppler ultrasound. Administration of 100 mg of oral indomethacin prior to sleep resulted in an almost doubling of the apnea-hypopnea index (14 to 24/h), compared with placebo. This was due to an increase in apneas, rather than hypopneas. Following the indomethacin, changes in arterial blood gases were unremarkable, but both CBF as indexed using transcranial Doppler ultrasound and CBF reactivity to a steady-state change in CO(2) (CBF-CO(2)) reactivity were reduced, and the ventilatory response to CO(2) was elevated. CBF was also further reduced during nonrapid eye movement sleep following the indomethacin when compared with the control night. Indomethacin-induced reductions in CBF and CBF-CO(2) reactivity and related increases in ventilatory instability may lead to a greater predisposition to upper airway collapse and related apnea; these factors may partly explain the exacerbation of OSA.
authors.affiliation: Peninsula Sleep Laboratory, Ste 3, Level 2, Frenchs Forest, NSW, Australia. krburgess@optusnet.com.au
authors.forename: Keith R
authors.initials: KR
authors.lastname: Burgess
authors.forename: Jue-Lin
authors.initials: JL
authors.lastname: Fan
authors.forename: Karen
authors.initials: K
authors.lastname: Peebles
authors.forename: Kate
authors.initials: K
authors.lastname: Thomas
authors.forename: Sam
authors.initials: S
authors.lastname: Lucas
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lucas
authors.forename: Andrew
authors.initials: A
authors.lastname: Dawson
authors.forename: Marianne
authors.initials: M
authors.lastname: Swart
authors.forename: Kelly
authors.initials: K
authors.lastname: Shepherd
authors.forename: Phil
authors.initials: P
authors.lastname: Ainslie
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D012008:Recurrence; D020181:Sleep Apnea, Obstructive / Q000139:chemically induced* / Q000503:physiopathology; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin