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Central Sleep Apnea: Improvement With Acetazolamide Therapy

Central Sleep Apnea: Improvement With Acetazolamide Therapy Abstract • Respiratory rhythm during sleep may be dependent on blood pH with apneas being associated with alkalosis. Acidification may therefore have therapeutic value in some forms of sleep apnea. We administered acetazolamide to six patients with symptomatic central sleep apnea, a disorder of respiratory rhythm with little or no upper airway obstruction. Sleep studies were carried out before and after one week of drug therapy, during which time the mean arterial pH decreased from 7.42 to 7.34. All six patients had significant improvement, demonstrating a 69% reduction in total apneas. Five of the six patients reported better-quality sleep and decreased daytime hypersomnolence. Subsequent studies in normal subjects showed that acetazolamide, like other agents known to produce a metabolic acidosis, shifted the hypercapnic ventilatory response to the left 5±0.54 mm Hg. This may be important in mediating the observed decrease in apneas. (Arch Intern Med 1982;142:1816-1819). References 1. Guilleminault C, Tilkian A, Dement WC: The sleep apnea syndromes. Annu Rev Med 1976;27:465-484.Crossref 2. Simmons FB, Guilleminault C, Dement WC, et al: Surgical management of airway obstruction during sleep. Laryngoscope 1977;87:326-338.Crossref 3. Glenn WWL, Gee JBL, Cole DR, et al: Combined central and obstructive alveolar hyperventilation: Treatment by tracheostomy and diaphragm pacing. Am J Med 1978;64:39-49.Crossref 4. Guilleminault C, van den Hoed J, Mitler MM: Clinical overview of sleep apnea syndromes , in Guilleminault C, Dement W (eds): Sleep Apnea Syndromes . New York, Alan R Liss Inc, 1978, pp 1-12. 5. Bulow K: Respiration and wakefulness in sleep. Acta Physiol Scand 1963;59( (suppl 209) ):1-110.Crossref 6. Phillipson EA, Sullivan CE: Respiratory control mechanisms during NREM and REM sleep , in Guilleminault C, Dement W (eds): Sleep Apnea Syndromes . New York, Alan R Liss Inc, 1978, pp 47-62. 7. Reite M, Jackson D, Cahoon R, et al: Sleep physiology at high altitude. Electroencephalogr Clin Neurophysiol 1975;38:463-471.Crossref 8. Weil JV, Kryger MH, Scoggin CH: Sleep and breathing at high altitude , in Guilleminault C, Dement W (eds): Sleep Apnea Syndromes . New York, Alan R Liss Inc, 1978, pp 119-135. 9. Rechtschaffen A, Kales A: A Manual of Standardized Terminology, Techniques, and Scoring System for Sleep Stages of Human Subjects . Brain Information Service/Brain Research Institute, Los Angeles, University of California, 1968. 10. Forster HV, Dempsey JA, Thompson J, et al: Estimation of arterial Po2, Pco2, pH and lactate from arterialized venous blood. J Appl Physiol 1972;32:134-137. 11. Weil J, Byrne-Quinn E, Sodal I, et al: Hypoxic ventilatory drive in normal man. J Clin Invest 1970;49:1061-1072.Crossref 12. Sahn SA, Zwillich CW, Dick N, et al: Variability of ventilatory response to hypoxia and hypercapnia. J Appl Physiol 1977;43:1019-1025. 13. Fencl V, Vale JR, Brock JA: Respiration and cerebral blood flow in metabolic acidosis and alkalosis in humans. J Appl Physiol 1969;27:67-76. 14. Cunningham DJ, Shaw DG, Lahiri S, et al: Effects of maintained ammonium chloride acidosis on the relation between pulmonary ventilation and alveolar oxygen and carbon dioxide in man. Q J Exp Physiol 1961;46:323-334. 15. Bellville JW, Howland WS, Seed JC, et al: The effect of sleep on the respiratory response to carbon dioxide. Anesthesiology 1959;20:628-634.Crossref 16. Reed DJ, Kellogg RH: Changes in respiratory response to CO2 during nocturnal sleep at sea level and at altitude. J Appl Physiol 1958;13:325-330. 17. Fleetham JA, Mezon B, West P, et al: Chemical control of ventilation and sleep arterial oxygen saturation in patients with COPD. Am Rev Respir Dis 1980;122:583-589. 18. Cain SA: A ventilatory effect of carbonic anhydrase in man. Proc Soc Exp Biol Med 1961;106:7-10.Crossref 19. Cain SA, Otis AB: Carbon dioxide transport in anesthetized dogs during inhibition of carbonic anhydrase. J Appl Physiol 1961;16:1023-1028. 20. Galdston M: Respiratory and renal effects of a carbonic anhydrase inhibitor (Diamox) on acid-base balance in normal man and in patients with respiratory acidosis. Am J Med 1955;19:516-532.Crossref 21. Leaf A, Schwartz WB, Relman AS: Oral administration of a potent carbonic anhydrase inhibitor ('Diamox'). N Engl J Med 1954;250:759-763.Crossref 22. Agnew HW Jr, Webb WB, Williams RL: The first night effect: An EEG study of sleep. Psychophysiology 1966;2:263-266.Crossref 23. Block AJ, Wynne JW, Boysen PG, et al: Menopause, medroxyprogesterone and breathing during sleep. Am J Med 1981;70:506-510.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

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Publisher
American Medical Association
Copyright
Copyright © 1982 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1982.00340230056012
Publisher site
See Article on Publisher Site

Abstract

Abstract • Respiratory rhythm during sleep may be dependent on blood pH with apneas being associated with alkalosis. Acidification may therefore have therapeutic value in some forms of sleep apnea. We administered acetazolamide to six patients with symptomatic central sleep apnea, a disorder of respiratory rhythm with little or no upper airway obstruction. Sleep studies were carried out before and after one week of drug therapy, during which time the mean arterial pH decreased from 7.42 to 7.34. All six patients had significant improvement, demonstrating a 69% reduction in total apneas. Five of the six patients reported better-quality sleep and decreased daytime hypersomnolence. Subsequent studies in normal subjects showed that acetazolamide, like other agents known to produce a metabolic acidosis, shifted the hypercapnic ventilatory response to the left 5±0.54 mm Hg. This may be important in mediating the observed decrease in apneas. (Arch Intern Med 1982;142:1816-1819). References 1. Guilleminault C, Tilkian A, Dement WC: The sleep apnea syndromes. Annu Rev Med 1976;27:465-484.Crossref 2. Simmons FB, Guilleminault C, Dement WC, et al: Surgical management of airway obstruction during sleep. Laryngoscope 1977;87:326-338.Crossref 3. Glenn WWL, Gee JBL, Cole DR, et al: Combined central and obstructive alveolar hyperventilation: Treatment by tracheostomy and diaphragm pacing. Am J Med 1978;64:39-49.Crossref 4. Guilleminault C, van den Hoed J, Mitler MM: Clinical overview of sleep apnea syndromes , in Guilleminault C, Dement W (eds): Sleep Apnea Syndromes . New York, Alan R Liss Inc, 1978, pp 1-12. 5. Bulow K: Respiration and wakefulness in sleep. Acta Physiol Scand 1963;59( (suppl 209) ):1-110.Crossref 6. Phillipson EA, Sullivan CE: Respiratory control mechanisms during NREM and REM sleep , in Guilleminault C, Dement W (eds): Sleep Apnea Syndromes . New York, Alan R Liss Inc, 1978, pp 47-62. 7. Reite M, Jackson D, Cahoon R, et al: Sleep physiology at high altitude. Electroencephalogr Clin Neurophysiol 1975;38:463-471.Crossref 8. Weil JV, Kryger MH, Scoggin CH: Sleep and breathing at high altitude , in Guilleminault C, Dement W (eds): Sleep Apnea Syndromes . New York, Alan R Liss Inc, 1978, pp 119-135. 9. Rechtschaffen A, Kales A: A Manual of Standardized Terminology, Techniques, and Scoring System for Sleep Stages of Human Subjects . Brain Information Service/Brain Research Institute, Los Angeles, University of California, 1968. 10. Forster HV, Dempsey JA, Thompson J, et al: Estimation of arterial Po2, Pco2, pH and lactate from arterialized venous blood. J Appl Physiol 1972;32:134-137. 11. Weil J, Byrne-Quinn E, Sodal I, et al: Hypoxic ventilatory drive in normal man. J Clin Invest 1970;49:1061-1072.Crossref 12. Sahn SA, Zwillich CW, Dick N, et al: Variability of ventilatory response to hypoxia and hypercapnia. J Appl Physiol 1977;43:1019-1025. 13. Fencl V, Vale JR, Brock JA: Respiration and cerebral blood flow in metabolic acidosis and alkalosis in humans. J Appl Physiol 1969;27:67-76. 14. Cunningham DJ, Shaw DG, Lahiri S, et al: Effects of maintained ammonium chloride acidosis on the relation between pulmonary ventilation and alveolar oxygen and carbon dioxide in man. Q J Exp Physiol 1961;46:323-334. 15. Bellville JW, Howland WS, Seed JC, et al: The effect of sleep on the respiratory response to carbon dioxide. Anesthesiology 1959;20:628-634.Crossref 16. Reed DJ, Kellogg RH: Changes in respiratory response to CO2 during nocturnal sleep at sea level and at altitude. J Appl Physiol 1958;13:325-330. 17. Fleetham JA, Mezon B, West P, et al: Chemical control of ventilation and sleep arterial oxygen saturation in patients with COPD. Am Rev Respir Dis 1980;122:583-589. 18. Cain SA: A ventilatory effect of carbonic anhydrase in man. Proc Soc Exp Biol Med 1961;106:7-10.Crossref 19. Cain SA, Otis AB: Carbon dioxide transport in anesthetized dogs during inhibition of carbonic anhydrase. J Appl Physiol 1961;16:1023-1028. 20. Galdston M: Respiratory and renal effects of a carbonic anhydrase inhibitor (Diamox) on acid-base balance in normal man and in patients with respiratory acidosis. Am J Med 1955;19:516-532.Crossref 21. Leaf A, Schwartz WB, Relman AS: Oral administration of a potent carbonic anhydrase inhibitor ('Diamox'). N Engl J Med 1954;250:759-763.Crossref 22. Agnew HW Jr, Webb WB, Williams RL: The first night effect: An EEG study of sleep. Psychophysiology 1966;2:263-266.Crossref 23. Block AJ, Wynne JW, Boysen PG, et al: Menopause, medroxyprogesterone and breathing during sleep. Am J Med 1981;70:506-510.Crossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Oct 1, 1982

References