Sleep and GER

  • Susan M. Harding
Part of the Respiratory Medicine book series (RM, volume 2)


Gastroesophageal reflux (GER) occurs during sleep. During sleep time, GER events are caused by transient lower esophageal sphincter (LES) relaxations occurring during arousals from sleep. Sleep-related GER events occur more commonly out of arousals from stage N2 NREM sleep, especially during the first 2 h of the sleep period, and esophageal refluxate clearance is delayed during sleep. Prevalence of sleep-related GER approximates 79 % in GER patients and 25 % of the adult population. Symptoms of sleep-related GER include heartburn, regurgitation, arousals, awakenings, insomnia, unrefreshing sleep, daytime sleepiness, and fatigue. Patients with obstructive sleep apnea commonly have sleep-related GER, and treatment with nasal CPAP improves sleep-related GER. The diagnosis of sleep-related GER is made on clinical grounds; however, esophageal testing is useful in selected patients. Treatment of sleep-related GER includes behavioral techniques and proton pump inhibitors (PPIs). There are less data available that address the role of surgical fundoplication and long-term medical therapy outcomes in sleep-related GER. Hopefully, future research will provide better insight.


Sleep-related GER Transient LES relaxations Upper esophageal sphincter Insomnia Sleep quality Arousals Wake time sleepiness Obstructive sleep apnea Nasal CPAP Proton pump inhibitors 


  1. 1.
    Harding SM. Sleep-related gastroesophageal reflux: evidence is mounting. Clin Gastroenterol Hepatol. 2009;7:919–20.PubMedCrossRefGoogle Scholar
  2. 2.
    Harding SM. Gastroesophageal reflux during sleep. Sleep Med Clin. 2007;2:41–50.CrossRefGoogle Scholar
  3. 3.
    Lagergren J, Bergström R, Lindgren A, et al. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med. 1998;345:825–31.Google Scholar
  4. 4.
    Green BT, Broughton WA, O’Connor JB, et al. Marked improvement in nocturnal gastroesophageal reflux in a large cohort of patients with obstructive sleep apnea treated with continuous positive airway pressure. Arch Intern Med. 2003;163:41–5.PubMedCrossRefGoogle Scholar
  5. 5.
    Orr WC, Craddock A, Goodrich S. Acidic and non-acidic reflux during sleep under conditions of powerful acid suppression. Chest. 2007;131:460–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Kahrilas PJ, Dodds WJ, Dent J, et al. Effect of sleep, spontaneous gastroesophageal reflux, and a meal on upper esophageal sphincter pressure in normal human volunteers. Gastroenterology. 1987;92:466–71.PubMedGoogle Scholar
  7. 7.
    Bajaj JS, Bajaj S, Dua KS, et al. Influence of sleep stages on esophago-upper esophageal sphincter contractile reflex and secondary esophageal peristalsis. Gastroenterology. 2006;130:17–25.PubMedCrossRefGoogle Scholar
  8. 8.
    Mittal RK, Balaban DH. The esophagogastric junction. N Engl J Med. 1997;336:924–32.PubMedCrossRefGoogle Scholar
  9. 9.
    Elsenbruch S, Orr WC, Harnish MJ, et al. Disruption of normal gastric myoelectric functioning by sleep. Sleep. 1999;22:453–8.PubMedGoogle Scholar
  10. 10.
    Sexton MW, Harding SM. Sleep-related reflux: a unique clinical challenge. J Respir Dis. 2003;24:398–406.Google Scholar
  11. 11.
    Dickman R, Parthasarathy S, Malagon IB, et al. Comparisons of the distribution of oesophageal acid exposure throughout the sleep period among the different gastro-oesophageal reflux diseases groups. Aliment Pharmacol Ther. 2007;26:41–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Orr WC, Heading R, Johnson LF, et al. Sleep and its relationship to gastroesophageal reflux. Aliment Pharmacol Ther. 2004;20 Suppl 9:39–46.PubMedCrossRefGoogle Scholar
  13. 13.
    Orr WC. Review article: sleep-related gastro-oesophageal reflux as a distinct clinical entity. Aliment Pharmacol Ther. 2010;31:47–56.PubMedCrossRefGoogle Scholar
  14. 14.
    Dickman R, Green C, Fass SS, et al. Relationships between sleep quality and pH monitoring findings in persons with gastroesophageal reflux disease. J Clin Sleep Med. 2007;3:505–13.PubMedGoogle Scholar
  15. 15.
    Poh CH, Gasiorowska AL, et al. Conscious awakenings are commonly associated with acid reflux events in patients with gastroesophageal reflux disease. Clin Gastroenterol Hepatol. 2010;8:851–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Budhiraja R, Quan SF, Punjabi NM, et al. Power spectral analysis of the sleep electroencephalogram in heartburn patients with or without gastroesophageal reflux disease: a feasibility study. J Clin Gastroenterol. 2010;44:91–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Orr WC, Elsenbruch S, Harnish MJ, et al. Proximal migration of esophageal acid perfusions during waking and sleep. Am J Gastroentrol. 2000;95:37–42.CrossRefGoogle Scholar
  18. 18.
    Fass R, Quan SF, O’Connor GT, et al. Predictors of heartburn during sleep in a large prospective cohort study. Chest. 2005;127:1658–66.PubMedCrossRefGoogle Scholar
  19. 19.
    Hila A, Castell DO. Nighttime reflux is primarily an early event. J Clin Gastroenterol. 2005;39:579–83.PubMedCrossRefGoogle Scholar
  20. 20.
    Allen L, Poh CH, Gasiorowska A, et al. Increased oesophageal acid exposure at the beginning of the recumbent period is primarily a recumbent-awake phenomenon. Aliment Pharmacol Ther. 2010;32:787–94.PubMedCrossRefGoogle Scholar
  21. 21.
    Sontag SJ, O’Connell S, Miller TQ, et al. Asthmatics have more nocturnal gasping and reflux symptoms than nonasthmatics, and they are related to bedtime eating. Am J Gastroenterol. 2004;99:789–96.PubMedCrossRefGoogle Scholar
  22. 22.
    Khoury RM, Camacho-Lobato L, Katz PO, et al. Influence of spontaneous sleep positions on nighttime recumbent reflux in patients with gastroesophageal reflux disease. Am J Gastroenterol. 1999;94:2069–73.PubMedCrossRefGoogle Scholar
  23. 23.
    Shaker R, Castell DO, Schoenfeld PS, et al. Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: the results of a Gallup survey conducted on behalf of the American Gastroenterological Association. Am J Gastroenterol. 2003;98:1487–93.PubMedCrossRefGoogle Scholar
  24. 24.
    Gerson LB, Fass R. A systematic review of the definitions, prevalence, and response to treatment of nocturnal gastroesophageal reflux disease. Clin Gastroenterol Hepatol. 2009;7:372–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Bruley des Varannes S, Errieau G, Tessier C. Two thirds of patients with gastroesophageal reflux have nocturnal symptoms: survey by 562 general practitioners of 36,663 patients. Presse Med. 2007;36(4 Pt 1):591–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Dean BB, Aguilar D, Johnson LF, et al. The relationship between the prevalence of nighttime gastroesophageal reflux disease and disease severity. Dig Dis Sci. 2010;55:952–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Orr WC, Goodrich S, Fernström P, et al. Occurrence of nighttime gastroesophageal reflux in disturbed and normal sleepers. Clin Gastroenterol Hepatol. 2008;6:1099–104.PubMedCrossRefGoogle Scholar
  28. 28.
    Orr WC, Allen ML, Robinson M. The pattern of nocturnal and diurnal esophageal acid exposure in the pathogenesis of erosive mucosal damage. Am J Gastroenterol. 1994;9:509–12.Google Scholar
  29. 29.
    Frazzoni M, De Micheli E, Savarino V. Different patterns of oesophageal acid exposure distinguish complicated reflux disease from either erosive reflux oesophagitis or non-erosive reflux disease. Aliment Pharmacol Ther. 2003;18:1091–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Orr WC, Lackey C, Robinson MG, et al. Esophageal acid clearance during sleep in patients with Barrett’s oesophagus. Dig Dis Sci. 1988;33:654–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Fass R, Achem SR, Harding S, et al. Supra-oesophageal manifestations of gastro-oesophageal reflux disease (GERD) and the role of nighttime gastro-oesophageal reflux. Aliment Pharmacol Ther. 2004;20 Suppl 9:26–38.PubMedCrossRefGoogle Scholar
  32. 32.
    Johnson DA, Orr WC, Crawley JA, et al. Effect of esomeprazole on nighttime heartburn and sleep quality in patients with GERD: a randomized placebo-controlled trial. Am J Gastroenterol. 2005;100:1914–22.PubMedCrossRefGoogle Scholar
  33. 33.
    DiMarino Jr JA, Banwait KS, Eschinger E, et al. The effect of gastro-oesophageal reflux and omeprazole on key sleep parameters. Aliment Pharmacol Ther. 2005;22:325–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Fass R, Johnson DA, Orr WC, et al. The effect of dexlansoprazole MR on nocturnal heartburn and GERD-related sleep disturbances in patients with symptomatic GERD. Am J Gastroenterol. 2011;106:421–31.PubMedCrossRefGoogle Scholar
  35. 35.
    Thurnheer R, Henz S, Knoblauch A. Sleep-related laryngospasm. Eur Respir J. 1997;10:2084–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Gislason T, Janson C, Vermeire P, et al. Respiratory symptoms and nocturnal gastroesophageal reflux: a population-based study of young adults in three European countries. Chest. 2002;121:158–63.PubMedCrossRefGoogle Scholar
  37. 37.
    Valipour A, Makker KH, Hardy R, et al. Symptomatic gastroesophageal reflux in subjects with a breathing sleep disorder. Chest. 2002;121:1748–53.PubMedCrossRefGoogle Scholar
  38. 38.
    Morse CA, Quan SF, Mays MZ, et al. Is there a relationship between obstructive sleep apnea and gastroesophageal reflux disease? Clin Gastroenterol Hepatol. 2004;2:761–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Kim HN, Vorona RD, Winn MP, et al. Symptoms of gastro-oesophageal reflux disease and the severity of obstructive sleep apnoea syndrome are not related in sleep disorders center patients. Aliment Pharmacol Ther. 2005;21:1127–33.PubMedCrossRefGoogle Scholar
  40. 40.
    Guda N, Paratington S, Vakil N. Symptomatic gastro-oesophageal reflux, arousals and sleep quality in patients undergoing polysomnography for possible obstructive sleep apnoea. Aliment Pharmacol Ther. 2004;20:1153–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Friedman M, Gurpinar B, Lin H, et al. Impact of treatment of gastroesophageal reflux on obstructive sleep apnea-hypopnea syndrome. Ann Otol Rhinol Laryngol. 2007;116:805–11.PubMedGoogle Scholar
  42. 42.
    Wang L, Liu JX, Qin YX, et al. Research on the relationship between obstructive sleep apnea hypopnea syndrome and gastroesophageal reflux. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2009;44:26–30.PubMedGoogle Scholar
  43. 43.
    Wise SK, Wise JC, DelGaudio JM. Gastroesophageal reflux and laryngopharyngeal reflux in patients with sleep-disordered breathing. Otolaryngol Head Neck Surg. 2006;135:253–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Hawrylkiewicz I, Plywaczewski R, Dziedzic D, et al. Gastroesophageal reflux disease (GERD) in patients with obstructive sleep apnoea syndrome (OSAS). Pneumonol Alergol Pol. 2006;74:361–4.PubMedGoogle Scholar
  45. 45.
    Demeter P, Visy KV, Magyar P. Correlation between severity of endoscopic findings and apnea-hypopnea index in patients with gastroesophageal reflux disease and obstructive sleep apnea. World J Gastroenterol. 2005;11:839–41.PubMedGoogle Scholar
  46. 46.
    Berg S, Hoffstein V, Gislason T. Acidification of distal esophagus and sleep-related breathing disturbances. Chest. 2004;125:2101–6.PubMedCrossRefGoogle Scholar
  47. 47.
    Penzel T, Becker HF, Brandenburg U, et al. Arousal in patients with gastro-oesophageal reflux and sleep apnoea. Eur Respir J. 1999;14:1266–70.PubMedCrossRefGoogle Scholar
  48. 48.
    Crowell MD, Bradley A, Hansel S, et al. Obesity is associated with increased 48-h esophageal acid exposure in patients with symptomatic gastroesophageal reflux. Am J Gastroenterol. 2009;104:553–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Romero-Corral A, Caples SM, Lopez-Jimenez F, et al. Interactions between obesity and obstructive sleep apnea: implications for treatment. Chest. 2010;137:711–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Kuribayashi S, Massey BT, Hafeezullah M, et al. Upper esophageal sphincter and gastroesophageal junction pressure changes act to prevent gastroesophageal and esophagopharyngeal reflux during apneic episodes in patients with obstructive sleep apnea. Chest. 2010;137:769–76.PubMedCrossRefGoogle Scholar
  51. 51.
    Tishler PV, Larkin EK, Schluchter MD, et al. Incidence of sleep-disordered breathing in an urban adult population: the relative importance of risk factors in the development of sleep-disordered breathing. JAMA. 2003;289:2230–037.PubMedCrossRefGoogle Scholar
  52. 52.
    Bujanda L. The effects of alcohol consumption upon the gastrointestinal tract. Am J Gastroenterol. 2000;95:3374–82.PubMedCrossRefGoogle Scholar
  53. 53.
    Scanlan MF, Roebuck T, Little PJ, et al. Effect of moderate alcohol upon obstructive sleep apnoea. Eur Respir J. 2000;16:909–13.PubMedCrossRefGoogle Scholar
  54. 54.
    Tawk M, Goodrich S, Kinasewitz G, et al. The effect of 1 week of continuous positive airway pressure treatment in obstructive sleep apnea patients with concomitant gastroesophageal reflux. Chest. 2006;130:1003–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Shepherd K, Holloway RH, Hillman DR, et al. The impact of continuous positive airway pressure on lower esophageal sphincter. Am J Physiol Gastroenterol Liver Physiol. 2007;292:G1200–1205.CrossRefGoogle Scholar
  56. 56.
    Shepherd K, Hillman D, Holloway R, et al. Mechanisms of nocturnal gastroesophageal reflux events in obstructive sleep apnea. Sleep Breath. 2011;15:561–70.PubMedCrossRefGoogle Scholar
  57. 57.
    Stewart DL. Pantoprazole for sleepiness associated with acid reflux and obstructive sleep disordered breathing. Laryngoscope. 2004;114:1525–8.CrossRefGoogle Scholar
  58. 58.
    Orr WC, Robert JJ, Houck JR, et al. The effect of acid suppression on upper airway anatomy and obstruction in patients with sleep apnea and gastroesophageal reflux disease. J Clin Sleep Med. 2009;5:330–4.PubMedGoogle Scholar
  59. 59.
    Hirano I, Richter JE. Practice parameters committee of the American college of gastroenterology. ACG practice guidelines: esophageal reflux testing. Am J Gastroenterol. 2007;102:668–85.PubMedCrossRefGoogle Scholar
  60. 60.
    Mainie I, Tutuian R, Shay S, et al. Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy: a multicentre study using combined ambulatory impedance pH monitoring. Gut. 2006;55:1398–402.PubMedCrossRefGoogle Scholar
  61. 61.
    Kahrilas PJ, Shaheen NJ, Vaezi MF, et al. American gastroenterological association medical position statement on the management of gastroesophageal reflux disease. Gastroenterology. 2008;135:1383–91.PubMedCrossRefGoogle Scholar
  62. 62.
    Becker DJ, Sinclair J, Castell DO, et al. A comparison of high and low fat meals on postprandial esophageal acid exposure. Am J Gastroenterol. 1989;84:782–6.PubMedGoogle Scholar
  63. 63.
    Pehl C, Pfeiffer A, Wendl B, et al. The effect of decaffeination of coffee on gastro-oesophageal reflux in patients with reflux disease. Aliment Pharmacol Ther. 1997;11:483–6.PubMedCrossRefGoogle Scholar
  64. 64.
    Holloway RH, Hongo M, Berger K, et al. Gastric distention: a mechanism for postprandial gastroesophageal reflux. Gastroenterology. 1985;89:779–84.PubMedGoogle Scholar
  65. 65.
    Koufman J, Stern J, Bauer M. Dropping acid: the reflux diet cookbook & cure. Minneapolis, MN: BRIO; 2010.Google Scholar
  66. 66.
    Waring JP, Eastwood TF, Austin JM, et al. The immediate effects of cessation of cigarette smoking on gastroesophageal reflux. Am J Gastroenterol. 1989;84:1076–8.PubMedGoogle Scholar
  67. 67.
    Hamilton JW, Boisen RJ, Yamamoto DT, et al. Sleeping on a wedge diminishes exposure to the esophagus to refluxed acid. Dig Dis Sci. 1998;33:518–22.CrossRefGoogle Scholar
  68. 68.
    Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures effective in patients with gastroesophageal reflux? An evidence-based approach. Arch Intern Med. 2006;166:965–71.PubMedCrossRefGoogle Scholar
  69. 69.
    Gagliardi GS, Shah AP, Goldstein M, et al. The effect of zolpidem on the sleep arousal response to nocturnal acid exposure. Clin Gastroenterol Hepatol. 2009;7:948–52.PubMedCrossRefGoogle Scholar
  70. 70.
    Strugala V, Avis J, Joliffe IG, et al. The role of an alginate suspension on pepsin and bile acids—key aggressors in the gastric refluxate. Does this have implications for the treatment of gastro-oesophageal reflux disease? J Pharm Pharmacol. 2009;61:1021–8.PubMedCrossRefGoogle Scholar
  71. 71.
    Wolfe MM. Overview and comparison of the proton pump inhibitors for the treatment of acid-related disorders.­proton-pump-inhibitors-for-the-treatment-of-acid-related-disorders?source=search_result&search=Overview+and+comparison+of+the+proton+pump+inhibitors+for+the+treatment+of+acid-related+disorders&selectedTitle=1%7E150. Accessed 12 Dec 2011.Google Scholar
  72. 72.
    Peghini PI, Katz PO, Bracy NA, et al. Nocturnal recovery of gastric acid secretion with ­twice-daily dosing of proton pump inhibitors. Am J Gastroenterol. 1998;93:753–7.CrossRefGoogle Scholar
  73. 73.
    Fackler WK, Ours TM, Vaezi MF, et al. Long-term effect of H2RA therapy on nocturnal acid breakthrough. Gastroenterology. 2002;122:625–32.PubMedCrossRefGoogle Scholar
  74. 74.
    Orr WC, Harnish MJ. The efficacy of omeprazole twice daily with supplemental H2 blockade at bedtime in the suppression of nocturnal oesophageal and gastric acidity. Aliment Pharmacol Ther. 2003;17:1553–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Metz DC, Vakily M, Dixit T, et al. Review article: dual delayed release formulation of dexlansoprazole MR, a novel approach to overcome the limitations of conventional single release proton pump inhibitor therapy. Aliment Pharmacol Ther. 2009;29:928–37.PubMedCrossRefGoogle Scholar
  76. 76.
    Zhang Q, Lehmann A, Rigda R, et al. Control of transient lower esophageal sphincter relaxations and reflux by the GABA (B) agonist baclofen in patients with gastroesophageal reflux disease. Gut. 2002;50:19–24.PubMedCrossRefGoogle Scholar
  77. 77.
    Cadière GB, Van Sante N, Graves JE, et al. Two-year results of a feasibility study on antireflux transoral incisionless fundoplication (TIF) using EsophyX. Surg Endosc. 2009;23:957–64.PubMedCrossRefGoogle Scholar
  78. 78.
    Dassinger MS, Torquati A, Houston HL, et al. Laparoscopic fundoplication: 5-year follow-up. Am Surg. 2004;70:694–5.Google Scholar
  79. 79.
    Lundell L, Miettinen P, Myrvold HE, et al. Comparison of outcomes twelve years after antireflux surgery or omeprazole maintenance therapy for reflux esophagitis. Clin Gastroenterol Hepatol. 2009;7:1292–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Department of Medicine/Division of Pulmonary, Allergy & Critical Care MedicineUniversity of Alabama Hospital, University of Alabama at BirminghamBirminghamUSA

Personalised recommendations