Journal of Gastroenterology

, Volume 47, Issue 7, pp 760–769 | Cite as

Gastroesophageal reflux disease and sleep disturbances

Review

Abstract

Nighttime reflux during sleep plays a crucial role in several conditions associated with gastroesophageal reflux disease (GERD). Reflux patterns during arousal and sleep are different because of delayed gastric emptying, reduced esophageal peristalsis, decreases in swallowing and salivary secretion, and prolonged esophageal clearance during sleep. Clinical evidence strongly suggests that GERD is associated with sleep disturbances such as shorter sleep duration, difficulty falling asleep, arousals during sleep, poor sleep quality, and awakening early in the morning. New mechanisms on how GERD affects sleep have been recently identified by using actigraphy, and sleep deprivation was found to induce esophageal hyperalgesia to acid perfusion. Thus, the relationship between GERD and sleep disturbances is bidirectional. Among lifestyle modifications, avoidance of a late night meal plays a role in prevention of nighttime reflux. Treatment with a proton pump inhibitor (PPI) improves both nighttime symptoms and subjective sleep parameters, but its effects on objective sleep parameters remain unclear. Better control of nighttime acid secretion by administering a PPI at different times or by providing a double-dose PPI, adding H2 receptor antagonists, or other new agents is proposed. The effects of such treatments on sleep disturbances remain to be elucidated. GERD patients with sleep disturbances report more severe symptoms and poorer quality of life as compared to those without sleep disturbances. Consequently, GERD should also be classified as GERD with sleep disturbance and GERD without sleep disturbance.

Keywords

Gastroesophageal reflux disease Sleep disturbance Proton pump inhibitor Quality of life 

Notes

Conflict of interest

Yasuhiro Fujiwara received honoraria for lectures for Eisai. Tetsuo Arakawa received a research grant, received honoraria, and serves as a consultant to Otsuka Pharmaceutical and Eisai. Ronnie Fass is a consultant for Takeda and Vecta, speaker for Takeda, and received a grant from AstraZeneca and Reckitt Benckiser.

References

  1. 1.
    Carskadon MA, Dement WC. Normal human sleep: an overview. In: Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep medicine. 4th ed. Philadelphia: Elsevier Saunders; 2005. p. 13–23.CrossRefGoogle Scholar
  2. 2.
    Czeisler CA, Winkelman JW, Richardson GS. Sleep disorders. In: Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo JL, editors. Harrison’s principles of internal medicine. 17th ed. New York: McGraw Hill Medical; 2008. p. 171–80.Google Scholar
  3. 3.
    Vakil N, van Zanten SV, Kahrilas P, Dent J, Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101:1900–20.PubMedCrossRefGoogle Scholar
  4. 4.
    The Gallup Organization. A Gallup Organization National Survey: HB Across America. Princeton. 1998, 2000.Google Scholar
  5. 5.
    Fujiwara Y, Arakawa T. Epidemiology and clinical characteristics of GERD in the Japanese population. J Gastroenterol. 2009;44:518–34.PubMedCrossRefGoogle Scholar
  6. 6.
    Suganuma N, Shigedo Y, Adachi H, Watanabe T, Kumano-Go T, Terashima K, et al. Association of gastroesophageal reflux disease with weight gain and apnea, and their disturbance on sleep. Psychiatry Clin Neurosci. 2001;55:255–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Farup C, Kleinman L, Sloan S, Ganoczy D, Chee E, Lee C, et al. The impact of nocturnal symptoms associated with gastroesophageal reflux disease on health-related quality of life. Arch Intern Med. 2001;161:45–52.PubMedCrossRefGoogle Scholar
  8. 8.
    Shaker R, Castell DO, Schoenfeld PS, Spechler SJ. 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
  9. 9.
    Fass R, Quan SF, O’Connor GT, Ervin A, Iber C. Predictors of heartburn during sleep in a large prospective cohort study. Chest. 2005;127:1658–66.PubMedCrossRefGoogle Scholar
  10. 10.
    Mody R, Bolge SC, Kannan H, Fass R. Effects of gastroesophageal reflux disease on sleep and outcomes. Clin Gastroenterol Hepatol. 2009;7:953–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Jung HK, Choung RS, Talley NJ. Gastroesophageal reflux disease and sleep disorders: evidence for a causal link and therapeutic implications. J Neurogastroenterol Motil. 2010;16:22–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Kusano M, Kouzu T, Kawano T, Ohara S. Nationwide epidemiological study on gastroesophageal reflux disease and sleep disorders in the Japanese population. J Gastroenterol. 2008;43:833–41.PubMedCrossRefGoogle Scholar
  13. 13.
    Fujiwara Y, Kohata Y, Kaji M, Nebiki H, Yamasaki T, Sasaki E, et al. Sleep dysfunction in Japanese patients with gastroesophageal reflux disease: prevalence, risk factors, and efficacy of rabeprazole. Digestion. 2010;81:135–41.PubMedCrossRefGoogle Scholar
  14. 14.
    Orr WC. Sleep-related gastro-oesophageal reflux as a distinct clinical entity. Aliment Pharmacol Ther. 2010;31:47–56.PubMedCrossRefGoogle Scholar
  15. 15.
    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
  16. 16.
    Adachi K, Fujishiro H, Katsube T, Yuki M, Ono M, Kawamura A, et al. Predominant nocturnal acid reflux in patients with Los Angeles grade C and D reflux esophagitis. J Gastroenterol Hepatol. 2001;16:1191–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Orr WC, Lackey C, Robinson MG, Johnson LF, Welsh JD. Esophageal acid clearance during sleep in patients with Barrett’s esophagus. Dig Dis Sci. 1988;33(6):654–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Moore JG. Circadian dynamics of gastric acid secretion and pharmacodynamics of H2 receptor blockade. Ann N Y Acad Sci. 1991;618:150–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Reinberg A, Smolensky MH. Biological rhythms and medicine: cellular, metabolic, physiopathologic, and pharmacologic aspects. New York: Springer; 1983.Google Scholar
  20. 20.
    Stacher G, Presslich B, Stärker H. Gastric acid secretion and sleep stages during natural night sleep. Gastroenterology. 1975;68:1449–55.PubMedGoogle Scholar
  21. 21.
    Peghini PL, Katz PO, Castell DO. Ranitidine controls nocturnal gastric acid breakthrough on omeprazole: a controlled study in normal subjects. Gastroenterology. 1998;115:1335–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Katsube T, Adachi K, Kawamura A, Amano K, Uchida Y, Watanabe M, et al. Helicobacter pylori infection influences nocturnal gastric acid breakthrough. Aliment Pharmacol Ther. 2000;14:1049–56.PubMedCrossRefGoogle Scholar
  23. 23.
    Fass R. Proton pump inhibitor failure–what are the therapeutic options? Am J Gastroenterol. 2009;104(Suppl 2):S33–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Goo RH, Moore JG, Greenberg E, Alazraki NP. Circadian variation in gastric emptying of meals in humans. Gastroenterology. 1987;93:515–8.PubMedGoogle Scholar
  25. 25.
    Mittal RK. Pathophysiology of gastroesophageal reflux: motility factors. J Gastroenterol. 2003;38(suppl 15):7–12.PubMedGoogle Scholar
  26. 26.
    Iwakiri K, Sugiura T, Hayashi Y, Kotoyori M, Kawakami A, Makino H, et al. Esophageal motility in Japanese patients with Barrett’s esophagus. J Gastroenterol. 2003;38:1036–41.PubMedCrossRefGoogle Scholar
  27. 27.
    Dent J, Dodds WJ, Friedman RH, Sekiguchi T, Hogan WJ, Arndorfer RC, et al. Mechanism of gastroesophageal reflux in recumbent asymptomatic human subjects. J Clin Invest. 1980;65:256–67.PubMedCrossRefGoogle Scholar
  28. 28.
    Pasricha PJ. Effect of sleep on gastroesophageal physiology and airway protective mechanisms. Am J Med. 2003;115(Suppl 3A):114S–8S.PubMedCrossRefGoogle Scholar
  29. 29.
    Orr WC. Gastrointestinal functioning during sleep: a new horizon in sleep medicine. Sleep Med Rev. 2001;5:91–101.PubMedCrossRefGoogle Scholar
  30. 30.
    Kahrilas PJ, Dodds WJ, Dent J, Haeberle B, Hogan WJ, Arndorfer RC. 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
  31. 31.
    Schneyer LH, Pigman W, Hanahan L, Gilmore RW. Rate of flow of human parotid, sublingual, and submaxillary secretions during sleep. J Dent Res. 1956;35:109–14.PubMedCrossRefGoogle Scholar
  32. 32.
    Lear CS, Flanagan JB Jr, Moorrees CF. The frequency of deglutition in man. Arch Oral Biol. 1965;10:83–100.PubMedCrossRefGoogle Scholar
  33. 33.
    Freidin N, Fisher MJ, Taylor W, Boyd D, Surratt P, McCallum RW, et al. Sleep and nocturnal acid reflux in normal subjects and patients with reflux oesophagitis. Gut. 1991;32:1275–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Fujiwara Y, Higuchi K, Watanabe Y, Shiba M, Watanabe T, Tominaga K, et al. Prevalence of gastroesophageal reflux disease and gastroesophageal reflux disease symptoms in Japan. J Gastroenterol Hepatol. 2005;20:26–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Watanabe Y, Fujiwara Y, Shiba M, Watanabe T, Tominaga K, Oshitani N, et al. Cigarette smoking and alcohol consumption associated with gastro-oesophageal reflux disease in Japanese men. Scand J Gastroenterol. 2003;38:807–11.PubMedCrossRefGoogle Scholar
  36. 36.
    Fujiwara Y, Higuchi K, Watanabe Y, Shiba M, Sasaki E, Watanabe T, et al. Association between sleep duration and gastroesophageal reflux disease. Jpn Gastroenterol. 2005;128:A384 (abstract).Google Scholar
  37. 37.
    Morse CA, Quan SF, Mays MZ, Green C, Stephen G, Fass R. Is there a relationship between obstructive sleep apnea and gastroesophageal reflux disease? Clin Gastroenterol Hepatol. 2004;2(9):761–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Fass R. Gastroesophageal reflux disease and sleep. J Clin Gastroenterol. 2007;41(Suppl 2):S154–9.CrossRefGoogle Scholar
  39. 39.
    Mizuta Y, Takashima F, Shikuwa S, Ikeda S, Kohno S. Is there a specific linkage between obstructive sleep apnea syndrome and gastroesophageal reflux disease? Dig Endosc. 2006;18:88–97.CrossRefGoogle Scholar
  40. 40.
    Orr WC, Goodrich S, Robert J. The effect of acid suppression on sleep patterns and sleep-related gastro-oesophageal reflux. Aliment Pharmacol Ther. 2005;21:103–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Poh CH, Allen L, Gasiorowska A, Navarro-Rodriguez T, Quan SF, Malagon I, 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
  42. 42.
    Allen L, Poh CH, Gasiorowska A, Malagon I, Navarro-Rodriguez T, Cui H, 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
  43. 43.
    Poh CH, Gasiorowska A, Allen L, Navarro-Rodriguez T, Mizyed I, Powers J, et al. Reassessment of the principal characteristics of gastroesophageal reflux during the recumbent period using integrated actigraphy-acquired information. Am J Gastroenterol. 2010;105:1024–31.PubMedCrossRefGoogle Scholar
  44. 44.
    Poh CH, Allen L, Malagon I, Gasiorowska A, Navarro-Rodriguez T, Powers J, et al. Riser’s reflux—an eye-opening experience. Neurogastroenterol Motil. 2010;22:387–94.PubMedCrossRefGoogle Scholar
  45. 45.
    Dickman R, Parthasarathy S, Malagon IB, Jones P, Han B, Powers J, et al. Comparisons of the distribution of oesophageal acid exposure throughout the sleep period among the different gastro-oesophageal reflux disease groups. Aliment Pharmacol Ther. 2007;26:41–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Morgenthaler T, Alessi C, Friedman L, Owens J, Kapur V, Boehlecke B, Standards of Practice Committee; American Academy of Sleep Medicine, et al. Practice parameters for the use of actigraphy in the assessment of sleep and sleep disorders: an update for 2007. Sleep. 2007;30:519–29.PubMedGoogle Scholar
  47. 47.
    Schey R, Dickman R, Parthasarathy S, Quan SF, Wendel C, Merchant J, et al. Sleep deprivation is hyperalgesic in patients with gastroesophageal reflux disease. Gastroenterology. 2007;133:1787–95.PubMedCrossRefGoogle Scholar
  48. 48.
    Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach. Arch Intern Med. 2006;166:965–71.PubMedCrossRefGoogle Scholar
  49. 49.
    Fujiwara Y, Machida A, Watanabe Y, Shiba M, Tominaga K, Watanabe T, et al. Association between dinner-to-bed time and gastro-esophageal reflux disease. Am J Gastroenterol. 2005;100:2633–6.PubMedCrossRefGoogle Scholar
  50. 50.
    Piesman M, Hwang I, Maydonovitch C, Wong RK. Nocturnal reflux episodes following the administration of a standardized meal. Does timing matter? Am J Gastroenterol. 2007;102:2128–34.PubMedCrossRefGoogle Scholar
  51. 51.
    Chiba N, De Gara CJ, Wilkinson JM, Hunt RH. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology. 1997;112:1798–810.PubMedCrossRefGoogle Scholar
  52. 52.
    Dimarino AJ Jr, Banwait KS, Eschinger E, Greenberg A, Dimarino M, Doghramji K, et al. The effect of gastro-oesophageal reflux and omeprazole on key sleep parameters. Aliment Pharmacol Ther. 2005;22:325–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Johnson DA, Orr WC, Crawley JA, Traxler B, McCullough J, Brown KA, 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
  54. 54.
    Fass R. Effect of gastroesophageal reflux disease on sleep. J Gastroenterol Hepatol. 2010;25(Suppl 1):S41–4.PubMedCrossRefGoogle Scholar
  55. 55.
    Hatlebakk JG, Katz PO, Kuo B, Castell DO. Nocturnal gastric acidity and acid breakthrough on different regimens of omeprazole 40 mg daily. Aliment Pharmacol Ther. 1998;12:1235–40.PubMedCrossRefGoogle Scholar
  56. 56.
    Pehlivanov ND, Olyaee M, Sarosiek I, McCallum RW. Comparison of morning and evening administration of rabeprazole for gastro-oesophageal reflux and nocturnal gastric acid breakthrough in patients with reflux disease: a double-blind, cross-over study. Aliment Pharmacol Ther. 2003;18:883–90.PubMedCrossRefGoogle Scholar
  57. 57.
    Katz PO, Hatlebakk JG, Castell DO. Gastric acidity and acid breakthrough with twice-daily omeprazole or lansoprazole. Aliment Pharmacol Ther. 2000;14:709–14.PubMedCrossRefGoogle Scholar
  58. 58.
    Shimatani T, Inoue M, Kuroiwa T, Horikawa Y. Rabeprazole 10 mg twice daily is superior to 20 mg once daily for night-time gastric acid suppression. Aliment Pharmacol Ther. 2004;19:113–22.PubMedCrossRefGoogle Scholar
  59. 59.
    Ours TM, Fackler WK, Richter JE, Vaezi MF. Nocturnal acid breakthrough: clinical significance and correlation with esophageal acid exposure. Am J Gastroenterol. 2003;98:545–50.PubMedCrossRefGoogle Scholar
  60. 60.
    Rackoff A, Agrawal A, Hila A, Mainie I, Tutuian R, Castell DO. Histamine-2 receptor antagonists at night improve gastroesophageal reflux disease symptoms for patients on proton pump inhibitor therapy. Dis Esophagus. 2005;18:370–3.PubMedCrossRefGoogle Scholar
  61. 61.
    Castell D. Review of immediate-release omeprazole for the treatment of gastric acid-related disorders. Expert Opin Pharmacother. 2005;6:2501–10.PubMedCrossRefGoogle Scholar
  62. 62.
    Behm BW, Peura DA. Dexlansoprazole MR for the management of gastroesophageal reflux disease. Expert Rev Gastroenterol Hepatol. 2011;5:439–45.PubMedCrossRefGoogle Scholar
  63. 63.
    Nwokolo CU, Prewett EJ, Sawyerr AM, Hudson M, Lim S, Pounder RE. Tolerance during 5 months of dosing with ranitidine, 150 mg nightly: a placebo-controlled, double-blind study. Gastroenterology. 1991;101:948–53.PubMedGoogle Scholar
  64. 64.
    Galmiche JP, Hatlebakk J, Attwood S, Ell C, Fiocca R, Eklund S, Långström G, Lind T, LOTUS Trial Collaborators. Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the LOTUS randomized clinical trial. JAMA. 2011;305:1969–77.PubMedCrossRefGoogle Scholar
  65. 65.
    Cohen JA, Arain A, Harris PA, Byrne DW, Holzman MD, Sharp KW, et al. Surgical trial investigating nocturnal gastroesophageal reflux and sleep (STINGERS). Surg Endosc. 2003;17:394–400.PubMedCrossRefGoogle Scholar
  66. 66.
    Rushnak MJ, Leevy CM. Effect of diazepam on the lower esophageal sphincter. A double-blind controlled study. Am J Gastroenterol. 1980;73:127–30.PubMedGoogle Scholar
  67. 67.
    Gagliardi GS, Shah AP, Goldstein M, Denua-Rivera S, Doghramji K, Cohen S, et al. Effect of zolpidem on the sleep arousal response to nocturnal esophageal acid exposure. Clin Gastroenterol Hepatol. 2009;7:948–52.PubMedCrossRefGoogle Scholar
  68. 68.
    Orr WC, Goodrich S, Fernström P, Hasselgren G. Occurrence of nighttime gastroesophageal reflux in disturbed and normal sleepers. Clin Gastroenterol Hepatol. 2008;6:1099–104.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2012

Authors and Affiliations

  • Yasuhiro Fujiwara
    • 1
  • Tetsuo Arakawa
    • 1
  • Ronnie Fass
    • 2
  1. 1.Department of GastroenterologyOsaka City University Graduate School of MedicineOsakaJapan
  2. 2.Neuroenteric Clinical Research Group, Section of Gastroenterology, Department of MedicineSouthern Arizona VA Health Care System, University of ArizonaTucsonUSA

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