Gastroesophageal reflux disease and sleep disturbances
First Online: 17 May 2012 Received: 08 February 2012 Accepted: 04 April 2012 DOI:
Cite this article as: Fujiwara, Y., Arakawa, T. & Fass, R. J Gastroenterol (2012) 47: 760. doi:10.1007/s00535-012-0601-4 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 H
2 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 References
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.
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.
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.
The Gallup Organization. A Gallup Organization National Survey: HB Across America. Princeton. 1998, 2000.
Fujiwara Y, Arakawa T. Epidemiology and clinical characteristics of GERD in the Japanese population. J Gastroenterol. 2009;44:518–34.
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.
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.
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.
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.
Mody R, Bolge SC, Kannan H, Fass R. Effects of gastroesophageal reflux disease on sleep and outcomes. Clin Gastroenterol Hepatol. 2009;7:953–9.
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.
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.
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.
Orr WC. Sleep-related gastro-oesophageal reflux as a distinct clinical entity. Aliment Pharmacol Ther. 2010;31:47–56.
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.
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.
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.
Moore JG. Circadian dynamics of gastric acid secretion and pharmacodynamics of H
receptor blockade. Ann N Y Acad Sci. 1991;618:150–8.
Reinberg A, Smolensky MH. Biological rhythms and medicine: cellular, metabolic, physiopathologic, and pharmacologic aspects. New York: Springer; 1983.
Stacher G, Presslich B, Stärker H. Gastric acid secretion and sleep stages during natural night sleep. Gastroenterology. 1975;68:1449–55.
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.
Katsube T, Adachi K, Kawamura A, Amano K, Uchida Y, Watanabe M, et al.
infection influences nocturnal gastric acid breakthrough. Aliment Pharmacol Ther. 2000;14:1049–56.
Fass R. Proton pump inhibitor failure–what are the therapeutic options? Am J Gastroenterol. 2009;104(Suppl 2):S33–8.
Goo RH, Moore JG, Greenberg E, Alazraki NP. Circadian variation in gastric emptying of meals in humans. Gastroenterology. 1987;93:515–8.
Mittal RK. Pathophysiology of gastroesophageal reflux: motility factors. J Gastroenterol. 2003;38(suppl 15):7–12.
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.
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.
Pasricha PJ. Effect of sleep on gastroesophageal physiology and airway protective mechanisms. Am J Med. 2003;115(Suppl 3A):114S–8S.
Orr WC. Gastrointestinal functioning during sleep: a new horizon in sleep medicine. Sleep Med Rev. 2001;5:91–101.
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.
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.
Lear CS, Flanagan JB Jr, Moorrees CF. The frequency of deglutition in man. Arch Oral Biol. 1965;10:83–100.
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.
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.
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.
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).
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.
Fass R. Gastroesophageal reflux disease and sleep. J Clin Gastroenterol. 2007;41(Suppl 2):S154–9.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Fass R. Effect of gastroesophageal reflux disease on sleep. J Gastroenterol Hepatol. 2010;25(Suppl 1):S41–4.
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.
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.
Katz PO, Hatlebakk JG, Castell DO. Gastric acidity and acid breakthrough with twice-daily omeprazole or lansoprazole. Aliment Pharmacol Ther. 2000;14:709–14.
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.
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.
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.
Castell D. Review of immediate-release omeprazole for the treatment of gastric acid-related disorders. Expert Opin Pharmacother. 2005;6:2501–10.
Behm BW, Peura DA. Dexlansoprazole MR for the management of gastroesophageal reflux disease. Expert Rev Gastroenterol Hepatol. 2011;5:439–45.
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.
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.
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.
Rushnak MJ, Leevy CM. Effect of diazepam on the lower esophageal sphincter. A double-blind controlled study. Am J Gastroenterol. 1980;73:127–30.
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.
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.