Best Practice & Research Clinical GastroenterologyVol. 18, No. S, pp. 31–38, 2004
Nighttime GERD: Clinical implications
and therapeutic challenges
Reza Shaker*Professor
Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 9200 W. Wisconsin Ave.,
Milwaukee, WI 53226, USA
Limited available data specifically addressing nocturnal gastroesophageal reflux indicate itsassociation with more severe injuries such as esophagitis and stricture, adenocarcinoma of theesophagus, respiratory and ENT disorders as well as sleep disturbances, diminished quality of lifeand undesired changes in activities of daily living.In a recent survey, altogether 79% of respondents reported experiencing heartburn at night.Among those, 75% reported that symptoms affected their sleep, 63% believed that heartburnnegatively affected their ability to sleep well, and 40% believed that nocturnal heartburn impairedtheir ability to function the following day. Of the 791 respondents with nighttime heartburn, 71%reported taking over-the-counter medicine for it, only 29% of these rated this approachextremely effective. Forty-one percent reported trying prescription medicines and 49% of theserated this approach extremely satisfactory.This recent understanding of the prevalence and impact of nighttime heartburn is an indicator ofnocturnal acid reflux events and suggests that nighttime heartburn occurs in a large majority ofadults with gastroesophageal reflux disease. The fact that expected result from implementedtherapy for heartburn is not achieved by a sizable percentage of patients can have significantmanagement implications.
Key words: gastroesophageal reflux disease; adenocarcinoma; nighttime heartburn.
Gastroesophageal reflux disease (GERD) is the most common malady of the esophagus.It is estimated that 7% of the individuals in the general population in United Statesexperience heartburn the cardinal symptoms of this disease daily, whereas 14% haveGERD symptoms at least once a week.1,2
A considerable amount of information exist about the prevalence of GERD ingeneral, however, data specifically addressing nocturnal reflux is limited.3–6
For example, it was only recently reported3 that prevalence of nocturnal heartburn,
doi:10.1016/j.bpg.2004.06.010available online at http://www.sciencedirect.com
1521-6918/$ - see front matter Q 2004 Published by Elsevier Ltd.
* Tel.: C1-414-456-6840; Fax: C1-414-456-6215.
E-mail address: [email protected]
32 R. Shaker
the cardinal symptom of reflux disease among individuals suffering from chronicheartburn, is at an unexpected level of 74%. In addition, this study3 demonstrated asignificantly more negative impact on quality of life in nocturnal heartburn suffererscompared to those with diurnal symptoms. Nocturnal acid reflux is reported to beassociated with more severe reflux induced injuries such as esophagitis and stricture4–6,as well as adenocarcinoma of the esophagus7, respiratory and ENT disorders as well assleep disturbances, diminished quality of life and undesired changes in activities of dailyliving. Furthermore, considering the reports indicating reasonable specificity ofheartburn for diagnosis of GERD8, a better understanding of the prevalence andimpact of nocturnal heartburn can have significant potential diagnostic and managementimplications. A national population-based telephone interview survey of 1000 adults, 18years of age or older, who reported experiencing heartburn at least once a weekconducted by The Gallup Organization on behalf of The American GastroenterologicalAssociation, evaluated (a) the prevalence of nighttime heartburn and reflux attributedsupraesophageal symptoms among patients with GERD and (b) the impact of nighttimeheartburn on sleep and some of the activities of daily living that could impact the qualityof life. The survey also allowed for collection of additional information aboutconcomitant respiratory symptoms, use of medication and seeking medical help.
Of the 1000 respondents, irrespective of time, about one-quarter reportedexperiencing heartburn once or more each day, 43% reported experiencing heartburn1–2 times per week, and 20% 3–6 times per week. Thirteen percent of the respondentscould not quantify the frequency of their heartburn episodes.
Chronicity of heartburn varied widely, with heartburn experienced at least once aweek. While nearly one-third of the respondents reported experiencing heartburn for10 years or longer, a total of 15% of respondents reported that their heartburn hadbeen present for only a year or less. Over 50% reported experiencing heartburnbetween 2 and 10 years.
Frequency of the reported nighttime and daytime heartburn is summarized inFigure 1. As seen, 13% of the respondents reported experiencing heartburn only duringnighttime, whereas 20% reported heartburn only during daytime. Sixty-five percent ofrespondents experienced heartburn both day and night. Altogether, 79% of theheartburn sufferers reported experiencing heartburn at night.
A large percentage of the respondents reported concomitant symptoms, potentiallyattributable to gastroesophageal reflux. Throat clearing was reported by 39% of the1000 respondents, while chronic cough, hoarse voice and asthma were reported by 16,18 and 13%, respectively. In addition, a burning sensation in the throat was reported by50%.
When inquired about the effect of heartburn on sleep, among respondents withnighttime heartburn, 75% reported that the symptom affected their sleep, and 63%believed that heartburn negatively affected their ability to sleep well. Forty percent ofrespondents with nocturnal heartburn believed that the sleep difficulties due to thenighttime heartburn impaired their ability to function the following day. Prevalence ofsleep disturbances among respondents increased with the increase in frequency of thenighttime heartburn episodes during the week (Figure 2).
Forty-two percent of the respondents stated that they have accepted the fact thatthey cannot sleep through the night, 39% reported that they take naps wheneverpossible, and 34% reported sleeping in a chair or in a seated position. Surprisingly, 27%reported that their heartburn-induced sleep disturbances kept their spouses fromhaving a good night’s sleep. In general, heartburn resulted in some degree of limitationor change in lifestyle of the respondents. Over half reported that heartburn caused
Daytime &Nighttime
Nighttimeonly
Daytimeonly
Do notknow
13%20%
2%
65%
(n=1000)
100
90
80
70
60
50
40
30
20
10
0
% W
ith H
eart
burn
Figure 1. Prevalence of nighttime and daytime heartburn. As seen, the majority of respondents experienced
both nighttime and daytime heartburn. However, a minority reported either nighttime or daytime heartburn.
In total, 79% of respondents reported experiencing nocturnal heartburn.
Gastroesophageal reflux disease 33
changes in the time, nature and quantity of their food intake. Tables 1 and 2 representsome of the effects of heartburn on the lifestyle of respondents.
A variety of medical and non-medical approaches to heartburn were reported by therespondents. Surprisingly, of the 791 respondents with nighttime heartburn about30% of respondents did not report taking any kind of medication, 71% reported takingover-the-counter medication for their heartburn, while 41% reported tryingprescription medicines. Altogether, the efficiency of remedies for heartburn was
80
70
60
50
40
30
20
10
0
% W
ith H
eart
burn
< Once 1 2x ≥ 3x
Kept awake (n=453)
Woke up duringnight (n=454)
Heartburn Episodes/Week
44%41%
53% 54%
67%70%
Figure 2. The frequency of sleep difficulties increased with an increase in the frequency of heartburn
experienced each week by respondents. Over two-thirds of those who experienced heartburn three times or
more per week reported being kept awake or being wakened during the night because of heartburn.
Table 1. Daily life affected by heartburn.
Greatly
(%)
Quite a
bit (%)
Moder-
ately (%)
Mildly
(%)
Not at
all (%)
DK/RF
(%)
Total
(%)
Ability to eat or
drink what you want
15 10 21 20 33 1 100
Ability to get a good
night’s sleep
11 8 21 23 36 1 100
Ability to eat or
drink when you want
11 7 19 23 39 1 100
Ability to sleep when
you want
9 7 19 21 43 1 100
Your mood or
general well-being
8 8 19 22 42 1 100
Social activities 7 4 12 16 59 2 100
Spouse’s ability to
get a good night’s
sleep
5 2 10 10 55 18 100
Ability to function
day-to-day
4 4 17 23 51 1 100
Ability to function
well at work the
next day
4 4 15 17 48 12 100
DK, do not know; RF, refused to answer. Experiencing heartburn affected a number of activities of daily
living and social functions of the responders. These included their eating, sleeping, social life and work.
34 R. Shaker
variable. Only 29% of those taking over-the-counter, and 42% of those takingprescription medicine rated these approaches completely satisfactory. Other measurestaken by respondents and their effectiveness are summarized in Figure 3.
The findings of this survey taken together with that of a previous report by Farupet al3 suggest that both the prevalence and the impact of nighttime heartburn have beenunderestimated, and that the symptom often is not treated adequately. These issueshave practical implications for the management of GERD in that they highlight severalimportant features of the disease: (1) only a minority of heartburn sufferers seekmedical help and are on adequate treatment, (2) although only a minority experiencenighttime heartburn exclusively almost 8 of 10 of those who report frequent heartburnexperience nighttime heartburn, and most patients have the symptom both during theday and at night, (3) it seems that the condition impairs sleep, and consequently has asubstantial negative impact on daily function and lifestyle. These findings suggest a needfor more specific inquiry about nocturnal reflux form patients and more effort inrecognising and treating the nocturnal manifestations of GERD.
Esophageal acid clearance is a two-step process and involves (a) volume clearanceand (b) acid neutralization.9,10 In this process, the majority of the refluxed gastric acid iscleared from the esophagus by either primary or secondary peristalsis, while theresidual hydrogen ion that remains behind is neutralized by salivary bicarbonate and, toa lesser extent, by bicarbonate secreted from the esophageal submucosal glands.11
During sleep acid clearance is curtailed. Swallowing virtually ceases during sleep and,consequently, primary peristalsis (that is induced by swallowing) is not stimulated.
Table 2. How respondents treated their heartburn.
All with heart-
burn (%)
Prescription
medication (%)
Over-the-counter
medication (%)
No medi-
cation (%)
Changed foods eaten 56 63 56 45
Eating smaller meals and
more often
50 56 50 44
Propped up head for
sleeping
48 58 43 41
Reduced stress 43 47 40 42
Accepted that cannot
sleep through the night
42 43 43 39
Take naps when possible 39 39 37 41
Sleep in chair or sitting
position
34 41 28 31
Reduced or quit drinking
alcohol
29 29 29 27
Changed frequency of
exercise
25 29 22 22
Quit smoking 14 14 15 14
Number of interviews 1000 386 340 274
Lifestyle changes made due to heartburn symptoms among all respondents, those taking prescription
medicine, those taking over-the-counter medicine and those who did not report taking any medicine. As
seen across the board, except for changes in frequency of exercise and smoking, one-third to one-half of
respondents from all groups reported that they have made various changes in their activities of daily living
and lifestyle due to heartburn.
Gastroesophageal reflux disease 35
Therefore, esophageal volume clearance during sleep is almost totally a function ofsecondary peristalsis that may not be stimulated by the reflux of small amounts ofgastric content. Experimental data suggest that a threshold volume ranging between 5and 30 ml is required to stimulate secondary peristalsis in healthy individuals.12
Furthermore, the triggering mechanism of secondary peristalsis among healthy elderlyindividuals13 and among patients with reflux esophagitis is deteriorated.14,15 Therefore,volume clearance of refluxed gastric acid during sleep may not be as reliable as in awakestate. In addition, not only recumbent position during sleep facilitates reflux, the effectof gravity after the reflux event retards esophageal clearance for individuals in therecumbent position. The cessation of swallowing during sleep also impairs acidclearance because there is no salivary bicarbonate available to neutralize hydrochloricacid dissolved in the esophageal unstirred water layer. Consequently as a result of thereduction in esophageal volume clearance and acid neutralization during sleep,nocturnal acid reflux might be especially damaging to the esophagus because theacid will have prolonged contact with the mucosa. Indeed, several studies havedocumented recumbent nocturnal acid exposure among the majority of patients withsevere consequences of reflux disease such as Barrett’s esophagus and erosiveesophagitis.16–19 In addition, the reduced esophageal peristaltic activity may predisposeto proximal migration of the acid refluxate23, thereby increasing the likelihood ofdamage to the oropharynx and airway.
70
60
50
40
30
20
10
0
% W
ith H
eart
burn
OTCMedication
AvoidingFood Before
Bed
Eating orDrinking
Something
ElevatingHead of
Bed
PrescriptionMedications
SleepingSitting up
Taking Pills
Sleeping
Tried this method
Completely satisfied withthis method
(n = 791)
71%
29%
61%
33%
52%
15%
44%
23%
41%
49%
27% 27%
16%
29%
Figure 3. Action taken by those experiencing nighttime heartburn. As seen, only half of those who took prescription medication and one-third of those who used over-the-
counter medications reported the results to be completely satisfied. Across the board, for other actions the results were less satisfactory.
36
R.Sh
aker
Gastroesophageal reflux disease 37
Information about the prevalence of nocturnal heartburn is scarce. Availablestudies3 have reported a 10% overall prevalence for nocturnal GERD symptoms inthe US population. The prevalence of nocturnal GERD symptoms among patients withfrequent heartburn is reported to be 74–79%.3,20
Association of supraesophageal and respiratory disorders with GERD hasincreasingly become the topic of investigation in recent years.21–24 Previousretrospective reviews of databases21 reported an increased risk for a variety ofrespiratory and aerodigestive tract diseases such as pharyngitis, sinusitis, laryngitis,chronic bronchitis, and asthma among patients with reflux esophagitis. In some studies,13–39% of heartburn sufferers reported supraesophageal symptoms, including asthma,hoarseness, chronic cough, and frequent throat clearing. The role of nighttime refluxevents in causing supraesophageal complications has not been systematically studied.Similar to heartburn, asthma, chronic cough, and hoarse voice are common clinicalproblems. Their concomitant presence with heartburn is a possibility and also moreserious conditions such as malignancy inducing the respiratory symptoms need to beruled out before these symptoms are attributed to reflux disease.
One of the unexpected findings of the available studies is the percentage ofrespondents who are dissatisfied with their GERD therapy, including both prescriptionand over-the-counter medications. In one survey20, among 70% of respondents whoreported taking any medication, less than half expressed satisfaction. More surprisingwas the percentage (15%) of those who used over-the-counter medication in additionto prescription drugs, suggesting either inadequate dosage or inappropriate usage ortiming of the latter.
A troublesome consequence of nighttime heartburn is sleep disturbances and itsnegative impact on the next day function.20 Especially disturbing is the limiting effect thatnighttime heartburn is reported to have on personal and social activities of the studiedpopulation.20 The socioeconomic impact of these findings could be important and againraise the question of appropriate treatment strategies for chronic nocturnal heartburn.
In summary, nighttime symptoms occur in the large majority of adults withheartburn. Limited available data specifically addressing nocturnal gastroesophagealreflux indicate its association with more severe injuries such as esophagitis andstricture, adenocarcinoma of the esophagus, respiratory and ENT disorders as well assleep disturbances, diminished quality of life and undesired changes in activities of dailyliving. The expected result from the implemented therapy for heartburn is not achievedby a substantial percentage of patients.
REFERENCES
1. Nebel OT, Formes MF & Castell DO. Symptomatic gastroesophageal reflux: incidence and precipitating
factor. Dig Dis Sci 1976; 21: 953–956.
2. A Gallup survey on heartburn across America. Princeton, NJ: The Gallup Organization, Inc.; 1988.
3. Farup C, Kleinman L, Sloan S 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.
4. DeMeester TR, Johnson LF, Guy JJ et al. Patterns of gastroesophageal reflux in health and disease. Ann
Surg 1996; 184: 459–470.
5. Kruse-Andersen S, Wallin L & Madsen T. Acid-gastro-oesophageal reflux and oesophageal pressure
activity during postprandial and nocturnal period. Scand J Gastroenterol 1987; 22: 926–930.
6. Orr W. Clinical implications of nocturnal gastroesophageal reflux. Pract Gastroenterol 1994; 28: 28D–28H.
38 R. Shaker
7. Lagergren J, Bergstrom R, Lindgren A & Nyren O. Symptomatic gastroesophageal reflux as a risk factor
for esophageal adenocarcinoma. N Engl J Med 1999; 340: 825–831.
8. Klauser AF, Schindlbeck NE & Muller-Lissner SA. Symptoms in gastro-oesophageal reflux disease. Lancet
1990; 335: 205–208.
9. Helm JF, Dodds WJ, Riedel DR et al. Determinants of esophageal acid clearance in normal subjects.
Gastroenterology 1983; 85: 607–612.
10. Helm JF, Dodds WJ, Hogan WJ et al. Effect of esophageal emptying and saliva on clearance of acid from
the esophagus. N Engl J Med 1984; 310: 284–288.
11. Helm JF, Dodds WJ, Hogan WJ et al. Acid neutralizing capacity of human saliva. Gastroenterology 1982; 83:
69–74.
12. Ulualp SO, Toohill RJ & Shaker R. Loss of secondary esophageal peristalsis is not a contributory
pathogenetic factor in posterior laryngitis. Ann Otol Rhinol Laryngol 2001; 110(2): 152–157.
13. Ren J, Shaker R, Kusano M et al. Effect of aging on the secondary esophageal peristalsis: presbyesophagus
revisited. Am J Physiol 1995; 268(Gastrointest Liver Physiol 31): G772–G779.
14. Schoeman MN & Holloway RH. Integrity and characteristics of secondary esophageal peristalsis in
patients with gastro-esophageal reflux disease. Gut 1995; 36: 499–504.
15. Williams S, Thompson D, Marples M et al. Identification of an abnormal esophageal clearance response to
intraluminal distention in patients with esophagitis. Gastroenterology 1995; 103: 943–953.
16. Katzka D, Sidhu M & Castell D. Hypertensive lower esophageal sphincger pressures and gastroesophageal
reflux: an apparent paradox that is not unusual. Am J Gastroenterol 1995; 90(2): 280–284.
17. Orr W, Allen M & Robinson M. The pattern of nocturnal and diurnal esophageal acid exposure in the
pathogenesis of erosive mucosal damage. Am J Gastroenterol 1994; 89(4): 509–512.
18. Timmer R, Breumelhof R, Nadorp J & Smout A. Oesophageal motility and gastro-oesophageal reflux
before and after healing of reflux oesophagitis: a study using 24 hour ambulartory pH and pressure
monitoring. Gut 1994; 35: 1519–1522.
19. Holloway RH, Dent J, Narielvala F & Mackinnon AM. Relation between oesophageal acid exposure and
healing of oesophagitis with Omeprazole in patients with severe reflux oesophagitis. Gut 1996; 38: 649–
654.
20. Shaker R, Castell DO, Schoenfeld PL & 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: 1487–1493.
21. El-Serag HB & Sonnenberg A. Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in
United States military veterans. Gastroenterology 1997; 113(3): 755–760.
22. Ulualp SO, Toohill RJ & Shaker R. Pharyngeal acid reflux in patients with single and multiple
otolaryngologic disorders. Otolaryngol Head Neck Surg 1999; 121(6): 725–730.
23. Ulualp SO, Toohill RJ & Shaker R. Outcomes of acid suppressive therapy in patients with posterior
laryngitis. Otolaryngol Head Neck Surg 2001; 124(1): 16–22.
24. El-Serag HB, Hepworth EJ, Lee P & Sonnenberg A. Gastroesophageal reflux disease is a risk factor for
laryngeal and pharyngeal cancer. Am J Gastroenterol 2001; 96(7): 2013–2018.
