DIAGNOSTIC CHALLENGES: Differentiating Nighttime GERD

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DIAGNOSTIC CHALLENGES: Differentiating Nighttime GERD

J Fam Pract. 2005 December;54(12):1073-1078

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References

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2. Frank L, Kleinman L, Ganoczy D, et al. Upper gastrointestinal symptoms in North America: prevalence and relationship to healthcare utilization and quality of life. Dig Dis Sci. 2000;45:809-818.

3. Locke GR, III, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ, III. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology. 1997;112:1448-1456.

4. 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.

5. Dubois RW, Fass R, Johnson LF, et al. Atypical nighttime symptoms of GERD among individuals with nighttime versus daytime GERD [abstract]. Gastroenterology. 2005;128(suppl 2):A288.-Abstract M999.

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12. Dubois RW, Orr WC, Lange SM, et al. GERD-related sleep impairment among individuals with nighttime versus daytime GERD [abstract]. Gastroenterology. 2005;128(suppl 2):A288.-Abstract M998.

13. Dubois RW, Lange SM, Fass R, et al. Work productivity loss associated with nighttime GERD [abstract]. Gastroenterology. 2005;128(suppl 2):A286.-Abstract M988.

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15. 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;98:1487-1493.

16. Dubois RW, Fass R, Lange SM, et al. Impact of nighttime GERD on health-related quality of life [abstract]. Gastroenterology. 2005;128:(4 Suppl 2):A286.-Abstract M989.

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Predictors of nighttime reflux

A high body mass index (BMI) may lead to a reduction in LES pressure and is a risk factor for GERD.^20,21 Social habits such as smoking and alcohol use are often cited as risk factors for GERD; however, data to confirm this premise are lacking.¹¹ Several other factors and the presence of some pulmonary disorders may be specific predictors and indications of nighttime GERD episodes.

A recent large prospective cohort study specifically evaluated predictors of heartburn during sleep. Symptoms of GERD were strongly associated with increased BMI, carbonated soft drink consumption (possibly due to low pH), snoring and daytime sleepiness, insomnia, hypertension, asthma, and usage of benzodiazepines (TABLE 5).²⁰ It was noted that the association of hypertension with nighttime heartburn likely is a reflection of factors associated with hypertension rather than hypertension itself. Possible factors of hypertension include antihypertensive medications, comorbidities, diet, and body habitus.²⁰

Several sleep-related and respiratory factors are associated with nighttime GERD. Among these, insomnia and sleepiness are probably consequences rather than causes of nighttime reflux. An association of GERD with obstructive sleep apnea has been established, although causality has not been determined. Similarly, asthma is clearly associated with GERD, but the extent of causality remains unclear. Nonetheless, nighttime GERD should be suspected in patients who present with one of these sleep disturbances, particularly obstructive sleep apnea, or adult-onset or difficult-to-treat asthma.²⁰

TABLE 5
Factors associated with nighttime GERD

Increased body mass index Carbonated soft drink consumption Insomnia Sleepiness (daytime) Asthma Obstructive sleep apnea Hypertension Benzodiazepines
Lagergren J, et al. N Engl J Med. 1999;340:825-831.¹¹
Fass R, et al. Chest. 2005;127:1658-1666.²⁰
Fisher BL, et al. Dig Dis Sci. 1999;44:2290-2294.²¹

Diagnostic tests for GERD

Various tests have been investigated for the diagnosis of all types of GERD, and there is no difference in the tests used when nighttime GERD is suspected. Endoscopy is an important diagnostic tool for either identifying or ruling out complications such as erosions or Barrett’s esophagus. Esophageal pH monitoring can be helpful in diagnosis.

Pathophysiology: potential differences between daytime and nighttime GERD

Several mechanisms have been established to contribute to the development of GERD. Included are transient LES relaxations and, less frequently, sustained LES pressure abnormalities. Other factors that contribute to the pathophysiology of GERD include hiatal hernia, which reduces LES pressure and impairs acid clearance, and poor esophageal clearance.²²

Despite their similarities, important pathophysiologic differences between daytime and nighttime gastroesophageal reflux can be seen. Increased acid secretion and gastric volume are associated with food consumption, so daytime reflux and associated symptoms tend to occur after meals. Nighttime gastroesophageal reflux occurs less frequently, but the episodes are of longer duration than those of daytime reflux, as a result of delayed acid clearance from the esophagus at night.^6,7,23

Sleep-related mechanisms combined with impairment of the LES and the supine position help explain the more common and severe symptoms and wider range of complications seen in nighttime compared with daytime GERD.

Protective processes impaired during sleep

Differences between daytime and nighttime GERD are thought to be due to the sleep state rather than just to differences in posture (TABLE 6).^24,25 Processes that occur normally during the day to facilitate refluxed acid clearance from the esophagus, such as swallowing and acid neutralization (via bicarbonate-containing salivation), are suppressed during sleep.²⁵

Saliva, composed of mucus, bicarbonate, and epidermal growth factor, neutralizes refluxed acid and protects esophageal tissue. Saliva production is diminished during sleep, with implications for GERD symptoms.^26,27 Swallowing is reduced during sleep and may not occur during deeper stages of sleep.²⁸ Absence of the voluntary swallow-initiated peristaltic wave of esophageal contractions during sleep also results in reduced volume clearance.²⁹

Delayed gastric emptying during sleep may result in increased gastric distention and contribute to the occurrence of nighttime reflux.^25,30

TABLE 6
Sleep-related mechanisms contributing to nighttime GERD

Depressed perception of heartburn Depressed arousal Decreased saliva production Decreased swallowing Delayed gastric emptying Impaired esophageal clearance
Orr WC, et al. Am J Gastroenterol. 2000;95:37-42.²⁴
Orr WC, et al. Aliment Pharmacol Ther. 2004;20(suppl 9):39-46.²⁵

Effect of reduced consciousness

Reflux during sleep may be accompanied by a brief period of arousal, which helps to hasten esophageal clearance of refluxate and protect the airway against aspiration and acid exposure.²⁵ However, arousal does not occur in all reflux episodes, since the conscious perception of heartburn is absent during sleep. Consequently, the sleep-induced mechanisms are allowed to persist leading to prolonged periods of acid exposure.²⁵

Summary

For the purposes of understanding symptoms and facilitating diagnosis, GERD can be divided into daytime and nighttime GERD. Compared with daytime GERD, nighttime reflux episodes occur less frequently but are more prolonged. In addition, nighttime symptoms are more common and more severe, and esophageal and nonesophageal complications are more likely. The presence of severe symptoms or at least one esophageal and/or nonesophageal symptom should prompt an investigation of nighttime GERD. In doing so, the history and physical examination findings are the most helpful; laboratory values and other test results are generally less so. Physiologic alterations during sleep are thought to be the primary factors that contribute to nighttime symptoms.

EDITOR’S NOTE:
This article is meant to alert the reader to different symptomatology in GERD at night; therefore, treatment will not be discussed.