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Failure of esophageal peristalsis in older patients: association with esophageal acid exposure
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2003 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
Vol. 98, No. 1, 2003 ISSN 0002-9270/03/$30.00 PII S0002-9270(02)05856-2
Failure of Esophageal Peristalsis in Older Patients: Association with Esophageal Acid Exposure A. Cristina Achem, Sami R. Achem, Mark E. Stark, and Kenneth R. DeVault Department of Medicine, Mayo Clinic, Jacksonville, Florida
OBJECTIVES: Gastroesophageal reflux disease (GERD) is common in all ages, but its prevalence appears to increase with age. Older patients often need aggressive medical therapy and are frequently being considered for antireflux surgery. We sought to evaluate the physiological defect (lower esophageal sphincter [LES] pressures, esophageal motility, and acid exposure) in a group of GERD patients ⱖ 65 yr old in comparison with a younger population (ⱕ40 yr). We hypothesized that age has an adverse impact on esophageal motility and reflux parameters. METHODS: Consecutive patients who completed esophageal manometry and ambulatory pH testing in our laboratory were evaluated for the study. The study group consisted of those ⱖ65 yr old and the control group of those ⱕ40 yr old. Each group was then divided according to their percent esophageal acid (pH ⬍ 4.0) exposure (⬍5%, 5–10%, ⬎10%). Motility parameters (LES and esophageal body) were compared between the two groups. RESULTS: Of 349 patients who underwent manometry and pH testing during the study period, 133 were ⱖ65 yr old, and 48 were ⱕ40 yr old. The degree of acid exposure was similar in both groups. The resting LES pressure was similar regardless of age but was lowest for both age groups in the patients with acid exposure ⬎ 10% (12.6 mm Hg in the ⱕ40-yr-old patients and 15.4 mm Hg in the ⱖ65-yr-old patients, p ⬍ 0.05). The percentage of swallows that induced normal peristalsis was lowest in the ⱖ65-yr-old patients compared with the ⱕ40-yr-old patients in the group with ⬎10% acid exposure (62.5% vs 95%, p ⬍ 0.05).
yr experienced heartburn or acid regurgitation once a week and 59% at least once a month (3). Older patients suffer from more severe GERD or from advanced complications associated with GERD. Collen et al. noted that 81% of GERD patients aged 60 yr or older developed erosive esophagitis, compared with 47% of those younger than 60 yr with GERD (4). The increase in the lifespan, particularly in the United States, underscores the importance of GERD in the elderly. Yet the factors that lead to a more severe form of GERD in patients of advancing age remain unknown. Hollis and Castell found a decrease in esophageal amplitude with aging for subjects older than 70 yr, although a more recent study by Richter et al. found no such association (5, 6). Hiatal hernias have also been found to increase proportionally with age (7). In our study, we sought to determine whether there are differences in distal esophageal motility and acid contact time between reflux patients aged 65 yr or older and those aged 40 yr or younger.
MATERIALS AND METHODS
INTRODUCTION
Patient Population All patients referred to our laboratory for evaluation of GERD who underwent esophageal manometry and ambulatory pH testing from April, 1999 through April, 2001 were included in the study. The patients who were ⱖ65 yr old constituted the study group, and those ⱕ40 yr old were the controls. Patients 41– 64 yr old were not included in this analysis to ensure a clear cutoff between the study and control groups, although we did examine the subgroup of patients aged 41– 64 yr who had higher acid exposure to help validate our findings. These two groups were then stratified according to percent acid exposure, pH ⱕ 4 (⬍5, 5%–10%, and ⬎10%). Additional data obtained included the following: demographics, lower esophageal sphincter (LES) pressure and percent effective peristalsis in esophageal body, mean esophageal body peristaltic pressure, and percentage distal esophageal acid exposure.
Gastroesophageal reflux disease (GERD) is one of the most common esophageal disorders (1). Acid regurgitation or heartburn, the cardinal symptoms of GERD, affect 10 –20% of the population on a weekly basis and 15– 40% monthly (2). Locke et al. reported that 20% of subjects older than 65
Esophageal Manometry and 24-h Ambulatory pH Testing The technique for measuring esophageal motility included the following. An 8-lumen, polyvinyl catheter (Arndorfer Specialties, Greendale, WI) was used. The four distal open-
CONCLUSION: Reflux in older patients is complicated by disordered esophageal motility. This impaired motility may decrease acid clearance, result in more difficult to control disease, and may render these patients susceptible to GERD complications. (Am J Gastroenterol 2003;98:35–39. © 2003 by Am. Coll. of Gastroenterology)
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Achem et al.
AJG – Vol. 98, No. 1, 2003
Table 1. Distribution of Patients According to Age and Acid Exposure pH ⱕ4 Age
⬍5% Acid Exposure
5–10% Acid Exposure
⬎10% Acid Exposure
ⱖ65 yr ⱕ40 yr
72/133 (54) 21/48 (44)
26/133 (20) 11/48 (23)
35/133 (26) 16/48 (33)
Values are n (%).
ings were 1 cm apart and the four proximal openings were 5 cm apart. Both sets of channels were located at 90-degree angles. Each channel was perfused with 0.5 ml/min of distilled water with a system of low compliance pneumohydraulic capillary perfusion. The four distal and the four proximal transducers were connected to external transducers with output to a personal computer– based analysis system (Medtronic, Minneapolis, MN). The patients were instructed to fast overnight and were evaluated in the supine position. The catheter was passed nasally into the stomach. After a brief adjustment period, the catheter was gradually removed in 1 cm intervals to record the LES pressure. LES pressure was measured at two points in each of four channels during a station pull-through. The first measurement was taken as an average of the midexpiratory pressure (relative to the gastric baseline) for three or more respiratory cycles. This average is taken from pressure at the highest level before the respiratory inversion point (8). A second measurement was obtained as a midexpiratory point just proximal to the respiratory inversion point (RIP) as described by O’Sullivan et al. (9). Six wet swallows at 30-s intervals were administered to evaluate the percentage of LES relaxation and the residual LES pressure compared with the gastric baseline. The catheter was then positioned so that esophageal peristalsis could be evaluated at 3, 8, 13, and 18 cm above the LES in response to 10, 5-ml water swallows. The distal esophageal amplitude was calculated as an average of the pressures obtained at 3 and 8 cm above the LES. Each contraction sequence was judged as peristaltic, nontransmit-
ted, simultaneous, or ineffective (amplitude less than 30 mm Hg in two or more transducers). Ambulatory pH studies were performed with a 2.1-mm, dual electrode antimony catheter (Medtronic), which was inserted through the nose. The catheter was placed so that the distal electrode monitored 5 cm above the manometrically determined LES. Intraesophageal pH was monitored by an electronic device (Medtronic) connected to the catheter. During the study period, the patients were instructed to perform their routine activities and observe no particular dietary restrictions. Proton pump inhibitors and H2 receptor antagonists were discontinued 7 days and 3 days, respectively, before the study. Statistical Analysis Statistical comparison of manometric data between the two age groups was performed using unpaired t tests. Chi-square test was used in the comparison of the demographic data. P values ⱕ 0.05 were considered significant.
RESULTS A total of 349 consecutive patients who underwent both an ambulatory pH test and an esophageal manometry were collected over a 24-month period. From this series, there were 133 patients (38%) aged 65 yr or older and 48 patients (14%) aged 40 yr or younger. The older patients were more likely to be female (69.9% vs 54.1%, p ⬍ 0.05). The distribution of patients according to age and acid exposure, pH ⱕ 4 (⬍5%, 5–10%, ⬎10%) is presented in Table 1, and the distributions among acid exposures for each age group were not statistically different. Table 2 shows the data from the LES and esophageal body. The LES pressures were lowest in patients with acid exposure ⬎ 10% in both age groups. There were otherwise no age-related differences in LES pressure for any particular degree of acid exposure. The data for the percentage of wet swallows resulting in a normal peristaltic sequence are also presented in Table 2.
Table 2. Motility Parameters by Both Age and Percentage Acid Exposure ⬍5% Acid Exposure ⱖ65 yr
ⱕ40 yr
5–10% Acid Exposure ⱖ65 yr
ⱕ40 yr
⬎10% Acid Exposure ⱖ65 yr
ⱕ40 yr
LESP distal to 23.9 (20.8–27.0) 19.5 (15.5–23.5) 22.8 (16.4–29.2) 20.6 (12.5–28.7) 15.4* (13.1–17.7) 12.6* (9.9–15.3) RIP (mm Hg) LESP proximal to 18.0 (15.2–20.8) 12.8 (10.1–15.5) 13.7 (9.2–18.2) 11.9 (6.8–17.0) 10.1* (8.0–12.2) 8.0* (5.5–10.5) RIP (mm Hg) Percentage normal 80 (73.5–86.5) 86 (79.8–97.2) 85 (73.8–96.2) 71 (46.7–95.3) 62† (49.1–74.9) 95 (90.3–99.7) peristalsis Mean distal 103.8 (90.7–116.9) 80.6 (70.7–90.5) 103.6‡ (89.7–117.5) 69.3 (40.8–97.8) 62.5§ (50.4–74.6) 74.1 (63.7–84.5) esophageal amplitude 95% CI: are presented in parentheses. LESP ⫽ lower esophageal sphincter pressure. * p ⬍ 0.05 compared with ⬍5% and 5–10% within same age group. † p ⬍ 0.05 compared with patients ⱕ40 with ⬎10% acid exposure and compared with patients ⱖ65 with ⬍5% and 5–10% acid exposure. ‡ p ⬍ 0.05 compared with patients ⱕ40 with 5–10% acid exposure. § p ⬍ 0.005 compared with ⬍5% and 5–10% within same age group.
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Failure of Esophageal Peristalsis in Older Patients
37
Table 3. Distribution of Swallow Sequences by Age and Acid Exposure Acid Exposure ⬍5% ⬎10%
Age (yr)
Normal
Ineffective
Nontransmitted
Simultaneous
ⱕ40 ⱖ65 ⱕ40 ⱖ65
86.2 79.9 95.0 62.6
1.0 3.1 0.0 3.4
11.4 12.1 5.0 21.7
1.4 5.0 0.0 12.6
Values are percentages.
In the patients ⱕ 40 yr old, there was no correlation between acid exposure and peristalsis. For the patients ⱖ 65 yr old with the highest acid exposure (⬎10%), a significant reduction in the percentage of normal peristaltic sequences was noted when compared with younger patients (62% vs 95%, p ⬍ 0.05) and when compared with older patients with less acid exposure. There was a trend toward higher distal esophageal pressure (average of the pressure from 3 and 8 cm above the LES) in the patients ⱖ 65 yr old in the ⬍5% and 5–10% acid exposure groups that only reached statistical significance in the 5–10% acid exposure group. The distribution of swallow-induced activity (normal, ineffective, nontransmitted, or simultaneous) is presented in Table 3 for the two extreme groups of acid exposure (⬍5% and ⬎10%). The table illustrates that the abnormalities seen in the older patients with ⬎10% acid exposure were mainly due to nontransmitted contractions, although there was an increase in simultaneous contractions as well. To determine whether the increased prevalence of peristaltic abnormalities in older patients was due to more severe acid reflux, we stratified patients with higher levels of acid exposure (10 –15%, 15–20%, ⬎20%) and compared the age groups. Figure 1 reveals that the distributions were the same between the age groups. Although we did not include the data from all of the intermediate-aged patients (41– 64 yr), we did extract motility data from the subset of inter-
Figure 1. Distribution of reflux parameters in patients with acid exposure greater than 10% subgrouped by degree of exposure. There were 7/16 (44%) younger (ⱕ40 yr) and 15/35 (42%) older (ⱖ65 yr) in the 10 –15% acid exposure subgroup, 3/16 (19%) younger and 8/35 (23%) older in the 15–20% acid exposure subgroup, and 6/16 (38%) younger and 12/35 (34%) older in the ⬎20% acid exposure subgroup (all ns).
mediate-aged patients with acid exposure greater than 10% (n ⫽ 71). Their LES pressures were similar to those seen in the other age groups (distal to RIP: 17.0 ⫾ 3.9 mm Hg; proximal to RIP: 9.4 ⫾ 2.1 mm Hg). The percentage of swallows resulting in peristalsis was intermediate between the younger and older groups (76.7 ⫾ 8.7%), and their peristaltic pressures were similar to the younger group with the same degree of acid exposure (79.8 ⫾ 11.0 mm Hg).
DISCUSSION GERD is a common problem, affecting up to one third of the U.S. population (10). Costs to the U.S. health care system related to GERD have been estimated to be $24.1 billion annually (11). The U.S. population is gradually aging, and it has been estimated that 16.5% will be older than 65 yr by 2020 (12). In addition, GERD in the older population, especially the complications of GERD, appears to be more common than in younger groups. For example, Collen et al. found that esophagitis and Barrett’s esophagus were almost twice as common in patients aged 60 yr or older compared with those younger than 60 yr (81% vs 47%, p ⬍ 0.002) (4). It is not clear what factors lead to more severe GERD in the older patients. The effect of aging on the lower esophageal sphincter has been previously examined in a series of 95 normal control subjects, in whom age did not seem to adversely affect LES pressure (6). Manometric studies in healthy older subjects (⬎70 yr old) did not show a consistent decrease in LES pressure with age (5). A hypotensive LES was suggested to be an uncommon finding in GERD, especially in those with mild or moderate GERD (13), whereas other studies have suggested an inverse correlation between the severity of esophageal damage from GERD and LES pressures (14, 15). These studies did not focus specifically on the effect of age on the LES. Our study indicates that LES pressure remains similar regardless of age, even when our population was segregated by percent acid exposure. The lowest LES pressures occurred in those subjects with worst acid exposure, but this phenomenon was independent of age. Decreased amplitude of esophageal peristalsis has been reported in older normal control subjects (5). In contrast, Richter et al. found an increase in esophageal pressures with aging in their manometry study of 95 healthy controls (6). Similarly, we found that when peristalsis was intact, the pressures tended to be higher in the older patients. The cause of this is not clear. It is possible that there is a loss of
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Achem et al.
inhibitory innervation in older patients, but it is also possible that this difference is due to some type of referral bias (related to who is referred to our laboratory for evaluation) or perhaps to the smaller sample size in the younger group of patients. A previous study found an increased proportion of abnormal peristalsis and delayed esophageal acid clearance in older patients (16), whereas another study found no increase in the proportion of specific motility disorders in older patients (5). It is possible that the variable changes in motility seen in older patients are more related to long term esophageal acid exposure than to the effects of aging on esophageal smooth muscle (17). Our study is the first to correlate distal esophageal peristalsis with the degree of esophageal acid exposure in older patients. We found that failed peristalsis occurs more commonly in the group of older patients with the most severe degree of acid exposure. In addition, whereas prior studies have indicated more severe disease in older patients, our study did not confirm higher percent acid exposure in our older patients. This could be owing to the possibility that many older patients have erosive esophagitis and are not referred for an ambulatory pH test. Our observations suggest that the increased prevalence of the complications of GERD noted in previous studies of elderly subjects (1, 4) may be due to impaired esophageal motility and hence delayed clearance. We attempted to correlate calculated clearance (total acid exposure/number of episodes) and found no association with age. We believe this is because of the imprecise definition of an “episode” by computer analysis, and additional studies are needed with new technologies, such as impedance testing, to more accurately evaluate esophageal clearance. Additionally, older patients may fail to perceive esophageal reflux episodes because of a defective visceral sensory mechanism (18). We speculate that the sustained and prolonged acid exposure experienced over time coupled with a blunted sensory perception may be the most plausible explanations for the severity of GERD recognized in patients aged 65 yr and older. We plan to evaluate neurosensory perception in these subjects during future studies. GERD is a multifactorial disorder. Several other mechanisms may operate to explain the more severe nature of this disorder in the elderly. Hiatal hernias are more common with advancing age (7). This structural defect of the antireflux barrier should result in lower LES pressure, but this has not been confirmed. Transient LES relaxations are the single most common cause of reflux. The frequency of transient LES relaxations in the elderly has not been evaluated. There is an age dependent fall in salivary bicarbonate production, which may also seem to increase esophageal acid exposure because of a delay in acid clearance (19). The integrity of the esophageal mucosa resistance and the status of gastric emptying or duodenogastric reflux in the elderly have not been evaluated. Our study did not address the potential contribution of these factors in our population. One might
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speculate that older patients have more severe underlying disease (diabetes, Parkinson’s disease, amyotrophic lateral sclerosis, etc), hence more disordered peristalsis. Although we do not have detailed information on underlying diseases in this population, our data do not support that supposition, because if the dysmotility was due to underlying disease it should not be so strongly correlated with acid exposure. Finally, when peristaltic dysfunction is discovered in an older patient, their medications should be reviewed for agents that might alter esophageal function (anticholinergics, calcium channel blockers, nitrates, etc). In conclusion, our findings indicate that esophageal peristaltic dysfunction is common in older patients with more severe GERD, whereas the fall in LES pressure seen with increased acid exposure does not seem to be age dependent. The impairment may result in a prolongation of acid exposure and potentially could increase older patients’ risk for complications of GERD, including ulcers, strictures, and Barrett’s esophagus. These findings may also impact the decision process and outcome for older patients considered for antireflux surgery. Additional studies are needed to determine how these physiological abnormalities translate into differences in clinical outcome in older patients with GERD. It will also be important to attempt to determine whether these motility abnormalities are caused by acid reflux or are the cause of the reflux itself. This may be an unanswerable question, but perhaps a little of each possibility is true. In some patients, reflux may impair motility, which subsequently worsens reflux and sets up a spiraling feedback loop that eventually results in both complications of GERD and impaired peristalsis. These events seem to be more common in older patients. Reprint requests and correspondence: Kenneth R. DeVault, M.D., Mayo Clinic, Division of Gastroenterology, 4500 San Pablo Road, Jacksonville, FL 32233. Received Mar. 20, 2002; accepted Aug. 19, 2002.
REFERENCES 1. Richter JE. Gastroesophageal reflux disease in the older patient: Presentation, treatment, and comparisons. Am J Gastroenterol 2000;95:368 –73. 2. Howard PJ, Heading RC. Epidemiology of gastroesophageal reflux disease. World J Surg 1992;16:288 –93. 3. Locke GR, III, Talley NJ, Fett SL, et al. Prevalence and clinical spectrum of gastroesophageal reflux: A population based study in Olmsted County, Minnesota. Gastroenterology 1997;112:1448 –56. 4. Collen MJ, Abdulian JD, Chen YK. Gastroesophageal reflux disease in the elderly: More severe disease that requires aggressive therapy. Am J Gastroenterol 1995;90:1053–7. 5. Hollis JB, Castell DO. Esophageal function in elderly men. A new look at presbyesophagus. Ann Intern Med 1974;91:897– 904. 6. Richter JE, Wu CW, Johns DN, et al. Esophageal manometry in 95 healthy adult volunteers. Dig Dis Sci 1987;32:583–92. 7. Stilson W. Hiatal hernia and gastroesophageal reflux. Radiology 1969;93:1323–37.
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8. Dalton CB, Castell IA. Measurement and interpretation. In: Castell DO, Castell JA, eds. Esophageal motility testing, 2nd ed. New York: Appleton and Lange, 1994:61–80. 9. O’Sullivan GC, DeMeester TR, Joelson BE, et al. Interaction of lower esophageal sphincter pressure and length of sphincter in the abdomen as determinants of gastroesophageal competence. Am J Surg 1982;143:40 –7. 10. Friedman LS. Gastrointestinal disorders in the elderly. Gastroenterol Clin N Am 1990;183:811–20. 11. Levin TR, Schmittdiel JA, Kunz K, et al. Costs of acid-related disorders to a health maintenance organization. Am J Med 1997;103:520 – 8. 12. U.S. Census Bureau. Projections of the total resident population by 5-year age groups, and sex with special age categories: Middle series, 2016 to 2020. Available at: http://www.census.gov/ population/projections/nation/summary/np-t3-e.txt. Accessed October 29, 2002. 13. Dent J, Holloway RH, Toouli J, Dodds WJ. Mechanisms of
Failure of Esophageal Peristalsis in Older Patients
14. 15. 16. 17. 18. 19.
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lower esophageal sphincter incompetence in patients with symptomatic gastroesophageal reflux. Gut 1988;29:1020 –8. Iascone C, DeMeester TR, Little AG, Skinner DB. Barrett’s esophagus. Functional assessment, proposed pathogenesis, and surgical therapy. Arch Surg 1983;118:543–9. Coenraad M, Masclee AA, Straathof JW, et al. Is Barrett’s esophagus characterized by more pronounced acid reflux than severe esophagitis? Am J Gastroenterol 1998;93:1068 –72. Ferriolli E, Oliveira RB, Matsuda NM, et al. Aging, esophageal motility, and gastroesophageal reflux disease. J Am Geriatr Soc 1998;46:1534 –7. Tack J, vanTrappen G. The aging oesophagus. Gut 1997;41: 422–4. Lasch H, Castell DO, Castell JA. Evidence for diminished visceral pain with aging: Studies using graded intraesophageal balloon distension. Am J Physiol 1997;272:G1–3. Sonnenberg A. Salivary secretion in reflux esophagitis. Gastroenterology 1982;83:889 –97.
Vol. 98, No. 1, 2003 ISSN 0002-9270/03/$30.00 PII S0002-9270(02)05856-2
Failure of Esophageal Peristalsis in Older Patients: Association with Esophageal Acid Exposure A. Cristina Achem, Sami R. Achem, Mark E. Stark, and Kenneth R. DeVault Department of Medicine, Mayo Clinic, Jacksonville, Florida
OBJECTIVES: Gastroesophageal reflux disease (GERD) is common in all ages, but its prevalence appears to increase with age. Older patients often need aggressive medical therapy and are frequently being considered for antireflux surgery. We sought to evaluate the physiological defect (lower esophageal sphincter [LES] pressures, esophageal motility, and acid exposure) in a group of GERD patients ⱖ 65 yr old in comparison with a younger population (ⱕ40 yr). We hypothesized that age has an adverse impact on esophageal motility and reflux parameters. METHODS: Consecutive patients who completed esophageal manometry and ambulatory pH testing in our laboratory were evaluated for the study. The study group consisted of those ⱖ65 yr old and the control group of those ⱕ40 yr old. Each group was then divided according to their percent esophageal acid (pH ⬍ 4.0) exposure (⬍5%, 5–10%, ⬎10%). Motility parameters (LES and esophageal body) were compared between the two groups. RESULTS: Of 349 patients who underwent manometry and pH testing during the study period, 133 were ⱖ65 yr old, and 48 were ⱕ40 yr old. The degree of acid exposure was similar in both groups. The resting LES pressure was similar regardless of age but was lowest for both age groups in the patients with acid exposure ⬎ 10% (12.6 mm Hg in the ⱕ40-yr-old patients and 15.4 mm Hg in the ⱖ65-yr-old patients, p ⬍ 0.05). The percentage of swallows that induced normal peristalsis was lowest in the ⱖ65-yr-old patients compared with the ⱕ40-yr-old patients in the group with ⬎10% acid exposure (62.5% vs 95%, p ⬍ 0.05).
yr experienced heartburn or acid regurgitation once a week and 59% at least once a month (3). Older patients suffer from more severe GERD or from advanced complications associated with GERD. Collen et al. noted that 81% of GERD patients aged 60 yr or older developed erosive esophagitis, compared with 47% of those younger than 60 yr with GERD (4). The increase in the lifespan, particularly in the United States, underscores the importance of GERD in the elderly. Yet the factors that lead to a more severe form of GERD in patients of advancing age remain unknown. Hollis and Castell found a decrease in esophageal amplitude with aging for subjects older than 70 yr, although a more recent study by Richter et al. found no such association (5, 6). Hiatal hernias have also been found to increase proportionally with age (7). In our study, we sought to determine whether there are differences in distal esophageal motility and acid contact time between reflux patients aged 65 yr or older and those aged 40 yr or younger.
MATERIALS AND METHODS
INTRODUCTION
Patient Population All patients referred to our laboratory for evaluation of GERD who underwent esophageal manometry and ambulatory pH testing from April, 1999 through April, 2001 were included in the study. The patients who were ⱖ65 yr old constituted the study group, and those ⱕ40 yr old were the controls. Patients 41– 64 yr old were not included in this analysis to ensure a clear cutoff between the study and control groups, although we did examine the subgroup of patients aged 41– 64 yr who had higher acid exposure to help validate our findings. These two groups were then stratified according to percent acid exposure, pH ⱕ 4 (⬍5, 5%–10%, and ⬎10%). Additional data obtained included the following: demographics, lower esophageal sphincter (LES) pressure and percent effective peristalsis in esophageal body, mean esophageal body peristaltic pressure, and percentage distal esophageal acid exposure.
Gastroesophageal reflux disease (GERD) is one of the most common esophageal disorders (1). Acid regurgitation or heartburn, the cardinal symptoms of GERD, affect 10 –20% of the population on a weekly basis and 15– 40% monthly (2). Locke et al. reported that 20% of subjects older than 65
Esophageal Manometry and 24-h Ambulatory pH Testing The technique for measuring esophageal motility included the following. An 8-lumen, polyvinyl catheter (Arndorfer Specialties, Greendale, WI) was used. The four distal open-
CONCLUSION: Reflux in older patients is complicated by disordered esophageal motility. This impaired motility may decrease acid clearance, result in more difficult to control disease, and may render these patients susceptible to GERD complications. (Am J Gastroenterol 2003;98:35–39. © 2003 by Am. Coll. of Gastroenterology)
36
Achem et al.
AJG – Vol. 98, No. 1, 2003
Table 1. Distribution of Patients According to Age and Acid Exposure pH ⱕ4 Age
⬍5% Acid Exposure
5–10% Acid Exposure
⬎10% Acid Exposure
ⱖ65 yr ⱕ40 yr
72/133 (54) 21/48 (44)
26/133 (20) 11/48 (23)
35/133 (26) 16/48 (33)
Values are n (%).
ings were 1 cm apart and the four proximal openings were 5 cm apart. Both sets of channels were located at 90-degree angles. Each channel was perfused with 0.5 ml/min of distilled water with a system of low compliance pneumohydraulic capillary perfusion. The four distal and the four proximal transducers were connected to external transducers with output to a personal computer– based analysis system (Medtronic, Minneapolis, MN). The patients were instructed to fast overnight and were evaluated in the supine position. The catheter was passed nasally into the stomach. After a brief adjustment period, the catheter was gradually removed in 1 cm intervals to record the LES pressure. LES pressure was measured at two points in each of four channels during a station pull-through. The first measurement was taken as an average of the midexpiratory pressure (relative to the gastric baseline) for three or more respiratory cycles. This average is taken from pressure at the highest level before the respiratory inversion point (8). A second measurement was obtained as a midexpiratory point just proximal to the respiratory inversion point (RIP) as described by O’Sullivan et al. (9). Six wet swallows at 30-s intervals were administered to evaluate the percentage of LES relaxation and the residual LES pressure compared with the gastric baseline. The catheter was then positioned so that esophageal peristalsis could be evaluated at 3, 8, 13, and 18 cm above the LES in response to 10, 5-ml water swallows. The distal esophageal amplitude was calculated as an average of the pressures obtained at 3 and 8 cm above the LES. Each contraction sequence was judged as peristaltic, nontransmit-
ted, simultaneous, or ineffective (amplitude less than 30 mm Hg in two or more transducers). Ambulatory pH studies were performed with a 2.1-mm, dual electrode antimony catheter (Medtronic), which was inserted through the nose. The catheter was placed so that the distal electrode monitored 5 cm above the manometrically determined LES. Intraesophageal pH was monitored by an electronic device (Medtronic) connected to the catheter. During the study period, the patients were instructed to perform their routine activities and observe no particular dietary restrictions. Proton pump inhibitors and H2 receptor antagonists were discontinued 7 days and 3 days, respectively, before the study. Statistical Analysis Statistical comparison of manometric data between the two age groups was performed using unpaired t tests. Chi-square test was used in the comparison of the demographic data. P values ⱕ 0.05 were considered significant.
RESULTS A total of 349 consecutive patients who underwent both an ambulatory pH test and an esophageal manometry were collected over a 24-month period. From this series, there were 133 patients (38%) aged 65 yr or older and 48 patients (14%) aged 40 yr or younger. The older patients were more likely to be female (69.9% vs 54.1%, p ⬍ 0.05). The distribution of patients according to age and acid exposure, pH ⱕ 4 (⬍5%, 5–10%, ⬎10%) is presented in Table 1, and the distributions among acid exposures for each age group were not statistically different. Table 2 shows the data from the LES and esophageal body. The LES pressures were lowest in patients with acid exposure ⬎ 10% in both age groups. There were otherwise no age-related differences in LES pressure for any particular degree of acid exposure. The data for the percentage of wet swallows resulting in a normal peristaltic sequence are also presented in Table 2.
Table 2. Motility Parameters by Both Age and Percentage Acid Exposure ⬍5% Acid Exposure ⱖ65 yr
ⱕ40 yr
5–10% Acid Exposure ⱖ65 yr
ⱕ40 yr
⬎10% Acid Exposure ⱖ65 yr
ⱕ40 yr
LESP distal to 23.9 (20.8–27.0) 19.5 (15.5–23.5) 22.8 (16.4–29.2) 20.6 (12.5–28.7) 15.4* (13.1–17.7) 12.6* (9.9–15.3) RIP (mm Hg) LESP proximal to 18.0 (15.2–20.8) 12.8 (10.1–15.5) 13.7 (9.2–18.2) 11.9 (6.8–17.0) 10.1* (8.0–12.2) 8.0* (5.5–10.5) RIP (mm Hg) Percentage normal 80 (73.5–86.5) 86 (79.8–97.2) 85 (73.8–96.2) 71 (46.7–95.3) 62† (49.1–74.9) 95 (90.3–99.7) peristalsis Mean distal 103.8 (90.7–116.9) 80.6 (70.7–90.5) 103.6‡ (89.7–117.5) 69.3 (40.8–97.8) 62.5§ (50.4–74.6) 74.1 (63.7–84.5) esophageal amplitude 95% CI: are presented in parentheses. LESP ⫽ lower esophageal sphincter pressure. * p ⬍ 0.05 compared with ⬍5% and 5–10% within same age group. † p ⬍ 0.05 compared with patients ⱕ40 with ⬎10% acid exposure and compared with patients ⱖ65 with ⬍5% and 5–10% acid exposure. ‡ p ⬍ 0.05 compared with patients ⱕ40 with 5–10% acid exposure. § p ⬍ 0.005 compared with ⬍5% and 5–10% within same age group.
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Table 3. Distribution of Swallow Sequences by Age and Acid Exposure Acid Exposure ⬍5% ⬎10%
Age (yr)
Normal
Ineffective
Nontransmitted
Simultaneous
ⱕ40 ⱖ65 ⱕ40 ⱖ65
86.2 79.9 95.0 62.6
1.0 3.1 0.0 3.4
11.4 12.1 5.0 21.7
1.4 5.0 0.0 12.6
Values are percentages.
In the patients ⱕ 40 yr old, there was no correlation between acid exposure and peristalsis. For the patients ⱖ 65 yr old with the highest acid exposure (⬎10%), a significant reduction in the percentage of normal peristaltic sequences was noted when compared with younger patients (62% vs 95%, p ⬍ 0.05) and when compared with older patients with less acid exposure. There was a trend toward higher distal esophageal pressure (average of the pressure from 3 and 8 cm above the LES) in the patients ⱖ 65 yr old in the ⬍5% and 5–10% acid exposure groups that only reached statistical significance in the 5–10% acid exposure group. The distribution of swallow-induced activity (normal, ineffective, nontransmitted, or simultaneous) is presented in Table 3 for the two extreme groups of acid exposure (⬍5% and ⬎10%). The table illustrates that the abnormalities seen in the older patients with ⬎10% acid exposure were mainly due to nontransmitted contractions, although there was an increase in simultaneous contractions as well. To determine whether the increased prevalence of peristaltic abnormalities in older patients was due to more severe acid reflux, we stratified patients with higher levels of acid exposure (10 –15%, 15–20%, ⬎20%) and compared the age groups. Figure 1 reveals that the distributions were the same between the age groups. Although we did not include the data from all of the intermediate-aged patients (41– 64 yr), we did extract motility data from the subset of inter-
Figure 1. Distribution of reflux parameters in patients with acid exposure greater than 10% subgrouped by degree of exposure. There were 7/16 (44%) younger (ⱕ40 yr) and 15/35 (42%) older (ⱖ65 yr) in the 10 –15% acid exposure subgroup, 3/16 (19%) younger and 8/35 (23%) older in the 15–20% acid exposure subgroup, and 6/16 (38%) younger and 12/35 (34%) older in the ⬎20% acid exposure subgroup (all ns).
mediate-aged patients with acid exposure greater than 10% (n ⫽ 71). Their LES pressures were similar to those seen in the other age groups (distal to RIP: 17.0 ⫾ 3.9 mm Hg; proximal to RIP: 9.4 ⫾ 2.1 mm Hg). The percentage of swallows resulting in peristalsis was intermediate between the younger and older groups (76.7 ⫾ 8.7%), and their peristaltic pressures were similar to the younger group with the same degree of acid exposure (79.8 ⫾ 11.0 mm Hg).
DISCUSSION GERD is a common problem, affecting up to one third of the U.S. population (10). Costs to the U.S. health care system related to GERD have been estimated to be $24.1 billion annually (11). The U.S. population is gradually aging, and it has been estimated that 16.5% will be older than 65 yr by 2020 (12). In addition, GERD in the older population, especially the complications of GERD, appears to be more common than in younger groups. For example, Collen et al. found that esophagitis and Barrett’s esophagus were almost twice as common in patients aged 60 yr or older compared with those younger than 60 yr (81% vs 47%, p ⬍ 0.002) (4). It is not clear what factors lead to more severe GERD in the older patients. The effect of aging on the lower esophageal sphincter has been previously examined in a series of 95 normal control subjects, in whom age did not seem to adversely affect LES pressure (6). Manometric studies in healthy older subjects (⬎70 yr old) did not show a consistent decrease in LES pressure with age (5). A hypotensive LES was suggested to be an uncommon finding in GERD, especially in those with mild or moderate GERD (13), whereas other studies have suggested an inverse correlation between the severity of esophageal damage from GERD and LES pressures (14, 15). These studies did not focus specifically on the effect of age on the LES. Our study indicates that LES pressure remains similar regardless of age, even when our population was segregated by percent acid exposure. The lowest LES pressures occurred in those subjects with worst acid exposure, but this phenomenon was independent of age. Decreased amplitude of esophageal peristalsis has been reported in older normal control subjects (5). In contrast, Richter et al. found an increase in esophageal pressures with aging in their manometry study of 95 healthy controls (6). Similarly, we found that when peristalsis was intact, the pressures tended to be higher in the older patients. The cause of this is not clear. It is possible that there is a loss of
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Achem et al.
inhibitory innervation in older patients, but it is also possible that this difference is due to some type of referral bias (related to who is referred to our laboratory for evaluation) or perhaps to the smaller sample size in the younger group of patients. A previous study found an increased proportion of abnormal peristalsis and delayed esophageal acid clearance in older patients (16), whereas another study found no increase in the proportion of specific motility disorders in older patients (5). It is possible that the variable changes in motility seen in older patients are more related to long term esophageal acid exposure than to the effects of aging on esophageal smooth muscle (17). Our study is the first to correlate distal esophageal peristalsis with the degree of esophageal acid exposure in older patients. We found that failed peristalsis occurs more commonly in the group of older patients with the most severe degree of acid exposure. In addition, whereas prior studies have indicated more severe disease in older patients, our study did not confirm higher percent acid exposure in our older patients. This could be owing to the possibility that many older patients have erosive esophagitis and are not referred for an ambulatory pH test. Our observations suggest that the increased prevalence of the complications of GERD noted in previous studies of elderly subjects (1, 4) may be due to impaired esophageal motility and hence delayed clearance. We attempted to correlate calculated clearance (total acid exposure/number of episodes) and found no association with age. We believe this is because of the imprecise definition of an “episode” by computer analysis, and additional studies are needed with new technologies, such as impedance testing, to more accurately evaluate esophageal clearance. Additionally, older patients may fail to perceive esophageal reflux episodes because of a defective visceral sensory mechanism (18). We speculate that the sustained and prolonged acid exposure experienced over time coupled with a blunted sensory perception may be the most plausible explanations for the severity of GERD recognized in patients aged 65 yr and older. We plan to evaluate neurosensory perception in these subjects during future studies. GERD is a multifactorial disorder. Several other mechanisms may operate to explain the more severe nature of this disorder in the elderly. Hiatal hernias are more common with advancing age (7). This structural defect of the antireflux barrier should result in lower LES pressure, but this has not been confirmed. Transient LES relaxations are the single most common cause of reflux. The frequency of transient LES relaxations in the elderly has not been evaluated. There is an age dependent fall in salivary bicarbonate production, which may also seem to increase esophageal acid exposure because of a delay in acid clearance (19). The integrity of the esophageal mucosa resistance and the status of gastric emptying or duodenogastric reflux in the elderly have not been evaluated. Our study did not address the potential contribution of these factors in our population. One might
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speculate that older patients have more severe underlying disease (diabetes, Parkinson’s disease, amyotrophic lateral sclerosis, etc), hence more disordered peristalsis. Although we do not have detailed information on underlying diseases in this population, our data do not support that supposition, because if the dysmotility was due to underlying disease it should not be so strongly correlated with acid exposure. Finally, when peristaltic dysfunction is discovered in an older patient, their medications should be reviewed for agents that might alter esophageal function (anticholinergics, calcium channel blockers, nitrates, etc). In conclusion, our findings indicate that esophageal peristaltic dysfunction is common in older patients with more severe GERD, whereas the fall in LES pressure seen with increased acid exposure does not seem to be age dependent. The impairment may result in a prolongation of acid exposure and potentially could increase older patients’ risk for complications of GERD, including ulcers, strictures, and Barrett’s esophagus. These findings may also impact the decision process and outcome for older patients considered for antireflux surgery. Additional studies are needed to determine how these physiological abnormalities translate into differences in clinical outcome in older patients with GERD. It will also be important to attempt to determine whether these motility abnormalities are caused by acid reflux or are the cause of the reflux itself. This may be an unanswerable question, but perhaps a little of each possibility is true. In some patients, reflux may impair motility, which subsequently worsens reflux and sets up a spiraling feedback loop that eventually results in both complications of GERD and impaired peristalsis. These events seem to be more common in older patients. Reprint requests and correspondence: Kenneth R. DeVault, M.D., Mayo Clinic, Division of Gastroenterology, 4500 San Pablo Road, Jacksonville, FL 32233. Received Mar. 20, 2002; accepted Aug. 19, 2002.
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8. Dalton CB, Castell IA. Measurement and interpretation. In: Castell DO, Castell JA, eds. Esophageal motility testing, 2nd ed. New York: Appleton and Lange, 1994:61–80. 9. O’Sullivan GC, DeMeester TR, Joelson BE, et al. Interaction of lower esophageal sphincter pressure and length of sphincter in the abdomen as determinants of gastroesophageal competence. Am J Surg 1982;143:40 –7. 10. Friedman LS. Gastrointestinal disorders in the elderly. Gastroenterol Clin N Am 1990;183:811–20. 11. Levin TR, Schmittdiel JA, Kunz K, et al. Costs of acid-related disorders to a health maintenance organization. Am J Med 1997;103:520 – 8. 12. U.S. Census Bureau. Projections of the total resident population by 5-year age groups, and sex with special age categories: Middle series, 2016 to 2020. Available at: http://www.census.gov/ population/projections/nation/summary/np-t3-e.txt. Accessed October 29, 2002. 13. Dent J, Holloway RH, Toouli J, Dodds WJ. Mechanisms of
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