J Vet Intern Med 2001;15:467–470
Evaluation of Esophageal Transit of Tablets and Capsules in 30 Cats Donald S. Westfall, David C. Twedt, Phillip F. Steyn, Elizabeth B. Oberhauser, and Joseph W. VanCleave We have reported tablet-induced focal esophagitis and esophageal stricture formation in cats. The proposed mechanism is thought to be abnormal esophageal tablet retention resulting in focal esophagitis with subsequent stricture formation. The objective of this study was to evaluate the passage of tablets and capsules when given alone (dry swallow) and when followed by a water bolus (wet swallow) to determine if this could, in part, explain the esophageal stricture formation we have observed in cats. Fluoroscopy was used to evaluate tablet or capsule passage after administration. The percentage of dry tablet swallows that successfully passed into the stomach was 0.0% at 30 and 60 seconds, 6.7% at 90 seconds, 13.3% at 120 seconds, 26.7% at 180 and 240 seconds, and 36.7% at 300 seconds. Wet tablet swallows successfully passed 90.0% of the time at 30 seconds, 93.3% of the time at 60 seconds, and 100.0% of the time thereafter. The percentage of dry capsule swallows that successfully passed was 16.7% at each time interval. Wet capsule swallows successfully passed 96.7% of the time at 30 seconds and 100% of the time thereafter. For each time interval, wet swallows achieved significantly greater percentage passage into the stomach when compared to dry swallows (P ⬍ .05). This study shows that tablets or capsules given by dry swallow have prolonged retention in the esophagus compared to those given by wet swallow. On the basis of this study, we recommend the routine administration of a water bolus to cats receiving tablets or capsules PO to facilitate esophageal clearance. This practice may help prevent medication-associated esophagitis or stricture formation. Key words: Doxycycline; Esophageal motility; Esophageal stricture; Esophagitis.
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sophagitis and benign esophageal strictures occur secondary to esophageal irritation and cause dysphagia and regurgitation.1–6 Etiologies include esophageal trauma secondary to foreign body ingestion, gastroesophageal reflux associated with incompetence of the lower esophageal sphincter, and damage secondary to administration of certain caustic substances that are irritating to the esophageal mucosa.1–10 Numerous examples of tablet-associated esophagitis and esophageal stricture formation have been reported in humans secondary to administration of medications.6–9 The most commonly reported drugs include nonsteroidal anti-inflammatory drugs (NSAIDs) and doxycycline.6–9 Because of the frequency of tablet-associated esophagitis and esophageal stricture formation, studies have been performed in humans to determine the transit time of barium-laden tablets through the esophagus.11–15 In one study,11 only 9% of pills passed into the stomach in a timely fashion when tablets were taken as a dry swallow without a water bolus. The percentage of pill passage increased to 95% when a 6.0-mL water bolus was given after tablet ingestion. At Colorado State University Veterinary Teaching Hospital, we reported 4 cats and subsequently identified a 5th cat as having esophageal strictures thought to be secondary to doxycycline tablet ingestion.10 The proposed mechanism is failure of adequate esophageal propagation of tablets into the stomach, leading to esophageal retention and resultant From the Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO. Reprint requests: David C. Twedt, DVM, Colorado State University, Veterinary Teaching Hospital, Department of Clinical Sciences, 300 W Drake Road, Fort Collins, CO 80523; e-mail: dtwedt@vth. colostate.edu. Submitted December 11, 2000; Revised March 16, 2001; Accepted April 4, 2001. Copyright 䉷 2001 by the American College of Veterinary Internal Medicine 0891-6640/01/1505-0006/$3.00/0
local tissue irritation due to the caustic nature of doxycycline. Delayed esophageal transit may have been prolonged, because these patients were sick and possibly dehydrated at the time. Doxycycline retention resulted in focal esophagitis that progressed to focal fibrosis with formation of an esophageal stricture. In all 5 cats, the esophageal stricture was identified in the midcervical esophagus. Clinical signs became evident between 1 and 2 weeks after doxycycline administration. The objective of this study was to determine the success of esophageal transit of tablets and capsules in cats after both dry and wet swallows and to investigate the reason for pill-associated esophagitis and esophageal stricture formation in cats.
Materials and Methods Study Population Thirty normal cats were used for the evaluation of esophageal transit of tablets and capsules. Study cats consisted of healthy cats owned by the faculty, staff, and students at the Colorado State University College of Veterinary Medicine and Biomedical Sciences and were of various ages (2–14 years old) and of both genders (16 spayed females and 14 castrated males). Sampling of the population was random but was based on voluntary participation of the owners. To encourage participation and ensure that patients were healthy, all cats had complete history and physical examination, CBC, serum biochemistry, urinalysis, fecal examination, feline leukemia virus, and feline immunodeficiency virus testing performed. Only normal cats were entered into the study. Cats with a history of vomiting, diarrhea, regurgitation, swallowing problems, long-term medication administration, or abnormal laboratory findings were excluded from the study. The study was reviewed and approved by the Animal Care and Use Committee at Colorado State University.
Tablets and Capsules Specifically formulated inert barium sulfate tablets were compounded into a 20-mg-size tablet (3.5-mm diameter, 2.0-mm thickness) for administration. This tablet size approximated the typical size of many medications used in cats, including the normal form of doxycycline
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Table 1. Number of times tablets successfully passed through the esophagus into the stomach in 30 cats at given time intervals following routine administration (dry swallow) and routine administration followed by a 6.0-mL water bolus (wet swallow).
Fig 1. Percentage of tablets successfully passing through the esophagus of cats into the stomach after wet and dry swallows. * denotes statistically significant difference.
used in cats (¼ of a 100-mg tablet). Capsules were similarly formulated into a 190-mg size (size 4 capsules).
Radiology A specially designed, ventilated, clear Plexiglass box was used to restrain the cats during fluoroscopic evaluation. The dimensions of the box were the approximate size of most commercial cat carriers and were large enough to allow the cat to change positions within the box. Further restraint was not required, and this method appeared to cause minimal or no stress to the cats. Barium tablet and capsule transit was determined by fluoroscopy.a Barium tablets were administered in a routine fashion (dry swallow), and the time and location of the tablet or capsule were recorded by fluoroscopy at 0, 30, 60, 90, 120, 240, and 300 seconds after administration. Fluoroscopic images were recorded at each time point for subsequent analysis. Retained tablets were passed into the stomach by administering a 6.0-mL water bolus. The study then was repeated, but immediately after tablet administration, a 6.0-mL bolus of water was given PO via syringe (wet swallow). An identical protocol then was employed by means of capsules rather than tablets. A 5-minute waiting period was used between each tablet and capsule study. Each cat had a total of 4 studies performed (a dry tablet swallow followed by a wet tablet swallow, then a dry capsule swallow followed by a wet capsule swallow). Successful passage was defined as tablet or capsule passage into the stomach. Unsuccessful passage was defined as retention of the tablet or capsule in the esophagus at the given time interval.
Statistical Evaluation
Time Interval (seconds)
No. Successful Passages (dry swallow)
No. Successful Passages (wet swallow)
30 60 90 120 180 240 300 ⬎300
0 0 2 2 4 0 3 19
27 1 2 0 0 0 0 0
30 cats (36.7%). After a dry tablet swallow, 19 of 30 cats (63.3%) retained tablets in the esophagus for greater than 300 seconds. Wet tablet swallows successfully passed in 27 of 30 cats (90.0%) at 30 seconds and in 1 additional cat (1 of 30, 3.3%) at 60 seconds, for a total of 28 of 30 cats (93.3%), and in the remaining 2 cats at 90 seconds (2 of 30, 6.7%) for a total of 30 of 30 cats (100.0%) at this time interval and thereafter. No tablets were retained longer than 90 seconds after a wet tablet swallow (Fig 1; Table 1). Dry capsule swallows successfully passed in 5 of 30 cats (16.7%) at 30 seconds. After a dry capsule swallow, the 25 remaining cats (25 of 30, 83.3%) retained capsules in the esophagus for greater than 300 seconds. Wet capsule swallows successfully passed in 29 of 30 cats (96.7%) at 30 seconds and in the 1 remaining cat (1 of 30, 3.3%) at 60 seconds for a total of 30 of 30 cats (100.0%) at this time interval and thereafter. No capsules were retained longer than 60 seconds after a wet capsule swallow (Fig 2; Table 2). For each time interval, wet swallows achieved significantly greater percentage passage into the stomach compared to dry swallows (P ⬍ .05). Most tablets were retained in the cervical esophagus (22 of 30, 73.33%). A smaller percentage of tablets was retained in the thoracic esophagus (7 of 30, 23.33%), and a small percentage was retained in the oropharyngeal region
Comparisons were made between groups (dry versus wet swallow) at each time interval after tablet or capsule administration (proportion of successful passages per group per time interval). The number of tablets and capsules successfully passing at each time interval was recorded as binary data and expressed as the proportion of successful passages per total number of attempts per time interval. Statistical analysis was achieved by a Z proportional test at each time interval.b
Results The percentage of dry tablet swallows that successfully passed into the stomach was 0 of 30 cats (0.0%) at 30 and 60 seconds, 2 of 30 cats (6.7%) at 90 seconds, and 2 additional cats (2 of 30, 6.7%) at 120 seconds for a total of 4 of 30 cats (13.3%); 4 additional cats (4 of 30, 13.3%) at 180 seconds for a total of 8 of 30 cats (26.7%); no additional cats at 240 seconds (8 of 30, 26.7%); and 3 additional cats (3 of 30, 10.0%) at 300 seconds for a total of 11 of
Fig 2. Percentage of capsules successfully passing through the esophagus of cats into the stomach after wet and dry swallows. * denotes statistically significant difference.
Esophageal Transit of Tablets and Capsules in Cats
Table 2. Number of times capsules successfully passed through the esophagus into the stomach in 30 cats at given time intervals following routine administration (dry swallow) and routine administration followed by a 6.0-mL water bolus (wet swallow). Time Interval (seconds)
No. Successful Passages (dry swallow)
No. Successful Passages (wet swallow)
30 60 90 120 180 240 300 ⬎300
5 0 0 0 0 0 0 25
29 1 0 0 0 0 0 0
(1 of 30, 3.33%). The majority of capsules also were retained in the cervical esophagus (22 of 25, 88.00%). A small percentage of capsules was retained in the thoracic esophagus (1 of 25, 4.00%) and in the oropharyngeal region (2 of 25, 8.00%).
Discussion This study documents that tablets and capsules have longer esophageal transit times after dry swallows when compared to wet swallows. The reported normal esophageal transit time of liquid barium or barium-impregnated food given to cats is 1–2 cm/s.3 This equates to the passage of contents through the esophagus of cats in approximately 10–20 seconds after a swallow. However, to stimulate normal esophageal transit, a strong swallow must occur followed by formation of an adequate size bolus distending the proximal esophagus to initiate primary and secondary esophageal peristalsis.3 Tablets or capsules given as a dry swallow may not be of sufficient size to initiate esophageal primary or secondary peristaltic activity. In a recent study, 19.4% of capsules given to cats were retained abnormally in the midcervical esophagus for 30– 240 seconds after routine administration.16 In the same study, 52.8% of capsules given to cats were trapped for greater than 240 seconds.16 Trapped capsules passed into the stomach if the cat was fed a small amount of food.16 The former study did not investigate the esophageal transit of tablets or the esophageal transit of capsules after a wet swallow. This study shows that retained tablets or capsules pass quickly to the stomach after a 6.0-mL water bolus. The administration of a water bolus is thought to be easier to achieve than feeding a small meal after administration of a medication PO, especially in sick patients. The location of esophageal retention of tablets and capsules in this study was predominantly the midcervical esophagus. Esophageal strictures in cats reported after doxycycline administration were located in the midcervical esophagus.10 These findings support the theory that abnormal esophageal retention of doxycycline tablets in the midcervical esophagus of cats may result in focal esophagitis and esophageal stricture formation.
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Esophagitis secondary to tablet administration may be overlooked in many ill cats, and secondary esophagitis from medications may contribute to disease morbidity and slow recovery. The clinical signs of esophagitis often are vague and include pain, dysphagia, regurgitation, salivation, and anorexia.1–6,10 Definitive diagnosis is made by means of contrast radiography or endoscopy to identify focal mucosal damage. We postulate that abnormal esophageal retention of tablets and capsules may be greater in sick, dehydrated, or debilitated patients receiving medications PO. A limitation of this study is that all cats were administered dry swallows followed by wet swallows. The shorter esophageal clearance times seen after wet swallows may have been caused by more effective stimulation of secondary esophageal peristalsis by subsequent tablet or capsule administration. Additionally, if a tablet or capsule was retained, a 6.0-mL water bolus was used to achieve esophageal clearance. This technique also may have resulted in more effective stimulation of secondary esophageal peristalsis by subsequent tablet or capsule administration or possibly may have lubricated the esophagus, making subsequent tablet or capsule passage more successful. However, in the authors’ opinion, an adequate amount of time occurred between dry and wet swallows to negate any bias possibly caused by repetitive stimulation of esophageal peristalsis. Additionally, tablet studies were followed by dry capsule studies, and no appreciable decrease in dry capsule esophageal clearance times was seen. If repetitive stimulation of esophageal peristalsis had been a factor in the decreased clearance times seen in wet swallows, one would have expected also to see faster clearance times of dry capsules, because the capsule studies immediately followed the tablet studies. In summary, results of this study demonstrate that tablets or capsules have markedly greater transit times through the esophagus of cats when given as a dry swallow when compared to transit times after a wet swallow. The administration of a 6.0-mL water bolus resulted in rapid passage of tablets and capsules into the stomach. Based on results of this study, we recommend that cats be given a 6.0-mL water bolus after tablet or capsule administration. This recommendation will ensure that proper medication dosages are achieved by facilitating esophageal transit and may prevent focal esophagitis and esophageal stricture formation associated with doxycycline or NSAID administration.
Footnotes Siemens威 Polydros 80s digitized fluoroscopy unit with an Inficon威 image intensifier, Iselin, NJ (Siemens), Liverpool, NY (Inficon) b Microsoft威 Excel 2000, Seattle, WA a
Acknowledgments Funded by the Winn Feline Foundation. The initial pilot study was funded by the Asmus Memorial Fund. The authors would like to extend thanks to Jim Green for his crafting of the Plexiglass cat box used in this study.
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