• Open Access

Prevalence of Gastroesophageal Reflux Disease in Premature Calves

Authors


  • This work was performed at the University of Selcuk.

  • This study was presented as poster at 19th International Congress of Mediterranean Federation of Health and Production of Ruminants in Serbia.

Corresponding author: Dr I. Sen, Department of Internal Medicine, Faculty of Veterinary Medicine, University of Selcuk 42079 Campus, Konya, Turkey; e-mail: ismailsen@selcuk.edu.tr

Abstract

Background

Gastroesophageal reflux (GER) is the presence of gastric contents proximal to the stomach. Pathologic consequences secondary to GER are termed gastroesophageal reflux disease (GERD).

Objectives

The purpose of this study was to determine the prevalence of GER and GERD in premature calves by endoscopic examination.

Animals

Ten healthy and 51 premature calves were included in the study. All premature calves also had respiratory distress syndrome.

Methods

Esophagoscopy of premature calves was conducted by fiber optic endoscopy. Abnormalities such as increased saliva, hyperemia, hemorrhage, petechiae, presence of abomasal content in the esophagus, and relaxation of the lower esophageal sphincter (LES) were evaluated by endoscopy.

Results

The prevalence of GERD and GER in the premature calves was 55 and 67%, respectively. Hyperemia and hyperemia with hemorrhage or petechiation of the esophageal mucosa were determined by endoscopic examination. Hyperemia was commonly observed in the distal esophageal mucosa, although a few hyperemic areas also were observed in other portions of the esophagus. In addition to these abnormalities, LES relaxation, abomasal fluid in the distal esophagus, abomasal content in the esophagus, and increased saliva also were observed in premature calves with GER.

Conclusions

The prevalence of both GER (67%) and GERD (55%) in premature calves was high in the study. Endoscopy provides a practical, rapid, noninvasive, and reasonably accurate method for determining the presence of GER and GERD in premature calves.

Abbreviations
GER

gastroesophageal reflux

GERD

gastroesophageal reflux disease

LES

lower esophageal sphincter

BE

base excess

Gastroesophageal reflux (GER) is the presence of gastric contents proximal to the stomach.[1] The major physiologic causes of GER include an increased number of transient lower esophageal sphincter (LES) relaxations, ineffective esophageal motility, and decreased LES tone.[2-4] GER is common in preterm human infants, occurring an average 3–5 times per hour.[5] When pathologic consequences exist secondary to GER, the condition is termed gastroesophageal reflux disease (GERD). The term GERD is used to encompass all of the manifestations of esophageal exposure to gastric contents.[1, 6] Davidson and Omari[7] showed that it is important to diagnose GERD in infants, which can manifest itself as malnutrition, respiratory disorders, or esophagitis as well as its complications, to effectively treat the condition. Esophageal acid exposure can lead to sequelae including esophagitis, strictures, and bleeding.[8, 9] In dogs, esophagitis most often occurs secondary to chronic gastritis or as a result of reflux of gastric juice.[10] Unfortunately, reports have not been published concerning GER or GERD in premature calves.

A single test for the diagnosis of GER or GERD currently does not exist. The diagnostic techniques most commonly used to establish the presence of GER or GERD are upper gastrointestinal endoscopy, barium fluoroscopy, radionuclide scintigraphy, and intraesophageal pH monitoring.[7] In human medicine, esophageal manometry and esophageal pH monitoring also are used.[11] Esophageal pH measurement is not readily available or practical in animals, although abomasal luminal pH measurements have been made in suckling calves through an abomasal cannula.[12] As a result of the difficulties associated with the use of a number of these techniques in animals, endoscopy has become increasingly important in veterinary medicine. The procedure is widely used in dogs,[13, 14] horses,[15] and cattle[16, 17] and supports clinical examinations for the diagnosis of gastrointestinal, urinary tract, and pulmonary diseases.[13-17] Esophagoscopy is a valuable supplementary technique that, in conjunction with clinical examination, may facilitate diagnosis in cattle,[17, 18] but there are no published reports on the use of esophagoscopy in calves. The purpose of this study was to determine the prevalence of GER and GERD by endoscopic examination in premature calves.

Material and Methods

Animals

This study was approved by the Ethics Committee of the Faculty of Veterinary Medicine, Selcuk University. Fifty-six premature calves were admitted to the School of Veterinary Medicine for diagnosis and treatment. Calves were defined as being premature if they were the product of a short gestation time (between 230 to 260 days) as determined by artificial insemination records. In addition to short gestational age, clinical signs of low birth weight, including an inability to stand, short and silky hair, and incomplete eruption of the incisor teeth also were present in the premature animals. A weak or absent suckling reflex was used to determine each animal's eligibility for the study. All of the calves were admitted to the clinic within 24 hours after birth. The body weight of the premature calves, upon admission, ranged from 20 to 30 kg. Fifty-one of the premature calves were Holsteins, and 5 were Swiss-Browns; 32 were bull calves. All premature calves also had respiratory distress syndrome (Table 1).

Table 1. Venous blood gas and acid-base values in 51 premature calves
npH (Mean ± SD)pCO2 (mmHg) (Mean ± SD)pO2 (mmHg) (Mean ± SD)HCO3 (mmol/L) (Mean ± SD)BE (mmol/L) (Mean ± SD)
  1. pH, blood pH; PO2, partial pressure of oxygen; PCO2, partial pressure of carbon dioxide; HCO3, bicarbonate; BE, Base excess.

517.22 ± 0.1172.0 ± 11.419.3 ± 5.326.1 ± 5.3−0.8 ± 6.9

Fifty-one of the premature calves were examined for abnormalities associated with GER by endoscopic instrumentation; 5 calves died before endoscopic evaluation. Three of the 5 calves that died before endoscopy succumbed to aspiration pneumonia whereas asphyxia was determined to be the cause of death, at necropsy, in 2 calves.

Ten healthy 3- to 5-day-old calves were used as controls. All of the healthy calves were Holsteins; 6 were bull calves. Endoscopic examination was performed on all control calves.

Sample Collection and Blood Analyses

Samples for blood gases and pH analyses (pH, pCO2, pO2, HCO3 , BE, and oxygen saturation) were collected anaerobically into heparinized 3 mL plastic syringes from the jugular vein and measured immediately using a blood gas analyzer.1

Standard Treatment Protocol for Premature Calves

Each calf was kept at a thermoneutral ambient temperature by covering it with a blanket. Intravenous fluids (lactated Ringer's solution2; 0.9% NaCl3 and 5% dextrose4) were administered, as needed. Fluid therapy was continued until the general condition of the calves improved. Vitamin ADE,5 Vitamin D,6 Vitamin B complex,7 calcium,8 and phosphorus9 were administrated by IM injection. All premature calves received oxygen therapy, as dictated by their oxygen saturation, and each calf also received a SC injection of 10 mg/kg caffeine.10 Oxygen therapy was available to all premature calves for 12–48 hours, and endoscopic examination was performed 12 hours after cessation of oxygen therapy on calves with improved respiration.

Treatment of Calves before Endoscopic Examination

Both healthy and premature calves were bottle-fed 2 hours before endoscopic examination of the esophagus (esophagoscopy). Sedatives or analgesic agents were not used before endoscopic examination. In 2 calves, a sedative solution (xylazine, 0.2 mg/kg11) was administered at the beginning of the study; these animals demonstrated increased salivation, dyspnea, abdominal tympany, and a general worsening of their condition after sedation. Therefore, sedation was not used before endoscopic examination in the study. The 2 sedated calves were excluded from the study. Esophagoscopy of premature calves was performed using a fiberoptic endoscopy instrument12 (9.8 mm diameter, 105 cm long).

Endoscopic Examination

Calves were placed in left lateral recumbency for endoscopic examination. The endoscope was inserted through the pharynx so that the cranial esophageal mucosa was visible (approximately 25–30 cm). To facilitate optimal visibility, it was necessary to create a lumen by means of insufflation of air, allowing unrestricted movement of the tip of the endoscope. The endoscope was advanced into the esophagus using only minor adjustments in tip deflection and torque to maintain a full panoramic view of the lumen and mucosal surfaces as well as the LES. The following parameters were evaluated: hyperemia, hemorrhage, petechiation, and the presence of abomasal content in the esophagus. The tip of the endoscope was deflected approximately 30 degrees to the left with a slight simultaneous upward motion as the LES was passed. The endoscope tip was directed and advanced to the abomasum (approximately 50–55 cm) to determine the presence of abomasal content. The most important finding for defining the presence of GER was the observation of LES relaxation. The presence of hemorrhage or petechiation and abomasal content in the esophagus, in conjunction with LES relaxation, were indicative of GERD.

Endoscopic examination of the esophagus of each animal in the study lasted approximately 15 minutes and was performed by the same investigator. The endoscopic examinations did not result in any complications.

Results

The esophageal mucosa was visible and abomasal content was not observed in the esophagus of healthy calves. In the healthy animals, the LES was closed, and there was little content within the abomasum. In addition, neither relaxation of the LES nor esophageal mucosal abnormalities were observed in these animals (Fig 1A,B). These observations indicated that none of the healthy calves had GER or GERD.

Figure 1.

Endoscopic view of normal esophagus mucosa (A and B).

None of the premature calves had a suckling reflex, and none were able to maintain a standing position. Despite intensive standard treatment, 5 of the 56 premature calves died within 2 hours of admission to the clinic and were consequently excluded from the study. All premature calves had forced respiratory movements and nasal flaring, periodic episodes of apnea, and some appeared cyanotic. The calves also had low venous pH and pO2 and high pCO2 (Table 1) consistent with hypoventilation, hypoxemia, and inadequate oxygen delivery.

GER was diagnosed in 34 (67%) of the premature calves by endoscopic examination. Most of the GER-related clinical signs such as LES relaxation, abomasal fluid in the distal esophagus, abomasal content in the esophagus, and increased salivation were present in the 34 animals (Fig 2A, B). Hyperemia and hemorrhage or petechiation on the esophageal mucosa was observed in 28 of the 34 calves with GER (Fig 3A–D). These calves were determined to have GERD.

Figure 2.

Endoscopic view of abomasal content in the esophagus and relaxed LES, but not GERD (A and B).

Figure 3.

Hyperemia and abomasal content in the esophagus (A), Hyperemia and hemorrhage on esophageal mucosa along with a relaxed LES (B), Hyperemia, hemorrhage and abomasal content in the esophagus and a relaxed LES (C), Hyperemia, hemorrhage, and petechial bleeding on esophagus mucosa (D).

Evaluation of GERD by Endoscopic Examination in Premature Calves

Hyperemia (n = 28, Fig 3A) and hyperemia with hemorrhage or petechiation (n = 18, Fig 3B,C,D) of the esophageal mucosa were identified by endoscopic examination. Hyperemia was commonly observed in the distal esophageal mocosa, but also was present in other parts of the esophagus. In addition to these abnormalities, abnormal relaxation of the LES (n = 34, Fig 3A, C), presence of abomasal fluid in the distal esophagus, presence of abomasal content in the esophagus (n = 34, Fig 3C) and increased salivation (n = 19) also were observed in premature calves with GERD.

Discussion

The American College of Gastroenterology has defined GER as mucosal damage produced by the abnormal reflux of gastric contents into the esophagus.[19] Rudolph et al[20] defined GER as passage of gastric contents into the esophagus, and GERD as clinical signs or complications of GER. The composition and pH of the refluxed material may help to determine whether or not esophagitis develops. The duration of time that refluxed material remains in the esophagus is likely a more important indicator of whether or not damage occurs.[11] This study effectively demonstrated that endoscopy is a valuable tool for determining mucosal changes in the esophagus of a premature calf. Endoscopic examination disclosed esophageal mucosal changes, such as hyperemia, hemorrhage, or petechiation, in 28 of 51 (55%) premature calves. These esophageal mucosal changes were symptomatic of GERD. In addition, 34 of the 51 premature calves had signs of GER. Although 28 of the 34 calves with GER also showed signs of GERD, 6 calves did not demonstrate any abnormalities of the esophageal mucosa. This observation suggests that the presence of GER does not necessarily lead to esophagitis.

Many investigations[21, 22] have shown that a premature calf typically has a clinically short gestational period, low birth weight, short silky hair, generalized weakness, inability to stand, a weak or absent suckling reflex, respiratory distress, soft lips, and soft claws. The premature animals included in this study demonstrated most of these typical clinical signs. The premature animals also exhibited acidemia, primarily because of respiratory acidosis (increased pCO2), although the low venous O2 tension (hypoxemia) and low bicarbonate concentrations combined with base excess values, in some calves, were consistent with arterial hypoxemia and inadequate oxygen delivery. Hypoxic neonates, most at risk to be affected by respiratory acidosis, are those reported to have a weak or absent suckling reflex, have difficulty maintaining sternal recumbency, and require more time before being able to stand.[23]

Esophagitis can be caused by GER, trauma, presence of foreign bodies, ingestion of caustic substances, structural abnormalities (eg, hiatal hernia, neoplasms), and chronic vomiting.[11] The major physiologic causes of GER in human infants include an increased number of transient LES relaxations, ineffective esophageal motility, and decreased LES tone.[3] Several factors can impair LES function and cause reflux, including many anesthetic agents, such as anticholinergics, acepromazine maleate, diazepam, narcotic analgesics, and xylazine. These agents are known to decrease LES pressure and predispose to GER.[24, 25] Prolonged fasting (ie, >24 hours) also has been shown to increase the acidity of refluxed gastric contents and increase the frequency of GER.[26, 27] Therefore, anesthetic agents were not used for premedication in the study.

Esophageal complications of GER in adult humans include esophagitis, esophageal ulceration, and Barrett's esophagus.[4] In 28 of the premature calves in this study, mucosal changes such as hyperemia, hemorrhage, and petechiation of the esophageal mucosa were observed by endoscopic examination. In addition, abomasal fluid was present in the distal esophagus. This was likely because of the premature animals not being able to stand, which facilitated the escape of abomasal fluid into the esophagus, in combination with the improper relaxation of the LES. The presence of acidic fluid in the esophagus likely caused the abnormalities observed in the esophageal mucosa. The refluxed gastric contents contain acid (the pH of abomasal fluid in neonatal calves is between 1 and 2[12]), pepsin, trypsin, bile acids, and lysolecithin, which all contribute to esophageal damage. Although the most important factor is acid, it is a combination of these gastric components that leads to esophageal damage.[28]

GER is one of the most prevalent gastrointestinal problems in children.[1] Unfortunately, literature concerning premature calves with GER or GERD is lacking. To the best of our knowledge, this is the first study concerning the determination of GER or GERD in premature calves, and the prevalence of these conditions was found to be high (67 and 55%. respectively). GER and GERD may cause esophageal ulcers in premature calves.

Endoscopy enables the clinician to visualize structural abnormalities as well as the gross appearance of the esophageal mucosa. The technique has become increasingly important in veterinary medicine in recent years and is used routinely in small animal and equine medicine. The procedure also is used in cattle to support clinical examinations in diagnosing gastrointestinal, urinary tract, and pulmonary diseases.[16, 17] Franz and Baumgartner[17] reported that endoscopy proved useful for the diagnosis of diverticula, ruptures, inflammation, and erosions of the esophagus in cattle. In the present study, clinical signs related to GER or GERD were not observed by inspection of the calves. However, changes typical of these conditions were observed in the esophageal mucosa in most of the premature calves during esophagoscopic examination. These findings indicate that this technique is of value in appropriately diagnosing these conditions in calves.

On the basis of the results of this study, the prevalence of both GER and GERD in premature calves appears to be high. In addition, endoscopy has been shown to provide a practical, rapid, noninvasive, and reasonably accurate method for diagnosing GER and GERD in premature calves. The addition of endoscopy to the diagnostic protocol for determining GERD in premature calves may facilitate the appropriate diagnosis and treatment of these conditions, possibly leading to a decrease in the death rate of premature calves.

Acknowledgments

This study was supported by “The Scientific and Technological Research Council of Turkey” and “University of Selcuk Scientific Research Project Office.”

Footnotes

  1. 1

    GEM Premier 3000, Instrumentation Laboratory, Lexington, MA

  2. 2

    Lactated Ringer's solution, I.E. Ulugay, Istanbul, Turkey

  3. 3

    0.9% NaCl solution, I.E. Ulugay

  4. 4

    5% dextrose solution, I.E. Ulugay

  5. 5

    Ademin, Ceva-Dif, Istanbul, Turkey

  6. 6

    Devit-3, Deva, Istanbul, Turkey

  7. 7

    Nervit, Vetaş Istanbul, Turkey

  8. 8

    Kalsimin, Vilsan, Istanbul, Turkey

  9. 9

    Fosfalin, Alke, Istanbul, Turkey

  10. 10

    Kafedif, Ceva-Dif

  11. 11

    Rompun, Bayer, Istanbul, Turkey

  12. 12

    Olympus GIF E, Japan

Ancillary