It is currently known that the monitoring of intragastric pH in human medicine is commonly used in hospital routine as a "gold-standard" tool for detecting changes in gastric physiology, diagnosis of gastrointestinal diseases such as gastroesophageal reflux (GERD), gastritis and disease by duodenogastric reflux [5, 10]. In equine medicine, research on the physiological intragastric environment involves studies in nutrition, pharmacology, and sports medicine [3, 9, 13–16], but studies involving general inhalational anesthesia while positioned at dorsal decubitus are unknown. This study is the first to report post-anesthetic gastric alkalinization in horses over a 24 h period.
Gastroesophageal reflux is a well-documented syndrome in human medicine [17, 18]. In veterinary medicine, there are studies in small animal medicine reporting episodes of esophagitis, and esophageal stenosis, due to the action of different drugs used in anesthesia, which have a relaxing effect on the lower esophageal sphincter . Cholinergic activation and anesthesia-induced vagal stimulation increases hydrochloric acid production and contributes to reported esophageal adverse effects [20, 21]. On the other hand, it was not verified in the consulted literature, the correlation of the anesthetic procedure and supine position in horses with the triggering or exacerbation of esophagitis, gastritis, or gastric ulcers.
General anesthesia and decubitus in horses are known to increase intra-abdominal pressure [22–24]. Lorenzo, Figueras & Merritt (2002) demonstrated that the increase in intra-abdominal pressure in horses can overcome the pressure of the lower esophageal sphincter, obeying Pascal's law, resulting in episodes of gastroesophageal reflux [25, 26]. Additionally, anesthetic drugs such as alpha-2 agonists, including detomidine, benzodiazepines, including midazolam, as well as inhaled anesthetics, such as isoflurane, promote relaxation of the esophageal smooth muscle, contributing to the occurrence of reflux of gastric contents into the esophagus in the transanesthetic period [27, 28]. It is noteworthy that, in this study, the pH of the esophageal content at the time of reflux was not evaluated, in order to detect the presence only of gastric acid or, also, the presence of bile salts, if the reflux occurred together duodenogastric. However, as there was no change in gastric pH in the trans-anesthetic period, it is assumed that duodenogastric reflux did not pass in this period.
The mean value of basal gastric pH, obtained after 8 h of fasting, reflected importance within the limit considered physiological for the species [20, 21, 29] and the mean values did not change over the 90 mins of general inhalational anesthesia and supine. On the other hand, after anesthetic recovery, alkalinization of gastric contents was observed, which could be explained by the presence of enterogastric reflux due to changes in post-anesthetic gastrointestinal motility [15, 21, 30]. In this case, the presence of bile salts would be responsible for the alkaline pH observed in post-anesthetic evaluations. Although not performed in this study, the resulting analysis of gastric juice with pHmetry would be interesting to demonstrate the presence and concentration of bile salts, diagnosing duodenogastric reflux [31–33].
It is reported that a disorder of gastric and duodenal motility results in an alkaline content in the stomach, generating mixed reflux (alkaline and acid) and greater exposure of the gastric mucosa to bile salts [34–36]. Changes in intestinal motility in the post-anesthetic period may have a direct relationship with the anesthetic protocol used. One of the side effects of detomidine is hypomotility, caused by presynaptic inhibition of α2 receptors, reducing the release of noradrenaline and acetylcholine in the enteric plexus . The isoflurane used in this study during general inhalation anesthesia may also be responsible for a reduction in postoperative gastrointestinal motility, as demonstrated in dogs after prolonged inhalation anesthesia with sevoflurane, where there was a reduction in gastric and small bowel motility, with the gradual return after 12 to 15 hours of the anesthetic procedure, while the time of gastric emptying extended up to a period between 30 and 40 hours .
Furthermore, it was found that post-anesthetic water and hay consumption did not change gastric pH, and concentrate consumption promoted acidification, which is physiological, due to the change in saliva production . Thus, the continuous alkalinization of gastric pH observed in the 24hours post-anesthetic cannot be correlated with food and water intake, which is possibly related to a post-anesthetic dysmotility promoted by the anesthetic procedure.
The assessment of the concentration of the gastrin hormone has been used in the clinical routine of horses for the diagnosis of gastric alterations and affections since this hormone provides information on the increase in gastric stimulation and on the increase in the production of acid in the stomach. In this study, there was no difference in the serum gastrin concentration about fasting or feeding the horses, with values ranging from 15.15 ± 3.82 pg/ml when fasting and 19.28 ± 6.26 pg/ml after feeding. These values are similar to those reported in the literature for the equine species, which range from less than 8pg/ml to 17.5 pg/ml during fasting [39–42]. However, after the procedure of general inhalation anesthesia and supine position, an increase in mean gastrin values (20.15±7.65 pg/ml) was observed. This elevation can be explained by the fact that, during general inhalational anesthesia, there is an increase in pressure in the abdominal cavity generated by the supine position, exerting pressure on the stomach, which results in stimulation of gastric mucosa G cells to production of gastrin . In addition, the gastrin elevation observed in the immediate post-anesthetic moment may be due to the inhibition of histamine and the acid response induced by gastrin, possibly correlated with the suppressive effects of anesthetic drugs on parietal cells and enterochromaffin cells, increasing serum gastrin, but without sufficient action to balance the acidity of gastric pH after anesthesia [44–46].
It´s known that the presence of gastroesophageal reflux or gastric duodenum can be considered physiological when transiently. However, when time is prolonged, this event is considered, pathological as observed in this study during 24hours [21, 34, 43, 47]. Duodenal contents, specifically bile salts, can have a more corrosive effect when mixed with acid in the gastric mucosa, are considered the primary cause of alkaline gastritis. It´s observed that duodenogastric reflux, in people, brings a significant number of lesions in the upper gastrointestinal tract, esophagitis, erythema, abdominal pain, gastric mucosal hyperplasia, represented by histological changes of this mucosa [35, 36], in addition to changes in the number of gastrin, somatostatin, and serotonin cells, which can result in chronic atrophic gastritis and intestinal metaplasia [34, 48, 49]. In adult horses, duodenogastric reflux has been shown to alter electrolyte transport and induce the formation of erosions and ulcers in the stratified squamous gastric mucosa, suggesting pathophysiological mechanisms similar to duodenogastric reflux disease in humans.
Equine gastric ulcer syndrome (EGUS) is commonly seen in the majority of the 80% - 90% horse population[50–54], but underdiagnosed and often undiagnosed, generating important losses, both in sports performance and in economic losses from treatments. According to the pH assessments in this study, there is alkalinization of the gastric pH for 24hours after general inhalational anesthesia and decubitus in horses, it´s relevant to consider the use of drugs that promote the protection of the gastric mucosa in a preventive manner. [55, 56].
The use of drugs that protect the gastric mucosa, such as sucralfate, which binds to positively charged proteins, forming a gel that adheres to the gastric mucosa, providing uniform protection against acid attack, pepsin and bile salts. It presents interesting results in the mechanism of pepsin inhibition and has bile salt chelating action, improving the increase in fibroblast growth factors and inducing an increase in prostaglandins in the mucosa, promoting the healing of gastric ulcers [10, 57, 58]. Also, alginates, being a composition of sodium alginate, sodium bicarbonate, and calcium carbonate, form, when in contact with gastric acid, an alginic acid gel film, with almost neutral pH, protective in the stomach and esophagus, reducing the symptoms of gastroesophageal reflux, and enterogastric . Another therapeutic option in the first 24hours after the anesthetic procedure would be the use of prokinetic drugs that stimulate duodenal peristalsis, thus avoiding the presence of mixed content (bile salts and hydrochloric acid) in the stomach, favoring the inflammatory condition of the gastric mucosa [60–62]. Also, the association of acupuncture as an integrative treatment may have favorable results, related to increased motilin, wave stimulation of the migrating myoelectric complex and acceleration of time for gastric emptying [63, 64].
A limitation for this study was the absence of a gastroscope to carry out a continuous evaluation of the stomach and esophagus to observe in real time the periods of reflux. Moreover, the concomitant evaluation of gastric juice with pH measurement was not carried out to demonstrate the presence of salts in the bile ducts, diagnosing duodenogastric reflux.