Gastrointestinal hypomotility (GIHM) is a term used to include both delayed gastric emptying and ileus. GIHM is common in hospitalized dogs and cats. Identification of GIHM may be based on clinical signs supportive of altered motility (e.g., abdominal pain, nausea, possibly large gastric residual volumes); however, GIHM is best diagnosed with ultrasonography. Initial management of GIHM should focus on environmental modification (e.g., enteral feeding, reducing systemic opioid administration, avoiding overhydration, careful attention to diet selection). In reaching for prokinetic agents, a multimodal approach may be best. Agents with prokinetic properties include metoclopramide, cisapride, macrolide antibiotics (e.g., azithromycin, erythromycin), and oral naloxone. Other agents (e.g., lidocaine, bethanechol, neostigmine, ranitidine, maropitant) do not seem to have significant beneficial effects on gastrointestinal motility.<\/p>\n
Take-Home Points<\/strong><\/p>\n <\/div><\/div><\/p>\n Gastrointestinal (GI) motility is a complex process that involves vagal control, myenteric nervous input, locally acting substances, and enteric-specific peptides. In response to various stimuli, excitatory substances (e.g., acetylcholine acting on M3<\/sub> receptors, serotonin acting on 5-HT4<\/sub> receptors, substance P acting on neurokinin-1 receptors) cause smooth muscle contraction. Other substances (e.g., nitric oxide, vasoactive intestinal peptide, somatostatin, norepinephrine acting on <\/span>\u03b2<\/span>2<\/sub> receptors, neuropeptide Y) cause smooth muscle relaxation. The coordinated constriction and relaxation results in propulsion of the ingesta in an aborad direction, a process known as peristalsis. <\/span><\/p>\n Ghrelin, a hormone released from ghrelin cells in the stomach, can increase GI motility. Conversely, cholecystokinin released from I-cells in the duodenum and jejunum can delay gastric emptying. Dopamine (via D2<\/sub> receptors) can inhibit acetylcholine release and therefore decrease GI motility. Motilin acts in the GI tract during the interdigestive period to activate migrating motor complexes (MMCs), resulting in motility during fasting.1-3<\/sup><\/span><\/p>\n Gastrointestinal hypomotility (GIHM) describes both delayed gastric emptying and ileus. GIHM has been reported to affect more than 50% of critically ill humans.1<\/sup> Although incidence among hospitalized dogs and cats has not been reported, GIHM is thought to be common.<\/span><\/p>\n GIHM may result from primary GI disease or be secondary to systemic disease. Common causes of GIHM in dogs and cats include parvoviral enteritis<\/a>, postoperative GIHM, inflammatory bowel disease<\/a>, GI ulceration, neoplasia, gastric dilatation\u2013volvulus<\/a>, sepsis<\/a>, pancreatitis<\/a>, opioid administration, and systemic inflammation.1<\/sup> One study involving healthy dogs found that hospitalization alone results in delayed gastric emptying.4<\/sup> Possibly implicated in the pathogenesis of GIHM are medication administration (especially opioids and vasopressors), tissue handling during surgery, loss of antropyloroduodenal coordination, gut edema, inflammation, nitric oxide\u2013induced enteric paralysis, increased cholecystokinin, and altered MMCs.1,2,5<\/sup><\/span><\/p>\n Identification of GIHM may be based on clinical signs supportive of altered motility, including abdominal pain, nausea, vomiting, regurgitation, anorexia, abdominal distension, and documentation of ingesta in the stomach despite prolonged fasting. It should be considered only after mechanical ileus has been ruled out. Diagnosis of GIHM is often based on abdominal ultrasonography findings. Gastric and intestinal dilation and GI contractile activity can be measured to determine hypomotility. Serial ultrasonography evaluations may enable more comprehensive evaluation of gut motility. The role of quantifying gastric residual volumes in the diagnosis of GIHM remains unclear. Left untreated, GIHM may result in regurgitation, aspiration pneumonia, reflux esophagitis, abdominal pain, lack of nutrition, increased intra-abdominal pressure, and bacterial translocation from the GI tract.1,2<\/sup><\/span><\/p>\n Mechanism of action: <\/b>Metoclopramide is both an antiemetic and prokinetic. Its antiemetic effects likely result from dopamine antagonism (predominantly D2<\/sub>) and serotonin 5-HT3<\/sub> antagonism, and its prokinetic effects likely result from dopamine antagonism and serotonin 5-HT4<\/sub> agonism. In dogs, metoclopramide has been shown to increase the rate of gastric emptying.1,6<\/sup> The prokinetic effects are usually ascribed to its effects on the stomach; however, older research suggests that metoclopramide may also stimulate small intestinal smooth muscle contraction.7 <\/sup>In cats, metoclopramide has similarly been shown to increase the rate of gastric emptying.8<\/sup><\/span><\/p>\n Administration:<\/b> The ideal dose for metoclopramide is unknown. It is commonly administered as a constant-rate infusion (CRI) at a rate of 2 mg\/kg\/day, which may be preceded by a 0.5 mg\/kg bolus. Alternatively, metoclopramide may be administered as an intermittent bolus (0.2 to 0.5 mg\/kg SC or IM). However, some studies have shown that these doses may not be sufficient to produce prokinetic effects.9 <\/sup>Instead, much higher rates may be needed (1 mg\/kg bolus followed by 1 mg\/kg\/h in the perianesthetic period).10 <\/sup>In addition, some research indicates that dosing may be breed dependent.11<\/sup> The author typically administers a 0.5 mg\/kg IV bolus followed by a 2 mg\/kg\/day CRI but will titrate to 8 mg\/kg\/day if needed based on persistence of the ileus. Oral formulations do exist; however, the short half-life of metoclopramide requires frequent dosing, and oral dosing may not be ideal for patients with GIHM.<\/span><\/p>\n Adverse reactions: <\/b>At high doses, metoclopramide may cause extrapyramidal signs (e.g., aggression, restlessness, hypersalivation, muscle spasms or rigidity). If these signs are recognized, treatment with a benzodiazepine or antihistamine will usually lead to their resolution.1<\/sup><\/span><\/p>\n Mechanism of action: <\/b>Cisapride is thought to work predominantly by increasing acetylcholine release, serotonin 5-HT1<\/sub> and 5-HT3<\/sub> antagonism, and serotonin 5-HT4<\/sub> and 5-HT2<\/sub> agonism. Through those mechanisms, cisapride increases the rate of gastric emptying, improves gastroduodenal coordination, augments small intestinal motility (effects on jejunal propulsion and jejunal nervous activity), and increases colonic motility.1,5,12<\/sup><\/span><\/p>\n Administration:<\/b> Cisapride is only available in compounded oral formulations and is typically administered at 0.5 to 1 mg\/kg PO (or via a feeding tube) q8h.<\/span><\/p>\n Adverse reactions: <\/b>Cisapride was withdrawn from the human market due to its propensity to prolong the QT <\/span>interval. Although this effect has not been demonstrated in clinical veterinary medicine, cisapride should be used <\/span>cautiously in dogs and cats at risk for QT prolongation.1<\/sup><\/p>\n Mechanism of action: <\/b>Macrolide antibiotics (e.g., erythromycin, azithromycin) stimulate motilin receptors, which act during the interdigestive period to stimulate phase III MMC activity, resulting in increased gastric and small intestinal motility in humans and dogs. Cats have motilin receptors throughout their GI tract but do not have phase III MMC activity; therefore, macrolides seem to work directly on motilin receptors to stimulate smooth muscle contraction in cats.2,13<\/sup><\/span><\/p>\n Administration: <\/b>The described prokinetic dose for azithromycin in cats is 3.5 mg\/kg IV or PO q24h and in dogs is 2 mg\/kg IV or PO q8h.2,13<\/sup> Erythromycin may be used in patients of both species at a dose of 0.5\u00a0to 1 mg\/kg IV or PO q8h.14<\/sup> Studies in humans have demonstrated the equivalence of the prokinetic effects of azithromycin and erythromycin. Because of <\/b>the cost, availability, safety profile, longer duration of action, and more favorable side effect profile, the author uses azithromycin rather than erythromycin.15,16<\/sup><\/span><\/p>\n Adverse reactions:<\/b> Side effects are rare, although retrograde peristalsis has been documented with higher doses of erythromycin. However, use of macrolide antibiotics may contribute to the development of antimicrobial resistance in human and veterinary medicine. In addition, erythromycin (but not azithromycin) is an inhibitor of cytochrome P450 enzymes; therefore, the clinician must be aware of possible drug interactions.1<\/sup><\/span><\/p>\n Mechanism of action: <\/b>In intensive care units, opioids are commonly prescribed, either postoperatively or for visceral pain associated with severe ileus. In addition, in critically ill patients, endogenous opioids may also be released. Opioids inhibit acetylcholine release, resulting in GIHM. Administration of naloxone via a feeding tube may inhibit the local actions of endogenous and exogenous \u00b5-agonist opioids, resulting in reduced gastric reflux, without blocking the systemic effects of opioids.1,17,18<\/sup><\/span><\/p>\n Administration: <\/b>For humans, administration of 8 mg (of the injectable formulation) via a feeding tube q6h has been described.18<\/sup> For refractory ileus in dogs and cats, the author has used 0.1 mg\/kg q6h via nasogastric tube.<\/span><\/p>\n Adverse reactions: <\/b>Although <\/b>administration of naloxone could result in decreased analgesia, this effect is unlikely due to naloxone\u2019s high rate of first-pass metabolism.17<\/sup><\/span><\/p>\n A mainstay for the treatment of GIHM is early enteral nutrition<\/a>; for patients who are not eating, nasogastric tube placement should be considered. Small, frequent, liquid meals that are low in calories, low in fat, and low in protein are likely to most significantly increase the rate of gastric emptying.1,2<\/sup> The measurement and removal of gastric residual volumes are likely not helpful for either diagnosing or treating GIHM. In dogs, higher gastric residual volumes are not associated with vomiting, regurgitation, or aspiration pneumonia. Currently, the relationship between high gastric residual volumes, outcome, and management of GIHM is unclear.1,2,19-21<\/sup><\/span><\/p>\n Avoiding overhydration is essential as it will increase intestinal edema and worsen GIHM. To avoid gut edema associated with the overuse of crystalloids, use of natural or synthetic colloids and hypertonic saline should be considered. Electrolyte imbalances should be corrected to exclude electrolyte disturbances<\/a> as a cause of altered motility. Ambulation has long been recommended to encourage gut motility; however, studies demonstrating the benefit during the acute phase are lacking. Electroacupuncture may increase gastrointestinal motility in veterinary patients, although the mechanisms are unclear.22-25<\/sup><\/span><\/p>\n\n
Pharmacologic Interventions for GIHM<\/h2>\n
Metoclopramide<\/h3>\n
Cisapride<\/h3>\n
Macrolide Antibiotics<\/h3>\n
Enteral Naloxone<\/h3>\n
Other Interventions for GIHM<\/h2>\n
Nonpharmaceutical Interventions<\/h3>\n
Other Medications<\/h3>\n