Vomiting

Vomiting is a clinical sign commonly found in small animals. The causes are varied, simple or complex, making both the diagnosis and the subsequent therapy extremely difficult. Vomiting is often caused by diseases of the digestive tract but it can also be caused by disorders affecting other organs.

ETYMOLOGY

The word “vomiting” derives from the Latin vomitus while the word “emesis” derives from the Greek  emetos, both referring to the act of throwing up from the mouth material contained in the stomach.

DEFINITION

Vomiting is a protective mechanism which allows the body to remove toxins and other dangerous substances that have been either ingested directly or absorbed via the blood. Vomiting takes place through forceful expulsion of the contents of the stomach, be they food or any other substance.

The act of throwing up has three stages: nausea, retching and vomiting

Nausea precedes retching and vomiting, and is often accompanied by anorexia/dysorexia, depression, yawning, muscle tremors and lip licking. Subsequently there is an increase in the production of saliva, rich in bicarbonates, which lubricates the oesophagus and neutralises the gastric juices from the stomach. The oesophageal sphincter relaxes while oesophageal motility increases together with an increase of retrograde motility (antiperistaltic waves) of the proximal small bowel; the gastric contents are, therefore, moved from the stomach to the oesophagus.

Retching consists in forced contractions of the abdominal muscles and of the diaphragm which generate a negative intrathoracic pressure and a positive abdominal pressure, events which  determine the movement of the gastric contents from the stomach to the oesophagus.

Vomiting is the last stage, with expulsion of the material from the mouth.

When vomit passes through the pharynx, breathing is inhibited and the glottis closes preventing the inhalation of food and gastric juices. The presence of retching is useful in order to distinguish between regurgitation, vomiting and cough.

CONSEQUENCES

Potential consequences of vomiting are dehydration, loss of electrolytes, alteration of blood-gas values and aspiration pneumonia.

Vomiting causes the loss of protons and  chlorine ions and may induce a hypochloraemic metabolic alkalosis (low chlorine, high bicarbonate and carbon dioxide and increased pH) and often hypokalaemia.

Vomiting-induced metabolic acidosis is less common and is a consequence of the loss of intestinal contents such as biliary acids and bicarbonate.

PATHOPHYSIOLOGY

Vomiting starts within the central nervous system. It is a complex nervous reflex, involving different neural pathways which activate synaptic connections within the vomiting centre in the medulla oblongata.

The essential components of the vomiting reflex are visceral receptors (within the pharynx, duodenum, jejunum, liver, gallbladder and other abdominal organs), vagal and sympathetic afferent nerves, the chemoreceptor trigger zone (CRTZ) which is found within the area postrema at the base of the fourth ventricle and is activated via humoral pathways which are sensitive to substances present within the blood (uraemic toxins, chemotherapeutic drugs, morphine, electrolytes, etc.) and the vomiting centre which is located within the medulla oblongata and receives information from vagal and sympathetic stimuli, from the CRTZ, from the vestibular apparatus and from the cerebral cortex.

The vomiting centre contains serotonergic (5HT₃), adrenergic (a₂) and neurokinergic (NK₁) receptors which can be activated either directly or indirectly (by the CRTZ, by humoral pathways, etc.). The concentration of emetic receptors is extremely high within the  duodenum, to the extent that it can be defined the “organ of nausea”. The CRTZ contains abundant dopaminergic (D₂), cholinergic (M₁), histaminergic (H₁), serotonergic (5HT₃), adrenergic (a₂), neurokinergic (NK₁) and encephalinergic (ENK) receptors, the roles of which are not totally clear.

In cats the D₂, H₁ and H₂ receptors are poorly developed (unlike in dogs) while the a₂ receptors are more developed.

Vomiting starts from the vomiting centre. An inflammatory process, distension of abdominal organs, ulceration or irritation can stimulate peripheral sensory receptors. The information reaches the vomiting centre which activates, via efferent nervous pathways, the abdominal muscles, the distal oesophagus and the diaphragm. Subsequently the antrum and the cranial duodenum contract and push the material which is present within the body of the stomach. At the same time the oesophagus contracts and propels the material to the proximal oesophagus. Finally, contractions of the abdominal muscles and the diaphragm move the entire gastric contents to the mouth. Retching and hypersalivation may precede the act of vomiting.

CAUSES

There are numerous causes of vomiting, ranging from simple ones to more complex ones. The most frequent causes of vomiting (acute or chronic) in small animals are listed in Table 1.

Causes of vomiting

• Alimentary
  • Indiscretion (ingestion of spoiled food/rubbish, foreign bodies, etc.)
  • Adverse reactions (food hypersensitivity)
  • Food allergies
• Parasites:
  • Intestinal
  • Gastric
• Drugs
  • Non-steroidal anti-inflammatory drugs
  • Erythromycin
  • Chemotherapeutic drugs
  • Cardiac glycosides
  • Apomorphine
  • Xylazine
  • Tetracycline
  • Penicillin
• Endocrine/metabolic disorders
  • Uraemia
  • Renal disorders
  • Hypoadrenocorticism[3]
  • Diabetes mellitus[4]
  • Hyperthyroidism[5]
  • Liver diseases
  • Hepatic encephalopathy
  • Endotoxaemia
  • Electrolyte disorders
• Toxins
  • Ethylene glycol
  • Zinc
  • Lead
  • Strychnine
• Abdominal diseases
  • Pancreatitis
  • Peritonitis
  • Neoplasms
  • Liver disorders
• Gastric diseases
  • Gastritis
  • Helicobacterspp. infections
  • Parasites
  • Ulcers
  • Neoplasms
  • Foreign bodies
  • Dilatation/volvulus
  • Hiatus hernia
  • Obstruction (hypertrophic gastropathy)
  • Motility disorders (hypomotility)
•  Gastrointestinal diseases
  • Inflammation
  • Neoplasms
  • Parasites
  • Foreign bodies
  • Intussusception

Table 1. Causes of vomiting in the dog and cat. 

CLINICAL APPROACH AND DIAGNOSIS

The first step in the diagnosis and treatment of vomiting is to take a thorough clinical history. The description of the vomiting episodes is fundamental. The differentiation between vomiting and regurgitation is also essential, since failing to make this distinction can lead to diagnostic mistakes. Regurgitation may take place immediately after a meal, or hours after the ingestion of food and water, and is a passive process (the animal opens its mouth and lets the material out without abdominal contractions or movements). Vomiting is associated with clinical signs such as depression, retching and hypersalivation and abdominal contractions ARE ALWAYS PRESENT before expulsion of the ingesta.

The questions to the owner are extremely important: onset (close to or far from meals), duration and severity of clinical signs, potential ingestion of/contact with toxins, previous disorders, drugs taken, other concomitant alterations, vaccinations, use of antiparasitic drugs, recent travel, etc. All this information, together with the findings of the physical examination can help to develop a targeted plan for diagnosis and therapy.

The diagnostic approach may vary from a minimum assessment (detailed clinical history and physical examination) with subsequent symptomatic and conservative treatment to a much more thorough evaluation.

Based on the clinical history and physical examination a haematocrit, biochemical profile (including electrolytes), complete urinalysis and faecal studies (including the test for Giardia) may be considered essential. If a foreign body or other abdominal disorders (pancreatitis, peritonitis, neoplasms, etc.) are suspected radiographs and abdominal ultrasound scans should be carried out.

The decision on whether to carry out more sophisticated and specific tests for specific disorders should be made based on the results of the preceding tests (e.g. the ACTH stimulation test in the case of suspected Addison’s disease, T4 assays in the case of hyperthyroidism) and/or the response to therapy (e.g. endoscopy and biopsy in the case of suspected inflammatory bowel disease or neoplasms). A laparotomy should be carried out in the presence of foreign bodies, neoplasms, intussusception, etc. During an exploratory laparotomy/laparoscopy biopsies should ideally be taken from all the abdominal organs (stomach, small bowel, pancreas, liver, lymph nodes) and subsequently analysed.

TREATMENT

The initial treatment for vomiting consists of eliminating any triggering factors and providing supportive therapy based on fluids and anti-emetics. There are different classes of anti-emetics including H₂ blockers (e.g. ranitidine and famotidine), proton pump inhibitors (e.g. omeprazole, lansoprazole), cytoprotective agents (e.g. sucralfate), prokinetics (e.g. ranitidine, metoclopramide, cisapride, erythromycin), prostaglandin analogues (e.g. misoprostol) and anti-emetics (e.g. metoclopramide, ondansentron, dolasetron, maropitant, chlorpromazine).

Metoclopramide_^1,2,3,4 is a broadly used anti-emetic in veterinary medicine. It can increase gastric and proximal bowel motility, decrease the enterogastric reflux and, via its action on D₂  (at low dosages) and 5HT₃ (at high dosages) receptors, inhibit the CRTZ (antiemetic effect). The dosage is 0.2-0.5 mg/kg i.m., s.c. or per os every 6-8 hours or a 1-2 mg/kg continuous infusion over 24 hours. Metoclopramide is contraindicated in cases of gastric obstruction, gastrointestinal tract perforation or in animals with epilepsy. Potential adverse events include hyperactivity, occasionally depression and at times aggressiveness. Diphenhydramine at a dosage of  2 mg/kg i.v. may at times reduce these adverse events.

Anti-emetics belonging to the group of phenothiazines (e.g. chlorpromazine, prochlorperazine)  are mixed a₁ and a₂ adrenergic antagonists which may control vomiting induced by different causes. Chlorpromazine acts on the vomiting centre, on the CRTZ and on peripheral receptors. The recommended dosage is 0.2-0.5 mg/kg i.m./s.c., bid/tid. At this dosage the sedative effect is minimal. In patients with liver or kidney failure the dosage may be decreased to 0.2-0.3 mg/kg sid/bid without compromising the drug’s efficacy.

Ondansetron_⁵ is a powerful anti-emetic used to control intractable vomiting. It acts on the CRTZ via 5HT₃ and S₃ receptors. Its main effect is on the area postrema although it does also have mild prokinetic activity. The recommended dosage is 0.5 mg/kg i.v. or 0.5-1 mg/kg per os every 12-24 hours. The biggest limitation to the use of this drug is its cost.

Maropitant_^6,7 is a new anti-emetic which inhibits NK₁ receptors and blocks the pharmacological action of substance P on the central nervous system. Substance P is found in significant concentrations in the nuclei of the vomiting centre and seems to play a major role in vomiting. The drug is administered only once a day and its action is extremely rapid. It can be administered at a dosage of 1 ml/10 kg s.c. or 2 mg/kg per os.

Ranitidine_^8,9 inhibits gastric H₂  recepors, thus reducing the production of gastric acid. It also has mild prokinetic activity as it stimulates gastric acetylcholine. It is more powerful than cimetidine but has a lower bioavailability. It is metabolised by the liver. The dosage is 2 mg/kg by slow intravenous infusion, subcutaneously or per os every 8-12 hours.

Omeoprazole_^10,11,12 is a proton pump inhibitor which inhibits the production of gastric acid. It is mostly used in the treatment of gastric and duodenal ulcers, gastritis, oesophagitis and in cases of gastric hypersecretion (such as in mast cell tumours or in the Zollinger-Ellison syndrome). The dosage is 0.5-1 mg/kg once a day for a maximum period of 8 weeks. In laboratory animals the chronic suppression of gastric acid caused hypergastrinaemia with the subsequent development of carcinoid tumours and hence continuous use of omeprazole for more than 8 weeks is not advisable.

Sucralfate_^13,14 binds to protein exudates in the stomach, forming a chemical barrier over the ulcers which protects them from further erosion by acids, pepsin and bile. It stimulates mucosal defences and the repair mechanisms (production of prostaglandins, stimulation of bicarbonate, etc.) which help to heal mucosal damage. In many texts its use is suggested during renal failure to bind phosphorus, however this action remains questionable. The dosage is 250 mg/cat; 500 mg/dog (<20 kg) and 1 g/dog (>20 kg) every 8-12 hours on an empty stomach.

References 

1. Wilson, DV, Evans T, Mauer WA Influence of metoclopramide on gastroesophageal reflux in anesthetized dogs. American Journal of Veterinary Research 2006, 67, 26-31.
2. Bakke OM, Segura J. The absorption and elimination of metoclopramide in three animal species. Journal of Pharmacy and Pharmacology, 1976, 28, 32-29.
3. Bateman DN, Kahn C, Davies DS. The pharmacokinetics of metoclopramide in man with observations in the dog. British Journal of Clinical Pharmacology 1980, 9, 371-377.
4. Mantione NL, Otto CM, Characterization of the use of antiemetic agents in dogs with parvoviral enteritis treated at a veterinary teaching hospital: 77 cases (1997-2000). Journal of the American Veterinary Medical Association 2005, 1, 1787-1793 
5. Jensen TN, Nielsen J, Frederiksen K, Ebert B. Molecular cloning and pharmacological characterisation of serotonin 5-HT(3) receptor subtype in dog. European Journal of Pharmacology 2006 538, 23-31
6. The anti-emetic efficacy of maropitant (Cerenia(tm)) in the treatment of ongoing emesis caused by a wide range of underlying clinical aetiologies in canine patients in Europe. Journal of Small Animal Practice 2007, 48, 93-98
7. Vail DM; Rodabaugh HS, Conder GA; Boucher JF; Mathur, S. Efficacy of injectable maropitant (Cerenia(tm)) in a randomized clinical trial for prevention and treatment of cisplatin-induced emesis in dogs presented as veterinary patients. Veterinary and Comparative Oncology 2007, 5, 38-46
8. Stables R, Daly MJ. Inhibition of gastric acid secretion in the dog by the histamine H2-receptor antagonists ranitidine and cimetidine. Inflammation Research, 1980, 10, 191-192
9. Eddershaw PJ, Chadwick AP, Higton DM, Fenwick SH, Linacre P, Jenner WN, Bell JA, Manchee GR. Absorption and disposition of ranitidine hydrochloride in rat and dog. Xenobiotica 1996, 26,947-956
10. Larsson H, Carlsson E, Junggten U, Olbe L, Sjöstrand SE, Skånberg I, Sundell G. Inhibition of gastric acid secretion in the dog and rat. Gastroenterology 1983, 85, 900-907,
11. Alder JD, Ewing PJ, Mitten MJ, Oleksijew A, Tanaka SK (1996) Relevance of the ferret model of Helicobacter-induced gastritis to evaluation of antibacterial therapies.American Journal of Gastroenterology. 91(11):2347-54.
12. Fox JG, Blanco MC, Yan L, Shames B, Polidor D, Dewhurst FE, Paster BJ (1993) Role of gastric pH in isolation of Helicobacter mustelae from the feces of ferrets. Gastroenterology. .104(1):86-92
13. Steiner K, Bühring KU, Faro HP, Garbe A, Nowak H. Sucralfate: pharmacokinetics, metabolism and selective binding to experimental gastric and duodenal ulcers in animals. Arzneimittel-Forschung. 1982;32(5):512-8
14. Hanson SM, Bostwick DR, Twedt DC, Smith MO. Clinical evaluation of cimetidine, sucralfate, and misoprostol for prevention of gastrointestinal tract bleeding in dogs undergoing spinal surgery. American Journal of Veterinary Research 1997, 58, 1320-1323.