Effective decontamination strategies for poisoned horses (Proceedings)

Principles of Case Management

Once a determination has been made that an animal has been exposed to a toxicant or is intoxicated, a general approach to case management should adhere to the following principles: (1) stabilize vital signs (this may include administration of an antidote if sufficient information concerning a specific toxin exposure is immediately available), (2) obtain a history and clinically evaluate the patient, (3) prevent continued systemic absorption of the toxin, (4) administer an antidote if indicated and available, (5) enhance elimination of absorbed toxicant, (6) provide symptomatic and supportive care, and (7) closely monitor the patient. It is recommended that the above principles be followed in sequence with modifications made depending on the circumstances of the case. For example, there may not be an antidote for a given plant toxin or a way to significantly enhance its elimination once systemically absorbed.

Gastrointestinal Decontamination

Gastrointestinal decontamination (GID) is a critical component of case management. Appropriate and timely decontamination may prevent the onset of clinical signs or significantly decrease the severity or shorten the course of intoxication. GID consists of three components: (1) gastric evacuation, (2) administration of an adsorbent and (3) catharsis.

Gastric Evacuation

Approaches to gastric evacuation include induction of emesis with emetics or gastric lavage (GL); either one or the other approach is used depending on the species affected and clinical condition of the animal. Since horses do not vomit, induction of emesis is not a viable option in this species. GL may be used as an alternative depending on the condition and temperament of the horse. GL requires the placement of a stomach tube and the repeated instillation of water or normal saline to remove stomach contents. Airway protection is essential whenever GL is performed. As large a nasogastric tube as possible with terminal fenestrations is introduced into the stomach. Tube placement is confirmed by visual inspection, palpation, detection of gurgling noises through the tube or reflux/aspiration of gastric contents. Tepid tap water or normal saline (5 to 10 ml/kg) is introduced into the stomach with minimal pressure application and is withdrawn by aspiration or allowed to return via gravity flow. The instillation of water or saline is repeated until the last several washings are clear; numerous cycles may be required. Activated charcoal (AC) +/- cathartic can be administered via the tube just before its removal. The initial lavage sample should be retained for possible toxicologic analysis.

Administration of an Adsorbent

Realistically, the only adsorbent routinely used in veterinary medicine is AC. AC is produced in a two-step process. The first step involves the pyrolysis of carbonaceous materials such as wood, coconut or peat followed by high temperature treatment with activating agents such as steam or carbon dioxide. The activation step increases the adsorptive capacity of the material by increasing its total surface area as a result of the formation of a maze of internal pores. The rate of adsorption of a toxicant is dependent on the external surface area while the adsorptive capacity is dependent on the internal surface area. Adsorption is believed to be due to hydrogen bonding, ion-ion, dipole and van der Waal's forces.

AC is likely to be an effective adsorbent for most organic toxicants, although the adsorptive capacity of AC for most has not been experimentally determined. Nonpolar, poorly water soluble organic substances are more likely to be adsorbed and adsorption is enhanced with an increase in molecular size of the toxicant. Small, polar, water-soluble organics are less well adsorbed. In vitro studies have demonstrated that adsorption begins almost immediately after instillation of AC but may not reach equilibrium for 10 to 25 minutes. AC has been shown to decrease the systemic absorption of a number of drugs including aspirin, acetaminophen, barbiturates, glutethimide, phenytoin, theophylline, cyclic antidepressants and most inorganic and organic chemicals. However, AC does not adsorb alcohols, strong acids and alkalies, iron and lithium. Even if a toxicant is not well adsorbed by AC, partial adsorption may be sufficient to affect clinical outcome. In general, the efficacy of AC administration is directly related to the rapidity of administration after toxicant ingestion.

AC is available as a powder, an aqueous slurry or combined with cathartics such as sorbitol. If using a powder, 2 to 5 g of AC should be mixed with tepid tap water (~ 1 g AC to 5 ml of water) to form a slurry. The slurry should be administered via a stomach tube using minimal pressure.

Repeated administration of AC is effective in interrupting enterohepatic recycling of a number of toxicants and the continued presence of AC in the gastrointestinal tract may allow the tract to serve as a sink for trapping toxicant passing from the circulation into the intestines. There is little hazard to repeated administration of AC, although cathartics should be given only once. Dosages of 2 to 5 g in water every 4 to 6 hours are recommended. The duration of dosing is variable depending on toxicant pharmacokinetics and clinical response of the individual.

Other adsorbents include bentonite clay and aluminum silicates such as kaolin. Their efficacy has not been established for most toxicants but is likely to be considerably less than that of AC. Although commonly recommended and administered, mineral oil has not been shown to be efficacious for decreasing the systemic absorption of toxicants in horses and therefore cannot be justified for routine GID. Also, if mineral oil is administered with AC, the oil may decrease the adsorptive ability of the AC. Therefore the combination is not recommended.

AC is relatively safe. In humans, emesis with resultant aspiration pneumonia secondary to AC administration has been the most serious complication. Intestinal obstruction has been reported following the repeated administration of AC in the presence of dehydration and prior bowel adhesions.

Catharsis

Both saline (sodium sulfate or magnesium sulfate or citrate) and saccharide (sorbitol) cathartics are available for GID. The mechanism of cathartic action is not entirely known. Traditionally, the cathartic effect of sodium and magnesium sulfate was attributed to the creation of an osmotic gradient with the lumen of the GI tract, increasing water retention and intestinal pressure and resulting in an increase in intestinal motility. However, other mechanisms may contribute to catharsis. Magnesium releases cholecystokinin from the duodenal mucosa which stimulates intestinal motor activity and alters fluid movement. Presumably, sorbitol, found naturally in many ripe fruits and synthesized industrially from glucose, works by osmotic action, but the mechanisms causing its cathartic action have not been thoroughly investigated.

In general, cathartics are safe, particularly if used only once. However, repeated administration of magnesium-containing cathartics can lead to hypermagnesemia manifested as hypotonia, altered mental status and respiratory failure. Also, repeated administration of sorbitol can cause fluid pooling in the GI tract, excessive fluid losses via the stool and severe dehydration. Mineral oil has a laxative, not cathartic, effect and can be used when saline or saccharide cathartics are not available. However, mineral oil is not as effective in inducing bowel evacuation and, as mentioned, it has the potential to interfere with the adsorptive capacity of AC if given concurrently with or shortly after AC. Contraindications to the use of cathartics include adynamic ileus, preexisting or anticipated diarrhea, abdominal trauma and intestinal obstruction.

The recommended dose of sodium or magnesium sulfate is 250 to 500 mg/kg body weight mixed in several liters of water. A recommended dose of sorbitol (70%) is 3 ml/kg. Additional cathartic should not be administered if it is included in the AC formulation. Formulations of AC + cathartic should be administered only once; if multiple doses of AC are given, those subsequent to the first should not include a cathartic. Make sure that the horse is adequately hydrated following cathartic administration.

Recent Reappraisal of Gastrointestinal Decontamination

In recent years, a critical reappraisal of GID approaches in human intoxications has occurred that is relevant for the management of intoxicated animals. There has been a movement away from gastric evacuation (induction of emesis or GL) followed by the administration of an adsorbent such as AC toward administration of only the adsorbent, especially in mild to moderate intoxications. Early administration of AC alone has been shown to be as efficacious as the combination of gastric evacuation followed by AC. Therefore, from a practical, logistical and economic standpoint, initial use of AC in lieu of gastric evacuation is recommended for most situations involving large animals.

The case for or against the inclusion of a cathartic with AC is less clear-cut, but the administration of a single dose of a cathartic along with the initial dose of AC is currently recommended. Again, those AC formulations that include a cathartic such as sorbitol should be administered only once followed by AC alone if repeated doses are indicated.

The Future

"GID is far from an exact science, and controversy and change are expected. The issues discussed should provide a framework on which to build and refine a clinical approach. As in all areas of medicine, it is expected that thoughtful analysis of further research, clinical experience, and the unique features of each case will suggest modification of current thinking and lead to improved patient care." MJ Smilkstein, Goldfrank's Toxicologic Emergencies (1998). Well said.

References

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Shannon MW and Haddad LM (1998), "The Emergency Management of Poisoning", in Clinical Management of Poisoning and Drug Overdose, Haddad LM et al., eds. Philadelphia, W.B. Saunders Co., pp. 2-31.

Howland MA (1998), "Antidotes in Depth: Activated Charcoal", In: Goldfrank's Toxicologic Emergencies, 6th ed. Goldfrank LR et al., eds. Stamford, CT, Appleton and Lange, pp. 527-534.

Levy, G (1982), "Gastrointestinal Clearance of Drugs with Activated Charcoal", N Engl J Med 307:676-678.

Stewart J (1983), "Effects of Emetics and Cathartic Agents on the Gastrointestinal Tract and the Treatment of Toxic Ingestions", Clin Toxicol 26:199-253.

Perry H and Shannon M (1996), "Emergency Department Gastrointestinal Decontamination", Pediatric Annals 25:19-26.