Drugs for Specific Purposes in the Ruminant Digestive System
Esophageal obstruction due to a foreign body (see Esophageal Obstruction in Large Animals) leads to severe discomfort and acute free-gas bloat. Physical removal of the object may be hampered by marked spasm of the surrounding muscle. Specific spasmolytic drugs such as acepromazine may be used (0.05–0.1 mg/kg, IV, IM, or SC in cattle). Alternatively, the moderate sedative and muscle relaxant effects of a low dose of xylazine (0.05 mg/kg, IM in cattle) or detomidine (0.02–0.05 mg/kg, IM in cattle) may aid removal of obstructions. None of these compounds has been approved by the FDA for use in cattle.
Agents and mixtures that promote forestomach function (fermentation and motility) are known as ruminotorics. Formulations that contain glucogenic substrates, minerals, cofactors, and bitters (eg, nux vomica) have limited application in current therapy of ruminoreticular indigestion. Generally, restoration of the normal ruminoreticular environment using a physiologic approach is much more satisfactory.
Oral administration of specific alkalinizing or acidifying agents should not be routinely undertaken in cases of indigestion. Magnesium oxide or magnesium hydroxide are strongly alkalinizing agents able to substantially increase rumen pH and thus create a hostile environment for rumen protozoa. These compounds, when given at label dose to dairy cattle, result in significant decrease in rumen fermentation and a decrease in number of rumen protozoa. Therefore, these compounds should only be administered to cattle with a confirmed diagnosis of grain overload.
Mineral oil (1–2 L) or dioctyl sodium sulfosuccinate (DSS, 90–120 mL in 1–2 L of water) administered PO or via nasogastric tube followed by gentle ruminal massage can help promote the dissolution and passage of impacted fibrous ruminal omasal or abomasal contents. DSS can markedly depress rumen protozoa; thus, ruminal transfaunation should follow use of this agent if ruminal hypomotility continues.
Fresh ruminal fluid is considered to be the best available “ruminotoric,” because it contains viable ruminal bacteria (1 × 108–1011/mL) and protozoa (1 × 105–106/mL) as well as many useful fermentation factors (volatile fatty acids, microbial protein, minerals, vitamins, buffers). Strained fresh ruminal juice (at least 3 L, but 8–16 L is ideal in cattle; sheep require ~1 L) given PO or by tube is indicated in cases of ruminoreticular stasis. Ruminal fluid can be aspirated through a stomach tube from the ruminoreticulum of healthy animals using an extractor pump or by siphoning, or it can be collected at slaughterhouses. A rumen-cannulated donor animal is particularly convenient. It is best for the donor to be on a ration similar to that of the recipient, because the ruminal microflora will then be more appropriately adapted. Provided the initiating condition or lesion is responding favorably, improvement almost invariably follows the reestablishment of normal ruminal microflora, with consequent normalization of the fermentation process and ruminoreticular motility. When the ruminoreticular contents are putrified, ingesta must first be removed before transfer of fresh ruminal fluid. This can be accomplished using a large-bore stomach tube or by performing a rumenotomy. Acetic acid (vinegar, 4–10 L, PO) can be administered to cattle with putrefaction of the rumen associated with high rumen pH.
Therapeutic approaches to the control of acute frothy bloat involve administration of antifoaming agents to reduce foam stability and to promote release of free gas, which is then promptly eructated. (Also see Bloat in Ruminants.)
Acute frothy bloat in cattle should be treated with poloxalene, which may be administered as a drench or by stomach tube (25–50 g). Frothy bloat can be prevented by administering poloxalene as a top dressing to feed (1 g/45 kg body wt/day) or in a molasses block (1.5 g/45 kg body wt/day). Polymerized methyl silicone (3.3% emulsion [cattle: 30–60 mL; sheep: 7–15 mL]) may be used in a similar manner as poloxalene, although direct intraruminal injection via a needle or cannula may be more satisfactory in this case. Administration of docusate sodium in emulsified soybean oil (6–12 fl oz containing 240 mg/mL) or administration of vegetable oils alone, such as peanut oil, sunflower oil, or soybean oil (cattle: 60 mL; sheep: 10–15 mL), also relieves acute frothy bloat when given PO. The incidence of frothy bloat in feedlot cattle may be reduced by including ionophores (such as monensin) either in the ration or administering as controlled-release capsules.
Ruminal alkalinizing agents are principally used to treat ruminal lactic acidosis (pH <5.5) due to grain engorgement or soluble carbohydrate overload. (Also see Grain Overload in Ruminants.) The resultant systemic dehydration and acidosis necessitate immediate correction of fluid and electrolyte balance and restoration of a viable microbial population. Often, the latter involves removal of ruminoreticular contents and replacement with fresh ruminoreticular fluid. Antacids that may be given PO, bid-tid, include magnesium hydroxide (cattle: 100–300 g; sheep: 10–30 g) and magnesium carbonate (cattle: 10–80 g; sheep: 1–8 g). Antacids should be mixed in ~10 L of warm water to ensure adequate dispersion through the ruminoreticular contents. Administration PO of activated charcoal (2 g/kg) is believed to protect the ruminoreticular mucosa from further injury by inactivating toxins. Oral administration of sodium bicarbonate (baking soda), either as powder dissolved in water or commercially available solutions prepared for IV infusion, rapidly neutralize the rumen pH but are accompanied by rapid release of large amounts of CO2. Because of decreased rumen motility in ruminants with acute rumen acidosis, these animals are at increased risk of developing potentially life-threatening free gas bloat.
Ruminal acidifying agents are used to treat ruminal stasis or simple indigestion as well as acute ammonia poisoning. In ruminal stasis, the intraruminal pH often increases to >7.5 because of the constant inflow of bicarbonate-rich saliva in the absence of active ruminal fermentation and formation of volatile fatty acids. In acute ammonia intoxication, the increased intraruminal pH increases the activity of urease and facilitates the absorption of free ammonia (pKa of ammonium is 9.1). Administration of weak acids in cold water returns the pH of ruminoreticular content toward physiologic levels, promotes the uptake of volatile fatty acids, depresses the absorption of ammonia, and inhibits excessive urease activity. Acetic acid (4%–5%) or vinegar (cattle: 4–8 L; sheep: 250–500 mL) is the most common acidifying agent used.
The use of motility modifiers in cattle is controversial, because evidence-based data demonstrating clinical efficacy are scarce. Several diseases, including paralytic ileus, cecal dilatation, and abomasal displacement, are accompanied by GI tract motility disorders. Pharmacologic motility modification may hasten recovery in some cases. However, in most instances, the most effective strategy to reestablish motility is correction of the underlying disorder (hypocalcemia, endotoxemia, alkalemia, obstruction, or organ displacement) followed by restoration of the normal ruminoreticular environment through transfaunation. Furthermore, conditioned responses to the presence of feed and feeding itself are physiologic means by which ruminoreticular motility can be notably enhanced.
Motility modifiers are categorized based on their mechanism of action. These can be cholinergics (parasympathomimetics), adrenergics, antidopaminergics, serotonergics, motilin agonists, opioid receptor blockers, or sodium channel blockers (lidocaine).
The use of parasympathomimetic agents (eg, neostigmine, physostigmine, bethanechol) is seldom appropriate. These drugs have cholinergic effects, which are potentially hazardous. Neostigmine (cattle: 0.02 mg/kg, SC; sheep: 0.01–0.02 mg/kg, SC) generally produces the fewest adverse effects but tends to increase frequency, rather than strength, of ruminoreticular contractions. Neostigmine given as a constant-rate IV infusion (87.5 mg in 10 L of sodium-glucose infusion at 2 drops/sec) has been used to treat cecal dilatation/dislocation. However, the stimulatory effect of neostigmine is not always reliable, and some inhibition of motility can be seen. This may be due to the adrenergic component associated with ganglion stimulation by cholinergic agents.
Bethanechol (0.07 mg/kg, SC, tid for 2 days) has been used to treat spontaneous cecal dilatation without torsion. Potential adverse effects include salivation and diarrhea. Recommendations involving neostigmine and bethanechol have not been confirmed in randomized, controlled experiments. Neither compound has been approved by the FDA for use in cattle. Parasympathomimetics are sometimes used in practice to conservatively treat left displaced abomasum in cows, although the literature indicates that use of these compounds is of no value for this purpose.
N-butylscopolammonium bromide (nonlactating adult cattle: 0.2 mg/kg, IM or IV; calves: 0.4 mg/kg, IM or IV) is a parasympatholytic agent approved for the control of diarrhea in cattle in some European countries. The commercial formulation is combined with an NSAID, metamizole (nonlactating adult cattle: 25 mg/kg, IM or IV; calves: 50 mg/kg, IM or IV). Administration of N-butylscopolammonium bromide (80 mg/cow) in combination with dipyrone has been proposed as a conservative treatment of spontaneously occurring right-side displacement of the abomasum in cattle. However, this has not been demonstrated in randomized, controlled studies. N-butylscopolammonium bromide is not approved by the FDA, and the use of dipyrone in food animals in the USA is prohibited.
Atropine (0.04 mg/kg, IV) has been found to mitigate abomasal contractions for 1–3 hr. Atropine sulfate (0.5 mg/kg, IV) administered 5 min before placement of a reticular magnet is suggested to prevent magnet loss into the cranial sac of the rumen. Atropine (40 mg/cow as a 1% solution, SC) is also used to determine disruption of forestomach motility in cattle suspected to have vagal indigestion. An increase of >16% in heart rate 15 min after atropine administration is considered indicative of severe disruption of forestomach motility.
Xylazine hydrochloride (0.2 mg/kg, IV) administered 5 min before placement of a reticular magnet may prevent loss into the cranial sac of the rumen but will also result in deep sedation of the animal and thus is unlikely to be of any practical use. Xylazine-induced atony of the reticulorumen may be reversed by pretreatment with tolazoline (0.5 mg/kg, IV), atipamezole hydrochloride (0.08 mg/kg), or yohimbine (0.2 mg/kg, IV). Adverse effects of xylazine in cattle include bradycardia, hypothermia, salivation, diuresis, ruminal bloat, and aspiration pneumonia. Neither xylazine nor its antidotes have been approved by the FDA for use in cattle.
Metoclopramide (cattle: 0.15 mg/kg, IM; sheep: 0.023–0.045 mg/kg) has cholinergic and antidopaminergic effects but does not appear to increase the myoelectric activity of the pyloric antrum in either species. However, metoclopramide at 0.5 mg/kg given IM or IV to goats has been shown to increase myoelectric activity of the pyloric antrum but not the body of the abomasum. Because metoclopramide can cross the blood-brain barrier, restlessness and excitement are potential adverse effects. Metoclopramide has not been approved by the FDA for use in cattle.
Erythromycin lactobionate is a macrolide antimicrobial that increases gut myoelectric activity by binding to motilin receptors in intestinal smooth muscle cells. In cows, erythromycin (0.1 mg/kg, IV, or 1 mg/kg, IM) was found to increase myoelectrical activity in the abomasum and duodenum for >2 hr. This effect was increased to 6–8 hr when erythromycin was administered in polyethylene glycol at 10 mg/kg, IM. Erythromycin is approved by the FDA only for treatment of shipping fever, pneumonia, footrot, and metritis at 2.2 mg/kg, IM. Deep IM injection in muscles of the neck is recommended because of the risk of pain, swelling, and tissue blemishes at the injection site.
The prokinetic serotoninergic drug cisapride (cattle: 0.08 mg/kg) is widely used in equine medicine, yet significant prokinetic effects have not been conclusively demonstrated in ruminants. Furthermore, definitive clinical and experimental data to support the use of opioids or lidocaine in ruminants have not been published.