FRANK J. MILNE STATE-OF-THE-ART LECTURE


combine neomycin with lactulose. It would be ideal if the treatments softened the stool (a cathartic ef- fect) without causing diarrhea. Ideally, all oral medication should be given by dose syringe because the nasal bleeding resulting from passage of a stom- ach tube (probably never happens to you) will result in ingestion of considerable amounts of blood pro- tein, which would be likely to increase blood ammo- nia production.251 Other oral treatments that have been used in humans in hopes of lowering enteric ammonia pro- duction include probiotics and prebiotics, which may have some efficacy in treating HE by increasing non-urease producing bacteria.263 Treatments to decrease neuroinflammation and disruption of the BBB are mostly unproven, but include N- acetylcysteine, minocycline, neurosteroids such as progesterone or allopregnanolone, and hypother- mia.238,242,245 Treatments to support energy me- tabolism and antioxidant activity to the brain include B vitamins, vitamin C, and DMSO, although all are unproven. Treatment of cerebral edema with mannitol or hypertonic saline may have some temporary effect in decreasing cerebral edema. There are no highly effective, safe, and specific parenteral treatments for decreasing ammonia that is present in the blood and CSF of patients with HE. Glycerol phenylbutyrate has been used in human clinical studies, sometimes combined with branch chain amino acids (BCAAs), to lower ammonia by providing an alternative to the ammonia-to-urea pathway with excretion of phenylacetylglutamine in the urine.264,265 L-ornithine-l-aspartate (LOLA) reduces ammonia levels by increasing hepatic am- monia disposal and its peripheral metabolism. It is available in Europe in both intravenous formu- lations and oral formulations and some clinical trials have found it to be effective in treating hepatic encephalopathy.266,267 Another commonly recommended administered treatment for HE is oral supplementation of BCAA valine, leucine, and isoleucine. Their role in treat- ing HE is controversial with some reports demon- strating beneficial effects possibly via improving glucose metabolism, decreasing protein and muscle catabolism, and as an alternative pathway (in mus- cle) for ammonia detoxification.268 They may, therefore, be of particular benefit in treatment ofHE caused by hepatic lipidosis, but other reports point out concerns of BCAA administration increasing glutamine synthesis and worsening of HE.269


Nutritional Management of Acute and Chronic Liver Failure


Nutritional management specific for horses with liver disease, other than removing potential hepato- toxins and feeding an adequate diet, is generally not necessary unless hepatic dysfunction has occurred. Nutritional support for miniature horses, donkeys, and ponies with hyperlipemia and hepatic lipidosis is the most important indication for nutritional in-


tervention in equine liver disease.183 Although there are few, if any, evidence-based guidelines for nutritional management of horses with severe liver disease, some recommendations may be made intu- itively based upon an understanding of the function of the healthy liver and its repair following disease. Provision of adequate enteric glucose or glucose pre- cursors to the equine with severe liver disease may help maintain normal plasma glucose concentra- tions, decrease the workload of the failing liver, and inhibit lipolysis and muscle protein breakdown. When the liver is sufficiently diseased, liver glyco- gen stores and hepatic glucose production via glycogenolysis and gluconeogenesis are likely dimin- ished. Depletion of glycogen reserves in addition to insulin resistance, which may occur with some causes of liver failure, increase reliance on gluconeo- genesis from protein and this, often coupled with inappetence, tends to lead to an increased reliance on body protein for energy. Despite this metabolic dysfunction, most adult horses with liver failure have normal or even elevated blood glucose values, possibly related to insulin resistance.20,29 In a small percentage of cases, hypoglycemia may occur, which could worsen the neurologic signs associated with liver failure (HE) and cause generalized neu- romuscular weakness. This is especially pro- nounced in foals with hepatic failure because foals consistently and quickly develop hypoglycemia with the onset of liver failure.36 With an enhanced reli- ance on protein and fat catabolism for energy, there is both a rapid muscle breakdown and increased ammonia production in addition to increased serum triglycerides, the latter of which can be life threat- ening to miniature equine, ponies, and don- keys.174,180 Provision of adequate enteric glucose or glucose precursors in horses may decrease the workload of the failing liver, inhibit lipolysis and muscle protein breakdown and in those foals or horses prone to hypoglycemia, maintain plasma glu- cose concentrations. It may, therefore, be impera- tive in normoglycemic or hypoglycemic horses with severe liver disease that are still eating to provide an appropriate supply of glucose or easily digestible glucose precursors to help supply daily energy re- quirements, inhibit muscle and fat catabolism, and decrease the need for the liver to perform gluconeo- genesis or glycogenolysis. Compared with other products of carbohydrate hindgut fermentation (e.g., acetate, propionate, lactate) that can be used for energy, glucose provides 2–3-fold more ATP.270 The frequent (every 4–6 hours) feeding of small amounts of sugars, easily hydrolyzable carbohy- drates, and nonresistant starches that are readily digested to glucose and absorbed in the small intes- tine should be beneficial in maintaining a constant supply of enteric derived glucose.271 Feeds with high amounts of sugars or hydrolyzable carbohy- drates include most sweet feeds (especially those containing ingredients such as oats, cooked corn/ barley, and molasses), whole oats, or soaked beet


AAEP PROCEEDINGS  Vol. 61  2015 95


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