Feline-feline Hepatic Lipidosis Treatment

Vol. 22, No. 10 October 2000

CE

Refereed Peer Review

FOCAL POINT ★ Cats with hepatic lipidosis (HL) require aggressive nutritional support; careful monitoring is needed because life-threatening complications may arise within 72 hours of initiation of nutritional therapy.

KEY FACTS ■ In contrast to the usual dietary recommendations for small animals with liver disease, most cats with HL should be fed highprotein diets. ■ Virtually all cats with HL require enteral nutritional support via a feeding tube. ■ Icteric cats with severe HL must be considered to be in critical condition at the time of presentation. ■ Life-threatening hypokalemia and hypophosphatemia may occur after initiating nutritional therapy in cats with HL. ■ Hypokalemia and hypophosphatemia may worsen despite adequate supplementation.

Feline Hepatic Lipidosis: Treatment Recommendations* Auburn University

Brenda Griffin, DVM, MS ABSTRACT: Aggressive nutritional support is the mainstay of treatment for feline hepatic lipidosis. The ideal diet would fulfill all basic protein and nutrient requirements, provide a positive energy balance, promote liver regeneration, and facilitate recovery from the metabolic derangements and clinical signs associated with the syndrome. For most cats, a high-protein diet is indicated. Patients should be monitored closely during the initial 72 hours of nutritional therapy, the period during which most serious complications occur.

F

eline hepatic lipidosis (HL), a syndrome in which hepatocellular lipid accumulation leads to intrahepatic cholestasis and liver dysfunction, is a common hepatobiliary disease in domesticated cats. All cats with HL need thorough systematic evaluation to rule out primary diseases that may be underlying their condition. Therapy for HL is aimed at reversing fat and protein catabolism, managing electrolyte abnormalities, and treating the clinical signs of hepatic disease as well as any underlying or concurrent conditions. Aggressive nutritional support is the cornerstone of treatment and is the only known effective therapy for cats with HL. The mortality rate associated with HL ranges from 10% to 40% in cats treated with aggressive nutritional therapy and is as high as 90% in cats not treated aggressively.1–3 Recurrence is rare.4

DIET The ideal diet for treatment of HL is unknown. The best clinical results are obtained with high-protein diets containing adequate calories and nutrients to meet known requirements.5 The need for increased dietary protein in patients with HL is in contrast to dietary recommendations in many other liver diseases in which increased protein may precipitate hepatoencephalopathy. In one study in which HL was induced by feeding 25% of maintenance energy requirements, cats fed calories as protein developed less lipid accumulation than did cats fed carbohydrate or fat,6 suggesting that protein improves mobilization of fat from hepatocytes. *A companion article entitled “Feline Hepatic Lipidosis: Pathophysiology, Clinical Signs, and Diagnosis” appeared in the September 2000 (Vol. 22, No. 9) issue of Compendium.

Compendium October 2000

Small Animal/Exotics

TABLE I Commercially Available Diets Used in the Treatment of Feline Hepatic Lipidosis For Cats without Clinical Signs of Hepatoencephalopathy

Manufacturer

For Cats with Hepatoencephalopathy

Abbott Laboratories (Abbott Park, IL)

Clinicare®—Feline Liquid Dieta

Clinicare® RF—Specialized Feline Liquid Dieta

Hill’s Pet Nutrition (Topeka, KS)

Prescription Diet® Feline p/d®b,c; Prescription Diet® Canine/Feline a/d™b,d

Prescription Diet® Feline l/d™b,e

The IAMS Company (Dayton, OH)

Maximum-Calorie™/Felinea,f

None

Ralston Purina Company (St. Louis, MO)

CNM CV-Formula®b,c

CNM NF-Formula®b,c

Waltham (Vernon, CA)

Waltham® Veterinary Diet Feline Selected Proteinb,c,g

Waltham® Veterinary Diet Feline Low Proteinb,c

a

Recommended for use with nasoesophageal and jejunostomy tubes. for use with esophagostomy and gastrostomy tubes. cMust be blenderized with water to make a gruel. d May be fed undiluted using an 18-Fr or larger tube. eMay be fed undiluted using a 20-Fr or larger tube. f May be fed undiluted using an 8-Fr or larger tube. g Contains novel protein and carbohydrate sources (venison and rice) and may be useful in cats with concurrent inflammatory bowel disease. bRecommended

When selecting a diet, one should consider that cats are true carnivores.7 Their physiology and metabolism require diets high in protein and fat and low in carbohydrate. Cats do not have the ability to synthesize such essential nutrients as taurine, arginine, vitamin A, niacin, and arachidonic acid that would be present in prey. Commercially prepared feline diets should be used to avoid nutritionally incomplete rations (Table I). Diets formulated for humans or other species require the addition of such supplements as the essential amino acid arginine, which is required for ammonia detoxification in cats. Cats have much higher protein requirements than do humans and dogs. Protein should provide at least 20% of a diet’s calories.7 Because protein is required to support a positive nitrogen balance and liver regeneration and because protein supplementation is known to reduce hepatic lipid accumulation during rapid weight loss in obese cats, cats with HL should receive the highest level of protein they can tolerate as soon as possible.6,7 Feline renal diets provide approximately 22% of calories as protein.7 Most cats with liver disease can tolerate higher dietary protein levels (up to 35% to 45%, which is typical of most commercial cat foods).7 Cats with overt signs of hepatoencephalopathy (severe depression and ptyalism), however, should be fed a reduced-protein diet, such as one designed to manage renal failure. Before feeding, diagnosis should be con-

firmed with a fasting ammonia concentration. Administration of oral lactulose (0.67-mg/ml solution, 0.5 to 1 ml/4.5 kg, three times daily) is often helpful because it lowers colonic pH, trapping ammonia as ammonium and thereby decreasing its absorption into portal circulation. In addition, oral metronidazole (7.5 to 15 mg/kg twice daily), oral neomycin (20 mg/kg three to four times daily), or oral amoxicillin (22 mg/kg two to three times daily) may be used to reduce intestinal bacterial flora, thereby decreasing ammonia synthesis in the intestinal tract.

ENTERAL SUPPORT Virtually all cats with HL require enteral support via a feeding tube. Nasogastric, esophagostomy, gastrostomy, or jejunostomy tubes may be used (Figure 1). Icteric cats with severe HL must be considered to be in critical condition at the time of presentation. Because most cats that die of HL do so within the first few days of therapy, treatment—including nutritional support— needs to be initially provided in noninvasive and nonstressful ways. Treatment for severe HL should be divided into an initial stabilization phase followed by a long-term phase.2 Investigators using this approach report lower mortality rates and recovery rates of 90%.1,2 During the initial stabilization phase (usually the first few days of therapy), dehydration and electrolyte imbalances should be corrected and monitored. Cats often look

SELECTING A DIET ■ PROTEIN REQUIREMENTS ■ INITIAL STABILIZATION

Small Animal/Exotics

Compendium October 2000

worse clinically (weaker, more may occur secondary to inflamdepressed) during the first few matory bowel disease or gasdays of treatment than when trointestinal lymphosarcoma, initially presented. Daily serum conditions that cannot be biochemistries and hematocrits definitively excluded based on are strongly recommended. Diclinical signs, laboratory findagnosis should be based on hisings, and diagnostic imaging tory, physical examination, clinialone. Esophagostomy tubes cal pathology, radiography, have become increasingly popabdominal ultrasonography, and ular because their placement recytology of fine-needle aspirates quires minimal technical skill of the liver. Invasive procedures, Figure 1—Common feeding tubes and sizes used in and no specialized equipment such as exploratory laparotomy cats (left to right): 5-Fr infant feeding tube, 14-Fr red and may be performed in less and liver biopsy, should not be rubber feeding tube (catheter), 22-Fr gastrostomy than 10 minutes.9,10 tube, and 8-Fr adult/pediatric feeding tube. The 5Esophagostomy and gastrosperformed. The least invasive and 8-Fr sizes may be used for both nasoesophageal method of nutritional support and jejunostomy tubes, depending on the size of the tomy tubes allow large boluses should be initiated (usually via a cat. For most cats, 14- and 22-Fr tubes are ideal for of blenderized cat food to be given because they are large nasoesophageal tube; Figure 2). esophagostomy and gastrostomy, respectively. bore and the stomach provides a Jugular catheters are useful for storage compartment for the administration of intravenous food. Slow infusion through a (IV) therapy and collection of jejunostomy tube (low-fat, serial blood samples, but their high-protein diet) is a rational insertion should be avoided therapy for cats with concurrent when clinically evident bleeding acute pancreatitis; concurrent tendencies are present. Use of surgical placement of a gastrosperipheral catheters is recomtomy tube is recommended bemended in cats with overt bleedcause it facilitates feeding after ing tendencies. All cats with HL pancreatitis resolves. Alternashould be evaluated for coagutively, partial or total parenteral lopathies. In addition, subcutanutrition can be administered neous administration of vitamin IV until pancreatitis resolves, afK1 (0.5 to 1.5 mg/kg at 0, 12, and 24 hours) is advised. For Figure 2—Cat with a nasoesophageal tube in place. ter which time a gastrostomy recommendations on fluid ther- Elizabethan collars are often necessary to prevent re- tube can be placed. apy, including selection, calcula- moval, especially after clinical improvement begins. FEEDING GUIDELINES tion, and administration, see Cats with HL should be fed Fluid Therapy for Anorectic 60 to 80 kcal/kg/day (i.e., approximately 250 to 300 Cats.8 After a patient is stable and able to safely tolerate the kcal/day for an average 4- to 5-kg cat).1,2,7 Because of necessary sedation/anesthesia and manipulation, a more ongoing gastric stasis and long-term anorexia, a slow substantial feeding tube can be placed for long-term increase in feeding over a few days is recommended to therapy. Liver biopsies can also be performed for definiminimize vomiting (see Suggested Feeding Schedule). tive diagnosis. Because mortality rates are higher in cats Tube feeding can be performed by owners after cats undergoing laparotomy, the least invasive means availare sent home. Owners should be instructed to warm able for tube placement and biopsy should be used. the gruel, administer it slowly over a few minutes, and For the long-term phase of therapy, many authors flush the tube with water after each feeding. Depending prefer gastrostomy tubes (Figure 3), which can be placed on the consistency of the blenderized diet, the gruel using percutaneous endoscopy, JorVet™ Eld gastrostomay need to be strained to facilitate passage through my tube applicators (Jorgensen Laboratories, Loveland, the tube. The tube may also be used for administration CO), Cook ® gastrostomy tube introduction sets (Cook of medications provided tablets are well crushed and Veterinary Products, Bloomington, IN), or surgery.1,3,5,7 dissolved. In the event a tube becomes clogged with I recommend endoscopic biopsy of the gastrointestinal food particles, a 3.5-Fr red rubber catheter may be used tract at the time of gastrostomy tube placement: HL to dislodge material from the tube lumen. If this is unLAPAROTOMY ■ LONG-TERM THERAPY ■ BIOPSY ■ PANCREATITIS

Compendium October 2000

Small Animal/Exotics

Fluid Therapy for Anorectic Cats8 Fluid Type ■ Select isotonic balanced electrolyte fluids (e.g., lactated Ringer’s solution) for initial support. ■ Consider serum potassium and sodium concentrations: —Begin potassium supplementation with 20 mEq potassium chloride/L. Adjust based on serum potassium concentrations (see Table II). —Avoid dextrose-containing solutions when possible because they lower both serum potassium and phosphorus concentrations through the action of insulin. —In cats with hypernatremia (hypertonic dehydration), 0.45% saline is preferred. —In cats with hyponatremia (hypotonic dehydration), 0.9% saline is preferred. ■ Add B-complex vitamins (2 ml/L). ■ Monitor packed cell volume, total solids, electrolytes, and phosphorus daily. (Postalimentation hypokalemia, hypophosphatemia, and anemia are common and may be life threatening.) ■ Note: Hypoproteinemic cats may require colloids. Fluid Needs Fluid requirements = Maintenance needs + Replacement needs + Ongoing losses Maintenance needs = 66 ml/kg/d (30 ml/lb/d) Replacement needs (L of fluid) = % Dehydration × Body weight (kg) Ongoing losses = An estimate of fluid lost through vomiting, diarrhea, polyuria, etc. Example: 8-lb cat with 6% dehydration that is vomiting once daily 8 lb = 3.6 kg

successful, 2 to 4 ml of a carbonated beverage (e.g., cola) may be flushed into the tube, followed in 5 to 10 minutes by 10 ml of warm water.9 Food aversion may be a complicating factor in cats with HL.7 Cats that refuse to eat a diet they associate with nausea may continue to avoid the diet even after full recovery. Exposing cats with HL to different commercial diets during tube feeding may predispose them to aversion of those diets. No food should be offered orally for the first 10 days of nutritional support.7 After

Maintenance needs = 66 ml × 3.6 kg = 240 ml/d Replacement needs = 0.06 × 3.6 kg = 0.21 L (210 ml) Ongoing losses (estimated amount of vomitus) = 15 ml Total to be infused over initial 24 hours = 240 + 210 + 15 = 465 ml (20 ml/hr) After rehydration and cessation of vomiting, this cat can be maintained with 240 ml/d (10 ml/hr). Note: Severely dehydrated cats may need front-loading of replacement fluids over 4 to 6 hours. Route of Administration ■ Intravenous fluids (an infusion pump is ideal; if unavailable, small bags of fluids, microdrip sets, and/or an in-line burette set is advised to prevent overdosing of fluids) —Unless bleeding tendencies are evident, jugular catheters (i.e., catheters specifically designed for use in the jugular vein) are preferred because they are less likely to kink and may be used for serial blood collection and measurement of central venous pressure. —Peripheral catheters (cephalic or lateral saphenous vein) are usually adequate, but leg bending may result in catheter kinking and/or slow fluid infusion. ■ Subcutaneous fluids —If 24-hr monitoring is unavailable, flush intravenous catheters with 2–3 ml of heparinized saline, cap securely, and cover overnight with a loose wrap. —Provided severe dehydration has been corrected, give a bolus of subcutaneous fluids until the intravenous infusion can be restarted the next day.

this time, cats expressing an interest in eating can be offered small amounts of a novel food. During the long-term phase of therapy, serum biochemical profiles should be monitored every 1 to 2 weeks depending on the patient’s stage of recovery. Resolution of icterus and hepatic function begins once the cat is receiving adequate energy and protein intake, but most cats require 3 to 6 weeks of diet therapy before clinicopathologic values normalize and the appetite returns.7 When biochemical parameters normalize, most

FOOD AVERSION ■ SERUM BIOCHEMICAL PROFILES

Small Animal/Exotics

Compendium October 2000

cats begin eating on their own and tube feedings can gradually be reduced. Tube removal is performed only after a cat is consistently eating its full caloric requirement for 1 week.

stasis, many cats may not have had a bowel movement for days to weeks before presentation. Removal of hard fecal material from the colon with a small glycerin enema or suppository may promote normal gastrointestinal motility. Cats with non–vitamin K responsive coagulopathies may require transfusions of plasma or fresh whole blood. Appetite stimulants (e.g., oxazepam, cyproheptadine) are seldom useful and are not recommended until the recovery phase of the disease, if at all.1,3,5 Antibiotic therapy is indicated when secondary infection is present. Because of their catabolic effects, corticosteroids are contraindicated unless indicated to treat an underlying disease. Ursodeoxycholic acid (Actigall®, Novartis, East Hanover, NJ) is used in humans with various liver diseases and may be beneficial in cats with HL. 12 Ursodeoxycholic acid promotes bile flow through modulation of bile acids and may increase hepatic peroxisomes and mitochondria. The recommended dose is 50 mg/cat/day orally; however, controlled studies are needed to evaluate the efficacy of this drug in cats with HL.

ADDITIONAL THERAPEUTIC RECOMMENDATIONS Several vitamin and dietary supplements, including carnitine, arginine, taurine, and antioxidants, have been advocated in the Figure 3A treatment of feline HL (see Current Recommendations for Dietary Supplements). Controlled studies of these supplements are needed for specific recommendations.1 Cats presenting with signs consistent with thiamine deficiency (e.g., ventroflexion of the head and neck; Figure 4) should receive two or three doses of supplemental thiamine (50 to 100 mg intramuscularly, twice daily).1 Lipotropic compounds that may Figure 3B potentiate hepatoencephalopathy Figure 3—Cat with a gastrostomy tube in place. (e.g., choline, methionine) are The tube may be covered with a bandage or prefercontraindicated and should not ably with a T-shirt. Elizabethan collars are rarely necessary. Shirts (which may be fashioned from cast be used.11 Other therapies include the stockinet or human infant clothing) offer the aduse of antiemetics and promotil- vantages of comfort and easy tube access and may ity drugs. Although vomiting be changed and washed by owners at home. may occur for many reasons (e.g., electrolyte imbalances, livCOMPLICATIONS er dysfunction, secondary to underlying diseases), gasComplications frequently occur during nutritional tric stasis caused by prolonged anorexia is common in therapy of feline HL, usually during the initial 72 hours, cats with HL. The absence of normal gut sounds (borand include tube-associated problems, hypokalemia, hyborygmi) on abdominal auscultation is consistent with pophosphatemia, and induction of hepatoencephalopagastric stasis. Gastric stasis can be treated with prothy. Because complications may be life threatening, motility drugs and by allowing ample time for the careful in-hospital monitoring of patients is essential stomach to empty between feedings. Metoclopramide during the initial stabilization phase of therapy. (0.2 to 0.4 mg/kg) can be administered through the feeding tube every 6 to 8 hours or subcutaneously 30 to Tube-Associated Problems 60 minutes before feedings or intravenously (1 to 2 Tube-associated complications include local irritation mg/kg/day, constant-rate infusion); oral cisapride (0.1 and infection, improper placement, and premature reto 0.5 mg/kg every 8 to 12 hours, or 1⁄4 of a 10-mg tablet for an average-sized cat) can also be used. Four moval. Nasoesophageal tubes often cause sneezing and daily feedings are adequate, tend to reduce the incinasal discomfort. Vomiting of the tube, aspiration dence of vomiting, and are practical for owner complipneumonia, and esophageal reflux are potential risks ance. A volume of 10 ml/lb/feeding should not be exwith nasoesophageal and esophagostomy tubes. 10 Esophagostomy, gastrostomy, and jejunostomy tubes ceeded. Because of prolonged anorexia and gastric THIAMINE DEFICIENCY ■ GASTRIC STASIS ■ URSODEOXYCHOLIC ACID

Small Animal/Exotics

Compendium October 2000

Suggested Feeding Schedule Daily caloric requirements = 60–80 kcal/kg Daily fluid requirements = 66 ml/kg Day 1: Day 2: Day 3: Day 4:

Feed 25% of daily caloric requirement divided into four feedings. Feed 50% of daily caloric requirement divided into four feedings. Feed 75% of daily caloric requirement divided into four feedings. Feed 100% of daily caloric requirement divided into four feedings, but do not exceed 22 ml/kg/feeding (10 ml/lb/feeding).

Note: During hospitalization, fluid requirements are supplemented parenterally. At home, adequate amounts of water should be given through the tube to ensure that requirements are met (most gruels are at least 80% water, but additional water is sometimes needed). Example Feeding Schedule for an 8-lb Cat 8 lb = 3.6 kg Energy requirements = 3.6 kg × 70 kcal/kg/d = 255 kcal/d Hill’s Prescription Diet® Feline p/d (Hill’s Pet Nutrition, Topeka, KS) contains 600 kcal/15-oz can; make a gruel a

by blenderizing one 15-oz can of the food with 7.5 oz (1⁄2 can) of water. This gruel can readily be passed through a 22-Fr gastrostomy tube. Remember to warm the gruel, and flush the tube with approximately 10 ml water after each feeding. Blenderized gruel = 600 kcal/22.5 oz; 22.5 oz × 30 ml/oz = 675 ml; 600 kcal/675 ml = 0.9 kcal/ml Total volume of gruel required to meet this cat’s daily energy requirements = 255 kcal × 1 ml/0.9 kcal = 283 ml/d Day 1: 283 ml × 0.25 = 70 ml, or four daily feedings of 17 ml each Day 2: 283 ml × 0.50 = 140 ml, or four daily feedings of 35 ml each Day 3: 283 ml × 0.75 = 212 ml, or four daily feedings of 53 ml each Day 4: 283 ml × 1.00 = 283 ml, or four daily feedings of 70 ml eacha Daily maintenance fluid requirements = 240 ml/d provided the cat is not dehydrated and has no ongoing fluid losses (see Fluid Therapy for Anorectic Cats). Water consumed through the diet = 283 ml gruel × 0.8 = 226 ml/day. In this case, the gruel plus the water used to flush the tube after feedings will provide daily fluid requirements.

This volume does not exceed 22 ml/kg/feeding (10 ml/lb/feeding).

tend to be well tolerated by patients; cats rarely require Elizabethan collars with these tubes. Minor stomal infections are common with both esophagostomy and gastrostomy tubes.10 Owners should be instructed to check and clean the tube stoma daily to prevent infection. Improper placement of a gastrostomy tube may result in obstruction of the pylorus and vomiting associated with feeding. Tube placement should be checked in persistently vomiting cats by administering a radiopaque, iodinated contrast solution through the tube. Although rare, premature tube extraction (less than 5 days) or tube migration may result in peritonitis (gastrostomy tube) or local infection (esophagostomy tube). Tube-associated complications are very rare when jejunostomy tubes are placed using newly described techniques.13

Hepatoencephalopathy Induction of hepatoencephalopathy is evidenced by

clinical signs (e.g., severe depression, ptyalism) that develop after the initial feeding. This complication is uncommon cats with HL14; if it occurs, it may be treated with low-protein diets and lactulose as discussed. Fasting at this time to obtain an ammonia concentration to document hepatoencephalopathy is not recommended. Smaller, more frequent feedings may be helpful. Cats should be monitored for exacerbation of hepatoencephalopathy-associated clinical signs after feedings. In most cases, clinical signs resolve within a few days, after which time most cats can be gradually switched to a higher-protein diet.

Electrolyte Imbalances Hypokalemia and hypophosphatemia are life-threatening electrolyte imbalances that may be sequelae to alimentation.15 The presumed mechanisms of hypokalemia and hypophosphatemia in cats with HL are similar. At

STOMAL INFECTIONS ■ PERITONITIS ■ PTYALISM

Small Animal/Exotics

Compendium October 2000

presentation, hypokalemia is Current Recommendations the most common elecfor Dietary Supplements trolyte abnormality in cats 14 with HL ; clinical signs of ■ Oral L-carnitine (DL-carnitine may be toxic): hypokalemia include lethar250–500 mg/cat/d, all at once or divided in gy, muscle weakness, ventral half, given in food neck flexion (Figure 4), my■ Subcutaneous vitamin K1: 0.5–1.5 mg/kg at ocardial depression, ileus, 0, 12, and 24 hr (excessive use may induce and urine retention and may progress to paralysis of the hemolysis) respiratory muscles and ■ B-complex vitamins in intravenous fluids: 2 death.15 Even if appropriate ml/L supplementation is imple■ Oral vitamin Ea: 100 IU/kg/d given in food mented, hypokalemia may worsen in the face of enteral ■ Oral vitamin Ca: 30 mg/kg/d given in food feeding because insulin re- ■ Oral taurineb: 250–500 mg/cat/d, all at once lease promotes intracellular Figure 4—Ventroflexion of the head and or divided in half, given in food uptake of potassium, thereby neck may occur because of severe potaslowering serum potassium a Vitamins E and C are antioxidants and may be useful sium depletion or thiamine deficiency. Treatment should include potassium concentrations (Table II). If because oxidative stress, which is common in cats, supplementation based on serial evaluaaggressive potassium-replace- may accompany the metabolic derangements and protein deficiency associated with HL. Formation of tions of electrolyte concentrations and ment therapy fails to nor- free radicals may damage hepatic peroxisomes.1,5 intramuscular thiamine injections (note malize serum potassium con- bOptional. the use of a jugular catheter). centrations within 48 hours, serum magnesium concenpromoting intracellular uptake of phosphate and glucose trations should be measured.15 Concurrent hypomagnesemia may cause refractory hypokalemia, which cannot for glycolysis.16,17 This transcellular shift of phosphate in the face of phosphate depletion causes hypophosbe corrected until the magnesium deficit is corrected. phatemia. Renal phosphate loss secondary to IV fluid Clinical signs of hypophosphatemia include muscle therapy may also be a contributing factor. In addition, weakness; clinical sequelae include hemolytic anemia, IV glucose infusions may contribute through the action leukocyte dysfunction, decreased tissue oxygenation of insulin. The role of hepatic dysfunction itself in the caused by decreased 2,3-diphosphoglycerate (2,3-DPG) development of hypophosphatemia deserves further inconcentrations, acute respiratory failure, and death.15,16 The mechanism of hypophosphatemia in cats with HL vestigation; studies of cats with severe hypophosphatemia may be secondary to low phosphorus intake, impaired inhave primarily involved cats with hepatobiliary disease testinal phosphate absorption, high renal phosphate loss, (89% in one study of nine cats).16 The onset of hypophosphatemia is reported to occur and transcellular shift of phosphate from the extracellular to the intracellular space.16,17 Normal serum phosphorus concentraTABLE II tions are often maintained in the Guidelines for Routine Intravenous Potassium Supplementation in Cats face of severe phosphorus depleSerum tion. Chronic malnutrition folAmount of Potassium Chloride to Add (mEq) Maximum Fluid Potassium lowed by alimentation can result Concentration To 250 To 1 L of Infusion Rate in refeeding syndrome, a term (mEq/L) ml of Fluid Fluid (ml/kg/hr) a coined in human medicine to de<2.0 20 80 6 scribe the metabolic derange2.1–2.5 15 60 8 ments associated with caloric re2.6–3.0 10 40 12 15 pletion of a starved patient. 3.1–3.5 7.5 30 17 Hypophosphatemia is the most 3.6–5.0 5 20 25 serious complication associated aCalculated to ensure that a rate of 0.5 mEq/kg/hr is not exceeded. with refeeding. Adapted from Macintire DK: Disorders of potassium, phosphorus, and magnesium in critiAdministration of enteral nucal illness. Compend Contin Educ Pract Vet 19(1):42, 1997. trition stimulates insulin release, HYPOKALEMIA ■ HYPOMAGNESEMIA ■ HYPOPHOSPHATEMIA ■ REFEEDING SYNDROME

Small Animal/Exotics

12 to 72 hours after initiation of enteral alimentation.16 If severe (serum phosphorus concentration below 2.2 mg/dl), hypophosphatemia can result in massive, acute hemolysis. Because cats may be more sensitive to hypophosphatemia-induced hemolysis than are other species and because hemolytic anemia and hypophosphatemia have been reported in cats with HL, careful postalimentation monitoring of hematocrit and serum phosphorus concentrations is indicated.17 (Experimentally, serum phosphorus concentrations must be reduced to less than 0.5 mg/dl to induce hemolysis in dogs.16) Adenosine triphosphate (ATP) depletion is the proposed mechanism by which hypophosphatemia causes hemolysis.16,17 ATP is necessary to maintain erythrocyte membrane integrity, shape, and deformability. ATP depletion causes malfunction of the sodium–potassium pump, resulting in decreased cell deformability and osmotic lysis. The spleen and liver may contribute by removing rigid erythrocytes. Cats with severe hypophosphatemia (below 2.2 mg/dl) should receive IV potassium phosphate or sodium phosphate at 0.01 to 0.06 mmol/kg/hour. The higher dose is often needed in severely affected cats.16 Parenteral potassium phosphate supplements contain 3 mmol of phosphate and 4.4 mEq/ml of potassium, whereas sodium phosphate solutions provide 3 mmol of phosphate and 4 mEq/ml of sodium. These phosphate supplements should be administered in calcium-free solutions (e.g., 0.9% saline) to prevent precipitation of insoluble calcium phosphate. The amount of supplemental potassium in the form of potassium chloride should be adjusted accordingly. Parenteral phosphorus should be used with caution in patients with renal failure and is contraindicated in patients with oliguria or hypercalcemia. The use of dextrose-containing fluids should be avoided in hypophosphatemic patients because such fluids may worsen hypokalemia and hypophosphatemia through the action of insulin. Phosphate binders (e.g., aluminum hydroxide, sucralfate) should also be avoided. Cats receiving IV phosphorus supplementation should be closely monitored for hemolysis, and serum phosphate and serum calcium levels should be monitored every 6 to 12 hours. In one study, four of five cats treated with IV phosphate developed hypocalcemia (5.4 to 8.7 mg/dl)17; only one cat, however, exhibited clinical signs of hypocalcemia (tetany, weakness). When serum phosphorus levels rise above 2.3 mg/dl, cats can be treated with oral phosphate supplementation, or IV doses may be reduced by 50% to 75%. If serum phosphorus concentrations remain normal over the following 24 hours, doses should be further tapered or discontinued. Cats with mild to moderate hypophosphatemia (2.3 to 3.3 mg/dl) may receive oral phosphate supplementation

Compendium October 2000

unless vomiting is present.17 Serum phosphate levels should be monitored every 12 hours until cats stabilize. Oral supplementation may be accomplished by feeding skim milk or commercial oral phosphate supplements. Cow’s milk contains 0.029 mmol/ml of phosphate.15 The oral phosphorus dose is 0.5 to 2.0 mmol/kg/day. An average 4-kg cat requires just over 2 oz of milk/day for adequate supplementation. Although many cats can tolerate this quantity of milk, using lactose-free milk (Lactaid®, distributed by H. P. Hood, Chelsea, MA) and dividing the milk dose over the day are recommended to prevent diarrhea caused by lactose intolerance.

CONCLUSION Cats with HL require aggressive nutritional support for recovery. In most cases, high-protein diets are indicated. Underlying diseases, if present, must be diagnosed and treated concurrently. Icteric cats with HL must be considered to be in critical condition. Their treatment should be divided into an initial stabilization phase followed by a long-term phase.2 Investigators using this treatment approach report recovery rates of 90%.1,2 Recurrence of HL is rare.4 Patients should be monitored closely during the initial 72 hours after alimentation because most serious complications, including life-threatening hypokalemia and hypophosphatemia, occur during this period. Without aggressive nutritional support and monitoring, most cats with HL die.1–3 REFERENCES 1. Center SA, Warner K: Feline hepatic lipidosis: Better defining the syndrome and its management. 16th Annu ACVIM Forum:56–58, 1998. 2. Norsworthy G: Improving survival in cats with hepatic lipidosis. Proc TNAVC:285, 1998. 3. Dimski DS, Taboada J: Feline idiopathic hepatic lipidosis. Vet Clin North Am Small Anim Pract 25:357–373, 1995. 4. Jacobs G, Cornelius LM, et al: Treatment of idiopathic hepatic lipidosis in cats: 11 cases (1986–1987). JAVMA 195: 635–638, 1989. 5. Dimski DS: Feline hepatic lipidosis. Semin Vet Med Surg Small Anim 12:28–33, 1997. 6. Biourge VC, Massat B, Groff JM, et al: Effects of protein, lipid, or carbohydrate supplementation on hepatic lipid accumulation during rapid weight loss in obese cats. Am J Vet Res 55:1406–1415, 1994. 7. Biourge VC: Nutrition and liver disease. Semin Vet Med Surg Small Anim 12:34–44, 1997. 8. Chew DJ: Intravenous fluid therapy for cats. 12th Annu Kal Kan Symp:53–60, 1988. 9. Norsworthy G: Placement of esophagostomy tubes in cats. TNAVC Proc:284, 1998. 10. Levine PB, Smallwood LJ, Buback JL: Esophagostomy tubes as a method of nutritional management in cats: A retrospective study. JAAHA 33:405–410, 1997. 11. Hubbard BS, Vulgamott JC: Feline hepatic lipidosis. Compend Contin Educ Pract Vet 14(4):459–464, 1992.

HEMOLYSIS ■ ATP DEPLETION ■ PHOSPHATE SUPPLEMENTS ■ HYPOCALCEMIA

Compendium October 2000

12. Center SA, Guida L, Zanelli MJ, et al: Ultrastructural hepatocellular features associated with severe hepatic lipidosis in cats. Am J Vet Res 54:724–731, 1993. 13. Daye RM, Huber ML, Henderson RA: Interlocking box jejunostomy: A new technique for enteral feeding. JAAHA 35(2):129–134, 1999. 14. Center SA, Crawford MA, Guida L, et al: A retrospective study of 77 cats with severe hepatic lipidosis: 1975–1990. J Vet Intern Med 7:349–359, 1993. 15. Macintire DK: Disorders of potassium, phosphorus, and magnesium in critical illness. Compend Contin Educ Pract Vet 19(1):41–48, 1997. 16. Justin RB, Hohenhaus AE: Hypophosphatemia associated with enteral alimentation in cats. J Vet Intern Med 9:228– 233, 1995.

Small Animal/Exotics

17. Adams LG, Hardy RM, Weiss DJ, et al: Hypophosphatemia and hemolytic anemia associated with diabetes mellitus and hepatic lipidosis in cats. J Vet Intern Med 7:266–271, 1993.

About the Author Dr. Griffin is affiliated with the Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Alabama. She is a Diplomate of the American College of Veterinary Internal Medicine.