Fielding Chapter 15: Fluid Therapy for Hepatic Failure

Causes of Intravascular Volume Deficits in Horses with Liver Failure

• Lack of fluid intake

• Decreased vascular tone and/or endothelial dysfunction

  • Decrease in vascular tone may be the most important factor

• Increased urinary loss

  • May in some cases be associated with a decrease in hepatic urea synthesis and a low serum BUN

    • Results in a decrease in urea-associated renal interstitial osmolality, which would decrease the effectiveness of vasopressin on renal water resorption

Hypertonic Saline for Resuscitation in Horses with Liver Failure

• Hypertonic saline (7.5%, 4 ml/kg) can be administered in adult horses with liver failure if there is clinical or measurable evidence of severe hypotension and abnormally low cardiac preload

  • Possible disadvantages would be the large-volume urination that usually occurs following treatment causing potassium loss in the urine (kaliuresis)

Crystalloids for Resuscitation in Horses with Liver Failure

• An alternative to the administration of hypertonic saline would be to administer in the first hours of therapy 50 ml/kg of a balanced crystalloid with 50 g of dextrose and 20 mEq of KCl added

  • Provides a volume of fluid nearly equal to a normal intravascular plasma volume

  • Ideally a crystalloid with an acetate buffer should be used rather than one with a lactate buffer

Monitoring for Resuscitation for Horses in Liver Failure

• Persistent elevations in PCV in spite of favorable findings for other cardiovascular parameters is not unusual in horses with acute liver failure, chronic liver disease that is severe, or hepatic neoplasia

• A decline in plasma lactate would be an indication of improved perfusion and is likely a favorable prognostic finding

  • Since the liver is a major organ for lactate metabolism and LRS may sometimes be given for resuscitation, it is possible that tissue perfusion has been improved but might not be reflected by a comparative decline in plasma lactate

Fluids Following Resuscitation for Horses in Liver Failure

• Following initial successful resuscitation, approximately twice maintenance fluid rate (120 ml/kg/day) with an acetate buffered balanced electrolyte solution is indicated

  • Dextrose (generally 50-100 g/L) and KCl (generally 20-240 mEq/L) should be continued depending upon the clinical condition of the horse, laboratory chemistry monitoring, and oral consumption of fluids

Factors to Avoid to Prevent Cerebral Edema in Horses with Hepatic Encephalopathy

Overhydration

Respiratory acidosis or alkalosis

Serum sodium derangements

Hypokalemia

Serum calcium derangements

Hypo-oncotic states

Low head position

Excessive sedation

Hypovolemia/hypotension

Hyperthermia

Sedatives in Horses with Hepatic Encephalopathy

• Sedatives may decrease ventilation, increase PCO2, and result in vasodilation within the brain which could contribute to cerebral edema

Decreasing Production of Ammonia/Ammonium in Horses with Hepatic Encephalopathy

• All efforts should be made to decrease the production of ammonia/ammonium, prevent their diffusion into the central nervous system, and increase their elimination

  • Maintaining adequate urine production and normal plasma K+ concentration will enhance renal ammonia/ammonium excretion

Should colloids be used in liver failure?

Colloid therapy will substantially increase the cost of treatment without proven benefit

If colloids are used, fresh-frozen plasma (FFP) or 25% human albumin may have some therapeutic advantages

25% Human Albumin for Liver Failure

• Plasma albumin treatment may increase plasma oncotic pressure, which will prolong and enhance the plasma volume restoration effect of crystalloid therapy

• Albumin may provide an antioxidant effect and potentially bind endogenous toxins that may be involved in the pathophysiology of HE

• Although the liver is the sole producer of albumin, severe hypoalbuminemia is rare in horses with either acute or chronic liver failure

  • May be related to the longer half-life of equine albumin (20 days) or the ability of the equine liver to produce albumin in spite of tremendous loss of function

• Administration of 25% human albumin would have a more dramatic effect on plasma oncotic pressure than fresh frozen equine plasma but is rarely used in horses

  • Would be a foreign antigen and doesn't provide regulating coagulation/inflammatory factors as does equine FFP

Fresh Frozen Plasma for Liver Failure

• FFP provides many proteins other than albumin that may be decreased with severe liver disease

  • Includes the non-endothelial derived clotting factors (II, V, VII, IX, X, XI, XIII) and other regulatory proteins such as protein C, protein S, antithrombin III, and fibronectin

• Prothrombin time (PT) can very quickly be prolonged following LF, naturally occurring bleeding abnormalities are uncommon in horses with liver failure

  • Liver biopsy rarely causes notable hemorrhage in horses with LF in spite of prolonged clotting times, possibly because of normal platelet counts in most horses with LF

• Horses with LF that require nasogastric intubation or those in need of surgery could be given FFP in an attempt to improve clotting function prior to the procedure

• Large amounts of plasma (10-15 ml/kg) may be needed to return PT and PTT to normal ranges

• Smaller amounts (2-8 ml/kg) would be less expensive, decrease the chance of volume overload, and may reduce the possibility of hemorrhage even if clotting function tests remain outside the normal range

  • If a whole blood transfusion is needed, it should be freshly collected because even with proper collection and storage for a short time (days), high ammonia concentrations can occur in the transfused blood and this should be avoided

Hetastarch in Horses with Liver Failure

• Hetastarch is best avoided in horses with LF as it may further prolong clotting times and its storage in hepatocytes and Kupffer cells may cause further deterioration in hepatic function

Ventral Edema with Equine Hepatic Lipidosis

• Ascites caused by LF is rarely reported in horses

• Equine hepatic lipidosis sometimes causes marked ventral edema

  • May be the result of an acute increase in hydrostatic pressure in the subcutaneous abdominal veins

  • Increased hydrostatic pressure may be caused by the acute need for these veins to carry a increased blood volume from the abdomen to the heart; this demand for alternate venous return may be due to the resistance to portal flow caused by the rapidly enlarging liver

Sodium Abnormalities in Hepatic Failure

• Possible that a part of the hyponatremia observed in horses with hepatic lipidosis may be spurious

  • Hyperlipemia may cause a false decrease in the sodium

• Ponies and miniature horses with hepatic lipidosis, hyperlipemia, and ventral edema may best be treated with a lower sodium fluid such as 0.45% NaCl + 2.5% dextrose + 20-40 mEq/L of KCl for maintenance purposes and 0.1 U of insulin/kg while monitoring both glucose and potassium concentrations

Potassium Abnormalities in Horses with Hepatic Failure

• Potassium homeostasis may be more important than sodium abnormalities in most horses with LF

• When horses become anorexic, as in LF, today body potassium and extracellular potassium may be quickly depleted

• Decrease in effective plasma volume as expected with LF would likely increase plasma aldosterone concentrations, which may further decrease plasma potassium through enhanced loss in the urine

• Plasma potassium concentrations may be variable depending upon renal function, acid-base abnormalities, and plasma glucose concentrations

• Horses with Theiler's disease and those with end stage liver disease may occasionally develop intravascular hemolysis, which may increase plasma potassium concentration

• Fluid therapy used to correct and maintain an adequate circulating intravascular volume will in most cases cause a net loss of potassium (even when added to the fluids) because of increased urine production and kaliuresis

• Proposed that potassium deficiency is a pathophysiologic factor in HE

  • May be a result of a relationship between potassium and ammonia metabolism, hypokalemia increases plasma ammonia and ammonium concentrations

Potassium Supplementation in Liver Failure

• In horses with LF that are producing urine following rehydration, potassium should be supplemented at 20-40 mEq/L

Abnormalities in Glucose Homeostasis with Liver Failure

• Glucose is the primary organ responsible for glucose production

• Glucose support should be considered in the fluid therapy plan for all patients with LF

• Most adult horses with LF are normoglycemic or hyperglycemic

  • Hyperglycemia may be at least partially the result of hyperammonemia

    • High NH3 enhances the release of glucagon and causes insulin resistance

Glucose Supplementation in Liver Failure

• Glucose as a 5% solution should initially be added to the crystalloid fluids provided to horses with LF but may need to be adjusted

• For marked hypoglycemia as is commonly seen in foals with LF, the initial intravenous fluid dextrose concentration should be 10%

• Insulin should be administered to equines with hyperlipemia and blood glucose concentrations above 180 mg/dL

• Glucose and/or insulin administration will decrease plasma potassium concentrations

Intravenous Nutritional Support for Hepatic Failure

• Glucose is the predominant intravenously administered nutritional support for horses with LF

• Forced enteral feeding is preferred, but partial parenteral nutrition using amino acids and glucose can be life saving in those that cannot be fed enterally

• Form of protein provided in parenteral nutrition or enteral support is controversial for patients with liver disease

  • Products high in branched chain amino acids are generally preferred

  • The less expensive standard protein solutions of crystalline amino acids might be equally useful in ponies, donkeys, and miniature horses with hyperlipemia that cannot be fed enterally

• Most horses with LF have a negative energy balance and any protein supplements will be primarily "burned" for calories

• Horses with LF should not be maintained for more than 5 days on dextrose alone without provision of some protein, as this may cause hepatic lipidosis

• All horses with LF should be administered multi-B vitamins to support cellular metabolism in the liver and other organs

What form of protein is preferred in horses with hepatic failure?

Products high in branched chain amino acids

What is the liver involved in the production and metabolism of?

Metabolism of organic acid anions (i.e. lactate)

Metabolism of ammonia

Production of albumin

What is the predominant acid base disturbance in horses with liver failure?

Metabolic acidosis and acidemia

Respiratory Compensation for Metabolic Acidosis in Liver Failure

• May be partial compensatory respiratory alkalosis in horses with HE, but these horses may be more prone to respiratory acidosis due to hypoventilation

What causes metabolic acidosis with liver failure?

• Metabolic acidosis in horses with acute liver failure is likely a result of hypoperfusion, increased anaerobic metabolism, and production of lactic acid as well as a decrease in the clearance of lactate by the failing liver and as a response to hyperammonemia

  • Liver is responsible for at least 50% of lactate metabolism

Lactic Acidosis in Horses in Liver Failure

• Lactic acidosis in horses with LF should be treated as it may cause impaired myocardial contractility and decrease vascular response to catecholamines

  • Treatment should focus on improving cardiac output and improving perfusion of all tissues including the liver

  • Best accomplished by administration of non-lactate containing crystalloids and correction of electrolyte abnormalities that may be undermining normal cardiac and endothelial cell function

    • Also normalize glucose concentrations and inhibit inflammatory cytokines and prostanoids

Using Sodium Bicarbonate to Treat Horses with Metabolic Acidosis Due to Liver Failure

• Sodium bicarbonate should not be used in the treatment of horses with metabolic acidosis and LF

  • It may rapidly increase the plasma ammonia concentration by shifting the ammonium:ammonia equilibration toward gaseous ammonia (NH3) which readily crosses an intact blood-brain barrier

  • May also lower plasma ionized calcium and potassium concentrations and even increase respiratory acidosis in horses with HE that are hypoventilating