Fluid Therapy for Renal Failure in Horses (Box 44.4)

C. Langdon Fielding • K. Gary Magdesian

Fluid therapy is the major component of treatment for renal failure in horses, regardless of cause. Renal replacement therapies have been reported in horses; however, they are not widely available, further highlighting the importance of fluid diuresis.^1-3 Peritoneal dialysis is an option to complement fluid therapy, particularly if unresponsive anuria is present.

For both oliguric/anuric and polyuric renal failure, there are two primary considerations when beginning fluid therapy: fluid type and rate. The total amount of fluid administered is usually determined by the response to treatment and does not necessarily need to be identified at initiation of therapy.

POLYURIC RENAL FAILURE. The goal of fluid therapy in these patients is to induce diuresis, with removal of uremic

■ BOX 44.4

Fluid Considerations for Horses With Acute Renal Failure toxins and maintenance of fluid, acid-base, and electrolyte balance.^4,5 The degree of renal failure that is reversible is often unknown at the onset; this is evaluated over time, particularly with response to fluid therapy. It should be noted that azotemia may not improve for up to 72 hours after initiation of fluid therapy when acute renal failure is severe. A lack of initial improvement in plasma creatinine or BUN during the first day or two of therapy should not necessarily prompt a poor prognosis or discontinuation of therapy.

The rate of fluid administration should facilitate diuresis.⁵ A rate of two times the maintenance fluid rate (4 to 6 mL/ kg/h, where the maintenance rate is 2 to 3 mL/kg/h) is a reasonable starting point; however, there is a paucity of literature to recommend evidence-based rates of fluid administration for treatment of acute renal failure or other disorders.

Fluid overload is a problem in renal failure and has been reported in human patients.^6,7 Excessive fluid administration may result in edema and associated morbidity and mortality. Measurement of CVP can be used to monitor excessive fluid administration and has become more practical in equine patients.^8-10 Reference ranges of less than 15 cm H₂O have been reported for adult horses; values exceeding 20 cm H₂O indicate a need to decrease the rate of fluid administration to avoid development of edema.⁹ The value of CVP monitoring continues to be controversial, and CVP measurement should not be used as the sole means for monitoring fluid overload.¹¹

A balanced isotonic crystalloid is suitable for diuresis while preventing significant electrolyte alterations.⁵ Horses should be allowed free access to water whenever possible while intravenous fluids are administered. This allows for some degree of self-regulation of water balance and can provide free water for renal excretion of the large sodium load provided by isotonic crystalloids.

Hyperkalemia is a relatively common feature of acute renal failure.^12,13 This is often corrected when renal perfusion is optimized and diuresis is instituted. When hyperkalemia is present, anuria should be ruled out. Cardiac dysrhythmias can develop during hyperkalemia; potassium-free fluids (isotonic sodium bicarbonate; possibly normal saline, although this is controversial as noted below) should be administered to patients with dangerous hyperkalemia (>6 mmol/L), along with calcium, dextrose, and possibly insulin.

LRS has the benefit of containing a minor amount of free water (osmolarity 273 mOsm/L) and slightly less sodium than other fluids (130 mEq/L).

Isotonic saline (0.9%) solution has an even higher chloride content (154 mEq/L) than LRS. In fact, neither the sodium nor the chloride concentration in this fluid is similar to those of equine plasma. Isotonic saline solution has been shown to cause hyperchloremia and a mild acidosis during prolonged administration.^15-17 This hyperchloremia may make isotonic saline a less ideal fluid for long-term management of acute renal failure. Saline does not contain potassium and therefore may be warranted in horses with hyperkalemia. However, creation of a metabolic acidosis because of hyperchloremia may also pose a risk for hyperkalemia by causing an extracellular shift of potassium; this shift occurs as a result of acute changes in blood hydrogen concentration, which occur in association with hyperchloremic metabolic acidosis.¹⁴ The effects of saline on potassium balance in horses warrant further study. Metabolic alkalosis, caused by hypochloremia or relative hypernatremia, is an indication for saline administration.

Normosol-R and Plasma-Lyte 148 (or Plasma-Lyte A) have a sodium and chloride concentration most similar to equine plasma among the commercial isotonic or nearly isotonic fluids and are excellent fluids for diuresis of acute renal failure cases. It should be noted that these contain the highest potassium concentration (5 mEq/L) of all commercial fluids described; however, this potassium content is unlikely to contribute to clinically significant hyperkalemia in polyuric animals because of urinary excretion of excessive potassium (possible exceptions are uroperitoneum and anuria).

Isotonic sodium bicarbonate solution can be made by mixing sterile water and sodium bicarbonate to create a solution with a sodium concentration of approximately 150 mmol/L. Isotonic sodium bicarbonate does not contain potassium or chloride and can be modified to contain an increased amount of free water as needed by lowering the sodium concentration. It exerts an alkalinizing effect by increasing strong cation (Na⁺) concentrations without a corresponding increase in strong anions (i.e., strong ion alkalosis).

Blending of fluids with different compositions is also an option in order to correct or maintain electrolyte and free water balance. Over time, horses often develop a plasma electrolyte profile similar to that of the administered fluid, especially when large volumes are administered for prolonged periods; therefore combining or changing fluids may be neces­sary if derangements develop. It is also clear that monitoring of electrolytes (one to four times per day) is particularly important in renal patients.

Synthetic colloids should be avoided in horses with acute kidney disease because renal injury is a known complication of administration of synthetic colloids in humans.

ANURIC OR OLIGURIC RENAL FAILURE. Anuria and oliguria should be considered emergency medical conditions; the longer the duration of little to no urine production, the lower the chances of correcting it. Urine output in healthy horses is approximately 1 mL/kg/h, but this may decrease by 80% (to 0.2 mL/kg/h) in horses deprived of water.^18,19 In humans without significant fluid deficits, a urine flow below 0.5 mL/kg/h is one criterion used to define acute renal injury, whereas acute renal failure is associated with a urine flow below 0.3 mL/ kg/h.²⁰ Oliguric renal failure should be suspected in azotemic horses with urine production below 0.5 mL/kg/h despite the administration of intravenous fluids. Once anuria or oliguria is suspected, a methodic approach to fluid administration and monitoring should be instituted immediately because of the associated high mortality rate.

■ Treatment of Anuria or Oliguria

1. Obtain baseline laboratory and hemodynamic parameters. These should include serum or plasma electrolyte levels, total plasma protein and blood lactate concentrations, packed cell volume (PCV), and clinical perfusion parameters. When possible, CVP, arterial blood pressure, and central venous oxygen tension should be measured as well. If possible, a body weight measurement should be obtained and recorded.

2. If CVP is not already significantly increased and there are no clinical signs of fluid overload (increased respiratory rate, peripheral edema, etc.), a fluid challenge should be initiated using 10 to 20 mL of an isotonic crystalloid per kilogram. CVP, clinical pathology, urine output, and physical examination status should be reevaluated for improvement after completion of the bolus.

3. If urine output has not increased significantly, additional fluid challenges should be given and the patient reevaluated until urine production begins or until CVP limitations are reached. A CVP value greater than 15 to 20 cm H₂O (>10 to 12 cm H₂O in foals) signifies an end point to fluid administration.

4. Arterial blood pressure should be monitored. If hypotension is present despite fluid loading, inotrope and vasopressor therapy should be considered. Dobutamine can be used as an inotrope (5 to 10 μg/kg/min). See the Fluid Therapy for Diarrhea and Colitis in Horses section earlier in this chapter.

5. Once urine flow has increased, fluids should be continued as described previously for polyuria; careful monitoring of CVP and fluid balance (measurement of serial body weight and urine output) should be done.

6. If urine flow does not begin over the next 30 to 60 minutes with fluid challenge, furosemide should be started with an initial bolus of 0.12 mg/kg IV followed by a constant rate infusion (CRI) of 0.12 mg/kg/h.²¹ If CRIs are not possible, a bolus dose of 1 mg/kg IV, which can be repeated a second time 30 to 60 minutes later, can be administered instead.

7. If urine production does not begin within 30 to 60 minutes of instituting furosemide therapy, a dose of mannitol should be administered (0.25 to 0.5 g/kg bolus as a 20% solution). If still no urine is produced after an additional 30 minutes, another dose of mannitol can be administered; a total dose of 1 g/kg should not be exceeded in the anuric patient to prevent hypervolemia and edema formation. Alternatively, a CRI of mannitol (1 to 2 mg/kg/min) can be used, with a maximum cumulative dose of 1 g/kg. Plasma osmolarity should be monitored.

8. If urine output has not improved after furosemide and man­nitol, the prognosis is grave without peritoneal dialysis or hemodialysis. Treatment with low-dose dopamine has been controversial in human medicine, and several large studies have failed to demonstrate a benefit.^23,24 In fact, furosemide, mannitol, and dopamine may increase urine flow but have not been shown to unequivocally improve outcome in humans with acute renal failure.²⁵ When dialysis is not an option for horses with anuric renal failure, dopamine can be tried in an attempt to produce urine flow (2 to 3 μg/kg/min); its proposed action is increasing renal perfusion with renal afferent arteriolar vasodilation.²⁶ Without urine flow, there is no opportunity to provide the patient with time to heal if the acute renal injury is reversible. If dopamine is successful at reversing anuria, this time can be provided.

9. Aminophylline can also be tried for reversal of anuria, at 0.5 mg/kg IV over 30 minutes. If improvement is noted, this can be repeated 2 to 3 times per day. It should be noted that aminophylline has a narrow therapeutic index, with toxicity occurring at plasma concentrations of 15 μg/ mL or greater.

Hyperkalemia and metabolic acid-base disorders are common in horses with anuric or oliguric renal failure.¹² As noted earlier, hyperkalemia can be associated with life-threatening dysrhyth­mias. Rapid initiation of diuresis and administration of sodium bicarbonate, dextrose, and insulin are therapeutic interventions for hyperkalemia. If dysrhythmias are present, calcium should be administered to raise membrane threshold potential, thereby reducing the likelihood of abnormal rhythms.

As mentioned previously, hemodialysis has been reported infrequently in horses for clinical cases of renal failure.¹ Peritoneal dialysis has been described as a cost-effective and practical approach for horses with acute renal failure.² More recently, continuous venovenous hemodiafiltration was per­formed in experimental horses for short periods (6 hours). These therapeutic options may become more commonly used in horses that do not respond to conventional fluid therapy and medical treatments of anuria described earlier.