Fluid Therapy for Specific Diseases and Disorders in Horses
Fluid Therapy for Liver Dysfunction and Hepatic Failure in Horses (Box 44.1)
K. Gary Magdesian
Acute liver disease may result in hypovolemia due to lack of water intake, third space losses into the gut and peritoneal cavity, and possibly pooling of blood in the portal circulation.
Portal hypertension may result in gut edema with subsequent fluid loss. Considerations of fluid therapy in cases with hepatic dysfunction include reduced metabolic capacity as well as compromised synthetic ability of the liver. Because lactate clearance primarily occurs in the liver, fluids containing lactate optimally should be avoided in horses with significant liver failure when other options are available. Isotonic replacement fluids containing acetate rather than lactate as the alkalinizing anion, such as Normosol-R (Abbott Laboratories, North Chicago, Ill.) and Plasma-Lyte A or Plasma-Lyte 148 (Baxter Healthcare Corporation, Deerfield, Ill.), and acetated Ringer's■ BOX 44.1
Fluid Considerations for Liver Failure
1. A combination of balanced, polyionic crystalloids and colloids is optimal.
2. Acetated fluids, rather than lactated Ringer's solution, should be used whenever available.
3. Colloids, particularly plasma, can be beneficial if hypoalbu- minemia is present and to minimize third space accumulation of fluids.
4. Potassium supplementation (20 to 80 mEq/L) may aid in reducing hyperammonemia (support. Blood glucose should be monitored and hyperglycemia should be avoided.
solution are preferred over LRS. One millimole (mmol) of acetate yields 1 mmol of bicarbonate during metabolism and is therefore alkalinizing.1 These balanced, polyionic fluids are optimal as compared with physiologic saline (0.9% sodium chloride) because of the propensity of the latter to produce a mild hyperchloremic metabolic acidosis (HCMA), and many horses with liver dysfunction have acidemia already.2 Hyperchloremic acidosis has potentially adverse effects, including renal afferent arterial constriction, and has negative effects on organ function, including gastrointestinal, central nervous system, and coagulation.3,4
Provision of dextrose, even in the face of normoglycemia, should be considered unless enteral nutrition is adequate.
The addition of dextrose to fluids will minimize gluconeogenesis demands on the liver as well as catabolism of endogenous tissues with subsequent increases in nitrogen turnover (and increased ammoniagenesis). With dextrose administration, the risk of hypoglycemia from liver dysfunction is also minimized, since patients may have insufficient liver and muscle glycogen reserves and impaired hepatic gluconeogenesis in order to maintain normal blood glucose concentrations. A common dextrose supplementation rate used by the author for adult horses is 1 mg/kg/min. This equates to 3% dextrose in fluids if 1 L/h of crystalloid is administered to a 500-kg horse. The author often begins with 0.3 to 0.5 mg/kg/min of dextrose and gradually advances the rate of administration as the horse tolerates the dextrose (aiming to keep the blood glucose concentration with acute colitis are often presented in a state of severe SIRS with endotoxemia, hypovolemia, and malperfusion of tissues. Fluid therapy is the cornerstone of hemodynamic support for these horses. Not only is low circulating volume an indication for fluid therapy in these cases, but acid-base and electrolyte derangements also warrant treatment with fluids. In addition to hypovolemia, horses with colitis often have both organic and inorganic acidoses as well as hyponatremia. Organic acidosis primarily results from hyperlactatemia, whereas inorganic acidosis is usually a result of relative hyperchloremia (or hyponatremia) from loss of sodium bicarbonate.Because of the poor sensitivity of physical examination in detecting hypovolemia in horses, estimates of percent dehydration and water deficit are not very accurate. A more structured means of providing fluids to sick horses is through the “fluid challenge” method described in the previous sections as adopted from human critical care.1 In this protocol a bolus dose of 10 to 20 mL/kg of isotonic crystalloid is administered over approximately 30 to 60 minutes to horses with hypovolemia, with subsequent reassessment of perfusion parameters.
Horses with marked fluid deficits may require the initial bolus to be administered as rapidly as possible, using a pressure bag. Perfusion parameters consist of mentation, peripheral pulse quality, heart rate, mucous membrane color, capillary refill time, and extremity temperature. Lactate, arterial blood pressure, and central venous oxygen saturation are monitoring tools that are used with the clinical examination in serial assessments to determine the best course of fluid therapy and serve as end points to replacement fluid therapy. Urine output is another clinical indicator of improvement in perfusion in response to fluid loading, and once urine production is present (as evidenced through ultrasonographic findings or urine collection) the rapid boluses can cease or slow in rate. Fluid challenge should continue as repeat boluses, albeit at progressively slower rates for each subsequent bolus, until perfusion parameters normalize or plateau in terms of improvement. No further improvement of perfusion parameters in response to boluses of fluids, with persistence of clinical indicators of hypoperfusion, suggests that inotrope or vasopressor support may be required and that further fluid therapy will not be of aid. Fluid overload is very detrimental to tissue oxygenation and cell function, and care should be taken to avoid it. A safety upper limit to fluid loading includes detection of a high normal CVP value, which should serve as a ceiling to fluid bolus administration.Crystalloid fluid choices for horses with colitis include isotonic, balanced replacement fluids, such as Normosol-R, LRS, Hartmann’s solution (compound sodium lactate solution), and Plasma-Lyte A or Plasma-Lyte 148. Normosol-R and Plasma-Lyte 148/A are slightly advantageous over LRS or Hartmann’s solution from the standpoint of providing a wider strong ion difference (sodium-chloride difference). The sodiumchloride difference in these acetated fluids is 42. In contrast, LRS has a sodium-chloride difference of only 21 and Hartmann’s solutions have a difference of 19 to 20.
These lactated fluids have a chloride concentration greater than that of equine plasma (109 mEq/L in LRS, 111 to 112 mEq/L in Hartmann’s solutions versus approximately 96 to 105 mEq/L in equine plasma), and this chloride excess can potentially compound an inorganic acidosis with large volume or duration of administration. Physiologic saline (0.9%) is even greater in its chloride concentration and produces a mild strong ion acidosis on administration of large volumes.1 There is emerging evidence in human medicine that saline may be associated with adverse effects as compared to balanced electrolyte fluids such as LRS or Plasma-Lyte. A meta-analysis investigating the effect of different fluid therapies on mortality in septic patients suggested that balanced crystalloids were associated with an increased survival rate in septic patients compared to normal saline.In addition, Normosol-R and Plasma-Lyte 148 or Plasma- Lyte A contain acetate (and gluconate) rather than lactate as the alkalinizing salt. This may be an advantage in horses with hepatic dysfunction because the liver is the primary site of lactate metabolism, whereas acetate and gluconate are metabolized by many tissues.
Colloids may be adjunctive to crystalloid therapy, particularly for horses with hypoproteinemia such as those with acute colitis. In human critical care medicine there is no consensus as to whether crystalloids or colloids provide more successful fluid resuscitation.1 A combination of both is likely optimal.1 Colloids may be useful for horses with hypoproteinemia, such as those with colitis. Concurrent hypovolemia and hypoproteinemia warrant administration of colloids, because the use of crystalloids alone could result in dilutional hypoproteinemia. Plasma may be considered the optimal colloid for use in horses with colitis at this time because of concerns over possible adverse effects of hetastarch on kidney function and mortality rates in humans and dogs, although the debate about possible negative versus positive effects of hetastarch is ongoing.3
Hypertonic saline (7% to 7.5%) is a rapid plasma volume expander that can be used in the early volume replacement period of volume resuscitation of the horse with colitis and acute diarrhea.
Hypertonic saline increases plasma volume by three to four times the volume administered. In comparison, crystalloids increase plasma volume by only 0.25 to 0.33 mL for each milliliter administered. Hypertonic saline has additional advantages beyond volume expansion, particularly for the horse with endotoxemia. These include immunomodulatory, antiinflammatory, anti-edema (particularly of the endothelium and erythrocytes), and inotropic effects.5-7 Microvasculature effects enhance microcirculatory perfusion, which is often disturbed during sepsis and endotoxemia. Reduction of endothelial and erythrocyte edema, two processes that contribute to multiple organ dysfunction during sepsis, results in reduced vascular resistance and blood viscosity.6,7 The hypertonicity created by hypertonic saline evokes vasodilation, which also contributes to microperfusion when coupled with an increase in cardiac output caused by contractility-enhancing effects of hypertonic saline. The antiinflammatory and immunomodulatory effects include anti-apoptosis, free-radical scavenging properties, inhibition of leukoactivation, and prevention of immunosuppression after sepsis.5-7 In an experimental model of hemorrhagic shock in horses, hypertonic saline resulted in improved cardiac output, stroke volume, cardiac contractility, and blood pressure as compared with isotonic saline.8 Hypertonic saline has demonstrated attenuation of cardiovascular derangements in equine endotoxemia models as compared with isotonic saline.9The dose for hypertonic saline is 4 mL/kg once, and it should be followed with, or administered concurrent to, isotonic crystalloids to replace the “borrowed” water from the intracellular space. Hypertonic saline is generally safe but should be avoided in horses with uncontrolled hemorrhage when hypotensive resuscitation is indicated. In addition, horses with marked sodium derangements should not be administered hypertonic saline. It should also be used with caution in neonatal foals.