Fluid Therapy for Sepsis (Peritonitis, Pleuritis, Pneumonia, Metritis, etc.) in Horses (Box 44.3)

K. Gary Magdesian

The optimal fluid for resuscitation of patients with sepsis remains an area of investigation, although recent work supports the use of balanced electrolyte solutions over hetastarch or normal (0.9%) saline.^1-4 A rational approach to fluid therapy in patients with sepsis is to optimize hemodynamics (increase oxygen delivery, blood pressure, and urine output) while attempting to limit fluid overload and edema formation.^1,5,6 There is no evidence to support the use of synthetic colloids over balanced crystalloids.¹ Older meta-analyses of clinical studies comparing crystalloids and colloids in human patient populations showed no outcome difference, but more recent studies point to a mortality decrease in patients receiving balanced crystalloids over normal saline or synthetic colloids.^1-4,6-8 Fluid therapy is a keystone in the management of severe sepsis and septic shock.

The recommendations for fluid therapy in septic horses are extrapolated from those in human medicine and similar to those for horses with acute enterocolitis discussed earlier in this chapter; both conditions are examples of a SIRS. In fact, enterocolitis can be thought of as a form of sepsis. Sepsis incites a host of hemodynamic derangements that challenge fluid therapy. It causes a myriad of microperfusion and hemo­dynamic abnormalities; these include hypovolemia, myocardial depression, vascular permeability derangements, vasodilation, DIC, and cellular changes resulting in abnormal membrane potential and membrane pump or channel function.⁸ These pathophysiologic processes must be considered when a fluid plan for horses with sepsis is designed.

Sepsis is a form of documented or suspected infection.^9,10 More recently, human medical organizations have redefined sepsis as a life-threatening organ dysfunction caused by a

■ BOX 44.3

Fluid Considerations for Horses With Sepsis dysregulated host response to infection and septic shock as persistent hypotension after fluid therapy (vasopressor depen­dency) and an increased lactate concentration in the absence of hypovolemia.¹¹ Many equine cases, including horses with peritonitis, pneumonia, pleuritis, enterocolitis, meningitis, and metritis, fall into this category. Sepsis and SIRS are states of cytokine milieu in which cytokines and inflammatory media­tors predominate. Aside from antimicrobials, the fundamental therapy is hemodynamic support, consisting of fluid and vasopressor therapy.

Initial fluid resuscitation centers on isotonic (or near isotonic) replacement-type fluids such as LRS, Hartmann’s solution, or Plasma-Lyte 148 or Plasma-Lyte A, with some indications for colloids or hypertonic saline. These have been associated with improved outcomes in human patients versus normal saline or synthetic colloids. Horses with sepsis often are presented with negative fluid balance resulting from both hypovolemia and dehydration. Fluid choices are the same as for horses with enterocolitis, and a combination of crystalloids and colloids, especially plasma, may have advantages in sepsis. Such a combination would address both blood volume and interstitial deficits, with plasma expanding the vascular space, providing albumin, antibodies, endogenous anticoagulants and clotting factors, and crystalloids that address both fluid spaces. The use of synthetic colloids such as hetastarch has decreased in recent times due to the possible adverse effects noted with its use.¹ Hypertonic saline may have some advantages during sepsis, including immunomodulatory, antiinflammatory, anti-edema, vascular, and inotropic effects.^12-14 A dose of 2 to 4 mL/kg of hypertonic saline may be added to the combination of isotonic crystalloids and administered during or just before administra­tion of isotonic crystalloids.

Care should be taken to avoid overexpansion of the extracel­lular fluid compartment with excessive fluid administration. Horses with sepsis have a predilection for edema because of the presence of concurrent hypoalbuminemia and increased vascular permeability. Therefore careful monitoring of fluid balance is warranted. Fluid balance refers to input and output of fluids, and it can be monitored with urinary collection systems. Under normal circumstances urine output should represent 50% or more of input, with the remaining output caused by fecal and evaporative losses (skin and pulmonary). CVP is also useful in monitoring for safety limits in this group of patients; maximal normal CVP (10 cm H₂O [8.8 mm Hg] in foals; 15 cm H₂O [11 mmHg] in adults) should not be exceeded. Serial ultrasonography and arterial blood gas analysis can be used to detect pulmonary edema from relative or absolute fluid overload, before the development of gross signs (froth, crackles, and tachypnea) of edema.

Because of thrombotic risks associated with sepsis-induced coagulopathies, these patients should be instrumented with minimally thrombogenic catheters, such as long-term poly­urethane catheters. Attention to asepsis and cleanliness is paramount.

In human critical care, “early goal-directed therapy” has been advocated by some clinical trials, although there is ongoing debate as to its universal effectiveness.¹⁵ These studies have used goal-oriented therapeutic adjustments of preload, afterload, and contractility to achieve a balance between oxygen delivery and demand. End points have included normalization of central venous oxygen saturation (70%), blood lactate, CVP (8 to 12 mm Hg in humans), urine output (0.5 mL/kg/h or greater), and MAP (65 mm Hg or greater in humans).¹⁶ The therapy consisted of crystalloids and colloids for correction of CVP, vasopressors and vasodilators for MAP, and dobutamine and red blood cell transfusions for central venous oxygen saturation. Patients receiving this early goal-directed therapy received a greater volume of fluids early (first 6 hours of treatment) and less later, as compared with patients in the conventional group. The treatment group had a lower mortality rate and less severe organ dysfunction, highlighting the importance of early identification of patients with insidious or occult malperfusion, consisting of patients with global hypoxia yet stable vital signs.¹⁵ Whether this type of targeted fluid therapy will have a place in equine medicine remains to be studied.

Glucose should be monitored closely in horses with sepsis, as both hypo- and hyperglycemia may develop. See the previous section for glucose regulation in critically ill patients. The current goal in human patients is to maintain a blood glucose of 180 mg/dL or less.