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Fluid Therapy
C H A P T E R 48 Fluid Therapy Rance K. Sellon
Dogs and cats with gastrointestinal (GI) disease commonly need fluid therapy. The most basic reasons for fluid therapy in patients with GI disease are replenishment or maintenance of intravascular fluid volumes and correction of specific metabolic deficits, such as electrolytes, serum protein concentrations, and others, that arise secondary to GI disease. As such, there is no “one-size-fits-all” approach to fluid therapy in patients with GI disease; rather, fluid therapy should be tailored to the needs unique to the individual patient. Provision of appropriate fluid therapy requires an inventory of a variety of fluid types, access to laboratory and other technologies for patient monitoring, and a staff trained in the monitoring and care of patients receiving fluid therapy.
Drug Classifications Crystalloids and colloids are the fluid types most commonly used in the treatment of dogs and cats with GI disease. Crystalloids are compositions of fluid and electrolytes in varying proportions that are divided generally into replacement fluids and maintenance fluids. Box 48-1 provides examples of each of these types of fluids. Replacement fluids, as the name suggests, are designed to replace water and electrolytes lost as a consequence of GI (or other) disease, and are characterized by higher concentrations of sodium than maintenance fluids, which have proportionally more water than replacement solutions. Colloids can be synthetic or natural. Box 48-1 also outlines examples of synthetic and natural colloids.
Pathophysiology The need for fluid therapy in patients with GI disease arises from a number of pathophysiologic conditions. Because of malaise and anorexia, dogs and cats with GI disease may have fluid intake reduced to a level unable to offset sensible and insensible fluid losses. Patients with GI disease are also susceptible to increased fluid losses as a result of vomiting, diarrhea, and, in some cases, polyuric states. Lastly, some types of GI disease put patients at risk for fluid redistribution into third spaces, such as edema or effusion caused by hypoalbuminemia and peritonitis. These pathophysiologic processes are not mutually exclusive, and all three mechanisms could be operative in a given patient. This chapter is a broad overview of fluid therapy in patients with GI disease. Readers interested in more in-depth information regarding fluid therapy are referred to other references.1,2
Goals of Fluid Therapy Some important goals of fluid therapy, and the general types of fluids commonly used to meet these goals, include the following:1,2 • Restoration and maintenance of circulating volume for tissue perfusion: crystalloid and colloidal fluids • Correction of abnormalities of electrolytes, glucose: crystalloids, electrolyte, and glucose supplements • Provision of oncotic support: synthetic and natural colloids • Restoration of oxygen-carrying capacity: whole blood and blood products • Provision of nutritional support: enteral and parenteral nutritional solutions
514
Rational Use in the Diagnosed Patient Indications for Fluid Therapy Determined by History and Physical Exam The decision to administer fluids to a patient with GI disease should take into account historical elements (e.g., is the patient voluntarily eating and drinking?), physical examination findings, results of laboratory or other diagnostic tests, and the underlying disease process. Patients that are unwilling, or unable, to drink emerge as more likely candidates for fluid therapy than those patients that can and will drink. Dogs or cats that are dehydrated, as suggested by the physical examination and/or laboratory results, also become candidates for fluid therapy. The physical examination assessment of hydration status has potential errors in interpretation. Animals that have lost considerable body weight commonly have reduced skin turgor, prolonged skin retraction, and ocular recession even if normally hydrated. Heart rates can be elevated for reasons other than dehydration. Nausea may contribute to a degree of mucous membrane moistness in the dehydrated patient, and mucous membranes may be overly dry in the patient that has been panting. Capillary refill times may be prolonged as a result of marked sympathetic stimulation and constriction of peripheral vascular beds, or may be very rapid in patients with peripheral vasodilation or hyperdynamic states of cardiovascular shock (as occurs, e.g., with sepsis). Determined by Laboratory Data Laboratory abnormalities that could suggest the need for fluid therapy include hemoconcentration, prerenal azotemia for reasons
CHAPTER 48 Fluid Therapy
Fluids Used in the Treatment of Box 48-1 Gastrointestinal Disease of Dogs and Cats Crystalloids Replacement
Lactated Ringer’s solution 0.9% Sodium chloride Normosol-R Plasmalyte
Maintenance
5% Dextrose Plasmalyte 0.45% Sodium chloride/half-strength lactated Ringer’s solution
Colloids Synthetic
Hetastarch Gentran VetStarch
Natural
Plasma (fresh or fresh frozen) Concentrated albumin solutions Human Canine
other than heart failure or reduced cardiac output, and abnormalities in electrolytes such as hyper- or hyponatremia, hyper- or hypokalemia, and acid–base disorders. Electrolyte abnormalities are nearly impossible to predict in patients with GI disease, so baseline laboratory evaluations should be obtained to guide choices in fluid therapy. Some volume-depleted patients may have a small cardiac silhouette or small pulmonary vessels evident on thoracic radiographs. It is common for abnormalities of hydration status to mask laboratory abnormalities—for example, the dehydrated and anemic patient may initially have a normal packed cell volume—so the clinician needs to be mindful of all the pathophysiologic processes that influence a given laboratory result and assess the patient for the presence of multiple pathophysiologic processes that could confound laboratory interpretation. Determined by Underlying Disease and Severity The underlying disease process may also influence fluid therapy decisions. For example, adult animals with acute, self-limiting gastroenteritis without physical examination or laboratory data abnormalities may be fine without fluid therapy, or with minimal fluid therapy, whereas puppies with acute parvoviral enteritis are likely to die without fluid therapy.
Fluid Selection The type of fluid administered to a dog or cat with GI disease is based on history, physical examination, and diagnostic test results. Patients that are dehydrated are usually candidates for replacementtype crystalloid fluids; patients that are profoundly hypotensive or hemodynamically unstable may benefit from boluses of colloid fluids in addition to initial replacement fluids. Patients with effusions from inflammatory disease, or hypoalbuminemic patients, commonly need colloidal support to help maintain a degree of effective circulating vascular volume. Patients that are not dehydrated, but for which a need for fluid supplementation is anticipated, may require little more than a maintenance type of fluid. Moderate to marked
515
hypoalbuminemia, or hypotension/shock are often indications for colloidal fluid administration.3
Route of Administration Fluids may be administered orally, intravenously, subcutaneously, or occasionally intraosseously. For most patients with GI disease, the most commonly employed routes are oral, intravenous (IV), and subcutaneous (SC). For animals, dogma has long held that patients with vomiting and diarrhea should receive fluids through routes other than oral.4 Dogma has been challenged, however, as Mohr and colleagues5 demonstrated that parvovirally infected puppies fared no worse, and were discharged from the hospital sooner, when oral nutrition solutions were administered. In people, oral electrolytecontaining fluids are commonly administered to diarrheic patients as the ability to absorb sodium, and thus water, remains intact in most diarrheal illnesses (see Chapter 1). Similar studies demonstrating a benefit of oral rehydration therapy in diarrheic dogs have not yet been performed, but it is likely that many would benefit from oral fluid therapy. IV fluids should be the prime consideration for patients that need rapid fluid volume replacement (e.g., shock, hypotension) and for patients with persistent vomiting. Fluids given subcutaneously may suffice for the normally hydrated patient that needs short-term fluid support, but this route is not ideal for volume replenishment given the comparatively small volumes of fluid that can be successfully given via this route. Intraosseous and intraperitoneal routes of fluid administration are typically reserved for those patients for which venous access is not possible. For a description of the technique of intraosseous fluid administration, the reader is referred to other sources.1
Monitoring of Fluid Administration Once fluid therapy has been initiated, monitoring becomes an important element of the therapeutic strategy, particularly for those patients with complicated or long-term fluid needs. Assessment of therapeutic responses should be based on changes in physical examination findings; for the GI disease patient for which changes are taking place rapidly, physical examination assessments may have to be done frequently to best monitor fluid therapy responses. Attention to general attitude and appearance, heart rate, pulse quality, capillary refill time, mucous membrane color, and blood pressure are among the simplest of physical examination parameters that can be used to judge responses to fluid administration. Other parameters that are particularly useful for assessing responses to fluid therapy include urine output (may require a urinary catheter), body weight, and central venous pressure (increased with increased vascular fluid volume). Urine output in an adequately hydrated patient should be at least 1 mL/kg/h and values less than that could reflect insufficient rehydration, or oliguria/anuria secondary to renal injury. Body weight should increase in patients that are rehydrated. Increases in body weight in the face of physical examination or laboratory parameters that suggest continued volume depletion likely reflect third-space losses (interstitial edema, peritoneal or pleural effusion, GI tract fluid accumulation). Conversely, patients losing weight in the face of fluid therapy likely have had an underestimation of GI, urinary, or insensible fluid losses. Central venous pressure, if measured, should be between 5 and 10 cm water. A number of laboratory values are likely to change with fluid therapy, and become part of the monitoring equation. Special attention should be paid to erythrocyte mass, serum total protein, serum albumin, blood urea nitrogen (BUN), serum creatinine, electrolytes, and acid–base status, typically as reflected by changes in total CO2 and anion gap. Adjustments in fluid rate, composition (e.g.,
516
SECTION V Pharmacologic Approach to Gastrointestinal Disease
electrolyte or other additives), or fluid type (e.g., addition of a colloid) are all potential outcomes of monitoring of fluid therapy responses.
Contraindications and Side Effects Although fluid therapy is often important, even lifesaving, in the patient with GI disease, fluid therapy is not without potential adverse effects. Adverse effects can be seen following administration of either crystalloids or colloids. Administration of excessive amounts of fluids, particularly if administered intravenously, can lead to overhydration. Overhydration increases the risk of edema or effusion formation as a result of increased hydrostatic pressure. In patients with underlying cardiac disease, excessive fluid administration can provoke overt signs of heart failure (pulmonary edema, pleural or peritoneal effusion). Additionally, overhydration can dilute serum albumin concentrations and oncotic pressure, creating an additional risk factor for edema or effusion formation. A common complication of crystalloid fluid therapy is hypokalemia, particularly if potassium supplements are not added to the fluids. Complications of colloid administration include coagulation disorders, which are more of a concern with synthetic colloids. Administration of natural colloids (plasma, albumin) can be associated with hypersensitivity reactions.6-8 The risk of transfusion reactions associated with plasma administration can be reduced by minor crossmatching (donor serum to recipient erythrocytes), but febrile reactions associated with plasma transfusion are still possible, likely mediated through leukocyte–platelet aggregates. Concentrated human albumin solutions have been used, primarily in dogs, for the provision of oncotic support. Although available literature suggests that hypersensitivity reactions in clinical patients are not common, deaths in normal dogs have developed secondary to administration of concentrated human albumin.6-8 Thus, this product should be used with caution in dogs. Albumin products given to dogs with protein-losing enteropathies are likely to be of only short-term benefit because of ongoing losses, but these products
can be quite helpful in perianesthetic/perioperative periods when anesthetic and surgical interventions are likely to exacerbate hypoalbuminemia and attendant consequences. In addition to the physiologic complications that can be seen with fluid therapy, other complications are possible. Catheter or catheter site infections are possible if aseptic technique is not followed when placing IV catheters. Thrombophlebitis can be a consequence of IV catheterization, and administration of hypertonic or irritant fluid types. Blood loss can arise if patients chew connections on catheter ends. Extravasation of fluids can also occur if catheters are not secured to the patient.
References 1. DiBartola S: Fluid, Electrolyte and Acid Base Disorders in Small Animal Practice, ed 3, 2002, Elsevier. 2. Brown AJ, Otto CM: Fluid therapy in vomiting and diarrhea. Vet Clin North Am Small Anim Pract 38:653–675, 2008. 3. Smiley LE, Garvey M: The use of hetastarch as adjunct therapy in 26 dogs with hypoalbuminemia: a phase two clinical trial. J Vet Intern Med 8:195–202, 1994. 4. Sen I, Altunok V, Ok M, et al: Efficacy of oral rehydration therapy solutions containing sodium bicarbonate or sodium acetate for treatment of calves with naturally acquired diarrhea, moderate dehydration, and strong ion acidosis. J Am Vet Med Assoc 234:926–934, 2009. 5. Mohr AJ, Leisewitz AL, Jacobson LS, et al: Effect of early enteral nutrition on intestinal permeability, intestinal protein loss, and outcome in dogs with severe parvoviral enteritis. J Vet Intern Med 17:791–798, 2003. 6. Trow AV, Rozanski EA, Delaforcade AM, Chan DL: Evaluation of use of human albumin in critically ill dogs: 73 cases (2003-2006). J Am Vet Med Assoc 233(4):607–612, 2008. 7. Francis A, Martin L, Haldorson GJ, et al: Adverse reactions suggestive of type III hypersensitivity in six healthy dogs given human albumin. J Am Vet Med Assoc 230(6):873–879, 2007. 8. Martin LG, Luther TY, Alperin DC, et al: Serum antibodies against human albumin in critically ill and healthy dogs. J Am Vet Med Assoc 232(7):1004–1009, 2008.
Dogs and cats with gastrointestinal (GI) disease commonly need fluid therapy. The most basic reasons for fluid therapy in patients with GI disease are replenishment or maintenance of intravascular fluid volumes and correction of specific metabolic deficits, such as electrolytes, serum protein concentrations, and others, that arise secondary to GI disease. As such, there is no “one-size-fits-all” approach to fluid therapy in patients with GI disease; rather, fluid therapy should be tailored to the needs unique to the individual patient. Provision of appropriate fluid therapy requires an inventory of a variety of fluid types, access to laboratory and other technologies for patient monitoring, and a staff trained in the monitoring and care of patients receiving fluid therapy.
Drug Classifications Crystalloids and colloids are the fluid types most commonly used in the treatment of dogs and cats with GI disease. Crystalloids are compositions of fluid and electrolytes in varying proportions that are divided generally into replacement fluids and maintenance fluids. Box 48-1 provides examples of each of these types of fluids. Replacement fluids, as the name suggests, are designed to replace water and electrolytes lost as a consequence of GI (or other) disease, and are characterized by higher concentrations of sodium than maintenance fluids, which have proportionally more water than replacement solutions. Colloids can be synthetic or natural. Box 48-1 also outlines examples of synthetic and natural colloids.
Pathophysiology The need for fluid therapy in patients with GI disease arises from a number of pathophysiologic conditions. Because of malaise and anorexia, dogs and cats with GI disease may have fluid intake reduced to a level unable to offset sensible and insensible fluid losses. Patients with GI disease are also susceptible to increased fluid losses as a result of vomiting, diarrhea, and, in some cases, polyuric states. Lastly, some types of GI disease put patients at risk for fluid redistribution into third spaces, such as edema or effusion caused by hypoalbuminemia and peritonitis. These pathophysiologic processes are not mutually exclusive, and all three mechanisms could be operative in a given patient. This chapter is a broad overview of fluid therapy in patients with GI disease. Readers interested in more in-depth information regarding fluid therapy are referred to other references.1,2
Goals of Fluid Therapy Some important goals of fluid therapy, and the general types of fluids commonly used to meet these goals, include the following:1,2 • Restoration and maintenance of circulating volume for tissue perfusion: crystalloid and colloidal fluids • Correction of abnormalities of electrolytes, glucose: crystalloids, electrolyte, and glucose supplements • Provision of oncotic support: synthetic and natural colloids • Restoration of oxygen-carrying capacity: whole blood and blood products • Provision of nutritional support: enteral and parenteral nutritional solutions
514
Rational Use in the Diagnosed Patient Indications for Fluid Therapy Determined by History and Physical Exam The decision to administer fluids to a patient with GI disease should take into account historical elements (e.g., is the patient voluntarily eating and drinking?), physical examination findings, results of laboratory or other diagnostic tests, and the underlying disease process. Patients that are unwilling, or unable, to drink emerge as more likely candidates for fluid therapy than those patients that can and will drink. Dogs or cats that are dehydrated, as suggested by the physical examination and/or laboratory results, also become candidates for fluid therapy. The physical examination assessment of hydration status has potential errors in interpretation. Animals that have lost considerable body weight commonly have reduced skin turgor, prolonged skin retraction, and ocular recession even if normally hydrated. Heart rates can be elevated for reasons other than dehydration. Nausea may contribute to a degree of mucous membrane moistness in the dehydrated patient, and mucous membranes may be overly dry in the patient that has been panting. Capillary refill times may be prolonged as a result of marked sympathetic stimulation and constriction of peripheral vascular beds, or may be very rapid in patients with peripheral vasodilation or hyperdynamic states of cardiovascular shock (as occurs, e.g., with sepsis). Determined by Laboratory Data Laboratory abnormalities that could suggest the need for fluid therapy include hemoconcentration, prerenal azotemia for reasons
CHAPTER 48 Fluid Therapy
Fluids Used in the Treatment of Box 48-1 Gastrointestinal Disease of Dogs and Cats Crystalloids Replacement
Lactated Ringer’s solution 0.9% Sodium chloride Normosol-R Plasmalyte
Maintenance
5% Dextrose Plasmalyte 0.45% Sodium chloride/half-strength lactated Ringer’s solution
Colloids Synthetic
Hetastarch Gentran VetStarch
Natural
Plasma (fresh or fresh frozen) Concentrated albumin solutions Human Canine
other than heart failure or reduced cardiac output, and abnormalities in electrolytes such as hyper- or hyponatremia, hyper- or hypokalemia, and acid–base disorders. Electrolyte abnormalities are nearly impossible to predict in patients with GI disease, so baseline laboratory evaluations should be obtained to guide choices in fluid therapy. Some volume-depleted patients may have a small cardiac silhouette or small pulmonary vessels evident on thoracic radiographs. It is common for abnormalities of hydration status to mask laboratory abnormalities—for example, the dehydrated and anemic patient may initially have a normal packed cell volume—so the clinician needs to be mindful of all the pathophysiologic processes that influence a given laboratory result and assess the patient for the presence of multiple pathophysiologic processes that could confound laboratory interpretation. Determined by Underlying Disease and Severity The underlying disease process may also influence fluid therapy decisions. For example, adult animals with acute, self-limiting gastroenteritis without physical examination or laboratory data abnormalities may be fine without fluid therapy, or with minimal fluid therapy, whereas puppies with acute parvoviral enteritis are likely to die without fluid therapy.
Fluid Selection The type of fluid administered to a dog or cat with GI disease is based on history, physical examination, and diagnostic test results. Patients that are dehydrated are usually candidates for replacementtype crystalloid fluids; patients that are profoundly hypotensive or hemodynamically unstable may benefit from boluses of colloid fluids in addition to initial replacement fluids. Patients with effusions from inflammatory disease, or hypoalbuminemic patients, commonly need colloidal support to help maintain a degree of effective circulating vascular volume. Patients that are not dehydrated, but for which a need for fluid supplementation is anticipated, may require little more than a maintenance type of fluid. Moderate to marked
515
hypoalbuminemia, or hypotension/shock are often indications for colloidal fluid administration.3
Route of Administration Fluids may be administered orally, intravenously, subcutaneously, or occasionally intraosseously. For most patients with GI disease, the most commonly employed routes are oral, intravenous (IV), and subcutaneous (SC). For animals, dogma has long held that patients with vomiting and diarrhea should receive fluids through routes other than oral.4 Dogma has been challenged, however, as Mohr and colleagues5 demonstrated that parvovirally infected puppies fared no worse, and were discharged from the hospital sooner, when oral nutrition solutions were administered. In people, oral electrolytecontaining fluids are commonly administered to diarrheic patients as the ability to absorb sodium, and thus water, remains intact in most diarrheal illnesses (see Chapter 1). Similar studies demonstrating a benefit of oral rehydration therapy in diarrheic dogs have not yet been performed, but it is likely that many would benefit from oral fluid therapy. IV fluids should be the prime consideration for patients that need rapid fluid volume replacement (e.g., shock, hypotension) and for patients with persistent vomiting. Fluids given subcutaneously may suffice for the normally hydrated patient that needs short-term fluid support, but this route is not ideal for volume replenishment given the comparatively small volumes of fluid that can be successfully given via this route. Intraosseous and intraperitoneal routes of fluid administration are typically reserved for those patients for which venous access is not possible. For a description of the technique of intraosseous fluid administration, the reader is referred to other sources.1
Monitoring of Fluid Administration Once fluid therapy has been initiated, monitoring becomes an important element of the therapeutic strategy, particularly for those patients with complicated or long-term fluid needs. Assessment of therapeutic responses should be based on changes in physical examination findings; for the GI disease patient for which changes are taking place rapidly, physical examination assessments may have to be done frequently to best monitor fluid therapy responses. Attention to general attitude and appearance, heart rate, pulse quality, capillary refill time, mucous membrane color, and blood pressure are among the simplest of physical examination parameters that can be used to judge responses to fluid administration. Other parameters that are particularly useful for assessing responses to fluid therapy include urine output (may require a urinary catheter), body weight, and central venous pressure (increased with increased vascular fluid volume). Urine output in an adequately hydrated patient should be at least 1 mL/kg/h and values less than that could reflect insufficient rehydration, or oliguria/anuria secondary to renal injury. Body weight should increase in patients that are rehydrated. Increases in body weight in the face of physical examination or laboratory parameters that suggest continued volume depletion likely reflect third-space losses (interstitial edema, peritoneal or pleural effusion, GI tract fluid accumulation). Conversely, patients losing weight in the face of fluid therapy likely have had an underestimation of GI, urinary, or insensible fluid losses. Central venous pressure, if measured, should be between 5 and 10 cm water. A number of laboratory values are likely to change with fluid therapy, and become part of the monitoring equation. Special attention should be paid to erythrocyte mass, serum total protein, serum albumin, blood urea nitrogen (BUN), serum creatinine, electrolytes, and acid–base status, typically as reflected by changes in total CO2 and anion gap. Adjustments in fluid rate, composition (e.g.,
516
SECTION V Pharmacologic Approach to Gastrointestinal Disease
electrolyte or other additives), or fluid type (e.g., addition of a colloid) are all potential outcomes of monitoring of fluid therapy responses.
Contraindications and Side Effects Although fluid therapy is often important, even lifesaving, in the patient with GI disease, fluid therapy is not without potential adverse effects. Adverse effects can be seen following administration of either crystalloids or colloids. Administration of excessive amounts of fluids, particularly if administered intravenously, can lead to overhydration. Overhydration increases the risk of edema or effusion formation as a result of increased hydrostatic pressure. In patients with underlying cardiac disease, excessive fluid administration can provoke overt signs of heart failure (pulmonary edema, pleural or peritoneal effusion). Additionally, overhydration can dilute serum albumin concentrations and oncotic pressure, creating an additional risk factor for edema or effusion formation. A common complication of crystalloid fluid therapy is hypokalemia, particularly if potassium supplements are not added to the fluids. Complications of colloid administration include coagulation disorders, which are more of a concern with synthetic colloids. Administration of natural colloids (plasma, albumin) can be associated with hypersensitivity reactions.6-8 The risk of transfusion reactions associated with plasma administration can be reduced by minor crossmatching (donor serum to recipient erythrocytes), but febrile reactions associated with plasma transfusion are still possible, likely mediated through leukocyte–platelet aggregates. Concentrated human albumin solutions have been used, primarily in dogs, for the provision of oncotic support. Although available literature suggests that hypersensitivity reactions in clinical patients are not common, deaths in normal dogs have developed secondary to administration of concentrated human albumin.6-8 Thus, this product should be used with caution in dogs. Albumin products given to dogs with protein-losing enteropathies are likely to be of only short-term benefit because of ongoing losses, but these products
can be quite helpful in perianesthetic/perioperative periods when anesthetic and surgical interventions are likely to exacerbate hypoalbuminemia and attendant consequences. In addition to the physiologic complications that can be seen with fluid therapy, other complications are possible. Catheter or catheter site infections are possible if aseptic technique is not followed when placing IV catheters. Thrombophlebitis can be a consequence of IV catheterization, and administration of hypertonic or irritant fluid types. Blood loss can arise if patients chew connections on catheter ends. Extravasation of fluids can also occur if catheters are not secured to the patient.
References 1. DiBartola S: Fluid, Electrolyte and Acid Base Disorders in Small Animal Practice, ed 3, 2002, Elsevier. 2. Brown AJ, Otto CM: Fluid therapy in vomiting and diarrhea. Vet Clin North Am Small Anim Pract 38:653–675, 2008. 3. Smiley LE, Garvey M: The use of hetastarch as adjunct therapy in 26 dogs with hypoalbuminemia: a phase two clinical trial. J Vet Intern Med 8:195–202, 1994. 4. Sen I, Altunok V, Ok M, et al: Efficacy of oral rehydration therapy solutions containing sodium bicarbonate or sodium acetate for treatment of calves with naturally acquired diarrhea, moderate dehydration, and strong ion acidosis. J Am Vet Med Assoc 234:926–934, 2009. 5. Mohr AJ, Leisewitz AL, Jacobson LS, et al: Effect of early enteral nutrition on intestinal permeability, intestinal protein loss, and outcome in dogs with severe parvoviral enteritis. J Vet Intern Med 17:791–798, 2003. 6. Trow AV, Rozanski EA, Delaforcade AM, Chan DL: Evaluation of use of human albumin in critically ill dogs: 73 cases (2003-2006). J Am Vet Med Assoc 233(4):607–612, 2008. 7. Francis A, Martin L, Haldorson GJ, et al: Adverse reactions suggestive of type III hypersensitivity in six healthy dogs given human albumin. J Am Vet Med Assoc 230(6):873–879, 2007. 8. Martin LG, Luther TY, Alperin DC, et al: Serum antibodies against human albumin in critically ill and healthy dogs. J Am Vet Med Assoc 232(7):1004–1009, 2008.