section epub:type=”chapter” id=”c0005″ role=”doc-chapter”> Nancy Sanders, Anthony S. Johnson and Katherine M. James Fluid therapy should be approached with the same attention to detail as any drug therapy. The foundation to this approach is an understanding of body fluid balance and perfusion. Without this knowledge, patients are at risk of complications of fluid mismanagement caused by a “cookbook” approach to fluid therapy. Potential complications of oversimplified approaches to fluid therapy include persistence or development of dehydration, fluid overload, hypoperfusion, acid–base imbalance, and electrolyte disorders. These complications can have profound effects on morbidity. A properly designed fluid therapy plan is an integral part of overall patient management. Acid-base; Acidosis; Albumin; Azotemia; Cardiorenal disease; Chronic kidney disease; Colloid; Colloid osmotic pressure; Congestive heart failure; Crystalloid; Dehydration; Diabetic ketoacidosis; Electrolytes; Extracellular fluid; Extravascular fluid; Fluid overload; Hetastarch; Hydroxyethyl starch; Hyperglycemic hyperosmolar syndrome; Hyperkalemia; Hypernatremia; Hypertonic; Hypokalemia; Hyponatremia; Hypophosphatemia; Hypotension; Hypovolemia; Insensible losses; Intracellular fluid; Intravascular fluid; Isotonic; Osmolality; Osmoregulation; Oxyglobin; Pentastarch; Perfusion; Postobstructive diuresis; Replacement fluids; Salt balance; Sensible losses; Starling’s forces; Third spacing; Total body water; Water balance Two of the kidney’s primary roles are homeostasis of body fluid composition and maintenance of fluid volume. Body fluid balance is best understood by looking at two interrelated processes: (1) salt balance and (2) water balance. Salt balance primarily refers to the sodium ion (Na+) because it is the principal extracellular cation. Water balance refers to the amount of water present relative to Na+. Although challenging to understand, the concepts of salt and water balance are essential to determining the type, amount, and rate of fluid to administer to a patient. It is counterintuitive but important to comprehend that disordered salt balance does not cause abnormalities of serum Na+ concentration but rather it results in abnormalities of extracellular fluid (ECF) volume. Alternatively, disorders of Na+ concentration result from abnormalities in water balance. Salt and water balance will be discussed in more depth in later sections; grasping the important distinctions between these two types of balance is an essential starting point. Other factors that affect body fluid balance include vascular tone and integrity, including endothelial glycocalyx layer function; hydrostatic pressure; and oncotic pressure. These variables are affected by patient disease, medications, and fluid therapy. Except for small steady changes during growth, the amount of water entering the body each day must equal the amount of water eliminated from the body over the same period. If water influx versus efflux is not balanced, a cat will have either a net water gain or a loss. Cats achieve fluid intake by ingesting food and water and generating it endogenously by metabolizing nutrients to carbon dioxide (CO2) and water. Physiologic (normal) water losses occur for the following reasons: Pathologic loss of water can occur for the following reasons: Similar to fluid balance, electrolytes must also be consumed and eliminated in approximately equal quantities daily to maintain electrolyte homeostasis. It is the body’s continual loss of electrolytes and need for prompt, nearly continual replacement, that underlie the concept of “maintenance fluids.” Maintenance needs, normally met by eating food and drinking water, are largely dependent on a cat’s lean body mass. Sick animals that are no longer eating or drinking will continue to have daily obligatory fluid and electrolyte losses that must be addressed by fluid therapy to prevent negative fluid and electrolyte balance. Very little changed regarding concepts of salt and water balance for many decades. Although studies have not been done specifically in cats, more recent work in other species suggests that Na+ is stored in the body around negatively charged surfaces such as in skin and bone. Additionally, the steady state for Na+ balance is hormonally controlled, rhythmic, and not necessarily tied to dietary intake. Whether body salt stores are important defenses in periods of low intake or excess losses remains to be demonstrated. However, there are new hypotheses that the amount of salt being stored in some tissues could impact other body functions, including immune function and autoimmunity.1 Newer concepts in Na+ balance may impact how we look at chronic high salt intake, including in the form of subcutaneous (SC) fluid therapy for cats with chronic kidney disease (CKD). For now, the foundational concepts of Na+ and water balance outlined in the following sections are still essential to understanding fluid therapy. The complexity of the topic is certainly changing, and it is expected to impact long-standing clinical practices in the coming years. Water is a major contributor to a cat’s body weight. In healthy animals, approximately 60% of body weight is water. This value can change slightly depending on age, body composition (percentage of lean and fat mass and composition of the lean mass), and sex. For example, neonatal and young kittens have a relatively higher percentage of body water compared to adults. Fig. 5.1 depicts the cat’s body fluid compartments. The body’s two main fluid compartments are the intracellular fluid (ICF) and the extracellular fluid (ECF). Approximately 66% of functional total body water is located within the ICF compartment, and 33% is in the ECF compartment. Conceptualization of the body compartments in this manner is intuitive considering cats (and mammals in general) are comprised of cells and water is the largest portion of those cells. The ICF is not a single compartment but rather a conceptualization of each of the body’s trillions of cells’ volumes combined as one. This simplification permits an approach to the ICF compartment as if it were a single space based on the commonalities of ICF composition and behavior. The ICF is high in potassium (K+) and magnesium (Mg++) ions and low in Na+ and chloride (Cl−) ions. Fluid inside all cells will respond similarly to tonicity changes in the ECF. The ECF space is composed of two main compartments: the intravascular fluid (IVF) and extravascular fluid (EVF) compartments. The EVF compartment is further divided into four subcompartments which are the interstitium, transcellular, bone, and dense connective tissues. The IVF is that which is contained within blood vessels; it contributes only 8% to 10% of total body water (5% of body weight) and has been estimated to be approximately 37 to 49 mL/kg in cats.2 The interstitial compartment (ISC) refers to that portion of the ECF located outside of the vascular space. It is named for its largest contributor, the interstitium, which is the space between cells in a tissue. Like the ICF, this is not a single space but rather a conceptualization, or “virtual space,” that would exist if all the interstitial fluid spaces were to be combined. The ISC contributes approximately 20% to 24% to total body water (15% of total body weight).3 Part of the ISC is the fluid contained in bone and dense connective tissue. It contributes about 15% of the total body water. However, this fluid is mobilized very slowly, decreasing its importance when considering the effects of acute fluid interventions. Transcellular fluid is a normally small compartment that represents all those body fluids that are formed from the transport activities of cells. It is distinguished from the interstitium because it is contained within epithelium-lined spaces. It includes cerebrospinal fluid (CSF), gastrointestinal (GI) fluid, urine in the bladder, aqueous humor, and joint fluid. The electrolyte compositions of the various transcellular fluids are dissimilar, and they are overall small in aggregate volume. Fluid fluxes involving GI fluid can be significant in disease. The water in bone and dense connective tissue and the transcellular spaces are subtracted from the total ECF volume to yield the functional ECF because of their slow mobilization. Thus, the functional ECF volume is that in the interstitial and intravascular volumes. The buildup of excess fluid in the transcellular compartments or ISCs is termed third spacing. Excess fluid in the peritoneal and pleural spaces, ISC, or GI tract can add considerably to body weight and can significantly diminish the effective ECF volume. Water in the body’s ECF compartments is in a constant state of flux. Fluid moves across capillary membranes, which are composed of endothelial cells that contain gap junctions through which fluid and solutes can flow. However, different body tissues have inherent differences in the function of their capillary beds. Solutes dissolved in fluid move from an area of higher to lower concentration down concentration gradients by the process of passive diffusion. The factors that regulate this transport of fluid and the electrolytes and other molecules it contains are called Starling’s forces ( Starling’s model has undergone revision based on new research findings. The principles are similar, but it has been discovered that the endothelial glycocalyx layer, endothelial basement membrane, and the extracellular matrix play important roles in limiting fluid egress from the capillaries.4 Fluid in the ECF compartment moves continuously between the IVF compartment and the ISC across the capillary endothelium to achieve tissue perfusion. Edema results when the balance of the hydrostatic and colloid oncotic pressure gradients shift to favor fluid egress from the capillary into the interstitium. Edema formation is promoted by (1) decreased plasma oncotic pressure, (2) increased capillary hydrostatic pressure, (3) increased capillary and lymphatic permeability, and (4) lymphatic and/or vascular obstruction. The other key requirement for edema formation is Na+ retention by the kidney and an increase in the ECF Na+ content. The ICF and ECF are separated by cell membranes. The protein components of these membranes permit substantial permeability to and rapid movement of water while carefully controlling permeability to solutes such as ions. Cell membranes are also flexible, thus, when water flows into or out of cells, those cells expand or shrink respectively. Hydrostatic pressure, therefore, does not play a significant role in fluid movement between ECF and ICF compartments; osmosis results in water flow rather than the development of pressure. Osmotic water flow occurs wherever there is a gradient of impermeable solute (such as Na+) across a water-permeable membrane (the body cell membranes). The ECF and ICF compartments are always in osmotic equilibrium, even though the composition of the fluids within them is very different. This is because water flows into or out of cells and changes their volume when an osmotic gradient exists between the ICF and ECF compartments. Perfusion refers to the process in which blood carries oxygen and nutrients to cells and transports waste products of cellular metabolism back to the IVF compartment. Perfusion (and oxygen delivery) is optimized when an animal is in a state of normal fluid balance or hydration. Oxygen delivery is a critical part of perfusion and is dependent on the animal’s cardiac output (CO) and the oxygen-carrying capacity of the blood. Cardiac output is a function of heart rate (HR) and stroke volume (SV). Stroke volume depends on ventricular preload, ventricular afterload, and contractility. The amount of blood that enters the ventricle, causing the ventricular wall to stretch, thus affects the ventricular preload because the amount of wall stretch is directly proportional to the force of contraction. When IVF volume is optimal, cardiac preload on the healthy ventricle results in a contraction of appropriate force. By contrast, hypovolemia reduces cardiac preload thus decreasing the force of ventricular contraction. Intravenous fluid therapy improves cardiac preload by replenishing IVF volume in hypovolemic states and restores CO. The Na+ content of the body largely determines the ECF and total body fluid volumes. This is because the osmolality of body fluids is regulated within a very narrow range. If Na+ ions (always with an accompanying anion) are added to the ECF, more water molecules must be added in the same proportion, or the osmolality will increase beyond the relatively narrow range that is compatible with health and normal cellular function. Thus, increasing the number of Na+ ions in the ECF (the Na+ content) effectively increases the ECF volume (i.e., preventing increase in Na+ concentration [Na+]). Similarly, if Na+ ions are removed from the ECF, water molecules must leave in proportion, resulting in a decreased ECF volume (i.e., preventing decrease in [Na+]), or the ECF osmolality could decrease so low that the body’s normal regulatory mechanisms would not function. In that sense, the Na+ content of the ECF space determines its volume. As was discussed previously, this simple model is changing because of the discovery of the storage of Na+ without water.5 Thus, two different types of body Na+ content, each affecting the body’s water content differently, must be considered in the future. Regulatory mechanisms exist to control both Na+ content and concentration, which are interrelated. Body Na+ content, which we call Na+ balance, is regulated by mechanisms that control the renal excretion of Na+; these regulatory mechanisms operate in response to body fluid volume (not [Na+]).6 Although not studied in cats, there are also important rhythmic fluctuations in Na+ excretion under the control of glucocorticoids in humans and mice.5 Control of [Na+], on the other hand, is determined by the osmoregulatory control mechanisms and is termed water balance. Evolutionarily, it appears that salt was a scarce commodity. Thus, the kidney has evolved mechanisms to conserve salt. Na+ excretion in the urine can vary over 500-fold depending on Na+ intake, body need, and hormonal influences. The homeostatic mechanisms that control Na+ content are poorly understood. Regulation is generally a slow process. For example, many hours will pass before excesses in Na+ content (e.g., when isotonic saline is infused) are corrected by increased renal Na+ excretion. Many physiologists believe that a set point for Na+ content regulation does not exist. Rather, they believe Na+ is retained in low volume states until a volume deficit, if present, is corrected.7 Sodium excess results in augmented ECF volume, which increases urinary Na+ excretion. A useful analogy is a bucket with a hole in its side. As a salt-containing fluid is poured into the bucket, Na+ excretion through the hole is minimal while the fluid rises. Once fluid reaches the level of the hole, the Na+ inflow into the bucket equals the Na+ outflow through the hole. When the level of fluid is above the hole (ECF expansion), the pressure of fluid in the bucket drives the fluid out of the hole more quickly. For example, when dietary Na intake is increased, it takes several days to reach a new steady state of neutral Na+ balance. The following factors are known to affect renal Na+ excretion: It is suspected that other factors affecting renal Na+ excretion exist. The speculated sensors (afferent signals) responsible for the regulation of Na+ excretion include intrathoracic volume receptors, atrial pressure receptors, arterial baroreceptors, intrarenal baroreceptors, the macula densa, hepatic volume receptors, CSF volume receptors, and possibly tissue receptors. The mediators of Na+ conservation or excretion include the sympathetic nervous system, the renin–angiotensin–aldosterone system (RAAS), glucocorticoids, urea metabolism, vasopressin, atrial natriuretic peptide (ANP), renal prostaglandins, the kallikrein–kinin system, nitric oxide, and renal pressure and flow phenomena (glomerular filtration rate [GFR], renal blood flow, and arterial pressure).8,9 States of salt excess include congestive heart failure (CHF), nephrotic syndrome, hepatic disease (particularly cirrhosis), hyperaldosteronism, Na+ channel defects, and pregnancy. In the pathogenesis of certain salt-retaining states, reference is made to the effective plasma volume. Effective plasma volume is not a measurable quantity, and the concept lacks a precise definition. Effective plasma volume refers to the “fullness” of the vascular volume and it is the portion of the vascular volume that is sensed by those mechanisms that regulate body fluid volume. An inadequate effective circulating volume is inferred when salt-retaining mechanisms are activated. Salt-deficient states occur secondary to several disease conditions that result in losses of Na+ or inadequate intake. Extrarenal losses are localized to diseases of the GI tract, skin, respiratory tract, and third space losses. Renal salt loss may occur with the following: Isotonic fluids, in which the [Na+] is like that of normal plasma, are often termed “high-Na+.” They are termed “high-Na+” only to distinguish them from fluids made isotonic to plasma using dextrose, the latter being so-called maintenance type fluids. High-Na+ isotonic fluids are used to replace Na+ and Cl– losses; they are used to augment the total ECF Na+ content and thus expand the functional ECF volume, both vascular and interstitial. They are termed replacement type fluids. A “high-Na+” isotonic fluid is not to be confused with hypertonic saline, which is high in Na+, but not isotonic to plasma. The next important concept of body fluid balance is water balance. Cells must be in osmotic equilibrium with the fluid that surrounds them, insofar as their membranes are permeable to water. Although ECF and ICF have very different compositions, they have the same total solute concentrations because of the free movement of water. In other words, the water concentration of the ECF and the ICF must be the same. Inequalities of water concentrations in body fluid compartments exist only transiently because water movement occurs rapidly to correct these inequalities. This basic concept underlies an understanding of fluid movement between ICF and ECF compartments during intravenous (IV) fluid therapy. The concentration of solutes in fluid defines a solution’s osmolality. Because cell membranes are water permeable and water movement occurs until solutions on either side of a membrane are iso-osmolar, the osmolality of plasma reflects the osmolality of the body fluid in total. Thus, the distinction between permeant and impermeant solutes is important. Permeant solutes (e.g., urea) move freely across cellular membranes and thus do not induce net water movement across cell membranes when they are introduced into a solution; they are termed ineffective osmoles. Impermeant solutes (e.g., Na+) are effective osmoles because they do not freely move across cell membranes and thus, they do induce water movement when introduced into a solution. The term tonicity refers to the effect a solution has on cellular volume. Hypertonicity results when impermeant solutes are added to the IVF; this promotes water efflux from the ICF to the IVF thus causing cellular dehydration and vascular expansion. Hypotonicity results from a decrease in the concentration of impermeant solutions; this results in water movement into cells and cellular swelling. Hypertonic solutions are always hyperosmolar. The reverse is not always the case; hyperosmolar solutions are not necessarily hypertonic because ineffective osmoles contribute to osmolality but not tonicity. Plasma [Na+] is the key determinant of the osmolality of body fluids. Glucose and urea make minor contributions under normal circumstances. Plasma osmolality may be calculated using the following equation: BUN, blood urea nitrogen; Na+, sodium The preceding equation is a simplified version of a more complex one because it does not consider the fact that plasma is only 93% water, that Na+ salts are not completely dissociated in solution, and that calcium (Ca++), Mg++, and K+ salts also contribute to plasma osmolality. However, these factors appear to cancel each other out because experimental evidence demonstrates that calculated osmolality and measured osmolality are in close agreement in normal animals. Plasma [Na+] reflects the plasma tonicity very well in most circumstances. Urea is an ineffective osmole because it equilibrates freely across cell membranes and does not induce fluid shifts; glucose is similarly an ineffective osmole most of the time. Equilibration of glucose differs from urea because it requires the presence of insulin. Thus, in untreated diabetics without adequate insulin, glucose becomes an effective osmole. Plasma [Na+] predicts, and is a good surrogate for, plasma tonicity when the glucose concentration is normal. However, hyperglycemia causes water efflux from cells because of the hypertonicity of the ECF. Water efflux from the intracellular space into ECF, including the IVF compartment, dilutes Na+ causing hyponatremia when hyperglycemia is present. The term osmoregulation refers to the control of body fluid tonicity. By stabilizing body fluid tonicity, osmoregulation controls cell volume. Osmoreceptors are hypothalamic cells that sense their own cell volume. Changes in plasma osmolality sensed by these cells affect secretion of arginine vasopressin (antidiuretic hormone [ADH]). This hormone is the primary regulator of renal water excretion. Changes in plasma osmolality also strongly affect the thirst mechanism which is why patients with central diabetes insipidus (ADH deficiency) can maintain a relatively normal osmolality if they can drink water freely. In contrast to the slow regulatory responses to changes in salt balance previously discussed, plasma osmolality is tightly regulated. When plasma osmolality is altered, changes in ADH secretion and thirst sensation occur, and the resulting renal responses are brisk. In addition to plasma osmolality, hypotension and hypovolemia also stimulate ADH release and thus this is a point where regulation of salt and water balance are interrelated. ADH release is not as sensitive to hemodynamic stimuli as it is to changes in osmolality; however, when the hemodynamic stimulus is sufficiently strong, the magnitude of ADH response will be higher. In the presence of a significant volume deficit, decreased water excretion by the kidney will in fact act to increase volume at the expense of a decrease in plasma osmolality. The primary function of ADH is to increase the water permeability of the luminal membrane of the collecting duct of the nephron. ADH, through a second-messenger system, causes insertion of water channels called aquaporins into the cell membrane. Water reabsorption in the collecting duct occurs through these channels, thus allowing the kidney to conserve water. Sensible fluid losses can be measured and include fluid lost in the form of urine, feces (particularly diarrhea), vomitus, body cavity effusions, and exudates. It is important to quantify fluid losses and incorporate them into the fluid prescription of seriously ill patients. For example, urine output can be determined by collecting voided urine or by determining the difference in weight of the bedding or litter when dry and again after urination. Similarly, the difference in weight of bedding or bandages prior to use and after soiled with eliminations or exudates can be used to calculate approximate fluid losses. One gram of fluid is equivalent to approximately 1 mL water. The amount of fluid produced from drains or chest tubes should also be measured to estimate fluid losses. Insensible losses cannot be measured directly; they primarily include solute-free water lost in the form of evaporated respiratory secretions, sweat, and saliva. This classical definition of insensible losses is sometimes replaced with a clinical definition that includes fecal water loss. This is because the amount of normal daily fecal water loss is small and is rarely measured.2 Sensible fluid losses account for approximately half of a healthy animal’s daily fluid requirement and insensible losses account for the other half. However, this partitioning is variable and is species- and environment-dependent. For example, dogs may have a higher percentage of insensible losses compared with cats because they pant more for thermoregulation. Similarly, cats may have considerable loss of fluid from saliva if grooming or licking is increased for any reason.10 Insensible fluid losses are generally considered solute-free because respiratory losses are the major contributor in small animal species, including cats. Insensible losses are estimated to be 12 to 30 mL/kg/day.2 In contrast to solute-free insensible fluid losses, sensible fluid losses contain solutes. Although an oversimplification, this fact explains why maintenance fluid types are hypotonic; hypotonic fluids replace a combination of the solute-free water of insensible and the solute-containing water of sensible fluid losses. As a matter of practicality, it is reasonable to assume that half of daily maintenance fluids replaces normal obligate urine output accounting for daily solute excretion (solute-containing fluid losses), and the other half of maintenance fluids replaces all other solute-free water losses. When adjusting the fluid prescription for “ins and outs,” calculation of obligate versus excessive urine production permits estimation of the portion of hourly urine production that is abnormal fluid loss is in polyuric cats (e.g., the ongoing urinary fluid loss that must be met by the replacement portion of the fluid prescription) and how much is normal obligate urine production (e.g., the maintenance portion of the fluid prescription). Total body water remains essentially the same day to day in a healthy animal. However, in disease, excessive loss of fluid can occur in various forms such as hemorrhage, vomiting, diarrhea, effusions, dermal exudates, polyuria, edema, and panting. Because rapid changes in body weight (e.g., over hours to a few days) are largely due to fluctuations in total body water, calculation of the changes in an animal’s weight are an invaluable tool in the assessment of its hydration status and fluid prescription. Cats are small and thus should be weighed on scales that can accurately detect changes of a few ounces or several grams (e.g., human pediatric scales). Because lean body mass is so important in determining an animal’s daily fluid need, resting energy requirement (RER, in kilocalories [Kcal]/day) is used to calculate an animal’s metabolic water requirements: metabolism of 1 Kcal of energy requires consumption of 1 mL of water. As such, calculation of an animal’s RER can be extrapolated to determine the volume of fluid in mL required in a 24-hour period. Several equations may be used to calculate RER and hence water requirement.11 The following is one of the most commonly used equations: This formula is accurate for animals weighing >2 kg and <25 kg and thus is applicable to adult domestic cats. The following formula should be used for cats weighing <2 kg: These calculations are just rough guides. The amount of free water generated or consumed in metabolism is dependent on the diet composition, including probably Na+ content, and hormonal influences and appears to undergo rhythmic changes, at least in the few species studied. The terminology used to describe body fluid balance can be vague. Dehydration refers to a decrease in total body water, which, by definition, is decreased fluid from both the ICF and ECF compartments. However, the physical examination (PE) findings used to estimate hydration, such as skin tent and mucous membrane moisture, are specifically assessments of the ICF volume and subject to significant individual variation and inaccuracy. Thus, when clinicians suggest that a patient appears dehydrated, they are referring to clinical signs of ICF volume depletion. This is different from hypovolemia, which refers to decreased IVF volume. The distinction is important because hypovolemia is a much more time-sensitive condition requiring rapid, aggressive treatment. It can be assumed that patients with excessive net fluid losses (e.g., vomiting, diarrhea, anorexia, and polyuria) have developed a decrease in total body water, even in the absence of a demonstrable increase in skin tenting and mucous membrane dryness. People report headaches with dehydration; dehydrated cats may thus experience the same and a headache may contribute to the lethargy seen in dehydrated cats. Physical examination findings supportive of dehydration are detectable at the earliest when 4% to 5% of total body weight has been lost (Table 5.1). At 7% total body weight loss, mild tachycardia is also usually present. At 10% total body weight loss, a patient might also have a palpably decreased pulse pressure. Signs of severe total body water loss may include sunken eyes, dry corneas, and altered mentation. Overt hypovolemia will occur with severe fluid loss (>12% body weight). Cats can be lethargic because of underhydration and overhydration. Table 5.1 The PE findings that are used to determine an animal’s hydration do not reflect intravascular volume and thus cannot be used to assess volemic state. Instead, capillary refill time (CRT), mucous membrane color, arterial blood pressure (BP), HR, pulse quality, and temperature of extremities should be used to assess peripheral perfusion. In the absence of ability to measure BP, peripheral pulse quality can be used to estimate systolic BP.12 Maintenance of IVF volume is a body’s priority. Thus, the body responds to fluid loss by redistributing the functional ECF volume. In other words, circulating blood volume is maintained by shifting fluid from the interstitium to the IVF space via the ISC. When the ISC can no longer replenish intravascular volume depletion, clinical signs of hypovolemia will result. Severe hypovolemia results in a marked deterioration of perfusion parameters and ultimately decompensated shock. Hypotension, bradycardia, prolonged CRT, pale pink to gray or cyanotic mucous membranes, hypothermia, decreased central venous pressure (CVP), altered mentation, and decreased urine output are signs of decompensated shock. Table 5.2 gives examples of the types of fluid losses that would be expected with selected medical problems. Table 5.2 Overhydration, like dehydration, is detrimental to patients. Iatrogenic fluid overload should therefore be avoided. Extracellular fluid volume excess can cause pulmonary edema, ascites, and generalized peripheral edema in many animal species. Pleural effusion is also a common sequelae of fluid overload unique to the cat, possibly because of a difference in the anatomy of pulmonary venous drainage. Cats with pre-existing cardiac disease, oliguria, or markedly decreased GFR have an even greater risk of complications from overhydration; body weight measurement is thus essential in such patients. Determination of urine output is also very helpful to identify patients with unexpected high or low urine output. However, an overreliance on “ins and outs” as a replacement for frequent body weight determination is not recommended. Early signs of overhydration may include loss of appetite and mental dullness. A clinician may detect subtle PE abnormalities suggestive of fluid overload such as a new heart murmur or gallop rhythm, mild tachypnea, dull lung sounds, increased bronchovesicular sounds or pulmonary crackles. Later signs of fluid overload include dyspnea and orthopnea and rarely open-mouth breathing. Cats should be weighed several times daily particularly if they are at high risk of fluid overload; detection of and reaction to small increases in weight can prevent overt fluid overload. No specific studies are available for review on this topic that are specific to cats. In human medicine, the term fluid accumulation is used to describe a patient that has up to 10% fluid excess. The term fluid overload defines a patient with greater than 10% fluid excess. The two states are differentiated because fluid overload is associated with increased hospitalization time and mortality.13 The determination of any given patient’s percent of volume excess is usually based on a comparison of current body weight to the weight at admission. This calculation is not optimal because it assumes a patient is euvolemic at admission. One small study about the association of fluid overload and mortality in dogs suggests the need to study the dangers of overhydration in cats.14 Clinicians should be aware that both dehydration and overhydration can have potential deleterious effects and thus diuresis should not always be viewed as beneficial. Intravascular volume status is sensed by baroreceptors in the carotid body and aortic arch. In euvolemic cats, stimulation of the stretch receptors triggers the vagus nerve to maintain an appropriate HR. When hypovolemic, the baroreceptors sense a decrease in wall tension and the sympathetic nervous system is activated. The resultant release of norepinephrine and epinephrine causes vasoconstriction, improved cardiac contractility, and an increase in HR. These effects are designed to compensate for decreased IVF volume by improving CO, systemic BP and, ultimately, perfusion. Hypovolemic shock ensues when IVF volume is reduced to the point that these compensatory mechanisms are overwhelmed, resulting in decreased tissue perfusion. Physical changes that often accompany poor perfusion include cold extremities and increases in CRT, BP, and HR. Compared to other species, cats are unique because their vasoconstrictor responses to volume loss are blunted in the presence of hypothermia.15,16 Once body temperature returns to normal, the vasoconstrictor response returns, and intravascular pressure rises. Cats are thus more likely to develop fluid overload if they are volume-resuscitated when hypothermic. Once normal body temperature is restored, the vasoconstrictor response returns, and intravascular pressure rises. Also, hypothermia can potentiate shock in cats. Therefore, cautious fluid resuscitation must coincide with aggressive rewarming efforts in hypothermic cats to prevent volume overload. Specific therapeutic endpoints for fluid resuscitation are discussed in subsequent sections and outlined in Box 5.1. Fluid therapy choices are often the product of educated guesswork and experience coupled with available fluid options. If a patient has normal kidney function, subpar fluid choices may still be adequate for the patient’s needs. There are many useful guidelines for selection of fluid types and IV infusion rates. Proper fluid management demands careful monitoring of body weight and PE. It is of utmost importance to determine a patient’s type of fluid losses and plasma electrolyte concentrations to provide the best fluid prescription. Initial fluid therapy plans merely provide starting points; the fluid prescription must be continuously reassessed and amended in response to changes in patient status. Vigilance for fluid overload is indicated for all patients, especially those with cardiovascular or oliguric renal disease. Similarly, vigilance for underhydration is indicated for patients with underestimated fluid losses. Fluid pumps, burettes, and similar devices should be used for feline patients to prevent accidental fluid overload and sequelae such as pulmonary edema or pleural effusion (Fig. 5.2). Serial patient evaluation (e.g., PE, BP, weight) will help prevent fluid over or underuse. The two main types of parenteral fluids, crystalloids and colloids, have fundamental differences that affect the way fluid distributes among body fluid compartments. Crystalloids are composed of smaller molecules that diffuse readily; therefore, approximately 80% of the fluid infused will leave the intravascular space (IVS) within 1 hour (Fig. 5.3). Colloids, made of larger molecules, stay within the IVS longer, which is an important advantage when managing hypovolemia. The tonicity of fluids determines distribution rates to the intracellular and extracellular spaces. When the [Na+] of a fluid approximates that of plasma (145 mEq/L), it will equilibrate rapidly with the interstitial space. Remaining fluid that is not lost in urine or as other ongoing losses will distribute to the ICF in proportion to the normal size of those compartments: two-thirds ICF and one-third ECF. Assuming the patient has normotonicity, hypotonic fluids (with [Na+] lower than that of plasma), will dilute plasma and drive water from the IVS into cells to equilibrate the water concentration inside and outside of cells. Decreased plasma osmolality (pOsm) will also result in decreased ADH production and, thus, increased water excretion by the kidney. Most of the Na+-free fluid thus either enters cells or is excreted. Hypertonic fluids (with [Na+] higher than plasma) will draw water out of cells and into the ECF, thus increasing the intravascular and interstitial volumes at the expense of ICF space. Thus, an understanding of which body compartments need fluid replenishment in any given patient is essential in fluid selection. This is true not only regarding fluid types selected but also in terms of route of administration. For example, fluids instilled into the SC space cannot be used readily to replenish the intravascular blood volume because they will be absorbed too slowly in a hypovolemic patient. A crystalloid is a solution that can pass through a semipermeable membrane, including the vascular endothelium. The ability of crystalloids to pass through the capillary endothelium allows them to replenish fluid losses both in the intravascular and interstitial compartments, making them ideal for rehydration therapy. All crystalloid fluids are true solutions, meaning that they are homogeneous and transparent, diffuse rapidly, and do not settle. Substances that are dissolved in crystalloids are termed solutes; these are predominantly electrolytes and dextrose. Solutes contained in crystalloid fluids move freely from the IVS to the interstitial space. Movement of impermeant solutes such as ions and glucose into the intracellular compartment is comparatively slower than is the movement of permeant solutes. Impermeant solutes move by facilitated diffusion or active transport. Most crystalloids are formulated with a solute concentration close to that of plasma to avoid osmotic cell damage, particularly red blood cell damage from tonicity-induced osmotic water movement. Some parenteral solutions, such as 0.45% sodium chloride (NaCl) and 5% dextrose in water (D5W), are hypotonic and can cause hemolysis if given too rapidly IV. Table 5.3 lists the composition of common crystalloids. Isotonic high-Na+ fluids are commonly referred to as replacement fluids because they are often used for rapid replacement of ECF volume deficits, such as caused by vomiting and diarrhea. The term “high-Na+” means they have a [Na+] near that of normal ECF, ranging from approximately 130 mEq/L (e.g., lactated Ringer’s solution [LRS]) to a high of 154 mEq/L (e.g., 0.9% saline). Thus “high-Na+” distinguishes this fluid type from a lower Na+ maintenance fluid type. Table 5.3 includes additional examples of replacement fluids, highlighted in red. Isotonic high-Na+ replacement fluids are used both for overt hypovolemia and for less severe ECF volume depletion, often called simply “dehydration.” When given rapidly, they can be used to restore the IVF volume in cats with hypovolemia. When administered more slowly, they are also used to replace ECF volume in states of isotonic dehydration that are not immediately life-threatening, such as occurs in patients with GI or urinary fluid losses when oral intake is insufficient to balance losses. Isotonic high-Na+ replacement fluids are not suitable for use as maintenance fluids. They lack sufficient solute-free water content to offset ongoing solute-free water loss, such as through respiratory evaporation. When used on a short-term basis, most patients with normal renal function will tolerate the excess Na+ that these fluids contain when they are being used primarily to compensate normal daily ongoing hypotonic fluid loss. This is particularly true when patients can drink in addition to their IV fluid therapy. Patients can become hypernatremic when replacement fluid types are used for purposes of maintenance. The use of high-Na+ fluids is contraindicated for use in conditions such as CHF, liver disease, oliguric renal disease, and some forms of edema. Such patients already have a body Na+ content that is too high. Once ECF volume has been restored through use of a replacement fluid, continued use of replacement fluids is indicated when excessive isotonic fluid losses are ongoing. These are losses beyond normal sensible and insensible fluid losses, which are considered maintenance and balanced by eating and drinking, or maintenance fluids. Another reason that replacement fluids should not be used for maintenance purposes is they are too low in K+. The problem of inadequate solute-free water for maintenance remains even if K+ is added to replacement fluids. After correction of fluid and electrolyte deficits, some patients require transition to a maintenance-type fluid solution, such as Normosol-M-D5 or Plasmalyte-56-D5. One indication that a patient’s fluids should be changed to a true maintenance fluid will be indicated by a progressive increase in serum [Na+]. Ideally, changes should be made well in advance of the development of hypernatremia. Sick cats that have been anorexic for 2 to 3 days or longer require nutritional support. Generally, the provision of enteral or parenteral nutrition sufficient to meet the patient’s caloric needs will also provide maintenance fluid needs. Thus, the use of additional isotonic, high-Na+ fluids in this setting should only be at a rate sufficient to replace excessive isotonic losses, such as losses associated with the GI tract or polyuria. When there are no such losses, no additional fluids are needed beyond the nutritional therapy. In other words, account for all sources of fluid intake including nutritional support when addressing the fluid therapy prescription. Because of the water content provided in nutrition, patients rarely need long-term maintenance fluid therapy. A worksheet for calculating a fluid therapy plan is seen in Table 5.7 1. Deficits 3. Maintenance 3. n/a Sick cats requiring fluid therapy may also have acid–base disorders; fluid therapy can concurrently address such disturbances. Restoration of ECF volume will improve tissue perfusion and help correct lactic acidosis by increasing glucose metabolism. The replenishment of water and electrolytes in appropriate concentrations will also improve renal perfusion and normalize renal management of electrolytes, thus promoting an improved acid–base balance. The result can be the normalization of acid–base balance without the need to resort to the use of sodium bicarbonate (NaHCO3). Sodium bicarbonate can cause adverse effects such as hypernatremia and central nervous system acidosis. High-Na+ replacement crystalloids are classified as either acidifying or alkalinizing solutions. When they contain more Cl− than is present in the patient’s ECF, they are acidifying. Although 0.9% (normal) saline has a high Na+ content and thus is frequently used to restore IVF in hypovolemic patients, it also has a high Cl− content and thus it is an acidifying fluid. Normal saline is most appropriate for treatment of patients with hypochloremic metabolic alkalosis because it provides the Cl− necessary to correct the metabolic derangement. A common clinical scenario associated with hypochloremic metabolic acidosis is the cat vomiting fluid that is primarily of gastric origin. Although the measured pH of parenteral fluid solutions in vitro ranges from about 4 to 6.5, the solutions are extremely weak acids, and the pH does not reflect their effects on pH in the patient resulting from buffering. Alkalinizing fluids, by contrast, do not have a [Cl−] higher than ECF fluid. A portion of the Cl– is replaced with a different anion such as lactate, acetate, or gluconate. The anions are metabolized by the liver to HCO3−. One example of a commonly used alkalinizing fluid is LRS. This fluid requires adequate liver function for metabolism of lactate, otherwise the solution is acidifying. In some situations, fluids must be supplemented with additional electrolytes; the decision to add electrolytes is based on an assessment of the history, PE findings, and measured electrolyte values. Common fluid additives are listed in Table 5.4. Electrolyte additives are used to replace electrolyte deficits, provide normal maintenance losses in anorectic patients, compensate for transcellular movement of ions, or replace ongoing GI or urine electrolyte losses. Potassium and Mg are found in some low-Na+ hypotonic fluids formulated as maintenance fluids. If not, they can be added to fluids to maintain homeostasis in animals that are not depleted. Table 5.4 mEq, milliequivalent; mL, milliliter; mM, millimolar From Abbott Animal Health Fluid Therapy Module 2, courtesy Dr. Steve Haskins. All isotonic high-Na+ fluids, apart from 0.9% NaCl, contain 4 or 5 mEq/L of K+. Although this amount of K+ is within the normal range of plasma [K+], it is not sufficient to maintain patient plasma [K+]. This is because therapy with IV isotonic high-Na+ fluids typically causes a solute diuresis. The rate of flow of filtrate through the renal tubule is one of the factors regulating renal K+ excretion. As urine flow rate increases in response to IV fluid administration, K+ loss in the urine will also increase. The loss of K+ from the body will be further compounded by decreased intake in patients that are hyporexic and by increased losses of K+ in GI secretions from vomiting or diarrhea. Many patients are also already full-body K+-depleted, which may be masked by serum K+ that is initially normal. For these reasons and with rare exceptions, it is necessary to supplement the fluids with additional K+ when isotonic high-Na+ fluids are used for maintenance of patients that are drinking (and thus contributing a portion of their own maintenance) or for support of patients with ongoing isotonic fluid losses. For a cat that is normokalemic, 20 mEq/L of KCl is commonly added to a liter bag of isotonic high-Na+ fluid; it is not necessary to subtract the small amount already present in the fluid bag. If K+ is not added to replacement fluids when used for more than a short time, hypokalemia commonly results, even in normokalemic patients. A sliding scale is used to calculate how much K+ to add to the fluids of hypokalemic patients (Table 5.5). When using a K+-containing replacement with a [K+] concentration that exceeds 5 mEq/L, the solution must not be infused rapidly for intravascular volume restoration because of the risk of hyperkalemia. Table 5.5 *If the [K+] of the fluid exceeds 5 mEq/L, the fluid must not be infused rapidly for intravascular volume restoration because of the risk of hyperkalemia. Cats that are hyporexic, polyuric, or that have GI fluid losses are particularly at risk for K+ depletion. When hypokalemia is nonresponsive to standard amounts of K+ supplementation, (e.g., in hyperaldosteronism, hypomagnesemia, or diabetic ketoacidosis [DKA]) a constant-rate infusion (CRI) of K+ may be indicated. A general K+ CRI dose is 0.05 to 0.1 mEq/kg per hour given over 4 to 6 hours; the patient’s serum [K+] should then be re-evaluated prior to determining if the K+ CRI should be continued. The highest infusion rate at which a K+ CRI can be administered is 0.5 mEq/kg per hour (known as the KMax). Potassium chloride (2 mEq/mL) can be diluted so only small volumes are required (e.g., 1:1 dilution with a crystalloid) or may even be administered undiluted if volume overload is a concern. Potassium CRIs should be reserved for intensive care situations in patients with life-threatening hypokalemia (e.g., serum [K+] below 1.5 mEq/L). A K+ CRI should be administered through a programmable syringe pump whenever possible and must be closely monitored to prevent iatrogenic hyperkalemia. Also, a K+ CRI should be administered via a fluid source separate from other fluids to allow for independent adjustment of each fluid type. Iatrogenic hyperkalemia caused by overzealous K+ supplementation or unattended K+ CRIs via drip sets can cause complications such as cardiac arrhythmias and sudden death. Hypophosphatemia is a rare electrolyte derangement; a classic case scenario is the cat with DKA that develops hypophosphatemia consequent to institution of insulin and fluid therapy. To correct hypophosphatemia, a portion or all the phosphate (PO4−) can be administered as potassium phosphate (KPO4). Use of KPO4 is typically indicated when the [PO4−] is <2 mEq/L or when serum [PO4−] rapidly decreases and a drop below 2 mEq/L is anticipated. Potassium phosphate also provides K+, which is indicated for concurrently hypokalemic patients. Hemolysis can occur when the [PO4−] is less than 1.5 mEq/L in cats. Sodium phosphate is used in the unusual case of phosphate-depleted patients that do not require K+. A common dose range to replace normal ongoing losses of phosphate is 0.01 to 0.03 mmol/kg/hour. Like K+ CRIs, PO4− CRIs should be administered over 4 to 6 hours and the patient’s serum [PO4+] should then be re-measured to determine if further supplementation is indicated. Dose rates as high as 0.12 mmol/kg per hour may be necessary in some patients treated for DKA. Magnesium depletion is common in critically ill patients, particularly those with decreased dietary intake and polyuria, such as patients with diabetes mellitus. Supplementation is generally recommended when total serum [Mg++] is <1.5 mg/dL. Because total serum [Mg++] does not represent the physiologically active form of the element, measurement of ionized Mg is preferred. Replacement doses of Mg++ are 0.03 to 0.04 mEq/kg/hour for severe hypomagnesemia requiring rapid replacement and 0.013 to 0.02 mEq/kg/hour for less severe hypomagnesemia. Magnesium chloride or MgSO4 are the typical Mg++-containing solutions used; Mg++ supplementation should not be mixed with Ca++– or HCO3−-containing fluids.17 Patients with reduced GFR are at risk for adverse events with supplementation of electrolytes, including Mg++. The kidneys help compensate for any misestimations of electrolyte needs. Magnesium is a cofactor for K+ homeostasis, thus Mg++ supplementation should be considered in any patient with refractory hypokalemia. Electrolyte monitoring and supplement adjustments are particularly important when renal function is impaired. For cats, this also mandates careful attention to minimizing the amount of blood used for monitoring to avoid causing iatrogenic anemia. Calcium gluconate (10% solution) is used as a Ca++ source for animals with symptomatic hypocalcemia, such as that associated with eclampsia, hypoparathyroidism, acute pancreatitis, ethylene glycol toxicity, and CKD. It may be administered on an emergency basis at a dosage of 0.5 to 1.5 mL/kg (10% solution), diluted and given over 10 to 15 minutes, or it may be added to a fluid bag and given more slowly. Calcium chloride (CaCl) contains about three times the amount of calcium per mL compared to calcium gluconate, and thus if used as the Ca++ supplement, only one-third the calculated calcium gluconate volume should be administered. Calcium gluconate is preferred to CaCl because it is less irritating if inadvertently given perivascularly. Chronic kidney disease patients often have hypocalcemia associated with hyperphosphatemia, and thus administration of Ca++ may lead to the precipitation of CaPO4 in tissues. The latter can occur when the product of [Ca++] and [PO4−] exceeds 70. Ideally, serum phosphate should be lowered as rapidly as possible in patients treated with Ca++ to minimize the risk of calcium precipitates. Because rapid infusion of K+, PO4–, Ca++, or Mg++ can cause cardiac arrhythmias and other side effects, they should be added to fluids administered at a constant rate for maintenance and separated from fluids that might require frequent changes in rate of administration or used for boluses to avoid inadvertent overdose. Delivery systems that guard against fluids being inadvertently left to run “wide open” are strongly recommended. Electrocardiographic monitoring is necessary when IV Ca++ or Mg++-containing solutions are given rapidly. Also, divalent cation salts of phosphate are insoluble, thus they should not be added to fluids containing Ca++, Mg++, or PO4− or precipitation of CaPO4 or MgPO4 in solution may result. Hypoglycemia may accompany critical illness and can be treated with dextrose supplementation. There is increasing evidence in humans that tight glycemic control improves outcomes in critically ill patients; whether this holds true in cats is unknown. When dextrose supplementation is indicated, 50% dextrose can be added to IV fluids in concentrations from 2.5% to 5% to maintain blood glucose in the 80 to 120 mg/dL (4.4 to 6.7 mmol/L) range. Final concentrations that are above 10% should be administered through central venous catheters to reduce the risk of thrombophlebitis. The concentration can be measured as a percentage or in g/dL. The calculations for making a 5% dextrose solution are found in Low-Na+ crystalloid fluids may be isotonic or hypotonic and are indicated for the short-term support of water and electrolyte homeostasis by replacing normal ongoing losses in patients in which oral intake is not appropriate or possible. Low-Na+ refers to lower than the normal plasma [Na+] and these fluids have historically been referred to as maintenance fluids. Given that normal insensible fluid losses (respiratory and other evaporative loss) do not contain Na+, these fluids are indicated when the patient needs a supply of solute-free water to replace daily requirements normally met through drinking and metabolism of food. The [Na+] of low-Na+ crystalloid fluids ranges from 0 mEq/L in the case of 5% dextrose in water to 77 mEq/L in the case of a half-strength, or 0.45%, saline solution. Solutions with less than 77 mEq/L of Na+ contain 2.5 or 5% dextrose to raise the osmolality closer to that of ECF. Nonetheless, some maintenance fluids are hypotonic, and they must therefore be given slowly to allow for equilibration and to prevent intravascular hemolysis. In the context of fluid balance, dextrose is added to Na+-free water to raise the osmolality thus allowing Na+-free water administration IV without causing hemolysis (provided the solution is given slowly). The dextrose is metabolized rapidly (and does not provide significant calories). The K+ content of the hypotonic low-Na+ crystalloids is highly variable. As previously discussed, a [K+] of 20 mEq/L is usually considered the minimum necessary for true maintenance of a normokalemic patient. Table 5.3 lists some examples of low-Na+ crystalloid fluids in green. The rate of administration of IV fluids used for maintenance is based on the metabolic body size and will only change when patients begin to eat and drink. Low-Na+ crystalloids are contraindicated in patients requiring rapid fluid administration, such as for hypovolemia, as doing so will rapidly reduce the ECF [Na+] and cause cell swelling due to rapid reduction in osmolality. Fluids administered to replace normal ongoing losses on a long-term basis are generally best provided orally, such as via an enteral feeding tube if the patient is not eating. This also allows for the essential provision of calories. Fluids can also be given subcutaneously in animals that are too ill to consistently maintain hydration, such as cats with increased fluid losses in the absence of increased fluid intake (e.g., the hyporexic cat with polyuria due to CKD). A low-Na+ maintenance fluid would be ideal in this situation; however, the addition of dextrose to make the solution isotonic can cause complications such as iatrogenic SC bacterial or fungal abscesses. Thus, isotonic fluids are more typically used for SC fluid administration. Lactated Ringers solution without dextrose is also an appropriate fluid type for SC administration. Although classified as a high-Na+ isotonic crystalloid, LRS is often used for SC fluid administration for cats that cannot maintain hydration orally. Lactated Ringers solution is slightly hypotonic to plasma and can provide some solute-free water. Anecdotally, LRS is better tolerated by patients during SC administration than is 0.9% NaCl or Normosol-R. However, LRS is still higher in [Na+] than is optimal for maintenance use and may result in a higher Na+ intake than is ideal. Increased Na+ intake may promote hypertension in predisposed patients and may even cause hypernatremia when given chronically at a high volume. An additional advantage of LRS is that it is alkalinizing; this is particularly beneficial to cats with CKD since they are often acidotic. Research in other species also suggests chronic high Na+ intake, which could be dietary or by SC fluids, may have adverse effects on the immune system. Thus, it is important to assess whether our feline patients truly need fluid therapy for prevention of dehydration and to resist inappropriate use of fluids for “dialysis.” Because the rate of administration of the maintenance component of a fluid therapy plan is often constant, maintenance fluids may be used as a vehicle for the continuous administration of drugs provided they are physically compatible with the fluid. Several references exist that provide compatibility information for various medications and fluid compositions. Addition of medications to maintenance fluids must be well planned as adjustments in the fluid rate to meet the patient’s changing fluid needs will also affect the rate of delivery of medications. For this reason, one should consider using separate fluid bags so that the rate of the bag containing medications is independent of the main fluid bag and the rate of administration of the medication is not inadvertently changed with changes in maintenance or replacement fluid rates. Low-Na+ crystalloid fluids are also used to treat hypertonic dehydration, which is loss of water in excess of solute. These patients are hypernatremic. Hypertonic dehydration is comparatively rare in cats and is more commonly encountered in dogs (e.g., heat stroke). However, hypertonic dehydration is occasionally seen in cats; situational examples include cats inadvertently denied access to water or cats with hypothalamic disease manifesting as hypodipsia. Hypertonic dehydration may also be seen in cats with hyperglycemic hyperosmolar syndrome. There are instances when high- and low-Na+ crystalloid fluids should be used concurrently in feline patients. Hyporexic cats may require replacement fluids (high-Na+) for correction of ECF volume deficits and ongoing excessive losses in addition to their maintenance fluid (low-Na+) needs. Combinations of fluids in these patients are often better able to meet their requirements than are prepackaged replacement or “maintenance” fluids used alone. To address dual Na+ content fluid needs, it is necessary to calculate both the amount of high- Na+ crystalloid necessary to restore baseline ECF Na+ content and replace any pathologic ongoing loss of high-Na+ fluid as well as the amount of low-Na+ crystalloid needed to replace normal daily losses of solute-free water. Nutrition should also be addressed early during hospitalization for cats with inadequate caloric intake. As previously mentioned, the fluid content of enteral or parenteral nutrition should be included in the fluid prescription. Hypertonic saline fluids contain Na+ at concentrations substantially higher than the ECF; thus, they facilitate rapid restoration of the ECF Na+ content during treatment of hypovolemic shock. Increasing the [Na+] in the ECF produces a rapid, although transient, osmotically driven movement of water from ICF to ECF compartment, which can occur far more quickly than when infusing isotonic high [Na+] fluids alone. The duration of the effect of volume expansion is approximately 0.5 to 3 hours.18 Because the ECF volume determines plasma volume, hypertonic saline is a rapid intravascular volume expander at the expense of the ICF fluid volume. Hypertonic saline administration must be followed by infusions of isotonic high-Na+ fluids to maintain their effect; otherwise, the IVF will rapidly re-equilibrate back into the ICF. Hypertonic saline effectively expands the intravascular volume by 2.5 to 3 mL for each mL of isotonic fluid infused.19,20 Clinical situations in which hypertonic saline may be useful in cats include resuscitation of animals with both hypovolemic shock and pre-existing tissue edema, particularly cerebral edema resulting from traumatic brain injury. Hypertonic saline promotes rapid restoration of blood volume to improve blood flow to the brain while simultaneously decreasing cell volume, thus reducing brain edema. It also has positive inotropic effects on the myocardium. There are several contraindications to the use of hypertonic saline, including CHF, uncontrolled hemorrhage, hypernatremia, and severe dehydration. Hypertonic saline is not an appropriate treatment for chronic hyponatremia because of the risk for severe neurologic side effects that ensue when hyponatremia is corrected by administration rates faster than 0.5 mEq/L/hour. Hypertonic saline solutions range in concentration from 3% to 23.4%. Solutions above 7.5% must be diluted before administration because they can cause phlebitis at the injection site. The dose for cats for the 7.5% solution is 2 to 4 mL/kg administered over 5 to 10 minutes.21 Hypertonic saline may be given in combination with a colloid. Hypertonic saline (23.4%) can be diluted to the desired 7.5% by adding one part hypertonic saline to two parts of hydroxyethyl starch (Hetastarch, HES); this yields a solution with a final concentration of just above 7.5%. Colloids are high-molecular-weight substances contained in an isotonic-Na+ solution, usually 0.9% saline. Unlike crystalloids, colloids will not readily diffuse through healthy vascular endothelium and will thus stay in the IVS longer than crystalloids. This effect is beneficial in achieving a sustained increase in intravascular volume when treating hypovolemia. In states of low oncotic pressure, such as is seen with sepsis, systemic inflammatory response syndrome (SIRS), and hypoalbuminemia, colloids can theoretically plug leaks in capillary endothelium and prevent extravasation of fluids and the resultant edema. Colloids are often used to restore and maintain intravascular colloid osmotic pressure (COP) and decrease edema that can result from the use of crystalloid fluids. However, colloids are rarely used alone; they are typically used in conjunction with crystalloid fluids. Because they are efficient at volume expansion, colloids can produce volume overload and pulmonary edema at lower volumes than crystalloids. The crystalloid versus colloid controversy for resuscitation of hypovolemic patients has been an ongoing discussion in human and veterinary medicine for decades. Results of studies have failed to show a clear benefit to colloids, despite numerous theoretical advantages. Some studies have concluded that colloids promote decreased mortality, whereas other studies have shown better results with crystalloid therapy. Until more veterinary studies have been undertaken, it is difficult to make specific recommendations. One clinical approach to hypovolemic feline patients is to begin with crystalloid therapy, reserving colloid therapy for patients who fail to respond. As previously discussed, hypothermic feline patients should be aggressively rewarmed concurrently with fluid therapy. For the markedly hypotensive patient, crystalloids, colloids, and potentially blood products may have to be provided concurrently.22 Natural colloids include blood products, human albumin, and hemoglobin-based products. They are significantly more expensive than the synthetic colloids; nonetheless, there are certain situations in which natural colloids are the preferred solution. Cats must always be blood-typed prior to receipt of any feline blood products as they may only receive same-type blood (human albumin and oxyglobin are exceptions). A crossmatch should be performed whenever possible. The main use of fresh whole blood (FWB) and packed red blood cells (PRBCs) is to treat patients with symptomatic anemia. As a general guideline, a blood transfusion should be considered when a patient’s packed cell volume (PCV) is below 20% (which corresponds to a hemoglobin concentration of 7 g/dL). The decision to transfuse should also be based on the patient’s clinical signs and not on numeric values alone. More details on blood transfusion medicine are found in Chapter 28: Hematology and Immunology. As a rule, administration of 1 mL of whole blood per kg body weight will raise the PCV by 1%. Thus, for a rise of 10%, one would administer 10 mL/kg whole blood. Packed red blood cells can be dosed at 75% of the whole blood dose because of the higher PCV. Fresh whole blood contains functional platelets and all the coagulation factors. Fresh whole blood can thus be used for coagulation or platelet disorders. No blood product transfusion will significantly change a platelet count; however, it will provide functional platelets for a short period of time. Also, platelet viability is markedly diminished 6 to 8 hours after blood donation, so FWB used for purposes of providing functional platelets should be transfused within a few hours after FWB collection. Fresh plasma, which, by definition, is no more than 6 to 8 hours old, contains all coagulation factors but is devoid of platelets unless platelet-rich plasma is specifically prepared. Refrigerator storage of whole blood or plasma results in the gradual loss of the unstable coagulation factors (factor VIII and von Willebrand’s factor) within about 24 hours and factor V and factor XI after about 1 week. What remains are the stable coagulation factors II, VII, IX, X, and XIII. Fresh frozen plasma (FFP) is created by freezing plasma within 4 to 6 hours of collection. Freezing destroys platelets but preserves all coagulation factors. Fresh frozen plasma is not appropriate to treat thrombocytopenias or thrombocytopathias. Plasma can be frozen for up to 1 year with the unstable coagulation factors preserved. Plasma that has been frozen after 6 hours from collection or frozen for longer than 1 year does not provide coagulation factors; it only provides albumin and is known as frozen plasma (FP). Albumin is the principal protein that contributes to COP. Fluids containing albumin include concentrated albumin and any blood product containing plasma. Concentrated albumin products are the most volume-effective providers of albumin; plasma may also be used primarily for albumin replacement, although the volume of plasma required to increase albumin is likely prohibitive in cats. In addition to supporting COP, albumin may have other important properties. However, the use of albumin-containing products for inflammatory and related conditions (such as pancreatitis) is controversial, and the use of human albumin in cats is controversial in general. Concentrated human albumin solution typically contains 20% or 25% albumin (200 or 250 mg/mL). By contrast, whole blood and plasma contain about 2.5% albumin; thus, they will not increase intravascular COP or albumin effectively. Similarly, the amount of plasma required to increase albumin concentration and COP is approximately 20 to 30 mL/kg. The plasma or whole blood volume required to change plasma protein concentration in cats are thus patient-prohibitive because they will cause volume overload. Concentrated 25% albumin may be the more appropriate colloid for resuscitation in patients with symptomatic hypoalbuminemia, particularly in postoperative or septic critical care feline patients. Albumin transfusions bear several risks; also, the availability of albumin products and supply is often limited. For these reasons, albumin transfusions should be reserved for patients that are clinically hypoalbuminemic (e.g., transudative effusions or severe peripheral edema) and have specific needs that synthetic colloids may not address; a low serum albumin or COP is not in itself an indication for albumin replacement. Also, the albumin administered to patients with uncorrected protein-losing disorders (e.g., protein-losing enteropathies or nephropathies), will be quickly lost by the same routes as the patient’s own albumin. Whenever possible, nutritional support by way of enteral or parenteral nutrition and treatment of the underlying cause of hypoalbuminemia is the preferred means for normalizing serum albumin through hepatic synthesis. The method for determining the amount of albumin to be transfused is:
Fluid Therapy
Abstract
Key Words
INTRODUCTION
BODY FLUID BALANCE
STEADY STATE AND THE CONCEPT OF MAINTENANCE
BODY FLUID COMPARTMENTS
Fluid Movement in the Extracellular Fluid Compartment
e-Box 5.1). The key factors are the hydrostatic and colloid oncotic pressure gradients between the intravascular and extravascular spaces. The hydrostatic pressure is greater in the capillaries than in the interstitium, thus the gradient favors fluid movement from capillaries into the interstitium. The colloid oncotic pressure, determined by plasma protein concentration (largely albumin), is also greater in the capillaries, and draws fluid from the interstitium into the capillaries. Albumin exerts more oncotic pressure than any of the other plasma proteins. Simplistically, high hydrostatic pressure at the proximal end of the capillary results in capillary fluid egress into interstitium. As blood travels distally in the capillary, fluid leaves along its length, the hydrostatic pressure falls because of fluid egression, the colloid oncotic pressure in turn increases distally in the capillary. Fluid leaves the ISC primarily by way of the lymphatics.
Fluid Movement Between the Intracellular and Extracellular Fluid Compartments
PERFUSION
SALT BALANCE: DISORDERS OF EXTRACELLULAR FLUID VOLUME
Sodium Content
Regulation of Sodium Balance
WATER BALANCE: DISORDERS OF SODIUM CONCENTRATION
Permeant and Impermeant Solutes
Tonicity
Regulation of Water Balance
UNDERSTANDING FLUID LOSSES
Sensible and Insensible Fluid Losses
Body Weight and Fluid Losses
Relationship to Lean Body Mass
Terminology of Body Fluid Balance
Assessment of Fluid Loss
Dehydration (%)
Physical Examination Findings
5–7
Dry mucous membranes, skin tenting, mild tachycardia
7–9
Dry mucous membranes, skin tenting, mild tachycardia, sunken eyes, doughy abdomen
9–12
Dry mucous membranes, skin tenting, palpably decreased pulse pressure, sunken eyes, dry corneas, doughy abdomen, evidence of hypovolemia may be present
12–15
All of the above plus evidence of hypovolemia will be present
Condition
Dehydration
Hypovolemia
Blood loss
X
Vomiting
X
X (if severe)
Diarrhea
X
X (if severe)
Sepsis/vasodilation
X
Hypoadrenocorticism
X
Polyuria
X (depending on cause)
X (depending on cause)
Hypodipsia or water deprivation
X
Assessment of Fluid Excess
Dangers of Fluid Excess
BODY RESPONSE TO HYPOVOLEMIA
GENERAL CONSIDERATIONS FOR FLUID THERAPY
FLUID TYPES
Crystalloids
Isotonic High-Sodium Crystalloids
General Characteristics and Indications for Isotonic High-Sodium Crystalloids
e-Table 5.1, and a case example is seen in Table 5.7.
Components of the Fluid Plan
Type of Fluid
Volume of Fluid
mL/day
mL/h
Isotonic
Balanced crystalloid containing 20 mEq/L K+ and Mg++
350
14.5
Hypertonic
Normal ongoing losses
Low-Na+ maintenance fluid
220
9
(Enteral contribution from feeding)
Will be added on day 2
(0)
(0)
Net normal loss to be provided by fluids
220
9
Gastrointestinal
Balanced crystalloid containing 20 mEq/L K+ and Mg++
Est 40
1.5
Urinary
0
0
Other sensible
0
0
Insensible
0
0
Totals
1. 390
1. 16
2. 220
2. 9
3. n/a
3. n/a
Acidifying and Alkalinizing Fluids
Supplements
Product
Concentration per mL
KCl
2 mEq each
KPO4
4.4 mEq K+, 3 mM PO4
MgCl
1.97 mEq each
MgSO4
4.06 mEq each
Ca gluconate 10%
0.465 mEq Ca++
CaCl2
1.36 mEq Ca++
NaPO4
4 mEq Na+, 3 mM PO4
Dextrose 50%
500 mg
POTASSIUM
Measured Serum K+ (mEq/L)
KCl to Add (mEq/L)
>5.5
None
3.6–5.5
20
3.1–3.5
30
2.6–3
40
2–2.5
60
<2
80
PHOSPHATE
MAGNESIUM
CALCIUM
ELECTROLYTE INFUSIONS
GLUCOSE
e-Box 5.2.
Hypotonic and Isotonic Low-Sodium Crystalloids
MAINTENANCE
SUBCUTANEOUS ADMINISTRATION
OTHER USES
INFUSION VEHICLE
HYPERTONIC DEHYDRATION
Combinations of High- and Low-Sodium Crystalloids
Hypertonic Saline Solutions
Colloids
General Characteristics of Colloids
Natural Colloids and Blood Products
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
Veterian Key
Fastest Veterinary Medicine Insight Engine
