Fluid therapy: Choosing the best solution for each patient

Lactated Ringer's solution isn't always the safest choice for fluid therapy. In fact, administering the right fluid, whether a crystalloid, a colloid, or both, is essential to ensuring a correct fluid balance without causing adverse effects that can worsen a patient's condition. This article will help you assess each patient's status and choose the best fluid therapy option.

NORMAL BODY FLUID RETENTION

Total body water normally constitutes about 60% of most mammals' body weight, although this percentage can vary slightly with age, gender, and body condition. The two main fluid compartments of the body are intracellular and extracellular. About 67% of total body water is intracellular.1-3 The remaining 33% is extracellular, in the intravascular and interstitial extravascular spaces. In addition, a small amount of extracellular fluid, known as transcellular fluid, is located in specialized compartments (i.e gastrointestinal tract fluids, synovial fluid, and cerebrospinal fluid).

Within the body, all fluids are in a constant state of flux between compartments. Fluid movement is largely governed by the concentration of electrolytes, proteins, and other osmotically active particles relative to the amount of fluid within each compartment.1-3

The correct balance of fluids and electrolytes is necessary for normal body functioning and cellular processes. In addition to normal fluid intake from eating and drinking, water is also produced during the oxidation of food materials. Fluid is lost with panting, vomiting, diarrhea, and urination. Sensible fluid losses can be measured and constitute about two-thirds of the body's daily maintenance fluid requirements. Sensible fluids include urine, feces, and, abnormally, vomitus. Insensible fluid loss, such as evaporation from the respiratory tract, is estimated. Insensible fluid losses can be excessive because of evaporation from open body cavities during prolonged surgeries and in animals with hyperthermia, hemorrhage, or severe panting or salivation.1,2

In healthy animals, fluid intake and excretion are kept in balance by sodium and chloride ion activity as well as serum osmolality.2,3 Osmoreceptors in the hypothalamus sense the sodium and chloride concentrations in the vascular space. As the serum sodium concentration rises because of increased sodium intake or an increase in free water loss, serum osmolality rises. An increase in serum osmolality stimulates the release of arginine vasopressin, or antidiuretic hormone, from the hypothalamus. Antidiuretic hormone stimulates the opening of water channels in the collecting ducts of the renal tubules, which stimulates water reabsorption. Once water is retained in the vascular space, sodium, urea, and glucose—the major contributors to serum osmolality—are diluted, and serum osmolality decreases. Hypothalamic secretion of antidiuretic hormone ceases once serum osmolality returns to normal.

CALCULATING DAILY FLUID REQUIREMENTS

Daily fluid requirements are based on the metabolic water requirements of a patient in a state of equilibrium. During a state of equilibrium, a patient's daily water intake equals water loss, creating no net loss or gain of fluid. For each kilocalorie of energy metabolized, 1 ml water is consumed. Metabolic energy requirements are calculated based on the following linear formula1 :

kcal/day = (30 × body weightkg) + 70

By substituting 1 ml water for 1 kcal, the following formula can be used to estimate a patient's daily metabolic water requirements:

ml/day = (30 × body weightkg) + 70

Recent studies indicate that metabolic energy requirements rarely increase during states of critical illness except in cases of sepsis.4,5 Because our patients frequently pant and may have excessive evaporative losses or sensible fluid losses from vomiting, diarrhea, wound exudates, or body cavity effusions, daily fluid requirements may be greater than that calculated above. Thus, the above formula should be used as a guideline, and careful assessment and measurement of ongoing losses should be added to a patient's daily fluid therapy as needed to prevent further dehydration.

DETERMINING THE PERCENTAGE OF DEHYDRATION

The percentage of dehydration can be subjectively estimated based on the presence and degree of loss of body weight, mucous membrane dryness, decreased skin turgor, sunken eyes, and altered mentation (Table 1).1 These parameters are largely subjective because they can also be affected by decreased body fat and increased age.

Table 1 Estimating the Percentage of Dehydration

The more severe stages of dehydration are also accompanied by signs of hypovolemic shock. Other factors, including hemorrhage and third spacing of body fluids, can also result in a decrease in intravascular circulating volume, resulting in signs of hypovolemia. Severe hypovolemia resulting in more than a 15% depletion of effective circulating volume leads to a transcompartmental fluid shift from the interstitial to the intravascular compartments, which occurs within one hour of fluid loss.6 When fluid loss is so severe that intravascular fluid volume is affected, hypovolemia can result in tachycardia, prolonged capillary refill time, decreased urine output, and hypotension.

The vascular space is sensitive to changes in the amount of circulating volume. During states of normovolemia, baroreceptors in the carotid body and aortic arch sense vascular wall tension and send pulsatile continuous feedback via vagal afferent stimuli to decrease heart rate. In the early stages of hypovolemic shock, the baroreceptors sense a decrease in vascular wall stretch or tension and blunt the tonic vagal stimulation. This allows sympathetic tone to increase heart rate and contractility in an attempt to normalize cardiac output. Later, decreased blood flow and sodium delivery to receptors in the juxtaglomerular apparatus activate the renin-angiotensin-aldosterone axis, stimulating sodium and fluid retention to replenish intravascular volume.1-3

CORRECTING FLUID IMBALANCES

When clinical signs of hypovolemic shock are present, intravascular fluids must be replaced immediately. Calculated fluid volumes for patients in shock are 90 ml/kg for dogs and 44 ml/kg for cats.1 A simple guideline to follow is to replace one-fourth of the calculated fluid volume as rapidly as possible and then reassess perfusion parameters including heart rate, blood pressure, capillary refill time, and urine output. In dogs, a simple method to calculate one-fourth of the fluid volume for treating shock is to take an animal's weight in pounds and add a zero, giving you the amount of fluid in milliliters to administer as a bolus.

About 80% of the volume of crystalloid fluid infused will re-equilibrate and leave the intravascular space within one hour of administration. A constant-rate infusion of a crystalloid fluid is recommended to provide continuous fluid support in patients that are dehydrated and have ongoing losses. In some cases, the fluid required to restore intravascular and interstitial volume can cause hemodilution and dilution of oncotically active plasma proteins, resulting in interstitial edema formation. In such cases, a combination of a crystalloid fluid along with a colloid-containing fluid can help restore oncotic pressure and prevent interstitial edema.6

Once immediate life-threatening fluid deficits are replaced, provide additional fluid based on the estimated percentage of dehydration and maintenance needs. Basic dehydration estimates can be calculated based on the fact that 1 ml water weighs about 1 g and by using the following formula:

Body weightkg × estimated percent dehydration × 1,000 ml/L

This formula helps you determine the amount of fluid deficit in liters. A frequent mistake when replenishing fluid deficits is to arbitrarily multiply a patient's daily water requirement by a factor of two or three to replenish intravascular and interstitial deficits. This practice frequently underestimates a patient's fluid needs and does little to treat volume depletion and interstitial dehydration. Instead, it is better to use the formula above and add the result to daily maintenance fluid requirements and ongoing losses.

Eighty percent of the calculated fluid deficit can be replaced in the first 24 hours. More rapid administration of an animal's estimated fluid deficit can result in diuresis and loss of the fluid administered. After successfully treating hypovolemic shock and replacing fluid deficits estimated based on the percentage of dehydration, you can administer only maintenance fluids until the animal can maintain hydration on its own, provided no signs of dehydration or ongoing excessive fluid losses are present. An objective way to assess whether the fluid volume is adequate is to evaluate body weight regularly throughout the day. Acute weight loss is commonly associated with fluid loss and can be used to determine whether the patient is at risk of becoming dehydrated again.

TYPES OF INTRAVENOUS FLUIDS

A variety of crystalloid and colloidal fluids are available, including isotonic, hypotonic, and hypertonic solutions and natural and synthetic colloids.

Crystalloid fluids

A wide variety of crystalloid fluids are available. Crystalloid fluids contain crystals or salts that are dissolved in solution. Specific crystalloid fluids are indicated for some diseases or conditions and may be contraindicated in others. So whenever you use a crystalloid fluid, carefully consider it to be another drug in the armamentarium, and assess the particular fluid's use or potential misuse in each patient.7

Basic categories of crystalloid fluids include isotonic, hypotonic, and hypertonic solutions, depending on the concentration and type of solute it contains relative to normal body plasma. A maintenance fluid contains electrolyte concentrations similar to serum, whereas replacement solutions contain slightly higher concentrations of potassium and slightly lower concentrations of sodium relative to serum.

Isotonic fluids

Isotonic fluids have tonicity, or solute relative to water, similar to that of serum. Examples of isotonic fluids are 0.9% (normal) saline solution, lactated Ringer's solution, Normosol-R (Abbott Laboratories), and Plasmalyte A (Baxter Healthcare). Isotonic fluids are indicated to restore fluid deficits, correct electrolyte abnormalities, and provide maintenance fluid requirements. Long-term use of isotonic fluids can lead to mild hypernatremia in some patients.

Hypotonic fluids

Hypotonic solutions have a tonicity less than that of serum. Examples of hypotonic fluid solutions are 0.45% saline solution, 0.45% sodium chloride plus 2.5% dextrose solution, and 5% dextrose solution in water. Dextrose-containing fluids are isotonic in the bag but become hypotonic once the glucose is metabolized in the body. Essentially, free water is being administered without the risk of causing iatrogenic hemolysis. Hypotonic fluids are indicated when treating patients with disease processes that cause sodium and water retention, namely, congestive heart failure and hepatic disease. Hypotonic fluid therapy is also indicated in patients with severe hypernatremia and allows you to slowly correct a free water deficit. To calculate a patient's free water deficit, use the following formula8 :

Free water deficit (L) = 0.6 × lean body weightkg × [(patient serum sodium concentration/140) – 1]

Correct the free water deficit slowly to avoid iatrogenic cerebral edema. Ideally, the patient's serum sodium concentration should not decrease by more than 15 mEq/L during a 24-hour period.

Hypertonic fluids

Hypertonic solutions draw fluid from the interstitial fluid compartment and into the intravascular space to correct hypovolemia. Hypertonic fluid administration is absolutely contraindicated if interstitial dehydration is present. Hypertonic solutions such as 3% or 7% saline solution have solute in excess of fluid relative to serum. Administer hypertonic saline solution in bolus increments of 3 to 7 ml/kg as a rapid infusion. The rapid rise in capillary hydrostatic pressure can force sodium to flow down its concentration gradient into the interstitium. Administering a low-sodium crystalloid fluid after a hypertonic saline solution can lead to interstitial edema. Therefore, always administer hypertonic saline solution in combination with a colloid (10 ml/kg hetastarch or dextran 70) to help retain fluid within the intravascular space, thus maintaining intravascular fluid volume and avoiding the secondary complication of interstitial edema.

Choosing a crystalloid solution

Carefully consider the pH, buffer content, and total electrolyte composition of each type of crystalloid fluid (Table 2) when choosing a fluid that is appropriate for specific diseases. For example, if an animal is hyponatremic, a low-sodium or no-sodium fluid such as 0.45% saline solution or 5% dextrose solution in water would exacerbate the hyponatremia. Administering an isotonic or a hypertonic fluid such as lactated Ringer's solution, Normosol-R, Plasmalyte M, or 0.9% sodium chloride solution may be most appropriate to replenish sodium. Also consider the animal's acid-base status. For example, if an animal has metabolic acidosis as well as hyponatremia, then administering 0.9% sodium chloride solution, which does not contain any buffers or bicarbonate precursors, could worsen the metabolic acidosis. Administering lactated Ringer's solution, which contains lactate, or Normosol-R, which contains acetate and gluconate, may be more appropriate.

Table 2 Electrolyte and Buffer Composition and pH of Common Isotonic and Hypotonic Crystalloids

Sodium chloride solution (0.9%) is an excellent choice for promoting renal calcium and potassium excretion. In addition, the fluid does not contain calcium or potassium, so it is useful in treating animals with hypercalcemia and hyperkalemia. Magnesium ions are required as cofactors for a number of metabolic processes, including potassium retention. Refractory hypokalemia, as that observed in animals with diabetic ketoacidosis, can be partially treated or prevented by using a magnesium-containing fluid such as Normosol-R or Plasmalyte M.

Colloids

The oncotic pressure is the force that holds fluid within a compartment. Starling's forces, which dictate the amount of fluid retention within the vascular space vs. transvascular fluid flux into the interstitium, depend on many factors, including intravascular and interstitial hydrostatic pressure, interstitial and intravascular oncotic pressure, and capillary pore size. As intravascular volume is replenished with a crystalloid fluid, the intravascular hydrostatic pressure increases and causes a dilutional decrease in oncotic pressure, which can result in the movement of osmotically active substances into the interstitium. A colloidal solution contains negatively charged, large-molecular-weight particles that are osmotically active, drawing sodium around their core structures. Wherever sodium is, water follows. By drawing sodium around the particle, water is held within the vascular space.

Colloids replace intravascular fluid deficits only. So colloids are always administered along with crystalloids to restore both intravascular and interstitial fluid volume. Consider colloids whenever hypoproteinemia, decreased oncotic pressure, and increased capillary pore size exist, as in conditions associated with sepsis or systemic inflammatory response syndrome. Although some of the colloid particles can potentially leak into the interstitial space, the net effect is to maintain fluid within the intravascular space to avoid interstitial edema. Whenever a colloid is administered with a crystalloid, reduce the calculated crystalloid fluid requirements by 25% to 50% to avoid volume overload.

Natural colloids

Natural colloid solutions include whole blood and plasma. Fresh whole blood is indicated when loss of both red blood cells and plasma has occurred. The Rule of Ones states that 1 ml fresh blood infused per 1 lb body weight will increase a patient's packed cell volume (PCV) by 1%, provided no ongoing losses are present. This rule is a simple method to calculate the amount of whole blood to administer to reach a target hematocrit. When working in kilograms, the Rule of Ones can be extrapolated: 2.2 ml/kg whole blood will increase an animal's PCV by 1%, provided the PCV of the transfused blood is 40%.9 A more accurate method to determine the volume of whole blood to administer is as follows:

ml donor blood needed = [(Desired PCV – Actual Recipient PCV) ÷ Donor PCV] × ml recipient blood volume

(Note: For recipient blood volume, use 90 ml/kg for dogs and 70 ml/kg for cats.)

Packed red blood cells can be administered if the degree of anemia is sufficient to cause clinical signs (e.g. lethargy, inappetence, tachycardia, tachypnea) but plasma proteins are within the normal range.

Fresh frozen plasma can be administered at 10 to 20 ml/kg/day to replenish clotting factors and provide antiproteinase activity in states of inflammation, such as pancreatitis, and provide small quantities of albumin.6 Infuse 20 ml/kg plasma for every 0.5 g/dl increase in plasma albumin needed, provided no ongoing losses are present. The goal of plasma administration is to raise a patient's serum albumin concentration to 2 g/dl; once this goal is achieved, provide the remainder of colloidal support with synthetic colloids.

Synthetic colloids

Examples of artificial colloids include hetastarch, dextran 40, dextran 70, and polymerized bovine hemoglobin glutamer-200 (Oxyglobin—Biopure). Hetastarch and dextrans are commonly used in veterinary practice. Concentrated human serum albumin (HSA) (25% albumin; ASD Healthcare) should be considered in severe cases of hypoalbuminemia (albumin < 2 g/dl).

Hetastarch. Hetastarch is a polymer of amylopectin suspended in a lactated Ringer's solution. The average molecular weight of hetastarch is 69,000 daltons. The hetastarch particles are broken down by serum amylase and last in circulation for about 36 hours. Because hetastarch can bind with von Willebrand factor, a patient's activated partial thromboplastin time (APTT) and activated clotting time (ACT) may become mildly prolonged, but this will not contribute to or cause bleeding.

Administer hetastarch in incremental boluses of 5 to 10 ml/kg in dogs and 5 ml/kg in cats. Because rapid hetastarch administration can cause histamine release and vomiting in cats, administer the bolus slowly over 15 to 20 minutes. Many authors recommend that the total daily dose of hetastarch should not exceed 20 to 30 ml/kg/day.6 After administering the boluses, administer hetastarch as a constant-rate infusion (20 to 30 ml/kg/day intravenously) until the patient is able to maintain its serum albumin concentration and colloidal support on its own. During hypovolemic shock, 5 to 10 ml/kg can be given as an intravenous bolus.

Dextran. Dextran solutions contain polymers of glucose with average molecular weights of 40 and 70 daltons. Most practitioners favor dextran 70 over dextran 40 because dextran 70's larger particles contribute to the water-holding capacity of blood. The smaller particles of dextran 40 last about four hours in circulation before being cleared by the kidneys. The larger particles of dextran 70 last about nine hours in circulation.

Both dextran 40 and dextran 70 coat platelets and red blood cells and can impair coagulation and interfere with cross-match procedures. For this reason, dextran 70 may be preferred over hetastarch in conditions of hypercoagulability and thrombosis. Anaphylaxis and renal failure have been reported in people that received dextran 40.6 The dose is 10 to 20 ml/kg/day given intravenously when administered along with a crystalloid. During hypovolemic shock, 5 ml/kg can be administered as an intravenous bolus to treat hypotension.

Polymerized bovine hemoglobin glutamer-200. This solution contains bovine stroma-free hemoglobin that acts both as a potent colloid and as an oxygen carrier in the face of thrombosis or anemia. Recommended doses are 20 to 30 ml/kg/day. Polymerized bovine hemoglobin glutamer-200 can be administered as an intravenous bolus of 3 to 7 ml/kg. Use caution when infusing this solution in normovolemic patients and in those with congestive heart failure because of the risk of causing iatrogenic volume overload.

HSA. Albumin contributes 80% of the oncotic pressure of blood and acts as a carrier for various essential compounds in the body, including hormones, zinc, copper, and drugs. Albumin is also a mediator of coagulation and a free-radical scavenger at sites of inflammation. Hypoalbuminemia (albumin < 2 g/dl) has been associated with delayed wound healing and an overall increase in patient mortality.10 Patients with conditions associated with increased capillary pore size, such as sepsis, vasculitis, and systemic inflammatory response syndrome, can benefit from maintaining the serum albumin concentration at or ideally above 2 g/dl.

As a general rule, the serum albumin concentration should be raised to at least 2 g/dl with fresh frozen plasma or HSA. Administering fresh frozen plasma can help restore some of the intravascular albumin, but it is largely inefficient on a ml/kg basis when compared with HSA. Plasma is better suited to replenish clotting factors and antithrombin and should be used in conjunction with a synthetic colloid such as hetastarch to maintain oncotic pressure. A volume of 20 ml/kg plasma will raise the serum albumin concentration by 0.5 g/dl, provided no ongoing protein loss is present.11

Chronic hypoalbuminemia results when the body's interstitial albumin pool becomes depleted and can no longer maintain intravascular albumin concentrations and oncotic pressure. The albumin contained in an infusion of fresh frozen plasma will replenish the interstitial albumin stores before an increase in serum albumin is detected. But in many cases, this can be costly and can deplete a hospital's resources of plasma. Instead, a more efficient means of restoring both interstitial and intravascular albumin is to administer HSA.

HSA has been used with success in a variety of critically ill dogs.12 It is a potent colloid and is effective in restoring serum and interstitial albumin in patients with acute or chronic hypoalbuminemia for the short term, but in animals with chronic hypoalbuminemia, the underlying cause of decreased albumin production or increased loss must also be addressed for the best long-term outcome.

HSA also helps retain fluid within the vascular space.11 Like other colloids, HSA can also pull fluid from the interstitium into the vascular space, so it may be helpful in treating interstitial edema. Carefully monitor the animal for signs of intravascular volume overload such as tachypnea, orthopnea, chemosis, or fulminant pulmonary edema.

Pretreat animals with 1 mg/kg intramuscular diphenhydramine, and then give 2 ml/kg HSA over four hours. Monitor for clinical signs of a reaction, including urticaria, angioneurotic edema, hypotension, salivation, and vomiting. Rare reports of delayed reactions and systemic vasculitis and polyarthritis have been observed in dogs about 14 days after albumin infusion.13 All patients had clinical signs of gastrointestinal inflammation or septic peritonitis at the time of albumin infusion. Treat vasculitis and polyarthritis with 1 mg/kg prednisone given orally twice a day for two weeks and then tapered over two additional weeks. Although the potential for a reaction exists, the benefits of albumin supplementation can outweigh this small risk and can improve overall outcome.

CONCLUSION

Intravenous fluid therapy is undoubtedly one of the mainstays of treatment of both acute and chronic illnesses. The fluid armamentarium available to veterinary practitioners has evolved dramatically over the past decades to include a variety of crystalloid and colloidal fluids. Similar to choosing an antibiotic to treat the most likely bacterial infection, a fluid should be chosen to treat a specific disease entity. Even in situations in which a specific diagnosis has not yet been made, the fluid should be chosen after careful consideration of an animal's acid-base, electrolyte, dehydration, and oncotic pressure status. It is not necessary to stock every crystalloid or colloid available. However, having a combination of replacement and maintenance crystalloids along with a colloid to choose from can decrease morbidity and mortality in your most critically ill patients.

Elisa M. Mazzaferro, MS, DVM, PhD, DACVECC

Wheat Ridge Veterinary Specialists

3695 Kipling St.

Wheat Ridge, CO 80033

This article is adapted from Dr. Mazzaferro's 2006 CVC East proceedings paper.

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10. Drobatz KJ, Macintire DK. Heat-induced illness in dogs: 42 cases (1976–1993). J Am Vet Med Assoc 1996;209:1894–1899.

11. Mazzaferro EM, Rudloff E, Kirby R. The role of albumin in health and disease. J Vet Emerg Crit Care 2002;12:113-124.

12. Mathews KA, Barry M. The use of 25% human serum albumin: outcome and efficacy in raising serum albumin and systemic blood pressure in critically ill dogs and cats. J Vet Emerg Crit Care 2005;15:110-118.

13. Mathews KA, Department of Clinical Sciences, Ontario Veterinary College, University of Guelph, Ontario, Canada: Personal communication, 2006.