In hypovolemic shock, compensatory neuroendocrine responses are initiated for restoring blood volume and meeting metabolic demands that occur during acutely decreased cardiac output states, increasing ATP demands. When perfusion becomes compromised in spite of these mechanisms, decompensatory shock ensues. An adequate fluid resuscitation plan is necessary to optimize survival.

The fluid resuscitation plan should include the following steps: l) determine where the fluid deficit lies, 2) select fluid(s) specific for the patient, 3) determine resuscitation endpoints, and 4) determine the resuscitation technique to be used.

Determination of the Fluid Deficit

Loss of fluid volume from the intra-vascular fluid compartment is manifested by poor perfusion (shock) and inadequate tissue oxygenation. This volume deficit results in a lower vessel wall tension and stimulation of the baroreceptors, which in turn stimulate the sympathetic system. Clinical changes in heart rate, pulse intensity, capillary refill time, mucous membrane color, level of consciousness, and rectal temperature are seen. These physical perfusion parameters, combined with blood pressure, are used clinically to detect intravascular volume deficits. Most animals with an intravascular deficit (poor perfusion) also have concurrent extra-vascular deficits.

Fluid deficit in the interstitial and intra-cellular spaces causes clinical signs of dehydration. Physical findings are used to estimate the percentage of dehydration. Semidry oral mucous membranes, normal skin turgor, and eyes maintaining normal moisture indicate 4–5% dehydration. Dry oral mucous membranes, mild loss of skin turgor, and eyes still moist indicate 6–7% dehydration. As dehydration becomes more severe, significant quantities of fluid shift from the intravascular space into the interstitium, causing concurrent perfusion deficits with dehydration. Dry mucous membranes, considerable loss of skin turgor, eyes retracted, acute weight loss, and weak rapid pulses (concurrent intravascular deficit) indicate 8–10% dehydration. Very dry oral mucous membranes, complete loss of skin turgor, severe retraction of the eyes, dull eyes, possible alteration of consciousness, acute weight loss, and thready weak pulses indicate 12% dehydration.

The physical guidelines for estimating dehydration are misleading in 2 common clinical situations. Chronically emaciated animals may have metabolized the fat from around the eyes and the collagen in the skin, resulting in poor skin turgor and sunken eyes despite normal hydration. Animals with rapid fluid loss into a third body fluid space (a space within the body cavity where fluid from the local interstitial and intravascular spaces leak) have rapid fluid shifts from the intravascular compartments into these spaces before clinical evidence of interstitial fluid loss is seen. Both situations require evaluation of mucous membrane and eye moisture, PCV, and total solids before dehydration can be estimated.

Selection of Fluids

Fluids must be administered that will concentrate within the body fluid compartment where the volume deficit lies. Crystalloids are water-based solutions with small-molecular-weight particles, freely permeable to the capillary “membrane.” Colloids are water-based solutions with a molecular weight that is too large to freely pass across the capillary “membrane.” Colloids are thought of as intravascular volume replacement fluids, and crystalloids as interstitial volume replacement solutions.

Crystalloids

The small-molecular-weight particles in crystalloids are primarily electrolytes and buffers (see Fluid Therapy: Crystalloids). When the sodium concentration of the solution is equivalent to that of the cell, the solution is called isotonic. Intravascular administration of isotonic crystalloids (eg, lactated Ringer's, 0.9% saline) will result in interstitial volume replacement and minimal intracellular fluid accumulation. Over 75% of the isotonic crystalloid administered IV can move into the extravascular space within 1 hr in a normal animal. This is because of the normal fluid shifts between fluid compartments. Hypotonic fluids (eg, 5% dextrose in water, half-strength saline) will result in intracellular water accumulation and are not used as resuscitation fluids.

Crystalloids are considered balanced when they contain molecules that act as buffers. Acetate, gluconate, and lactate are common buffers that are converted to bicarbonate and raise the pH of the solution to normal blood pH (7.4). Normal saline (0.9%) is isotonic but not balanced; it is used initially for specific clinical problems, including hyponatremia, hypernatremia, hypercalcemia, hypochloremic metabolic alkalosis, head trauma, and oliguric renal failure.

The particular crystalloid to administer is determined by the measured or estimated sodium and potassium concentrations and by the osmolality of both the animal's serum and the fluid to be administered (see Fluid Therapy: Crystalloids). Most clinical problems will benefit from the use of balanced, isotonic crystalloids (eg, lactated Ringer's, Normosol-R^®, Plasmalyte-A^®) as part of the resuscitation fluid plan.

Sodium Content

When serum sodium estimations are normal, a balanced isotonic electrolyte solution can be used for volume replacement. Serum sodium levels that are moderately to severely decreased (<130 mEq/L) or moderately to severely increased (>170 mEq/L) may contribute to serum osmolality changes and result in neurologic abnormalities. Care must be taken not to increase or decrease the sodium concentration too quickly. In general, sodium concentrations should not be altered by >0.5 mEq/L/hr or 8–12 mEq/L/day. This allows for increased or decreased osmolality of neurons to adjust over time and avoids cerebral edema or dehydration.

Table 1
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Crystalloids Crystalloid Tonicity Sodium (mEq/L) Potassium (mEq/L) Calcium (mEq/L) Osmolality (mOsm/L) Lactated Ringer's solution Isotonic 130 4 3 273 (pH 6.7) Plasmalyte-A® Isotonic 140 5 0 294 (pH 7.4) Normosol-R® Isotonic 140 5 0 295 (pH 7.4) Normal saline (0.9%) Isotonic 154 0 0 308 (pH 5.7) Dextrose (2.5% in 0.45% saline) Isotonic 77 0 0 280 (pH 4.5) Dextrose (5%) in water Hypotonic 0 0 0 253 (pH 5.0) Saline (7.5%) Hypertonic 1,232 0 0 2,464 (pH 5.2) Normosol-M® with 5% dextrose Hypertonic 40 13 0 363 (pH 5.2) Crystalloids Crystalloid Tonicity Sodium (mEq/L) Potassium (mEq/L) Calcium (mEq/L) Osmolality (mOsm/L) Lactated Ringer's solution Isotonic 130 4 3 273 (pH 6.7) Plasmalyte-A® Isotonic 140 5 0 294 (pH 7.4) Normosol-R® Isotonic 140 5 0 295 (pH 7.4) Normal saline (0.9%) Isotonic 154 0 0 308 (pH 5.7) Dextrose (2.5% in 0.45% saline) Isotonic 77 0 0 280 (pH 4.5) Dextrose (5%) in water Hypotonic 0 0 0 253 (pH 5.0) Saline (7.5%) Hypertonic 1,232 0 0 2,464 (pH 5.2) Normosol-M® with 5% dextrose Hypertonic 40 13 0 363 (pH 5.2)

Serum sodium alterations with fluid administration (Δ[Na]) can be estimated using the following formula:

In animals with decreased serum sodium content, volume replacement should be with isotonic saline (0.9%). Increased serum sodium values most commonly reflect a loss of solute-free water. The animal should be perfused and hydrated using isotonic saline. The free water can then be replaced, if necessary, using 2.5% dextrose in half-strength lactated Ringer's, 2.5% dextrose in half-strength saline, 0.45% saline, or 5% dextrose in water when hypernatremia persists. This must be done carefully, and the sodium concentration lowered slowly. Desmopressin may be required if hypernatremia persists after appropriate fluid therapy, especially when the patient has hyposthenuria or head injury.

Potassium Content

When serum potassium estimates are normal, a balanced electrolyte solution can be used. Hypokalemia can be difficult to recognize clinically. Few clinical situations warrant potassium supplementation beyond the content of lactated Ringer's or Plasmalyte-A^® during initial volume replacement. Once the animal has been stabilized, potassium chloride should be added to the fluids, administered at ≤0.5 mEq/kg/hr. This rate may be administered more rapidly when severe hyperkalemia (<2 mEq/L) is associated with catastrophic clinical signs, eg, respiratory distress from paresis of the diaphragm or generalized lower motor paresis or paralysis. The serum potassium level must be closely monitored with more rapid infusions. More commonly, 20–40 mEq of potassium chloride is added to 1 L of balanced isotonic crystalloids administered as maintenance fluids. Serum potassium values should be obtained before supplementation when possible and monitored closely during continued therapy.

In animals with hyperkalemia, fluids should be selected carefully. When oliguric renal failure is suspected as the cause of the hyperkalemia, potassium-free solutions, such as 0.9% saline, are used for volume replacement. Clinical conditions requiring potassium-free solutions include oliguric renal failure, heat stroke, adrenal insufficiency (Addison's disease), and massive muscle breakdown. After volume replacement and fluid diuresis resolve the hyperkalemia, a balanced electrolyte solution should be used. These solutions have a normal pH and promote potassium excretion.

Osmolality

Osmolality is defined as the number of solute particles per unit of solvent. Serum osmolality can be calculated using the following formula:

Normal serum osmolality is 290–310 mOsm/L. Fluids that do not contribute significantly to serum osmolality should be used for volume replacement.

Hyperosmolar solutions include hypertonic saline, Normosol-M^® with 5% dextrose, or any isotonic fluid that has glucose added. Except for hypertonic saline, the hyperosmolar glucose-containing solutions are meant to be maintenance solutions used in animals in which fluids are not shifting rapidly from the vascular compartment to a third body fluid space. They are usually not used as volume replacement solutions.

Hypertonic saline provides a supranormal concentration of sodium and is generally given in a 3%, 7%, or 7.5% IV solution. The effect is to rapidly draw water from the interstitial space into the intravascular space, rapidly expanding the intravascular volume. Hypertonic saline may also decrease cellular swelling and improve myocardial contractility. If the patient has concurrent interstitial fluid deficits (dehydration) or a disease that results in free water loss (eg, hyperthermia, diabetes, etc), administration of hypertonic saline could result in severe hyperosmolality with neurologic complications. Because hypertonic crystalloid solution will leak into the interstitium <1 hr, combining hypertonic saline with a colloid is recommended to offset the interstitial edema resulting from interstitial extravasation.

Colloids

When colloids are to be administered, it must be decided whether a natural colloid (eg, plasma, albumin, or whole blood) or a synthetic colloid (see Fluid Therapy: Synthetic Colloids) is to be used. When the animal requires RBC, clotting factors, antithrombin III, or albumin, blood products are the colloids of choice.

When the initial goal is to rapidly improve perfusion in an animal with adequate RBC, a synthetic colloid can achieve the desired volume expansion rapidly. Choices of synthetic colloids include dextran, hydroxyethyl starch (HES), and stroma-free hemoglobin.

Dextrans are polysaccharides composed of linear glucose residues. They are produced by the enzyme dextran sucrase during growth of various strains of Leuconostoc bacteria in media containing sucrose. Dextrans are isotonic and can be stored at room temperature. Dextran is broken down completely to CO₂ and H₂O by dextranase present in spleen, liver, lung, kidney, brain, and muscle at a rate approaching 70 mg/kg every 24 hr. In normal dogs, dextran 70 increases plasma volume 1.38 times (138%) the volume infused.

Hemostatic changes in healthy experimental dogs given dextran 70 include an increase in the buccal mucosal bleeding time and partial thromboplastin time and a decrease in Von Willebrand's factor antigen and factor VIII coagulant activity, without clinical bleeding. Dextran copolymerizes with the fibrin monomer, destabilizing clot formation. Blood glucose levels may be elevated during dextran metabolism. Dextran 70 may cause a change in the total solids value that does not reflect actual protein content and may interfere with blood crossmatching. Moderate to life-threatening reactions in dogs have been rare.

Hydroxyethyl starch (HES) is the parent name of a polymeric molecule made from a waxy species of either maize or sorghum and is composed primarily of amylopectin (98%). The disappearance of HES molecules from the body depends on their rate of absorption by tissues (liver, spleen, kidney, and heart), gradual return to circulation, uptake by the reticuloendothelial system, enzymatic degradation to smaller particles by amylase, and clearance through urine and bile. Blood α-amylase-mediated hydrolysis reduces the molecular weight to <72,000 daltons. Metabolism of HES retained in tissue is probably performed by cytoplasmic lysosomes. A rise in serum amylase is to be expected without alteration in pancreatic function.

The degree of substitution, rather than molecular weight, is the major determinant of how long the different types of HES survive in the blood. When hetastarch (the most common HES) is infused at 25 mL/kg in healthy dogs, the initial increase in plasma volume is 1.37 times (137%) the volume infused. Intravascular persistence is significantly greater than that of dextran 70, with 38% of hetastarch remaining compared with 19% of dextran 24 hr after infusion. Administration by constant rate infusion may provide a constant supply of larger molecular weight particles, perhaps maintaining and augmenting plasma COP and intravascular volume in animals with albumin loss or increased capillary permeability.

Hetastarch favors retention of intravascular fluid and prevents washout of interstitial proteins. In hypooncotic situations, hetastarch infusion has a great advantage over other colloids because the larger molecules remain intravascular, limiting pulmonary fluid flux. It is nontoxic and nonallergenic in dosages up to 100 mL/kg in dogs. Many cats have a moderate reaction—nausea and occasional vomiting—with rapid infusion. However, when hetastarch is given slowly (over 5–15 min), this side effect is minimal.

Hetastarch is associated with minor alterations in laboratory coagulation measurements but not with clinical bleeding unless daily minimal dosages (20–40 mL/kg/day) are exceeded. Dilutional effects on coagulation, cells, and proteins are produced in response to the volume expansion of the plasma. Patients that receive large volumes of HES solutions may have more oozing if surgery is performed, and diligent hemostasis is warranted.

Table 2
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Synthetic Colloids Colloid Average Molecular Weight (daltons) Molecular Weight Range (daltons) Half-life (hr) Colloid Oncotic Pressure (mm Hg) Concentration (%) Maximum Water Binding (mL water/g colloid) Dextran 70 70,000 10,000–80,000 25 59 6 29 Hetastarch 450,000 10,000–3.4 million 25 30 10 20 Stroma-free hemoglobin (Oxyglobin®) 65,000–130,000 Up to 500,000 30–40 20 13 — Synthetic Colloids Colloid Average Molecular Weight (daltons) Molecular Weight Range (daltons) Half-life (hr) Colloid Oncotic Pressure (mm Hg) Concentration (%) Maximum Water Binding (mL water/g colloid) Dextran 70 70,000 10,000–80,000 25 59 6 29 Hetastarch 450,000 10,000–3.4 million 25 30 10 20 Stroma-free hemoglobin (Oxyglobin®) 65,000–130,000 Up to 500,000 30–40 20 13 —

Stroma-free hemoglobin (Oxyglobin ^® ) is a polymerized bovine hemoglobin-based solution that increases plasma and total hemoglobin concentration. This solution is indicated for the treatment of anemia and hypovolemia with tissue hypoxia. It has colloidal properties similar to those of hetastarch and exerts mild vasopressor activity. The dark hue of the solution causes discoloration of the serum that can interfere with some serum chemistry tests, depending on the type of analyzer and reagents used. Bilirubinuria will be present. Dosages ≤30 mL/kg/day have been approved for dogs, with the rate of infusion <10 mL/kg/hr. When given to an animal that has a normal blood volume, administration must be slow and carefully monitored to avoid volume overload resulting from the colloidal and pressor properties of the solution.

Fluid Selection

Interstitial and intracellular volume deficits (dehydration) are replaced by the administration of crystalloids. Intravascular volume (perfusion) deficits can also be replaced with crystalloids alone. However, when large quantities of isotonic crystalloids are rapidly administered IV, there is an immediate increase in intravascular hydrostatic pressure, a decrease in intravascular COP, and extravasation of large fluid quantities into the interstitial spaces. By administering colloids in conjunction with crystalloids during fluid resuscitation of perfusion deficits, less total fluid volume is required (crystalloids reduced by 40–60%), there is less tendency toward fluid overload, and resuscitation times are shorter.

Many conditions can increase capillary permeability and cause systemic inflammation, including parvoviral diarrhea, pancreatitis, septic shock, massive trauma, heat stroke, cold exposure, burns, snake bite, and systemic neoplasia. Hetastarch or stroma-free hemoglobin are the colloids of choice for intravascular volume resuscitation when there is increased capillary permeability and loss of albumin through the capillary membrane. Using crystalloids alone in animals that require large volumes for resuscitation or that have increased capillary permeability will eventually result in significant interstitial edema.

Many of these animals also have third-space fluid losses, most likely due to significant regional inflammation, that result in massive fluid requirements and make it difficult to predict the volume required for maintaining fluid balance.

Determination of Resuscitation Endpoints

There are no “standard” formulas for crystalloid or colloid infusion that will guarantee complete volume resuscitation in a small animal. Variables such as renal function, presence of a third body fluid space, brain injury, lung injury, heart disease or failure, or closed cavity hemorrhage require that fluid resuscitation rate and volumes be individualized for the patient. Sufficient volumes of fluid should be administered to reach desired endpoints of resuscitation. This has also been termed early goal-directed therapy. The endpoints typically reflect perfusion status, and include heart rate, blood pressure, central venous pressure, mucous membrane color, capillary refill time, and pulse intensity. A resolution of an elevated blood lactate to <2 mmol/dL supports adequate tissue oxygenation. More advanced endpoints, which can be used if additional instrumentation is available, include a central venous pressure of 5–8 cm H₂0, central venous oxygen saturation >70%, and a urine output of at least 1–2 mL/kg/hour.

Shock will deplete cellular energy stores, with subsequent cellular and organ dysfunction. Restoring the circulation to “normal,” with normal oxygenation and perfusion parameters, may not be enough to allow sufficient ATP production for repair as well as maintenance. When a patient is suspected of having a disease process related to systemic inflammatory response syndrome such as vasodilation, increased capillary permeability, or depressed cardiac output, resuscitation endpoints are chosen for supranormal resuscitation (see Fluid Therapy: Endpoint Resuscitation). The goal is to deliver oxygen and glucose to the cells in higher than normal concentrations to promote sufficient energy production for both repair and maintenance of the cells.

Table 3
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Endpoint Resuscitation Endpoints ______________________________________ Monitored Parameter Supranormal Hypotensive Blood pressure Systolic Mean arterial 90–120 mmHg 80–90 mmHg 80–90 mmHg 60–80 mmHg Central venous pressure 6–8 cm H2O 3–5 cm H2O Heart ratea Dog Cat <140 bpm 160–200 bpm <140 bpm 160–200 bpm Capillary refill time 1–2 sec 1–2 sec Pulse intensity (femoral) Strong Strong Resuscitation technique Dog Cat Large volume Small volume Small volume Small volume Clinical indications SIRS diseases Hypoadrenocorticism Heart failure Closed cavity hemorrhage Ongoing hemorrhage Brain disease Lung edema Oliguric renal failure Lung edema Oliguric renal failure a After appropriate analgesia

There are situations, however, when supranormal resuscitation can be detrimental. Increased vessel wall tension can dislodge a life-saving clot in the vasculature of a traumatized animal, resulting in significant hemorrhage. Brain and lung edema or hemorrhage can be worsened by aggressive and sudden increases in hydrostatic pressure. Hypotensive resuscitation provides endpoints that are at the lower limit of normal (see Fluid Therapy: Endpoint Resuscitation). The goal is to administer the smallest volume of fluids possible to successfully resuscitate the intravascular compartment, while minimizing extravasation of fluids into the interstitium (especially brain or lungs), titrating the amount of preload to minimize excess fluid load to a potentially disabled heart, and reducing the probability of dislodging clots. Small-volume resuscitation techniques should be used to reach hypotensive resuscitation endpoints.

Determination of Appropriate Resuscitation Technique

Dogs in hypovolemic shock that require supranormal endpoint values can benefit from large-volume resuscitation techniques. Typically, an initial infusion of 20–50 mL/kg of balanced isotonic crystalloids is given, followed by 5–15 mL/kg of hetastarch or dextran 70. When stroma-free hemoglobin is selected as the colloid, the dosage is 5 mL/kg. Additional colloids can be administered using small-volume intravascular resuscitation techniques if perfusion has not improved to the desired supranormal endpoints after the initial large volume dose of fluids.

Whole blood products can be administered by large-volume resuscitation techniques in catastrophic hemorrhagic situations. However, initial administration of stroma-free hemoglobin will allow for a slower administration of whole blood and less chance for transfusion reaction from rapid whole blood administration.

Small-volume resuscitation techniques are recommended in the hypovolemic cat and any dog with closed cavity hemorrhage, head injury, pulmonary contusions or edema, cardiogenic shock, or oliguric renal failure. An initial dosage of balanced isotonic crystalloids (10–15 mL/kg for dogs; 5–10 mL/kg for cats) is given. Either hetastarch or dextran 70 is then administered (5 mL/kg in dogs; 2–5 mL/kg in cats) over 1–5 min. The perfusion parameters are reassessed, and the initial bolus dose repeated as needed until the endpoint of resuscitation is reached. When stroma-free hemoglobin is used as the colloid in dogs, the dosage is 2–5 mL/kg. Stroma-free hemoglobin is not approved for use in cats, but it has been used successfully at a dosage of 1–5 mL/cat (0.25–l.0 mL/kg) given slowly over 5 min.

Hypothermia, especially in cats, can significantly limit the cardiovascular response to fluid resuscitation. Active external warming with circulating water blankets should be done once fluid resuscitation has been initiated. Aggressive volume administration without active warming of hypothermic cats can result in pulmonary edema despite continued hypotension.

Last full review/revision March 2012 by Rebecca Kirby, DVM, DACVIM, DACVECC; Andrew Linklater, DVM, DACVECC