In hypovolemic shock, compensatory neuroendocrine responses are initiated to restore blood volume and meet metabolic demands that occur during acutely decreased cardiac output states, increasing ATP demands. When perfusion continues to be compromised despite these mechanisms, cells can no longer generate ATP, compensatory mechanisms become exhausted, and decompensatory shock ensues. An adequate fluid resuscitation plan is necessary to optimize survival.
The fluid resuscitation plan should include the following steps:
Loss of fluid volume from the intravascular fluid compartment is manifested by poor perfusion (shock) and inadequate tissue oxygenation. This volume deficit results in a lower vessel wall tension. Decreased wall tension in the aortic arch and carotid arteries results in decreased stimulation of the baroreceptors. This decreased rate of firing, sent via the glossopharyngeal and vagus nerves to the medulla oblongata, results in decreased inhibition (stimulation) of the sympathetic system. Stimulation of the sympathetic nervous system is manifested by clinical changes in heart rate, pulse intensity, blood pressure, capillary refill time, mucous membrane color, level of consciousness, and rectal temperature. 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 extravascular (interstitial and intracellular) deficits.
Fluid deficit in the interstitial and intracellular 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, retracted eyes, 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 to estimate dehydration are misleading in two common clinical situations. Chronically emaciated and geriatric 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.
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 too large to freely pass across the capillary membrane. Colloids are thought of as intravascular volume replacement solutions, and crystalloids as interstitial volume replacement solutions.
The small-molecular-weight particles in crystalloids are primarily electrolytes and buffers (see Table: Crystalloid Fluid Types). When the sodium concentration of the solution is equivalent to that of the (red blood) 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. More than 75% of the isotonic crystalloid administered IV can move into the extravascular space within 1 hour in a healthy 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 should not be used as resuscitation fluids. Hypertonic solutions (eg, 7% NaCl) contain higher concentrations of sodium and are best used when hydration is normal and concurrently with other fluids.
Crystalloids are considered buffered when they contain molecules (such as acetate, gluconate, and lactate) that are converted to bicarbonate in the liver, equilibrating the pH of the fluid to normal blood pH (7.4). Normal saline (0.9%) is isotonic but not buffered; it is used initially for specific clinical problems, including hyponatremia, hypernatremia, hypercalcemia, hypochloremic metabolic alkalosis, head trauma, and oliguric renal failure.
Crystalloids are considered balanced when they contain electrolytes in addition to Na and Cl (such as K, Mg, Ca), making them similar to plasma. Lactated Ringer's is an example of a balanced solution; normal saline is not balanced.
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 table: Crystalloid Fluid Types). Most clinical problems will benefit from the use of buffered, balanced, isotonic crystalloids (eg, lactated Ringer’s) as part of the resuscitation fluid plan.
When serum sodium measurements 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, which may result in cerebral edema or dehydration (and can lead to intracranial hemorrhage). In these patients, it may be necessary to make a custom solution that has a sodium content that is similar to the patient's during resuscitation phases. In general, sodium concentrations should not be altered by >0.5 mEq/L/hour 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.
Crystalloids are also classified as either replacement or maintenance fluids. Replacement fluids are intended to replace fluids lost from the body (such as through hemorrhage, vomiting, diarrhea, etc) and often contain a sodium concentration near that of plasma (such as lactated Ringer's or 0.9% saline); these fluids result in excessive concentrations of sodium if given over prolonged periods of time (>24–72 hours) or for animals with free water loss; however, they are ideal resuscitation fluids for animals with sodium-rich fluid losses. Maintenance fluids contain significantly less sodium (such as half-strength saline or 5% dextrose in water) and are intended for animals that have free water loss or require prolonged fluid administration. Replacement fluids given to an animal with free water deficits or for prolonged periods of time (without access to water) will result in hypernatremia and hyperosmolarity.
Crystalloid Fluid Types
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%) or other replacement/isotonic fluids. Increased serum sodium values most commonly reflect a loss of solute-free water. The animal should be perfused and hydrated using isotonic saline or other replacement/isotonic fluids. 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 animal has hyposthenuria or head injury.
When serum potassium estimates are normal, a balanced electrolyte solution can be used. Unless severe, 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/hour. This rate may be increased when severe hypokalemia (<2 mEq/L) is associated with catastrophic clinical signs, (eg, respiratory distress/hypoventilation 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, potassium chloride is added to 1 L of balanced isotonic crystalloids administered as maintenance fluids based on serum potassium concentration (see Table: Guideline for Potassium Supplementation in Dogs and Cats). Serum potassium concentration should be monitored closely during continued therapy. Potassium phosphates may be used if a concurrent phosphorus deficiency is present.
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 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. Recent evidence suggests that with hyperkalemia secondary to feline urinary obstruction, any isotonic balanced fluid can be used, with minimal concern for increasing serum potassium as long as the underlying obstruction is treated.
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 or hypertonic saline 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 animal 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 in <1 hour, combining hypertonic saline with a colloid is recommended to offset the interstitial edema resulting from interstitial extravasation.
When colloids are to be administered, it must be decided whether a natural colloid (eg, plasma, albumin, or whole blood) or a synthetic colloid is to be used. When the animal requires RBCs, 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 RBCs, 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 hours. 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 factor antigen and factor VIII coagulant activity, without clinical bleeding. Dextran copolymerizes with the fibrin monomer, destabilizing clot formation. Blood glucose levels may be increased 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. Dextran 70 is being used much less commonly in favor of other colloids, and dextran 40 is not recommended because it is known to cause renal injury.
Hydroxyethyl starch is the parent name of a polymeric molecule made from a waxy species of either corn or potatoes and is composed primarily of amylopectin (98%). HES molecules vary in size from ten thousand to several million daltons (average 70–670 thousand daltons). The disappearance of HES molecules from the body depends primarily on their rate of enzymatic degradation by alpha-amylase and subsequent renal excretion. Other methods of elimination include absorption by tissues (liver, spleen, kidney, and heart), uptake by the reticuloendothelial system, and clearance through bile. Blood alpha-amylase–mediated hydrolysis (primarily at the C6 position) reduces the molecular weight to <72,000 daltons; these smaller particles are more osmotically active but eliminated at a faster rate through the kidney. Metabolism of HES retained in tissue is probably performed by cytoplasmic lysosomes. An increase in serum amylase is to be expected without alteration in pancreatic function.
Along with molecular weight, the degree of molar substitution, which is the number of glucose units on the starch molecule that have been replaced by hydroxyethyl units, is the major determinant of how long the different types of HES survive in the blood. Molar substitution rates vary from 0.35 to 0.7, and the higher the molar substitution, the longer the half-life in blood. The position of the molar substitution also impacts half-life; this can occur at the C2, C3, and C6 positions. Stereotactically, substitution at the C2 site impedes degradation by amylase, prolonging the half-life of HES; this is often referred to as the C2:C6 ratio. Higher ratios imply impeded breakdown and therefore longer half-lives in 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; most hetastarches will expand plasma volume 100%–150%. Intravascular persistence is significantly greater than that of dextran 70, with 38% of hetastarch remaining, compared with 19% of dextran, 24 hours 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. Most HES molecules may persist in the body for 2–7 days.
Hydroxyethyl starches favor retention of intravascular fluid and prevent washout of interstitial proteins. In hypooncotic situations, HES 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 as high as 100 mL/kg in dogs. Many cats have a moderate reaction—nausea and occasional vomiting—with rapid infusion. However, when hetastarch is given slowly (throughout 5–15 minutes), this adverse effect is minimal. Renal injury, reported to occur from an osmotic nephrosis in people, has been poorly documented in dogs and cats, and allergic reactions are rare. Although there has been much controversy and decreased use of HES solutions due to concern for kidney injury, more recent evidence from animal studies does not suggest that kidney injury develops with 7% or lower solutions.
Hetastarch is associated with minor alterations in laboratory coagulation measurements but not with clinical bleeding unless daily minimal dosages (20–50 mL/kg/day, depending on the type) are exceeded. Molecular weight seems to have the biggest impact on coagulation, with larger molecular weight starches impacting coagulation to a greater degree. The proposed mechanisms of impact on coagulation include "coating" platelets or impeded platelet receptor signalling, dilution of coagulation factors, and interference with von Willebrand factor/factor VIII interaction. Dilutional effects on coagulation, cells, and proteins are produced in response to the volume expansion of the plasma. Animals that receive large volumes of HES solutions may have more oozing if surgery is performed, and diligent hemostasis is warranted.
A variety of HES solutions are currently available, each with its own advantages and disadvantages based on its molecular composition.
Synthetic Colloid Fluid Types
Stroma-free hemoglobin , also called hemoglobin-based oxygen carrier (HBOC), is a polymerized bovine hemoglobin-based solution that increases plasma and total hemoglobin concentration. These solutions are not currently available in the USA. These solutions are 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, believed to be through scavenging of nitric oxide, a potent constitutive and inducable vasodilator. The dark hue of the solution causes discoloration of the serum (and sometimes the urine) 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/hour. When given to an animal with 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. HBOC has also been used in cats as infusions (4–25 mL/kg/24 hours) and/or rapid infusions (1–5 mL/cat). Anecdotally, the pressor effects in cats seem pronounced, and blood pressure should be monitored. HBOC has been associated with development of pulmonary edema, pleural effusion, and respiratory distress, particularly in cats with underlying heart disease.
Lyophilized canine albumin is available as a 5% lypophilized solution that can be reconstituted. It has been administered to dogs with septic peritonitis and hypoalbuminemia and has been demonstrated to increase oncotic pressure, measured albumin levels, and Doppler-measured blood pressure, with increased albumin levels persisting for as long as 24 hours. Minimal adverse effects have been noted. Replacement volume in mL of albumin 5% solution (50 mg/mL) can be calculated using the following formula:
body wt (kg) × 90 mL/kg × (target albumin level [eg, 2 mg/dL] - patient's current albumin level) × 0.2 g/dL
It may also be administered as a more concentrated solution (16% or 166 mg/mL) for hypotensive patients, at a dosage of 800 mg/kg throughout 6 hours. Human serum albumin is available as well and has been used with success in critically ill veterinary patients; however, when administered to healthy animals, severe adverse effects, including multiple organ failure, have been noted.
Blood products are important in many situations. Animals that need clotting proteins may require frozen (or fresh frozen) plasma or cryoprecipitate, which contains concentrated amounts of factor VIII and von Willebrand factor; platelet-rich plasma or lyophilized platelets may be necessary for platelet deficiencies. Animals with severe anemia or blood loss may require whole blood or packed red blood cells. Cavitary hemorrhage may allow collection of blood either with centesis or in surgery for autologous blood administration when banked blood is not available.
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, including disruption of the endothelial glycocalyx layer, and result in systemic inflammation response syndrome (SIRS):
other severe GI disease
Hetastarch, blood products, 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 and disruption of the endothelial glycocalyx layer will often 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 to maintain fluid balance.
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, continued losses, 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 increased blood lactate to <2 mmol/dL supports adequate tissue oxygenation. Supplementary endpoints may be used but require additional patient instrumentation: central venous pressure of 5–8 cm H2O, 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 an animal is suspected of having a disease process related to SIRS, such as vasodilation, increased capillary permeability, or depressed cardiac output, resuscitation endpoints are chosen for supranormal resuscitation (see Table: Resuscitation Endpoints). 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.
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, exacerbating 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 Table: Resuscitation Endpoints). 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.
Large- and small-volume techniques are used to reach endpoints discussed above. These doses of fluids should be administered throughout 10–15 minutes as a rapid IV infusion, and then the animal should be reassessed for restoration of normal clinical perfusion parameters and objective measurements of perfusion. Continual reassessment and titration of fluid doses will achieve resuscitation from shock in most cases (while the underlying disease is investigated and therapy instituted). 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 buffered, balanced isotonic crystalloids is given, followed by 5–15 mL/kg of a hydroxyethyl starch solution. 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. Colloids should be added immediately in any animal with proteinaceous fluid losses (SIRS disease, GI fluid losses, etc).
Whole blood products can be administered by large-volume resuscitation techniques in catastrophic hemorrhagic situations. However, initial administration of an HBOC 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 hypovolemic cats 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. A colloid solution can be administered (5 mL/kg in dogs; 2–5 mL/kg in cats) over 5 minutes as well. The perfusion parameters are reassessed, and the initial bolus dose repeated as needed until the resuscitation endpoint is reached. When stroma-free hemoglobin is used as the colloid in dogs, the dosage is 2–5 mL/kg. HBOCs have not been approved for use in cats, but they have been used successfully at a dosage of 1–5 mL/cat (0.25–1 mL/kg) given slowly throughout 5 minutes.
Hypothermia, especially in cats, can significantly limit the cardiovascular response to endogenous sympathetic stimulus (catecholamines) and to fluid resuscitation. Active external warming with circulating water blankets should be done once fluid resuscitation has been initiated. Additional warming techniques such as fluid line warmers, and warm air blowers can be used to warm cats; water bottles can result in burns and should be avoided. Aggressive volume administration without active warming of hypothermic cats can result in pulmonary edema despite continued hypotension.