Chapter 20 Fluid Therapy in Endocrine and Metabolic Disorders
Metabolic disorders such as complicated diabetes mellitus, hypoadrenocorticism, and heatstroke are associated with marked disturbances in fluid homeostasis, electrolyte balance, and acid-base status. Prompt recognition of the complications associated with these and other metabolic disorders is essential for effective management. The dynamic nature of these illnesses during treatment requires the attending clinician to be vigilant in monitoring and to recognize when therapy needs to be altered. An understanding of the pathophysiology of the metabolic abnormalities encountered in each disorder is necessary for proper management.
Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus that results from a combination of factors, including insulin resistance (counter-regulatory hormones), fasting, a lack of insulin, and dehydration in an animal with diabetes mellitus. Dehydration, electrolyte disturbances, and metabolic acidosis are consistent findings in affected patients that must be addressed during treatment. Most animals with DKA have concurrent diseases, including pancreatitis, urinary tract infection, hyperadrenocorticism, neoplasia, hepatic disease, and renal failure. In addition to clinical signs typical of diabetes mellitus, dogs and cats with ketoacidosis frequently exhibit lethargy, anorexia, vomiting, weakness, depression, dehydration, tachypnea, and weight loss. Other clinical signs may be present depending on the underlying illness. A tentative diagnosis is made by documenting ketonuria in a diabetic animal with clinical signs of systemic illness and diabetes mellitus. Many dogs with uncomplicated diabetes mellitus will have ketonuria at the time of initial diagnosis,56 and it is important to distinguish ketosis that does not necessitate the aggressive treatment described below from dogs with true ketoacidosis. The prognosis more often is determined by the nature and severity of the concurrent disease than by the ketoacidotic state.
A combination of events must take place for ketoacidosis to occur. Insulin deficiency, presence of counter-regulatory hormones, fasting, and dehydration combine to create the metabolic aberrations that result in the syndrome of DKA.43 The insulin deficiency may be relative or absolute. The diagnosis of diabetes mellitus is most often made at the time of presentation for DKA, but a minority of dogs and cats are receiving insulin at the time of diagnosis. The concurrent illness present in the majority of cases of DKA is the cause of insulin resistance and contributes to the increase in counter-regulatory hormones.
Hyperglycemia occurs as a result of insulin deficiency, increases in counter-regulatory hormones, and dehydration. Increased hepatic glucose output primarily caused by increased gluconeogenesis appears to be the primary factor causing hyperglycemia.18,43 Gluconeogenic substrates include amino acids derived from proteolysis and decreased protein synthesis, lactate from glycolysis, and glycerol from lipolysis. Increased glucagon and β-adrenergic activation by catecholamines in the face of inadequate insulin stimulate glycolysis and gluconeogenesis. The osmotic diuresis induced by glycosuria contributes to dehydration and subsequent hyperglycemia.18,43 Dehydration also may cause decreased insulin delivery to sensitive tissues such as skeletal muscle and therefore may reduce insulin action. In addition, antagonism of the cellular actions of insulin by growth hormone and cortisol contribute to insulin resistance.
Ketoacids are derived from the increased free fatty acids that are present as a consequence of increased lipolysis. An increase in catecholamines results in activation of hormone-sensitive lipase in adipose tissue, liberating free fatty acids and glycerol.18,43 In the liver, the large quantity of free fatty acids is oxidized to ketone bodies under the influence of glucagon, although cortisol, epinephrine, and growth hormone also play a role in stimulating ketogenesis. Anorexia that is usually present in patients with DKA contributes to the hormonal changes mentioned above and lack of substrate for anabolic functions. Use of ketones is impaired in DKA as well, contributing to their increased concentration. Low serum insulin and elevated serum glucagon concentrations are correlated with increasing serum ketone concentrations in dogs with diabetes mellitus.23
Dehydration is a consistent finding in dogs and cats with DKA.15,17,20,53 It occurs because of osmotic diuresis secondary to glycosuria and ketonuria, and as a result of gastrointestinal losses associated with vomiting and diarrhea. Electrolyte loss also occurs in these patients because of the diuresis and the cation excretion that accompanies ketoacid excretion.43 Insulin deficiency also results in loss of electrolytes because insulin is required for normal sodium, chloride, potassium, and phosphorus reabsorption in tubular epithelial cells. Loss of sodium, potassium, chloride, magnesium, phosphorus, and calcium occur to a substantial degree in DKA. However, the resulting electrolyte abnormalities are reflected variably in plasma concentrations.15,17,20,53 Hyponatremia is reported in 40% to 54% of dogs and 34% to 81% of cats with DKA,15,20,37,45,69 but correction of the serum sodium concentration for hyperglycemia reduces the prevalence of this finding.45 Because glucose has an osmotic effect in the plasma, hyperglycemia results in a shift of water into the intravascular space, diluting the plasma sodium. This effect can be corrected by adding 1.6 mEq/L to the measured sodium concentration for each 100 mg/dL that the plasma glucose exceeds 100 mg/dL.
Loss of ketoacids in urine results in buffering by plasma bicarbonate. Urinary bicarbonate excretion contributes to the metabolic acidosis induced by accumulation of ketoacids.43 Retention of these unmeasured anions results in an increased anion gap. The prognosis of dogs with DKA is negatively affected by a worsening base deficit.37
The goals of fluid therapy in DKA are to restore circulating volume, replace water and sodium deficits, correct electrolyte imbalances, improve tissue delivery of nutrients, and decrease the blood glucose concentration. Initial fluid therapy should improve intravascular volume, reduce secretion of counter-regulatory hormones, and enhance tissue delivery of insulin. It is recommended that insulin administration be delayed for 1 to 2 hours after fluid therapy is instituted, particularly when hyperglycemia is severe, hypotension is present, or clinically relevant hypokalemia exists. Reduction of blood glucose concentration before replacement of intravascular volume could result in loss of water from the intravascular space along with glucose and worsening of hypotension. Severe hyperglycemia and hypotension are likely. A substantial reduction of blood glucose will occur despite a delay in insulin administration because fluid therapy alone reduces insulin resistance, increases insulin availability at peripheral tissues such as skeletal muscle, dilutes the blood glucose, and enhances urinary loss subsequent to an increase in glomerular filtration rate (GFR).76 After initial rehydration, consideration should be given to the decrease in the plasma effective osmolality and thus the plasma volume that occurs after reduction of the blood glucose concentration, necessitating administration of fluids at a higher rate than would be needed in a euglycemic patient. After hydration status has been normalized and blood glucose concentration reduced, additional fluid administration should be based on the calculation of maintenance needs plus ongoing losses from the gastrointestinal tract (e.g., vomiting, diarrhea) and in urine (i.e., polyuria caused by continued glycosuria). Aggressive treatment is not necessary in dogs or cats with ketonuria if metabolic acidosis and signs of systemic illness are not present. The presence of a concurrent disease, present in most dogs and cats with DKA, may necessitate modification of the fluid therapy plan.
Because of the marked deficits of water and sodium present in animals with DKA, 0.9% saline is the fluid of choice for initial management. Administration of an isotonic solution allows for rapid expansion of intravascular volume in patients with severe dehydration or hypovolemic shock.
Serum osmolality usually is high in animals with DKA, often moderately to markedly so. The median measured osmolality in 23 cats with DKA was 353 mOsm/kg (reference range, 280 to 300 mOsm/Kg), and the median calculated osmolality in 19 other cats was 333 mOsm/kg.15 An increase in the calculated osmolality was confirmed in another recent study of 13 cats with DKA.45 The hyperosmolality is attributable primarily to hyperglycemia, azotemia, and ketone bodies. Because treatment rapidly resolves these abnormalities, the osmolality would be expected to decrease predictably without the use of hypotonic solutions. Cerebral edema has been documented in humans, particularly children during treatment of DKA. Clinical signs of cerebral edema are rare despite its common occurrence.46 Rapid reduction in plasma osmolality is a major factor in development of cerebral edema. Cerebral edema is caused in part by the accumulation of idiogenic osmoles in the central nervous system (CNS) secondary to chronic hyperosmolality.25 Idiogenic osmoles are produced in response to plasma hyperosmolality, and they increase the osmolality of the brain to prevent cerebral dehydration. If the plasma osmolality decreases quickly, the idiogenic osmoles will persist and cause water accumulation in the cerebrum because of the difference in osmolality between the brain and plasma. Because of this, administration of hypotonic fluids such as 0.45% saline is discouraged during initial treatment.18,43 The importance of this pathophysiology in dogs and cats is unknown and cerebral edema occurring during treatment has not been reported, but it seems prudent to avoid rapid reduction in plasma osmolality during treatment of DKA. Serum tonicity, calculated from corrected serum sodium and glucose concentrations, did not change significantly during treatment of diabetic ketosis in cats despite a decrease in serum glucose concentration.45 This is because serum sodium concentration increased in most cats, and sodium contributes considerably more to plasma tonicity and osmolality than glucose. Attention to replacement of sodium deficits will offset reduction in plasma osmolality that occurs when the blood glucose and ketoacid concentrations decrease in initial management of patients with DKA.73 Although 0.45% saline approximates the composition of electrolytes lost as a result of osmotic diuresis and has been recommended for administration after rehydration, the author rarely uses it for treatment of DKA. However, if hypernatremia is noted during ongoing treatment and rehydration, one could consider administration of 0.45% NaCl.
Once the blood glucose concentration decreases to less than 250 mg/dL, 50% dextrose should be added to the 0.9% saline to make a 2.5% to 5% dextrose solution.17,52,53 Adjustments in the dextrose content of the fluids should be made based on Table 20-1. The addition of dextrose will prevent hypoglycemia and allow for continued insulin administration to stop ketoacid formation.
Table 20-1 Adjustment in Insulin and Dextrose Administration Using the Continuous Low-Dose Intravenous Insulin Infusion Protocol
| Blood Glucose Concentration (mg/dL) | Intravenous Fluid Solution | Rate of Intravenous Insulin Solution (mL/hr)* |
|---|---|---|
| *250 | 0.9% saline | 10 |
| 200-250 | 0.9% saline, 2.5% dextrose | 7 |
| 150-200 | 0.9% saline, 2.5% dextrose | 5 |
| 100-150 | 0.9% saline, 5% dextrose | 5 |
| <100 | 0.9% saline, 5% dextrose | Stop insulin infusion |
* Intravenous insulin solution contains 2.2 U/kg (dog) or 1.1 U/kg (cat) of regular insulin in 250 mL of 0.9% saline.
Adapted from Macintire DK. Treatment of diabetic ketoacidosis in dogs by continuous low-dose intravenous infusion of insulin. J Am Vet Med Assoc 1993;202:1266–1272.
The primary goal of initial fluid therapy is to restore intravascular fluid volume to improve tissue perfusion, including GFR. Fluids should be administered at a rate sufficient to replace volume deficits in 12 to 24 hours, with 50% of the estimated deficit replaced in the first 4 to 6 hours. An estimated volume of fluid to account for ongoing losses should be added to the maintenance and replacement fluid volume, with special consideration of urine output in the presence of polyuria. Fluids should be administered cautiously to animals with impaired cardiac function or the potential for oliguric renal failure. Monitoring should consist of estimates or quantitation of urine output, serial body weights, packed cell volume, total solids, and serum concentrations of creatinine, electrolytes, and glucose. Urine output should be evident within 2 to 4 hours of initiating fluid therapy unless oliguric renal failure is present.
Intravenous fluid therapy will decrease the blood glucose concentration and reduce lactic acidosis, but insulin administration is required to halt ketogenesis, increase ketone body use, decrease gluconeogenesis, promote glucose use, and decrease proteolysis.18,43 Ketogenesis will be decreased by an insulin concentration 50% less than that required for promotion of peripheral use of glucose, and consequently ketoacid formation is decreased rapidly after insulin administration. For insulin to be most effective, tissue perfusion must be restored, so intravenous fluid therapy should be instituted first. Insulin sensitivity is increased by a reduction in hyperosmolality and decreased concentrations of counter-regulatory hormones that is accomplished by fluid administration. An additional important effect of insulin is its action on electrolyte transport and resolution of acidosis that cause a transcellular shift of potassium into cells, causing hypokalemia. In patients with serum potassium concentrations less than 3.5 mEq/L, insulin administration ideally should be delayed until potassium supplementation has successfully increased the serum potassium concentration above this limit to avoid worsening of hypokalemia. In addition, hypotensive animals should receive fluid therapy sufficient to stabilize the circulatory status before insulin administration to prevent the decrease in plasma volume that occurs when glucose and water are translocated into cells in response to insulin.
Administration of small doses of regular insulin has a clear advantage over large doses because the smaller doses are less likely to cause severe hypokalemia or hypoglycemia.42 In addition, if the reduction in the blood glucose concentration is too rapid, the associated decrease in osmolality has the potential to contribute to development of cerebral edema. Two methods of delivering low-dose insulin therapy to dogs have been described: the low-dose intramuscular technique and the continuous low-dose intravenous infusion.17,53 With either technique, regular insulin is administered with a desired effect of decreasing the blood glucose by not more than 50 to 75 mg/dL/hr. Similar treatment has been used in cats with DKA.52
The low-dose intramuscular insulin protocol is an effective and straightforward, but somewhat time-consuming, method for insulin administration in DKA.17 Intramuscular administration is recommended because absorption from subcutaneous sites may be reduced or inconsistent in the presence of dehydration. However, absorption is similar from the two administration sites in humans with DKA.30 Regular insulin is the only product that has been reported to be used in dogs. Recently, subcutaneous administration of the insulin analogs insulin lispro and insulin aspart, have been shown to be as effective as intravenous regular insulin in humans with uncomplicated DKA.74,75 These analogs have a more rapid onset of action (10 to 20 minutes) compared with regular insulin (1 to 2 hours) and a shorter duration of effect. Any advantages over the use of regular insulin in veterinary medicine await investigation. In dogs the initial dose of regular insulin is 0.2 U/kg intramuscularly, followed by hourly measurement of blood glucose concentrations.17 Subsequent insulin administration continues hourly at 0.1 U/kg intramuscularly until the blood glucose concentration is 250 mg/dL or less. Dogs weighing less than 10 kg are given 2 U and cats are given 1 U initially, followed by 1 U every hour unless diluted insulin is available.17 If the blood glucose concentration decreases by more than 100 mg/dL/hr, the dosage is decreased. Once the blood glucose concentration is less than 250 mg/dL, the hourly insulin injections are stopped, and 50% dextrose is added to the intravenous fluid solution in a quantity sufficient to make a 5% dextrose solution. Additional doses of regular insulin are administered every 4 to 6 hours at 0.1 to 0.4 U/kg subcutaneously with the dosage and dosing interval determined by measurement of blood glucose concentration every 1 to 2 hours to maintain blood glucose concentration between 200 and 300 mg/dL. The primary disadvantage of the low-dose intramuscular protocol is that it requires considerable technical effort to accomplish hourly injections and blood glucose measurements. In addition, the decrease in blood glucose concentration seems to occur more rapidly and less predictably than with the continuous intravenous infusion method.
The continuous low-dose intravenous infusion protocol involves administration of regular insulin diluted in normal saline using an intravenous infusion pump.53 It is my preferred technique of insulin administration to dogs with DKA because of the predictable and consistent response, the gradual decrease in blood glucose concentration (mean of 28 mg/dL/hr in dogs), and the ease of use.53 Unlike the low-dose intramuscular protocol, treatment is not dependent on hourly injections, and the decrease in blood glucose concentration is more gradual using the intravenous protocol. An insulin solution is made by adding regular insulin at 2.2 U/kg for dogs and 1.1 U/kg for cats to 250 mL 0.9% saline.52,53 This solution is administered as a constant-rate infusion at 10 mL/hr to deliver a dosage of 0.09 U/kg/hr in dogs and 0.045 U/kg/hr in cats. Because insulin may adhere to plastic in the administration set, it is recommended that 50 mL of the insulin solution be allowed to flow through the administration set before use. During insulin administration, intravenous fluid therapy with 0.9% saline is continued through a separate line as indicated for rehydration and maintenance needs. Blood glucose concentration is measured every 60 to 90 minutes. When the blood glucose is less than 250 mg/dL, the infusion rate is decreased according to Table 20-1, and dextrose is added to the hydration fluids to a final concentration of 2.5% to 5% (see Table 20-1).53 The primary disadvantage of the continuous low-dose intravenous infusion protocol is the need for an infusion pump and the time required to monitor blood glucose serially.
The high-dose intramuscular or subcutaneous insulin protocol is the simplest for management of DKA, requiring the least amount of monitoring and equipment.12 However, it has some shortcomings, including a rapid decrease in blood glucose concentration that predisposes to hypoglycemia, a greater magnitude of hypokalemia, and a substantial decrease in osmolality over a short period. It is for these reasons that this technique is no longer used in humans and is considered less desirable for use in dogs and cats. Regular insulin is administered at 0.25 U/kg every 4 hours intramuscularly until the patient is rehydrated, followed by subcutaneous administration every 6 to 8 hours.12 The dosage and frequency of insulin administration are based on monitoring blood glucose concentration hourly, with a goal of decreasing the glucose concentration by approximately 50 mg/dL/hr. Once the glucose concentration is near 250 mg/dL, dextrose is added to the intravenous saline solution to a final concentration of 5%, and the subsequent insulin dosage is decreased by 25% to 50%.
Regardless of the initial insulin administration protocol used, intermediate or long-acting insulin treatment can be instituted when the animal is eating normally.
Regardless of the serum potassium concentration, almost all patients with DKA have a deficit of total body potassium.18,43 Before treatment, hypokalemia is found in approximately 30% to 45% of dogs and 55% to 67% of cats, whereas hyperkalemia is found in less than 10% of cases.* Hypokalemia occurs because of urinary potassium losses caused by osmotic diuresis, deficient renal tubular potassium absorption caused by insulin deficiency, and excretion with ketoacids, as well as through gastrointestinal losses from vomiting and diarrhea. Treatment of DKA rapidly lowers plasma potassium concentration because correction of acidosis causes a transcellular shift of potassium into cells, insulin enhances transport of potassium into cells, and intravenous fluid administration causes diuresis and dilution of plasma potassium. Hypokalemia is present at sometime during hospitalization in over 90% of cases.15,37 Hypokalemia can cause muscle weakness, arrhythmias, and impaired renal function.
Potassium should be supplemented in virtually all animals with DKA, but the initial dose rate is dependent on the pretreatment serum potassium concentration. If the serum potassium concentration is above the reference range, intravenous fluids should be administered without the addition of potassium for 2 hours, at which time the serum potassium concentration should be rechecked if possible. If the serum potassium concentration has decreased into the normal range, supplementation is given according to Table 20-2. The dose rate of KCl should not exceed 0.5 mEq/kg/hr because of the risk of cardiac arrhythmia. If a serum potassium measurement is not available after initial treatment and urine output appears adequate, 30 to 40 mEq KCl should be added to each liter of fluids. Urine production should be monitored closely to ensure that oliguric renal failure is not present. In humans with hypokalemia before treatment, it is recommended that insulin administration be delayed until the serum potassium concentration can be increased into the normal range because the potassium concentration will decrease during insulin administration.43 A similar recommendation is made for veterinary patients with substantial hypokalemia (<3.5 mEq/L). Serum potassium concentration should be monitored 4 hours after initiating potassium supplementation and at least every 8 to 12 hours thereafter, with dosage adjustments to maintain normokalemia (see Table 20-2).
Table 20-2 Potassium Supplementation in Intravenous Fluids
| Serum Potassium Concentration (mEq/L) | Potassium Supplement (mEq) in 1 L Intravenous Fluid |
|---|---|
| >3.5 | 20 |
| 3.0-3.5 | 30 |
| 2.5-3.0 | 40 |
| 2.0-2.5 | 60 |
| <2.0 | 80 |
Similar to potassium, phosphate is deficient in animals with DKA regardless of the serum phosphorus concentration. Phosphorus is lost in patients with DKA because of a shift from the intracellular to the extracellular compartment secondary to hyperosmolality that is followed by urinary loss, decreased cellular uptake caused by insulin deficiency, inhibition of renal tubular phosphate absorption caused by acidosis, and osmotic diuresis.33,43 During treatment of DKA, the reduction in osmolality and insulin administration result in translocation of phosphate into the cell from the extracellular compartment. This translocation frequently causes a marked decrease in the plasma phosphorus concentration. However, clinically important consequences of hypophosphatemia are noted only when the serum phosphorus concentration is less than 1.0 to 1.5 mg/dL, and these signs are observed inconsistently. Hemolysis, muscle weakness, seizures, depression, and decreased leukocyte and platelet function leading to infection and bleeding can result from hypophosphatemia. The only abnormalities documented as caused by hypophosphatemia in veterinary DKA patients are hemolytic anemia in cats and possibly stupor and seizures in a dog.1,15,77 Hemolysis can occur despite phosphate supplementation and may have causes other than hypophosphatemia including oxidative injury.15,19 Hypophosphatemia is present at initial evaluation in 13% to 48% of cats and in 29% of dogs with DKA.15,20,37 Careful monitoring of serum phosphorus concentration during the initial 24 to 48 hours of management is important to identify severe hypophosphatemia necessitating phosphorus supplementation.
Treatment of hypophosphatemia is indicated when the serum phosphorus concentration before treatment is less than 1.5 mg/dL or if the serum phosphorus concentration is less than 1.0 mg/dL in the dog and less than 1.5 mg/dL in the cat at any time. Potassium phosphate typically is the treatment of choice because potassium supplementation is also necessary in most cases, but sodium phosphate is also available for use. Potassium phosphate is available as a solution containing 3 mmol/mL of phosphorus (99 mg/dL) and 4.36 mEq/mL of potassium. Excessive phosphate supplementation can cause hypocalcemia, hyperphosphatemia, tetany, soft tissue mineralization, and renal failure.29,33 Because phosphate deficits vary widely and are not necessarily reflected by serum phosphorus concentrations, phosphate administration should be guided by repeated serum phosphorus measurements during treatment. Potassium phosphate should be administered by constant-rate infusion at an initial dosage of 0.01 to 0.06 mmol/kg/hr. Higher infusion rates can be administered as necessary. Monitoring should consist of measurement of serum potassium, phosphorus, and calcium concentrations every 8 to 12 hours during phosphate administration. Hyperphosphatemia, clinically relevant hypocalcemia, and hyperkalemia are indications to discontinue phosphate administration. Treatment also should be discontinued when the serum phosphorus concentration is normal and the animal is eating. Some have suggested that potassium phosphate be routinely administered to animals with DKA regardless of the initial serum phosphorus concentration, but there is no evidence in veterinary or human medicine that such treatment is beneficial.29
Magnesium deficiency is present in some cats with DKA as reflected by measurement of ionized magnesium concentrations.60 However, total magnesium concentrations were high in many of the same cats, and the widely available total magnesium concentration is unlikely to reflect active plasma magnesium status.60 Because clinical signs such as arrhythmia, weakness, seizures, and refractory hypocalcemia and hypokalemia have not been documented to result from hypomagnesemia in dogs or cats with DKA, magnesium supplementation is not recommended.
The acidosis of DKA typically is a high anion gap acidosis, although hyperchloremic acidosis also can be present at presentation. The unmeasured anions are ketoacids that act as precursors of bicarbonate during treatment with insulin because insulin enhances use of ketones and inhibits further production of ketoacids by decreasing lipolysis.18,43 Because of this, the acidosis associated with DKA does not usually need to be treated with bicarbonate, although animals with severe acidosis may benefit from treatment. Studies in humans have not shown a beneficial effect of bicarbonate administration in DKA.35,57 However, few patients with severe acidosis have been studied, and it is currently recommended to administer bicarbonate to individuals with a blood pH less than 7.0, particularly if the pH does not improve after the first hour of intravenous fluid administration.43 Humans with hyperchloremic metabolic acidosis have a slower recovery from acidosis compared with those with a high anion gap, probably because they have relatively less ketoacid to convert to bicarbonate. Therefore patients that have hyperchloremic metabolic acidosis may be more likely to benefit from bicarbonate administration.4 Potential complications of bicarbonate administration in animals with ketoacidosis include impaired ketone use, paradoxical intracellular or CNS acidosis, and contribution to cerebral edema. The most common detrimental effect of bicarbonate is likely to be worsening of hypokalemia because concurrent intravenous fluid therapy and insulin administration cause a decrease in serum potassium concentration.
Recommendations for bicarbonate therapy are to administer a conservative dose when acidosis is severe. If the blood pH is less than 7.0 or the plasma bicarbonate concentration is less than 8 mEq/L, bicarbonate treatment should be instituted. The bicarbonate deficit in milliequivalents can be estimated by the following formula: 0.3 × body weight (kg) × (24 − patient bicarbonate). One fourth to one half of this dose is administered over 2 to 4 hours. Blood gases should be measured after completion of bicarbonate administration with additional bicarbonate administered if the blood pH remains less than 7.2 or the plasma bicarbonate concentration is less than 12 mEq/L. If blood gases are not available, bicarbonate should not be administered.
Formerly named hyperglycemic hyperosmolar nonketotic coma, hyperglycemic hyperosmolar state (HHS) is defined as diabetes mellitus with a blood glucose concentration greater than 600 mg/dL and serum osmolality more than 350 mOsm/kg in the absence of ketonuria.26,44 In humans, acidosis is mild if present, but acidosis may be more common in dogs and cats with HHS.43,44 The pathogenesis of this syndrome is similar to that of ketoacidosis, but it is thought that plasma insulin concentrations are higher in HHS than in DKA.43 This difference results in insulin activity sufficient to prevent ketosis but inadequate to prevent hyperglycemia. Reductions in secretion or activity of growth hormone, glucagon, or both also may play a role in development of HHS. Loss of water in urine and decreased water intake cause dehydration with subsequent decreased renal perfusion and resultant retention of glucose. The stress of concurrent illness that usually is present results in increased counter-regulatory hormones, which contribute to further increases in blood glucose concentration.
Clinical signs are related to diabetes mellitus, concurrent disease, and hyperosmolality. Dehydration, hypothermia, and abnormalities of mentation ranging from depression to stupor or coma are common.44 Other neurologic signs include weakness, abnormal pupillary light reflexes, cranial nerve deficits, and seizures. Neurologic signs likely result from intracellular dehydration of the brain secondary to hyperosmolality. Typical laboratory abnormalities include severe hyperglycemia, azotemia, hyperphosphatemia, and hypochloremia.44 Concurrent diseases, including renal failure, congestive heart failure, and various infections, are common in cats with HHS, while little information on the syndrome is available in dogs.44
Management of HHS is similar to management of DKA. Osmolality should be reduced gradually to prevent cerebral edema. Because volume depletion is integral to the pathology of HHS, restoration of circulating volume is critical to early, successful management. The goals of fluid therapy initially are to restore circulating volume and then to completely replace the estimated fluid deficits plus maintenance requirements over 36 to 48 hours. Blood glucose concentration is expected to decrease as a result of increased renal perfusion and increased urine glucose excretion, as well as increased perfusion of other tissues, causing enhanced cellular glucose uptake. Administration of 0.9% NaCl is indicated for the initial 4 to 6 hours of treatment. Subsequent intravenous fluids should be either 0.9% or 0.45% saline. The composition of urine electrolyte losses closely resembles 0.45% saline, but sodium deficits typically are present in these patients. Because renal function often is impaired in patients with HHS, caution should be used when considering the appropriate potassium and phosphate supplementation, and supplementation should be based on serial measurements of serum electrolyte concentrations.
It is recommended that insulin administration be withheld until intravascular volume has been restored because intracellular movement of glucose and water from the extracellular space could cause a further decrease in intravascular volume resulting in shock. Therefore insulin administration should be delayed until fluid therapy has successfully replenished vascular volume. Insulin should be administered in a manner similar to that recommended for DKA, but additional caution is warranted to ensure that a rapid decrease in blood glucose concentration does not occur. Frequent monitoring of electrolytes and appropriate supplementation is necessary, as is the case for patients with DKA.
Hypoadrenocorticism (Addison’s disease) usually is the result of destruction of the adrenal cortex, resulting in deficiencies of both glucocorticoids and mineralocorticoids. Less frequently, glucocorticoid deficiency occurs alone, resulting in a more vague presentation without the typical electrolyte abnormalities. Clinical signs vary considerably, and dogs with chronic illness have nonspecific clinical signs, whereas those with acute manifestations may have a life-threatening hypotensive crisis and severe hyperkalemia.27,55,62 Prompt, appropriate treatment of this life-threatening illness should include correction of the volume depletion, hyperkalemia, hyponatremia, and glucocorticoid deficiency.
Hypoadrenocorticism typically results in combined mineralocorticoid and glucocorticoid deficiency. Aldosterone, the primary mineralocorticoid secreted by the adrenal cortex, enhances reabsorption of sodium and water, and excretion of potassium and hydrogen ions by the connecting segment and cortical collecting ducts of the kidneys. Aldosterone deficiency causes loss of sodium and water in urine, resulting in hyponatremia and dehydration, as well as retention of potassium and hydrogen ions, resulting in hyperkalemia and metabolic acidosis. Gastrointestinal losses caused by vomiting and diarrhea may contribute to worsening dehydration, hyponatremia, and hypochloremia. Glucocorticoids are necessary for normal vascular tone, endothelial function, vascular permeability, water distribution, and the vasoconstrictive response to catecholamines.48 Decreased cardiac contractility and vascular tone secondary to glucocorticoid deficiency can result in hypotension. In addition, cortisol enhances gluconeogenesis and glycogenolysis and modulates cytokine production and leukocyte response during inflammation. Cortisol deficiency is associated with hypotension, gastrointestinal signs (vomiting, diarrhea, melena), hypoglycemia, and an impaired response to stress.
Primary hypoadrenocorticism accounts for the majority of cases, with the cause presumed to be immune-mediated adrenalitis in most instances. The resultant mineralocorticoid and glucocorticoid deficiencies result in the typical clinicopathologic picture. Glucocorticoid deficiency alone occurs infrequently and may be primary in origin (caused by loss of the zona fasciculata and zona reticularis) or secondary to adrenocorticotropic hormone (ACTH) deficiency. Primary and secondary “atypical” hypoadrenocorticism can be distinguished by measurement of plasma ACTH concentration, which is high in primary hypoadrenocorticism and low to undetectable in secondary hypoadrenocorticism. Iatrogenic hypoadrenocorticism secondary to treatment of hyperadrenocorticism with mitotane or trilostane is also relatively common, and can result in cortisol deficiency with or without concurrent mineralocorticoid deficiency.
Dogs with chronic hypoadrenocorticism or atypical disease usually are evaluated because of lethargy, vomiting, anorexia or inappetence, weight loss, weakness, polyuria, polydipsia, and regurgitation, occasionally with a waxing and waning course.27,55,62 Findings on physical examination are nonspecific and include lethargy, generalized weakness, dehydration, poor body condition, and melena. Dogs with an addisonian crisis have a shorter history of weakness, lethargy, collapse, and gastrointestinal signs, such as vomiting and melena.27,55,62 Physical examination abnormalities include dehydration, weakness, hypothermia, weak pulses, bradycardia, prolonged capillary refill time, and melena. Bradycardia or low-normal heart rate in an animal with evidence of dehydration or shock should prompt the veterinarian to consider hypoadrenocorticism and other diseases causing hyperkalemia. An electrocardiogram often is the most expedient method for confirming the presence of hyperkalemia. Severe hypotension and shock are caused by volume depletion, decreased vascular tone, and decreased cardiac output secondary to the inappropriately slow heart rate.
Laboratory tests provide important information that will lead the clinician to test specifically for hypoadrenocorticism. A mild to moderate nonregenerative anemia is common but frequently is masked by dehydration. Lack of a stress leukogram in an ill dog with normal numbers of lymphocytes and eosinophils is consistent with an absence of glucocorticoid activity and provides evidence for hypoadrenocorticism.27,55,62 The majority of dogs with hypoadrenocorticism have hyperkalemia, hyponatremia, and hypochloremia.3,27,55,62 However, other causes of low sodium/potassium ratios exist, including oliguric renal failure, urinary tract obstruction, uroabdomen, severe gastrointestinal diseases including trichuriasis, pancreatitis, DKA, pleural effusion, hepatic diseases, and congestive heart failure.34,59,68 Moderate to severe increases in BUN, creatinine, and phosphorus concentrations are common and usually are the result of decreased renal blood flow caused by hypovolemia and hypotension. Urine specific gravity usually is less than 1.030 because hyponatremia results in the loss of the renal medullary concentration gradient. Hypoglycemia occurs in approximately 33% of cases and may be of sufficient severity to result in clinical signs including weakness, ataxia, and seizures.27,55,62 Hypercalcemia also occurs in 30% to 50% of cases.2,27,55,62 Hypoalbuminemia, mild increases in liver enzymes, and hypocholesterolemia are present in some cases. Dogs with isolated glucocorticoid deficiency have similar hematologic changes, although anemia may be more severe. Serum electrolyte concentrations are normal and azotemia is mild and less frequent in atypical hypoadrenocorticism than in dogs with concurrent mineralocorticoid deficiency.50,69,72 Dogs with atypical hypoadrenocorticism frequently have hypocholesterolemia, hypoalbuminemia, and hypoglycemia.50,69,72 Hypoadrenocorticism is rare in cats, but affected animals have clinical signs and laboratory abnormalities similar to dogs.
Only by demonstration of subnormal concentrations of plasma cortisol after ACTH administration can diagnosis of hypoadrenocorticism be made. However, a basal cortisol concentration greater than 2 µg/dL indicates that a diagnosis of hypoadrenocorticism is very unlikely.49 Testing should be performed before administration of a glucocorticoid or, if deemed necessary, dexamethasone should be used because most other corticosteroids will be detected by the cortisol assay. Blood samples are collected before and 1 hour after intravenous administration of cosyntropin (5 µg/kg; 250 µg maximum) or before and 2 hours after intramuscular administration of ACTH gel (2.2 U/kg; 40 U maximum).27 The serum cortisol response to ACTH gels that have been prepared by compounding pharmacies varies in its peak, and samples should be obtained 1 and 2 hours after administration if using one of these compounds.40 Cortisol concentrations are very low in dogs with primary hypoadrenocorticism, with the post-ACTH cortisol concentration typically below the normal resting range.27,55,62,70 Recent administration of a glucocorticoid can suppress the pituitary-adrenal axis and decrease the post-ACTH cortisol concentration; therefore a careful history about systemic or topical corticosteroid use should be obtained. Serum aldosterone concentration can be measured during the ACTH response test if recent corticosteroid administration is likely to suppress the cortisol response.
The goals of initial treatment of hypoadrenocorticism are to resolve hypotension, replace the volume deficit, decrease the plasma potassium concentration, correct other electrolyte abnormalities, and resolve the metabolic acidosis. These goals are most rapidly and effectively achieved by appropriate intravenous fluid therapy. Correction of hypoglycemia and replacement of glucocorticoids and mineralocorticoids also are important considerations during the initial management of hypoadrenocorticism.
Fluid therapy should rapidly increase intravascular fluid volume, replace fluid deficits, and decrease the serum potassium concentration. Deficits of water, sodium, and chloride in the animal with an addisonian crisis are large, and the magnitude of volume depletion usually is greater than estimated on physical examination. Many dogs present in hypovolemic shock and require immediate resuscitation.
Because of the deficits of sodium and chloride, as well as the hyperkalemia that is found in hypoadrenocorticism, 0.9% NaCl is the most appropriate fluid for initial treatment. If normal saline is not available, lactated Ringer’s or similar replacement solutions can be used despite the presence of 4 mEq/L of potassium.
Administration of a bolus of NaCl will not only be effective for treatment of hypovolemia but also will reduce hyperkalemia and metabolic acidosis and subsequently increase heart rate, cardiac output, and blood pressure. Initially, fluids should be given at a rate of 40 to 80 mL/kg/hr for the first 1 to 2 hours depending on the severity of hypotension and hyperkalemia.27 Once an adequate response to the initial fluid therapy is observed, the fluid rate can be decreased to two to three times maintenance, based on the estimated fluid deficit and ongoing losses. It is crucial to note urine output to ensure that oliguric renal failure is not present as a primary condition (rather than hypoadrenocorticism) or has occurred because of inadequate renal perfusion secondary to hypoadrenocorticism. Inadequate urine output may be the result of continued volume depletion caused by inadequate fluid therapy or ongoing losses, or as the result of oliguric renal failure. If urine output appears inadequate, placement of a urinary catheter is indicated to document oliguria and institute treatment for acute renal failure if present. Rapid improvement is generally seen in dogs treated appropriately, but the clinical response in cats occurs more slowly and may require several days before substantial improvement occurs.
A rapid increase in serum sodium concentration and osmolality in the patient with hyponatremia and hypoosmolality may be associated with dehydration of the brain and neurologic signs caused by myelinolysis. This complication is more likely to occur with chronic hyponatremia than with that of 24 hours’ duration or less. Myelinolysis appears to be rare during treatment of dogs with hypoadrenocorticism.10,54 However, in animals with severe hyponatremia, this potential complication should be considered and treatment adjusted so that the serum sodium concentration increases by not more than 0.5 to 0.75 mEq/L/hr.
Hypoglycemia should be treated with an initial bolus of 0.5 to 1 mL/kg 50% dextrose if clinical signs are present. If signs are not present and hypoglycemia is mild to moderate, sufficient 50% dextrose to make a 5% solution should be added to the normal saline.
Glucocorticoids should be administered after fluid therapy has corrected the severe hypovolemia. Because appropriate intravenous fluid administration alone is very effective in resolving the most serious manifestations of the hypoadrenocortical crisis, glucocorticoid treatment can be delayed for several hours if necessary. Unless dexamethasone is administered, glucocorticoid treatment should be delayed until the ACTH response test is completed because other glucocorticoids will interfere with the cortisol assay. A rapid-acting glucocorticoid should be administered intravenously. Hydrocortisone sodium succinate or phosphate (cortisol) probably is the best initial glucocorticoid treatment, primarily because it has mineralocorticoid activity as well. Hydrocortisone should be administered as a constant-rate infusion of 0.3 mg/kg/hr or as an initial intravenous bolus (given over 5 minutes) of 5 mg/kg followed by 1 mg/kg every 6 hours.27,47 Alternatively, dexamethasone sodium phosphate (0.1 to 0.2 mg/kg intravenously) or prednisolone sodium succinate (1 to 2 mg/kg intravenously) can be administered if hydrocortisone is not available.65,70 There is no evidence that the higher doses of dexamethasone commonly recommended are beneficial and could contribute to gastrointestinal bleeding and other deleterious effects. Subsequent treatment should consist of subcutaneous administration of dexamethasone every 12 hours or prednisolone every 6 hours until oral treatment with prednisone (0.4 to 0.6 mg/kg daily) can be tolerated. The oral prednisone dosage should be reduced over 7 to 10 days to a maintenance dose of approximately 0.2 mg/kg daily and then adjusted as necessary to control clinical signs. The glucocorticoid dosage should be increased if stress or illness occurs in a dog with hypoadrenocorticism.
Because electrolyte abnormalities are rapidly corrected with intravenous administration of normal saline, and a short-acting injectable mineralocorticoid preparation is not available, specific mineralocorticoid treatment generally is delayed until oral fludrocortisone (0.01 mg/kg twice daily) can be administered.27,41,70 Hydrocortisone has some mineralocorticoid activity and for this reason is the preferred glucocorticoid replacement. Administration of the long-acting injectable mineralocorticoid desoxycorticosterone pivalate (DOCP) should be reserved for use once a definitive diagnosis has been made, although it reportedly can be safely administered to dogs with normal adrenocortical function.27 Serum electrolyte concentrations should be monitored and dosage adjustments of mineralocorticoids made as appropriate.41,51
Rarely is specific treatment of hyperkalemia indicated because appropriate fluid therapy rapidly corrects this electrolyte abnormality by dilution of plasma, increasing urine output, and shift of potassium into cells during correction of acidosis. Indications for more aggressive treatment of hyperkalemia are severe bradyarrhythmia or failure to respond to initial appropriate fluid therapy. Sodium bicarbonate administration will correct acidosis and decrease serum potassium concentration. The bicarbonate deficit can be calculated as described in the section on DKA, and 25% of the deficit should be administered. Alternatively, 1 to 2 mEq/kg of sodium bicarbonate can be administered slowly intravenously. Another effective method to rapidly decrease the plasma potassium concentration is administration of regular insulin (0.2 U/kg intravenously) with concurrent administration of 1 g dextrose per unit of insulin as an intravenous bolus and 1 to 2 g dextrose per unit of insulin added to the volume of intravenous fluids to be administered during a 6-hour period.61 Blood glucose concentrations should be monitored hourly if insulin is administered. The most rapid protection against the cardiac effects of hyperkalemia is accomplished by administration of calcium gluconate (2 to 10 mL or 0.5 ml/kg intravenously over 10 minutes with electrocardiographic monitoring).70 Calcium does not alter serum potassium concentration; rather, it temporarily counteracts the impairment of myocardial membrane excitability induced by hyperkalemia, allowing time for other treatments to decrease the serum potassium concentration.
Metabolic acidosis associated with hypoadrenocorticism, present in about 60% of dogs, usually is mild to moderate, with the total CO2 14 mEq/L or more in at least 75% of cases.3,62 The acidosis usually is corrected by fluid therapy alone. If acidosis is severe (pH <7.1 or bicarbonate <10 mEq/L), sodium bicarbonate may be provided by administering 50% of the calculated bicarbonate deficit over 2 to 4 hours. The need for additional bicarbonate treatment is determined by repeated blood gas analysis, with a bicarbonate less than 12 and pH less than 7.2 being indications for further therapy. If acidosis is persistent, concurrent disorders such as renal failure should be considered.
Hypoglycemia is a common metabolic abnormality with a variety of causes, including neonatal hypoglycemia, juvenile hypoglycemia, xylitol toxicity, starvation, hepatic insufficiency, hypoadrenocorticism, insulin overdose, sepsis, insulinoma, non-islet cell tumors, glycogen storage disease, pregnancy, hunting dog hypoglycemia, and an error in sample handling or analysis.61 When severe, clinical signs including weakness, seizures, ataxia, collapse, stupor, and muscle tremors commonly are observed.
Animals in the home environment with mild clinical signs can be fed a normal meal if willing to eat or can be administered a sugar solution orally. During a hypoglycemic crisis in the hospital, intravenous administration of 0.5 to 1 mL/kg of 50% dextrose given to effect is recommended.61 It is preferable to dilute the dextrose to a 25% or less concentrated solution to prevent phlebitis that may occur with 50% dextrose. This dose can be repeated if hypoglycemia does not resolve. Blood glucose concentration initially should be monitored after dextrose administration and then hourly with a goal of maintaining blood glucose concentration between 60 and 150 mg/dL. After administration of the intravenous dextrose bolus and resolution of signs of hypoglycemia, intravenous fluids with 2.5% to 5% dextrose are administered. In some cases, a 10% dextrose solution must be administered to maintain euglycemia. If a balanced electrolyte solution is indicated, dextrose can be added to the appropriate crystalloid solution. Hypertonic solutions should be administered through a central vein if possible. If hypoglycemia persists despite appropriate intravenous dextrose administration, glucagon can be administered as a constant-rate infusion.28,71 The initial dosage is 5 ng/kg/min, which can be increased in 5 ng/kg/min increments up to 20 ng/kg/min or higher as necessary to maintain the blood glucose concentration greater than 60 mg/dL.71 The neurologic signs caused by hypoglycemia should resolve within several minutes of dextrose administration. If they do not and if the blood glucose concentration is normal, neuroglycopenic brain injury may be present. It can result in temporary or permanent neurologic deficits including coma, blindness, ataxia, and behavioral changes. A glucocorticoid (dexamethasone sodium phosphate, 1 to 2 mg/kg intravenously), mannitol (0.5 to 1.0 g/kg intravenously over 20 minutes), and furosemide (1 to 2 mg/kg intravenously) can be administered, but the efficacy of this treatment is questionable.
Myxedema coma is a rare, life-threatening complication of hypothyroidism that has only been reported in dogs. In addition to typical clinical signs of hypothyroidism, impaired mental status ranging from obtundation to coma, hypothermia without shivering, bradycardia, cold extremities, poor pulse quality, systemic arterial hypotension, and myxedema (nonpitting edema) usually are present.6,16,36,39,64 Common laboratory findings consist of nonregenerative anemia, hyponatremia, hypercholesterolemia, lipemia, hypercapnia, and hypoxemia.6,16,36,39,64 Pleural effusion and pulmonary edema have been reported, but idiopathic dilated cardiomyopathy could have been present in some of these dogs based on the case descriptions.36,39 Concurrent disease almost always is present in humans with myxedema coma and has been found in about half of the dogs reported with this disease.* A high index of suspicion is necessary to make the diagnosis of myxedema stupor because the syndrome is rare and many of the clinical signs are similar to those of other disorders.
Fluid therapy with 0.9% NaCl should be administered judiciously because although blood volume is decreased, cardiac function often is decreased. In addition, water excretion is impaired secondary to inappropriate secretion of arginine vasopressin and reduced renal perfusion.58 Alternatively, water restriction is effective in correcting hyponatremia if the patient is well hydrated. Initial treatment in humans consists of intravenous administration of levothyroxine, but the initial dosage is controversial.38,58,66,78 A loading dose of levothyroxine three to five times the standard daily dose (0.066 to 0.11 mg/kg in the dog) generally is recommended, but a lower dose approximating the standard replacement levothyroxine dose in uncomplicated hypothyroidism (0.022 mg/kg in the dog) also has been used. After the initial loading dose, intravenous treatment is continued at 0.022 mg/kg daily until oral treatment can be administered at 0.022 mg/kg every 12 hours. If an intravenous preparation of levothyroxine is not available, the hormone should be administered orally or by orogastric intubation at a dosage similar to that suggested for intravenous use. Supportive treatment is critical to successful management and consists of resolution of hypothermia, treatment of dehydration and hypotension, correction of hypoglycemia, and resolution of glucocorticoid deficiency.36,38,58 Passive warming to relieve the hypothermia is recommended unless hypothermia is severe because active warming by applying an external heat source may cause vasodilatation of cutaneous vessels, leading to worsening of hypotension and circulatory collapse. If present, hypoglycemia should be managed by dextrose administration and ventilatory support given if indicated. Glucocorticoid supplementation is recommended in humans because plasma cortisol concentrations may be inappropriately low for the degree of illness, but there is no evidence to suggest it is beneficial in dogs. If evidence of infection is present, broad-spectrum antibiotic treatment should be instituted. The prognosis is guarded.
Heatstroke is a progressive and life-threatening illness caused by severe hyperthermia. In dogs and cats, hyperthermia usually is induced by increased environmental temperature or excessive exercise or muscle activity. Thermal injury extends to all tissues, and multiple organ failure, intravascular coagulation, and CNS dysfunction ensue. Prompt and aggressive treatment and monitoring are necessary to prevent or treat irreversible and fatal organ damage.
The normal response to hyperthermia is increased cardiac output as a result of increased heart rate, improved atrial and ventricular systolic function, and decreased peripheral vascular resistance.7,11,32 A shift of blood flow from the central to peripheral circulation increases delivery of blood to the muscles and skin to dissipate heat. If dehydration, impaired cardiac function, or prolonged hyperthermia occurs, decreased splanchnic blood flow will result in hypoxic injury to the intestinal tract and liver, causing cytokine production, endothelial dysfunction, bacterial translocation, endotoxemia, and hepatocellular dysfunction.7,32 These abnormalities cause splanchnic vasodilatation and hypotension that will contribute to continued hyperthermia. Myocardial injury caused by direct heat injury, hypoxia, acidosis, and thromboembolic events decreases cardiac contractility and causes cardiac arrhythmias.13 Thus shock associated with heatstroke is a combination of hypovolemic, cardiogenic, and endotoxic shock. Pulmonary endothelial damage causes increased pulmonary vascular resistance and permeability that contribute to pulmonary edema and hemorrhage, as well as acute respiratory distress syndrome.14,32 Endothelial and platelet damage secondary to hyperthermia and release of cytokines lead to disseminated intravascular coagulation (DIC) that is common in heatstroke.5,13,22 Platelet, megakaryocyte, and hepatocellular injury, as well as DIC, can lead to hemorrhage that frequently is evident on presentation and can worsen during management. A combination of factors, including hyperthermic injury, ischemia caused by endothelial swelling and intravascular coagulation, and edema can cause severe and irreversible brain injury, resulting in stupor, coma, blindness, seizures, and other signs of CNS injury.* Acute renal failure can result from impaired renal perfusion, myoglobinemia or hemoglobinemia, or thermal injury.5,13,14 Hypoglycemia is commonly reported in dogs with heatstroke, and may be the result of increased glucose use due to seizures or hyperthermia, or could occur secondary to hepatic dysfunction or sepsis.5,13,22 A mixed metabolic acidosis and respiratory acidosis also is common.
The goals of treatment of heatstroke are to decrease the core body temperature, support cardiovascular function, correct fluid and electrolyte abnormalities, and address other complications as they arise. Correction of hyperthermia is the priority. Owners should initiate this treatment before transporting the animal if possible because it appears to improve survival in dogs.22 Cooling can be accomplished by spraying with or immersing the animal in cold water, followed by placing it in the airflow of a fan.31 The most rapid cooling in humans with hyperthermia occurs with immersion in ice water when compared with other temperatures.63 Concerns regarding ice water causing cutaneous vasoconstriction that would impair heat dissipation and shivering that would cause heat generation apparently do not affect cooling with ice water.8,63 Massaging the skin can help increase blood flow and speed cooling. The target temperature should be 103° F to prevent hypothermia as the body temperature continues to decrease.31
Isotonic fluids (0.9% NaCl or lactated Ringer’s solution) should be administered initially at a rapid rate (up to 90 mL/kg/hr) to restore intravascular volume and reduce core body temperature.31 The volume and rate of fluid administration should be determined by severity of signs and response to the therapy. Hypokalemia can occur in some animals with heatstroke, and it may be necessary to add potassium chloride to intravenous fluids after initial resuscitation. If hypoalbuminemia is present, a colloid (hetastarch at 10 mL/kg) may be combined with the crystalloid treatment.31 Monitoring should be performed frequently during initial treatment, consisting of pulse rate and quality, capillary refill time, blood pressure, respiratory rate, urine output, and central venous pressure when necessary. A coagulopathy usually is present, most often consistent with DIC.5,13,22 Therefore plasma transfusion and, if indicated, treatment for DIC should be considered early in therapy.13 Gastrointestinal hemorrhage is common and may be of sufficient severity to result in anemia, necessitating transfusion with packed red blood cells or whole blood. Because of compromise of the gastrointestinal tract and bacterial translocation, intravenous administration of a broad-spectrum antibacterial drug is indicated. Gastroprotective treatment can be administered but is likely to be of limited efficacy. Acid-base disturbances should be managed when present, but the acidosis associated with heatstroke often responds to intravenous fluid therapy alone. If cerebral edema is suspected, administration of mannitol, furosemide, and dexamethasone should be considered. The efficacy of corticosteroids in treatment of heatstroke has not been established and should be avoided unless indicated for a specific complication.9 Hypoglycemia is common and may be severe, so periodic monitoring and intravenous dextrose administration when indicated is recommended.
After an adequate response to initial fluid therapy, subsequent rates of administration and composition of fluids should be determined by estimating fluid deficits, noting urine output, and monitoring serum electrolyte concentrations. Recognition of complications including DIC, coagulation factor deficiency, severe thrombocytopenia, hepatic failure, renal failure, pulmonary edema, cardiac arrhythmias, seizures, hypoglycemia, acidosis, and sepsis requires careful monitoring. Many of these complications may not develop until 48 to 72 hours after presentation, so frequent adjustments to treatment are often necessary.
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4 Androgue J.C., Wilson H., Boyd A.E., et al. Plasma acid-base patterns in diabetic ketoacidosis. N Engl J Med. 1982;301:1603-1610.
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