A 6-year-old castrated male Shetland Sheepdog weighing 18.6 kg (41 lb) was examined at the University of Florida Veterinary Medical Center for evaluation of rapidly progressive quadriparesis and severe hypokalemia. On the evening prior to admission, the dog vomited approximately 2 to 3 hours after the evening meal. The dog was seen by the referring veterinarian the next morning after developing hind limb paresis while playing outside with other dogs. Physical examination at that time revealed severe hind limb paresis with inability to support weight in the hind limbs, although voluntary motor function was evident. Spinal reflexes were normal in all 4 limbs. The remainder of the physical examination was considered normal. Lateral radiographie views of the vertebral column revealed moderate spondylosis deformans affecting much of the lumbar portion of the column, with no calcified disk material or collapsed intervertébral disk spaces. During a period of approximately 1 hour, paresis progressed to involve all 4 limbs, and cervical ventroflexion developed. Initial CBC results were within reference range with the exception of mild leukocytosis (19.9 × 103 WBCsμL; reference range, 6.0 to 17.0 × 103 WBCsμL), mild mature neu-trophilia (18.1 × 103 neutrophils/μL; reference range, 3.5 to 12.O × 103 neutrophils/μL), and mild erythrocytosis (Hct, 56.6%; reference range, 37.0% to 55.0%). Results of a limited serum biochemical analysis (eg, SUN, glucose, total protein, creatinine, and calcium concentrations and alkaline phosphatase and alanine amino-transferase activities) were within reference range with the exception of mild hyperglycemia (glucose concentration, 150 mg/dL; reference range, 72 to 124 mg/dL). Severe hypokalemia (serum potassium concentration < 2.0 mmol/L; reference range, 3.4 to 4.9 mmol/L) was the only abnormality detected on electrolyte analysis. Electrolyte analysis was repeated, and severe hypokalemia was confirmed. Initial treatment consisted of IV administration of an electrolyte solutiona (4 mL/kg/h [1.8 mL/lb/h]) supplemented with 80 mEq of KCF/L (end administration rate of KCl, 0.3 mEq/kg/h [0.14 mEq/lb/h]) prior to referral. One episode of vomiting was reported during initial evaluation. No previous pertinent medical history was reported. The dog was vaccinated and was receiving no medications other than orally administered heartworm preventative and a topical flea control product.
On admission to the Veterinary Medical Center and approximately 2 hours after initial examination by the referring veterinarian, the dog was febrile (rectal temperature, 39.8°C [103.7°F]) and tachypneic (112 breaths/ min) and had hyperemic mucous membranes. Physical examination revealed severe forelimb paresis and hind limb paraplegia, with intact superficial and deep pain responses in all 4 limbs. Forelimb spinal reflexes were normal, and hind limb reflexes were normal to slightly hyperreflexive. The panniculus response was normal, and cranial nerve reflexes were intact. Ocular examination revealed moderate mydriasis in both eyes, with appropriate direct and consensual pupillary light reflexes. Thoracic auscultation and the remainder of the physical examination were unremarkable.
Diagnostic evaluation included a CBC, serum biochemical analysis, urinalysis, blood gas analysis, thoracic radiography, abdominal ultrasonographic evaluation, indirect blood pressure measurement, and electrocardiography Complete blood count revealed mild leukocytosis (24.0 × 103 leukocytes/μL; reference range, 6.0 to 17.0 × 103 leukocytes/μL) with mild neutrophilia (22.0 × 103 neu-trophils/μL; reference range, 3.0 to 11.5 × 103 neutro-phils/μL) and mild erythrocytosis (PCY 59%; reference range, 37% to 54%). Serum biochemical values revealed mildly high activities of alkaline phosphatase (118 U/L; reference range, 16 to 111 U/L) and aspartate amino-transferase (102 U/L; reference range, 14 to 46 U/L), mild hypophosphatemia (1.6 mg/dL; reference range, 1.9 to 5.8 mg/dL), and severe hypokalemia (1.7 mEq/L; reference range, 3.7 to 5.5 mEq/L). Results of urinalysis were within reference limits. Urine was isosthenuric (specific gravity, 1.012), but the dog had received fluids IV prior to admission. Initial blood gas analysis values, including pH, were within reference range. Results of thoracic radiographie imaging were unremarkable except for spondylosis deformans at the T5-6 intervertébral disk space. Abdominal ultrasonography revealed a distended urinary bladder, but was otherwise unremarkable. Indirect measurements of systolic and diastolic blood pressure were within reference limits (122/64 mm Hg; mean, 84 mm Hg), and continuous electrocardiography revealed normal sinus rhythm.
Treatment was instituted with IV administration of an electrolyte solutiona (2.4 mL/kg/h [1.1 mL/lb/h]) and continuous rate infusion of KCP (0.3 mEq/kg/h). Continuous ECG monitoring was initiated, as were periodic indirect blood pressure measurements and blood gas analyses. The dog's serum potassium concentration increased from 1.7 mEq/L to 2.4 mEq/L 2 hours after treatment was begun, at which point the rate of KCl supplementation was decreased (0.13 mEq/kg/h [0.06 mEq/lb/h]). At that time, the dog was able to stand and ambulate without assistance. Seven hours after initiation of treatment, serum potassium concentration was within reference range (4.6 mEq/L). Intravenous potassium administration was gradually decreased during the next 24 hours, and serum potassium concentrations remained within reference range. The dog's rectal temperature and respiratory rate returned to normal within 12 hours of admission. Throughout the treatment period, heart rate, blood pressure, respiratory rate, and temperature remained within reference limits. By the next morning, the dog was bright, alert, and responsive and had a normal activity level. Potassium concentration at the time of discharge was 4.1 mEq/L, and further oral supplementation was not prescribed.
Further questioning of the owner revealed that a horse on the property was being treated with 4-mg al-buteroL tablets, administered in the feed, for chronic obstructive pulmonary disease. The dog reportedly ate dropped feed from the ground while the horse was eating. Serum obtained during the initial hypokalemic period was submitted for drug screening via immunoassay to the University of Florida Analytical Toxicology Core Laboratory, and results were suggestive of albuterol toxicosis (serum albuterol concentration, 20 to 25 ng/mL; normal, 0 ng/mL). Testing by means of mass spectrom-etry to rule out cross-reactivity with other bronchodila-tors was not performed. The dog's access to the horse's medicated feed was the likely source of intoxication because the dog had no other access to albuterol or other bronchodilators.
Discussion
Hypokalemia in veterinary patients can develop from numerous causes that can be grouped into 3 categories: decreased potassium intake (although decreased intake alone does not typically cause hypokalemia), increased potassium loss (through the gastrointestinal or urinary tract), and translocation of potassium from extracellular to intracellular fluid (Appendix). Clinical signs may or may not be manifested in a hypokalemic dog or cat. When signs are evident, muscle weakness, polyuria, polydypsia, and impaired urine-concentrating ability are the most commonly recognized signs.1 The dog of the present report had profound muscle weakness as a result of severe hypokalemia. Muscle weakness develops when serum potassium concentration decreases below 3.0 mEq/L, creatine kinase activity increases when potassium concentration decreases below 2.5 mEq/L, and rhabdomyolysis may develop when serum potassium concentration decreases to less than 2.0 mEq/L.1 With severe hypokalemia, muscle weakness can progress to include respiratory muscle paralysis, which necessitates mechanical ventilation. Serum creatine kinase activity was not determined in the dog of this report, but overt evidence of rhabdomyolysis was not noticed.
Hypokalemia can alter acid-base balance by inducing metabolic acidosis (via alteration of urinary acid excretion secondary to a distal renal tubular acidification defect), contribute to ECG changes and cardiac arrhythmias, and cause functional and morphologic changes in the kidneys. The dog of this report did not develop ECG changes or cardiac arrhythmias. In humans, low-amplitude T waves, S-T segment depression, and appearance of U waves may be seen on an ECG as a result of hypokalemia. These changes are not consistently detected in dogs and cats, but supraventricular and ventricular arrhythmias may be seen because low serum potassium concentration delays ventricular re-polarization, prolongs action potential duration, and increases automaticity1 Renal effects of hypokalemia include decreased glomerular filtration rate secondary to renal vasoconstriction; impaired responsiveness to antidiuretic hormone and subsequent polyuria, polydypsia, and decreased concentrating ability; and increased renal ammoniagenesis and net urinary acid excretion.1 It is not possible to know whether the isosthenuria detected in the dog of this report resulted from hypokalemia and secondary nephrogenic diabetes insipidus or from the fluids administered before arrival at the Medical Center. High serum albuterol concentrations were detected, presumably secondary to ingestion of a horse's medication. Albuterol is a relatively selective β2-adrenergic receptor agonist with potent bronchodilator activity and minimal inotropic or chronotropic effect that is used primarily as a bronchodilator in dogs, cats, and horses.2 β2-Adrenergic receptors are found predominantly in the smooth muscle of the bronchi, gastrointestinal tract, blood vessels of skeletal muscle, and uterus. When stimulated, these receptors induce smooth muscle relaxation, vasodilation, and skeletal muscle contraction. βi-Adrenergic receptors are found principally in cardiac muscle and adipose tissue.2 At typical doses, albuterol has minimal β-adrenergic effects. β-Adrenergic receptor agonists, including albuterol, activate the cell membrane enzyme adenyl cyclase, which converts ATP to 3'-5'-cAMP A series of intracellular events is triggered by cAMP, which results in inhibition of bronchial smooth muscle contraction and resultant bronchodilation. Albuterol is available in oral and inhalant preparations and is rapidly absorbed after administration, with effects seen within 5 minutes after inhalation and 30 minutes after oral administration. Effects last for 3 to 6 hours after inhalation and for up to 12 hours (depending on dose) after oral administration.3 The onset of clinical signs in the dog in the present report correlated to the morning feeding of the horse and subsequent ingestion of the albuterol. Adverse effects are dose related. Signs of overdosage include arrhythmias, hypertension, fever, vomiting, mydriasis, CNS stimulation, and hypokalemia.
The human medical literature includes multiple reports4-8 of hypokalemia associated with albuterol overdosage. Hypokalemia also develops after administration of prescribed dosages of albuterol in humans,9 and albuterol administration has even been proposed as a method of decreasing serum potassium concentration in humans with hyperkalemia secondary to chronic renal failure and in premature infants.10,11 Albuterol toxicosis resulting in severe hypokalemia and ventricular tachyarrhythmia has been reported in a dog that chewed on an inhalant canister.12 A typical dosage of albuterol for oral administration is 0.05 mg/kg (0.023 mg/lb) every 8 to 12 hours. The dog of this report would have ingested an approximate dose as high as 0.43 mg/kg (0.2 mg/lb) if the entire dose administered to the horse was ingested.
Several hypotheses have been proposed for alb-uterol-induced hypokalemia. The most commonly supported theory is that β-adrenergic receptor stimulation of membrane-bound Na-K-ATPase in eryth-rocytes, liver, and muscle cells causes intracellular influx of circulating serum potassium and relative hypokalemia.5,7,8,10,11 Other theories involve changes in carbohydrate metabolism induced by β-adrenergic receptor agonists, including hyperglycemia and insulin release.5,7,8 Stimulation of β-adrenergic receptors in the pancreatic β cells results in increased insulin secretion, which promotes intracellular movement of potassium. In addition, stimulation of β-adrenergic receptors in the liver promotes gluconeogenesis and gly-cogenolysis, resulting in hyperglycemia and increased endogenous insulin production.
The mainstay of treatment of animals with alb-uterol-induced hypokalemia is supportive care. In animals with known recent oral ingestion in the absence of cardiac or CNS effects, gastric emptying should be performed and activated charcoal should be administered.3 Severe hypokalemia can usually be managed by parenteral supplementation with KCl. Intravenous administration of KCl should not exceed a rate of 0.5 mEq/kg/h to avoid possible adverse cardiac effects, namely slowed impulse conduction leading to bradycardia, ventricular fibrillation, or ventricular asystole.1 To the authors' knowledge, there are no reports of iat-rogenic hyperkalemia associated with potassium supplementation as the effects of the albuterol dissipate, despite the fact that animals with albuterol-induced hypokalemia are not systemically potassium depleted. However, frequent monitoring of serum potassium concentration is recommended during supplementation. Administration of propranolol, a nonselective β-adrenergic receptor blocker, can successfully reverse the signs of severe albuterol toxicosis in humans, although this is rarely required.8 The dog of this report responded well to supportive care and parenteral administration of KCl and was discharged 48 hours after admission. Serum potassium concentration remained within reference limits 48 hours after discharge (4.3 mmol/L), and the dog had a complete return to normal function and activity. No related health problems or persistent clinical signs have been reported by the owner since the time of discharge.
Appendix
Common causes of hypokalemia in small animals.
Lactated Ringer's solution, Baxter Healthcare Corp, Deerfield, Ill.
Potassium chloride, American Pharmaceutical Partners Inc, Schaumburg, Ill.
Mutual Pharmaceutical Co, Philadelphia, Penn.
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