Hypokalemia after pediatric albuterol overdose: A case series

Hypokalemia After Pediatric Albuterol Overdose: A Case Series JERROLD B. LEIKIN, MD,* KIMBERLY ANNE LINOWIECKI, PHARM D,$ DAVID F. SOGLIN, MD,*t FRANK PALOUCEK, Sympathomimetic use results in a triad of hypokalemia, hyperglycemia, and elevated white blood cell count. Transient hypokalemia results from activation of the Na+/K+ pump and transport of potassium intracellularly. Increased serum glucose and insulin may also contribute to the intracellular shift of potassium after sympathomimetic use. Four cases of accidental pediatric albuterol ingestion with significant hypokalemia are reported. Four children between 1 and 6 years of age presented to the emergency department within 5 hours of ingesting 3.0, 1.1, 3.7, and 1.7 mg/kg albuterol, respectively. All four presented alert and oriented in no apparent distress. The most common findings were vomiting, sinus tachycardia, and hypokalemia (2.3, 2.5, 2.8, and 2.5 mmol/L, respectively). Each child received a single dose of activated charcoal and intravenous potassium replacement. All patients recovered uneventfully within 12 to 24 hours with supportive care only. These cases demonstrated that significant depressions in serum potassium can occur after pediatric albuterol overdose. Although transient, the dose-response relationship and duration of effect is unknown. Although significant hypokalemia can occur after ingestion of oral sympathomimetics, replacement should be managed on an individual basis until further studies are completed. (Am J Emerg Med 1994;12:64-66. Copyright 0 1994 by W.B. Saunders Company) Several drugs and toxins have been demonstrated to cause hypokalemia in an overdose setting (Table I).‘.‘” With regards to p-agonist toxicity, it is believed that these laboratory abnormalities result from a sympathomimetic mechanism with the hypokalemia developing from activation of the sodium/potassium ATPase pump and the resultant transfer of potassium intracellularly. ” The cases of four pediatric patients younger than 6 years of age with hypokalemia resulting from an acute albuterol overdose are reported.

Patient No. 1 A 21-month-old black female with an unremarkable medical history presented to the emergency department (ED) 5 hours after

From the *Section of Emergency Medicine and TDepartment of Pediatrics, Rush Presbyterian St. Luke’s Medical Center; *Department of Pharmacy Practice, Olympia Fields Hospital; and the 9Department of Pharmacy Practice, University of Illinois Hospital, Chicago, IL. Manuscript received November 9, 1992; revision accepted June 4, 1993. Presented at the Ambulatory Pediatric Association, Midwest

64

ingesting approximately 100 mL of Ventolin syrup (2 mg/mL) (Allen and Hanburgs, Research Triangle Park, NC). Although some of the medication had spilled onto her clothes and the floor, the approximate amount of ingestion was no more than 3 mgikg. The patient had three spontaneous emeses before arrival. lnitial vita) signs were blood pressure, 82/52 mm Hg; heart rate, 185 beats/min; respiratory rate. 30 breathsimin; and the patient was afebrile. Physical examination showed an alert. well-hydrated female (12.4 kg) in no acute distress. Cardiac monitor showed sinus tachycardia. Laboratory values are summarized on Table 2 with the potassium being remarkable for 2.3 mmol/L. The patient was given DSiO.2 NS with 5 mEq KCI in 250 mL at 50 mL/hr (during approximately 6 hours) in addition to 15 g of activated charcoal. During the next 24 hours. her heart rate decreased to 136 beats/min: there was no additional symptomatology; and the potassium level increased to 3.9 mmol/L. The patient was discharged with no apparent sequelae.

Patient No. 2 A 2-year-old black female with an unremarkable medica history was brought to the ED immediately after an accidental ingestion of Ventolin syrup (2 mg/mL). The maximum quantity ingested was 40 mL or I. 1 mg/kg. Spontaneous emesis was not noted. Initial vital signs were blood pressure, 121/78 mm Hg: heart rate. 169 beatsimin: and respiratory rate, 28 breaths/min. The patient was afebrile and weighed 14.7 kg. Physical examination was otherwise unremarkable. Laboratory values are noted on Table 2 with serum potassium of 2.5 mmol/L. Patient was treated with a saline gastric lavage along with 25 g of activated charcoal. Potassium replacement consisted of 40 mEq KCI (2.7 mmoL/kg/d) in 0.2 normal saline (during an approximate l2-hour period). During the next 24 hours, the patient’s potassium level reached 4.5 mmol/L. and she was subsequently discharged without any sequelae.

Patient No. 3

CASE REPORTS

Region Meeting, October 22, 1992, Madison, WI. Address reprint requests to Dr Leikin, Associate Medical rector, 1753 W Congress Parkway, Chicago, IL 60612. Key Words: Albuterol, hypokalemia, overdose. Copyright 0 1994 by W.B. Saunders Company 0735-6757/94/l 201-0016$5.00/O

PHARM D§

Di-

A ?-year-old male (weight, 16.4 kg) with a history of asthma ingested at most I50 mL of albuterol (3.7 mgikg) 1 I12 hours before arrival at the ED. The patient was alert and playful on arrival; there was no spontaneous emesis. Initial vital signs were pulse rate, 160 beats/mini respiratory rate, 36 breaths/min; and temperature, 97.O”C. Physical examination was unremarkable. Cardiac monitor showed tachycardia. Laboratory values (Table 2) were remarkable for a serum potassium of 2.8 mmol/L. White blood cell count was 7.3. Fifteen grams of activated charcoal with sorbitol were given, and an intravenous infusion of 10 mEq was also given. KCI during a I l/2-hour period was also administered, along with a maintenance infusion of 40 mEq KC1 in D5.2 NS liter at 50 mL/h for approximately 3 hours. The patient was observed for approximately 18 hours when the serum potassium level reached 3.9 mmol/L and was discharged. Patient No. 4 A 6-year-old male (weight, 23.6 kg) with a medical history of asthma who has previously been on albuterol ingested 100 mL of

LElKEN ET AL m HYPOKALEMIA

TABLE1.

Medications,

Drugs,

AFTER PEDIATRIC

and Toxins

ALBUTEROL

Associated

With Hypokalemia Cocaine Salicylate (respiratory alkalosis) Bupropion Alcoholism-alcohol withdrawal Barium Laxative abuse Licorice abuse Steroid Colchicine Diuretics (osmotic, loop, and thiazide) Penicillin

Fluoxetine Gossypol Cadmium Cesium Quinine Digoxin (chronic)Digoxin immune Theophylline Insulin Toluene Albuterolp agonists Amphotericin f3 Cisplatin Aminoglycosides Glycol ethers Lithium Hydroxocobalamin

FAB

(1.7 mg/kg) I hour before arrival at the ED. The patient complained of nausea and developed spontaneous pink-colored emesis while in triage. Initial vital signs were blood pressure, 120/60 mm Hg; pulse rate, 170 beatsimin; and respiratory rate, 28 breaths/ min. Physical examination was unremarkable. Cardiac monitor showed sinus tachycardia. Laboratory values are shown in Table 2 with a serum potassium level of 2.5 mmol/L noted. Saline gastric lavage and 25 g of activated charcoal were administered. Patient was given two 20 mEq of KC1 intravenous riders each at a 4-hour rate with DY0.45 NS at a rate of 60 mL/h. In 16 hours, the patient’s potassium level reached 3.8 mmol/L, and he was discharged without any sequelae. albuterol

DISCUSSION Of the 17,051 toxic exposures secondary to asthma therapies called into poison control centers in 1991, 9,869 involved terbutaline or other l3-agonists.‘3 Whereas children younger than 6 years of age comprised the majority of P-agonists exposures (7,279 cases or 73%), the only death involving albuterol was in an adult patient who also took theophylline and lorazepam in a successful suicide attempt.13

TABLE 2.

Patient

Characteristics

of Acute Albuterol Maximum Albuterol Ingestion

Patient 1 2 3 4

No.

Time

ABBREVIATION: ND, Not done;

WBC, white

3.0

185 136 169 144 160 166 170 113

1.1

3.7 1.7

blood

cell.

The relationship of albuterol and hypokalemia in pediatric patients is just now becoming c1arified.‘4-30 In a review of 40 adult and pediatric patients, only 2 patients had hypokalemia.16 In a recent study of 64 children exhibiting albuterol toxicity, the most common findings of toxicity were tachycardia (73%), metabolic acidosis (50%), and hyperglycemia (50%). Hypokalemia was noted in 26% of the patients.“’ The signs of toxicity were observed within 4 hours in 88% of patients, whereas 13% of the patients received supplemental potassium. Only 17% of these patients were admitted, and no serious sequelae were noted. The mechanism of hypokalemia caused by P-agonists has been studied on human volunteers.*“*’ It has been demonstrated that a 15 to 30-fold increase in epinephrine results in hypokalemia, tachycardia, and a decrease in plasma insulin; the hypokalemia was prevented by the addition of @antagonists.‘5-25 It is believed that the hypokalemia results from stimulation of the Na/K pump, resulting in intracellular shifts of potassium and not total body depletion. Recently, a prospective study of 23 patients with acute bronchospasm showed significant decreases in serum potassium, magnesium, and phosphate, with the average potassium decrease approaching 0.53 mEq/L at 2 hours after nebulized P-agonist therapy. Fifty-seven percent of the patients developed hypokalemia during the treatment.30 Albuterol lowered potassium to a lesser degree and for a more brief period of time than fenoterol or terbutaline (2 hours compared with 4 hours).‘* Albuterol has also been used to treat hyperkalemia in patients with renal failure.‘9.28 Additionally, albuterol has been reported to cause hypoglycemia and resultant seizures in a toddler after a 4 mg/kg ingestion.3’ Although it is clear that the effects of acute albuterol toxicity are relatively mild, there is growing debate regarding the chronic effects of albuterol relative to mortality rates from asthma.3’-34 A recent case-control study demonstrated an increase in asthma deaths in patients receiving albuterol with an odds ratio of 2.4 (confidence intervals, 1.5 to 3.8).32 Although several mechanisms have been suggested, the effect of hypokalemia (especially of chronic duration) on arrhythmogenesis could be considered.30,3’ Our cases illustrate that significant depressions in serum potassium can occur after pediatric albuterol overdose. These patients can usually be treated with decontamination procedures, electrolyte replacement and observation.

Ingestion

Heart Rate (beats/min)

(mglkg)

Initial presentation Discharge Initial presentation Discharge Initial presentation Discharge Initial presentation Discharge

65

OD

co*

Na

K

Cl

141 141 138

2.3 3.9 2.5 4.5 2.8 3.9 2.5 3.8

111 106 107

13 19 18

99 105 100 106

23 23 22 21

137 141 139 140

Glucose 285 ND 200 108 203 89 ND 91

Comments

WBC count

was 21.6

66

AMERICAN

JOURNAL

REFERENCES 1. Hall KW, Dobson KE, Dalton JG, et al: Metabolic abnormalities associated with intentional theophylline overdose. Ann Intern Med 1984;101:457-462 2. Halliwell M, Berry D: Theophylline poisoning in adults. Br Med J 1979;2:1114 3. Buckley BM, Braithwaite RA, Vale JA: Theophylline poisoning. Lancet 1983;2:618 4. Robin ED, Davis RP, Rees SB: Salicylate intoxication with special reference to hypokalemia. Am J Med 1959;26:869-882 5. Kerr F, Kenoyer G, Bilach M: Quinidine overdose, neurological and cardiovascular toxicity in a normal person. Br Heart J 1971;33:629-631 6. Woie L, Oyri A: Quinidine intoxication treated with hemodialysis. Acta Med Stand 1974;195:237-239 7. Fischman CM, Oster JR: Toxic effects of toluene: A new cause of high anion gap metabolic acidosis. JAMA 1979;241: 1713-1715 8. Tattersal MH, Battersby G, Spiers AS: Antibiotics and hypokalemia. Lancet 1972;1:630-631 9. Roza 0, Berman LB: The pathophysiology of barium. Hypokalemic and cardiovascular effects. J Pharmacol Exp Ther 1971 ;177:433-439 10. Zull DN: Disorders of potassium metabolism. Emerg Med Clin North Am 1989;7:71 l-794 11. Knochel JP: Diuretic-induced hypokalemia. Am J Med 1984;77:18-27 12. Gonzalez JJ, Owens W, Ungaro PC, et al: Clay ingestion, a rate cause of hypokalemia. Ann Intern Med 1982;97:65-66 13. Litovitz TL, Holm KC, Bailey KM, et al: 1991 Annual report of the American Association of Poison Control Centers National Data Collection System. Am J Emerg Med 1992;10:452-505 14. Gelmont DM, Balmes JR: Hypokalemia induced by inhaled bronchodilators. Chest 1988;94:763-766 15. Connell JM, Cook GM, Mclnnes GT: Metabolic consequences of salbutamol poisoning reversed by propranolol. Br Med J 1982;285:779 16. Prior JG, Cochrane GM, Raper SM, et al: Self-poisoning with oral salbutamol. Br Med J 1981;282:1932 17. O’Brien IA, Fitzgerald-Fraser J, Levin IG, et al: Hypokalemia due to salbutamol overdosage. Br Med J 1981;282:15151516 18. Health A, Hulten BA: Terbutaline concentrations in selfpoisoning: A case report. Hum Toxicol 1987;6:525-526

OF EMERGENCY

MEDICINE

n Volume

12, Number

1 n January

1994

19. Price AH, Clissold SP: Salbutamol in the 1980’s: A reappraisal of its clinical efficacy. Drugs 1989;38:77-122 20. Spiller HA, Wiley JF, Krenzelok EP, et al: Accidental albuterol ingestion in children. Vet Hum Toxicol 1992;34:325 (abstr) 21. Tabachnick II: A summary of the pharmacology and toxicology of albuterol. Ann Allergy 1981;47:379-383 22. Burgess ED, Flatt A, Siebers R, et al: A comparison of the extent and duration of hypokalemia following three nebulized beta*-adrenoceptor agonist. Br J Clin Pharmacol 1989;36:415417 23. Rohr AS, Spector SL, Rachelefsky GS, et al: Efficacy of parenteral albuterol in the treatment of asthma - Comparison of its metabolic side effects with subcutaneous epinephrine. Chest 1986;89:348-351 24. Kung M: Parenteral adrenergic bronchodilators and potassium. Chest 1986;89:322-323 25. Brown MJ, Brown DC, Murphy MB: Hypokalemia from beta*-receptor stimulation by circulating epinephrine. N Engl J Med 1983;309:1414-1419 26. Scheinin M, Koulu M, Laurikainen E, et al: Adrenergic bronchodilators and potassium. Chest 1987;91:794-795 27. Lulich KM, Goldie RG, Ryan G, et al: Adverse reactions to beta*-agonist bronchodilators. Med Toxicol 1986;1:289-299 28. Allon M, Dunlay R, Copkney C: Nebulized albuterol for acute hyperkalemia in patients on hemodialysis. Ann Intern Med 1989;110:426-429 29. King W, Holloway M, Palmisano P: Albuterol Overdose: A case report and differential diagnosis. Pediatr Emerg Care 1992; 8:268-271 30. Bodenhaner J, Bergstrom R, Brown D, et al: Frequently nebulized beta-agonists for asthma: Effects on serum electrolytes. Ann Emerg Med 1992;21 :1337-1342 31. Wasserman D, Amitai Y: Hypoglycemia following albuterol overdose in a child. Am J Emerg Med 1992;10:556-557 32. Spitzer WO, Suissa S, Ernst P, et al: Beta-agonists and the risk of death or near death from asthma. N Engl J Med 1992; 326:501-506 33. Burrows B, Lebowitz MD: The beta-agonist dilemma. N Engl J Med 1992;326:560-561 34. Mullen M, Mullen 6, Carey M: The association between beta-agonist use and death from asthma: A meta-analytic integration of case control studies. JAMA 1993;270:1842-1845