Hypoglycemia Following Albuterol Overdose in a Child DROR WASSERMAN,
MD, YONA AMITAI, MD
Acute overdose with p-sympathomimetics results in transient elevation of blood glucose levels. Hypoglycemia has previously been reported in newborns of mothers following prolonged use of sympathomimetics used as tocolytic therapy. The authors report the first case of symptomatic hypoglycemia in a child, occurring 16 hours after acute albuterol overdose. Hypoglycemia may occur as a complication of acute p-sympathomimetic overdose, probably as a reaction to acute elevation of blood sugar and resultant hyperinsulinemia. The authors suggest that in children with a large overdose of p-sympathomimetics, blood glucose levels should be monitored for several hours. In those with marked hyperglycemia, monitoring should be extended until normalization of blood glucose levels. (Am J Emerg Med lgg2;10:666-667. Copyright 0 1992 by W.6. Saunders Company)
Acute overdose with P-sympathomimetic agents characteristically results in tachycardia, jitteriness. hypokalemia, and elevation of blood glucose levels. I-4 The occurrence of hypoglycemia as an adverse reaction to sympathomimetics is less recognized and has been reported only in newborns of mothers treated with repeated doses of P-sympathomimetits. We report a patient presenting with hypoglycemia and generalized tonic clonic seizures following albuterol overdose. CASE REPORT A 3-year-old female was admitted to our department with generalized tonic clonic seizures and hypoglycemia 16 hours after ingestion of a large dose of albuterol. She was previously healthy, other than being asthmatic, requiring intermittent treatment with oral albuterol. There was no family history of convulsive disorders. Sixteen hours prior to admission she ingested approximately 60 mg (4 mgikg) of albuterol syrup and 250 mg of amoxicillin (17 mg/kg). She had no access to other medications and was not given any medications by her parents. The child had neither spontaneous nor induced emesis, and had not been seen at that stage by a physician. There were no apparent symptoms up until the time that she went to sleep several hours later. She woke up early in the morning, however. complaining of thirst, and drank four glasses of waler. Sudden onset of drowsiness and ataxia preceded loss of consciousness and generalized tonic clonic seizures. Ten minutes later she was brought to our emergency department in a convulsive state, with hypertonicity and bradycardia (60 beats/min). On admission, blood glucose levels revealed profound hypoglycemia both by finger stick dextrose analysis (0.4 mmol/L) and by biochemical assay (0.9 mmol/L). After receiving 0.5 gm/kg intravenous bolus of glucose she regained consciousness promptly and her pulse stabilized at 96 beats per minute.
From the Department of Pediatrics, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel. Manuscript received February 5, 1992; revision accepted May 20, 1992. Address reprint requests to Dr Amitai, Department of Pediatrics, Hadassah University Hospital, Mount Scopus, PO Box 24035, Jerusalem, 91240, Israel. Copyright Q 1992 by W.B. Saunders Company 0735-6757/92/l 006-0012$5.00/O
556
She received additional amounts of glucose by mouth. She was afebrile and both physical and neurologic examination were normal. Other laboratory tests were: hemoglobin: 11.5 gr%, white blood cell count. 23,00O/mm~: sodium, 133 mEq/L; potassium, 5.2 mEq/L; urea, 4.9 mmol/L; calcium, 1.98 mmol/L; serumglutamicoxaloacetictransaminase, 46 IU; lactate, 1.24 mmol/L (normal 0.52.4 mmol/L); blood alcohol level, 0. Venous blood gases were: pH, 7.25; Hco,, 16.7 mEq/L; base excess, - 10.1 mEq/L; urine, normal (no ketones). Repeated measurements of blood glucose during the next 24 hours were all within the normal range. She recovered uneventfully and was discharged after 30 hours in good health.
DISCUSSION Our patient presented with generalized tonic clonic seizures due to hypoglycemia I6 hours after an albuteral overdose. She regained consciousness after receiving an intravenous bolus of glucose, and had no other episodes of hypoglycemia during the next 24 hours. There was no clinical or laboratory evidence of diabetes, other pancreatic disorders, glycogen storage disease, Reye’s syndrome, sepsis, ingestion of other hypoglycemic agents, or other metabolic disorders. Alterations in glucose metabolism following intoxication by P-sympathomimetics usually consist of hyperglycemia shortly after ingestion accompanied by hypokalemia, an expression of sympathomimetic activity.’ Hypoglycemia in association with P-sympathomimetics was described in newborns of mothers treated repeatedly by these agents as tocolytic therapy.5-7 One hypothesis to explain this association is the depletion of hepatic glycogen stores due to the prolonged sympathomimetic effect on the liver. Another hypothesis that has been suggested is a direct action of sympathomimetics on pancreatic p-cells, leading to hyperinsulinemia which results in delayed hypoglycemia.‘,’ Indeed, hyperinsulinemia has been documented in cord blood of newborns of mothers exposed to P-sympathomimetic tocolytic therapy.’ Since plasma insulin levels were not measured in our patient, the possibility of hyperinsulinemia remains hypothetical. Currently, the management of patients with acute P-sympathomimetic overdose is focused on the immediate alteration in the heart rate, potassium, and glucose levels, which usually resolve within several hours. We suggest that hypoglycemia may also be a manifestation in children and that ongoing blood glucose monitoring may thus be warranted. However, the frequency of P-sympathomimetic overdose (5,574 preschool children reported to the American Association of the Poison Control Centers National Data Collection System in 1990),9 would preclude routine monitoring of all cases. We therefore recommend that at least those children with large P-sympathomimetic overdose have their blood glucose levels monitored closely for several
WASSERMAN
AND AMITAI
n HYPOGLYCEMIA
FROM ALBUTEROL
557
OVERDOSE
hours. In those with marked hyperglycemia, monitoring should be extended until blood glucose levels have normalized. In the event of a hypoglycemic episode, documentation of plasma insulin levels will help to elucidate the mechanism of this phenomenon.
mimetic Amines. In Goodman, Gilman (eds): The Pharmacological Basis of Therapeutics, (ed 7). New York, NY, Macmillan, 1985, pp 145-180
REFERENCES
6. Svenningsen NW: Follow-up studies on preterm infants after maternal p-receptor agonist treatment. Acta Obstet Gynecol Stand 1982;108:67-7O(Suppl)
1. Wong CS, Pavord ID, Williams J, et al: Bronchodilator, cardiovascular and hypokalemic effects of fenoterol, salbutamol, and terbutaline in asthma. Lancet 1990;336:1396-1399 2. Brown MJ, Brown DC, Murphy MB: Hypokalemia from beta 2 receptor stimulation by circulating epinephrine. N Engl J Med 1983;309:1414-1419 3. Ahrens RC, Smith GD: Albuterol: An adrenergic agent for use in the treatment of asthma. Pharmacology, pharmacokinetits and clinical use. Pharmacotherapy 1984;4:105-121 4. Weiner N: Norepinephrine, Epinephrine and the Sympatho-
5. Epstein MF, Nicholls E, Stubblefield PG: Neonatal hypoglycemia after beta-sympathomimetic tocolytic therapy. J Pediatr 1979;94:449-453
7. Jovanovic R: Serial serum potassium and glucose during treatment of premature labor with oral terbutaline. Gynecol Obstet 1985;23:399-404 8. Sharp mechanism
levels Int J
GWG, Whollheim C, Muller WA, et al: Studies of insulin release. Fed Proc 1975;34:1537-1548
on
9. Litovitz TL, Bailey KM, Schmitz BF, et al: 1990 Annual Report of the American Association of Poison Control Centers National Data Collection System. Am J Emerg Med 1991;9:461-509
MD, YONA AMITAI, MD
Acute overdose with p-sympathomimetics results in transient elevation of blood glucose levels. Hypoglycemia has previously been reported in newborns of mothers following prolonged use of sympathomimetics used as tocolytic therapy. The authors report the first case of symptomatic hypoglycemia in a child, occurring 16 hours after acute albuterol overdose. Hypoglycemia may occur as a complication of acute p-sympathomimetic overdose, probably as a reaction to acute elevation of blood sugar and resultant hyperinsulinemia. The authors suggest that in children with a large overdose of p-sympathomimetics, blood glucose levels should be monitored for several hours. In those with marked hyperglycemia, monitoring should be extended until normalization of blood glucose levels. (Am J Emerg Med lgg2;10:666-667. Copyright 0 1992 by W.6. Saunders Company)
Acute overdose with P-sympathomimetic agents characteristically results in tachycardia, jitteriness. hypokalemia, and elevation of blood glucose levels. I-4 The occurrence of hypoglycemia as an adverse reaction to sympathomimetics is less recognized and has been reported only in newborns of mothers treated with repeated doses of P-sympathomimetits. We report a patient presenting with hypoglycemia and generalized tonic clonic seizures following albuterol overdose. CASE REPORT A 3-year-old female was admitted to our department with generalized tonic clonic seizures and hypoglycemia 16 hours after ingestion of a large dose of albuterol. She was previously healthy, other than being asthmatic, requiring intermittent treatment with oral albuterol. There was no family history of convulsive disorders. Sixteen hours prior to admission she ingested approximately 60 mg (4 mgikg) of albuterol syrup and 250 mg of amoxicillin (17 mg/kg). She had no access to other medications and was not given any medications by her parents. The child had neither spontaneous nor induced emesis, and had not been seen at that stage by a physician. There were no apparent symptoms up until the time that she went to sleep several hours later. She woke up early in the morning, however. complaining of thirst, and drank four glasses of waler. Sudden onset of drowsiness and ataxia preceded loss of consciousness and generalized tonic clonic seizures. Ten minutes later she was brought to our emergency department in a convulsive state, with hypertonicity and bradycardia (60 beats/min). On admission, blood glucose levels revealed profound hypoglycemia both by finger stick dextrose analysis (0.4 mmol/L) and by biochemical assay (0.9 mmol/L). After receiving 0.5 gm/kg intravenous bolus of glucose she regained consciousness promptly and her pulse stabilized at 96 beats per minute.
From the Department of Pediatrics, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel. Manuscript received February 5, 1992; revision accepted May 20, 1992. Address reprint requests to Dr Amitai, Department of Pediatrics, Hadassah University Hospital, Mount Scopus, PO Box 24035, Jerusalem, 91240, Israel. Copyright Q 1992 by W.B. Saunders Company 0735-6757/92/l 006-0012$5.00/O
556
She received additional amounts of glucose by mouth. She was afebrile and both physical and neurologic examination were normal. Other laboratory tests were: hemoglobin: 11.5 gr%, white blood cell count. 23,00O/mm~: sodium, 133 mEq/L; potassium, 5.2 mEq/L; urea, 4.9 mmol/L; calcium, 1.98 mmol/L; serumglutamicoxaloacetictransaminase, 46 IU; lactate, 1.24 mmol/L (normal 0.52.4 mmol/L); blood alcohol level, 0. Venous blood gases were: pH, 7.25; Hco,, 16.7 mEq/L; base excess, - 10.1 mEq/L; urine, normal (no ketones). Repeated measurements of blood glucose during the next 24 hours were all within the normal range. She recovered uneventfully and was discharged after 30 hours in good health.
DISCUSSION Our patient presented with generalized tonic clonic seizures due to hypoglycemia I6 hours after an albuteral overdose. She regained consciousness after receiving an intravenous bolus of glucose, and had no other episodes of hypoglycemia during the next 24 hours. There was no clinical or laboratory evidence of diabetes, other pancreatic disorders, glycogen storage disease, Reye’s syndrome, sepsis, ingestion of other hypoglycemic agents, or other metabolic disorders. Alterations in glucose metabolism following intoxication by P-sympathomimetics usually consist of hyperglycemia shortly after ingestion accompanied by hypokalemia, an expression of sympathomimetic activity.’ Hypoglycemia in association with P-sympathomimetics was described in newborns of mothers treated repeatedly by these agents as tocolytic therapy.5-7 One hypothesis to explain this association is the depletion of hepatic glycogen stores due to the prolonged sympathomimetic effect on the liver. Another hypothesis that has been suggested is a direct action of sympathomimetics on pancreatic p-cells, leading to hyperinsulinemia which results in delayed hypoglycemia.‘,’ Indeed, hyperinsulinemia has been documented in cord blood of newborns of mothers exposed to P-sympathomimetic tocolytic therapy.’ Since plasma insulin levels were not measured in our patient, the possibility of hyperinsulinemia remains hypothetical. Currently, the management of patients with acute P-sympathomimetic overdose is focused on the immediate alteration in the heart rate, potassium, and glucose levels, which usually resolve within several hours. We suggest that hypoglycemia may also be a manifestation in children and that ongoing blood glucose monitoring may thus be warranted. However, the frequency of P-sympathomimetic overdose (5,574 preschool children reported to the American Association of the Poison Control Centers National Data Collection System in 1990),9 would preclude routine monitoring of all cases. We therefore recommend that at least those children with large P-sympathomimetic overdose have their blood glucose levels monitored closely for several
WASSERMAN
AND AMITAI
n HYPOGLYCEMIA
FROM ALBUTEROL
557
OVERDOSE
hours. In those with marked hyperglycemia, monitoring should be extended until blood glucose levels have normalized. In the event of a hypoglycemic episode, documentation of plasma insulin levels will help to elucidate the mechanism of this phenomenon.
mimetic Amines. In Goodman, Gilman (eds): The Pharmacological Basis of Therapeutics, (ed 7). New York, NY, Macmillan, 1985, pp 145-180
REFERENCES
6. Svenningsen NW: Follow-up studies on preterm infants after maternal p-receptor agonist treatment. Acta Obstet Gynecol Stand 1982;108:67-7O(Suppl)
1. Wong CS, Pavord ID, Williams J, et al: Bronchodilator, cardiovascular and hypokalemic effects of fenoterol, salbutamol, and terbutaline in asthma. Lancet 1990;336:1396-1399 2. Brown MJ, Brown DC, Murphy MB: Hypokalemia from beta 2 receptor stimulation by circulating epinephrine. N Engl J Med 1983;309:1414-1419 3. Ahrens RC, Smith GD: Albuterol: An adrenergic agent for use in the treatment of asthma. Pharmacology, pharmacokinetits and clinical use. Pharmacotherapy 1984;4:105-121 4. Weiner N: Norepinephrine, Epinephrine and the Sympatho-
5. Epstein MF, Nicholls E, Stubblefield PG: Neonatal hypoglycemia after beta-sympathomimetic tocolytic therapy. J Pediatr 1979;94:449-453
7. Jovanovic R: Serial serum potassium and glucose during treatment of premature labor with oral terbutaline. Gynecol Obstet 1985;23:399-404 8. Sharp mechanism
levels Int J
GWG, Whollheim C, Muller WA, et al: Studies of insulin release. Fed Proc 1975;34:1537-1548
on
9. Litovitz TL, Bailey KM, Schmitz BF, et al: 1990 Annual Report of the American Association of Poison Control Centers National Data Collection System. Am J Emerg Med 1991;9:461-509
