November 1976 TheJournalofPEDIATRICS

833

Letter to the Editor Metabolic effect of theophylline in the premature neonate ,..

To the Editor: Recent studies have shown that theophylline, 1,3 dimethylxanthine may prevent or decrease the occurrence of apnea in the premature newborn infant: ' Besides the pharmacologic actions of the methylxanthines, which include stimulation of respiration, augmentation of cardiac inotropy and chronotropy, relaxation of smooth muscles of the bronchi and blood vessels other than cerebral vessels, and diuresis,:' there are effects on metabolic homeostasis which may be deleterious or beneficial to the neonate. The metabolic effects include increase in plasma free fatty acids:' and stimulation of glucagon and insulin release: The present report describes the glucose response following intravenous infusion of aminophylline at a dose of 2.5 and 5 mg/ kg given in ten minutes ~' into two premature neonates with recurrent apneic spells. Patients 1 and 2 weighed 1,010 and 1,080 gm at birth, respectively. The gestational age of each was 27 weeks. Postnatal ages when aminophylline was given were nine days (Patient 1) and three days (Patient 2), respectively. Patient 1 received nothing by mouth since birth, after initial attempts of gavage feeding resulted in abdominal distention. At the time of the study, maintenance fluids containing electrolytes in 10% glucose were given intravenously via a constant infusion pump to give 120 ml/kg/day. Aminophylline was administered via a second intravenous site to prevent changes in the rate of glucose infusion, Following aminophylline infusion, blood samples of glucose were obtained from heel punctures, and the blood glucose concentrations were measured immediately by the glucose oxidase method (Beckman glucose analyzer, Beckman instruments, Inc., Fullerton, Calif.). Fig. 1 shows the rise in blood glucose concentration within 15 minutes which was sustained for at least 60 minutesl Patient 2 was taking milk formula (Similac 20) via a continuous nasogastric infnsion at the rate of 5 ml/hour. Preaminophyllinc infusion blood glucose concentration was higher than that of Patient 1; however, a similar rise in blood sugar concentration was noted within five minutes, which was sustained for 60 minutes with a return to near baseline in 120 minutes (Fig.l). DISCUSSION Theophylline and related methylxanthines (caffeine, theobromine) are known competitive inhibitors of cyclic nucleotide phosphodiesterase leading to increase in cyclic 3'5' adenosine monophosphate levels.'" The increase in blood glucose concen-

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M i n u t e s after I.V. A m i n o p h y l l i n e Fig. 1. Blood glucose concentrations following intravenous infusion of aminophylline with doses of 2.5 mg/kg and 5 mg/kg in Patients 1 and 2, respectively.

tration may be due to activation of hepatic phosphorylase by cyclic 3'5' adenosine monophosphate leading to glycolysis and increased formation of blood glucose. Stimulation of glucagon

S e e related article, p. 829. release by theophylline ~ will also lead to increased blood glucose concentration; however, this effect may be counteracted by the simultaneous release of insulin: Further studies are needed to elucidate the effect of the methylxanthines on glucose homeostasis in the newborn infant. Jacob IZ Aranda, M.D. Ph.D. Queen Elizabeth I i Research Scientist Claire Dupont, M.D, Ph.D. The Departments of Pediatrics Pharmacology, and Therapeutics McGill Universi O' The Department of Newborn Medicine and Clinical Biochemisfr), Montreal Children's Hospital 2300 Tupper St. Montreal, Quebec' H3H tP3, Canada

Vol. 89, No. _5, pp. 833-834

834

Letter to the Editor

REFERENCES

1. Kuzemko JA, and Paala J: Apnoeic attacks in the newborn treated with aminophylline, Arch Dis Child 48:404, 1973. 2. Shannon DC, Gotay F, Stein IM, Roger MD, Todres ID, and Moylan FM: prevention of apnea and bradycardia in low-birthweight infants, Pediatrics 55:589, 1975. 3. Uauy R, Shapiro DE, Smith B, and Warshaw J: Treatment of severe apnea in prematures with orally administered theophylline, Pediatrics 55:595, 1975. 4. Lucey JF: The xaathine treatment of apnea of prematurity, Pediatrics 55:584, 1975. 5. Murdoch-Ritchie J: Central nervous system stimulants II: The xanthines, in Goodman LS, and Gilman A, editor: Tl~e pharmacological basis of therapeutics, ed 4, New York, The Macmillan Company, p. 358-370.

The Journal of Pediatrics No~ember 1976

6. -Bellet S, Kershbaum A, and Aspe J: The effect of caffeine on free fatty acids, Arch Intern Med 116:750, 1965. 7. Leach FN, Ashworth MA, Barson AJ, and Milner RDG: Insulin release from human fetal pancreas in tissue culture, J Endocrinoi 59:65, 1973. 8. Goldman H, and Colle E: Human pancreatic islets in culture: Effects of supplementing the medium with homologous and heterologous serum. Science (in preSs). 9. Aranda JV, Sitar DS, Parsons WD, and Neims AH: Pharmacokinetic aspects of theophylline in premature newborns, N Engl J Med (submitted 1975). 10. Butcher RW, and Sutherland EWi Adenosine 3'5'-phgsphate in biological materials, J Biol Chem 237-1244, 1962.

Metabolic effect of theophylline in the premature neonate.

November 1976 TheJournalofPEDIATRICS 833 Letter to the Editor Metabolic effect of theophylline in the premature neonate ,.. To the Editor: Recent s...
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