Infants and atropine: A dangerous mixture

zyxwvutsrqponm zyxwvutsrq J. Paediafr. Child Health (1991) 27, 55-56 Infants and atropine: A dangerous mixture E. J. PICKFORD, R. M. HANSON, M. T. O’HALLORAN, D. FENWICK, P. NOBLE and J. D. McDONALD The Children’s Hospital, Camperdown, New South Wales, Australia zyx Abstract Colic in infants is a common but short-lived problem. Many different theories and treatments for this distressing ailment have been tried over the years, yet the definitive cure remains elusive. Although the risks associated with the use of atropine and its derivatives are well known, they are still prescribed by some in the management of colic. We report a case of serious side effects from the treatment of colic with an atropine containing mixture, in which an error in preparation was identified. In view of the potential for serious toxicity resulting from either inappropriate prescription, preparation or administration, alternative methods of treatment should be employed. Key words: atropine; colic: overdose. The problem of the colicky baby has plagued both parents and physicians for centuries. Theories abound on the cause of this symptom complex,’-5 which affects 20-30% of infants. However, little progress has been made towards a universal cure for the discomfort these babies (and their parents) appear to suffer. Opinion is divided on the cause and treatment of colic. Varying reliance is placed on pharmacological agents. Treatment with a phenobarbitone and atropine mixture is advocated by some to break the cycle of maternal and infant distress. Although only recommended for short-term use, and on a limited basis? our experience suggests that its prolonged use may be widespread. We present a case of atropinization, resulting from an accidental pharmaceutical error in product preparation, as a warning against its widespread use. CLINICAL RECORD A 5 week old male infant was presented to the Casualty Department of the Children’s Hospital, Camperdown. He had an uneventful perinatal history, and was noted by his parents to be ‘colicky’ from the age of 2 weeks. His local doctor had prescribed a phenobarbitone and atropine mixture (phenobarbitone 15 mg, atropine 0.06 mg/5 mL, giving 1.7 mg/kg per dose of phenobarbitone, and 0.007 mg/kg per dose of atropine) in a dose of 2 mL 4 times per day from the age of 2 weeks. He showed no ill effect. Whilst away on holidays his parents purchased a new bottle of this mixture from a retail pharmacy, with a legible although ambiguous prescription in which the concentration of both drugs in the final mixture was unclear. A single 2 mL dose had been given from this new bottle on the evening prior to presentation. Twelve hours following the administration of this mixture he would not feed, had not passed urine for a number of hours, and was unable to be woken. There was no other relevant history. On initial examination, the infant was deeply asleep with dilated pupils and a palpable bladder. He was normotensive and was not flushed. No other cause for his coma was found. He was considered to have signs and symptoms of atropinization. His serum phenobarbitone level was 80 pmol/L, which is in the therapeutic range for seizure prophylaxis (40-130 pmol/L), and was not felt to be responsible for his symptoms. The serum concentration of atropine could not be quantitated. Analysis of the medication showed the phenobarbitone (12 mg/5 mL) to be as prescribed but the atropine (28 mg/5 mL) to be 500 times that prescribed. This gave a calculated dose of atropine of 3.2 rng/kg bodyweight. Treatment was supportive as he was neither hypertensive nor tachycardic and cardiac conduction defects were not detected. The infant was discharged from hospital 48 h later, having woken without complication. The error resulted from a measurement error of the amount of atropine added to the solution as a result of inaccurate weighing scales. Appropriate measures were taken by the pharmacy to ensure that the error would not recur, in addition to an official investigation by the Department of Health. DISCUSSION The cause of ‘infantile colic’ remains controversial,’ -5 and opinion on treatment is similarly divided with many authors recommending counselling for parents as the primary treatment of infantile Others have relied on a broad range of pharmacological agents, although no single agent has been shown to be effective.’a2 Whilst dicyclomine hydrochloride enjoyed widespread use for some years, subsequent reports of toxicity, particularly in infants under 6 months, led to its use being c~rtailed.’~~’~ Anticholinergics are recommended as treatment for colic on the basis of reducing gastrointestinal motility. The benefits of phenobarbitone appear to be those of sedation. The potential zyxwvutsrqpo zyxwvutsrqpo Correspondence: Dr R.M. Hanson, The Children’s Hospital, Camperdown, NSW 2050, Australia. E. J. Pickford. MS, BS (Hons), Paediatric Registrar. R. M. Hanson, BSc (Med), MBBCH, FRACP, Staff Physician in Accident and Emergency. M. T. O’Halloran. BSc. FAACB, Head, Department of Biochemistry. D. Fenwick, BPharm, Head Pharmacist. P. Noble, BPharm, Deputy Head Pharmacist. J. D. McDonald. MB, SS,FRACP. Consultant Physician. Accepted for publication 19 October 1989. zy zyx 56 E. J, Pickford e t a / , for overdose and the toxic effects of such medications are well d e s ~ r i b e d .Toxicity ~ ~ ’ ~ has been reported with atropine doses of 0.39-3.55 mg/kg.” The dose given to this child falls towards the upper end of this range. Diagnosis of anticholinergic toxicity is made on clinical grounds. Serum levels of the drug are said not to be clinically . ~ alternative method of relevant, and are difficult to ~ b t a i nAn diagnosis in suspected anticholinergic ingestion is the administration of intravenous physostigmine. Reversal within minutes of all or almost all of the symptoms would be consistent with anticholinergic ingestion9 This is not without risk and should be reserved for those patients with significant toxicity, including convulsion, severe hallucinations, hypertension or cardiac arrhythmias which are haemodynamically significant. However, physostigmine should not be used in those patients with cardiac conduction defects for fear of inducing malignant ventricular arrhythmias. Without the knowledge that ‘colic’ is a common but shortlived symptom in young babies and, in the absence of reports of long-term ill effects resulting from it, the risks of side effects from treatment outweigh the benefits of routine use of such medications. Although on occasions there may be indications for the judicious use of pharmacologic agents, we favour addressing the cycle of maternal and infant distress through counselling and support. We have not formally assessed the extent of the problem, but judging from the number of enquiries to our pharmacy, the mixture of atropine and phenobarbitone may be more widely used by general practitioners than by paediatricians. Although its use is still recommended by some paediatricians,6 their guideline for its short-term use is often forgotten. The frequent use of this mixture on a long-term basis is highlighted by the patient presented, who had been prescribed the mixture for 3 weeks. Although dispensing errors are, in general, rare, in view of the potential for serious toxicity resulting from inappropriate pre- scription, preparation or administration, alternative methods for the treatment of infantile colic should be employed. ACKNOWLEDGEMENTS We acknowledge with thanks the help given us by the Division of Analytical Laboratories, NSW Department of Health. zyxwvutsrq REFERENCES 1 Gillies C. Infant colic: Is there anything new? J. Paediatr. 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