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ACADEMIC EMERGENCY MEDICINE • February 2001, Volume 8, Number 2
Selected Tricyclic Antidepressant Ingestions Involving Children 6 Years Old or Less ROBIN B. MCFEE, DO, MPH, THOMAS R. CARACCIO, PHARMD, HOWARD C. MOFENSON, MD
Abstract. Objective: According to the annual report of the American Association of Poison Control Centers, tricyclic antidepressant (TCA) ingestions accounted for 15,708 exposures in 1998, of which 70% (all age groups) were treated at health care facilities (HCFs), with an estimated 2,022 children less than 6 years of age exposed. The study objective was to evaluate the manifestations, referral patterns, HCF management, and medical outcomes in pediatric patients 6 years old or less with TCA ingestions reported to a regional poison control center. Methods: All TCA (amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline) ingestions from January 1, 1993, to December 31, 1997, involving patients aged 6 years or less managed by the poison control center were evaluated for dose, symptoms, treatments, disposition, and outcome. Results: Forty-four of 48 patients (92%) were asymptomatic. All were single-drug exposures. Forty-three patients (90%) ingested a TCA dose that was less than the normally prescribed pediatric dose (5 mg/kg). Of the five chil-
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RICYCLIC and cyclic antidepressants (TCAs) are frequently involved in pharmaceutical overdose. According to the American Association of Poison Control Centers (AAPCC) annual report, 15,708 cases of TCA exposure were reported for 1998.1 Of these, 11,707 (75%) were treated in a health care facility (HCF). There were 96 deaths, most of which involved adults.1 Tricyclic antidepressants are widely used in adults for a variety of chronic pain syndromes (e.g., diabetic neuropathies, fibromylagia rheumatica), migraines, phobias, and endogenous depression. As a drug class they have generally been considered to have a narrow margin of safety. In spite of this, TCAs are increasingly being prescribed to From the Department of Preventive Medicine (RBM), Department of Emergency Medicine (TRC, HCM), and Department of Pediatrics (HCM), SUNY/Stony Brook, University Medical Center, Stony Brook, NY; and The Long Island Regional Poison Control Center at Winthrop, University Hospital, Mineola, NY (RBM, TRC, RBM). Received June 19, 2000; revision received September 21, 2000; accepted October 12, 2000. Address for correspondence and reprints: Robin McFee, DO, MPH, 48-151B Piedmont Drive, Port Jefferson Station, NY 11776. E-mail:
[email protected]
dren ingesting >5 mg/kg (range 5–9.4 mg/kg), only one (5.3 mg/kg) was mildly symptomatic (drowsy) prior to admission. Thirty-one of the 48 (65%) were sent to the emergency department (dose range 0.59– 9.4 mg/kg). Fourteen of the 31 were admitted for 12– 24-hour observation and none subsequently developed symptoms. Twenty-three (74%) received activated charcoal (AC). There was no difference in outcome between the children who did and did not receive AC. Conclusions: No case of significant toxicity occurred in the children who experienced unintentional TCA ingestions in this study population. None of the children in the study had toxicity at doses 15 mg/kg of imipramine, asserted that children show toxic effects with relatively small ingestions.18 This was supported in earlier observations suggesting children were at increased risk of cardiovascular side effects at daily doses of more than 3.5 mg/kg of imipramine.19,20 Manoguerra reported a case in which a 3-year-old developed seizure and cardiac dysrhythmia following a 100-mg ingestion of desipramine (6.7 mg/kg).9 More recent studies have failed to find a strong association between TCA dose and cardiovascular effects, even at 5
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mg/kg daily doses.6,7,14 Wilens et al. reported that despite higher weight-corrected doses of desipramine, children and adolescents tend to have lower circulating desipramine and 2-hydroxydesipramine levels than adults and are in fact at lower risk for ECG changes associated with these circulating substances than adults.7 According to Benowitz, doses less than ten times the therapeutic daily dose may produce severe intoxication, and in general ingestion of 10–20 mg/kg is potentially life-threatening.21 It appears that sudden cardiac complications do not develop unless some symptoms have been occurring beforehand, albeit subtly. In Pentel and Sioris’s study, ‘‘no patient developed arrhythmias after being alert and having a normal cardiogram for one hour.’’13 Forty-three of 48 children in our study ingested amounts that by today’s standards are medically appropriate doses2,5,7,8,14 (Tables 1 and 2). Had these children suffered from enuresis, and thus been prescribed 5 mg/kg or less, presumably there would not have been a call to poison control unless the child was symptomatic. Ninety percent of these children were and remained asymptomatic. Only four had mild initial symptoms, which rapidly resolved. One of these four children became symptomatic iatrogenically. This child received at the hospital a 50-mg dose of diphenhydramine and subsequently became ataxic. It is unknown why the patient was given diphenhydramine, since it is not recommended for the treatment of TCA exposures. Iatrogenic events are not an uncommon phenomenon. Exposing children to increased risks inherent in hospitalizations should be considered in the management of pediatric TCA ingestions, especially when a safe alternative exists. This study suggests the need to develop combination triage guidelines to include considerations of symptoms, dose in mg/kg, historian/call reliability, and the PCC ability to follow up with the patient, to aid in determining treatment recommendations. Poison control centers are increasingly focusing on such considerations and reexamining their referral patterns of the practice of referring all exposures to an HCF.18 For example, if we retrospectively applied 5 mg/kg as a benchmark, below which asymptomatic patients can safely be observed at home, then only eight children (five with ingestions >5 mg/kg and three with questionable symptoms) would have been referred to a hospital instead of 31. This represents a 74% reduction in ED visits and hospitalizations, and a substantial cost reduction estimated between $16,000 and $100,000 based on data from the Health Care Financing Administration (HCFA).22 Also of great importance is preventing the stress placed on children and families by having to go to the hospital. At a time when the health care sys-
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McFee et al. • TRICYCLIC ANTIDEPRESSANT INGESTIONS IN SMALL CHILDREN
tem in general and PCCs specifically are increasingly under significant financial pressure, the reduction in unnecessary hospitalizations can make a major contribution to saving precious resources.
LIMITATIONS AND FUTURE QUESTIONS We acknowledge that this study was retrospective using information from a single PCC gathered via the telephone. Every effort was made to verify the information, including follow-up calls to the patient and the HCF. Laboratory analyses of urine or serum were not conducted on every patient to document these exposures to a TCA. Our small sample size precludes making global recommendations. While our data are suggestive that home observation for asymptomatic children who ingest low doses of TCA (
