Inadvertent Iatrogenic Misuse of Intravenous Diphenhydramine in an Adolescent: Implications for Routine Medication Administration

[Author Affiliation]Kendra J. Grim. 1 Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.Philip R. Fischer. 2 Department of Pediatrics, Mayo Clinic, Rochester, Minnesota.Jason S. Eldrige. 1 Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.Address correspondence to: Kendra J. Grim, MD, 200 First Street SW, Rochester MN 55905, E-mail: grim.kendra@mayo.eduTo The Editor:Diphenhydramine has been considered a relatively safe medication, with multiple indications. Common uses in pediatrics include sedation and treatment of pruritus and nausea. Many hospitalized children and adolescents receive intravenous diphenhydramine. Anecdotally, adolescents report a very pleasant feeling with rapid intravenous infusion and sometimes request administration this way for the "high" they experience. Actual abuse of repeated intravenous diphenhydramine has only very rarely been reported.Case ReportA 22-year-old female was admitted to our hospital for evaluation of a possible intra-abdominal abscess following transplanted kidney removal at an outside institution. She had a history of three prior renal transplants, the first occurring at 3 years of age. Her latest transplanted kidney failed>1 year prior, and she was dependent on intermittent hemodialysis. Psychiatric consultation diagnosed her with a mood disorder secondary to her medical condition, and did not find an Axis II diagnosis. Global Assessment of Functioning was rated to be 50-55. Input from a pain medicine specialist was requested for acute or chronic abdominal pain management. The patient was requesting intravenous diphenhydramine 50 mg every 4 hours for pruritus provoked by multiple triggers, including narcotics, intravenous antibiotics, blood transfusion, and dialysis. Historically, she had been treated with intravenous diphenhydramine starting at 8 years of age, with initial doses of 25 mg intravenously. At her current outpatient hemodialysis appointments (three times weekly), she received one 50 mg intravenous dose prior to the start of dialysis, and a second 50 mg dose at the conclusion of each dialysis session.While hospitalized, she requested that diphenhydramine be administered while she was awake to observe the administration, and demanded that rapid intravenous injection be followed by saline flush. She became visibly upset when she was not awoken for her scheduled diphenhydramine doses. After observing this behavior, the intravenous diphenhydramine was discontinued, and she was offered oral diphenhydramine to treat pruritus instead. She subsequently displayed further anger, stating "I demand to have my IV Benadryl." When told that intravenous delivery was no longer indicated, she denied secondary or euphoric effects of diphenhydramine. Although she was offered oral diphenhydramine to treat pruritus, and prevent withdrawal, she continued to demand intravenous diphenhydramine. She threatened to refuse intravenous antibiotics and dialysis. The patient was not listed for renal transplant for multiple reasons, including the need for further testing such as stress echocardiogram, vascular computed tomography study, and Pap smear. The patient's demand for diphenhydramine was also listed as requiring treatment prior to transplantation.After hospital discharge, the patient did not complete the required testing for transplantation at our institution, and did not return follow-up phone calls. Notification of her death was received, having occurred 10 months after her hospital discharge. The cause of death was not available.The patient had consented to research via Minnesota Research Authorization, and institutional review board (IRB) approval was obtained.DiscussionDiphenhydramine is a first generation antihistamine of the ethanolamine family. A competitive inhibitor of H1-receptors, diphenhydramine also has anticholinergic/antimuscarinic and antiserotonergic activity. …