Abstract
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A 6-year-old 28 kg girl with medical history of ADHD presented to our emergency department with 48 hours of lethargy and somnolence. The mother reported this to be entirely unlike the child's usual hyperactive state. The child's medications included clonidine 0.1 mg daily, and guanfacine 2 mg (0.07 mg/kg) each morning and 1 mg each evening (0.03 mg/kg). The mother denied any other medications in the home other than children's multivitamins and denied any likelihood of the child unintentionally ingesting extra clonidine or guanfacine. The mother reported that the child in fact had not received any medications in 48 hours due to running out of all medications.
The patient's vital signs on arrival were temperature 37.1°C, heart rate 42 beats per minute (below the 1st percentile for age), blood pressure 100/75 mmHg (∼90th percentile for age, gender, and height), respiratory rate of 21 breaths per minute, and her room air oxygen saturation was 100%. Her general physical examination was notable for a somnolent young girl with 2 mm equally reactive pupils that aroused with minimal physical stimuli, but promptly returned to sleep. A serum toxicological screen was negative for barbiturates, benzodiazepines, cocaine, and opiates. Extended testing for common synthetic, semisynthetic, and natural opioids was also negative. Electrocardiogram showed sinus bradycardia at 50 beats per minute with normal intervals. Naloxone 3 mg was given intravenously without improvement.
The patient was admitted for unconfirmed central alpha-2 agonist toxicity. She was discharged 48 hours later upon return to her usual baseline mental status for a total of 96 hours of depressed mental status. Postdischarge, a plasma guanfacine concentration of 40 ng/mL was reported from plasma obtained on admission, thus, ∼48 hours since the onset of lethargy and >48 hours since the last known dose of guanfacine. For comparison, peak plasma guanfacine concentrations of about 4 ng/mL have been reported to occur 4–5 hours after daily ingestion of 2 mg guanfacine extended release in children aged 6–12 years (Boellner et al. 2007). Clonidine was not detected in the sample.
Central alpha-2 agonist poisoning is a common presentation among pediatric poisonings, typically due to exploratory unintentional ingestions (Winograd et al. 2020). Central alpha-2 agonist poisoning can present remarkably similar to opioid toxicity, making the diagnosis unclear. Guanfacine and clonidine concentrations are not usually obtained to confirm the diagnosis, but may be useful in the setting of unobserved exposure or unclear presentation. Only one prior clinical report has provided guanfacine concentrations to confirm diagnosis (Van Dyke et al. 1990). We speculate that the child had unintentionally ingested additional tablets while unobserved, resulting in prolonged clinical toxicity starting 48 hours before presentation and continuing for another 48 hours of hospitalization.
Elimination half-life of guanfacine in therapeutic dosing has been reported as 14–15 hours (Boellner et al. 2007). However, it is critical for clinicians to understand that the toxicodynamic effects of pharmaceuticals in overdose are unpredictable due to prolonged absorption, and/or saturated metabolism or elimination pathways. Duration of effect cannot be inferred from pharmacokinetics determined with therapeutic dosing. A longer than expected monitoring period may be required. Plasma testing of guanfacine and/or clonidine concentrations may provide clinical utility to confirm the diagnosis in cases of unclear toxicity.
Footnotes
Authors' Contributions
J.W.D. and B.K.W. drafted the text of the article. C.E.W. performed laboratory analysis and reviewed the article. K.L.C. and S.R.R. reviewed and edited the article.
Disclosures
The authors declare that there are no conflicts of interests to disclose.