Case #18: A Rapid Drop
Author: Brendan Devine, MD
Peer Reviewer: Michael Nelson, MD
A 5 year old male is brought into the ED by his father after being found limp and unresponsive at home. His past medical history is significant for ADHD which is treated currently with methylphenidate and clonidine. The patient had received his AM dose just one hour prior to presentation. The father denies any change in dose or the child having access to other medications. The exam is notable for a pale and listless child that responds to noxious stimuli and has miotic pupils.
Vitals: Temp: 94, HR: 52, RR: 40, BP: 147/97, O2 Sat: 94% on RA.
After your initial assessment the patient’s blood pressure drops to 75/35 and the patient develops severe respiratory depression.
What toxic ingestion are you concerned about at this time?
Although both methylphenidate and clonidine can cause hypertension and unresponsiveness, the subsequent hypotension and respiratory depression is most consistent with
acute clonidine overdose.
Clonidine is a centrally acting alpha-2 agonist that typically resembles opiate overdose (miosis, hypotension, bradycardia, bradypnea, hypothermia, and lethargy/coma). However, clonidine initially present with a transient hypertension secondary to its agonism of alpha receptors in the periphery.
What is your initial management of this patient?
Intubate and ventilate the patient. Give an initial IV fluid bolus and consider pressor support if the BP is not improving with fluids.
There are no diagnostic tests that confirm clonidine (or any other imidazoline) toxicity other than the history and presentation. The bradycardia typically responds well to atropine. Because clonidine has some activity at opioid receptors (hence its usefulness for opiate withdrawal), naloxone has been proposed as a potential treatment. Typically, much higher doses than those used for opioid overdose are needed. There is no direct antidote, however, and the majority of treatment is directed at supportive care as noted above.
What is the typical onset of action for this drug?
For oral clonidine pills, the toxic effects are usually seen within one hour of ingestion. For clonidine patches, the peak effect is reached in 40-80 hours and thus the time to toxicity is variable. A search for clonidine patches should be done on any patient presenting with signs and symptoms of clonidine overdose. The half-lives of the oral and transdermal forms of clonidine are 12-16 and 26-55 hours, respectively.
What other medications are in this class of drugs?
Clonidine is in the imidazoline class of drugs. Other commonly seen medications in this class include alpha-methyldopa, guanfacine, guanabenz, and dexmedetomidine. Alpha-methyldopa toxicity can cause a Coombs-test positive hemolytic anemia, thrombocytopenia, and granulocytopenia.
What is the most common symptom from rapid clonidine withdrawal?
Rapid clonidine withdrawal can lead to profound hypertension. Treatment consists of resuming clonidine with slow titration to another antihypertensive medication.
What is the disposition of these patients?
For clonidine toxicity the disposition is dependent upon the drug form ingested (oral versus topical), as well as the presence or absence of symptoms. For patients who have taken the oral form and are asymptomatic, supportive care and observation is recommended for at least 6 hours. The patient with transdermal toxicity will typically need 24 hour observation due to the prolonged duration of action.
References:
Ahmad SA, Scolnik D, Snehal V, et al. Use of Naloxone for Clonidine Intoxication in the Pediatric Age Group: Case Report and Review of the Literature. Am J Ther. 2013 Jun 18.
Anderson RJ, Hart GR, Crumpler CP, et al. Clonidine overdose: report of six cases and review of the literature. Ann Emerg Med. 1981 Feb;10(2):107-12.
Farooqi M, Seifert S, Kunkel S, et al. Toxicity from a clonidine suspension. J Med Toxicol. 2009 Sep;5(3):130-3.
Romano MJ, Dinh A. A 1000-fold overdose of clonidine caused by a compounding error in a 5-year-old child with attention-deficit/hyperactivity disorder. Pediatrics. 2001 Aug;108(2):471-2.
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