Case Presentation: A 53-year-old African American woman with a history of systemic lupus erythematosus, refractory hypertension, and cerebrovascular accident, was found unresponsive and hypotensive at home. On presentation, the patient was drowsy but arousable and oriented to person, place and time. Vitals were notable for sinus bradycardia (50s) and hypotension (SBP in 90s). She was on multiple medications for hypertension, including amlodipine, carvedilol, lisinopril, clonidine, nifedipine, and spironolactone. She did not take any of the antihypertensive medications for previous one month except on the day of presentation when she restarted clonidine and carvedilol. Labs were noted for acute kidney injury (AKI) (creatinine: 1.92 baseline 0.8). Urine toxicology screen including opioids and benzodiazepines was unremarkable. CT head was negative for acute findings.Following the initial evaluation, the patient became disoriented and somnolent with slurred speech. She also became hypotensive (SBP in 60’s to 70’s), and was fluid resuscitated. Interestingly, naloxone (8 mg IV) administration resulted in a rapid and dramatic improvement in her alertness to baseline levels. Toxicology workup including – acetaminophen and aspirin levels returned as unremarkable. She was diagnosed with likely Clonidine overdose (CIO) and monitored carefully with supportive care off clonidine. She did not need any more naloxone. Toxicology consultation confirmed the diagnosis. AKI resolved with IV fluid resuscitation.
Discussion: Clonidine inhibits central norepinephrine release through alpha-2 adrenergic receptors. Usual clinical presentation of clonidine overdose includes profound hypotension, and bradycardia due to inhibition of sympathetic outflow as noted in our patient. Respiratory depression, hypopnea, lethargy and coma may also be seen in severe cases of clonidine poisoning.
Clonidine is renally excreted and with AKI in our patient, despite the low dose given the narrow therapeutic index, ClO likely resulted. Though clonidine overdose could masquerade opioid overdose with similar CNS and respiratory depression, and response to naloxone; bradycardia, significant hypotension, temporal ingestion of clonidine, lack of opioid intake with confirmation on drug screen were strong pointers towards clonidine as the offending agent.
Therapy is typically supportive (IV fluid resuscitation, atropine) and aimed at countering clonidine’s autonomic effects. Naloxone also has been successfully used in clonidine overdose. Though the mechanism remains unclear, it is thought to be through its action at the locus ceruleus, which is one of the primary sites of adrenergic catecholamine production in the brain.
Responses to naloxone in clonidine overdose are variable: lack of response to clonidine should not be used to rule out the diagnosis of clonidine overdose. Nonetheless, a dramatic and favorable response to naloxone, as seen in this case, can help support the diagnosis of clonidine overdose. Though there is a paucity of rigorous research on naloxone for this purpose, it appears to be a relatively safe, fast-acting and potentially efficacious therapy for proven or suspected clonidine toxicity in some patients.
Conclusions: #Clonidine overdose can be a cause of altered mental status in a patient on multiple antihypertensive medications.
#Naloxone has a diagnostic and therapeutic utility in of clonidine overdose.