EMCrit 415 – Medetomidine Overdose and Withdrawal

The Opioid Series

Jeanmarie Perrone, MD

• used in veterinary sedation/analgesia
• an equal mixture of two enantiomers, dexmedetomidine and levomedetomidine (inactive)
• highly selective and potent alpha-2 agonist (100x more than xylazine)
• known to cause bradycardia and hypotension in animals

(from PennCamp)

Overdose

• Looks Like Clonidine OD
• Bradycardia (sinus without other conduction delays. May be persistent for up to 30 hours)
• Hypotension, usually mild; not requiring vasopressors
• Drowsiness, not reversed by nalaxone

Atipamezole

long-acting alpha-2 antagonist used as an antidote for medetomidine in veterinary medicine

Withdrawal

Signs and symptoms of Medetomidine withdrawal syndrome:

• Tachycardia
• Severe hypertension (may even cause, be associated with PRES)
• Nausea and vomiting
• Waxing and waning alertness
• Anxiety
• Diaphoresis
• Restlessness
• Tremor – also described as myoclonic jerks that can appear like seizure activity; however, to date, there has been no evidence that medetomidine is associated with seizures.

(from Philadelphia DOH)

refractory to increasing doses of opioids (e.g. hydromorphone, methadone, oxycodone, fentanyl), sedatives (e.g. lorazepam, diazepam, midazolam, phenobarbital, propofol, haloperidol, droperidol), and adjunctive opioid and xylazine withdrawal medications (ketamine, clonidine, tizanidine, ondansetron). (from PennCamp)

ED Management

Clonidine 0.2-0.3 mg Q4-6 hrs if pt has vital sign abnormalities in addition to the treatment for the opioid withdrawal

ICU Care of Withdrawal

(from PennCamp)

Recommended Medication Regimen

Note: Degree of alertness will influence regimen. Opioid administration should be prioritized.

• Long and short-acting opioid

Rationale: High quantities of fentanyl remain prevalent in the illicit opioid supply

• Dexmedetomidine (in lieu of clonidine)

Rationale: Drug checking reports a high prevalence of medetomidine in the illicit opioid supply

Rationale: Regionally supported (addiction medicine) adjunctive in patients using fentanyl and/or xylazine

Rationale:  Antiemetic and agitation treatment, may be particularly helpful in patients using xylazine and/or medetomidine

Rationale: Severe hypertension may persist despite aggressive treatment with the above therapies.  Earlier initiation is warranted if the patient has end organ dysfunction (hypertensive emergency).

• Additional adjunctive medications

(1a) Long-Acting Opioid

• Methadone is the preferred long-acting opioid for all patients regardless of patient desire to be on long term methadone maintenance. Transitioning to a patient’s Medication for Opioid Use Disorder (MOUD) of choice (buprenorphine vs methadone) can occur once withdrawal is controlled.

(1b) Short-acting Opioid

• Oral regimen:
  • For patients using < 10 bags per day: Oxycodone IR 30 PO q4h
  • For patients using > 10 bags per day: Oxycodone IR 40mg PO q4h
  • Increase oxycodone IR dose by 10mg as frequently as every 2 hours for COWs > 8. Goal is COWs ≤ 5.
• Unable to tolerate oral therapy: Hydromorphone 4mg IV q2h
  • Increase hydromorphone IV by 1-2mg as frequently as every 30 minutes for COWs > 8. Goal is COWs ≤ 5.

(2) Dexmedetomidine

• Start infusion at 0.5mcg/kg/hr. Titrated, by nursing, no more than 0.4mcg/kg/hr every 20 minutes up to 1.5mcg/kg/hr. Doses > 1.5mcg/kg/hr should be provider driven to a maximum of 2.5mcg/kg/hr. Titrate to SBP <160.

• Considerations for dexmedetomidine bolus:
  • A dexmedetomidine bolus of 0.5-1 mcg/kg may be given with initiation at the discretion of the provider​ OR
  • If the patient is rapidly deteriorating clinically due to suspected medetomidine withdrawal​
    • Sustained (>5 min) HR increase of >20% and/or >120 beats/min +/- sustained (>5 min) SBP increase of >20% and/or >180 mmHg​
    • With minimal improvement in vital signs, vomiting, and or tremor on dexmedetomidine infusion​
  • If bolus dose is tolerated (SBP > 100, HR > 60), increase dexmedetomidine infusion rate by 0.5 mcg/kg/hr
• Contraindications: Heart rate < 50 BPM, MAP < 65 mmHg, Second/Third degree heart block
• De-escalate to clonidine once withdrawal has started to abate and can tolerate oral medications (estimated in 24-48 hours).

(3) Ketamine (Oral/Intravenous)

• Oral: 1.5-3mg/kg divided into q6h dosing
  • Example: 70kg patient would receive 30mg PO q6h
• Unable to tolerate oral therapy: Start infusion at 0.1-0.5mg/kg/hr (maximum initial rate of 50mg/hr, maximum overall rate of 0.5mg/kg/hr). Further dosing instructions can be found in the subanesthetic Ketamine for Analgesia Guideline.
• Contraindications: Recent/active CVA or cardiovascular disease, Child Pugh C

(4) Olanzapine/Prochlorperazine (Nausea/ Agitation Management)

• Olanzapine IV or PO: 10mg x1, then 5mg daily at bedtime
  • Contraindications: QTc > 500 mm/sec
• Prochlorperazine IV: 10mg q8h (Combination with olanzapine may be considered)
  • Contraindications: QTc > 500 mm/sec

(5) Antihypertensive agents

• If severe hypertension persists despite the use of the above medications, treat with short acting blood pressure lowering agents as per ICU protocol for the management of hypertensive emergency
• Easily titratable agents such as IV nicardipine drip, IV esmolol drip, IV labetalol, or IV hydralazine

(6) Additional adjunctive medications

• Adjunctive medications orderable via Opioid Withdrawal order set
  • Clonidine PO in particular may be helpful for managing autonomic symptoms. If unable to tolerate PO, consider utilizing the patch formulation.
• Can consider the use of phenobarbital (utilizing pre-existing ICU guidelines for managing alcohol withdrawal) or benzodiazepines (scheduled taper preferred over CIWA symptom-triggered dosing) if requiring additional sedation. Not routinely indicated, unless the patient also reports benzodiazepine or alcohol use.

(from PennCamp site)

For Full Document on UPHS ICU Management of Opioid with Adulterants Withdrawl, go to the PennCamp Medetomidine Page

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Editor-in-Chief, at EMCrit.org

An ED Intensivist from NY.
Professor
Nassau University Medical Center
No conflicts of interest (coi).

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