Medetomidine / Opioid Withdrawal Syndrome A local treatment pathway for ME/OWS at Jefferson Einstein Philadelphia Hospital

Read before using this pathway

  • Do not use this flow diagram unless you have been told to do so by the consulting service.
  • This was developed primarily for internal use but may serve as a reference guide.
  • This is not officially endorsed by Jefferson, Einstein, the Department of Emergency Medicine, or the Division of Toxicology. It is merely a local workflow that appears to work thus far anecdotally.
  • Nothing here replaces bedside clinical judgment, an individualized assessment, or direct discussion with Toxicology or Addiction Medicine.

01 The pathway

ME/OWS is two withdrawal syndromes at once, and both have to be treated. Opioid titration alone frequently fails to capture symptoms, because the alpha-2 agonist withdrawal is left untreated. Check the hold criteria before every dose.

Start here
Do you suspect combined medetomidine/opioid withdrawal (ME/OWS)
and a COWS > 10?
No → pathway does not apply Stop here. Reassess the differential: isolated opioid withdrawal, an alternative toxidrome, or a non-withdrawal cause of the presentation. Discuss with Toxicology if the picture is unclear.
Treat both withdrawal syndromes concurrently
OPIOID

Opioid withdrawalHydromorphone

Hydromorphone 4 mg IV × 1
Reassess COWS in 5 minutes.
COWS < 10 → captured No further boluses needed. Go to scheduled dosing.
Hydromorphone 8 mg IV × 1
Reassess COWS in 5 minutes.
COWS < 10 → captured No further boluses needed. Go to scheduled dosing.
Hydromorphone 12 mg IV × 1
This usually captures their symptoms at this point. Reassess COWS in 5 minutes.
COWS < 10 → captured No further boluses needed. Go to scheduled dosing.
Reconsider the diagnosis
Suspect a mixed withdrawal/toxidrome or an alternative cause of tachycardia:
  • Alcohol or benzodiazepine withdrawal
  • Sepsis
  • Injury or uncontrolled pain
Confirm the alpha-2 withdrawal has been treated before concluding the pathway has failed.
ALPHA-2

Medetomidine withdrawalClonidine / Precedex

Decision
Can the patient tolerate PO?
Yes
Clonidine 0.6 mg PO × 1
Schedule clonidine 0.3 mg PO q3h
Standing scheduled order.
No
Treat the opioid withdrawal first.
Work the opioid side before reaching for a drip. Nausea and vomiting from untreated opioid withdrawal is a common reason PO fails, and treating it often restores the ability to take PO.
Dexmedetomidine (Precedex) drip at institutional max 2.5 mcg/kg/hr, titrated down as needed.
Once admitted
If the patient becomes bradycardic or hypotensive and is on both agents, hold the Precedex before the clonidine.
Full alpha-2 hold criteria are in the hold criteria below.
Maintenance, once symptoms are captured
  • Continue hydromorphone 4 mg IV q3h scheduled
  • and hydromorphone 4 mg IV q3h PRN for COWS > 10
  • Continue scheduled clonidine 0.3 mg PO q3h, or the Precedex drip, titrating down
Withdrawal typically peaks 24 to 48 hours after last use, so requirements may rise before they fall. Keep reassessing.
Clonidine taper

Taper clonidine over 3 to 4 days once withdrawal has peaked. Example taper, to be titrated clinically as needed:

Day 1
Clonidine 0.3 mg q6h
Day 2
Clonidine 0.2 mg q8h
Day 3
Clonidine 0.1 mg q12h
Clonidine patches Patches do not start being effective until 24 hours in, so they will not cover an acute withdrawal. They are also pricy, at roughly $100 per patch.
Timing Medetomidine/opioid withdrawal typically peaks 24 to 48 hours after last use. Requirements often escalate over that window, so a patient captured early may need more later.

STOP Hold criteria

These override every step in the pathway. Re-check them before each escalation.

Hold alpha-2 agonism (clonidine / Precedex)

  • Heart rate < 50
  • Systolic blood pressure < 90
  • Complicating factors such as sepsis, where sympathetic tone is desirable
  • If the patient is on both agents and becomes bradycardic or hypotensive, hold the Precedex before the clonidine.

Hold opioids

  • Respiratory depression
  • Inability to protect the airway

02 MAT starts & transitions

Timing matters more than dose here. Starting buprenorphine before 48 hours from last illicit use is the most common avoidable harm on this pathway. Microinduction is the way around that wait when the patient will not or cannot hold off.

Buprenorphine/naloxone (Suboxone)standard start

Suboxone 8 mg TID, starting 48 hours from last illicit use.

Any sooner, even by a few hours, almost always precipitates withdrawal.

This holds even if the COWS score is very high. A COWS of 30 or more does not make it safe to start early. Go by the time since last use, not by the number.

Microinduction (Suboxone / Belbuca)4-day start

Useful to get patient buy-in and to buy the 48 hours needed to avoid precipitated withdrawal. The trade-off is that it takes 4 days. There is a power plan for this.

Day 1
300 mcg QID
Day 2
600 mcg QID
Day 3
2 mg QID
Day 4
8 mg TID or QID

Anecdotally, it takes at least 2 mg of buprenorphine to precipitate withdrawal, if it happens at all.

Methadonenew start

Methadone 40 mg PO daily per the power plan. Three requirements:

  • Confirm QTc < 500. Methadone is a known QTc prolonger.
  • Outpatient methadone clinic follow-up must be arranged prior to discharge, per the law.
  • The patient must be admitted for a reason other than opioid withdrawal. Add nausea/vomiting or inability to tolerate PO to the admitting diagnosis. This institution is not an ASAM-certified addiction center.

Already on methadonecontinuation

Give methadone 40 mg PO daily until the primary team has confirmed dosing with the patient's methadone center.

Methadone → buprenorphinetransition

Discuss the case with the Addiction Medicine team or Toxicology.

03 Before discharge: harm reduction

Easy to forget in a busy department.

  • Prescribe naloxone (Narcan) prior to discharge for harm reduction, for every patient on this pathway.
  • If history of IVDU: recommend screening Hepatitis C with reflex to titer.
  • If of childbearing age: recommend a urine HCG.
  • If starting methadone: confirm outpatient clinic follow-up is in place before the patient leaves. This is required by law.

04 FAQ & pitfalls

Common questions on this pathway.

I've given narcan and it didn't work!

Naloxone is really good at reversing opioid toxidromes. 10 mg is enough to reverse even the most potent of analogues.

Start at 0.04 mg IV and double the dose after waiting a few minutes.

Continue doubling until there is a response, or until roughly 10 mg total has been given. A single doubling is not an adequate trial. Allow a few minutes between doses so that each dose is titrated to response. Doubling from 0.04 mg reaches about 10 mg cumulative after eight doses:

mg IV 0.04 0.08 0.16 0.32 0.64 1.28 2.56 5.12 ≈ 10 mg total

Starting low and doubling limits the risk of precipitating withdrawal in a patient who would have responded to a much smaller dose.

If 10 mg total has been given without a response, further naloxone is unlikely to help.

If it doesn't reverse, it is either because it is not an opioid toxidrome, they are so hypercarbic that their respiratory centers are dysfunctional, or because there is a potent alpha-2 agonist like medetomidine on board.

Narcan doesn't sound very helpful when much of the street fentanyl in the area is contaminated with medetomidine.

But it is. The opioid and alpha-2 agonist toxidromes look very similar, with one clinically important difference:

Alpha-2 agonism typically does not cause respiratory depression. That is why the ICU extubates on Precedex.

So in a mixed opioid/alpha-2 toxidrome, naloxone may make your patient start breathing again even if their mental status doesn't improve. If the patient is still somnolent but now breathing after naloxone, that finding supports a mixed toxidrome.

My COWS score seems too high for how the patient looksScoring pitfall

The COWS items for nausea, vomiting, and diarrhea refer only to the last 30 minutes, not last night and not hours ago. Patients frequently report the whole day, which inflates the COWS score.

Weight the objective portions of the score more heavily:

  • Tachycardia
  • Diaphoresis
  • Piloerection
  • Dilated pupils

Patients will often report extreme anxiety despite dozing off mid-conversation.

What if the patient wants to start MAT like suboxone?

You can start suboxone 8 mg TID, beginning 48 hours from last illicit use.

Any sooner, even by a few hours, almost always precipitates withdrawal.

This holds even if the COWS score is very high. A COWS of 30 or more is not permission to start early, and a floridly withdrawing patient at 40 hours is still at 40 hours. Go by the time since last use, not by the number. See the scoring pitfall on why these scores run high.

If the patient will not wait, or you want to improve the odds they stay engaged, consider the microinduction protocol. It buys the 48 hours and helps with patient buy-in, at the cost of taking 4 days.

I've accidentally precipitated withdrawal with suboxone. What do I do? Can I power through it with more suboxone?

Anecdotally, no. Even large doses, up to 32 mg of suboxone, have not been enough to counteract precipitated withdrawal in the North Philadelphia area.

Manage supportively and involve Toxicology or Addiction Medicine.

What if the patient wants to start methadone while in withdrawal?

You can give methadone 40 mg PO daily per the power plan, with three conditions:

  • Make sure the QTc is < 500. Methadone is a known QTc prolonger.
  • They must have outpatient methadone clinic follow-up set up prior to discharge, per the law.
  • They must also be admitted for a different reason than opioid withdrawal. Add nausea/vomiting or inability to tolerate PO to the admitting diagnosis, as our institution is not an ASAM-certified addiction center.
What if the patient is already on methadone?

You can give methadone 40 mg PO daily until the primary team has confirmed dosing with their methadone center.

What if the patient wants to transition from methadone to suboxone?

Discuss the case with the Addiction Medicine team or Toxicology.

These doses of medications are really high. Should I be concerned?

The literature is scant on doses this high. Lower doses of Precedex have been used for procedural sedation.

Yes. Your patient's body is unfortunately accustomed to frankly ludicrous doses of drugs in the drug supply:

  • A baggie of fentanyl is 2,000 to 5,000 mcg of fentanyl.
  • A typical patient uses 6 to 24 bags a day.
  • A bundle is roughly 12 to 16 baggies.

The drug supply in North Philadelphia is constantly adulterated with varying amounts of medetomidine. While xylazine is still occasionally seen, it is not present in clinically significant doses.

The hold criteria above still apply, as does continuous monitoring at these doses.

Internal reference only. Not for use unless directed by the consulting service. Not officially endorsed by Jefferson, Einstein, the Department of Emergency Medicine, or the Division of Toxicology.