Opioid withdrawal resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vidit Bhargava, M.B.B.S [2]; Vendhan Ramanujam M.B.B.S [3]

Definition

Opioid withdrawal refers to the arrays of signs and symptoms following the abrupt cessation of opioids among chronic users.

Shown below is a table indicative of time to withdrawal symptoms for different opioids:

Opioid	Peak withdrawal symptoms	Duration of symptoms
Heroin	36-72 hours	7-10 days
Methadone	72-96 hours	14 days or more
Buprenorphine	36-72 hours	Intermediate between 7-14 days

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Opioid withdrawal is a life-threatening condition and must be treated as such irrespective of the causes.

Common Causes

• Discontinuation of heroin
• Discontinuation of methadone
• Rapid detoxification with naloxone or naltrexone in opioid dependent subjects
• Use of partial agonists (buprenorphine) and/or agonist-antagonists (pentazocine) in subjects not known to be opioid dependent

Management

Diagnostic Approach

Shown below is an algorithm depicting the management of opioid withdrawal.

Characterize the symptoms: ❑ Flu like illness ❑ Lacrimation ❑ Rhinorrhea ❑ Sneezing ❑ Yawning ❑ Anorexia ❑ Nausea ❑ Vomiting ❑ Abdominal cramps ❑ Diarrhea ❑ Myalgia ❑ Arthralgia

Examine the patient: ❑ Increased or unchanged blood pressure ❑ Increased or unchanged heart rate ❑ Increased or unchanged respiratory rate ❑ Mydriasis ❑ Piloerection ❑ Tremor ❑ Increased bowel sounds

Consider alternative diagnosis: ❑ Alcohol withdrawal ❑ Sedative hypnotic withdrawal ❑ Cholinergic poisoning ❑ Sympathomimetic intoxication

Diagnostic criteria: ❑ A. Either of the following ❑ Cessation of or reduction in opioid use that has been heavy and for several weeks or longer ❑ Administration of an opioid antagonist after a period of opioid use ❑ B. Three or more of the following (developing within minutes to several days after criterion A) ❑ Diarrhea ❑ Dysphoric mood ❑ Fever ❑ Insomnia ❑ Lacrimation or rhinorrhea ❑ Muscle aches ❑ Nausea or vomiting ❑ Pupillary dilation, piloerection, or sweating ❑ Yawning

Consider treatment with: ❑ Opioid maintenance treatment or ❑ Medically supervised withdrawal (detoxification)

Treatment Approach

Opioid Maintenance Treatment

Induction-day 1

Identify the opioid(s) that the patient has been using

Short acting opioids

Long acting opioids

❑ Discontinue short acting opioids ❑ Look for withdrawal symptoms (12-24 hours after last dose)

Withdrawal symptoms absent: ❑ Reevaluate the suitability for induction

❑ Taper down long acting opioids ❑ Methadone to ≤30 mg/day ❑ LAAM to ≤40 mg/48 hours ❑ Look for withdrawal symptoms: ❑ For methadone: 24+ hours after last dose ❑ For LAAM: 48+ hours after last dose

Withdrawal symptoms present: ❑ Administer buprenorphine 4mg & Naloxone 1 mg ❑ Observe for 2+ hours

Withdrawal symptoms relieved: ❑ Day 1 dose established ❑ Send home patient ❑ Patient should return on day 2 for forward induction

Withdrawal symptoms present: ❑ Administer buprenorphine 2 mg ❑ Observe 2+ hours

Withdrawal symptoms not relieved: ❑ Repeat ❑ Buprenorphine 4mg (up to maximum of 8mg/24 hours) ❑ Naloxone 1 mg (up to maximum of 2 mg/24 hours)

Withdrawal symptoms not relieved: ❑ Repeat ❑ Buprenorphine 2mg (up to maximum of 8mg/24 hours)

Withdrawal symptoms relieved: ❑ Day 1 dose established ❑ Send home patient ❑ Patient should return on day 2 for forward induction

Withdrawal symptoms not relieved: Manage withdrawal symptoms symptomatically ❑ Clonidine 0.2 mg every 4 hours, tapered after day 3, or ❑ Lofexidine 0.2 mg BD daily, titrated to 1.2 mg BD daily ❑ Chlordiazepoxide as needed ❑ Return next day for repeat induction attempt

Induction-day 2 forward

On return withdrawal symptoms absent: ❑ Administer a daily dose established equal to total buprenorphine & naloxone administered on previous day

On return withdrawal symptoms present: ❑ Administer dose equal to Total amount of buprenorphine & naloxone administered on previous day + 4mg of buprenorphine (up to maximum of 12mg on day 2) & 1mg of naloxone (up to maximum of 3mg on day 2) ❑ Observe 2+ hours

Withdrawal symptoms relieved: ❑ Daily buprenorphine & naloxone dose established

Withdrawal symptoms not relieved: ❑ Administer buprenorphine 4 mg (up to maximum of 16mg on day 2) & naloxone 1 mg (up to maximum of 4 mg on day 2)

Withdrawal symptoms relieved: ❑ Daily buprenorphine & naloxone dose established

Withdrawal symptoms not relieved: Manage withdrawal symptoms symptomatically ❑ Clonidine 0.2 mg every 4 hours, tapered after day 3, or ❑ Lofexidine 0.2 mg BD daily, titrated to 1.2 mg BD daily ❑ Chlordiazepoxide as needed ❑ On subsequent induction days, if the patient returns experiencing withdrawal symptoms, continue increasing dose (up to a maximum of buprenorphine 32 mg/day & naloxone 8 mg/day

Stabilization phase (1-2 months): ❑ Transition when patient has: ❑ No withdrawal symptoms ❑ Minimal or no side effects ❑ No uncontrollable craving for opioid agonists ❑ Begin with buprenorphine/naloxone combination, increasing dose by 2/0.5-4/1 mg per week till stabilization is achieved, most stabilizing at 16/4-24/6 mg ❑ As patient stabilizes, transition to alternate day or every third day regimen by doubling and tripling daily doses respectively

Maintenance phase: ❑ Maintain at same dose as daily stabilization dose ❑ Decide total treatment duration based on: ❑ Stable housing & income ❑ Patients motivation, doctors comfort in tapering ❑ Presence of psychosocial support ❑ Absence of legal support ❑ Other drugs & alcohol abuse

Detoxification (Medically Supervised Withdrawal) With Buprenorphine

Detoxification

Short acting opioids

OAT (methadone/LAAM)

Induction phase: ❑ Take patient off offending agent, inducing withdrawal ❑ Administer 1st dose of buprenorphine/naloxone 4/1 mg, when patient shows initial symptoms of withdrawl ❑ Repeat once after 2-4 hours if indicated ❑ ↑ dose to 12/3 - 16/4 mg over next 2 days, to establish stabilization dose

Induction phase: ❑ Taper methadone to ≤ 30 mg/day Taper LAAM ≤ 40 mg/48 hour ❑ Induce by buprenorphine monotherapy 2 mg, repeated after 2-4 hours to a maximum dose of 8mg in 24 hour period

Dose reduction phase: ❑ Begin only if documented negative toxicology results, or patient admitted to hospital Long period reduction: ❑ Reduce dose by 2 mg every week Moderate period reduction: ❑ Perform detoxification over 10-14 days ❑ Reduce dose by 2 mg every 2-3 days Short period reduction: Perform over 3 days Dose reduction by half every day

Dose reduction phase

Rapid discontinuation: ❑ Taper buprenorphine monotherapy over 3-6 days, then discontinue

Gradual dose reduction: ❑ Switch to buprenorphine/naloxone combination therapy ❑ Stabilize combination dosage over 1 week ❑ Taper gradually over next 2 weeks, then discontinue

Do's

• Treat the patient for a duration of 10 days for heroin withdrawal and 14 days for methadone withdrawal.
• Restrict methadone and other opioid agonists to inpatient settings or licensed programs.
• Administer chlordiazepoxide, a longer-acting benzodiazepine to augment clonidine in patients with insomnia or muscle cramps.
• Detoxification should be undertaken only under clinicians with special training, equipment, or both.
• Start buprenorphine at least two days before starting naltrexone during detoxification.

Dont's

• Do not abruptly stop drugs that are being used to treat withdrawal.

References

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