Withdrawal Syndromes

Lorri Beatty, MD, FRCPCEmergency Medicine

February 19, 2014

Disclosures

• Sadly, none.

Objectives

• By the end of this presentation, participants will be able to:– Recognise and treat acute opioid withdrawal– Describe the features of ethanol and

benzodiazepine withdrawal– Use first- and second-line approaches to treat

alcohol and benzodiazepine withdrawal– Recognise and manage antidepressant

discontinuation syndrome– Describe cocaine washout

Case 1

• 64♂ with prostate cancer, mets to pelvis and spine (followed by Palliative Care)

• 3 day history of nausea, vomiting, diarrhea• Now worsening back pain, myalgias,

abdominal cramps, runny nose, restlessness

• Followed by palliative care

Case 1 (continued)

HR 106 BP 106/56 RR 20 SaO2 98% T 37.2°

• Looks unwell, cachectic, uncomfortable• Diffuse muscle tenderness

• Med list:– hydromorph contin 24mg BID - lactulose 30mg BID– hydromorphone 4mg q2h PRN - metoclopramide 10mg QID– acetominophen 650mg QID

Case 2

• 32♀ in methadone program for 14 months– Doing well

• Stopped methadone 4 days ago as “I don’t want to be a druggie anymore”

• Now nausea, abdominal pain, loose stool, insomnia since yesterday

Case 2 (continued)

HR 96 BP 148/82 RR 22 SaO2 97% T 36.6°

• On exam – Well-hydrated, looks uncomfortable, irritable

• mydriasis, yawning++, piloerection, ++ bowel sounds

• Normal muscle tone, normal skin, reflexes 2+, no tremor

Opioid Withdrawal - Mechanism

Opioid Withdrawal - Symptoms

• Autonomic:– Yawning, sneezing, lacrimation, rhinorrhea, mydriasis– ↑HR (mild), ↑BP (mild), ↑RR (mild), ↑T° (if severe)

• Neuro/mood:– Dysphoria, anxiety, restlessness, insomnia– NORMAL level of consiousness, NORMAL motor exam

• Somatic:– Myalgias, arthralgias, piloerection

• GI:– Nausea, vomiting, diarrhea, abdominal cramps, ↑MS

Opioid Withdrawal - Management

1) Use opioids

2) Treat Symptoms

3) Replace opioids

• Restart usual dose if able

• Consider alternate route if can’t take PO– SC, IM, IV, transdermal

• Methadone– Consider using lower dose – 20mg PO or 10mg IM

Drug Dose Symptoms

Diazepam 1 – 10mg PO/IM/IV Anxiety, restlessness, muscle cramps, insomnia

Gravol 25 – 50mg PO/IM/IV Nausea, vomiting

Loperamide 4mg PO then 2mg PRN Abdominal cramps, diarrhea

Acetaminophen, ibuprofen Pain

Clonidine• Mechanism:– 2-agonist, opens similar K+-channels

• Symptoms:– restlessness, dysphoria, GI symptoms

• Dosing:– 0.1 – 0.2mg PO q1-2h PRN in ED (monitor BP!)– 0.1 – 0.2mg PO q6h x 3 – 4 doses to go

• Risks – hypotension, sedation

Case 3

• 31 ♀, 3 visits in last 10 days for non-specific complaints

• Presents at 0900 with sore throat, trouble breathing, nausea

• Denies any PMHx, no meds, no allergies, smoker, social drinker

• Looks unwell, placed in resuscitation room

Case 3 (continued)

HR 120 BP 166/88 RR 24 SaO2 97% T 38.2°

• Looks anxious, tripod posture, mild respiratory distress, agitated, slightly confused

• On exam – normal oropharynx, chest clear, S1S2 normal with no murmur, bounding pulses

• Skin flushed & diaphoretic; pupils equal & reactive; mild tremor; slightly increased tone

Case 3 (continued)

• CXR – normal• EKG – sinus tachycardia• Labs – normal, d-dimer negative

• While in ED patient becomes more agitated, anxious, worsening respiratory distress

HR 154 BP 178/94 RR 30 SaO2 97% T 38.7°

Case 4 (continued)

• Given ceftriaxone, acyclovir, vancomycin• CT head arranged – patient unable to lie flat –

intubated for CT – Propofol, succinylcholine; propofol drip started

• CT head negative• LP attempted, patient +++ agitated despite

250mg/hour propofol → midazolam 5mg IV

HR 110 BP 136/86 RR vent SaO2 98% T 38.9°

Case 5

• 76 brought to ED by EHS after neighbours hadn’t seen him in 2 days

• Found in apartment – dishevelled, incontinent, confused

HR 106 BP 148/74 RR 20 SaO2 95% T 37.1°

Case 5 (continued)

• GCS 14, not oriented to place or time, appears anxious, agitated

• No evidence of trauma• Tremor; nil focal on neuro exam

• Pharmacy tech provides medication list:– Metformin, ASA, Lipitor, clonazepam– Not filled this month

Alcohol Withdrawal - Mechanism

Finn DA, Crabbe JC. Alcohol Health and Research World, 1997, 21(2):149-56.

Alcohol Withdrawal – Mechanism

Finn DA, Crabbe JC. Alcohol Health and Research World, 1997, 21(2):149-56.

Alcohol Withdrawal – Clinical Features

Autonomic Dysfunction-↑HR , ↑BP, ↑T°-tremor, increased tone, mydriasis-altered level of consiousness

Seizure-T/C, single, brief-short post-ictal

period

CNS Excitation-nausea, vomiting

-↑HR , ↑BP-tremor, increased tone, diaphoresis

Hallucinations

-visual

-auditory

-tactile

Alcohol Withdrawal - Management

1) Benzodiazepines

2) Fluids/electrolytes

3) Nutritional deficiencies

• Diazepam (Valium) is best choice– 5 – 10mg PO or IV– Quick onset (<30 minutes)– LONG halflife (33 hours; up to 50 hours for

metabolites)

• Front loading is better– Quicker improvement of symptoms– Less overall drug

1) Benzodiazepines

CIWAScale

• Elevated temperature, respiratory rate and sweating → ++ fluids losses– Severely ill patients may be normo- or hypotensive

• Check lytes if unwell, unstable, altered LOC

• Remember magnesium!

• Thiamine– Often thiamine deficient– Required to run Krebs cycle– Lack of thiamine → Wernicke/Korsakoff syndromes

• Glucose– Required to maintain high metabolic rate

• Folate/multivitamin– Often replace food with alcohol

• Barbituates• Actively opens GABA channels• Risk of sedation, hypotension, respiratory depression• Phenobarbital 60 – 120mg IV q30min

• Propofol• Acts on GABA and NMDA receptor• Risk of sedation, hypotension, respiratory depression

• AVOID• Antipsychotics, clonidine, β-blockers

What if that doesn’t work???

Antidepressant Discontinuation Syndrome - Mechanism

Long-term use(> 6 weeks)

↑ serotonin in synapse

Downregulation of receptors

Antidepressant Discontinuation Syndrome - Symptoms

• Neuro:– Dizzyness, headache, tremor, paresthesias,

“electric shocks”, myoclonus, ataxia, vision changes

• Mood:– anxiety/hyperarousal, dysphoria, insomnia,

lethagy• GI:– Nausea, diarrhea, GI upset

Onset: 2 - 3 daysDuration: 1 - 2 weeks

Antidepressant Discontinuation Syndrome - Management

1) Restart SSRI• Restart previous dose, gradual taper

2) Treat Symptoms

3) Replace SSRI• Switch to fluoxetine 20mg with taper

DrugStarting

dose (mg)1st dose

reduction (mg)

2nd dose reduction

(mg)

3rd dose reduction

(mg)

4th dose reduction

mg)

fluoxetine (Prozac) 60 mg 40 30+ 20 10++

paroxetine (Paxil) 60 mg 40 30 20 10

sertraline (Zoloft) 200 mg 150 100 75 50

citalopram (Celexa) 40 mg 30 20 10

escitalopram (Lexapro) 20 mg 15 10 5

venlafaxine (Effexor) 300 mg 225 150 75 37.5

duloxetine* (Cymbalta) 90 mg 60 30 20

bupropion* (Wellbutrin) 300 mg 200 150 100

From: Harvard Women’s Health Watch, November 2010

Cocaine “Withdrawal”

• Cocaine– ↑ dopamine, NE, serotonin– Short-term use – euphoria,

CNS stimulant– Long-term use exhausts

stores

• Cocaine Abstinence– NOT withdrawal– NOT dangerous– FEW physical symptoms

Cocaine Abstinence Syndrome

Three Stages of Cocaine Abstinence

• Stage 1 – Cocaine Crash (1 – 4 days)• Profound lack of neurotransmitters• Dysphoria, anxiety, irritability, hypersomnia,

exhaustion, increased appetite, cravings

• Stage 2 – Cocaine Washout (1 – 10 weeks)• Gradual recovery of neurotransmitters• Anergia, listlessness, depression• Gradual ↑ in concentration, ↓ in cravings

• Stage 3 - Extinction

In Conclusion. . .

• Opioid Withdrawal– Restart if possible/indicated– Methadone – use 20mg PO or 10mg IM– Consider clonidine

• Alcohol/Benzodiazepine Withdrawal– Benzos, benzos, benzos – Valium – repeat doses until asymptomatic– Remember fluid and nutrition replacement

In Conclusion. . .

• Antidepressant Discontinuation Syndrome– Have a low threshold; ask about SSRIs– Restart drug with a slow taper, or treat symptoms

• Cocaine Abstinence Syndrome– Largely psychological symptoms, depression– Not life-threatening, and few clinical symptoms– Treat symptomatically if needed