![Page 1: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/1.jpg)
Withdrawal Syndromes
Lorri Beatty, MD, FRCPCEmergency Medicine
February 19, 2014
![Page 2: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/2.jpg)
Disclosures
• Sadly, none.
![Page 3: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/3.jpg)
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
![Page 4: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/4.jpg)
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
![Page 5: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/5.jpg)
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
![Page 6: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/6.jpg)
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
![Page 7: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/7.jpg)
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
![Page 8: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/8.jpg)
Opioid Withdrawal - Mechanism
![Page 9: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/9.jpg)
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
![Page 10: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/10.jpg)
Opioid Withdrawal - Management
1) Use opioids
2) Treat Symptoms
3) Replace opioids
![Page 11: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/11.jpg)
• 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
![Page 12: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/12.jpg)
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
![Page 13: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/13.jpg)
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
![Page 14: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/14.jpg)
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
![Page 15: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/15.jpg)
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
![Page 16: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/16.jpg)
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°
![Page 17: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/17.jpg)
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°
![Page 18: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/18.jpg)
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°
![Page 19: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/19.jpg)
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
![Page 20: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/20.jpg)
Alcohol Withdrawal - Mechanism
Finn DA, Crabbe JC. Alcohol Health and Research World, 1997, 21(2):149-56.
![Page 21: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/21.jpg)
Alcohol Withdrawal – Mechanism
Finn DA, Crabbe JC. Alcohol Health and Research World, 1997, 21(2):149-56.
![Page 22: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/22.jpg)
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
![Page 23: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/23.jpg)
Alcohol Withdrawal - Management
1) Benzodiazepines
2) Fluids/electrolytes
3) Nutritional deficiencies
![Page 24: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/24.jpg)
• 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
![Page 26: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/26.jpg)
• 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!
![Page 27: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/27.jpg)
• 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
![Page 28: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/28.jpg)
• 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???
![Page 29: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/29.jpg)
Antidepressant Discontinuation Syndrome - Mechanism
Long-term use(> 6 weeks)
↑ serotonin in synapse
Downregulation of receptors
![Page 30: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/30.jpg)
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
![Page 31: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/31.jpg)
Antidepressant Discontinuation Syndrome - Management
1) Restart SSRI• Restart previous dose, gradual taper
2) Treat Symptoms
3) Replace SSRI• Switch to fluoxetine 20mg with taper
![Page 32: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/32.jpg)
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
![Page 33: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/33.jpg)
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
![Page 34: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/34.jpg)
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
![Page 35: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/35.jpg)
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
![Page 36: Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency Medicine February 19, 2014](https://reader036.vdocument.in/reader036/viewer/2022062321/56649de45503460f94adb6dc/html5/thumbnails/36.jpg)
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