Withdrawal Syndromes Lorri Beatty, MD, FRCPC Emergency 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 SaO 2 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 SaO 2 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 1) Use opioids

2) Treat Symptoms DrugDoseSymptoms Diazepam1 – 10mg PO/IM/IV Anxiety, restlessness, muscle cramps, insomnia Gravol25 – 50mg PO/IM/IVNausea, vomiting Loperamide4mg PO then 2mg PRNAbdominal 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 3) Replace opioids

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 SaO 2 97% T 38.2° Looks anxious, tripod posture, mild respiratory distress, agitated, slightly confused On exam – normal oropharynx, chest clear, S 1 S 2 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 SaO 2 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 SaO 2 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 SaO 2 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):

Alcohol Withdrawal – Mechanism Finn DA, Crabbe JC. Alcohol Health and Research World, 1997, 21(2):

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

CIWA Scale

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! 2) Fluids/electrolytes

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 3) Nutritional deficiencies

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: days Duration: 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

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