Management of Alcohol Withdrawal March 27, 2014 Megan Schabbing, MD Consult Liaison Psychiatrist OhioHealth Behavioral Health

Objectives Describe the variable presentation of alcohol withdrawal Demonstrate the appropriate therapy in various clinical scenarios Understand the appropriate use of CIWA

21 y/o M college student admitted after being found by his roommates down in his apartment. On arrival, he was unresponsive, intubated in ED, now markedly agitated, requiring manual restraints.

80 y/o M POD #2 s/p hip replacement with acute onset confusion, UE tremor, & tachycardia. His medical history is notable for CHF, HTN & COPD.

35 y/o F admitted s/p fall, suspected syncope vs 35 y/o F admitted s/p fall, suspected syncope vs. seizure, CT, EEG, echo negative. The patient is disoriented & unable to provide a history but appears very anxious and tearful.

Pathophysiology: Ethanol & CNS Effect of EtOH on CNS Enhances inhibitory tone (GABA agonist) Induces excitatory tone (inhibits glutamate binding) Chronic EtOH use>>insensitivity to GABA….abrupt cessation>>CNS hyperactivity (withdrawal) Blood alcohol concentration (BAC) & clinical presentation ~40 mg/dL: memory impairment (+/- blackout), ataxia 150-250 mg/dL: argumentative or assaultive behavior 400-500 mg/dL: coma or death

Alcohol Withdrawal: Uncomplicated Symptoms emerge within hours & resolve in 3-5 days Early signs: loss of appetite, irritability, tremulousness Generalized tremor

Alcohol withdrawal seizures Seizures occur typically within first 48h Alcohol withdrawal seizures are self-limited In a patient with prolonged seizures, consider other etiology (structural abnormality, infection) If left untreated, 1/3 w/d seizures progress to DTs Treatment: benzodiazepines, barbiturates *avoid phenytoin (limited evidence in w/d seizures)

Alcoholic Hallucinosis Onset ~12-24h following alcohol cessation Resolution ~24-48h following alcohol cessation Vivid auditory illusions & hallucinations Clear sensorium (vs. delirium) Ideas of persecution often follow hallucinations Olfactory hallucinations may occur (rarely visual) ***Auditory hallucinations in the absence of tremor, agitation, or disorientation

Alcohol Withdrawal Delirium: Delirium Tremens Incidence 5% in hospitalized patients with AD Incidence 33% in patients with withdrawal seizures Classic time frame: 72h following last alcohol use Clinical features Disorientation Tremor Hyperactivity, increased wakefulness Increased autonomic tone Hallucinations (visual>auditory)

Alcohol Withdrawal Delirium: Delirium Tremens Risk factors: history of DTs, comorbid medical problems, age>30, chronic alcohol use, withdrawal in the presence of an elevated BAC Treatment of choice: benzodiazepines (lorazepam) Refractory cases: barbiturates (phenobarbital), propofol

Alcohol Withdrawal Management Address medical comorbidities Differential diagnosis for increased sympathetic activity: anti-cholinergic toxicity cocaine or amphetamine intoxication Thyrotoxicosis Sedative-hypnotic withdrawal Consider other etiologies of altered mental status, seizure: CNS infection, intracranial hemorrhage

Alcohol withdrawal management No universal protocol; must individualize treatment plan Symptom-triggered dosing of benzodiazepines (CIWA) Fixed-dose bezodiazepine therapy In patients with impaired liver function (cirrhosis, elderly patients), avoid drugs which require oxidative metabolism (use lorazepam, oxazepam)

Alcohol withdrawal management Benzodiazepines: stimulate GABA receptors>decreased neuronal activity>sedation *studies support increased efficacy in preventing withdrawal seizures Barbiturates: increase duration of GABA Cl channel opening, used with benzos in severe cases of delirium tremens Anti-convulsants: limited evidence (withdrawal seizures are self-limited)

Alcohol withdrawal management Anti-psychotics: limited evidence, can lower seizure threshold; used for comorbid psychosis or agitation management in withdrawal delirium Alpha 2 agonists: limited evidence, used as adjunct to target autonomic instability Baclofen: limited evidence, selective agonist of GABA-B receptor Gabapentin: structurally similar to GABA, low toxicity Ethanol: difficult to titrate, safety not proven…DON’T DO IT!

Alcohol Withdrawal Management: Fixed dose therapy Uses a long-acting agent (e.g. diazepam t 1/2=10-15h) PROS: Self-tapering due to long half-life>>ease of administration, minimal breakthrough symptoms; useful in preventing withdrawal in patients at risk who are asymptomatic CONS: patients may receive unnecessary medication>>oversedation>>prolonged hospitalization

Alcohol Withdrawal Management: Symptom-triggered therapy Assesses symptoms on real-time Benzodiazepine dosing given in response to symptom severity PROS: generally safe & effective, can reduce medication doses & duration of treatment CONS: need for constant monitoring & frequent medication administration, requires staff training, greater risk of benzodiazepine dependence, OFTEN MISUSED E.g. CIWA-AR Clinical Institue Withdrawal Assessment Alcohol-Revised Scale

Clinical Institute Withdrawal Assessment for Alcohol-Revised scale (CIWA-Ar) Patient is evaluated q15 min – hourly, dependent upon severity of symptoms Nausea/vomiting, tremors, anxiety, agitation, paroxysmal sweats, sensorium, tactile disturbances, auditory & visual disturbances, headache Each criterion is rated on a scale from 0 to 7, except for Orientation/sensorium, which is rated on scale 0 to 4 Total CIWA-Ar score >8: start prophylactic medication should Total CIWA-AR score >15: give additional PRN medication https://www.ihs.gov/NC4/Documents/AlcoholWithdrawalAssessmentSheets(PIMC%20Apr%2005).doc

CIWA Inclusion Criteria *INTACT VERBAL COMMUNICATION …the patient must have clear enough sensorium to reply logically to questions (7/10 questions require answers) *RECENT ALCOHOL USE

Clinical Institute Withdrawal Assessment for Alcohol-Revised scale (CIWA-Ar) Examples of when NOT to use CIWA *patient intubated & sedated on propofol *patient who is a recovering alcoholic (no recent use) *a delirious patient Verbal communication NOT intact Agitation resulting from delirium secondary to underlying medical issues (metabolic abnormalities, infection) may lead to inappropriate excess dosing of benzodiazepines, which may worsen delirium

CIWA vs. Fixed dose taper Numerous early trials support symptom-triggered therapy (e.g. CIWA) due to advantages of rapid symptom control & reduced total benzodiazepine doses HOWEVER, most trials involved medically cleared patients in detox units The few trials which involved medically ill patients DID NOT attempt to validate CIWA-Ar scale as a tool for managing seriously ill patients on specialty services or in ICU

Alcohol withdrawal management: On the Horizon CIWA-based algorithms http://www.nahq.org/uploads/apps/files/ETOHWithdrawlGuideline.pdf Non-benzodiazepine withdrawal protocol: alpha 2 agonists (clonidine, dexmedetomidine), anti-convulsants, anti-psychotics, beta blockers, baclofen

Summary Alcohol withdrawal can present across patient populations in various clinical scenarios, so always consider it in the differential diagnosis, but keep your differential diagnosis open. To date, benzodiazepines remain the treatment of choice in managing alcohol withdrawal When choosing the method of benzodiazepine dosing, consider whether the patient has intact verbal communication and recent alcohol use Avoid CIWA in patients who are unconscious or delirious

References Bayard M et al. Alcohol withdrawal syndrome. Am Fam Physician. 2004 Mar 15;69(6):1443-1450. Daeppen JB et al. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial, Arch Intern Med 162: 1117-1121, 2002. Hecksel KA et al. Inappropriate use of symptom-triggered therapy for alcohol withdrawal in the general hospital. Mayo Clin Proc 2008 Mar;83(3):274-9. Hoffman RS et al. Management of moderate and severe alcohol withdrawal syndrome. UpToDate 2014. Jaeger TM, et al. Symptom-triggered therapy for alcohol withdrawal syndrome in medical inpatients. Mayo Clin Proc 2001; 76 (7): 695-701. Maldonado JR et al. Benzodiazepine loading versus symptom-triggered treatment of alcohol withdrawal: a prospective, randomized clinical trial. General Hospital Psychiatry 2012; 34: 611-617. Minozzi AL and M Davoli. Efficacy and safety and pharmacological interventions for the treatment of Alcohol Withdrawal Syndrome (Review). Cochrane Database Syst Rev 2011; 6: CD008537. Ross JD et al. Alcoholic Patients: Acute and Chronic. Massachusetts General Hospital Handbook of General Hospital Psychiatry 2010: 153-162. Saitz R et al. Individualized treatment for alcohol withdrawal: a randomized double-blind controlled trial, JAMA 272: 519-23, 1994. Sullivan JT, et al. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict 1989; 84 (11): 1353-7.