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

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

3. 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.

4. 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.

5. 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.

6. 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
mg/dL: argumentative or assaultive behavior
mg/dL: coma or death

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

8. 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)

9. 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

10. 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)

11. 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

12. 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

13. 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)

14. 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)

15. 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!

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. Alcohol withdrawal management: On the Horizon
CIWA-based algorithms
Non-benzodiazepine withdrawal protocol: alpha 2 agonists (clonidine, dexmedetomidine), anti-convulsants, anti-psychotics, beta blockers, baclofen

23. 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

24. References
Bayard M et al. Alcohol withdrawal syndrome. Am Fam Physician. 2004 Mar 15;69(6):
Daeppen JB et al. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial, Arch Intern Med 162: , 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):
Maldonado JR et al. Benzodiazepine loading versus symptom-triggered treatment of alcohol withdrawal: a prospective, randomized clinical trial. General Hospital Psychiatry 2012; 34:
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: CD
Ross JD et al. Alcoholic Patients: Acute and Chronic. Massachusetts General Hospital Handbook of General Hospital Psychiatry 2010:
Saitz R et al. Individualized treatment for alcohol withdrawal: a randomized double-blind controlled trial, JAMA 272: , 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):