Syndromes Hasan Shabbir, MD January 10th, 2008 Background • 8 million Alcoholics in US1,2 • 4 million hospitalizations for AWS/yr4 • 12-30% of inpatients have ongoing excess alcohol intake3 Pathophysiology • Not well understood • Alcohol causes CNS depression • Inhibits dopaminergic and adrenergic receptors • GABA like effects • Cessation results in brain hyperexcitability Definition-DSM IV • A. Cessation of (or reduction in) alcohol use that has been heavy and prolonged. B. Two (or more) of the following, developing within several hours to a few days after Criterion A: 1) autonomic hyperactivity (e.g., sweating or pulse rate greater than 100) 2) increased hand tremor 3) insomnia 4) nausea or vomiting 5) transient visual, tactile, or auditory hallucinations or illusions 6) psychomotor agitation 7) anxiety 8) grand mal seizures C. The symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. D. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder. TIMELINE Alcoholic Hallucinosis • 10-25% of patients with AWS hallucinate • Usually in first 24-48hrs of cessation 7,10 • Does not predict DT’s • Usually auditory or visual • Formication (bugs crawling on skin) “Minor” Withdrawal • May occur within 6-12hrs of cessation • Need to treat promptly • May take up to 2 weeks to resolve • Autonomic hyperactivity – anxiety, tremulousness, insomnia – hypertension, tachyarrythmias – nausea, vomiting, or diarrhea – Myalgias Alcohol Withdrawal Seizures • Usually Generalized Tonic Clonic Seizures • Usually self-limited • 90% occur within 8-48hrs of cessation • Usually 12-24hrs post-cessation • May occur without any warning • Most recurrent seizures within 6hrs of first seizure Alcohol Withdrawal Seizures (cont.) • Further work-up if – Fever – Trauma – 1st seizure – Focal seizure – No clear history of alcohol use & cessation – Status Epilepticus Delirium Tremens • Occurs in 5-8% of patients hospitalized with alcohol withdrawal10,16 • Occurs 2-14 days after cessation, can last 2 weeks! • Fever, severe autonomic hyperactivity, agitation, hallucinations • Global disorientation is a key feature • Mortality 5% with treatment (20% without Tx) • Risk factors – Age>30 – Hx of DTs or AW Seizures – Concurrent Medical Illness – Time since last drink Assessment • Differential Dx? • Special History Questions – Quantity and Frequency of Consumption – Detoxification History – History of DTs and AW Seizures – History “Crosscheck” – Hallucinations – Time of last drink Assessment (cont.) • Physical – Hemodynamics, Neurologic Exam, Mental Status – Stigmata of Liver Disease – Nutritional Status
– Labs General Treatment • ICU? HR>130, • Vitamins SBP>180, severe • Nutrition agitation • Volume replacement • Electrolyte correction • 10-20% need to be • Benzodiazepines hospitalized • Other – Severe withdrawal pharmacotherapies – Poor social support – Inability to tolerate liquids or oral meds Benzodiazepines • Prophylactic dose to reduce risk of AW Seizures for all patients being admitted with a medical or surgical problem AND • Symptom Triggered OR • Fixed Dose Sample Regimens Fixed Dose Regimen Symptom Triggered Regimen • Standing dose, THEN: • Standing dose, THEN:
• Diazepam 20 mg PO QID for 4 • Diazepam 20 mg PO
doses then once PRN CIWA-Ar ≥8 every • Diazepam 10 mg PO QID for 8 two hours doses
• Modified from: Saitz R, Mayo-
Smith MF, Roberts MS, et al. Individualized treatments for alcohol withdrawal: a randomized double-blind controlled trial. JAMA 1994; 272(7):519–523 CIWA-Ar • NAUSEA AND VOMITING — Ask "Do you feel sick to your stomach? Have you vomited?" Observation.
• TREMOR — Arms extended and fingers spread apart. Observation.
• PAROXYSMAL SWEATS — Observation.
• ANXIETY — Ask "Do you feel nervous?" Observation.
• AGITATION — Observation.
• TACTILE DISTURBANCES — Ask "Have you any itching, pins and needles sensations, burning sensations, numbness or do you feel bugs crawling on or under your skin?" Observation.
• AUDITORY DISTURBANCES — Ask "Are you more aware of sounds around you? Are they harsh? Do they frighten you? Are you hearing anything that is disturbing to you? Are you hearing things you know are not there?" Observation.
• VISUAL DISTURBANCES — Ask "Does the light appear to be too bright? Is its colour different? Does it hurt your eyes? Are you seeing anything that is disturbing to you? Are you seeing things you know are not there?" Observation.
• HEADACHE, FULLNESS IN HEAD — Ask "Does your head feel different? Does it feel as if there is a band around your head?" Do not rate for dizziness or lightheadedness. Otherwise, rate severity.
• ORIENTATION AND CLOUDING OF SENSORIUM — Ask "What day is this? Where are you? Who am I?" Choice of Benzodiazepines • Drug Half-Life Route Dose Equivalence
• Diazepam (Valium) IV 20–50 hr IV, PO 10 mg
• Chlordiazepoxide (Librium)6–25 hr IV, PO 50 mg
• Clorazepate (Tranxene)48–96 hrPO 15 mg
• Lorazepam (Ativan) 10–15 hr PO, IV, IM 2mg
• Oxazepam (Serax) 6–8 hr PO 30 mg
Seizures • Dose of IV Lorazepam post-seizure – Recurrence 3% vs 22% Delirium Tremens • Usually need ICU setting • Vascular access • Telemetry monitoring • Pharmacotherapy until patient alert and calm • Benzodiazepines are mainstay • May need additional medications for cases refractory to benzodiazepines Adjunctive Pharmacotherapy • Haloperidol • Baclofen • Beta Adrenergic Antagonists • Propofol • Phenobarbital Discharge • Mental Status & Hemodynamics • Substance abuse follow-up • Meds to decrease alcohol craving? – Atenolol – Topiramate – Acamprosate Take Home Points • Common and Potentially Fatal • Catch early by careful history • One-time benzo for AW Seizure Prophylaxis • Long-acting benzos are mainstay of treatment • Fixed Dose and Symptom Triggered • DTs includes global confusion • Substance Abuse follow-up • Don’t forget phenobarbital and propofol References • REFERENCES • 1. Kosten TR, O'Connor PG: Management of drug and alcohol withdrawal. N Engl J Med 2003; 348:1786. • 2. Kozak LJ, Hall MJ, Owings MF: National Hospital Discharge Survey: 2000 Annual Summary with Detailed Diagnosis and Procedure Data. Vital Health Stat 2002; 153(13):1-194. • 3. Moore RD, Bone LR, Geller G, et al: Prevalence, detection, and treatment of alcoholism in hospitalized patients. JAMA 1989; 261(3):403-407. • 4. HCUP. National and regional estimates on hospital use for all patients from the HCUP Nationwide Inpatient Sample (NIS). Available at www.hcup.ahrq.gov/hcupnet.asp . Accessed 8/5/05. • 5. Bayard M, Mcintyre J, Hill KR, et al: Alcohol withdrawal syndrome. Am Fam Phys 2004; 69:1443-1450. • 6. Alcohol Withdrawal. In: First M, ed. Diagnostic and Statistical Manual- Text Revision, 4th ed.. Washington, DC: American Psychiatric Association; 2000. • 7. Chang PH, Steinberg MB: Alcohol Withdrawal. Med Clin North Am 2001; 85(5):1191-1212. • 8. Turner RC, Lichstein PR, Peden Jr JG, et al: Alcohol withdrawal syndromes: a review of pathophysiology, clinical presentation, and treatment. J Gen Int Med 1989; 4(5):432-444. • 9. Saitz R, O'Malley SS: Pharmacotherapies for alcohol abuse: withdrawal and treatment. Med Clin North Am 1997; 81(4):881-907. • 10. Foy A, Kay J, Taylor A: The course of alcohol withdrawal in a general hospital. Quarterly Journal of Medicine (QJMed) 1997; 90(4):253-261. • 11. Rathlev NK, Ulrich A, Fish SS, et al: Clinical characteristics as predictors of recurrent alcohol-related seizures. Acad Emerg Med 2000; 7(8):886-891. • 12. Malcolm R, Herron JE, Anton RF, et al: Recurrent detoxification may elevate alcohol craving as measured by the obsessive compulsive drinking scale. Alcohol 2000; 20(2):181-185. • 13. Manwell LB, Fleming MF, Johnson K, et al: Tobacco, alcohol, and drug use in a primary care sample: 90 day prevalence and associated factors. J Addict Dis 1998; 17(1):67-81. • 14. Alldredge BK, Lowenstein DH: Status epilepticus related to alcohol abuse. Epilepsia 1993; 34(6):1033-1037. • 15. Erwin WE, Williams DB, Speir WA: Delerium tremens. South Med J 1998; 91(5):425-432. • 16. Ferguson JA, Suelzer CJ, Eckert GJ, et al: Risk factors for delirium tremens development. J Gen Int Med 1996; 11(7):410-414. • 17. American Society of Addiction Medicine: American Society of Addiction Medicine's Working Group on Pharmacological Management of Alcohol Withdrawal. Pharmacological Management of Alcohol Withdrawal. A Meta-analys JAMA 1997; 278(2):144-151. • 18. Hack JB, Hoffman RS: Thiamine before glucose to prevent Wernicke encephalopathy: examining the conventional wisdom. JAMA 1998; 279(8):583-584. • 19. Kaim SC, Klett CJ, Rothfeld B: Treatment of the acute alcohol withdrawal state: a comparison of four drugs. Am J Psych 1969; 125(12):1640-1646. • 20. Schuckit MA: Alcohol and alcoholism. In: Braunwald E, ed. Harrisons Principles of Internal Medicine, 15th ed. New York, NY: McGraw-Hill; 2001:2565. • 21. Reoux JP, Miller K.: Routine hospital alcohol detoxification practice compared to symptom triggered management with an objective withdrawal scale (CIWA-Ar). Am J Addict 2000; 9:135-144. • 22. Saitz R, Mayo-Smith MF, Roberts MS, et al: Individualized treatments for alcohol withdrawal: a randomized double-blind controlled trial. JAMA 1994; 272(7):519- 523. • 23. Mayo-Smith MF, Beecher LH, Fischer TL, et al: Management of alcohol withdrawal delirium: an evidence-based practice guideline. Arch Int Med 2004; 164(13):1405-1412. • 24. Lexi-Comp. Lexi-Comp Online Drug Information. Available at www.lexi.com . Accessed 1/6/05. • 25. McCowan C, Marik P: Refractory delirium tremens treated with propofol: a case series. Crit Care Med 2000; 28(6):1781-1784. • 26. D'Onofrio G, Rathlev NK, Ulrich AS, et al: Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med 1999; 340(12):915-919.
