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Alcohol Withdrawal

Alcohol Withdrawal. Best Practice Tom Shiffler, MD 7/23/10. Goals. Understand the pathophysiology of alcohol withdrawal Recognize why we use symptom triggered therapy (CAGE or CIWA) Discuss the role of “prophylaxis” (oral benzodiazepine) Discuss when/where to use benzodiazepine drips

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Alcohol Withdrawal

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  1. Alcohol Withdrawal Best Practice Tom Shiffler, MD 7/23/10 UNM Hospitalist Best Practices- Alcohol Withdrawal

  2. Goals • Understand the pathophysiology of alcohol withdrawal • Recognize why we use symptom triggered therapy (CAGE or CIWA) • Discuss the role of “prophylaxis” (oral benzodiazepine) • Discuss when/where to use benzodiazepine drips • Become familiar with evidence on other agents (haldol, clonidine, barbiturates, baclofen, precedex) • Substance abuse resources for patients UNM Hospitalist Best Practices- Alcohol Withdrawal

  3. Epidemiology of Alcohol Withdrawal • 500,000 cases per year requiring pharmacologic treatment • Delirium tremens mortality 5% (down from 37% in the early 1900s) • Arrhythmia • Complication • Pneumonia • Pancreatitis • Hepatitis UNM Hospitalist Best Practices- Alcohol Withdrawal

  4. Course of Alcohol Withdrawal • Minor symptoms • 6 hours after cessation • Resolve in 24-48 hours • Insomnia • Tremulousness • Mild anxiety • GI upset • HA • Diaphoresis • palpitations UNM Hospitalist Best Practices- Alcohol Withdrawal

  5. Course of Alcohol Withdrawal • Withdrawal Seizures • 12-48 hours after cessation • Generalized tonic-clonic • More common in those with chronic alcoholism • Progress to delirium tremens in 1/3 if untreated UNM Hospitalist Best Practices- Alcohol Withdrawal

  6. Course of Alcohol Withdrawal • Alcoholic Hallucinosis • NOT DT’s • Develop within 12-24 hours of cessation • Resolve within 24-48 hours of cessation • Visual, auditory and tactile are possible • NOT associated with global sensorial clouding, rather specific hallucinations • Vital signs usually normal UNM Hospitalist Best Practices- Alcohol Withdrawal

  7. Course of Alcohol Withdrawal • Delirium Tremens • 48-96 hours after cessation • Hallucinations, disorientation, tachycardia, hypertension, fever, agitation and diaphoresis • Generally last 5-7 days • Risk factors • Sustained drinking • Previous DT • Age >30 • Concurrent illness • Withdrawal with elevated alcohol level UNM Hospitalist Best Practices- Alcohol Withdrawal

  8. Goals • Understand the pathophysiology of alcohol withdrawal • Recognize why we use symptom triggered therapy (CAGE OR CIWA) • Discuss the role of “prophylaxis” (oral benzodiazepine) • Discuss when/where to use benzodiazepine drips • Become familiar with evidence on other agents (haldol, clonidine, barbiturates, baclofen, precedex) • Substance abuse resources for patients UNM Hospitalist Best Practices- Alcohol Withdrawal

  9. Pathophysiology-general considerations • Apparent genetic predisposition • Longer period of continual use associated with more severe withdrawal UNM Hospitalist Best Practices- Alcohol Withdrawal

  10. Pathophysiology-Molecular • Alcohol increases inhibitory tone via enhancement of GABA activity (an inhibitory neurotransmitter) • Chronic alcohol reduces functional GABA receptors • Cellular internalization • Gene expression • Removal of alcohol leads to functional loss of GABA and unchecked excitatory neurotransmitters • Dopamine • Glutamate • norepinephrine UNM Hospitalist Best Practices- Alcohol Withdrawal

  11. Pathophysiology-acute Alcohol www.niaaa.nih.gov/.../31_4_acute_gaba.htm UNM Hospitalist Best Practices- Alcohol Withdrawal

  12. Pathophysiology-absence of alcohol after chronic use www.niaaa.nih.gov/.../31_4_acute_gaba.htm UNM Hospitalist Best Practices- Alcohol Withdrawal

  13. Goals • Understand the pathophysiology of alcohol withdrawal • Recognize why we use symptom triggered therapy (CAGE OR CIWA) • Discuss the role of “prophylaxis” (oral benzodiazepine) • Discuss when/where to use benzodiazepine drips • Become familiar with evidence on other agents (haldol, clonidine, barbiturates, baclofen, precedex) • Substance abuse resources for patients UNM Hospitalist Best Practices- Alcohol Withdrawal

  14. Symptom Triggered Therapy (CIWA or CAGE) • Benzodiazepine given in RESPONSE to signs or symptoms • Why is this standard of care? UNM Hospitalist Best Practices- Alcohol Withdrawal

  15. Individualized Treatment for Alcohol Withdrawal. Saitz et al. JAMA Aug 17, 1994 • Clinical question: • Is symptom triggered superior to fixed schedule in reducing quantity and duration of treatment of alcohol withdrawal? • Methods • Randomized Double-Blind Controlled Trial • 101 patients admitted to VA alcohol withdrawal unit • Control • Chlordiazepoxide q6h SCHEDULED • 50mg x4 • 25mg x8 • 25-100mg q 1hour per CIWA-Ar scale • Not administered if somnolent or refused UNM Hospitalist Best Practices- Alcohol Withdrawal

  16. Individualized Treatment for Alcohol Withdrawal. Saitz et al. JAMA Aug 17, 1994 • Symptom triggered group • 25-100mg chlordiazepoxide at CIWA-Ar >7 • See hand out UNM Hospitalist Best Practices- Alcohol Withdrawal

  17. Individualized Treatment for Alcohol Withdrawal. Saitz et al. JAMA Aug 17, 1994 • Outcomes • Duration of medication treatment from admission to last dose of benzodiazepine • Fixed schedule group: 68 hours mean • Symptom triggered group: 9 hours mean (p<0.001) • Amount of chlordiazepoxide administered • Fixed schedule group: 425mg mean • Symptom triggered group: 100mg mean (p<0.001) UNM Hospitalist Best Practices- Alcohol Withdrawal

  18. Individualized Treatment for Alcohol Withdrawal. Saitz et al. JAMA Aug 17, 1994 • Conclusions • “Symptom-triggered therapy individualizes treatment, decreases both treatment duration and the amount of benzodiazepine used, and is as efficacious as standard fixed-schedule therapy for alcohol withdrawal.” UNM Hospitalist Best Practices- Alcohol Withdrawal

  19. Individualized Treatment for Alcohol Withdrawal. Saitz et al. JAMA Aug 17, 1994 • Limitations/concerns • Results expected • 66 hours • 400 mg chlordiazepoxide • morbidity/mortality differences? (n too small) • Take home • Symptom-triggered was better than standard of care (American Society for Addiction Medicine guidelines) for alcohol withdrawal • Weaning built into symptom-triggered treatment • Thank these authors for any alcohol withdrawal patient discharged in < 3 days UNM Hospitalist Best Practices- Alcohol Withdrawal

  20. Symptom-Triggered vs Fixed-Schedule Doses of Benzodiazepine for Alcohol Withdrawal Daeppen et al. Arch Intern Med May 27 2002 • Clinical question: • Is symptom triggered superior to fixed schedule in reducing quantity and duration of treatment in patients AT RISK of withdrawal? • Methods • Prospective RCT • 117 patients entering alcohol TREATMENT program UNM Hospitalist Best Practices- Alcohol Withdrawal

  21. Symptom-Triggered vs Fixed-Schedule Doses of Benzodiazepine for Alcohol Withdrawal Daeppen et al. Arch Intern Med May 27 2002 • Methods (cont) • Control (n=61) • 30mg oxazepam q6h for 4 doses scheduled • 15mg oxazepam q6h for 8 doses scheduled • Plus 15-30mg oxazepam q30 minutes for CIWA-Ar score >7 and >14 respectively • Experimental (n=56) • Received placebo, then q 30 minutes evaluated • CIWA-Ar >7 received 15mg oxazepam • CIWA-Ar >14 received 30mg oxazepam • Patients observed for 48 hours after study UNM Hospitalist Best Practices- Alcohol Withdrawal

  22. Symptom-Triggered vs Fixed-Schedule Doses of Benzodiazepine for Alcohol Withdrawal Daeppen et al. Arch Intern Med May 27 2002 • Results • 22 of 56 (39%) in symptom-triggered received oxazepam • Dosage • 37.5mg mean symptom triggered group • 231.4mg mean fixed schedule group (p<0.001) • Duration • 20 hours mean symptom triggered group • 62.7 hours mean fixed schedule group (p<0.001) UNM Hospitalist Best Practices- Alcohol Withdrawal

  23. Symptom-Triggered vs Fixed-Schedule Doses of Benzodiazepine for Alcohol WithdrawalDaeppen et al. Arch Intern Med May 27 2002 • Conclusion • “Symptom-triggered benzodiazepine treatment for alcohol withdrawal is safe, comfortable, and associated with a decrease in the quantity of medication and duration treatment.” UNM Hospitalist Best Practices- Alcohol Withdrawal

  24. Goals • Understand the pathophysiology of alcohol withdrawal • Recognize why we use symptom triggered therapy (CAGE OR CIWA) • Discuss the role of “prophylaxis” (oral benzodiazepine) • Discuss when/where to use benzodiazepine drips • Become familiar with evidence on other agents (haldol, clonidine, barbiturates, baclofen, precedex) • Substance abuse resources for patients UNM Hospitalist Best Practices- Alcohol Withdrawal

  25. Symptom-Triggered vs Fixed-Schedule Doses of Benzodiazepine for Alcohol WithdrawalDaeppen et al. Arch Intern Med May 27 2002 • Limitations/concerns • Results expected • 66 hours • 240mg oxazepam • Patients were NOT in alcohol withdrawal • Safety not addressed (1 seizure in symptom-triggered group) • Take home • Used to support symptom-triggered management • Sort of addresses “prophylaxis” • Only 39% of “heavy” drinkers needed oxazepam per CIWA-Ar • When do we use “prophylactic” oral benzodiazepine? UNM Hospitalist Best Practices- Alcohol Withdrawal

  26. CIWA-Arvs CAGE • NO STUDIES COMPARING CIWA-Arvs CAGE • Thank you Sarah Morley • CIWA-Ar (see handout) • Used at VA (in ER, all inpatient wards and Psych) • “Gold standard” in studies, review articles • Symptom based evaluation (8 categories with 0-7 point scale) • Vital signs taken but not part of the scoring mechanism • Starts treatment much earlier in withdrawal UNM Hospitalist Best Practices- Alcohol Withdrawal

  27. CIWA-Arvs CAGE • CAGE (see handout) • Used at UNMH • More objective measures • Pulse • Temperature • Blood pressure • Respiratory rate • Tremor • Visible mild/marked • palpable UNM Hospitalist Best Practices- Alcohol Withdrawal

  28. CIWA-Arvs CAGE • Take Home • Anyone looking for a research project? • Neither group should feel superior UNM Hospitalist Best Practices- Alcohol Withdrawal

  29. Goals • Understand the pathophysiology of alcohol withdrawal • Recognize why we use symptom triggered therapy (CAGE OR CIWA) • Discuss the role of “prophylaxis” (oral benzodiazepine) • Discuss when/where to use benzodiazepine drips • Become familiar with evidence on other agents (haldol, clonidine, barbiturates, baclofen, precedex) • Substance abuse resources for patients UNM Hospitalist Best Practices- Alcohol Withdrawal

  30. How about a benzodiazepine drip? • Alcohol withdrawal severity is decreased by symptom-oriented adjusted bolus therapy in the ICU. Spies et al. Intensive Care Med 2003 29:2230-38 • Clinical Question: Does bolus vs continuous infusion adjustment affect severity and duration of alcohol withdrawal syndrome, medication requirements and effect on ICU stay? • Confounded by use of clonidine and haloperidol in addition to flunitrazepam (Rohypnol-yes that Rohypnol) • Summarized conclusion: Bolus titrated therapy decreased severity, medication requirements and ICU stay • Limitations: • In ICU setting • Flunitrazepam is illegal in the US • Again, use of clonidine and haloperidol confounds the study UNM Hospitalist Best Practices- Alcohol Withdrawal

  31. How about a lorazepam drip? • Where can this be used at UNMH? • 5 West • No cage or lorazepam drip allowed • Q4h IV lorazepam and/or chlordiazepoxide • No written protocol-d/w Aiko (charge nurse) • 4 West (All SAC floors the same, 4 E, 7S and ED the same) • Yes (on cardiac monitor and o2 sat monitor) • Close monitoring by physician • >10mg/hour room close to RN station, 3:1 • >25 mg/hour must be transferred to ICU • Weaned by 1mg/hour UNM Hospitalist Best Practices- Alcohol Withdrawal

  32. How about a lorazepam drip? • Where can this be used at the VA? • Emergency Room, Ward 7 • Have individual protocols for treatment • 3A, 5A, 5D telemetry • Low intensity CIWA Protocol • Q4 hour oral or iv bolus therapy • Nursing driven protocol, can be initiated by Physician or Nursing based on patient history • 5D Step-Down • Low or High intensity protocols • Q2 hour evaluation • Close monitoring by physician • <20mg/hour IV drip • 5C MICU • High intensity Protocol • Q1-2 hour monitoring • >20mg/hour IV drip +/- additional medications • So, when do you use a benzodiazepine drip? UNM Hospitalist Best Practices- Alcohol Withdrawal

  33. Goals • Understand the pathophysiology of alcohol withdrawal • Recognize why we use symptom triggered therapy (CAGE OR CIWA) • Discuss the role of “prophylaxis” (oral benzodiazepine) • Discuss when/where to use benzodiazepine drips • Become familiar with evidence on other agents (haldol, clonidine, barbiturates, baclofen, precedex) • Substance abuse resources for patients UNM Hospitalist Best Practices- Alcohol Withdrawal

  34. ADJUVANT Agents • Ethanol (Enhances GABA activity) • IV Ethanol for the Treatment of Alcohol Withdrawal Syndrome in Critically Ill Patients Hodges et al. Pharmacotherapy 2004:24 (11): 1578-1585. • Review article (looked at 9 studies) • Ethanol NOT recommended for alcohol withdrawal syndrome • Few well designed clinical trials • ? Efficacy of IV ethanol • Inconsistent pharmacokinetic profile (absorption, distribution, etc) • Narrow therapeutic index (difference between minimum therapeutic and minimum toxic concentration) UNM Hospitalist Best Practices- Alcohol Withdrawal

  35. ADJUVANT Agents • Ethanol (Enhances GABA activity) • Take home • Avoid as adjuvant or first line UNM Hospitalist Best Practices- Alcohol Withdrawal

  36. ADJUVANT Agents • Baclofen (GABA receptor agonist) • Baclofen in the Treatment of Alcohol Withdrawal Syndrome: A comparative study vs diazepam. Addolorato et al. American Journal of Medicine (2006) 119, 276.e13-e18. • Clinical question: In patients with alcohol withdrawal does baclofen compared to diazepam provide efficacious, tolerable and safe treatment of alcohol withdrawal? UNM Hospitalist Best Practices- Alcohol Withdrawal

  37. ADJUVANT Agents • Baclofen • Methods • 37 patients in alcohol withdrawal (CIWA-Ar >9) • Control • 19 patients • 0.5-0.75mg/kg 6 times per day for 10 days • Tapered 25% days 7-10 • Experiment • 18 patients • 10mg Baclofen TID for 10 days UNM Hospitalist Best Practices- Alcohol Withdrawal

  38. ADJUVANT Agents • Baclofen • Results Both baclofen and diazepam significantly decreased CIWA-Ar score (p<0.0001) UNM Hospitalist Best Practices- Alcohol Withdrawal

  39. ADJUVANT Agents • Baclofen • Conclusion • “The efficacy of baclofen in treatment of uncomplicated AWS is comparable to that of the “gold standard” diazepam. These results suggest that baclofen may be considered as a new drug for treatment of uncomplicated AWS.” • Limits • Excluded DT or hallucinations • Small n • Outpatient • Not clearly placebo controlled UNM Hospitalist Best Practices- Alcohol Withdrawal

  40. ADJUVANT Agents • Baclofen • Take home points • Consider baclofen as ADJUVANT to benzodiazepine • Makes sense molecularly • Thin data to support 1st line inpatient use • Potential outpatient use • “higher quality” studies needed UNM Hospitalist Best Practices- Alcohol Withdrawal

  41. ADJUVANT Agents • Haloperidol (Dopamine 2 antagonist) • “Frequently” used at UNMH • Recommend against per Up To Date • Lower the seizure threshold • based on study from 1976 on mice • Noted in JAMA review article from 1997 also • Take home • Absolutely not to be used as single agent • Would avoid ADJUVANT use • Medical-legal reasons UNM Hospitalist Best Practices- Alcohol Withdrawal

  42. ADJUVANT Agents • Anticonvulsants (Phenobarbital, carbamazepine) • No role for seizures in alcohol withdrawal • Recommended as a first ADJUVANT by UTD • BUT combination associated with respiratory depression • Pt. should be in ICU setting • Take home • Adjuvant use is dangerous • Withdrawal seizures self limited UNM Hospitalist Best Practices- Alcohol Withdrawal

  43. ADJUVANT Agents • Clonidine (alpha 2 agonist) • May prevent minor symptoms • Not shown to prevent seizures/DT • Take home • Not to be used as monotherapy • ? Adjuvant if indicated • Opioid withdrawal • On as outpatient (rebound hypertension) • May mask worsening withdrawal (CAGE) • Antihypertensive • Reduced heart rate UNM Hospitalist Best Practices- Alcohol Withdrawal

  44. ADJUVANT Agents • Beta-Blockers (Metoprolol, atenolol, etc) • May prevent minor symptoms • Not shown to prevent seizures/DT • Take home • Not to be used as monotherapy • ? Adjuvant if indicated • CAD • On as outpatient • May mask worsening withdrawal (CAGE) • Antihypertensive • Reduced heart rate UNM Hospitalist Best Practices- Alcohol Withdrawal

  45. ADJUVANT Agents • Precedex (Dexmedetomidine) • Central alpha(2)-receptor agonist that induces a state of cooperative sedation and does not overly suppress respiratory drive • Few (but very promising) case reports of primary treatment for alcohol withdrawal which does not respond to benzodiazepine • Currently used for difficult cases at VA and UNM ICU • Does not mask neurologic-exams • Major side effect are hypotension, bradycardia and respiratory depression UNM Hospitalist Best Practices- Alcohol Withdrawal

  46. Goals • Understand the pathophysiology of alcohol withdrawal • Recognize why we use symptom triggered therapy (CAGE OR CIWA) • Discuss the role of “prophylaxis” (oral benzodiazepine) • Discuss when/where to use benzodiazepine drips • Become familiar with evidence on other agents (haldol, clonidine, barbiturates, baclofen, precedex) • Substance abuse resources for patients UNM Hospitalist Best Practices- Alcohol Withdrawal

  47. Substance Abuse ResourcesDetox is only the first step • UNMH • Social worker • RN Case Manager • Included in handout • VA • SUD walk in clinic M-F 1-4pm • Social worker • SARRTP (residential program) • Inpatient Substance Abuse consultation • 4 available Addiction boarded attendings UNM Hospitalist Best Practices- Alcohol Withdrawal

  48. Conclusion • Alcohol withdrawal occurs when GABA mediated neuro inhibition is lost • Symptom triggered therapy (CAGE OR CIWA-Ar) with a benzodiazepine is standard of care • Consider low dose cage (or equivalent) instead of oral benzodiazepine prophylaxis • Clear evidence does not exist supporting the use of benzodiazepine drip vs bolus therapy • Adjuvant therapies have limited evidence supporting their use and may be contraindicated. • Substance abuse resources for patients are readily available from your social worker UNM Hospitalist Best Practices- Alcohol Withdrawal

  49. References • Addolorate, G et al. Baclofen in the Treatment of Alcohol Withdrawal Syndrome: a comparative study vs diazepam. Amer J Med 2006 119, 276.e13-276.e18. • Daeppen JB et al. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Arch Intern Med. 2002 May 27;162(10):1117-21. • Hodges B et al. Intravenous Ethanol for the Treatment of Alcohol Withdrawal Syndrome in Critically Ill Patients. Pharmacotherapy 2004: 24 (11): 1578-85. • Hoffman RS et al. Management of moderate and severe alcohol withdrawal syndromes. UpToDate. • Jaeger, TM et al. Symptom-Triggered Therapy for Alcohol Withdrawal Syndrome in Medical Inpatients. Mayo Clinic Proceedings vol 76 (7), July 2001. pp 695-701. • Mayo-Smith MF. Pharmacological Management of Alcohol Withdrawal: a Meta-analysis and Evidence-Based Practice Guideline. JAMA vol 278 (2), 9 July 1997, p144-151. • Saitz R et al. Individualized Treatment for Alcohol Withdrawal. JAMA, Aug 17, 1994. Vol 272 no. 7. • Spies CD et al. Alcohol withdrawal severity is decreased by symptom-oriented adjusted bolus therapy in the ICU. Intensive Care Med 2003 29:2230-38. • Dave Olson, MD UNM Hospitalist Best Practices- Alcohol Withdrawal

  50. Thank you, no really. UNM Hospitalist Best Practices- Alcohol Withdrawal

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