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Slide 2 Alcohol Withdrawal Best Practice Tom Shiffler, MD 7/23/10 1 UNM Hospitalist Best Practices- Alcohol Withdrawal Slide 3 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 2 UNM Hospitalist Best Practices- Alcohol Withdrawal Slide 4 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 3 UNM Hospitalist Best Practices- Alcohol Withdrawal Slide 5 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 4 Slide 6 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 5 Slide 7 Course of Alcohol Withdrawal Alcoholic Hallucinosis NOT DTs 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 6 Slide 8 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 7 Slide 9 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 8 UNM Hospitalist Best Practices- Alcohol Withdrawal Slide 10 Pathophysiology-general considerations Apparent genetic predisposition Longer period of continual use associated with more severe withdrawal 9 UNM Hospitalist Best Practices- Alcohol Withdrawal Slide 11 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 10 UNM Hospitalist Best Practices- Alcohol Withdrawal Slide 12 Pathophysiology-acute Alcohol 11 UNM Hospitalist Best Practices- Alcohol Withdrawal www.niaaa.nih.gov/.../31_4_acute_gaba.htm Slide 13 Pathophysiology-absence of alcohol after chronic use 12 UNM Hospitalist Best Practices- Alcohol Withdrawal www.niaaa.nih.gov/.../31_4_acute_gaba.htm Slide 14 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 13 UNM Hospitalist Best Practices- Alcohol Withdrawal Slide 15 Symptom Triggered Therapy (CIWA or CAGE) Benzodiazepine given in RESPONSE to signs or symptoms Why is this standard of care? 14 UNM Hospitalist Best Practices- Alcohol Withdrawal Slide 16 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 15 UNM Hospitalist Best Practices- Alcohol Withdrawal Slide 17 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 16 UNM Hospitalist Best Practices- Alcohol Withdrawal Slide 18 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 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 21 UNM Hospitalist Best Practices- Alcohol Withdrawal Slide 23 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 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 31 UNM Hospitalist Best Practices- Alcohol Withdrawal Slide 33 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 +/- additional medications So, when do you use a benzodiazepine drip? UNM Hospitalist Best Practices- Alcohol Withdrawal 32 Slide 34 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 33 UNM Hospitalist Best Practices- Alcohol Withdrawal Slide 35 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 34 Slide 36 ADJUVANT Agents Ethanol (Enhances GABA activity) Take home Avoid as adjuvant or first line UNM Hospitalist Best Practices- Alcohol Withdrawal 35 Slide 37 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 36 Slide 38 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 37 Slide 39 ADJUVANT Agents Baclofen Results Both baclofen and diazepam significantly decreased CIWA-Ar score (p