Alcohol Withdrawal

Alcohol Withdrawal

Alcohol WithdrawalBest PracticeTom Shiffler, MD7/23/101UNM Hospitalist Best Practices- Alcohol Withdrawal

GoalsUnderstand the pathophysiology of alcohol withdrawalRecognize why we use symptom triggered therapy (CAGE or CIWA)Discuss the role of prophylaxis (oral benzodiazepine)Discuss when/where to use benzodiazepine dripsBecome familiar with evidence on other agents (haldol, clonidine, barbiturates, baclofen, precedex)Substance abuse resources for patients 2UNM Hospitalist Best Practices- Alcohol Withdrawal

Epidemiology of Alcohol Withdrawal500,000 cases per year requiring pharmacologic treatmentDelirium tremens mortality 5% (down from 37% in the early 1900s)ArrhythmiaComplicationPneumoniaPancreatitisHepatitis

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Course of Alcohol WithdrawalMinor symptoms 6 hours after cessationResolve in 24-48 hoursInsomniaTremulousnessMild anxietyGI upsetHADiaphoresispalpitationsUNM Hospitalist Best Practices- Alcohol Withdrawal4

Course of Alcohol WithdrawalWithdrawal Seizures12-48 hours after cessationGeneralized tonic-clonicMore common in those with chronic alcoholismProgress to delirium tremens in 1/3 if untreatedUNM Hospitalist Best Practices- Alcohol Withdrawal5

Course of Alcohol WithdrawalAlcoholic HallucinosisNOT DTsDevelop within 12-24 hours of cessationResolve within 24-48 hours of cessationVisual, auditory and tactile are possibleNOT associated with global sensorial clouding, rather specific hallucinationsVital signs usually normalUNM Hospitalist Best Practices- Alcohol Withdrawal6

Course of Alcohol WithdrawalDelirium Tremens48-96 hours after cessationHallucinations, disorientation, tachycardia, hypertension, fever, agitation and diaphoresisGenerally last 5-7 daysRisk factorsSustained drinkingPrevious DTAge >30Concurrent illnessWithdrawal with elevated alcohol level

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GoalsUnderstand the pathophysiology of alcohol withdrawalRecognize why we use symptom triggered therapy (CAGE OR CIWA)Discuss the role of prophylaxis (oral benzodiazepine)Discuss when/where to use benzodiazepine dripsBecome familiar with evidence on other agents (haldol, clonidine, barbiturates, baclofen, precedex)Substance abuse resources for patients 8UNM Hospitalist Best Practices- Alcohol Withdrawal

Pathophysiology-general considerationsApparent genetic predispositionLonger period of continual use associated with more severe withdrawal


Pathophysiology-MolecularAlcohol increases inhibitory tone via enhancement of GABA activity (an inhibitory neurotransmitter)Chronic alcohol reduces functional GABA receptorsCellular internalizationGene expression

Removal of alcohol leads to functional loss of GABA and unchecked excitatory neurotransmittersDopamineGlutamatenorepinephrine10UNM Hospitalist Best Practices- Alcohol Withdrawal

Pathophysiology-acute Alcohol

11UNM Hospitalist Best Practices- Alcohol Withdrawalwww.niaaa.nih.gov/.../31_4_acute_gaba.htm

Pathophysiology-absence of alcohol after chronic use

12UNM Hospitalist Best Practices- Alcohol Withdrawalwww.niaaa.nih.gov/.../31_4_acute_gaba.htm


Symptom Triggered Therapy (CIWA or CAGE)Benzodiazepine given in RESPONSE to signs or symptomsWhy is this standard of care?


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?MethodsRandomized Double-Blind Controlled Trial101 patients admitted to VA alcohol withdrawal unitControlChlordiazepoxide q6h SCHEDULED50mg x425mg x825-100mg q 1hour per CIWA-Ar scaleNot administered if somnolent or refused


Individualized Treatment for Alcohol Withdrawal. Saitz et al. JAMA Aug 17, 1994 Symptom triggered group25-100mg chlordiazepoxide at CIWA-Ar >7See hand out16UNM Hospitalist Best Practices- Alcohol Withdrawal

Individualized Treatment for Alcohol Withdrawal. Saitz et al. JAMA Aug 17, 1994 OutcomesDuration of medication treatment from admission to last dose of benzodiazepineFixed schedule group: 68 hours meanSymptom triggered group: 9 hours mean (p14 respectivelyExperimental (n=56)Received placebo, then q 30 minutes evaluatedCIWA-Ar >7 received 15mg oxazepamCIWA-Ar >14 received 30mg oxazepamPatients observed for 48 hours after study21UNM Hospitalist Best Practices- Alcohol Withdrawal

Symptom-Triggered vs Fixed-Schedule Doses of Benzodiazepine for Alcohol Withdrawal Daeppen et al. Arch Intern Med May 27 2002Results22 of 56 (39%) in symptom-triggered received oxazepamDosage37.5mg mean symptom triggered group 231.4mg mean fixed schedule group (p25 mg/hour must be transferred to ICU Weaned by 1mg/hour


How about a lorazepam drip?Where can this be used at the VA?Emergency Room, Ward 7 Have individual protocols for treatment3A, 5A, 5D telemetryLow intensity CIWA ProtocolQ4 hour oral or iv bolus therapyNursing driven protocol, can be initiated by Physician or Nursing based on patient history5D Step-DownLow or High intensity protocolsQ2 hour evaluationClose monitoring by physician20mg/hour IV drip +/- additional medicationsSo, when do you use a benzodiazepine drip?



ADJUVANT AgentsEthanol (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 syndromeFew well designed clinical trials? Efficacy of IV ethanolInconsistent pharmacokinetic profile (absorption, distribution, etc)Narrow therapeutic index (difference between minimum therapeutic and minimum toxic concentration)


ADJUVANT AgentsEthanol (Enhances GABA activity)Take homeAvoid as adjuvant or first line


ADJUVANT AgentsBaclofen (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 Withdrawal36

ADJUVANT AgentsBaclofenMethods37 patients in alcohol withdrawal (CIWA-Ar >9)Control19 patients0.5-0.75mg/kg 6 times per day for 10 daysTapered 25% days 7-10Experiment18 patients10mg Baclofen TID for 10 daysUNM Hospitalist Best Practices- Alcohol Withdrawal37

ADJUVANT AgentsBaclofenResults

Both baclofen and diazepam significantly decreased CIWA-Ar score (p

Alcohol Withdrawal

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