Inpatient Inpatient Management of Management of

Alcohol WithdrawalAlcohol Withdrawal

Kim Tartaglia, MDKim Tartaglia, MD

ObjectivesObjectives

Describe the different types of Describe the different types of alcohol withdrawalalcohol withdrawal

Recognize the symptoms of alcohol Recognize the symptoms of alcohol withdrawal delirium (AWD or DTs)withdrawal delirium (AWD or DTs)

Review the management of AWDReview the management of AWD

Scope of the problemScope of the problem

8 million people dependent on alcohol 8 million people dependent on alcohol is the USis the US

3.5 million dependent on illicit drugs3.5 million dependent on illicit drugs 500,000 episodes/yr of alcohol 500,000 episodes/yr of alcohol

withdrawalwithdrawal 15% of pts in primary care have 15% of pts in primary care have

either an alcohol-related health either an alcohol-related health problem or “at-risk” pattern of alcohol problem or “at-risk” pattern of alcohol useuse

Spectrum of EtOH Spectrum of EtOH withdrawalwithdrawal

Mild withdrawalMild withdrawal Withdrawal-associated seizuresWithdrawal-associated seizures Alcoholic HallucinosisAlcoholic Hallucinosis Alcohol Withdrawal Delirium (aka Alcohol Withdrawal Delirium (aka

Delerium Tremens)Delerium Tremens)

Alcohol Withdrawal Alcohol Withdrawal PathophysiologyPathophysiology

GABA receptors have binding site for GABA receptors have binding site for EtOHEtOH EtOH induces an insensitivity to GABAEtOH induces an insensitivity to GABA More EtOH needed to maintain inhibitory More EtOH needed to maintain inhibitory

tonetone EtOH inhibits glutamate-induced EtOH inhibits glutamate-induced

excitationexcitation Withdrawal occurs w/ abrupt cessation Withdrawal occurs w/ abrupt cessation

after prolonged exposure (after prolonged exposure (notnot a binge) a binge) Leads to over-activity of CNSLeads to over-activity of CNS

Mild EtOH withdrawalMild EtOH withdrawal

6hrs after stop drinking (may occur 6hrs after stop drinking (may occur w/ significant blood-alcohol levels)w/ significant blood-alcohol levels)

Resolves in 1-2 daysResolves in 1-2 days CNS overactivityCNS overactivity

Insomnia, anxietyInsomnia, anxiety TremulousnessTremulousness DiaphoresisDiaphoresis GI upsetGI upset HeadachesHeadaches

Withdrawal-associated Withdrawal-associated seizuresseizures

Occurs 12-48hr after last drink (can Occurs 12-48hr after last drink (can occur as soon as 2hr)occur as soon as 2hr)

Generalized tonic-clonicGeneralized tonic-clonic Usually single sz (but may be several Usually single sz (but may be several

clustered over short time)clustered over short time) Status epilepticus NOT consistentStatus epilepticus NOT consistent If untreated, 30% will progress to If untreated, 30% will progress to

DTsDTs

Alcoholic HallucinosisAlcoholic Hallucinosis

Develops 12hr after cessationDevelops 12hr after cessation Resolves within 48hrResolves within 48hr Usually visual (can be tactile or Usually visual (can be tactile or

auditory)auditory) Not part of DTsNot part of DTs: Normal vitals and : Normal vitals and

sensoriumsensorium

These are hallucinations that occur These are hallucinations that occur before DTsbefore DTs

Alcohol Withdrawal Alcohol Withdrawal DeliriumDelirium

SymptomsSymptoms Risk factorsRisk factors TimingTiming PrognosisPrognosis

Diagnostic Criteria for Diagnostic Criteria for Alcohol Withdrawal Alcohol Withdrawal

Delirium (AWD)Delirium (AWD) Disturbance of Consciousness, with Disturbance of Consciousness, with

reduced ability to focus, sustain, or shift reduced ability to focus, sustain, or shift attentionattention

Change in cognition or development of Change in cognition or development of perceptual disturbance that is not better perceptual disturbance that is not better accounted for by pre-existing dementiaaccounted for by pre-existing dementia

Develops in short period and tends to Develops in short period and tends to fluctuate throughout dayfluctuate throughout day

Evidence that symptoms developed Evidence that symptoms developed during or shortly after a withdrawal during or shortly after a withdrawal syndromesyndrome

Arch Int Med Vol 164, July 12, 2004

Symptoms of AWDSymptoms of AWD

AgitationAgitation DisorientationDisorientation HallucinationsHallucinations Autonomic Autonomic

instability instability TachycardiaTachycardia HTNHTN Hyperthermia Hyperthermia DiaphoresisDiaphoresis

Alcohol Withdrawal Alcohol Withdrawal DeliriumDelirium

Occurs in ~5% of patients who Occurs in ~5% of patients who experience alcohol withdrawalexperience alcohol withdrawal

Occurs 2-4 days after last drink and Occurs 2-4 days after last drink and lasts 1-5 days (average of 2-3 days).lasts 1-5 days (average of 2-3 days).

Be cognizant of a concurrent illness Be cognizant of a concurrent illness that may precipitate DTs that may precipitate DTs Infection, pancreatitis, hepatitis, GI Infection, pancreatitis, hepatitis, GI

bleed, cardiac ischemiableed, cardiac ischemia

Timing of WithdrawalTiming of Withdrawal

UpToDate, 03/2009

MortalityMortality

Mortality is ~5% Mortality is ~5% Increased by older age, coexisting Increased by older age, coexisting

lung or liver disease, and temp>104 lung or liver disease, and temp>104 FF

Death due to arrhythmia, Death due to arrhythmia, complicating illness (pneumonia), or complicating illness (pneumonia), or failure to recognize trigger illness failure to recognize trigger illness (CNS infection, pancreatitis)(CNS infection, pancreatitis)

Risk Factors for AWDRisk Factors for AWD

History of Previous DTsHistory of Previous DTs Age >30 yrAge >30 yr Presence of concurrent illnessPresence of concurrent illness H/O sustained drinkingH/O sustained drinking Experiencing EtOH withdrawal in Experiencing EtOH withdrawal in

presence of elevated alcohol levelpresence of elevated alcohol level Longer period since last drink (develop Longer period since last drink (develop

w/drawal >2 days since last drink)w/drawal >2 days since last drink)

Associated findings w/ Associated findings w/ DTsDTs

Dehydration (increased losses)Dehydration (increased losses) Hypokalemia (renal and extrarenal Hypokalemia (renal and extrarenal

losses)losses) Hypomagnesemia (increases risk for Hypomagnesemia (increases risk for

seizures and arrhythmias)seizures and arrhythmias) Hypophosphatemia (increases risk Hypophosphatemia (increases risk

for rhabdomyolysis and cardiac for rhabdomyolysis and cardiac failure)failure)

ManagementManagement of EtOH of EtOH withdrawalwithdrawal

Evaluate for other conditions Evaluate for other conditions Labs for metabolic causes Labs for metabolic causes Consider Head CT or LP for intracranial Consider Head CT or LP for intracranial

causescauses Consider GI bleedConsider GI bleed

Supportive careSupportive care MedicationsMedications

Supportive Care for DTsSupportive Care for DTs

Replace volume deficits w/ isotonic Replace volume deficits w/ isotonic fluidsfluids

Thiamine 100mg IV and glucoseThiamine 100mg IV and glucose MVI w/ folateMVI w/ folate Aggressively correct abnormal K, Aggressively correct abnormal K,

Mg, Phos, and glucoseMg, Phos, and glucose

Overview of TreatmentOverview of Treatment

Benzodiazepines = Mainstay of EtOH Benzodiazepines = Mainstay of EtOH withdrawal treatmentwithdrawal treatment 6 prospective trials comparing BZD to 6 prospective trials comparing BZD to

placeboplacebo Risk reduction of 7.7 in preventing seizures Risk reduction of 7.7 in preventing seizures Risk reduction of 4.9 in preventing deliriumRisk reduction of 4.9 in preventing delirium

Work by stimulation GABA receptorsWork by stimulation GABA receptors Treats agitation and prevents Treats agitation and prevents

progressionprogression

Kosten TR. NEJM 2003; 348: 1786

Benzos vs NeurolepticsBenzos vs Neuroleptics

Meta-analysis based on 5 studiesMeta-analysis based on 5 studies

Benzos more effective in reducing Benzos more effective in reducing mortality from AWD (RR 6.6 for mortality from AWD (RR 6.6 for neuroleptics, CI 1.2-34)neuroleptics, CI 1.2-34)

Time to achieve adequate sedation Time to achieve adequate sedation was less w/ BZDs (1.1 vs 3 hr, was less w/ BZDs (1.1 vs 3 hr, p=0.02)p=0.02)

Arch Int Med, vol 164, 2004.

Fixed vs symptom-triggered Fixed vs symptom-triggered dosingdosing

Double-blind RCTDouble-blind RCT Fixed dose: rec’d chlordiazepoxide Fixed dose: rec’d chlordiazepoxide

q6h (50mg x1d then 25mg x2d) plus q6h (50mg x1d then 25mg x2d) plus prn for CIWA-Ar >8prn for CIWA-Ar >8

Symptom-triggered: Rec’d 25-100mg Symptom-triggered: Rec’d 25-100mg q1h prn CIWA-Ar>8q1h prn CIWA-Ar>8

Primary outcome: Duration of med Primary outcome: Duration of med txtmt and total amt of BZD giventxtmt and total amt of BZD given

Saitz R. JAMA 1994; 272: 519.

Individualized treatment for alcohol withdrawal. A randomized double-

blind controlled trial

Figure 1 . Kaplan-Meier curves illustrate treatment times for both groups. Treatment time was shorter in the patients receiving symptom-triggered therapy (log rank test P <.001)

RESULTS: Fixed vs RESULTS: Fixed vs symptom-triggered dosingsymptom-triggered dosing

Median txtmt duration was shorter Median txtmt duration was shorter in symptom-triggered group (9hr vs in symptom-triggered group (9hr vs 68hr, p<.001) 68hr, p<.001)

Symptom triggered group rec’d less Symptom triggered group rec’d less BZD (100mg vs 425mg, p<.001)BZD (100mg vs 425mg, p<.001)

No difference b/w groups in severity No difference b/w groups in severity (CIWA-Ar scores), incidence of DTs, (CIWA-Ar scores), incidence of DTs, hallucinations, seizures, leaving hallucinations, seizures, leaving AMA, or readmission ratesAMA, or readmission rates

Saitz R. JAMA 1994; 272: 519.

Clinical Institute Clinical Institute Withdrawal Assessment Withdrawal Assessment

(CIWA-Ar) scale(CIWA-Ar) scale- Maximum score of 67- Score > 8 necessitates treatment

The Bottom Line:The Bottom Line:2004 Practice Guidelines2004 Practice Guidelines

Benzos should be primary agent for Benzos should be primary agent for managing AWD (gr A)managing AWD (gr A) Reduce mortality, duration of sx and Reduce mortality, duration of sx and

have less complications than have less complications than neurolepticsneuroleptics

Initial goal is control of agitation Initial goal is control of agitation Rapid, adequate control of agitation Rapid, adequate control of agitation

reduces adverse eventsreduces adverse events

Arch Int Med, vol 164, 2004.

BenzodiazepinesBenzodiazepines

Long-acting formulations preferred Long-acting formulations preferred Shorter acting (lorazepam) may be Shorter acting (lorazepam) may be

preferred in elderly or liver diseasepreferred in elderly or liver disease Continuous infusions of BZDs are Continuous infusions of BZDs are

not cost-effective.not cost-effective. Onset of action for BZDs: 15sec – Onset of action for BZDs: 15sec –

2min2min Peak action: 5-15 minPeak action: 5-15 min

Examples of Med Examples of Med RegimensRegimens

Diazepam 5mg IV (over 2 min)Diazepam 5mg IV (over 2 min) Repeat in 10min if no effectRepeat in 10min if no effect If still no effect, increase dose to 10mg IVIf still no effect, increase dose to 10mg IV Give 5-20mg qhr prn light somnolenceGive 5-20mg qhr prn light somnolence

Lorazepam 1-4mg IVLorazepam 1-4mg IV Repeat q15 min prn, then q1hr to maintain Repeat q15 min prn, then q1hr to maintain

light somnolencelight somnolence

Prophylaxis against AWDProphylaxis against AWD

Can be considered in pts w/ history of Can be considered in pts w/ history of withdrawal seizures, AWD, or prolonged, withdrawal seizures, AWD, or prolonged, heavy alcohol useheavy alcohol use

Benefit unclear and may lead to Benefit unclear and may lead to increased BZD overall dose and increased BZD overall dose and treatment durationtreatment duration

Can give chlordiazepoxide 50mg q6 x1 Can give chlordiazepoxide 50mg q6 x1 day, then 25mg q6 x2 daysday, then 25mg q6 x2 days

Must still have CIWA-Ar scores and prn Must still have CIWA-Ar scores and prn BZD.BZD.

Adjunctive meds: Adjunctive meds: NeurolepticsNeuroleptics

Inferior to benzodiazepinesInferior to benzodiazepines Increased risk of side effects, Increased risk of side effects,

including lower seizure threshold, including lower seizure threshold, prolonged QTc and hypotensionprolonged QTc and hypotension

No studies done on “newer” atypicalsNo studies done on “newer” atypicals Can be used in conjunction w/ benzo Can be used in conjunction w/ benzo

in setting of perceptual disturbances in setting of perceptual disturbances (gr C)(gr C)

Adjunctive medsAdjunctive meds

Beta-blockers: not well studied Beta-blockers: not well studied Mild reduction in autonomic manifestationsMild reduction in autonomic manifestations One controlled study w/ propranolol: One controlled study w/ propranolol:

increased incidence of deliriumincreased incidence of delirium Can be used if persistent HTN or Can be used if persistent HTN or

tachycardia (gr C)tachycardia (gr C) Ethyl Alcohol – not recommendedEthyl Alcohol – not recommended

No controlled trials, potential GI/neuro No controlled trials, potential GI/neuro effectseffects

Difficult to titrate, not readily availableDifficult to titrate, not readily available

Adjunctive medsAdjunctive meds

ClonidineClonidine Effective for mild-mod symptoms of Effective for mild-mod symptoms of

withdrawalwithdrawal No studies that show decrease rate of No studies that show decrease rate of

delirium or seizuresdelirium or seizures CarbamazepineCarbamazepine

Effective for mild-mod symptoms of Effective for mild-mod symptoms of withdrawalwithdrawal

Limited data on preventing seizures or Limited data on preventing seizures or deliriumdelirium

SummarySummary

Alcohol withdrawal includes a number of Alcohol withdrawal includes a number of clinical syndromes that exists along a clinical syndromes that exists along a time and severity continuumtime and severity continuum

Benzodiazepines are the mainstay of Benzodiazepines are the mainstay of txtmttxtmt Admin should be guided by CIWA scores Admin should be guided by CIWA scores

(>8)(>8) Identification of a trigger for AWD and Identification of a trigger for AWD and

supportive txtmt w/ thiamine, glucose supportive txtmt w/ thiamine, glucose and electrolyte replacement are crucialand electrolyte replacement are crucial

References and ReadingReferences and Reading Ferguson JA, et al. Risk factors for delirium Ferguson JA, et al. Risk factors for delirium

tremens development. J Gen Intern Med 1996; 11: tremens development. J Gen Intern Med 1996; 11: 410.410.

Hack JB, et al. Thiamine before glucose to prevent Hack JB, et al. Thiamine before glucose to prevent Wernicke Encephalopathy: examining the Wernicke Encephalopathy: examining the conventional wisdom. JAMA 1998; 279: 583.conventional wisdom. JAMA 1998; 279: 583.

Kosten TR. Management of Drug and Alcohol Kosten TR. Management of Drug and Alcohol Witdrawal. NEJM 2003; 348: 1786.Witdrawal. NEJM 2003; 348: 1786.

Mayo-Smith MF. Pharmacological management of Mayo-Smith MF. Pharmacological management of alcohol withdrawal. JAMA 1997; 278: 144alcohol withdrawal. JAMA 1997; 278: 144

Mayo-Smith MF, et al. Management of Alcohol Mayo-Smith MF, et al. Management of Alcohol Withdrawal Delirium. Arch Intern Med 2004; 164: Withdrawal Delirium. Arch Intern Med 2004; 164: 14051405

Ntais C, et al. Benzodiazepines for alcohol Ntais C, et al. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev 2005.withdrawal. Cochrane Database Syst Rev 2005.

Saitz R, et al. Individualized treatment for alcohol Saitz R, et al. Individualized treatment for alcohol withdrawal. JAMA 1994; 272: 519.withdrawal. JAMA 1994; 272: 519.