Substance Withdrawal

Substance Substance WithdrawalWithdrawal

Jay GreenJay GreenEmergency Medicine Resident, PGY-Emergency Medicine Resident, PGY-

22February 28, 2008February 28, 2008

OutlineOutline Pre-testPre-test Substance Withdrawal CasesSubstance Withdrawal Cases

– AlcoholAlcohol– OpioidOpioid– BenzodiazepineBenzodiazepine– CocaineCocaine

Post-testPost-test Evidence of a proud father!Evidence of a proud father!

Pre-test Q1Pre-test Q1 What percentage of hospitalized What percentage of hospitalized

patients are ethanol dependent?patients are ethanol dependent?A.A. 5-10%5-10%B.B. 15-20%15-20%C.C. 30-40%30-40%D.D. >40%>40%

Pre-test Q2Pre-test Q2 What is the current mortality from What is the current mortality from

alcohol withdrawal syndrome?alcohol withdrawal syndrome?A.A. 5%5%B.B. 7%7%C.C. <1%<1%D.D. 10%10%

Pre-test Q3Pre-test Q3 Alcohol acts as a/an ______________ Alcohol acts as a/an ______________

on the GABA receptor.on the GABA receptor.A.A. Indirect agonistIndirect agonistB.B. Direct agonistDirect agonistC.C. Indirect antagonistIndirect antagonistD.D. Direct antagonistDirect antagonist

Pre-test Q4Pre-test Q4 In alcohol withdrawal, which of the In alcohol withdrawal, which of the

following agents is best used in following agents is best used in patients at risk for oversedation and patients at risk for oversedation and those with liver disease?those with liver disease?

A.A. DiazepamDiazepamB.B. LorazepamLorazepamC.C. PhenytoinPhenytoinD.D. ThiamineThiamine

Pre-test Q5Pre-test Q5 Which of the following agents is Which of the following agents is

best used for AWS if high doses of best used for AWS if high doses of benzodiazepines are ineffective?benzodiazepines are ineffective?

A.A. CarbamazepineCarbamazepineB.B. PhenytoinPhenytoinC.C. EthanolEthanolD.D. PhenobarbitalPhenobarbital

Pre-test Q6Pre-test Q6 Symptom-triggered therapy in Symptom-triggered therapy in

alcohol withdrawal has been shown alcohol withdrawal has been shown to reduce which of the following to reduce which of the following factors?factors?

A.A. Amount of medication usedAmount of medication usedB.B. Duration of treatmentDuration of treatmentC.C. Both A and BBoth A and BD.D. Neither A nor BNeither A nor B

Pre-test Q7Pre-test Q7 Neuroleptic agents:Neuroleptic agents:

A.A. Effectively control autonomic instability Effectively control autonomic instability associated with AWSassociated with AWS

B.B. Control alcohol-induced seizuresControl alcohol-induced seizuresC.C. Improve hyperthermia related to AWSImprove hyperthermia related to AWSD.D. Reduce the seizure thresholdReduce the seizure threshold

Pre-test Q8Pre-test Q8 The use of phenytoin is indicated in The use of phenytoin is indicated in

which of the following situations?which of the following situations?A.A. A patient with AWS and non-alcohol-A patient with AWS and non-alcohol-

related seizuresrelated seizuresB.B. A patient with an AWSA patient with an AWSC.C. A patient with HTN and tachycardia A patient with HTN and tachycardia

related to AWSrelated to AWSD.D. An intoxicated patient with a history of An intoxicated patient with a history of

AWSAWS

Pre-test Q9Pre-test Q9 The benzodiazepine of choice for The benzodiazepine of choice for

treating benzodiazepine withdrawal treating benzodiazepine withdrawal is:is:

A)A) MidazolamMidazolamB)B) LorazepamLorazepamC)C) DiazepamDiazepamD)D) AlprazolamAlprazolam

Pre-test Q10Pre-test Q10 ED management of opioid ED management of opioid

withdrawal consists primarily of:withdrawal consists primarily of:A)A) BenzodiazepinesBenzodiazepinesB)B) ββ-blockers-blockersC)C) Supportive careSupportive careD)D) MethadoneMethadone

Pre-test Q11Pre-test Q11 Patients with acute cocaine Patients with acute cocaine

withdrawal often require admission.withdrawal often require admission.TrueTrueFalseFalse

Case 1Case 1 43M previously healthy, no meds43M previously healthy, no meds Unemployed, brought in by sisterUnemployed, brought in by sister N, V today, sister worried about hand N, V today, sister worried about hand

tremortremor SocHx: Smoker, “few beers”/day x yearsSocHx: Smoker, “few beers”/day x years O/EO/E

– HR 112, bp 160/96HR 112, bp 160/96– Appears a bit anxiousAppears a bit anxious– TremulousTremulous

Case 2Case 2 43M no known PMH/meds43M no known PMH/meds Brought in by EMSBrought in by EMS Found to be agitated, vomiting, ?hallucinatingFound to be agitated, vomiting, ?hallucinating Hx from pt unhelpfulHx from pt unhelpful O/EO/E

– Not oriented, GCS 13 (E4V4M5)Not oriented, GCS 13 (E4V4M5)– Vitals 130, 175/100, 38Vitals 130, 175/100, 3877, 20, 95%, 20, 95%– Volatile, ?visual hallucinations/anxiousVolatile, ?visual hallucinations/anxious– ++tremulous, ?hyperreflexia++tremulous, ?hyperreflexia

Alcohol WithdrawalAlcohol Withdrawal

Alcohol Withdrawal - HistoryAlcohol Withdrawal - History First described by Pliny the Elder, 1First described by Pliny the Elder, 1stst century century

BC BC – Naturalis HistoriaNaturalis Historia– "...drunkenness brings pallor and sagging cheeks, "...drunkenness brings pallor and sagging cheeks,

sore eyes, and trembling hands that spill a full sore eyes, and trembling hands that spill a full cup, of which the immediate punishment is a cup, of which the immediate punishment is a haunted sleep and unrestful nights. ..."haunted sleep and unrestful nights. ..."

OslerOsler– Initial txInitial tx

Supportive, KBr, chloral hydrate, hyoscine, opiumSupportive, KBr, chloral hydrate, hyoscine, opium Isbell Isbell et al,et al, 1955 1955

– Alcohol Alcohol withdrawal syndrome withdrawal syndrome– Amount/duration of alcohol intake Amount/duration of alcohol intake severity severity

Isbell H, Frasier HF, Wilkler A et al. An experimental study of the etiology of “rum fits” and delirium tremens. QJ Study Alcohol 1955;16:1.

Alcohol W/D - EpidemiologyAlcohol W/D - Epidemiology 22% of Americans >12y report binge 22% of Americans >12y report binge

drinking at least once during the past 30ddrinking at least once during the past 30d 7% report heavy regular drinking7% report heavy regular drinking

– 2003 US National 2003 US National Survey on Drug Use and HealthSurvey on Drug Use and Health These are the people who actually answer surveysThese are the people who actually answer surveys

15-20% hospitalized pts are alcohol 15-20% hospitalized pts are alcohol dependentdependent

– Hodges and Mazur, Pharmacotherapy 2004;24:1578-85Hodges and Mazur, Pharmacotherapy 2004;24:1578-85 Mortality <1%Mortality <1%

Alcohol W/D - Alcohol W/D - PathophysiologyPathophysiology

Chronic EtOH Chronic EtOH CNS depressant CNS depressant– ↑ ↑ GABAminergic tone GABAminergic tone sedation via GABAa- sedation via GABAa-

receptorreceptor Downregulation of GABAa-receptorDownregulation of GABAa-receptor

– Normal level of consciousness with Normal level of consciousness with ↑↑EtOH↑↑EtOH

– NMDA inhibitionNMDA inhibition Upregulation of NMDA-receptorsUpregulation of NMDA-receptors

W/D of EtOHW/D of EtOHCNS excitation (CNS excitation (↓GABA, ↑NMDA)↓GABA, ↑NMDA)– Inhibitory control of excitatory NT’s is lostInhibitory control of excitatory NT’s is lost

CNS excitation (tremor, sz, hallucination)CNS excitation (tremor, sz, hallucination) ANS stimulation (HTN, sweating, hyperthermia, ANS stimulation (HTN, sweating, hyperthermia,

tachycardia)tachycardia)

Case 1Case 1 43M previously healthy, no meds43M previously healthy, no meds Unemployed, brought in by sisterUnemployed, brought in by sister N, V today, sister worried about hand tremorN, V today, sister worried about hand tremor SocHx: Smoker, “few beers”/day x yearsSocHx: Smoker, “few beers”/day x years O/EO/E

– HR 112, bp 160/96HR 112, bp 160/96– Appears a bit anxiousAppears a bit anxious– TremulousTremulous

What else is on the ddx?What else is on the ddx?

DDxDDx What else is on the ddx?What else is on the ddx?

– Acute psychosisAcute psychosis– CNS infectionCNS infection– ThyrotoxicosisThyrotoxicosis– Anticholinergic poisoningAnticholinergic poisoning– W/D from other sedative-hypnoticsW/D from other sedative-hypnotics

Alcohol W/D - Alcohol W/D - Signs/SymptomsSigns/Symptoms

Do you need to stop EtOH Do you need to stop EtOH consumption to get EtOH W/D?consumption to get EtOH W/D?

When do signs of W/D begin?When do signs of W/D begin?

Alcohol W/D - Alcohol W/D - Signs/SymptomsSigns/Symptoms

Begin 6-24h after decreasing EtOHBegin 6-24h after decreasing EtOH– Can occur with continued lower volume Can occur with continued lower volume

EtOHEtOH Lasts 2-7dLasts 2-7d Severity Severity dose/duration of EtOH dose/duration of EtOH

Alcohol W/D - ClassificationAlcohol W/D - Classification How do you classify EtOH W/D?How do you classify EtOH W/D? 4 stages:4 stages:

1)1) Tremulousness (6-12h)Tremulousness (6-12h)2)2) Hallucinations (12-48h)Hallucinations (12-48h)3)3) Seizures (12-48h)Seizures (12-48h)4)4) DT’s (>48h)DT’s (>48h)

Minor Minor Major Major DT’s DT’s Timing & severityTiming & severity

– early/late & complicated/uncomplicatedearly/late & complicated/uncomplicated

Alcohol W/D - ClassificationAlcohol W/D - Classification Minor Minor Major Major DT’s DT’s What are some symptoms of minor W/D?What are some symptoms of minor W/D?

– Early onset, peak 24-36hEarly onset, peak 24-36h– N, anorexia, tremor, tachycardia, HTN, N, anorexia, tremor, tachycardia, HTN,

hyperreflexia, insomnia, anxietyhyperreflexia, insomnia, anxiety What are some symptoms of major W/D?What are some symptoms of major W/D?

– Later onset (24h), peaks 2-5dLater onset (24h), peaks 2-5d– ++anxiety, insomnia, irritability, tremor, ++anxiety, insomnia, irritability, tremor,

anorexia, tachycardia, hyperreflexia, HTN, fever, anorexia, tachycardia, hyperreflexia, HTN, fever, seizure, auditory/visual hallucinations, deliriumseizure, auditory/visual hallucinations, delirium

Alcohol Withdrawal - Alcohol Withdrawal - DiagnosisDiagnosis

DSM-IV diagnostic criteriaDSM-IV diagnostic criteriaAlcohol WithdrawalAlcohol Withdrawal– Cessation/reduction of heavy/prolonged Cessation/reduction of heavy/prolonged

alcohol use resulting in the development alcohol use resulting in the development of two or more of the following:of two or more of the following: ANS hyperactivity, increased hand tremor, ANS hyperactivity, increased hand tremor,

insomnia, N, V, transient hallucinations, insomnia, N, V, transient hallucinations, psychomotor agitation, anxiety, sz, affected psychomotor agitation, anxiety, sz, affected global function global function

Alcohol Withdrawal - Alcohol Withdrawal - DiagnosisDiagnosis

DSM-IV diagnostic criteriaDSM-IV diagnostic criteriaAlcohol Withdrawal with Delirium (‘DT’s’)Alcohol Withdrawal with Delirium (‘DT’s’)– Also includes Also includes decreased consciousness, decreased consciousness,

change in cognition, perceptual change in cognition, perceptual disturbancedisturbance

Case 2 revisitedCase 2 revisited 43M no known PMH/meds43M no known PMH/meds Brought in by EMSBrought in by EMS Found to be agitated, vomiting, ?hallucinatingFound to be agitated, vomiting, ?hallucinating Hx from pt unhelpfulHx from pt unhelpful O/EO/E


You think they have DT’s.You think they have DT’s. What else is on the ddx?What else is on the ddx?

Case 2Case 2 You think this patient has delirium tremensYou think this patient has delirium tremens

What else could this be?What else could this be?– SepsisSepsis– MeningitisMeningitis– SAHSAH– Heat strokeHeat stroke– Serotonin syndromeSerotonin syndrome– NMSNMS– Cocaine/amphetamine toxicityCocaine/amphetamine toxicity– Malignant hyperthermia Malignant hyperthermia

Alcohol W/D – Delirium Alcohol W/D – Delirium TremensTremens

Extreme end of the spectrumExtreme end of the spectrum Almost never before 3dAlmost never before 3d 5% of pts hospitalized for EtOH W/D5% of pts hospitalized for EtOH W/D

– Difficult to predict who will get itDifficult to predict who will get it Can last up to 2 weeksCan last up to 2 weeks THESE PATIENTS ARE SICK!THESE PATIENTS ARE SICK!

Case 2 revisitedCase 2 revisited 43M no known PMH/meds43M no known PMH/meds Brought in by EMSBrought in by EMS Found to be agitated, vomiting, ?hallucinatingFound to be agitated, vomiting, ?hallucinating Hx from pt unhelpfulHx from pt unhelpful O/EO/E


What investigations?What investigations?

Alcohol Withdrawal - IxAlcohol Withdrawal - Ix C/SC/S CBC, lytes, BUN, Cr, LFT’s, lipase, INR, EtOHCBC, lytes, BUN, Cr, LFT’s, lipase, INR, EtOH U/AU/A CXRCXR ECGECG

±±VBGVBG ±CT head±CT head ±LP±LP ±Tox screen±Tox screen

Case 2Case 2 Labs sentLabs sent ECG – tachycardiaECG – tachycardia CXR pendingCXR pending C/S – 2.9C/S – 2.9

What would you like to do now?What would you like to do now?

Case 2 - TxCase 2 - Tx Initial StabilizationInitial Stabilization

– ABCsABCs– NGTNGT– ±Restraints±Restraints

What about giving glucose before What about giving glucose before thiamine?thiamine?

Wernicke-Korsakoff Wernicke-Korsakoff SyndromeSyndrome

Symptoms/signs?Symptoms/signs? Oculomotor disturbances (nystagmus and ocular Oculomotor disturbances (nystagmus and ocular

palsies), confusion, ataxia – 12% have triadpalsies), confusion, ataxia – 12% have triad– Mortality 10-20%Mortality 10-20%

Can you precipitate it with glucose administration?Can you precipitate it with glucose administration?

Slovis: “The concept that glucose preceding thiamine Slovis: “The concept that glucose preceding thiamine in an alcoholic can precipitate Wernicke’s in an alcoholic can precipitate Wernicke’s encephalopathy is unfounded/unproven. It is encephalopathy is unfounded/unproven. It is accepted that it takes hours-days for this to occur, accepted that it takes hours-days for this to occur, and so thiamine given within a reasonable time of and so thiamine given within a reasonable time of glucose administration (minutes-hours) is glucose administration (minutes-hours) is acceptable.”acceptable.”

Wernicke-Korsakoff Wernicke-Korsakoff SyndromeSyndrome

Case reportsCase reports– WK syndrome after WK syndrome after prolongedprolonged IV glucose IV glucose

administrationadministration

BOTTOM LINEBOTTOM LINE– Don’t delay glucose for thiamineDon’t delay glucose for thiamine

Waton et al. Ir J Med Sci 1981 Oct;150(10):301-3

Alcohol Withdrawal - TxAlcohol Withdrawal - Tx 4 principles of treatment4 principles of treatment

1) Evaluate for concurrent illness1) Evaluate for concurrent illness2) Restore inhibitory tone to CNS2) Restore inhibitory tone to CNS3) ID/correct lyte/fluid deficiencies3) ID/correct lyte/fluid deficiencies4) Allow pt to recover with the least 4) Allow pt to recover with the least

amount of physical restraint to decrease amount of physical restraint to decrease the risk of hyperthermia and the risk of hyperthermia and rhabdomyolysisrhabdomyolysis

EM Reports 26(16) July 25, 2005



amount of physical restraint to decrease amount of physical restraint to decrease the risk of hyperthermia and the risk of hyperthermia and rhabdomyolysisrhabdomyolysis


Alcohol Withdrawal - TxAlcohol Withdrawal - Tx >150 drug combinations>150 drug combinations Benzos are mainstayBenzos are mainstay

– Interact with GABAa-receptorInteract with GABAa-receptor– Substitute for removal of EtOH as a GABAa-Substitute for removal of EtOH as a GABAa-

agonistagonist

Cl-

GABAa-RBZ

GABA

BZ-r

GABA-r

Cl-Cl-Cl-Cl-

Extracellular Intracellular

ZZZZ….Hyperpolarized

Alcohol Withdrawal - TxAlcohol Withdrawal - Tx >150 drug combinations>150 drug combinations Benzos are mainstayBenzos are mainstay

– Interact with GABAa-receptorInteract with GABAa-receptor– Substitute for removal of EtOH as a GABAa-agonistSubstitute for removal of EtOH as a GABAa-agonist– Reduce DT’s, mortality, duration of W/DReduce DT’s, mortality, duration of W/D

N=574, randomized pts to benzo, antipsychotic, N=574, randomized pts to benzo, antipsychotic, antihistamine, thiamineantihistamine, thiamine

– Benzo had lowest risk of DT’s and alcohol W/D szBenzo had lowest risk of DT’s and alcohol W/D sz– Antipsychotic increased sz risk Antipsychotic increased sz risk

N=229, 2mg IM Ativan N=229, 2mg IM Ativan ↓ risk of recurrent sz from 24%↓ risk of recurrent sz from 24%3% 3% and ↓admission from 42%and ↓admission from 42%29%29%

Kaim et al. Am J Psychiatry 1969;125: 1640-1646 Goldfrank's Toxicologic Emergencies - 8th Ed. (2006)

Alcohol Withdrawal - BenzosAlcohol Withdrawal - Benzos Which benzo?Which benzo? Ideal: quick onset, long t½Ideal: quick onset, long t½ Diazepam Diazepam

– Most rapid time to peak clinical effectsMost rapid time to peak clinical effects Limits oversedationLimits oversedation

– Long t½ (Long t½ (↑↑↑↑↑↑ in advanced liver dz) in advanced liver dz)***?NOT AVAILABLE IN OUR ED******?NOT AVAILABLE IN OUR ED***

LorazepamLorazepam– Shorter t½Shorter t½– Inactive metabolitesInactive metabolites– Large doses may lead to propylene glycol A/E Large doses may lead to propylene glycol A/E

(hypotension, dysrrhythmias)(hypotension, dysrrhythmias)

Alcohol Withdrawal - BenzosAlcohol Withdrawal - Benzos How much?How much? DosingDosing

– PO for mild W/DPO for mild W/D– Diazepam 5-20mg IV q5-10minDiazepam 5-20mg IV q5-10min– Lorazepam 1-4mg IV q5-10minLorazepam 1-4mg IV q5-10min

Goal breathing spontaneously, N vitals, sedatedGoal breathing spontaneously, N vitals, sedated

– SlovisSlovis Diazepam 5, 5, 10, 10, 20, 20, 20…Diazepam 5, 5, 10, 10, 20, 20, 20… Lorazepam 1, 1, 2, 2, 4, 4, 4…Lorazepam 1, 1, 2, 2, 4, 4, 4…

– Can be massiveCan be massive 2640mg diazepam + 35mg haloperidol over 48h2640mg diazepam + 35mg haloperidol over 48h

– Mayo-Smith Mayo-Smith et al,et al, JAMA JAMA 1997;278:1-241997;278:1-24

Alcohol Withdrawal - BenzosAlcohol Withdrawal - Benzos Do we use fixed-interval dosing or Do we use fixed-interval dosing or

symptom-triggered dosing?symptom-triggered dosing?

Symptom triggered dosingSymptom triggered dosing– Clinical Institute Withdrawal Assessment Clinical Institute Withdrawal Assessment

of Alcohol Scale, Revised (of Alcohol Scale, Revised (CIWA-Ar)CIWA-Ar) 10 clinical variables, <5min to complete10 clinical variables, <5min to complete

Br J Addict 1989;84:1353-1357

Alcohol Withdrawal - BenzosAlcohol Withdrawal - Benzos 3 prospective RCT’s supporting 3 prospective RCT’s supporting

symptom-triggered dosingsymptom-triggered dosing– ↓↓Total amount of medicationTotal amount of medication– ↓↓Duration of treatmentDuration of treatment– ??↓DT’s↓DT’s– Eg:Eg:

Oxazepam 37.5mg vs 231.4mgOxazepam 37.5mg vs 231.4mg Duration of treatment 20h vs 63hDuration of treatment 20h vs 63h

Manikant Manikant et alet al, , Indian J Med ResIndian J Med Res 1993;98:170-31993;98:170-3Saitz Saitz et alet al, , JAMA JAMA 1994;272:519-231994;272:519-23Daeppen Daeppen et alet al, , Arch Int Med Arch Int Med 2002;162:1117-212002;162:1117-21

Alcohol Withdrawal - BenzosAlcohol Withdrawal - Benzos Typically sufficient for prevention of Typically sufficient for prevention of

alcohol withdrawal seizures (AWS)alcohol withdrawal seizures (AWS)

What next if benzo’s not really working?What next if benzo’s not really working?– More benzos?More benzos?– Phenobarb?Phenobarb?– Propofol?Propofol?– Haldol?Haldol?

Alcohol Withdrawal – Alcohol Withdrawal – BarbituratesBarbiturates

Effectiveness shown in uncontrolled Effectiveness shown in uncontrolled studiesstudies

MechanismMechanism– Directly open GABAa ClDirectly open GABAa Cl-- channels channels

Phenobarbital 260mg IV over 5min Phenobarbital 260mg IV over 5min then 130mg IV over 3min q30min prnthen 130mg IV over 3min q30min prn– Onset 20-40minOnset 20-40min– A/E: hypoTN, resp depressionA/E: hypoTN, resp depression

Mayo-Smith Mayo-Smith et alet al, , JAMAJAMA 1997;278:1-24 1997;278:1-24

Alcohol Withdrawal – Alcohol Withdrawal – NeurolepticsNeuroleptics

Meta-analysis of 5 controlled trialsMeta-analysis of 5 controlled trials– Compared sedative-hypnotics to Compared sedative-hypnotics to

neurolepticsneuroleptics Inferior in reducing mortality and durationInferior in reducing mortality and duration Potential for NMS, Potential for NMS, ↓sz threshold↓sz threshold Relative risk of mortality with neuroleptics vs Relative risk of mortality with neuroleptics vs

sedative-hypnotics of 6.6 (95%CI 1.2-34.7)sedative-hypnotics of 6.6 (95%CI 1.2-34.7) No good studies looking at atypicalsNo good studies looking at atypicals

Mayo-Smith Mayo-Smith et alet al, Arch Intern Med 2004;164:1405-12, Arch Intern Med 2004;164:1405-12

Alcohol Withdrawal – Alcohol Withdrawal – NeurolepticsNeuroleptics

Haloperidol (Haldol)Haloperidol (Haldol)– ‘‘Typical’ neurolepticTypical’ neuroleptic– Dopamine antagonistDopamine antagonist– Indication for use:Indication for use:

Continued agitation unresponsive to IV benzosContinued agitation unresponsive to IV benzos– Little effect on myocardial fn or resp driveLittle effect on myocardial fn or resp drive– No anticonvulsant activity, lowers sz No anticonvulsant activity, lowers sz

thresholdthreshold– Not to be used alone!Not to be used alone!

Alcohol Withdrawal – Alcohol Withdrawal – AlternativesAlternatives

Propofol, thiopentalPropofol, thiopental– Likely in consult with ICULikely in consult with ICU

What about ethanol?What about ethanol?– Historically usedHistorically used– Ideal ‘drug’ to Ideal ‘drug’ to ↓ ↓ symptoms of EtOH W/Dsymptoms of EtOH W/D– Literature conflicting on efficacyLiterature conflicting on efficacy– Toxic A/EToxic A/E

Weinberg et al. J Trauma 2008;64(1):99-104

Case 2 cont…Case 2 cont… DT’sDT’s Despite benzo txDespite benzo tx

– HTN, tachycardiaHTN, tachycardia

Any other agents that might help Any other agents that might help here?here?

Alcohol Withdrawal – Alcohol Withdrawal – AdjunctsAdjuncts

ββ-adrenergic antagonists-adrenergic antagonists– Adjunctive in mild/moderate W/D with HTN/tachyC Adjunctive in mild/moderate W/D with HTN/tachyC

(Grade C)(Grade C)– Can decrease the need for benzosCan decrease the need for benzos

Decreased tremor, agitation, anxietyDecreased tremor, agitation, anxiety– BUT…can mask ANS signs making it more difficult BUT…can mask ANS signs making it more difficult

to assess need for txto assess need for tx– 1 controlled study of propranolol1 controlled study of propranolol

Increased incidence of deliriumIncreased incidence of delirium– Zilm Zilm et alet al. . Alcohol Clin Exp ResAlcohol Clin Exp Res 1980;4:400-5 1980;4:400-5

– Not recommended unless other tx fail – Goldfrank’sNot recommended unless other tx fail – Goldfrank’s***Potentially can use them in pts with cardiac ***Potentially can use them in pts with cardiac

history, but beware if ?sympathomimmetic on history, but beware if ?sympathomimmetic on board***board***



amount of physical restraint to decrease amount of physical restraint to decrease the risk of hyperthermia and rhabdothe risk of hyperthermia and rhabdo


Alcohol Withdrawal – Alcohol Withdrawal – AdjunctsAdjuncts

Thiamine 100mg IVThiamine 100mg IV– Before/after glucose – doesn’t matterBefore/after glucose – doesn’t matter

Mg 2-5g IVMg 2-5g IV– May ↑ rate of AST ↓

Poikolainen & Alho. Poikolainen & Alho. Subst Abuse Treat Prev PolicySubst Abuse Treat Prev Policy 2008;3(1):12008;3(1):1

– No effect on severity of W/D or incidence of W/D No effect on severity of W/D or incidence of W/D seizuresseizures Wilson & Vulcano. Alcohol Clin Exp Res 1984;8:542-5

– No evidence of benefit, give it anywayNo evidence of benefit, give it anyway MultivitaminsMultivitamins

– ““magic yellow water”…makes everyone feel bettermagic yellow water”…makes everyone feel better ±K±K++ replacement replacement

Alcohol Withdrawal - Alcohol Withdrawal - DispositionDisposition

Observe 4-6hObserve 4-6h– Most can be tx successfully as outptMost can be tx successfully as outpt– If mild-mod If mild-mod W/D does not progressW/D does not progress– D/C with F/U (Renfrew, etc)D/C with F/U (Renfrew, etc)***Practically this is usually less***Practically this is usually less

--D/C when sympt resolved, eating/drinking, not D/C when sympt resolved, eating/drinking, not requiring IV fluids, ambulatoryrequiring IV fluids, ambulatory

Admission for severe W/DAdmission for severe W/D

Bayard Bayard et al.et al. Am Fam Physician.Am Fam Physician. 2004;69(6):1443-50 2004;69(6):1443-50

Alcohol Withdrawal – Outpt Alcohol Withdrawal – Outpt TxTx

Outpatient vs inpatient detox for mild-moderate W/DOutpatient vs inpatient detox for mild-moderate W/D– N=87 outpts, 77 inpts; pRCTN=87 outpts, 77 inpts; pRCT– OutptOutpt

Daily clinic visits, decreasing oxazepam dosesDaily clinic visits, decreasing oxazepam doses– InptInpt

Oxazepam, rehab treatmentOxazepam, rehab treatment– ResultsResults

Mean duration of tx 6.5d (OP) vs 9.2d (IP)Mean duration of tx 6.5d (OP) vs 9.2d (IP) 95% IP vs 72% OP completed detox95% IP vs 72% OP completed detox No complicationsNo complications No group difference at 6 months post-detoxNo group difference at 6 months post-detox $3319-3665/IP vs $175-388/OP$3319-3665/IP vs $175-388/OP

– ConclusionConclusion OP detox for mild-mod W/D is effective, safe, and low-costOP detox for mild-mod W/D is effective, safe, and low-cost

No outpt detox program in CalgaryNo outpt detox program in Calgary

Hayashida et al. NEJM. 1989 Feb 9;320(6):358-65

RenfrewRenfrew 40-bed recovery centre, free40-bed recovery centre, free

– Usually 36 clientsUsually 36 clients No appointment necessary 9am-4pmNo appointment necessary 9am-4pm

– Show up at 8:15amShow up at 8:15am– 297-3337 otherwise297-3337 otherwise– EtOH EtOH benzo benzo opioids opioids crack in order crack in order

Typical 5-day stay, (8-9 benzo/opioids)Typical 5-day stay, (8-9 benzo/opioids) Client care assistants and 24-hour RNClient care assistants and 24-hour RN Assessment bed Assessment bed program bed program bed Non-invasive (no IV’s, no Ix, no abx, etc)Non-invasive (no IV’s, no Ix, no abx, etc) Immunizations, mental health services, counsellors for Immunizations, mental health services, counsellors for

referralsreferrals Avg age 37, 70% male, increasing incidence of crack useAvg age 37, 70% male, increasing incidence of crack use Budget $1.7 million/year, gov’t funding through AADACBudget $1.7 million/year, gov’t funding through AADAC

Case 3Case 3 56M homeless alcoholic, EMS called for sz 56M homeless alcoholic, EMS called for sz

downtowndowntown– Received total of 4mg lorazepam IV enrouteReceived total of 4mg lorazepam IV enroute

By the time of your assessmentBy the time of your assessment– AAO x 3, vitals 95, 114/78, 18, 37AAO x 3, vitals 95, 114/78, 18, 3755, 96%, 96%– Nothing remarkable on examNothing remarkable on exam– PMH: seizures; Rx: none; NKDAPMH: seizures; Rx: none; NKDA

The clinical clerk asks you if you want to The clinical clerk asks you if you want to load the patient with Dilantin…thoughts?load the patient with Dilantin…thoughts?

Alcohol Related SeizuresAlcohol Related Seizures Want to r/o life-threatening causesWant to r/o life-threatening causes

– Hypoglycemia, CNS infection, ICHHypoglycemia, CNS infection, ICH

Up to 40% of seizures and 25% of Up to 40% of seizures and 25% of status epilepticus are EtOH relatedstatus epilepticus are EtOH related

Alcohol Withdrawal Seizures Alcohol Withdrawal Seizures (AWS)(AWS)

“Rum Fits”“Rum Fits” Most occur within 24h of decreasing Most occur within 24h of decreasing

EtOHEtOH 5% of pts with AWS’s progress to DT’s 5% of pts with AWS’s progress to DT’s

b/c of inadequate txb/c of inadequate tx Tend to have rapid post-ictal recoveryTend to have rapid post-ictal recovery FeverFever

– Secondary to W/D or to szSecondary to W/D or to sz– CNS infection?CNS infection?

Rare in febrile alcoholic with AWSRare in febrile alcoholic with AWS Obligated to look for it!Obligated to look for it!

Wren Wren et alet al. Amer J Emerg Med 1991;9:57. Amer J Emerg Med 1991;9:57

Alcohol Withdrawal – Alcohol Withdrawal – AnticonvulsantsAnticonvulsants

Do we use Dilantin in preventing recurrence of Do we use Dilantin in preventing recurrence of AWS?AWS?

Mechanism?Mechanism?– Promotion of NaPromotion of Na++ efflux from motor cortex neurons efflux from motor cortex neurons– Does Does NOTNOT involve GABA/NMDA receptors involve GABA/NMDA receptors

Multiple placebo-controlled trialsMultiple placebo-controlled trials– No better than placeboNo better than placebo at preventing alcohol withdrawal at preventing alcohol withdrawal

seizure recurrenceseizure recurrence– Alldredge Alldredge et alet al. AM J Med 1989;87:645-8. AM J Med 1989;87:645-8– Chance. Ann Emerg Med 1991;20:520-2Chance. Ann Emerg Med 1991;20:520-2– Rathlev Rathlev et al. Ann Emerg Medet al. Ann Emerg Med 1994;23:513-8 1994;23:513-8

When might you use Dilantin in AWS?When might you use Dilantin in AWS?– Basically only if pt is already on DilantinBasically only if pt is already on Dilantin

See ASAM CPG for other recommendationsSee ASAM CPG for other recommendations

http://www.asam.org/CMS/images/PDF/AboutASAM/ASAM%20Clinical%20Practice%20Guideline.pdfhttp://www.asam.org/CMS/images/PDF/AboutASAM/ASAM%20Clinical%20Practice%20Guideline.pdf

Case 3Case 3 Disposition?Disposition? Observation x 4-6hObservation x 4-6h

– If symptom free and no recurrenceIf symptom free and no recurrence D/C – get the man some booze!D/C – get the man some booze! ±±Short course of PO benzosShort course of PO benzos Appropriate referral (Renfrew, FP, neuro?)Appropriate referral (Renfrew, FP, neuro?)

Case 3bCase 3b The seizure was witnessed by EMS The seizure was witnessed by EMS

and involved the R arm/face onlyand involved the R arm/face only

Any change in your thought process?Any change in your thought process?– 20% of focal alcohol related seizures 20% of focal alcohol related seizures

have a structural lesionhave a structural lesion

Ernest, Neurology 1988;38:1561Ernest, Neurology 1988;38:1561

Case 3cCase 3c Pt post-ictal on initial assessmentPt post-ictal on initial assessment 5 min later RN tells you he’s having 5 min later RN tells you he’s having

another seizureanother seizure Thoughts?Thoughts? Plan?Plan? Dilantin?Dilantin?

– Still indicated for alcohol-related status Still indicated for alcohol-related status epilepticus (Grade C recommendation)epilepticus (Grade C recommendation) ASAM CPGASAM CPG

Alcohol Withdrawal – Take-Alcohol Withdrawal – Take-homehome

EtOH W/D is a common ED presentationEtOH W/D is a common ED presentation

CNS/ANS excitationCNS/ANS excitation

Sympt 6h, sz 12-24h, DT’s 72hSympt 6h, sz 12-24h, DT’s 72h

Benzo’s, benzo’s, benzo’s….Benzo’s, benzo’s, benzo’s….

Status is status – tx the sameStatus is status – tx the same

QuestionsQuestions??

Case 4Case 4 37F37F N, V, tremor, H/AN, V, tremor, H/A PMH: depression, anxiety, panic PMH: depression, anxiety, panic

attacksattacks Taking clonazepam until 5d agoTaking clonazepam until 5d ago O/EO/E

– Vitals 120, 135/85, 37Vitals 120, 135/85, 3722, 20, 96%, 20, 96%– Diaphoretic, tremulousDiaphoretic, tremulous

Remind you of anything?Remind you of anything?

Benzodiazepines - HistoryBenzodiazepines - History Chlordiazepoxide (Librium)Chlordiazepoxide (Librium)

– First benzo, synthesized in 1955First benzo, synthesized in 1955 Diazepam (Valium)Diazepam (Valium)

– Marketed for seizures in 1963Marketed for seizures in 1963 Improvement on older sedative-Improvement on older sedative-

hypnoticshypnotics– Barbiturates, chloral hydrate, etcBarbiturates, chloral hydrate, etc

Now > 50 benzos on the marketNow > 50 benzos on the market

BenzodiazepinesBenzodiazepines Mechanism of actionMechanism of action

– Bind to benzo receptor (part of GABAa-Bind to benzo receptor (part of GABAa-R)R)

– Potentiates GABA effect on GABAa ClPotentiates GABA effect on GABAa Cl-- channel channel

– Hyperpolarizes cell (Hyperpolarizes cell (↑Cl↑Cl-- in) in)– Diminished ability to initiate action Diminished ability to initiate action

potentialpotential– CNS inhibitory effectCNS inhibitory effectCl-

GABAa-RBZ

GABA

BZ-r

GABA-r

Cl-Cl-Cl-Cl-

Extracellular Intracellular

ZZZZ….Hyperpolarized

Benzo Withdrawal - BasicsBenzo Withdrawal - Basics Risk related to duration/dose/t½ Risk related to duration/dose/t½ Need ~4mo tx before W/D occursNeed ~4mo tx before W/D occurs 1/3 of benzo users experience W/D1/3 of benzo users experience W/D Lorazepam W/D more severe than Lorazepam W/D more severe than

diazepamdiazepam W/D can occur with change in benzoW/D can occur with change in benzo

Benzo Withdrawal - Benzo Withdrawal - SymptomsSymptoms

Symptom onsetSymptom onset– 1-3d for short acting (loraz, alpraz)1-3d for short acting (loraz, alpraz)

↑ ↑ severity, severity, ↓ ↓ durationduration– 3-7d for long acting (diaz, clonaz)3-7d for long acting (diaz, clonaz)

May persist for weeksMay persist for weeks– Immediate with flumazenil use!Immediate with flumazenil use!

Benzo Withdrawal - Benzo Withdrawal - SymptomsSymptoms

Similar to EtOH W/DSimilar to EtOH W/D ANS instability (tachycardia, ANS instability (tachycardia,

diaphoresis)diaphoresis) Anxiety, insomnia, tremor, H/A, N, VAnxiety, insomnia, tremor, H/A, N, V SevereSevere

– Disorientation, visual hallucinations, Disorientation, visual hallucinations, delirium, seizuresdelirium, seizures

Benzo Withdrawal - Benzo Withdrawal - TreatmentTreatment

Best treatment for benzo W/D? Best treatment for benzo W/D? Reinstitution of long-acting benzoReinstitution of long-acting benzo

– Diazepam 5-10mg IV q5-10min prnDiazepam 5-10mg IV q5-10min prn Outpt PO diazepam at = dose to pts Outpt PO diazepam at = dose to pts

benzobenzo Gradual taper if discontinuation is Gradual taper if discontinuation is

desireddesired– MD supervisedMD supervised– 6-8 weeks6-8 weeks

Case 5Case 5 20F found down, minimally responsive20F found down, minimally responsive Empty bottle of diazepam by bedsideEmpty bottle of diazepam by bedside

Your clinical clerk asks if she can try a trial Your clinical clerk asks if she can try a trial of flumazenil?of flumazenil?

You say ‘go for it’, and the pt begins to You say ‘go for it’, and the pt begins to have a seizure shortly after flumazenilhave a seizure shortly after flumazenil– Management?Management?

FlumazenilFlumazenil Competitive BZ receptor antagonist Competitive BZ receptor antagonist Duration of action shorter than most Duration of action shorter than most

benzosbenzos

FlumazenilFlumazenil Few case reports of flumazenil-induced Few case reports of flumazenil-induced

W/D, including seizures & deathW/D, including seizures & death– Haverkos Haverkos et alet al. . Ann PharmacotherAnn Pharmacother 1994; 28:1347 1994; 28:1347– Spivey. Spivey. Clin TherClin Ther 1992; 14:292 1992; 14:292– Whitwam Whitwam et al.et al. Acta Anaesh Scand SupplActa Anaesh Scand Suppl 1995; 108:3 1995; 108:3

Severe withdrawal symptomsSevere withdrawal symptoms– Treat with phenobarbitalTreat with phenobarbital

BOTTOM LINE: Risks >>> benefitsBOTTOM LINE: Risks >>> benefits

Benzodiazepine Withdrawal – Benzodiazepine Withdrawal – SummarySummary

W/D = less inhibitory GABA activityW/D = less inhibitory GABA activity

Similar to EtOH W/DSimilar to EtOH W/D

Short acting benzo = more severe Short acting benzo = more severe W/DW/D

Long acting benzo for managementLong acting benzo for management

Questions?Questions?

Case 6Case 6 20F decreased LOC, found by boyfriend20F decreased LOC, found by boyfriend O/EO/E

– Drousy, pinpoint pupils, hypoventilatingDrousy, pinpoint pupils, hypoventilating PMH “?”PMH “?” Normally takes “a white pill & an oval pill”Normally takes “a white pill & an oval pill” Management?Management? You try naloxoneYou try naloxone

– More alert and vomiting, tachycardic, More alert and vomiting, tachycardic, diaphoreticdiaphoretic

Diagnosis?Diagnosis?

NaloxoneNaloxone Competitive opioid antagonistCompetitive opioid antagonist Onset 1-2minOnset 1-2min Duration 20-90minDuration 20-90min Hepatic metabolismHepatic metabolism Can precipitate acute opioid Can precipitate acute opioid

withdrawalwithdrawal– Usually short-livedUsually short-lived

OpioidsOpioids Medicinal value of opium - 1500 B.C.Medicinal value of opium - 1500 B.C. Many formulations, essentially same drugMany formulations, essentially same drug

– Laudanum, paregoric, Dover's powder, Laudanum, paregoric, Dover's powder, Godfrey's cordial, morphineGodfrey's cordial, morphine

Analgesia, euphoria, anti-tussiveAnalgesia, euphoria, anti-tussive TerminologyTerminology

– Opiate = derived from opium poppyOpiate = derived from opium poppy– OpioidOpioid

Binds opioid receptorBinds opioid receptor Produces opioid-like effectProduces opioid-like effect

Opioid Withdrawal - BasicsOpioid Withdrawal - Basics Not usually life-threateningNot usually life-threatening Onset depends on t½Onset depends on t½

– Heroin 4-6hHeroin 4-6h– Methadone 24-48hMethadone 24-48h

DurationDuration– Days-weeksDays-weeks– ±Persistent weakness/insomnia/anxiety ±Persistent weakness/insomnia/anxiety

x 6mx 6m

Opioid Withdrawal - Opioid Withdrawal - PathophysPathophys

Many opioid receptorsMany opioid receptors Stimulation of some Stimulation of some

– Reduced CNS NE release (locus ceruleus)Reduced CNS NE release (locus ceruleus) Chronic opioid useChronic opioid use

– Excitability of neurons in the locus Excitability of neurons in the locus ceruleusceruleus

W/D of opioidW/D of opioid– Noradrenergic hyperactivityNoradrenergic hyperactivity

Opioid WithdrawalOpioid Withdrawal Symptoms?Symptoms? PsychologicalPsychological

– Craving, dysphoria, anxiety, insomniaCraving, dysphoria, anxiety, insomnia PhysiologicalPhysiological

– Tachycardia, tachypnea, HTNTachycardia, tachypnea, HTN– Diaphoresis, lacrimation, rhinorrhea, Diaphoresis, lacrimation, rhinorrhea,

myalgias, abdo pain, V, Dmyalgias, abdo pain, V, D– ““Dope sick”Dope sick”

Opioid Withdrawal - SignsOpioid Withdrawal - Signs Mydriasis, yawning, piloerection, Mydriasis, yawning, piloerection,

increased bowel soundsincreased bowel sounds ±HR/RR/bp increase±HR/RR/bp increase

Alert, oriented, afebrileAlert, oriented, afebrile

Opioid, Sed-hyp, or EtOH?Opioid, Sed-hyp, or EtOH? How do you tell the difference?How do you tell the difference?

OpioidOpioid Sed-Hyp/EtOHSed-Hyp/EtOHBPBP N/HTN (ohTN if N/HTN (ohTN if

volume depleted) volume depleted) N/HTN (ohTN if N/HTN (ohTN if

volume depleted)volume depleted)HRHR TachyCTachyC TachyCTachyCRRRR TachyPTachyP TachyPTachyP

TempTemp NN N or N or ↑↑Mental statusMental status N/anxiousN/anxious N/abNN/abN

Physical Physical signs/symptomssigns/symptoms

Yawning, Yawning, lacrimation, lacrimation, rhinorrhea, rhinorrhea,

mydriasis, tremor, mydriasis, tremor, piloerection, NVD, piloerection, NVD,

muscle muscle pain/spasm, pain/spasm,

neonatal seizuresneonatal seizures

Tremors, Tremors, fasciculations, fasciculations, diaphoresis, diaphoresis,

seizures seizures

Goldfrank’s

OpioidOpioid Sed-Hyp/EtOHSed-Hyp/EtOHBPBP

HRHRRRRR

TempTempMental statusMental status

Physical Physical signs/symptomssigns/symptoms

Opioid Withdrawal - Opioid Withdrawal - ManagementManagement

R/O other causes of presentationR/O other causes of presentation SupportiveSupportive

– IV fluids, KIV fluids, K++, anti-emetics, anti-emetics ±Evaluation for complications of ±Evaluation for complications of

IVDUIVDU– Endocarditis, AIDS-related illnesses, etcEndocarditis, AIDS-related illnesses, etc

Opioid Withdrawal - Opioid Withdrawal - ManagementManagement

ClonidineClonidine– Central presynaptic α2-receptor agonistCentral presynaptic α2-receptor agonist

↑ ↑ NE reuptakeNE reuptake– Reduces noradrenergic activityReduces noradrenergic activity– 0.1-0.2mg PO q4-6h prn (monitor bp)0.1-0.2mg PO q4-6h prn (monitor bp)

±±BZBZ– If significant anxietyIf significant anxiety

±±Methadone 20mg POMethadone 20mg PO– Synthetic opioid with long t½Synthetic opioid with long t½– Used in outpt programs, not our EDUsed in outpt programs, not our ED

Freitas. Am J Emerg Med 1985;3(5):456-60

Opioid WithdrawalOpioid Withdrawal Goals/Disposition?Goals/Disposition? Temporary control of symptomsTemporary control of symptoms Other disease ruled outOther disease ruled out Referral to methadone program prnReferral to methadone program prn

Opioid Withdrawal - Opioid Withdrawal - SummarySummary

Narcan can precipitate acute opioid Narcan can precipitate acute opioid W/DW/D

Sympt = noradrenergic hyperactivitySympt = noradrenergic hyperactivity

Not usually life-threateningNot usually life-threatening

Clonidine, symptomatic treatmentClonidine, symptomatic treatment


Case 7Case 7 23M, brought in by Mom, 2 day hx of23M, brought in by Mom, 2 day hx of

– Increasing anxiety, some suidical thoughtsIncreasing anxiety, some suidical thoughts– ++Fatigue, increased appetite/sleep++Fatigue, increased appetite/sleep– Myalgias, tremorMyalgias, tremor

O/EO/E– Vitals 85, 125/85, 36Vitals 85, 125/85, 3655, 20, 96%, 20, 96%– AAO x 3, nothing remarkable on examAAO x 3, nothing remarkable on exam

Thoughts?Thoughts?

CocaineCocaine ““I am just now collecting the I am just now collecting the

literature for a song of praise to this literature for a song of praise to this magical substance”magical substance”

-Sigmund Freud, 1884-Sigmund Freud, 1884

Cocaine - BasicsCocaine - Basics Natural alkaloid found in Natural alkaloid found in Erythroxylon cocaErythroxylon coca

Causes release ofCauses release of– DopamineDopamine– EpinephrineEpinephrine– NorepinephrineNorepinephrine– Serotonin Serotonin

NaNa++ channel blocker channel blocker Blocks presynaptic NE reuptakeBlocks presynaptic NE reuptake

Cocaine Withdrawal - Cocaine Withdrawal - SymptomsSymptoms

Psychological symptomsPsychological symptoms– Depression, anxiety, fatigue, difficulty Depression, anxiety, fatigue, difficulty

concentrating, anhedonia, craving, concentrating, anhedonia, craving, increased appetite, increased increased appetite, increased sleep/dreaming, suicidal ideationsleep/dreaming, suicidal ideation

Physiological signs/symptomsPhysiological signs/symptoms– MSK pain, tremor, chills, involuntary MSK pain, tremor, chills, involuntary

motor movement, myocardial ischemiamotor movement, myocardial ischemia

N=21 cocaine addicts in 28d inpt rehabN=21 cocaine addicts in 28d inpt rehab Holter and stress test admission/dischargeHolter and stress test admission/discharge ResultsResults

– 38% had silent STE38% had silent STE– Only 1 pt had +stress testOnly 1 pt had +stress test– 3 agreed to cath 3 agreed to cath all N all N– No MI’s, no information on outcomesNo MI’s, no information on outcomes

ConclusionConclusion– Risk of vasospasm during withdrawal periodRisk of vasospasm during withdrawal period

Likely reflects delayed vasospasm after Likely reflects delayed vasospasm after cocaine use, not necessarily a ‘withdrawal’ cocaine use, not necessarily a ‘withdrawal’ phenomenonphenomenon

Cocaine Withdrawal - Cocaine Withdrawal - ManagementManagement

SupportiveSupportive ±Lorazepam for insomnia/agitation±Lorazepam for insomnia/agitation

Admission rarely indicatedAdmission rarely indicated Referral to addiction treatment Referral to addiction treatment

programprogram

Resolves within 1-2 weeks without txResolves within 1-2 weeks without tx

Cocaine Withdrawal – Take Cocaine Withdrawal – Take homehome

Prominent psychological featuresProminent psychological features

Rarely medically seriousRarely medically serious

Treatment is supportiveTreatment is supportive


Post-test Q1Post-test Q1 What percentage of hospitalized What percentage of hospitalized

patients are ethanol dependent?patients are ethanol dependent?A.A. 5-10%5-10%B.B. 15-20%15-20%C.C. 30-40%30-40%D.D. >40%>40%

Post-test Q2Post-test Q2 What is the current mortality from What is the current mortality from

alcohol withdrawal syndrome?alcohol withdrawal syndrome?A.A. 5%5%B.B. 7%7%C.C. <1%<1%D.D. 10%10%

Post-test Q3Post-test Q3 Alcohol acts as a/an ______________ Alcohol acts as a/an ______________

on the GABA receptor.on the GABA receptor.A.A. Indirect agonistIndirect agonistB.B. Direct agonistDirect agonistC.C. Indirect antagonistIndirect antagonistD.D. Direct antagonistDirect antagonist

Post-test Q4Post-test Q4 In alcohol withdrawal, wWhich of In alcohol withdrawal, wWhich of

the following agents is best used in the following agents is best used in patients at risk for oversedation and patients at risk for oversedation and those with liver disease?those with liver disease?

A.A. DiazepamDiazepamB.B. LorazepamLorazepamC.C. PhenytoinPhenytoinD.D. ThiamineThiamine

Post-test Q5Post-test Q5 Which of the following agents is Which of the following agents is

best used for AWS if high doses of best used for AWS if high doses of benzodiazepines are ineffective?benzodiazepines are ineffective?

A.A. CarbamazepineCarbamazepineB.B. PhenytoinPhenytoinC.C. EthanolEthanolD.D. PhenobarbitalPhenobarbital

Post-test Q6Post-test Q6 Symptom-triggered therapy for Symptom-triggered therapy for

alcohol withdrawal has been shown alcohol withdrawal has been shown to reduce which of the following to reduce which of the following factors?factors?

A.A. Amount of medication usedAmount of medication usedB.B. Duration of treatmentDuration of treatmentC.C. Both A and BBoth A and BD.D. Neither A nor BNeither A nor B

Post-test Q7Post-test Q7 Neuroleptic agents:Neuroleptic agents:

A.A. Effectively control autonomic instability Effectively control autonomic instability associated with AWSassociated with AWS

B.B. Control alcohol-induced seizuresControl alcohol-induced seizuresC.C. Improve hyperthermia related to AWSImprove hyperthermia related to AWSD.D. Reduce the seizure thresholdReduce the seizure threshold

Post-test Q8Post-test Q8 The use of phenytoin is indicated in The use of phenytoin is indicated in

which of the following situations?which of the following situations?A.A. A patient with AWS and non-alcohol-A patient with AWS and non-alcohol-

related seizuresrelated seizuresB.B. A patient with an AWSA patient with an AWSC.C. A patient with HTN and tachycardia A patient with HTN and tachycardia

related to AWSrelated to AWSD.D. An intoxicated patient with a history of An intoxicated patient with a history of

AWSAWS

Post-test Q9Post-test Q9 The benzodiazepine of choice for The benzodiazepine of choice for

treating benzodiazepine withdrawal treating benzodiazepine withdrawal is:is:

A)A) MidazolamMidazolamB)B) LorazepamLorazepamC)C) DiazepamDiazepamD)D) AlprazolamAlprazolam

Post-test Q10Post-test Q10 ED management of opioid ED management of opioid

withdrawal consists primarily of:withdrawal consists primarily of:A)A) BenzodiazepinesBenzodiazepinesB)B) ββ-blockers-blockersC)C) Supportive careSupportive careD)D) MethadoneMethadone

Post-test Q11Post-test Q11 Patients with acute cocaine Patients with acute cocaine

withdrawal often require admission.withdrawal often require admission.TrueTrueFalseFalse

The endThe end

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