substance withdrawal

of 117 /117
Substance Substance Withdrawal Withdrawal Jay Green Jay Green Emergency Medicine Resident, Emergency Medicine Resident, PGY-2 PGY-2 February 28, 2008 February 28, 2008

Author: anoush

Post on 13-Feb-2016

67 views

Category:

Documents


1 download

Embed Size (px)

DESCRIPTION

Substance Withdrawal. Jay Green Emergency Medicine Resident, PGY-2 February 28, 2008. Outline. Pre-test Substance Withdrawal Cases Alcohol Opioid Benzodiazepine Cocaine Post-test Evidence of a proud father!. Pre-test Q1. What percentage of hospitalized patients are ethanol dependent? - PowerPoint PPT Presentation

TRANSCRIPT

  • Substance WithdrawalJay GreenEmergency Medicine Resident, PGY-2February 28, 2008

  • OutlinePre-testSubstance Withdrawal CasesAlcoholOpioidBenzodiazepineCocainePost-testEvidence of a proud father!

  • Pre-test Q1What percentage of hospitalized patients are ethanol dependent?5-10%15-20%30-40%>40%

  • Pre-test Q2What is the current mortality from alcohol withdrawal syndrome?5%7%
  • Pre-test Q3Alcohol acts as a/an ______________ on the GABA receptor.Indirect agonistDirect agonistIndirect antagonistDirect antagonist

  • Pre-test Q4In alcohol withdrawal, which of the following agents is best used in patients at risk for oversedation and those with liver disease?DiazepamLorazepamPhenytoinThiamine

  • Pre-test Q5Which of the following agents is best used for AWS if high doses of benzodiazepines are ineffective?CarbamazepinePhenytoinEthanolPhenobarbital

  • Pre-test Q6Symptom-triggered therapy in alcohol withdrawal has been shown to reduce which of the following factors?Amount of medication usedDuration of treatmentBoth A and BNeither A nor B

  • Pre-test Q7Neuroleptic agents:Effectively control autonomic instability associated with AWSControl alcohol-induced seizuresImprove hyperthermia related to AWSReduce the seizure threshold

  • Pre-test Q8The use of phenytoin is indicated in which of the following situations?A patient with AWS and non-alcohol-related seizuresA patient with an AWSA patient with HTN and tachycardia related to AWSAn intoxicated patient with a history of AWS

  • Pre-test Q9The benzodiazepine of choice for treating benzodiazepine withdrawal is:MidazolamLorazepamDiazepamAlprazolam

  • Pre-test Q10ED management of opioid withdrawal consists primarily of:Benzodiazepines-blockersSupportive careMethadone

  • Pre-test Q11Patients with acute cocaine withdrawal often require admission.TrueFalse

  • Case 143M previously healthy, no medsUnemployed, brought in by sisterN, V today, sister worried about hand tremorSocHx: Smoker, few beers/day x yearsO/EHR 112, bp 160/96Appears a bit anxiousTremulous

  • Case 243M no known PMH/medsBrought in by EMSFound to be agitated, vomiting, ?hallucinatingHx from pt unhelpfulO/ENot oriented, GCS 13 (E4V4M5)Vitals 130, 175/100, 387, 20, 95%Volatile, ?visual hallucinations/anxious++tremulous, ?hyperreflexia

  • Alcohol Withdrawal

  • Alcohol Withdrawal - HistoryFirst described by Pliny the Elder, 1st century BC Naturalis Historia"...drunkenness brings pallor and sagging cheeks, sore eyes, and trembling hands that spill a full cup, of which the immediate punishment is a haunted sleep and unrestful nights. ..." OslerInitial txSupportive, KBr, chloral hydrate, hyoscine, opiumIsbell et al, 1955Alcohol withdrawal syndromeAmount/duration of alcohol intake severityIsbell 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 - Epidemiology22% of Americans >12y report binge drinking at least once during the past 30d7% report heavy regular drinking2003 US National Survey on Drug Use and HealthThese are the people who actually answer surveys15-20% hospitalized pts are alcohol dependentHodges and Mazur, Pharmacotherapy 2004;24:1578-85Mortality
  • Alcohol W/D - PathophysiologyChronic EtOH CNS depressant GABAminergic tone sedation via GABAa-receptorDownregulation of GABAa-receptorNormal level of consciousness with EtOHNMDA inhibitionUpregulation of NMDA-receptorsW/D of EtOHCNS excitation (GABA, NMDA)Inhibitory control of excitatory NTs is lostCNS excitation (tremor, sz, hallucination)ANS stimulation (HTN, sweating, hyperthermia, tachycardia)

  • Case 143M previously healthy, no medsUnemployed, brought in by sisterN, V today, sister worried about hand tremorSocHx: Smoker, few beers/day x yearsO/EHR 112, bp 160/96Appears a bit anxiousTremulousWhat else is on the ddx?

  • DDxWhat else is on the ddx?Acute psychosisCNS infectionThyrotoxicosisAnticholinergic poisoningW/D from other sedative-hypnotics

  • Alcohol W/D - Signs/SymptomsDo you need to stop EtOH consumption to get EtOH W/D?

    When do signs of W/D begin?

  • Alcohol W/D - Signs/SymptomsBegin 6-24h after decreasing EtOHCan occur with continued lower volume EtOHLasts 2-7dSeverity dose/duration of EtOH

  • Alcohol W/D - ClassificationHow do you classify EtOH W/D?4 stages:Tremulousness (6-12h)Hallucinations (12-48h)Seizures (12-48h)DTs (>48h)Minor Major DTsTiming & severityearly/late & complicated/uncomplicated

  • Alcohol W/D - ClassificationMinor Major DTsWhat are some symptoms of minor W/D?Early onset, peak 24-36hN, anorexia, tremor, tachycardia, HTN, hyperreflexia, insomnia, anxietyWhat are some symptoms of major W/D?Later onset (24h), peaks 2-5d++anxiety, insomnia, irritability, tremor, anorexia, tachycardia, hyperreflexia, HTN, fever, seizure, auditory/visual hallucinations, delirium

  • Alcohol Withdrawal - DiagnosisDSM-IV diagnostic criteriaAlcohol WithdrawalCessation/reduction of heavy/prolonged alcohol use resulting in the development of two or more of the following:ANS hyperactivity, increased hand tremor, insomnia, N, V, transient hallucinations, psychomotor agitation, anxiety, sz, affected global function

  • Alcohol Withdrawal - DiagnosisDSM-IV diagnostic criteriaAlcohol Withdrawal with Delirium (DTs)Also includes decreased consciousness, change in cognition, perceptual disturbance

  • Case 2 revisited43M no known PMH/medsBrought in by EMSFound to be agitated, vomiting, ?hallucinatingHx from pt unhelpfulO/ENot oriented, GCS 13 (E4V4M5)Vitals 130, 175/100, 387, 20, 95%Volatile, ?visual hallucinations/anxious++tremulous, ?hyperreflexiaYou think they have DTs.What else is on the ddx?

  • Case 2You think this patient has delirium tremens

    What else could this be?SepsisMeningitisSAHHeat strokeSerotonin syndromeNMSCocaine/amphetamine toxicityMalignant hyperthermia

  • Alcohol W/D Delirium TremensExtreme end of the spectrumAlmost never before 3d5% of pts hospitalized for EtOH W/DDifficult to predict who will get itCan last up to 2 weeksTHESE PATIENTS ARE SICK!

  • Case 2 revisited43M no known PMH/medsBrought in by EMSFound to be agitated, vomiting, ?hallucinatingHx from pt unhelpfulO/ENot oriented, GCS 13 (E4V4M5)Vitals 130, 175/100, 387, 20, 95%Volatile, ?visual hallucinations/anxious++tremulous, ?hyperreflexiaWhat investigations?

  • Alcohol Withdrawal - IxC/SCBC, lytes, BUN, Cr, LFTs, lipase, INR, EtOHU/ACXRECG

    VBGCT headLPTox screen

  • Case 2Labs sentECG tachycardiaCXR pendingC/S 2.9

    What would you like to do now?

  • Case 2 - TxInitial StabilizationABCsNGTRestraints

    What about giving glucose before thiamine?

  • Wernicke-Korsakoff SyndromeSymptoms/signs?Oculomotor disturbances (nystagmus and ocular palsies), confusion, ataxia 12% have triadMortality 10-20%Can you precipitate it with glucose administration?

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

  • Wernicke-Korsakoff SyndromeCase reportsWK syndrome after prolonged IV glucose administration

    BOTTOM LINEDont delay glucose for thiamineWaton et al. Ir J Med Sci 1981 Oct;150(10):301-3

  • Alcohol Withdrawal - Tx4 principles of treatment1) Evaluate for concurrent illness2) Restore inhibitory tone to CNS3) ID/correct lyte/fluid deficiencies4) Allow pt to recover with the least amount of physical restraint to decrease the risk of hyperthermia and rhabdomyolysisEM Reports 26(16) July 25, 2005

  • Alcohol Withdrawal - Tx4 principles of treatment1) Evaluate for concurrent illness2) Restore inhibitory tone to CNS3) ID/correct lyte/fluid deficiencies4) Allow pt to recover with the least amount of physical restraint to decrease the risk of hyperthermia and rhabdomyolysisEM Reports 26(16) July 25, 2005

  • Alcohol Withdrawal - Tx>150 drug combinationsBenzos are mainstayInteract with GABAa-receptorSubstitute for removal of EtOH as a GABAa-agonist

  • Cl-GABAa-RBZGABABZ-rGABA-rCl-Cl-Cl-Cl-ExtracellularIntracellularZZZZ.Hyperpolarized

  • Alcohol Withdrawal - Tx>150 drug combinationsBenzos are mainstayInteract with GABAa-receptorSubstitute for removal of EtOH as a GABAa-agonistReduce DTs, mortality, duration of W/DN=574, randomized pts to benzo, antipsychotic, antihistamine, thiamineBenzo had lowest risk of DTs and alcohol W/D szAntipsychotic increased sz risk N=229, 2mg IM Ativan risk of recurrent sz from 24%3% and admission from 42%29%

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

  • Alcohol Withdrawal - BenzosWhich benzo?Ideal: quick onset, long tDiazepam Most rapid time to peak clinical effectsLimits oversedationLong t ( in advanced liver dz)***?NOT AVAILABLE IN OUR ED***LorazepamShorter tInactive metabolitesLarge doses may lead to propylene glycol A/E (hypotension, dysrrhythmias)

  • Alcohol Withdrawal - BenzosHow much?DosingPO for mild W/DDiazepam 5-20mg IV q5-10minLorazepam 1-4mg IV q5-10minGoal breathing spontaneously, N vitals, sedated

    SlovisDiazepam 5, 5, 10, 10, 20, 20, 20Lorazepam 1, 1, 2, 2, 4, 4, 4

    Can be massive2640mg diazepam + 35mg haloperidol over 48hMayo-Smith et al, JAMA 1997;278:1-24

  • Alcohol Withdrawal - BenzosDo we use fixed-interval dosing or symptom-triggered dosing?

    Symptom triggered dosingClinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar)10 clinical variables,

  • Br J Addict 1989;84:1353-1357

  • Alcohol Withdrawal - Benzos3 prospective RCTs supporting symptom-triggered dosingTotal amount of medicationDuration of treatment?DTsEg:Oxazepam 37.5mg vs 231.4mgDuration of treatment 20h vs 63h

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

  • Alcohol Withdrawal - BenzosTypically sufficient for prevention of alcohol withdrawal seizures (AWS)

    What next if benzos not really working?More benzos?Phenobarb?Propofol?Haldol?

  • Alcohol Withdrawal BarbituratesEffectiveness shown in uncontrolled studiesMechanismDirectly open GABAa Cl- channels

    Phenobarbital 260mg IV over 5min then 130mg IV over 3min q30min prnOnset 20-40minA/E: hypoTN, resp depressionMayo-Smith et al, JAMA 1997;278:1-24

  • Alcohol Withdrawal NeurolepticsMeta-analysis of 5 controlled trialsCompared sedative-hypnotics to neurolepticsInferior in reducing mortality and durationPotential for NMS, sz thresholdRelative risk of mortality with neuroleptics vs sedative-hypnotics of 6.6 (95%CI 1.2-34.7)No good studies looking at atypicalsMayo-Smith et al, Arch Intern Med 2004;164:1405-12

  • Alcohol Withdrawal NeurolepticsHaloperidol (Haldol)Typical neurolepticDopamine antagonistIndication for use:Continued agitation unresponsive to IV benzosLittle effect on myocardial fn or resp driveNo anticonvulsant activity, lowers sz thresholdNot to be used alone!

  • Alcohol Withdrawal AlternativesPropofol, thiopentalLikely in consult with ICU

    What about ethanol?Historically usedIdeal drug to symptoms of EtOH W/DLiterature conflicting on efficacyToxic A/E

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

  • Case 2 contDTsDespite benzo txHTN, tachycardia

    Any other agents that might help here?

  • Alcohol Withdrawal Adjuncts-adrenergic antagonistsAdjunctive in mild/moderate W/D with HTN/tachyC (Grade C)Can decrease the need for benzosDecreased tremor, agitation, anxietyBUTcan mask ANS signs making it more difficult to assess need for tx1 controlled study of propranololIncreased incidence of deliriumZilm et al. Alcohol Clin Exp Res 1980;4:400-5Not recommended unless other tx fail Goldfranks***Potentially can use them in pts with cardiac history, but beware if ?sympathomimmetic on board***

  • Alcohol Withdrawal - Tx4 principles of treatment1) Evaluate for concurrent illness2) Restore inhibitory tone to CNS3) ID/correct lyte/fluid deficiencies4) Allow pt to recover with the least amount of physical restraint to decrease the risk of hyperthermia and rhabdoEM Reports 26(16) July 25, 2005

  • Alcohol Withdrawal AdjunctsThiamine 100mg IVBefore/after glucose doesnt matterMg 2-5g IVMay rate of AST Poikolainen & Alho. Subst Abuse Treat Prev Policy 2008;3(1):1No effect on severity of W/D or incidence of W/D seizuresWilson & Vulcano. Alcohol Clin Exp Res 1984;8:542-5No evidence of benefit, give it anywayMultivitaminsmagic yellow watermakes everyone feel betterK+ replacement

  • Alcohol Withdrawal - DispositionObserve 4-6hMost can be tx successfully as outptIf mild-mod W/D does not progressD/C with F/U (Renfrew, etc)***Practically this is usually less-D/C when sympt resolved, eating/drinking, not requiring IV fluids, ambulatoryAdmission for severe W/DBayard et al. Am Fam Physician. 2004;69(6):1443-50

  • Alcohol Withdrawal Outpt TxOutpatient vs inpatient detox for mild-moderate W/DN=87 outpts, 77 inpts; pRCTOutptDaily clinic visits, decreasing oxazepam dosesInptOxazepam, rehab treatmentResultsMean duration of tx 6.5d (OP) vs 9.2d (IP)95% IP vs 72% OP completed detoxNo complicationsNo group difference at 6 months post-detox$3319-3665/IP vs $175-388/OPConclusionOP detox for mild-mod W/D is effective, safe, and low-costNo outpt detox program in Calgary

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

  • Renfrew40-bed recovery centre, freeUsually 36 clientsNo appointment necessary 9am-4pmShow up at 8:15am297-3337 otherwiseEtOH benzo opioids crack in order

    Typical 5-day stay, (8-9 benzo/opioids)Client care assistants and 24-hour RNAssessment bed program bedNon-invasive (no IVs, no Ix, no abx, etc)Immunizations, mental health services, counsellors for referralsAvg age 37, 70% male, increasing incidence of crack useBudget $1.7 million/year, govt funding through AADAC

  • Case 356M homeless alcoholic, EMS called for sz downtownReceived total of 4mg lorazepam IV enrouteBy the time of your assessmentAAO x 3, vitals 95, 114/78, 18, 375, 96%Nothing remarkable on examPMH: seizures; Rx: none; NKDA

    The clinical clerk asks you if you want to load the patient with Dilantinthoughts?

  • Alcohol Related SeizuresWant to r/o life-threatening causesHypoglycemia, CNS infection, ICH

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

  • Alcohol Withdrawal Seizures (AWS)Rum FitsMost occur within 24h of decreasing EtOH5% of pts with AWSs progress to DTs b/c of inadequate txTend to have rapid post-ictal recoveryFeverSecondary to W/D or to szCNS infection?Rare in febrile alcoholic with AWSObligated to look for it!

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

  • Alcohol Withdrawal AnticonvulsantsDo we use Dilantin in preventing recurrence of AWS?Mechanism?Promotion of Na+ efflux from motor cortex neuronsDoes NOT involve GABA/NMDA receptorsMultiple placebo-controlled trialsNo better than placebo at preventing alcohol withdrawal seizure recurrenceAlldredge et al. AM J Med 1989;87:645-8Chance. Ann Emerg Med 1991;20:520-2Rathlev et al. Ann Emerg Med 1994;23:513-8

    When might you use Dilantin in AWS?Basically only if pt is already on DilantinSee ASAM CPG for other recommendationshttp://www.asam.org/CMS/images/PDF/AboutASAM/ASAM%20Clinical%20Practice%20Guideline.pdf

  • Case 3Disposition?Observation x 4-6hIf symptom free and no recurrenceD/C get the man some booze!Short course of PO benzosAppropriate referral (Renfrew, FP, neuro?)

  • Case 3bThe seizure was witnessed by EMS and involved the R arm/face only

    Any change in your thought process?20% of focal alcohol related seizures have a structural lesion

    Ernest, Neurology 1988;38:1561

  • Case 3cPt post-ictal on initial assessment5 min later RN tells you hes having another seizureThoughts?Plan?Dilantin?Still indicated for alcohol-related status epilepticus (Grade C recommendation)ASAM CPG

  • Alcohol Withdrawal Take-homeEtOH W/D is a common ED presentation

    CNS/ANS excitation

    Sympt 6h, sz 12-24h, DTs 72h

    Benzos, benzos, benzos.

    Status is status tx the same

  • Questions?

  • Case 437FN, V, tremor, H/APMH: depression, anxiety, panic attacksTaking clonazepam until 5d agoO/EVitals 120, 135/85, 372, 20, 96%Diaphoretic, tremulousRemind you of anything?

  • Benzodiazepines - HistoryChlordiazepoxide (Librium)First benzo, synthesized in 1955Diazepam (Valium)Marketed for seizures in 1963Improvement on older sedative-hypnoticsBarbiturates, chloral hydrate, etcNow > 50 benzos on the market

  • BenzodiazepinesMechanism of actionBind to benzo receptor (part of GABAa-R)Potentiates GABA effect on GABAa Cl- channel Hyperpolarizes cell (Cl- in)Diminished ability to initiate action potentialCNS inhibitory effectCl-GABAa-RBZGABABZ-rGABA-rCl-Cl-Cl-Cl-ExtracellularIntracellularZZZZ.Hyperpolarized

  • Benzo Withdrawal - BasicsRisk related to duration/dose/t Need ~4mo tx before W/D occurs1/3 of benzo users experience W/DLorazepam W/D more severe than diazepamW/D can occur with change in benzo

  • Benzo Withdrawal - SymptomsSymptom onset1-3d for short acting (loraz, alpraz) severity, duration3-7d for long acting (diaz, clonaz)May persist for weeksImmediate with flumazenil use!

  • Benzo Withdrawal - SymptomsSimilar to EtOH W/DANS instability (tachycardia, diaphoresis)Anxiety, insomnia, tremor, H/A, N, VSevereDisorientation, visual hallucinations, delirium, seizures

  • Benzo Withdrawal - TreatmentBest treatment for benzo W/D? Reinstitution of long-acting benzoDiazepam 5-10mg IV q5-10min prnOutpt PO diazepam at = dose to pts benzoGradual taper if discontinuation is desiredMD supervised6-8 weeks

  • Case 520F found down, minimally responsiveEmpty bottle of diazepam by bedside

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

    You say go for it, and the pt begins to have a seizure shortly after flumazenilManagement?

  • FlumazenilCompetitive BZ receptor antagonist Duration of action shorter than most benzos

  • FlumazenilFew case reports of flumazenil-induced W/D, including seizures & deathHaverkos et al. Ann Pharmacother1994;28:1347Spivey. Clin Ther1992;14:292Whitwam et al. Acta Anaesh Scand Suppl1995;108:3Severe withdrawal symptomsTreat with phenobarbital

    BOTTOM LINE: Risks >>> benefits

  • Benzodiazepine Withdrawal SummaryW/D = less inhibitory GABA activity

    Similar to EtOH W/D

    Short acting benzo = more severe W/D

    Long acting benzo for management

  • Questions?

  • Case 620F decreased LOC, found by boyfriendO/EDrousy, pinpoint pupils, hypoventilatingPMH ?Normally takes a white pill & an oval pillManagement?You try naloxoneMore alert and vomiting, tachycardic, diaphoretic

    Diagnosis?

  • NaloxoneCompetitive opioid antagonistOnset 1-2minDuration 20-90minHepatic metabolismCan precipitate acute opioid withdrawalUsually short-lived

  • OpioidsMedicinal value of opium - 1500 B.C.Many formulations, essentially same drugLaudanum, paregoric, Dover's powder, Godfrey's cordial, morphineAnalgesia, euphoria, anti-tussiveTerminologyOpiate = derived from opium poppyOpioidBinds opioid receptorProduces opioid-like effect

  • Opioid Withdrawal - BasicsNot usually life-threateningOnset depends on tHeroin 4-6hMethadone 24-48hDurationDays-weeksPersistent weakness/insomnia/anxiety x 6m

  • Opioid Withdrawal - PathophysMany opioid receptorsStimulation of some Reduced CNS NE release (locus ceruleus)Chronic opioid useExcitability of neurons in the locus ceruleusW/D of opioidNoradrenergic hyperactivity

  • Opioid WithdrawalSymptoms?PsychologicalCraving, dysphoria, anxiety, insomniaPhysiologicalTachycardia, tachypnea, HTNDiaphoresis, lacrimation, rhinorrhea, myalgias, abdo pain, V, DDope sick

  • Opioid Withdrawal - SignsMydriasis, yawning, piloerection, increased bowel soundsHR/RR/bp increase

    Alert, oriented, afebrile

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

    Goldfranks

  • Opioid Withdrawal - ManagementR/O other causes of presentationSupportiveIV fluids, K+, anti-emeticsEvaluation for complications of IVDUEndocarditis, AIDS-related illnesses, etc

  • Opioid Withdrawal - ManagementClonidineCentral presynaptic 2-receptor agonist NE reuptakeReduces noradrenergic activity0.1-0.2mg PO q4-6h prn (monitor bp)BZIf significant anxietyMethadone 20mg POSynthetic opioid with long tUsed in outpt programs, not our EDFreitas. Am J Emerg Med 1985;3(5):456-60

  • Opioid WithdrawalGoals/Disposition?Temporary control of symptomsOther disease ruled outReferral to methadone program prn

  • Opioid Withdrawal - SummaryNarcan can precipitate acute opioid W/D

    Sympt = noradrenergic hyperactivity

    Not usually life-threatening

    Clonidine, symptomatic treatment

  • Questions?

  • Case 723M, brought in by Mom, 2 day hx ofIncreasing anxiety, some suidical thoughts++Fatigue, increased appetite/sleepMyalgias, tremorO/EVitals 85, 125/85, 365, 20, 96%AAO x 3, nothing remarkable on examThoughts?

  • CocaineI am just now collecting the literature for a song of praise to this magical substance-Sigmund Freud, 1884

  • Cocaine - BasicsNatural alkaloid found in Erythroxylon coca

    Causes release ofDopamineEpinephrineNorepinephrineSerotonin Na+ channel blockerBlocks presynaptic NE reuptake

  • Cocaine Withdrawal - SymptomsPsychological symptomsDepression, anxiety, fatigue, difficulty concentrating, anhedonia, craving, increased appetite, increased sleep/dreaming, suicidal ideationPhysiological signs/symptomsMSK pain, tremor, chills, involuntary motor movement, myocardial ischemia

  • N=21 cocaine addicts in 28d inpt rehabHolter and stress test admission/dischargeResults38% had silent STEOnly 1 pt had +stress test3 agreed to cath all NNo MIs, no information on outcomesConclusionRisk of vasospasm during withdrawal periodLikely reflects delayed vasospasm after cocaine use, not necessarily a withdrawal phenomenon

  • Cocaine Withdrawal - ManagementSupportiveLorazepam for insomnia/agitation

    Admission rarely indicatedReferral to addiction treatment program

    Resolves within 1-2 weeks without tx

  • Cocaine Withdrawal Take homeProminent psychological features

    Rarely medically serious

    Treatment is supportive

  • Questions?

  • Post-test Q1What percentage of hospitalized patients are ethanol dependent?5-10%15-20%30-40%>40%

  • Post-test Q2What is the current mortality from alcohol withdrawal syndrome?5%7%
  • Post-test Q3Alcohol acts as a/an ______________ on the GABA receptor.Indirect agonistDirect agonistIndirect antagonistDirect antagonist

  • Post-test Q4In alcohol withdrawal, wWhich of the following agents is best used in patients at risk for oversedation and those with liver disease?DiazepamLorazepamPhenytoinThiamine

  • Post-test Q5Which of the following agents is best used for AWS if high doses of benzodiazepines are ineffective?CarbamazepinePhenytoinEthanolPhenobarbital

  • Post-test Q6Symptom-triggered therapy for alcohol withdrawal has been shown to reduce which of the following factors?Amount of medication usedDuration of treatmentBoth A and BNeither A nor B

  • Post-test Q7Neuroleptic agents:Effectively control autonomic instability associated with AWSControl alcohol-induced seizuresImprove hyperthermia related to AWSReduce the seizure threshold

  • Post-test Q8The use of phenytoin is indicated in which of the following situations?A patient with AWS and non-alcohol-related seizuresA patient with an AWSA patient with HTN and tachycardia related to AWSAn intoxicated patient with a history of AWS

  • Post-test Q9The benzodiazepine of choice for treating benzodiazepine withdrawal is:MidazolamLorazepamDiazepamAlprazolam

  • Post-test Q10ED management of opioid withdrawal consists primarily of:Benzodiazepines-blockersSupportive careMethadone

  • Post-test Q11Patients with acute cocaine withdrawal often require admission.TrueFalse

  • The end

  • Pliny the Elder first described EtOH W/D, William Osler first described txIsabell et al subjected 9 male prisoners to chronic alcohol ingestion for a period of 6-12 weeks followed by 2 weeks of abstinence. 6/9 tremor,>bp,>HR, diaphoresis, and varying degrees of auditory/visual hallucinations. 2/9 developed szOpposite effect at NMDA receptor: ethanol binds causing inhibition and upregulationComplex, not fully understood, chronic alcohol consumption affects central adrenergic -receptors, glutamate, central adrenergic -receptors, the inhibitory neurotransmitter GABA, and dopamine turnoverExacerbated by manifestations of alcoholism: nutritional depletion, impaired immunity, anemia, cirrhosis, head trauma Normally, presynaptic 2-adrenergic receptors function by inhibiting the release of norepinephrine. Diminished sensitivity of these receptors may be responsible for the increased catecholamines found in ethanol withdrawal.Acute psychosis (younger, oriented pt), encephalitis (H/A, fever), drug-induced psychosis, thyrotoxicosis (F, palpitations, insomnia), anticholinergic poisoning (>pupils, >vitals, dry, are reversed (hMg)No known effect of haldol on GABA, and no dopaminergic theory for EtOH W/D, so it is important to use this only if benzos have failedPropofol directly opens GABAa-Cl channels and antagonizes NMDA receptorsbarbiturates and propofol can directly open the chloride channel and cause hyperpolarization without need for GABA (i.e. they are direct agonists)Weinberg et al. JTrauma 2008 - Recent pRCT on IV ethanol vs diazepam in trauma ICU pts with >5 drinks/d; one pt failed etoh tx, no difference in AW syndrome preventionB-blockers dont address the underlying pathophysiologic mechanism of AWS, they mask the symptoms risk of underdosing benzos Poikolainen DBRCT of Mg vs no Mg during W/D tx, outcomes were serum GGT, ALT, AST changes x 8 weeks, found faster AST decrease in Mg groupWilson DBRCT of Mg vs no Mg during W/D tx, N=100, Mg 2g IM q6h x 4, no effect on either severity of alcohol withdrawal or incidence of withdrawal seizures But Mg deficiency is common in this group, and symptoms overlap with W/D symptoms, serum Mg level not indicative of total body MgGive especially if youre giving haldol!Relative indications for admission: history of severe withdrawal symptoms, history of withdrawal seizures or delirium tremens, multiple previous detoxifications, concomitant psychiatric or medical illness, recent high levels of alcohol consumption, pregnancy, and lack of a reliable support network 12 bed assessment area Repeat C/S, CT head, LPStatus epilepticus, tx: IV x 2 lines, lorazepam 2mg IV q5min prn x 2-3, 2nd line is still Dilantin 18mg/kg (can get hTN/bradyC from propylene glycol solvent in Dilantin avoid by infusing at