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Substance Withdrawal

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Title: Substance Withdrawal


1
Substance Withdrawal
  • Jay Green
  • Emergency Medicine Resident, PGY-2
  • February 28, 2008

2
Outline
  • Pre-test
  • Substance Withdrawal Cases
  • Alcohol
  • Opioid
  • Benzodiazepine
  • Cocaine
  • Post-test
  • Evidence of a proud father!

3
Pre-test Q1
  • What percentage of hospitalized patients are
    ethanol dependent?
  • 5-10
  • 15-20
  • 30-40
  • gt40

4
Pre-test Q2
  • What is the current mortality from alcohol
    withdrawal syndrome?
  • 5
  • 7
  • lt1
  • 10

5
Pre-test Q3
  • Alcohol acts as a/an ______________ on the GABA
    receptor.
  • Indirect agonist
  • Direct agonist
  • Indirect antagonist
  • Direct antagonist

6
Pre-test Q4
  • In alcohol withdrawal, which of the following
    agents is best used in patients at risk for
    oversedation and those with liver disease?
  • Diazepam
  • Lorazepam
  • Phenytoin
  • Thiamine

7
Pre-test Q5
  • Which of the following agents is best used for
    AWS if high doses of benzodiazepines are
    ineffective?
  • Carbamazepine
  • Phenytoin
  • Ethanol
  • Phenobarbital

8
Pre-test Q6
  • Symptom-triggered therapy in alcohol withdrawal
    has been shown to reduce which of the following
    factors?
  • Amount of medication used
  • Duration of treatment
  • Both A and B
  • Neither A nor B

9
Pre-test Q7
  • Neuroleptic agents
  • Effectively control autonomic instability
    associated with AWS
  • Control alcohol-induced seizures
  • Improve hyperthermia related to AWS
  • Reduce the seizure threshold

10
Pre-test Q8
  • The use of phenytoin is indicated in which of the
    following situations?
  • A patient with AWS and non-alcohol-related
    seizures
  • A patient with an AWS
  • A patient with HTN and tachycardia related to AWS
  • An intoxicated patient with a history of AWS

11
Pre-test Q9
  • The benzodiazepine of choice for treating
    benzodiazepine withdrawal is
  • Midazolam
  • Lorazepam
  • Diazepam
  • Alprazolam

12
Pre-test Q10
  • ED management of opioid withdrawal consists
    primarily of
  • Benzodiazepines
  • ß-blockers
  • Supportive care
  • Methadone

13
Pre-test Q11
  • Patients with acute cocaine withdrawal often
    require admission.
  • True
  • False

14
(No Transcript)
15
Case 1
  • 43M previously healthy, no meds
  • Unemployed, brought in by sister
  • N, V today, sister worried about hand tremor
  • SocHx Smoker, few beers/day x years
  • O/E
  • HR 112, bp 160/96
  • Appears a bit anxious
  • Tremulous

16
Case 2
  • 43M no known PMH/meds
  • Brought in by EMS
  • Found to be agitated, vomiting, ?hallucinating
  • Hx from pt unhelpful
  • O/E
  • Not oriented, GCS 13 (E4V4M5)
  • Vitals 130, 175/100, 387, 20, 95
  • Volatile, ?visual hallucinations/anxious
  • tremulous, ?hyperreflexia

17
Alcohol Withdrawal
18
Alcohol Withdrawal - History
  • First 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. ..."
  • Osler
  • Initial tx
  • Supportive, KBr, chloral hydrate, hyoscine, opium
  • Isbell et al, 1955
  • Alcohol ? withdrawal syndrome
  • Amount/duration of alcohol intake ? severity

Isbell H, Frasier HF, Wilkler A et al. An
experimental study of the etiology of rum fits
and delirium tremens. QJ Study Alcohol 1955161.
19
Alcohol W/D - Epidemiology
  • 22 of Americans gt12y report binge drinking at
    least once during the past 30d
  • 7 report heavy regular drinking
  • 2003 US National Survey on Drug Use and Health
  • These are the people who actually answer surveys
  • 15-20 hospitalized pts are alcohol dependent
  • Hodges and Mazur, Pharmacotherapy 2004241578-85
  • Mortality lt1

20
Alcohol W/D - Pathophysiology
  • Chronic EtOH ? CNS depressant
  • ? GABAminergic tone ? sedation via GABAa-receptor
  • Downregulation of GABAa-receptor
  • Normal level of consciousness with ??EtOH
  • NMDA inhibition
  • Upregulation of NMDA-receptors
  • W/D of EtOH?CNS excitation (?GABA, ?NMDA)
  • Inhibitory control of excitatory NTs is lost
  • CNS excitation (tremor, sz, hallucination)
  • ANS stimulation (HTN, sweating, hyperthermia,
    tachycardia)

21
Case 1
  • 43M previously healthy, no meds
  • Unemployed, brought in by sister
  • N, V today, sister worried about hand tremor
  • SocHx Smoker, few beers/day x years
  • O/E
  • HR 112, bp 160/96
  • Appears a bit anxious
  • Tremulous
  • What else is on the ddx?

22
(No Transcript)
23
DDx
  • What else is on the ddx?
  • Acute psychosis
  • CNS infection
  • Thyrotoxicosis
  • Anticholinergic poisoning
  • W/D from other sedative-hypnotics

24
Alcohol W/D - Signs/Symptoms
  • Do you need to stop EtOH consumption to get EtOH
    W/D?
  • When do signs of W/D begin?

25
Alcohol W/D - Signs/Symptoms
  • Begin 6-24h after decreasing EtOH
  • Can occur with continued lower volume EtOH
  • Lasts 2-7d
  • Severity ? dose/duration of EtOH

26
Alcohol W/D - Classification
  • How do you classify EtOH W/D?
  • 4 stages
  • Tremulousness (6-12h)
  • Hallucinations (12-48h)
  • Seizures (12-48h)
  • DTs (gt48h)
  • Minor ? Major ? DTs
  • Timing severity
  • early/late complicated/uncomplicated

27
Alcohol W/D - Classification
  • Minor ? Major ? DTs
  • What are some symptoms of minor W/D?
  • Early onset, peak 24-36h
  • N, anorexia, tremor, tachycardia, HTN,
    hyperreflexia, insomnia, anxiety
  • What 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

28
Alcohol Withdrawal - Diagnosis
  • DSM-IV diagnostic criteria
  • Alcohol Withdrawal
  • Cessation/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

29
Alcohol Withdrawal - Diagnosis
  • DSM-IV diagnostic criteria
  • Alcohol Withdrawal with Delirium (DTs)
  • Also includes decreased consciousness, change in
    cognition, perceptual disturbance

30
Case 2 revisited
  • 43M no known PMH/meds
  • Brought in by EMS
  • Found to be agitated, vomiting, ?hallucinating
  • Hx from pt unhelpful
  • O/E
  • Not oriented, GCS 13 (E4V4M5)
  • Vitals 130, 175/100, 387, 20, 95
  • Volatile, ?visual hallucinations/anxious
  • tremulous, ?hyperreflexia
  • You think they have DTs.
  • What else is on the ddx?

31
Case 2
  • You think this patient has delirium tremens
  • What else could this be?
  • Sepsis
  • Meningitis
  • SAH
  • Heat stroke
  • Serotonin syndrome
  • NMS
  • Cocaine/amphetamine toxicity
  • Malignant hyperthermia

32
Alcohol W/D Delirium Tremens
  • Extreme end of the spectrum
  • Almost never before 3d
  • 5 of pts hospitalized for EtOH W/D
  • Difficult to predict who will get it
  • Can last up to 2 weeks
  • THESE PATIENTS ARE SICK!

33
Case 2 revisited
  • 43M no known PMH/meds
  • Brought in by EMS
  • Found to be agitated, vomiting, ?hallucinating
  • Hx from pt unhelpful
  • O/E
  • Not oriented, GCS 13 (E4V4M5)
  • Vitals 130, 175/100, 387, 20, 95
  • Volatile, ?visual hallucinations/anxious
  • tremulous, ?hyperreflexia
  • What investigations?

34
Alcohol Withdrawal - Ix
  • C/S
  • CBC, lytes, BUN, Cr, LFTs, lipase, INR, EtOH
  • U/A
  • CXR
  • ECG
  • VBG
  • CT head
  • LP
  • Tox screen

35
Case 2
  • Labs sent
  • ECG tachycardia
  • CXR pending
  • C/S 2.9
  • What would you like to do now?

36
Case 2 - Tx
  • Initial Stabilization
  • ABCs
  • NGT
  • Restraints
  • What about giving glucose before thiamine?

37
Wernicke-Korsakoff Syndrome
  • Symptoms/signs?
  • Oculomotor disturbances (nystagmus and ocular
    palsies), confusion, ataxia 12 have triad
  • Mortality 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.

38
Wernicke-Korsakoff Syndrome
  • Case reports
  • WK syndrome after prolonged IV glucose
    administration
  • BOTTOM LINE
  • Dont delay glucose for thiamine

Waton et al. Ir J Med Sci 1981 Oct150(10)301-3
39
Alcohol Withdrawal - Tx
  • 4 principles of treatment
  • 1) Evaluate for concurrent illness
  • 2) Restore inhibitory tone to CNS
  • 3) ID/correct lyte/fluid deficiencies
  • 4) Allow pt to recover with the least amount of
    physical restraint to decrease the risk of
    hyperthermia and rhabdomyolysis

EM Reports 26(16) July 25, 2005
40
Alcohol Withdrawal - Tx
  • 4 principles of treatment
  • 1) Evaluate for concurrent illness
  • 2) Restore inhibitory tone to CNS
  • 3) ID/correct lyte/fluid deficiencies
  • 4) Allow pt to recover with the least amount of
    physical restraint to decrease the risk of
    hyperthermia and rhabdomyolysis

EM Reports 26(16) July 25, 2005
41
Alcohol Withdrawal - Tx
  • gt150 drug combinations
  • Benzos are mainstay
  • Interact with GABAa-receptor
  • Substitute for removal of EtOH as a GABAa-agonist

42
GABA-r
GABA
ZZZZ.
Cl-
Cl-
Cl-
Cl-
Cl-
BZ-r
Hyperpolarized
BZ
GABAa-R
Intracellular
Extracellular
43
Alcohol Withdrawal - Tx
  • gt150 drug combinations
  • Benzos are mainstay
  • Interact with GABAa-receptor
  • Substitute for removal of EtOH as a GABAa-agonist
  • Reduce DTs, mortality, duration of W/D
  • N574, randomized pts to benzo, antipsychotic,
    antihistamine, thiamine
  • Benzo had lowest risk of DTs and alcohol W/D sz
  • Antipsychotic increased sz risk
  • N229, 2mg IM Ativan ? risk of recurrent sz from
    24?3 and ?admission from 42?29

Kaim et al. Am J Psychiatry 1969125 1640-1646
Goldfrank's Toxicologic Emergencies - 8th Ed.
(2006)
44
Alcohol Withdrawal - Benzos
  • Which benzo?
  • Ideal quick onset, long t½
  • Diazepam
  • Most rapid time to peak clinical effects
  • Limits oversedation
  • Long t½ (??? in advanced liver dz)
  • ?NOT AVAILABLE IN OUR ED
  • Lorazepam
  • Shorter t½
  • Inactive metabolites
  • Large doses may lead to propylene glycol A/E
    (hypotension, dysrrhythmias)

45
Alcohol Withdrawal - Benzos
  • How much?
  • Dosing
  • PO for mild W/D
  • Diazepam 5-20mg IV q5-10min
  • Lorazepam 1-4mg IV q5-10min
  • Goal breathing spontaneously, N vitals, sedated
  • Slovis
  • Diazepam 5, 5, 10, 10, 20, 20, 20
  • Lorazepam 1, 1, 2, 2, 4, 4, 4
  • Can be massive
  • 2640mg diazepam 35mg haloperidol over 48h
  • Mayo-Smith et al, JAMA 19972781-24

46
Alcohol Withdrawal - Benzos
  • Do we use fixed-interval dosing or
    symptom-triggered dosing?
  • Symptom triggered dosing
  • Clinical Institute Withdrawal Assessment of
    Alcohol Scale, Revised (CIWA-Ar)
  • 10 clinical variables, lt5min to complete

47
Br J Addict 1989841353-1357
48
Alcohol Withdrawal - Benzos
  • 3 prospective RCTs supporting symptom-triggered
    dosing
  • ?Total amount of medication
  • ?Duration of treatment
  • ??DTs
  • Eg
  • Oxazepam 37.5mg vs 231.4mg
  • Duration of treatment 20h vs 63h

Manikant et al, Indian J Med Res
199398170-3 Saitz et al, JAMA
1994272519-23 Daeppen et al, Arch Int Med
20021621117-21
49
Alcohol Withdrawal - Benzos
  • Typically sufficient for prevention of alcohol
    withdrawal seizures (AWS)
  • What next if benzos not really working?
  • More benzos?
  • Phenobarb?
  • Propofol?
  • Haldol?

50
Alcohol Withdrawal Barbiturates
  • Effectiveness shown in uncontrolled studies
  • Mechanism
  • Directly open GABAa Cl- channels
  • Phenobarbital 260mg IV over 5min then 130mg IV
    over 3min q30min prn
  • Onset 20-40min
  • A/E hypoTN, resp depression

Mayo-Smith et al, JAMA 19972781-24
51
Alcohol Withdrawal Neuroleptics
  • Meta-analysis of 5 controlled trials
  • Compared sedative-hypnotics to neuroleptics
  • Inferior in reducing mortality and duration
  • Potential for NMS, ?sz threshold
  • Relative risk of mortality with neuroleptics vs
    sedative-hypnotics of 6.6 (95CI 1.2-34.7)
  • No good studies looking at atypicals

Mayo-Smith et al, Arch Intern Med 20041641405-12
52
Alcohol Withdrawal Neuroleptics
  • Haloperidol (Haldol)
  • Typical neuroleptic
  • Dopamine antagonist
  • Indication for use
  • Continued agitation unresponsive to IV benzos
  • Little effect on myocardial fn or resp drive
  • No anticonvulsant activity, lowers sz threshold
  • Not to be used alone!

53
Alcohol Withdrawal Alternatives
  • Propofol, thiopental
  • Likely in consult with ICU
  • What about ethanol?
  • Historically used
  • Ideal drug to ? symptoms of EtOH W/D
  • Literature conflicting on efficacy
  • Toxic A/E

Weinberg et al. J Trauma 200864(1)99-104
54
Case 2 cont
  • DTs
  • Despite benzo tx
  • HTN, tachycardia
  • Any other agents that might help here?

55
Alcohol Withdrawal Adjuncts
  • ß-adrenergic antagonists
  • Adjunctive in mild/moderate W/D with HTN/tachyC
    (Grade C)
  • Can decrease the need for benzos
  • Decreased tremor, agitation, anxiety
  • BUTcan mask ANS signs making it more difficult
    to assess need for tx
  • 1 controlled study of propranolol
  • Increased incidence of delirium
  • Zilm et al. Alcohol Clin Exp Res 19804400-5
  • Not recommended unless other tx fail
    Goldfranks
  • Potentially can use them in pts with cardiac
    history, but beware if ?sympathomimmetic on
    board

56
Alcohol Withdrawal - Tx
  • 4 principles of treatment
  • 1) Evaluate for concurrent illness
  • 2) Restore inhibitory tone to CNS
  • 3) ID/correct lyte/fluid deficiencies
  • 4) Allow pt to recover with the least amount of
    physical restraint to decrease the risk of
    hyperthermia and rhabdo

EM Reports 26(16) July 25, 2005
57
Alcohol Withdrawal Adjuncts
  • Thiamine 100mg IV
  • Before/after glucose doesnt matter
  • Mg 2-5g IV
  • May ? rate of AST ?
  • Poikolainen Alho. Subst Abuse Treat Prev Policy
    20083(1)1
  • No effect on severity of W/D or incidence of W/D
    seizures
  • Wilson Vulcano. Alcohol Clin Exp Res
    19848542-5
  • No evidence of benefit, give it anyway
  • Multivitamins
  • magic yellow watermakes everyone feel better
  • K replacement

58
Alcohol Withdrawal - Disposition
  • Observe 4-6h
  • Most can be tx successfully as outpt
  • If mild-mod W/D does not progress
  • D/C with F/U (Renfrew, etc)
  • Practically this is usually less
  • -D/C when sympt resolved, eating/drinking, not
    requiring IV fluids, ambulatory
  • Admission for severe W/D

Bayard et al. Am Fam Physician. 200469(6)1443-50
59
Alcohol Withdrawal Outpt Tx
  • Outpatient vs inpatient detox for mild-moderate
    W/D
  • N87 outpts, 77 inpts pRCT
  • Outpt
  • Daily clinic visits, decreasing oxazepam doses
  • Inpt
  • Oxazepam, rehab treatment
  • Results
  • Mean duration of tx 6.5d (OP) vs 9.2d (IP)
  • 95 IP vs 72 OP completed detox
  • No complications
  • No group difference at 6 months post-detox
  • 3319-3665/IP vs 175-388/OP
  • Conclusion
  • OP detox for mild-mod W/D is effective, safe, and
    low-cost
  • No outpt detox program in Calgary

Hayashida et al. NEJM. 1989 Feb 9320(6)358-65
60
Renfrew
  • 40-bed recovery centre, free
  • Usually 36 clients
  • No appointment necessary 9am-4pm
  • Show up at 815am
  • 297-3337 otherwise
  • EtOH ? benzo ? opioids ? crack in order
  • Typical 5-day stay, (8-9 benzo/opioids)
  • Client care assistants and 24-hour RN
  • Assessment bed ? program bed
  • Non-invasive (no IVs, no Ix, no abx, etc)
  • Immunizations, mental health services,
    counsellors for referrals
  • Avg age 37, 70 male, increasing incidence of
    crack use
  • Budget 1.7 million/year, govt funding through
    AADAC

61
Case 3
  • 56M homeless alcoholic, EMS called for sz
    downtown
  • Received total of 4mg lorazepam IV enroute
  • By the time of your assessment
  • AAO x 3, vitals 95, 114/78, 18, 375, 96
  • Nothing remarkable on exam
  • PMH seizures Rx none NKDA
  • The clinical clerk asks you if you want to load
    the patient with Dilantinthoughts?

62
Alcohol Related Seizures
  • Want to r/o life-threatening causes
  • Hypoglycemia, CNS infection, ICH
  • Up to 40 of seizures and 25 of status
    epilepticus are EtOH related

63
Alcohol Withdrawal Seizures (AWS)Rum Fits
  • Most occur within 24h of decreasing EtOH
  • 5 of pts with AWSs progress to DTs b/c of
    inadequate tx
  • Tend to have rapid post-ictal recovery
  • Fever
  • Secondary to W/D or to sz
  • CNS infection?
  • Rare in febrile alcoholic with AWS
  • Obligated to look for it!

Wren et al. Amer J Emerg Med 1991957
64
Alcohol Withdrawal Anticonvulsants
  • Do we use Dilantin in preventing recurrence of
    AWS?
  • Mechanism?
  • Promotion of Na efflux from motor cortex neurons
  • Does NOT involve GABA/NMDA receptors
  • Multiple placebo-controlled trials
  • No better than placebo at preventing alcohol
    withdrawal seizure recurrence
  • Alldredge et al. AM J Med 198987645-8
  • Chance. Ann Emerg Med 199120520-2
  • Rathlev et al. Ann Emerg Med 199423513-8
  • When might you use Dilantin in AWS?
  • Basically only if pt is already on Dilantin
  • See ASAM CPG for other recommendations

http//www.asam.org/CMS/images/PDF/AboutASAM/ASAM
20Clinical20Practice20Guideline.pdf
65
Case 3
  • Disposition?
  • Observation x 4-6h
  • If symptom free and no recurrence
  • D/C get the man some booze!
  • Short course of PO benzos
  • Appropriate referral (Renfrew, FP, neuro?)

66
Case 3b
  • The 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 1988381561
67
Case 3c
  • Pt post-ictal on initial assessment
  • 5 min later RN tells you hes having another
    seizure
  • Thoughts?
  • Plan?
  • Dilantin?
  • Still indicated for alcohol-related status
    epilepticus (Grade C recommendation)
  • ASAM CPG

68
Alcohol Withdrawal Take-home
  • EtOH 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

69
Questions?
70
Case 4
  • 37F
  • N, V, tremor, H/A
  • PMH depression, anxiety, panic attacks
  • Taking clonazepam until 5d ago
  • O/E
  • Vitals 120, 135/85, 372, 20, 96
  • Diaphoretic, tremulous
  • Remind you of anything?

71
Benzodiazepines - History
  • Chlordiazepoxide (Librium)
  • First benzo, synthesized in 1955
  • Diazepam (Valium)
  • Marketed for seizures in 1963
  • Improvement on older sedative-hypnotics
  • Barbiturates, chloral hydrate, etc
  • Now gt 50 benzos on the market

72
Benzodiazepines
  • Mechanism of action
  • Bind to benzo receptor (part of GABAa-R)
  • Potentiates GABA effect on GABAa Cl- channel
  • Hyperpolarizes cell (?Cl- in)
  • Diminished ability to initiate action potential
  • CNS inhibitory effect

GABA-r
GABA
ZZZZ.
Cl-
Cl-
Cl-
Cl-
Cl-
BZ-r
Hyperpolarized
BZ
GABAa-R
Intracellular
Extracellular
73
Benzo Withdrawal - Basics
  • Risk related to duration/dose/t½
  • Need 4mo tx before W/D occurs
  • 1/3 of benzo users experience W/D
  • Lorazepam W/D more severe than diazepam
  • W/D can occur with change in benzo

74
Benzo Withdrawal - Symptoms
  • Symptom onset
  • 1-3d for short acting (loraz, alpraz)
  • ? severity, ? duration
  • 3-7d for long acting (diaz, clonaz)
  • May persist for weeks
  • Immediate with flumazenil use!

75
Benzo Withdrawal - Symptoms
  • Similar to EtOH W/D
  • ANS instability (tachycardia, diaphoresis)
  • Anxiety, insomnia, tremor, H/A, N, V
  • Severe
  • Disorientation, visual hallucinations, delirium,
    seizures

76
Benzo Withdrawal - Treatment
  • Best treatment for benzo W/D?
  • Reinstitution of long-acting benzo
  • Diazepam 5-10mg IV q5-10min prn
  • Outpt PO diazepam at dose to pts benzo
  • Gradual taper if discontinuation is desired
  • MD supervised
  • 6-8 weeks

77
Case 5
  • 20F found down, minimally responsive
  • Empty 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 flumazenil
  • Management?

78
Flumazenil
  • Competitive BZ receptor antagonist
  • Duration of action shorter than most benzos

79
Flumazenil
  • Few case reports of flumazenil-induced W/D,
    including seizures death
  • Haverkos et al. Ann Pharmacother 1994 281347
  • Spivey. Clin Ther 1992 14292
  • Whitwam et al. Acta Anaesh Scand
    Suppl 1995 1083
  • Severe withdrawal symptoms
  • Treat with phenobarbital
  • BOTTOM LINE Risks gtgtgt benefits

80
Benzodiazepine Withdrawal Summary
  • W/D less inhibitory GABA activity
  • Similar to EtOH W/D
  • Short acting benzo more severe W/D
  • Long acting benzo for management

81
Questions?
82
Case 6
  • 20F decreased LOC, found by boyfriend
  • O/E
  • Drousy, pinpoint pupils, hypoventilating
  • PMH ?
  • Normally takes a white pill an oval pill
  • Management?
  • You try naloxone
  • More alert and vomiting, tachycardic, diaphoretic
  • Diagnosis?

83
Naloxone
  • Competitive opioid antagonist
  • Onset 1-2min
  • Duration 20-90min
  • Hepatic metabolism
  • Can precipitate acute opioid withdrawal
  • Usually short-lived

84
(No Transcript)
85
Opioids
  • Medicinal value of opium - 1500 B.C.
  • Many formulations, essentially same drug
  • Laudanum, paregoric, Dover's powder, Godfrey's
    cordial, morphine
  • Analgesia, euphoria, anti-tussive
  • Terminology
  • Opiate derived from opium poppy
  • Opioid
  • Binds opioid receptor
  • Produces opioid-like effect

86
Opioid Withdrawal - Basics
  • Not usually life-threatening
  • Onset depends on t½
  • Heroin 4-6h
  • Methadone 24-48h
  • Duration
  • Days-weeks
  • Persistent weakness/insomnia/anxiety x 6m

87
Opioid Withdrawal - Pathophys
  • Many opioid receptors
  • Stimulation of some
  • Reduced CNS NE release (locus ceruleus)
  • Chronic opioid use
  • Excitability of neurons in the locus ceruleus
  • W/D of opioid
  • Noradrenergic hyperactivity

88
Opioid Withdrawal
  • Symptoms?
  • Psychological
  • Craving, dysphoria, anxiety, insomnia
  • Physiological
  • Tachycardia, tachypnea, HTN
  • Diaphoresis, lacrimation, rhinorrhea, myalgias,
    abdo pain, V, D
  • Dope sick

89
Opioid Withdrawal - Signs
  • Mydriasis, yawning, piloerection, increased bowel
    sounds
  • HR/RR/bp increase
  • Alert, oriented, afebrile

90
Opioid, Sed-hyp, or EtOH?
  • How do you tell the difference?

Opioid Sed-Hyp/EtOH
BP N/HTN (ohTN if volume depleted) N/HTN (ohTN if volume depleted)
HR TachyC TachyC
RR TachyP TachyP
Temp N N or ?
Mental status N/anxious N/abN
Physical signs/symptoms Yawning, lacrimation, rhinorrhea, mydriasis, tremor, piloerection, NVD, muscle pain/spasm, neonatal seizures Tremors, fasciculations, diaphoresis, seizures
Opioid Sed-Hyp/EtOH
BP
HR
RR
Temp
Mental status
Physical signs/symptoms
Goldfranks
91
Opioid Withdrawal - Management
  • R/O other causes of presentation
  • Supportive
  • IV fluids, K, anti-emetics
  • Evaluation for complications of IVDU
  • Endocarditis, AIDS-related illnesses, etc

92
Opioid Withdrawal - Management
  • Clonidine
  • Central presynaptic a2-receptor agonist
  • ? NE reuptake
  • Reduces noradrenergic activity
  • 0.1-0.2mg PO q4-6h prn (monitor bp)
  • BZ
  • If significant anxiety
  • Methadone 20mg PO
  • Synthetic opioid with long t½
  • Used in outpt programs, not our ED

Freitas. Am J Emerg Med 19853(5)456-60
93
Opioid Withdrawal
  • Goals/Disposition?
  • Temporary control of symptoms
  • Other disease ruled out
  • Referral to methadone program prn

94
Opioid Withdrawal - Summary
  • Narcan can precipitate acute opioid W/D
  • Sympt noradrenergic hyperactivity
  • Not usually life-threatening
  • Clonidine, symptomatic treatment

95
Questions?
96
Case 7
  • 23M, brought in by Mom, 2 day hx of
  • Increasing anxiety, some suidical thoughts
  • Fatigue, increased appetite/sleep
  • Myalgias, tremor
  • O/E
  • Vitals 85, 125/85, 365, 20, 96
  • AAO x 3, nothing remarkable on exam
  • Thoughts?

97
Cocaine
  • I am just now collecting the literature for a
    song of praise to this magical substance
  • -Sigmund Freud, 1884

98
Cocaine - Basics
  • Natural alkaloid found in Erythroxylon coca
  • Causes release of
  • Dopamine
  • Epinephrine
  • Norepinephrine
  • Serotonin
  • Na channel blocker
  • Blocks presynaptic NE reuptake

99
Cocaine Withdrawal - Symptoms
  • Psychological symptoms
  • Depression, anxiety, fatigue, difficulty
    concentrating, anhedonia, craving, increased
    appetite, increased sleep/dreaming, suicidal
    ideation
  • Physiological signs/symptoms
  • MSK pain, tremor, chills, involuntary motor
    movement, myocardial ischemia

100
  • N21 cocaine addicts in 28d inpt rehab
  • Holter and stress test admission/discharge
  • Results
  • 38 had silent STE
  • Only 1 pt had stress test
  • 3 agreed to cath ? all N
  • No MIs, no information on outcomes
  • Conclusion
  • Risk of vasospasm during withdrawal period
  • Likely reflects delayed vasospasm after cocaine
    use, not necessarily a withdrawal phenomenon

101
Cocaine Withdrawal - Management
  • Supportive
  • Lorazepam for insomnia/agitation
  • Admission rarely indicated
  • Referral to addiction treatment program
  • Resolves within 1-2 weeks without tx

102
Cocaine Withdrawal Take home
  • Prominent psychological features
  • Rarely medically serious
  • Treatment is supportive

103
Questions?
104
Post-test Q1
  • What percentage of hospitalized patients are
    ethanol dependent?
  • 5-10
  • 15-20
  • 30-40
  • gt40

105
Post-test Q2
  • What is the current mortality from alcohol
    withdrawal syndrome?
  • 5
  • 7
  • lt1
  • 10

106
Post-test Q3
  • Alcohol acts as a/an ______________ on the GABA
    receptor.
  • Indirect agonist
  • Direct agonist
  • Indirect antagonist
  • Direct antagonist

107
Post-test Q4
  • In alcohol withdrawal, wWhich of the following
    agents is best used in patients at risk for
    oversedation and those with liver disease?
  • Diazepam
  • Lorazepam
  • Phenytoin
  • Thiamine

108
Post-test Q5
  • Which of the following agents is best used for
    AWS if high doses of benzodiazepines are
    ineffective?
  • Carbamazepine
  • Phenytoin
  • Ethanol
  • Phenobarbital

109
Post-test Q6
  • Symptom-triggered therapy for alcohol withdrawal
    has been shown to reduce which of the following
    factors?
  • Amount of medication used
  • Duration of treatment
  • Both A and B
  • Neither A nor B

110
Post-test Q7
  • Neuroleptic agents
  • Effectively control autonomic instability
    associated with AWS
  • Control alcohol-induced seizures
  • Improve hyperthermia related to AWS
  • Reduce the seizure threshold

111
Post-test Q8
  • The use of phenytoin is indicated in which of the
    following situations?
  • A patient with AWS and non-alcohol-related
    seizures
  • A patient with an AWS
  • A patient with HTN and tachycardia related to AWS
  • An intoxicated patient with a history of AWS

112
Post-test Q9
  • The benzodiazepine of choice for treating
    benzodiazepine withdrawal is
  • Midazolam
  • Lorazepam
  • Diazepam
  • Alprazolam

113
Post-test Q10
  • ED management of opioid withdrawal consists
    primarily of
  • Benzodiazepines
  • ß-blockers
  • Supportive care
  • Methadone

114
Post-test Q11
  • Patients with acute cocaine withdrawal often
    require admission.
  • True
  • False

115
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