Download Withdrawal - Calgary Emergency Medicine

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?
A.
B.
C.
D.
5-10%
15-20%
30-40%
>40%
Pre-test Q2

What is the current mortality from
alcohol withdrawal syndrome?
A.
B.
C.
D.
5%
7%
<1%
10%
Pre-test Q3

Alcohol acts as a/an ______________ on
the GABA receptor.
A.
B.
C.
D.
Indirect agonist
Direct agonist
Indirect antagonist
Direct antagonist
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?
A.
B.
C.
D.
Diazepam
Lorazepam
Phenytoin
Thiamine
Pre-test Q5

Which of the following agents is best
used for AWS if high doses of
benzodiazepines are ineffective?
A.
B.
C.
D.
Carbamazepine
Phenytoin
Ethanol
Phenobarbital
Pre-test Q6

Symptom-triggered therapy in alcohol
withdrawal has been shown to reduce
which of the following factors?
A.
B.
C.
D.
Amount of medication used
Duration of treatment
Both A and B
Neither A nor B
Pre-test Q7

Neuroleptic agents:
A. Effectively control autonomic instability
associated with AWS
B. Control alcohol-induced seizures
C. Improve hyperthermia related to AWS
D. Reduce the seizure threshold
Pre-test Q8

The use of phenytoin is indicated in
which of the following situations?
A. A patient with AWS and non-alcohol-related
seizures
B. A patient with an AWS
C. A patient with HTN and tachycardia related
to AWS
D. An intoxicated patient with a history of AWS
Pre-test Q9

The benzodiazepine of choice for treating
benzodiazepine withdrawal is:
A)
B)
C)
D)
Midazolam
Lorazepam
Diazepam
Alprazolam
Pre-test Q10

ED management of opioid withdrawal
consists primarily of:
A)
B)
C)
D)
Benzodiazepines
β-blockers
Supportive care
Methadone
Pre-test Q11

Patients with acute cocaine withdrawal
often require admission.
True
False
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
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
Alcohol Withdrawal
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 1955;16:1.
Alcohol W/D - Epidemiology
22% of Americans >12y 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 2004;24:1578-85

Mortality <1%
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 NT’s is lost
 CNS excitation (tremor, sz, hallucination)
 ANS stimulation (HTN, sweating, hyperthermia, tachycardia)
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?
DDx

What else is on the ddx?
– Acute psychosis
– CNS infection
– Thyrotoxicosis
– Anticholinergic poisoning
– W/D from other sedative-hypnotics
Alcohol W/D - Signs/Symptoms

Do you need to stop EtOH consumption to
get EtOH W/D?

When do signs of W/D begin?
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

Alcohol W/D - Classification

How do you classify EtOH W/D?

4 stages:
1)
2)
3)
4)


Tremulousness (6-12h)
Hallucinations (12-48h)
Seizures (12-48h)
DT’s (>48h)
Minor  Major  DT’s
Timing & severity
– early/late & complicated/uncomplicated
Alcohol W/D - Classification

Minor  Major  DT’s

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
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
Alcohol Withdrawal - Diagnosis

DSM-IV diagnostic criteria
Alcohol Withdrawal with Delirium (‘DT’s’)
– Also includes decreased consciousness,
change in cognition, perceptual disturbance
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 DT’s.
What else is on the ddx?
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
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!

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?
Alcohol Withdrawal - Ix





C/S
CBC, lytes, BUN, Cr, LFT’s, lipase, INR, EtOH
U/A
CXR
ECG




±VBG
±CT head
±LP
±Tox screen
Case 2
Labs sent
 ECG – tachycardia
 CXR pending
 C/S – 2.9


What would you like to do now?
Case 2 - Tx

Initial Stabilization
– ABCs
– NGT
– ±Restraints

What about giving glucose before
thiamine?
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 Wernicke’s encephalopathy is
unfounded/unproven. It is accepted that it takes hoursdays for this to occur, and so thiamine given within a
reasonable time of glucose administration (minuteshours) is acceptable.”
Wernicke-Korsakoff Syndrome

Case reports
– WK syndrome after prolonged IV glucose
administration

BOTTOM LINE
– Don’t delay glucose for thiamine
Waton et al. Ir J Med Sci 1981 Oct;150(10):301-3
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
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
Alcohol Withdrawal - Tx
>150 drug combinations
 Benzos are mainstay

– Interact with GABAa-receptor
– Substitute for removal of EtOH as a GABAa-agonist
GABA-r
GABA
Cl-
BZ-r
Cl-
Hyperpolarized
BZ
Extracellular
GABAa-R
Intracellular
ZZZZ….
Alcohol Withdrawal - Tx
>150 drug combinations
 Benzos are mainstay

– Interact with GABAa-receptor
– Substitute for removal of EtOH as a GABAa-agonist
– Reduce DT’s, mortality, duration of W/D
 N=574, randomized pts to benzo, antipsychotic,
antihistamine, thiamine
– Benzo had lowest risk of DT’s and alcohol W/D sz
– Antipsychotic 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 - 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)
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 1997;278:1-24
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, <5min to complete
Br J Addict 1989;84:1353-1357
Alcohol Withdrawal - Benzos

3 prospective RCT’s supporting symptomtriggered dosing
– ↓Total amount of medication
– ↓Duration of treatment
– ?↓DT’s
– Eg:
 Oxazepam 37.5mg vs 231.4mg
 Duration of treatment 20h vs 63h
Manikant et al, Indian J Med Res 1993;98:170-3
Saitz et al, JAMA 1994;272:519-23
Daeppen et al, Arch Int Med 2002;162:1117-21
Alcohol Withdrawal - Benzos

Typically sufficient for prevention of
alcohol withdrawal seizures (AWS)

What next if benzo’s not really working?
– More benzos?
– Phenobarb?
– Propofol?
– Haldol?
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 1997;278:1-24
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 (95%CI 1.2-34.7)

No good studies looking at atypicals
Mayo-Smith et al, Arch Intern Med 2004;164:1405-12
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!
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 2008;64(1):99-104
Case 2 cont…
DT’s
 Despite benzo tx

– HTN, tachycardia

Any other agents that might help here?
Alcohol Withdrawal – Adjuncts

β-adrenergic antagonists
– Adjunctive in mild/moderate W/D with HTN/tachyC
(Grade C)
– Can decrease the need for benzos
 Decreased tremor, agitation, anxiety
– BUT…can 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 1980;4:400-5
– Not recommended unless other tx fail – Goldfrank’s
***Potentially can use them in pts with cardiac history,
but beware if ?sympathomimmetic on board***
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
Alcohol Withdrawal – Adjuncts

Thiamine 100mg IV
– Before/after glucose – doesn’t matter

Mg 2-5g IV
– May ↑ rate of AST ↓
 Poikolainen & Alho. Subst Abuse Treat Prev Policy 2008;3(1):1
– No effect on severity of W/D or incidence of W/D seizures
 Wilson & Vulcano. Alcohol Clin Exp Res 1984;8:542-5
– No evidence of benefit, give it anyway

Multivitamins
– “magic yellow water”…makes everyone feel better

±K+ replacement
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. 2004;69(6):1443-50
Alcohol Withdrawal – Outpt Tx

Outpatient vs inpatient detox for mild-moderate W/D
– N=87 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 9;320(6):358-65
Renfrew

40-bed recovery centre, free
– Usually 36 clients

No appointment necessary 9am-4pm
– Show up at 8:15am
– 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 IV’s, 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, gov’t funding through AADAC
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 Dilantin…thoughts?
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
Alcohol Withdrawal Seizures (AWS)
“Rum Fits”
Most occur within 24h of decreasing EtOH
 5% of pts with AWS’s progress to DT’s 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 1991;9:57
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 1989;87:645-8
– Chance. Ann Emerg Med 1991;20:520-2
– Rathlev et al. Ann Emerg Med 1994;23:513-8

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%20Clinical%20Practice%20Guideline.pdf
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?)
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 1988;38:1561
Case 3c
Pt post-ictal on initial assessment
 5 min later RN tells you he’s having
another seizure

Thoughts?
 Plan?
 Dilantin?

– Still indicated for alcohol-related status
epilepticus (Grade C recommendation)
 ASAM CPG
Alcohol Withdrawal – Take-home

EtOH W/D is a common ED presentation

CNS/ANS excitation

Sympt 6h, sz 12-24h, DT’s 72h

Benzo’s, benzo’s, benzo’s….

Status is status – tx the same
Questions?
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?
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 > 50 benzos on the market
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
Cl-
BZ-r
Cl-
Hyperpolarized
BZ
Extracellular
GABAa-R
Intracellular
ZZZZ….
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

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!
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
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
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?
Flumazenil
Competitive BZ receptor antagonist
 Duration of action shorter than most
benzos

Flumazenil

Few case reports of flumazenil-induced
W/D, including seizures & death
– Haverkos et al. Ann Pharmacother 1994; 28:1347
– Spivey. Clin Ther 1992; 14:292
– Whitwam et al. Acta Anaesh Scand Suppl 1995; 108:3

Severe withdrawal symptoms
– Treat with phenobarbital

BOTTOM LINE: Risks >>> benefits
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
Questions?
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?
Naloxone
Competitive opioid antagonist
 Onset 1-2min
 Duration 20-90min
 Hepatic metabolism
 Can precipitate acute opioid withdrawal

– Usually short-lived
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
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
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
Opioid Withdrawal

Symptoms?

Psychological
– Craving, dysphoria, anxiety, insomnia

Physiological
– Tachycardia, tachypnea, HTN
– Diaphoresis, lacrimation, rhinorrhea, myalgias,
abdo pain, V, D
– “Dope sick”
Opioid Withdrawal - Signs
Mydriasis, yawning, piloerection, increased
bowel sounds
 ±HR/RR/bp increase


Alert, oriented, afebrile
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
HR
RR
RR
TachyC
TachyC
TachyP
TachyP
Temp
Temp
Mental status
status
Mental
N
N or ↑
N/anxious
N/abN
Yawning, lacrimation,
rhinorrhea, mydriasis,
tremor, piloerection,
NVD, muscle
pain/spasm, neonatal
seizures
Tremors,
fasciculations,
diaphoresis, seizures
Physical
Physical
signs/symptoms
signs/symptoms
Goldfrank’s
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
Opioid Withdrawal - Management

Clonidine
– Central presynaptic α2-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 1985;3(5):456-60
Opioid Withdrawal

Goals/Disposition?
Temporary control of symptoms
 Other disease ruled out
 Referral to methadone program prn

Opioid Withdrawal - Summary

Narcan can precipitate acute opioid W/D

Sympt = noradrenergic hyperactivity

Not usually life-threatening

Clonidine, symptomatic treatment
Questions?
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?
Cocaine

“I am just now collecting the literature for
a song of praise to this magical substance”
-Sigmund Freud, 1884
Cocaine - Basics

Natural alkaloid found in Erythroxylon coca

Causes release of
–
–
–
–
Dopamine
Epinephrine
Norepinephrine
Serotonin
Na+ channel blocker
 Blocks presynaptic NE reuptake

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



N=21 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 MI’s, no information on outcomes
Conclusion
– Risk of vasospasm during withdrawal period

Likely reflects delayed vasospasm after cocaine
use, not necessarily a ‘withdrawal’ phenomenon
Cocaine Withdrawal - Management
Supportive
 ±Lorazepam for insomnia/agitation

Admission rarely indicated
 Referral to addiction treatment program


Resolves within 1-2 weeks without tx
Cocaine Withdrawal – Take home

Prominent psychological features

Rarely medically serious

Treatment is supportive
Questions?
Post-test Q1

What percentage of hospitalized patients
are ethanol dependent?
A.
B.
C.
D.
5-10%
15-20%
30-40%
>40%
Post-test Q2

What is the current mortality from
alcohol withdrawal syndrome?
A.
B.
C.
D.
5%
7%
<1%
10%
Post-test Q3

Alcohol acts as a/an ______________ on
the GABA receptor.
A.
B.
C.
D.
Indirect agonist
Direct agonist
Indirect antagonist
Direct antagonist
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?
A.
B.
C.
D.
Diazepam
Lorazepam
Phenytoin
Thiamine
Post-test Q5

Which of the following agents is best
used for AWS if high doses of
benzodiazepines are ineffective?
A.
B.
C.
D.
Carbamazepine
Phenytoin
Ethanol
Phenobarbital
Post-test Q6

Symptom-triggered therapy for alcohol
withdrawal has been shown to reduce
which of the following factors?
A.
B.
C.
D.
Amount of medication used
Duration of treatment
Both A and B
Neither A nor B
Post-test Q7

Neuroleptic agents:
A. Effectively control autonomic instability
associated with AWS
B. Control alcohol-induced seizures
C. Improve hyperthermia related to AWS
D. Reduce the seizure threshold
Post-test Q8

The use of phenytoin is indicated in
which of the following situations?
A. A patient with AWS and non-alcohol-related
seizures
B. A patient with an AWS
C. A patient with HTN and tachycardia related
to AWS
D. An intoxicated patient with a history of AWS
Post-test Q9

The benzodiazepine of choice for treating
benzodiazepine withdrawal is:
A)
B)
C)
D)
Midazolam
Lorazepam
Diazepam
Alprazolam
Post-test Q10

ED management of opioid withdrawal
consists primarily of:
A)
B)
C)
D)
Benzodiazepines
β-blockers
Supportive care
Methadone
Post-test Q11

Patients with acute cocaine withdrawal
often require admission.
True
False
The end