Toxic Withdrawals - Calgary Emergency Medicine

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Transcript Toxic Withdrawals - Calgary Emergency Medicine

•Toxic Withdrawals
Jennifer Nicol PGY-1
Dr. Yael Moussadji
May 27th, 2010
• Will cover withdrawal from:
– Alcohol
– Opioids
– Benzodiazepines
– Cocaine
The Facts: addiction and withdrawal
• Emergency physicians must recognize and
treat many phases of substance abuse
• 80% Canadians drink alcohol
– Majority moderation without harm
– 17% high risk drinking
• 2002: Cost of illicit drugs, tobacco, and alcohol
– Canada $40 billion
– Alberta $4.4 billion
Principles of Withdrawal
• Every withdrawal syndrome has two
– pre-existing adaptation to a drug, the continuous
presence of which prevents withdrawal
– decreasing concentrations of that drug
Principles of Withdrawal
• Withdrawal syndromes that fulfil both criteria
are treated by re-administration followed by
weaning of drug
– Opiates, benzodiazepines, alcohol
• Withdrawals that fulfil only first criteria are
treated by supportive measures only
– I.e. cocaine, marijuana
DSM-IV: withdrawal
• Withdrawal is manifested by either of the
– a characteristic withdrawal syndrome for the
– the same (or a closely related) substance is taken
to relieve withdrawal symptoms.
• 56 yo F chronic alcoholic
• Stopped drinking 3 days prior. Now feels
tremulous, nauseous, disoriented,
• Has had numerous falls in the past 3 days,
can’t use her right hand
• Thoughts?
Case (con’t)
• PMHx:
– alcohol withdrawal seizures, DT
– CAD, HTN, Afib, COPD
– ICU admission 2 months ago for DTs
• NSTEMI during admission
• Meds:
– ASA, tinzaparin, metoprolol, trazadone, advair,
• Do you have any concerns?
Alcohol Withdrawal Syndrome (AWS)
• 15-20% inpatients and ED patients are alcohol
• Many present with unrelated problems
– Trauma
– Infections / sepsis
– Pancreatitis, renal failure
– ACS, stroke
Historical Perspective
• Alcohol has depressant effect on CNS
• Effects of alcohol dependency and tolerance
mediated primarily through 2 receptor
• Withdrawal characterised by CNS excitation
• EtOH inhibits excitatory neurotransmitter
glutamate function at NMDA
• chronic EtOH use – upregulation of NMDA
• When EtOH withdrawn, increased NMDA
receptor activity
Clinical Presentation
• “The patient is restless and agitated, requiring
restraints… conversation being garbled and
unintelligible. Autonomic over-activity is
manifested by dilated pupils, tachycardia, and
an elevated temperature, attributable
occasionally to no other cause other than
– Victor and Adams 1953
I swear, I only
had one drink
2 nights ago.
Clinical Presentation
• Three sets of symptoms:
– Autonomic hyperactivity
• Tremor, hypertension, hyperthermia, hyper-reflexia
• Sleep disturbances, diaphoresis, nausea, vomiting,
– Neuronal excitation
• Alcohol withdrawal seizures
– DT’s
• Extreme end of AWS spectrum
• Profound confusion, delirium, hallucinations
• Hyperadrenergic state
Clinical Presentation
• Symptoms develop 6-12 hrs after reduction of
EtOH intake.
• Spectrum of withdrawal:
– Mild
– Moderate
– Delirium tremens
• Duration of withdrawal up to 7 days
Clinical Presentation - Classification
• Minor
– Early onset 6hrs, peak 24-48 hrs
– Mild autonomic hyperactivity: nausea, anorexia,
coarse tremor, hypertension, tachycardia, sleep
• Major
– Later onset 24 hrs, peak 50hrs-5days
– Tremor, fever, irritation, ++anxiety, insomnia, anorexia,
hypertension, tachycardia
– Decreased seizure threshold, hallucinations, hyperreflexia
Clinical Presentation - Classification
• Delirium Tremens
– Serious complication of, not synonymous with
– 5-10% pts admitted for alcohol WD
– Appears day 3-5 post abstinence (rarely before)
– Lasts 5-10 days, up to 2 weeks
– Main concern is recognition and early
Delirium Tremens
DeBellis et al. J Intens Care Med.2005;20:164
DT: Risk Factors
Tachycardia at admission
WD signs with BAL >0.16 mmol/l (1g/L)
Infectious process
History of withdrawal seizures
History of delirious episodes associated with
DeBellis et al. J Intens Care Med.2005;20:164
DT: Mortality
• 5-15% mortality rate
– Secondary to complications
• RF’s for Mortality
– Khan et al. Acad emerg Med. 2008;15:787
– Risk factors:
• Physical Restraints
• Hyperthermia
– Protective:
• Use of clonidine
• Diagnosis in ED
DeBellis et al. J Intens Care Med.2005;20:164
Back to the case
• VS: HR130, BP160/90, temp37.6, RR18, SaO2
96 2LNP
• On exam:
– Confused but oriented, agitated, PERL, tremulous
– Large bruise right arm and face
– Think she can’t extend right wrist but can’t be
sure – she is so tremulous
• What other conditions do you want to rule
AWD – Differential Considerations
Wren et al. Amer J Emerg Med. 1991;9(1):57
Differential Considerations
CNS: encephalitis, meningitis, IC bleed
Infectious: Numerous sources.
GI: hepatic encephalopathy
– Toxidromes: anticholinergic, stimulant
– WD: Sedative hypnotics (opiates, benzos, barbituates)
– Contemporary alcoholic often polydrug users
• Metabolic: thyrotoxicosis, hypoglycemia
• Psychiatric: drug induced psychosis,
Physical Exam
Level of consciousness
Signs hepatic failure
Signs of focal infection
Complete neuro exam
Pupils, occulomotor function
Gait if possible, coordination
CBC, lytes, LFT’s, lipase, coags, BUN, Cr, BG
EtOH +/- toxic EtOH
Blood Cultures
Urinalysis, urine culture
• Consider
– LP, CT head, VBG, tox screen
• Look at your anion & osmolar gaps
Diagnosis of Alcohol Withdrawal
Cessation or reduction of alcohol use that has been heavy and prolonged
Two or more of the following, developing within several hours to a few
days after criterion A:
autonomic hyperactivity (sweating, HR>100/min)
Increased hand tremor
Nausea or vomiting
Transient visual, tactile, or auditory hallucinations or illusions
Psychomotor agitation
grand mal seizures
The symptoms in criterion B cause clinically significant distress or
impairment in social, occupational, or other important areas of
The symptoms are not sue to a general medical condition and are not
better accounted for by another mental disorder.
Return to Case
Hbg 107, WBC 7.4, plt 174
Na 113! K 2.6, Mg 0.47, PO4 0.5
Urinalysis: +nitrates, WBC, RBC
CT head: nil acute
Management Principles
• 4 principles of treatment
1) Evaluate for concurrent illness
2) Restore inhibitory tone to CNS
3) Identify and correct electrolyte & fluid
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
Pharmacologic Intervention
• Ideal drug profile for EtOH withdrawal:
– Rapid onset
– Wide margin safety
– Minimal hepatic metabolism
– Limited abuse potential
– (Cost effective)
• High doses, infusions
Pharmacologic Intervention
• >150 drugs have been used in the last 30 years
to treat alcohol withdrawal
• Benzodiazepines are the mainstay of current
– Potentiate the effects of GABA
– Restore the inhibitory tone
Mechanism of BZD in Alcohol WD
• GABAα downregulated
• Loss of chronic
inhibition from EtOH
• Benzos restores
inhibitory tone provided
by EtOH
Pharmacotherapy - BZD
• Numerous prospective trials demonstrating
benzos more effective than placebo in decreasing
signs and sx of WD
– Bowman et al. Dis Nerv Syst. 1966;27:342
– Sellers et al. J Stud Alcohol. 1977;3:575
– Adinoff et al. Alcohol Clin Exp Res. 1995;18:873
• Also beneficial over placebo in decreasing
incidence of Sz and delirium
– Mayo-Smith, JAMA 1997 278(2):144
• meta analysis 5 pRCTs
Choice of Benzo
• When considering which benzo to initiate,
need to consider:
– Route of administration
– Hepatic function
– Half life
– Formulary status
– Regime
• Symptom triggered vs. Fixed scheduled
Benzo profiles
Choice of Benzo
• No significant difference has been shown
between benzos in reducing Sx/signs of WD
• Generally:
– Long acting:
• smoother WD course with fewer rebound and
breakthrough WD.
• Better seizure prevention
– Rapid onset:
• control agitation more quickly
– Diazepam: long acting and rapid acting
• Not on ED formulary
Mayo-Smith. Arch int Med. 2004 164:1405
Choice of Benzo
• No significant difference has been shown
between benzos in reducing Sx/signs of WD
• However, long acting can result in increased
– Elderly, hepatic failure
– Lorazepam: no active metabolites, shorter t½
Benzo Dosing
Diazepam 5-10mg IV q5-10 min
Lorazepam 2-4 mg IV q15-20min
May require massive doses - >2000mg/48hrs
Titrate to desired balance between
agitation/withdrawal and level of
consciousness (don’t want to intubate the
– “light somnolence”
Benzos – Dosing regime
• Fixed dose regime
– Give set amount of medication at regular intervals
– Breakthrough doses for WD symptoms
– Taper at end of therapy (ie day7)
• Loading Dose
– Give initial large dose of long acting medication, which
is decreased through metabolism
– Not commonly used
• Symptom Triggered dosing
– Quantify symptoms of WD and dose accordingly
Symptom Triggered
• Monitored by a structured assessment scale
• Given medication only when crosses threshold of
• Dappen Arch Int Med. 2002;162:1117
– N=117, comparing Sx triggered to fixed dosing
– Six fold decrease in amount benzo required (37.5mg
vs. 231.4mg)
– Shorter duration of therapy (20 vs. 62.7 hrs)
• Jaegger et al. Mayo Clinic Proceedings 2001;76
– No change in duration of stay
– Decreased DT
Kosten et al. NEJM 348;18: 1786
• Doctor, your patient has received 250 mg IV
benzos, and now has significant abrasions
from his 4 point restraints
• Failure of benzo to control symptoms and
signs of WD?
• What are you going to do now?
Resistant Alcohol Withdrawal
• Subgroup who require very large doses of benzos
to achieve sedation
• ICU admission for close monitoring, +/intubation
– Symptom triggered vs. fixed dosing vs. benzo infusion
– Spies CD et al. Intensive Care Med. 2003;29:2230
• Second line GABAergic drug
• Barbituates
• Propofol
• Good alternative for WD resistant to BZD
• Directly open GABA ion channels
– Usually do not fail to manage AW symptoms
• PRO:
– Low abuse potential
– Long acting
– Increased respiratory depression
– Lower safety profile in larger doses
Young et al. Ann Emerg Med.1987;16:847-850
Yeh et al. J Gen Intern Med. 1992;7:123
• Phenobarbital
Long acting (t½ 80-100hrs)
Difficult to titrate to sedation vs loss of consciousness
260mg IV over 5min
Repeat at 30 min 130mg over 3min until desired effect
• Pentobarbital
– Short acting
– 3-5mg/kg IV bolus followed by 100mg/hr infusion
• GABAα agonist & NMDA antagonist
• Rapid onset, short t½
• S/E: hypotension, bradycardia, respiratory
– More rigorous monitoring than BZD
• ICU setting for refractory WD or DT
– McCowan et la. Crit Care Med. 2000;28:17811784
• Dose 0.3-1.25mg/kg
Adjuncts to Alcohol Withdrawal
• To be used IN CONJUNCTION with BZD
• Neuroleptics
• Adrenergic blockade
– Beta blockers
– Alpha-1 blockade
• Carbamazepine
• Magic Vitamins!
Adjuncts - Neuroleptics
• Increase seizure compared to placebo
– 4 pRCTs
– Lower seizure threshold
– Impair temperature regulation
• Sedative hypnotics better at preventing
seizures and decreasing mortality
• Useful in agitated / hallucinating patient in
concert with BZD
• Not safe or useful as monotherapy
Mayo-Smith. Arch int Med. 2004 164:1405
Adjuncts – Adrenergic blockade
• Beta blockers
– Decrease WD symptoms
– No evidence for an increase, decrease or no effect
on WD seizures
– Precipitate delirium
– Use only in persistent hypertension, tachycardia
• Alpha adrenergic blockers
– Clonidine decreases WD symptoms
– No evidence on seizure effect
Adjuncts – Carbamazepine
• Used widely in Europe
• Antikindling, GABA agonist
• Superior to placebo, equal to oxazepam and
barbital in mild to moderate WD
– Bjorkquist et al. Acta Psychiatr Scanf. 1976;53:333
– Malcom et al. Am J Psychiatry. 1989;146:617
• Limited evidence for treating seizures or
• Not recommended for routine use in AW
Adjuncts – The Vits!
• Thiamine and glucose
– Alcoholics are malnourished with deplete
thiamine stores
– WD pts often left NPO in ED for airway concerns
• Hepatic failure – low glycogen stores
• Hypoglycemia as ddx for seizure
• Wernicke-Korsokoff syndrome
Wernicke-Korsokoff syndrome
• WE: Acute life threatening neurologic disorder
– Encephalopathy
– Occulomotor dysfunction
– Gait ataxia
• Korsokoff: Chronic neuropsychiatric
manifestation of WE
– Anterograde and retrograde amnesia
– Confabulate, long term memory intact
Wernicke-Korsokoff syndrome
• The real deal on thiamine & glucose
– Case reports showing WE after glucose infusions
• Koguchi et al. Neurology. 2004;62:512
• Watson et al. Ir J Med Sci. 1981;150:301-303.
• Drenick EJ et al. NEJM. 1966;274:937-939.
– Signs WE present before administration of glucose
– Prolonged parenteral dextrose
• “The evidence supports neither the need to
precede glucose administration with thiamine.
The established biochemical link between the 2
substances reminds clinicians that their
contemporaneous administration is desirable. It
is our experience that if the first provider fails to
give parenteral thiamine at the time of glucose
administration, thiamine is often forgotten. We
cannot advocate any delay in glucose delivery
while awaiting thiamine administration.”
1998; Hack & Hoffman New York City Poison Control Center
Adjuncts – The Vits!
• Magnesium
– Alcoholics are magnesium deplete
• Normal on admission, decreased during WD,
spontaneously revert to normal after WD
– No difference in severity or duration of WD
• Wilson et al. Alcohol Clin Exp Res. 1984;8:452
– No evidence to support use, but if really low
replace it
Adjuncts – just get drunk again
• Ethyl Alcohol
– Medicine used by alcoholics everywhere to
prevent and treat their withdrawals at home
– Toxicity, increased monitoring
– Conflicting evidence
– No role for ED management of AWS
Case Conclusion
• Your patient is admitted to Teams. Becomes
very delirious during admission, but is
managed with +++ lorazepam and some
haldol, on CIWA.
• Lytes and UTI are treated.
• When delirium clears she is diagnosed with
Erb’s palsey
• Referred to Foothills addiction program,
motivated for change.
• 64 year old first nations man arrived by EMS
following a witnessed ground level fall.
– ? Shaking activity ?
– homeless alcoholic, new in town from Hobbema
• Brought to ER by EMS
• Confused, disoriented, can’t tell you what
• Unkept, malodorous, incontinent of urine.
• 2 cm lac above L eye, GCS 12, not much else
on exam
• STAT labs: hbg 120, WBC 15, EtOH 12
• He is given ativan 2mg IV, thiamine, glucose
• You send your medical student to suture his
lac before his CT head.
– Just as she is finishing, pt defecates, rubs it all over
his body, and seizes.
Alcohol Related Seizures
• 8% AW complicated by seizures
• One third seizure related admissions are
secondary to alcohol
• Alcohol causative factor in 11-24% pts with
status epilepticus
• 90% occur within 48hrs of abstinence
• Recurrence risk during same WD episode is
Differential Considerations... Again
• Large DDx to think about:
Exacerbation idiopathic/post traumatic seizure
Acute intoxication – you name it, it does it
Metabolic: hypo-glc,Na,Ca; hyperNa, severe
CNS infections
Sleep deprivation
Non-compliance with anticonvulsants
Rosens 7th Ed.
AW Seizures
EFNS task force. European Journal of Neurology 2005;12:575–581
AWSz: Classification
• Alcohol withdrawal syndrome and:
– No seizure history
– Positive seizure history – not alcohol related
• May be on an antiepileptic for reason pt does not
remember or know!
– History of withdrawal seizures
– Other possible etiologies of seizure (infection,
trauma, etc)
– Alcohol related status epilepticus
ASAM Clinical Practice Guideline
Dilantin Dilemma
• Placebo controlled trials
• No difference in seizure rates between placebo and
• N=90 Alldredge et al. AM J Med 1989;87:645-8
• N=55 Chance. Ann Emerg Med 1991;20:520-2
• N=100 Rathlev et al. Ann Emerg Med 1994;23:513-8
• Comparison study
• No seizures in either arm
• N=200 Rothstein. Am J Psychiatry. 1973;130:1381
Dilantin – when to use
• Yes, go ahead
– Alcohol withdrawal
syndrome and a known
history of seizure
disorder unrelated to
• Grade C recommendation
Kasser, CC. ASAM Clinical Practice Guidelines
Dilantin – when to use
• Have a think about it
– Acute AW syndrome +
history alcohol WD seizures
– AW syndrome other
possible causative factors
for seizure (meningitis, CNS
• Grade C Recommendation
Kasser, CC. ASAM Clinical Practice Guidelines
Dilantin – when to use
• Nope, don’t do it!
– AW and no AW Seizure Hx
(Prophylaxis for AW
• Grade A recommendation
– Isolated AW seizures
• Grade C recommendation
Kasser, CC. ASAM Clinical Practice Guidelines
Dilantin Dilemma
• In context of alcohol
withdrawal, best
strategy is seizure
prevention with benzos
• Administer in context of
known seizure disorder
What if... In context of Alcohol WD
Seizure is focal
New onset alcohol related seizure
Abnormal neurological deficits
Pt is obtunded
• These patients warrant a workup
Alcohol Withdrawal – Disposition
Alcohol Withdrawal – Disposition
• Minor withdrawal:
– Usually safe to discharge home
– “follow up” and referral
• Major withdrawal:
– admit, usually to MTU, hospitalist
• Delirium Tremens, resistant withdrawal
– Consider ICU for monitoring, sedation
Disposition – Minor WD
• Inpatient Detox:
– Supervised WD, brief length of stay
– Free standing treatment centre vs hospital
• Outpatient
– Hayashida et al. NEJM 1989;320:358-65.
– Safe, efficacious method of detox
– Significantly less expensive, no difference at six
months of follow up
– Don’t have this option in Calgary
• Other resources: ADAC
Disposition – Alcohol Related Seizures
• Return to baseline LOC, no focal neurological
deficits, imaging and other cause for Sz ruled
– d/c home after 4-6 hours observation
– “appropriate” follow up
• Persistently altered LOC, focal neurological
concerns, co-morbid medical
– Admit for observation and further workup
Calgary Resources
• Alpha house
– Shelter, detox, outreach (DOAP team, CUPS)
• Renfrew House
– Detox 40 bed unit.
– Intake daily at 8:45, first come first serve basis
• AADAC Youth Services
– Inpatient detox, family counselling, 3 month
residential treatment program
– Drop in counselling sessions
• Shelters:
– DI, Mustard Seed, YWCA, Mary Dover
• 32 yo male presents in crisis
• 2 days ago stole his dealers car in East Van
then crashed it.
• Took a bus out West back home.
• No family or friends will take him in.
• Last heroin the night before. He is tremulous,
diaphoretic, and threatening to defecate on
the bed in front of you.
Opiate withdrawal
“The anal clenching misadventure”
• Opioid: natural, synthetic, semi synthetic
materials with morphine like action.
• Opiate: Natural agents only
• Opium: Greek for poppy juice
• Narcotic: any agent that induces sleep
• Endorphins: endogenous opioids
– Enkephalins, beta-endorphins, dynorphins
• 3 main types of endorphin receptors
– Mu, kappa, delta
– CNS: pain pathways, areas associated with pain
– Systemic: sensory nerve cell endings, mast cells,
GI tract
• Effect is inhibitory
Goldfrank’s 8th ed.
• Early (4-6 hrs)
– Restlessness, yawning
– insomnia,
• Delayed (36-72 hrs)
– nausea/vomiting, diarrhea, abdominal cramps
• Second stage:
– Persistent weakness, insomnia, anxiousness
– Can last up to 6 months
• Lacrimation, rhinorrhea, perspiration
• Piloerection, mydriasis
• +/- hypertension, hyperthermia, tachypnea,
• No seizures
• Normal mental status throughout
– Offensive +/- violent behaviour
Kosten et al. NEJM 348;18: 1786
Control nausea and vomiting
Correct volume status
Rule out other causes accounting for
• Look for pathology associated with IVDU
– IE, abscesses, HCV/HIV and their complications
α2 adrenergic agonist
• Inhibitory in CNS:
• decreases sympathetic activity
• Overall effect: depression CNS function, sedation,
bradycardia, general sedation
• Side Effects:
– Hypotension
– Dry mouth, lethargy, sedation
– Worse with EtOH
The Cochrane Library 2009;3
Freitas et al. Amer J Emerg Med. 1985;3:456
Kosten et al. NEJM 348;18: 1786
α2 adrenergic adrenergic agonist
• Inhibitory in CNS:
• decreases sympathetic activity
• Overall effect: depression CNS function, sedation,
bradycardia, general sedation
• Caution in patients with severe CAD, CVD,
chronic renal failure, concurrent alcoholics.
The Cochrane Library 2009;3
Freitas et al. Amer J Emerg Med. 1985;3:456
Kosten et al. NEJM 348;18: 1786
• 0.1-0.2mg q4h x 10 days
– Taper 0.2 mg/day starting at day 3
– Abrupt cessation:
• rebound WD, headache
• No rebound hypertension
• Can be initiated in ED
Kosten et al. NEJM 348;18: 1786
Opiate regimes
Not initiated in the ED
Outpatient detox and addiction services
• 36 yo M found down in industrial park.
• Brought in by EMS after call from unidentified
• PMHx: (SCM)
– Known seizure disorder, takes dilantin
– Last ED visit one month earlier for seizure.
– Chronic back pain
• Netcare: recently filled Rx for oxycodone
Case: On exam
GCS 8 (E2 V2 M4)
Protecting airway, hypoventilating
Pinpoint pupils
Nothing else of note
He receives 0.5mg naloxone
A few minutes later...
• He turns into gorilla
• Becomes nauseous,
with gooseflesh, pupils
• Still confused, agitated.
• Quick! Get that man
some morphine!!
Later on that day
• He rouses enough to tell you that he had a
• His back was also really sore that day so he
took extra “pain killers”
• Dilantin level undetectable.
Opioid antagonist
Rapid onset: 1-2min
Half life 1.1 hours
Overshoot dosing can precipitate acute
– Manage conservatively
– Do not administer additional opioids – will outlast
effect of naloxone
• 32 yo F brought in by CPS. Found lying passed
out on a park bench
• You try to take a history but she keeps falling
asleep half way through her sentences.
• She does manage to tell you something about
a “wild few days...”
• Plant derived alkaloid
– Coca plant used for centuries in South America for
medicinal purposes
– Cocaine used for over 100 years as recreational
drug by in North America and Europe
• Acute cocaine use causes release of and
inhibits reuptake of:
– Dopamine
– Seratonin
– Norepinephrine
– Epinephrine
• Sodium channel blocker
How to cook yourself on Coke
• Snort, smash, eat, shoot, muscle, smoke,
“Cocaine Crash: The Washout”
• Hx:
– Hypoactivity: Lethargy, exhaustion, decreased
– Increased appetite, vivid, unpleasant dreams
• Px:
– Vital signs usually relatively normal. No
hypotension, bradycardia, depressed respiration
– Psychomotor retardation
– Again, look for signs of IVDU and sequelae
• Underlying pathology
– Diagnosis of exclusion if presenting with ALOC
– High index of suspicion for infection, metabolic
• Myocardial ischemia
Myocardial ischemia
• Koonlowee N et al Annals int med.
– N = 21 consecutive male patients admitted to
outpatient treatment facility
– All received 24 hr holter and treadmill soon after
– Holter monitor: 38% spontaneous episodes
ischemia (2% control)
– 1 had ischemia on stress test
Back to Case
• Px: HR90, BP100/60, RR12 T37.7, SaO2 98RA
– Grimaces during abdo exam
– Tender legs and arms to palpation
– PERL 3mm, no neuro deficits
• WBC 13, nil else
• Want a urine sample, but she won’t pee.
• Near the end of your shift, tidying up for
– Finally get fed up, do in&out.
– ++nitrates, WBC, RBC
• She starts to rouse, tells you her right back hurts
– Temp 38, HR 100(after tot 2L NS)
– Right CVA tenderness
– Ando us: shows obstructing right sided
nephrolithiasis. Transfer to RGH for management of
infected stone.
Cocaine WD: Management
• Mainly supportive
– Most regain normal LOC and are safe for d/c several hours
after admission.
• Symptoms resolve spontaneously
– Washout: 25-40 hrs
– All within 1-2 weeks
• Anxiety
– Short Rx benzo
• Rarely need admit, unless underlying condition
• Refer to treatment program
• 65 yo M presents with SOB, cough, edema
• Been feeling unwell for past 2 weeks
• 10 lbs weight gain, increasing exertional
dyspnea, cough
• Feeling very anxious, had several panic attacks
in the past few days
• PMHx:
– CHF: last ECHO 2009 EF<30%
– HTN, obesity, DMII, OSA, EtOH use
– CAD: ACS x 2 2008, 2009 with cath
– Generalised Anxiety Disorder
• Lorazepam 6 mg q4h on most days. Netcare: multiple
Rx lorazepam filled by many MD’s
• Not taken in 3 days
• How are you going to approach this patient?
First BZD chlordiazepoxide 1955
Diazepam 1963
Flumazenil 1987
Net effect is inhibitory
– Increase inhibitory GABA
– Suppress excitatory NMDA
• Tolerance
• Sound familiar??
• First description of BZD withdrawal
– Hollister LE et alPsychopharmacologica;1961:63
– Single blinded study of inpatient psychiatric
– Again, sound familiar?
BDZ Withdrawal
• Course of BZD WD depends on:
– Half life
• Short half life early onset, shorter duration
– Baseline dose:
• Higher dose more profound WD
– Duration of therapy / abuse
• Case reports >6 weeks high dose BZD use
• Most studies conclude >4 months required
– Underlying medical / psychiatric illness
BZD Withdrawal
• Short acting (lorazepam, oxazepam)
– Onset Sx 1-2 days
– Last up to 7 days
• Long acting (diazepam)
– Onset Sx 7-10 days
– Can last for weeks
• Instant withdrawal with flumazenil
– Withdrawal in a bottle!!
• Very similar to EtOH WD
• Anxiety, nausea, vomiting, insomnia, tremor
• Autonomic hyperactivity:
– HTN, tachycardia, hyperthermia, diaphoresis
• In severe cases:
– Delirium, seizures, hallucinations
Back to Case
• On Exam:
– 37.6, 24, 110, 115/70, 90% NRB
– Appears to be in heart failure, ↑JVP, grossly
edematous, crackles to lung bases
– Decreased a/e to right lung base
– Slight tremor, looks anxious
• Ix:
– CBC 130, WBC 18,
– CXR: c/w CHF ?consolidation RLL
– TTE: EF <30%
• Several hours later...
– Diuresis, NTG, BIPAP (fails, pulls mask off)
– Sa02 90 NRB, looking exhausted
– Now so tremulous can’t hold cup ice chips to face
– HR 120, BP 130/90, temp 38.5
• What do you want to do? Concerns?
• ICU called, they take him for observation, BZD
+/- intubation if needed.
• Acute management similar to EtOH WD:
– Manage ABCs, r/o other causes
– Use long acting benzodiazepines to prevent and
manage signs and symptoms of withdrawal
– 20mg diazepam loading / hr po
– 5-10mg diazepam IV prn
– titrate to effect
• Admission if refractory or severe WD, poor
follow up
Sellers. 1988. CMAJ;139:113
• Start on long acting BZD at equivalent dose to
patients pre-existing dose
• Initiate taper of 5-10% per day. Goal is to
taper off BZD in:
– 8 weeks if WD from long acting
– 4-6 weeks if WD from short acting
• Must have reliable supervision and follow up
for outpatient withdrawal
Sellers. 1988. CMAJ;139:113
BDZ equivalents
• Diazepam 5mg equal to:
– Oxazepam 30 mg
– Lorazepam 1mg
– Alprazolam 0.25 mg
– Chlordiazepoxide 25mg
• 17 yo F in resuscitation bay to the PLC with
decrease LOC
• Mother called 911 after finding her daughter
unconscious with mom’s empty bottle of
diazepam and a suicide note beside her
– Mom is sure her little girl never takes pills or
drugs, she is a “good girl”
• Mom knows best!
• Shortly after flumazenil IV pt seizes
Peak Effect 6-10 min
Half life 60 min,
Competitive inhibitor at GABAa
– No role in EtOH intoxication
• Useful for solely BDZ OD for the BDZ naive
• Not useful and DANGEROUS for:
– Chronic BZD user
– Mixed OD
• Reverses effects of CNS depression but not
reliably effects on respiratory depression
Flumazenil adverse effects
• Seizures
– Secondary to severe WD and reversal of antiepileptic properties
Cardiac dysrhythmias
Dangerous in co-ingestions
Increases ICP
Risks far outweigh benefits of use
• “I was pulling needles out of my mom and
dad’s arms by the time I was 3. I always told
myself I would never end up there. I was 10
the first time my dad gave me meth”
• “I came here because if I didn’t I would be
dead in a month”
• “I woke up in the hospital one morning with
no pants, and no idea how I got there”
• “There is no drug of choice. When you are an
addict they are all drugs of choice”
• “I needed the oxy’s to function. Ever since the
accident my back has been unbearable. My
doctor, he kept prescribing these oxy’s then he
stopped and I needed them because I kept
getting sick. I didn’t know these could do that
to you. My husband is off work and I have 2
babies to feed. I need to work, and they need
me. I’m not a junkie like these people, and
can’t believe I’m here”
Hooper detox patients