Transcript 2007_08_02-Hall - Calgary Emergency Medicine

Ethanol Abuse and
Toxic Alcohol Ingestion
Chris Hall, PGY-5
McMaster University
U of C Academic Day
August 2, 2007
Objectives
Approach to the “intoxicated” patient
 Pharmacology of alcohols
 Common clinical scenarios in EtOH
 Diagnostic and management challenges of
toxic alcohols

***Case-based and evidence-centred
Case #1
56 yo male
 “Known alcoholic”
 Unresponsive on park bench
 No witnesses; no apparent trauma
 “Smells of alcohol” as per EMS

Case #1
Afebrile, HR 102, BP 140/85, RR 22, O2
sat 91%
 CBS: 5.5
 Neuro: GCS 11; moves 4 limbs
 Sonorous resps; Gag present
 Chest: scattered crackles
 Abdo, extremities: WNL

Case #1

Any additional information you’d like?

What is your working Dx?

How will you proceed from this point?
The “Intoxicated” Patient

VITAMIN CDE

AEIOU TIPS

“Intracranial” vs. “Extracranial”
The “Intoxicated” Patient





Intracranial
Seizures
Vascular
Infectious
Neoplastic
Traumatic





Extracranial
O2 / CO2
Infectious
Toxins / WD
Metab. / Endo.
Environmental
The “Intoxicated” Patient

Reasonable DDx for Case #1:
–
–
–
–
–
–
Ethanol / other co-ingestions
Head trauma
CNS / other infection
Hypoglycemia / AKA
Wernicke encephalopathy
Alcohol withdrawal (+/- seizures)
Immediate Action

Airway / Breathing

Hemodynamic stability

Reversible causes
– The “Coma Cocktail” (?!)
Further Management

History and P/E

Investigations
– Which ones?
Case #1

TAKE HOME MESSAGE:
– DO NOT assume EtOH to be the cause of the
“intoxicated” patient’s presentation
– Keep the differential broad; systematic
approach to eliminate other DDx
Ethanol: Pharmacology
Alcoholic Trivial Pursuit

What is “100-proof alcohol”?
– 50% EtOH by weight
Alcoholic Trivial Pursuit

What is considered “one alcoholic drink”?
– 15g of EtOH
» 1 oz 50% (liquor)
» 4 oz 12% (wine)
» 10 oz 5% (beer)
Alcoholic Trivial Pursuit

How much EtOH would a 70kg male need
to drink to reach an EtOH level of 30
mmol/L?
a)
b)
c)
d)
e)
3
5
7
9
11
Alcoholic Trivial Pursuit

TRUE OR FALSE:
– Men are less susceptible to acute alcohol
intoxication
– Caffeine masks EtOH intoxication
– Prickly pear is an antidote for veisalgia
– Hydration accelerates metabolism of EtOH
– Intoxication is lessened by co-ingesting food
Pharmacology

EtOH rapidly absorbed
– Stomach and small bowel
– Multifactorial effects on rate
» Food
» GI disease
» Meds (gastric emptying)
» Idiopathic
Pharmacology

EtOH metabolized by ADH and ALDH
– Stomach and liver; 5-10% unchanged via urine
– Gender / ethnic differences in metabolism
– Rate: 3-4mM/h (non-drinker) up to 7.5mM/h
(chronic drinker)
Ethanol: Metabolism
Clinical Presentation

CNS Effects:
– GABA Agonism + NMDA Antagonism
» Inebriation, poor impulse control, ataxia
» “Set-up” for withdrawal

CVS Effects:
– Vasodilation, reduced CO
– Dysrhythmias
Clinical Presentation

GI Effects:
– N/V/D  volume loss
– Pancreatitis, gastritis, hepatitis
– GI Bleeding

Metabolic Effects:
– HypoNa, Hypoglycemia
–  osmol gap; no anion gap
– Ketonemia after binges
Clinical Presentation

Hematologic Effects:
– Anemia ( MCV)
– Thrombocytopenia
– Lymphopenia
Case #2
46 yo male
 CC: “Unwell”
 HR: 115, BP 165/100, RR 25, sat 100%
 Tremulous
 Sweaty
 Alert, not confused
 Exam otherwise WNL

Case #2

Discuss:
– Your working / differential diagnoses
– Your initial management and approach to this
patient
Alcohol Withdrawal

GABA receptor downregulation + NMDA
receptor upregulation

Anxiety, sweating, tremor, autonomic
overdrive, altered LOC, seizures

Generally in chronic abusers
Spectrum of Illness

Simple Withdrawal

Alcoholic Hallucinosis

Withdrawal Seizures

Delirium Tremens
Alcohol Withdrawal: Rx

Holbrook et al (CMAJ 1999)
– Metaanalysis of WD Rx
– BZD vs placebo or other Rx
– BZD better than placebo
» More successful outcomes
» Less likely to drop out of Rx
– Unable to properly pool results otherwise
Choice of BZD?

Ritson et al, (Drug Alc Dependence 1986)
– RCT; N=40
– Standing lorazepam vs diazepam
– Less anxiety; smoother course with valium
Choice of BZD?

Diazepam is the traditional choice

Lorazepam is preferred in patients with
severe liver disease
Benzodiazepines

Dosing
– Diazepam: 5 mg iv / 10 mg po q 10 min
– Lorazepam: 1-2 mg iv / 2 mg po q 15 min
» NB: longer time of onset; beware dose stacking
– Titrate to effect
» (But how?)
CIWA
10-item scale
 Min score = 0, Max score = 67
 Score < 8 considered mild withdrawal (Rx
threshold)
 Takes 5 min to complete

Symptom-Guided Rx

2002 Arch Int Med & 1994 JAMA:
– 2 RCTs
– CIWA-guided Rx reduces BZD use, length of
Rx vs. standing BZD protocol
Guide therapy with symptoms; avoid
standing dosing schedules
 Do not fear huge doses

Adjunctive Rx

Carbamazepine
– 2 RCTs (Am J Psych 1989; J Gen Int Med
2002)
» Similar to BZD in Rx of withdrawal symptoms

Valproate
– 1 RCT (Alc Clin Exp Res 2001)
» Less BZD needed when Rx with VA
Simple Withdrawal: Rx

Adjuncts, cont’:
– Beta Blockers
– Clonidine
– Haldol
– Magnesium
Withdrawal: Disposition

RCT (NEJM, 1989)
– CIWA < 15; no comorbidities
– Outpatient Rx as safe as Inpatient Rx, cost less,
lasted less time
– Inpatients more likely to complete Rx
– Outpatients got daily follow-up and BZD
dosing
Withdrawal: Disposition

Discharge home if:
– Mild withdrawal at time of d/c (CIWA < 8 - 15
after 4-6 h observation)
– Easily controlled w/ BZD
– Not intoxicated
– Responsible supervision preferred
– No prior hx of seizures or DT
Case #2 ,Part 2

BZD sedation is ordered for the patient

60 min later, patient is more tremulous,
agitated

While trying to get out of bed, has
generalized T/C sz
Case #2, Part 2

What are your initial steps?

How will you treat this patient?
Withdrawal Seizures

Usually GTC, self-terminating

15-25% have > 1 seizure
– < 8% go into status

May herald onset of DT
Seizure Management
ABCs
 Rule out reversible causes
 Lorazepam likely longer anticonvulsant
effect than diazepam

Seizure Management
BZD (e.g. Ativan 2-4 mg iv)

Phenobarbital 15-20 mg/kg

Propofol / Midazolam / Pentobarb

Inhalational Anaesthesia, paralysis, EEG
monitoring
What about Dilantin?

EBM (Ann Emerg Med 1991 & 1994):
– 2 RCTs; 55 & 147 patients
– No difference in relapse of seizures vs placebo
Mechanism of action unlikely to affect
seizures in EtOH withdrawal
 Likely to have little impact on Rx

Withdrawal Seizures

Some Questions to ponder:
– Who can be released from the ED?
– When is a CT Head warranted?
– When should patients start an anticonvulsant?
CT Head
New / changed seizures
 Focal seizure
 Focal examination / meningismus
 Failure to recover usual mental status
 Mental status out of proportion to EtOH
 Recent head trauma
 +/- fever (prior to LP?)

Disposition
Normal workup and exam
 Single seizure
 Withdrawal well-controlled
 Not intoxicated
 Adequate supervision / follow-up

Starting an Anticonvulsant

Controversial

Seizure may be due to withdrawal or may
represent underlying epileptic d/o

Generally, leave it to neurology!
Case #3
60 yo male
 “Alcoholic” by own report
 2-week “binge” until yesterday
 Since then, N/V, AP, “dizziness & blurred
vision”

Case #3
HR 114, BP 105/60, RR 28, sat 100%
 CBS: 3.0
 Chest: clear
 Neuro: slightly drowsy; no focality; no
tremor
 Abdo: tender epigastrium
 Urine dip: negative for ketones, blood,
WBC

Case #3

Working diagnosis / differential?

Approach to management?
Metabolic Derangements in
EtOH
Hypoglycemia
 Hyponatremia, hypokalemia
 Hypomagnesemia, hypocalcemia
 Ketoacidosis
 Wernicke Encephalopathy / Korsakoff
Amnesia

Ketoacidosis

Pathophysiology
–  NADH:NAD ratio
– Loss of EtOH block of ketogenesis
– Starvation
Ketoacidosis

Presentation:
– Recent EtOH binge
– Dehydrated, N/V, abdo pain
– High AG acidosis
– Ketonuria w/o glucosuria
Ketoacidosis

Diagnosis
– Rule out other causes of AG acidosis
– Assess for underlying medical illness
» Infection, AMI
– Beware relying on urine dipstick
Ketoacidosis
Ketoacidosis

Management
– Thiamine replacement
» Needed for pyruvate  Krebs Cycle
– Mg replacement
» Cofactor for thiamine
– IVF rehydration
– Dextrose / Glucose replacement
– HCO3 in severe acidosis (e.g. pH < 7.1)
Hypoglycemia

Causes:
– Starvation (during binge)
– Hepatic glycogen depletion
– Impaired gluconeogensis
May be a sentinel phenomenon prior to
onset of AKA
 Treated with glucose, thiamine, magnesium

Differential Diagnosis?
Thiamine Deficiency

Chronic Alcoholism
– Malnutrition
– Vomiting
– Malabsorption

Other Chronic Illnesses
– Chronic vomiting (AIDS, hyperthyroidism,
hypermesis gravidarum)
– Dialysis
– Long-term Lasix use
Thiamine Deficiency

“Beri Beri”
– “Dry” beri beri = neurologic disease
» Wernicke encephalopathy
» Korsakoff amnesia
– “Wet” beri beri = cardiovascular disease
» CHF / DCM
» More often in countries w/o thiamine supplements
Wernicke’s Encephalopathy

Classic Presentation
– EOM palsy
– Ataxia
– Altered LOC / cognition
***(only 12% of patients have all 3)
•
Other Sx:
• Hypothermia
•  DTRs
Korsakoff’s Amnesia

Presentation
– Memory impairment
– Unable to learn / remember new facts
– Apathy
– Confabulation
***May be abrupt or insidious onset
Treatments

Thiamine
– 100mg iv; repeat prn to 1000mg
– 100-200mg po/day
– Concern for anaphylaxis?

Magnesium

Abstinence
Prognosis

Wernicke’s:
– 25% recover well
– 50% some recovery
– 25% poor recovery
– Almost 80% chance of Korsakoff’s in the
future
Case #4
15 yo female
 Recent dispute with parents; last seen 4 hrs
prior
 Found unresponsive in garage by father
 Brought to a rural ED via EMS with this
container…

Case #4
Afebrile, HR 105, BP 100/40, RR 25, sat
100%
 CBS 5.5
 Chest, Abdomen WNL
 GCS 6; PERL 5mm
 Bidirectional nystagmus
 No evidence of head trauma or IVDU
 Neck supple

Case #4

Electrolytes:
– Na 139, Cl 95, HCO3 14, K 3.9, Glc 5.5
CBC: Normal
 Renal: BUN 5.1, CR 115, Osm 320
 VBG: pH 7.20 / pCO2 30

Case #4
What is your working diagnosis? Your
differential?
 Any additional testing which may be
helpful?

– Any simple tests to help confirm a toxic alcohol
ingestion?
Ethylene Glycol

Sources:
– Radiator antifreeze

Metabolism:
– Sequential oxidation via ADH / ALDH
pathway
– Multiple toxic metabolites
– Glycolic acid causes wide AG acidosis
Ethylene Glycol
Ethylene Glycol

Presentation
–
–
–
–
Renal failure w/ crystalluria
Intoxication, seizures
Hypocalcemia, long QT, dysrhythmias
Opthalmoplegia, nystagmus
Calcium Oxalate Crystals

Approx. 60% Sens
Methanol

Sources:
–
–
–
–

Model airplane fuel
Gas line antifreeze
Windshield washer fluid
Photocopying fluid
Metabolism:
– ADH / ALDH
– Formate is toxic
Methanol
Methanol

Presentation
–
–
–
–
–
–
Visual changes (“snowstorm”)
N/V, AP, Pancreatitis
Hypothermia
Altered LOC, seizures
Acute renal failure
Bilateral basal ganglia lesions (CT Head)
Diagnostic Testing

Toxic Alcohol levels
– Often not available immediately
– May be falsely low
– Use of “Toxic” level is misleading
Diagnostic Testing

Anion Gap
– Na – (HCO3 + Cl)
– “Norm = 7 +/- 4 mEq/l
– Rises as toxic alcohol metabolized
» Due to Glycolate (EG) or Formate (MeOH)
Diagnostic Testing

Anion Gap, cont’
–
–
–
–
Lacks sensitivity (absent early on)
Lacks specificity (MUDPILES CAT)
Cannot rule in / out toxic alcohol poisoning
BUT Very high values highly suggestive of
serious underlying disease / ingestion
Diagnostic Testing

Osmolar Gap
– OG = Osmmeasured – Osmcalculated
– (Osmcalculated = 2 x Na + BUN + Glc)
– “Norm” is disputed
» Classic = 10 +/- 6
» More recent = 5 +/- 10 (or –2 +/- 6, etc…)
– Rises as EG is absorbed; drops as EG
metabolized
Osmolar vs Anion Gap
Diagnostic Testing

Osmolar Gap
– Lacks sensitivity (can be “normal” with fatal
ingestion)
– Lacks specificity
» EtOH, MeOH, EG, Isoprop., Mannitol
– Cannot rule out / in toxic alcohol ingestion
– BUT very high value (> 50) is suggestive
Diagnostic Testing

Evaluate the following:
– Na 135, Bun 6.7, Glc 7.8
– Osm 342
– EtOH 55
Does this add up?
 What does this imply?

EtOH and the Osmolar Gap

EtOH : OG ratio is ~ 1.25 : 1
– (Purssell et al Ann Emerg Med, 2001)
Residual difference does not necessarily
mean toxic alcohol
 Large discrepancy is suggestive
 Lack of discrepancy doesn’t rule out toxic
alcohol

EtOH and the Osmolar Gap

Contribution of EtOH to clinical toxicity:
– Affinity of ADH for EtOH 67x higher than EG
& 15x higher than MeOH
– EtOH is protective
– Levels > 20mmol/L make toxic alcohol
unlikely cause of wide AG acidosis
Management: Overview
ABC
 Decontamination
 ADH inhibition
 Adjunctive measures

Decontamination

Is activated charcoal appropriate in this
patient?
– Why / why not?

Are any decontamination modalities of
value in toxic alcohols?
ADH Inhibition

EtOH
–
–
–
–
“Occupies” ADH
Blocks toxic alcohol metabolism
May be difficult to find / prepare
Requires load and infusion
ADH Inhibition

Indications: (AACT Guidelines)
– Documented level (>7.5 MeOH / >4 EG)
– Documented ingestion and OG > 10
– Suspected ingestion and 2 of:
» pH < 7.3
» HCO3 < 20
» OG > 10
» Urinary oxalate crystals
ADH Inhibition

EtOH
– Adverse Effects:
» Obtundation / inebriation
» Respiratory depression
» Hypotension
» Hyponatremia / glycemia
» Gastritis / pancreatitis
» Phlebitis (infusion site)
ADH Inhibition

EtOH:
– Dosing:
» 5-10% IV solution (preferably CVL)
» Load: 8cc/kg over 30-60 min
» Infusion: ~45cc/hr (70 kg person)
» Goal: EtOH of ~20mmol/L or molar ratio of 1:4
(whichever greater)
» Monitor Glc, Na
ADH Inhibition

Fomepizole
– Inhibits ADH
– Advantages:
» Avoid essentially all S/E of EtOH
» Q12h dosing
– Disadvantages:
» COST
Fomepizole: EBM

Brent et al. (NEJM 1999):
– Case series (N=19) of EG poisoning
» Reduction in acidosis, serum glycolate and urinary
oxaluria
» Preservation of renal function (if normal initially)
» No comparison to EtOH
» 1 patient died
– “Safe and effective”
Fomepizole: EBM

Brent et al. (NEJM 2001):
– Case series (N=11) in MeOH toxicity
» Reduction in formate levels
» Improvement in acidosis
» No patients with significant S/E
» No comparison with EtOH
» 2 patients died
– “Safe and effective”
Fomepizole

Indications:
– Same as for EtOH
– Institutional preference (COST)

Continue dosing until “non-toxic” level and
not acidotic
– MeOH ~ 7.5 mmol/L; EG ~ 4 mmol/L
Hemodialysis

Eliminates toxic alcohols

Can address toxin plus electrolyte or acidbase disturbance

Not always necessary if ADH inhibited;
may serve to shorten duration of Rx
Hemodialysis

Indications (AACT Guidelines)
– Acidosis
– Renal Failure
– End organ damage
» Visual changes, coma, seizures
– Methanol > 15 / EG > 8 (controversial)
– Electrolyte or vital sign disturbance
unresponsive to usual Rx
Hemodialysis

HD may be withheld if
– ADH inhibited
– No acidosis
– No clinical indications for dialysis

(NB: will prolong duration of Rx)
Adjuncts

Methanol:
– Bicarbonate
– Folinic acid

Ethylene glycol:
– Thiamine
– Pyridoxine
Sodium Bicarbonate

Mechanism
– Shifts formic acid to formate (less toxic)
– “Ion trapping” in urine

Indications
– pH < 7.15 (Goldfrank) - 7.3 (AACT)
– May consider in EG and significant acidosis
Folinic Acid
Reduced form of Folic Acid
 Mechanism:

–  Formic acid metabolism

Indications:
– All MeOH ingestions
Thiamine / Pyridoxine

Mechanism:
– Encourage glycoxylic acid metabolism to nontoxic compounds

Indications:
– Consider in any EG ingestion
Case #5
59 yo male
 Found outside homeless shelter
 Decreased LOC
 Hematemesis / Hemoptysis
 Sweet odor on breath
 Empty bottle found next to patient

Case #5
HR 105, BP 130/75, RR 10, sat 91%
 Chest: scattered crackles
 Abdomen: epigastric tenderness
 GCS 10, PERL 3mm
 Urine:

– dip 3+ RBC, 3+ ketones
– microscopy normal
Case #5
CBC: Hb 100, otherwise WNL
 Na 139, Cl 100, HCO3 25, K 3.0
 BUN 8.0, CR 129
 Glc 8.1
 Serum ketones present
 Osmolarity 320
 Ethanol: undetectable

Case #5:

What is your diagnosis / differential?

What further testing would you like to do?

What is your management at this time?
Isopropanol

Source:
– “Rubbing alcohol”

Clinical:
– Significant inebriation
» NB: IP ~ EG > EtOH > MeOH
– Hemorrhagic gastritis / tracheobronchitis
– Acetone odor
– Rhabdomyolysis
Isopropanol: Metabolism
Isopropanol

Investigations:
–
–
–
–
“Ketosis without acidosis”
No anion gap
Osmolar gap present
Urine may show myoglobinuria
Management
Secure ABC’s
 Address complications

– Gastritis, tracheobronchitis, rhabdomyolysis

Usually no specific interventions
– HD shortens half-life
Bonus: Case #6
Case #6
47 yo male
 Drinking at a bar, involved in altercation
 Struck in side of head with bottle
 ~ 30 sec LOC
 No vomiting, headache, seizure activity

Case #6
All VS WNL
 GCS 15; patient slurring speech, slightly
ataxic
 No focal neurologic weakness
 3 cm laceration on vertex
 No spinal tenderness
 Patient is requesting to leave the ED

Case #6

Main Issues:
– Does this patient require imaging?
– What is the physician’s obligation regarding the
patient’s request to leave?
Head Trauma and EtOH

Confounding Issues
– Higher risk of brain injury with same
mechanism
– Intoxication clouds assessment
– Direct toxicity of EtOH on injured brain
– Patients often not cooperative
– Time / resource constraints
Head Trauma and EtOH

New Orleans CT Head Rule (NEJM 2000)
– EtOH an independent predictor of risk of
positive CT
– OR = 3.2
– LR(+) = 11.3
– Conclusion: image all “intoxicated” patients
Head Trauma and EtOH

Canadian CT Head Rule (Lancet 2001)
– “Acute intoxication” not included among
variables
– Intoxicated patients not excluded (but unclear
how many included)
– “Suspected chronic alcoholism” not predictive
– Conclusion: “No comment”
Head Trauma and EtOH

Retrospective review of NEXUS II data
(Ann Emerg Med, 2007)
– Suggests over-imaging in intoxicated patients
– “Intoxication” not predictive of positive CT
head
– Conclusion: weak evidence of utility of
NEXUS II CDR in intoxicated patients
Head Trauma and EtOH

Summary of Evidence:
– No strong evidence to guide imaging choice
– Evidence highlights increased risk but likely
overuse of CT Head
– Bottom line: clinical judgment required; CDR
(CCR, NEXUS II) may help
Summary

Ethanol
– Major cause of morbidity / mortality
– Withdrawal may be a medical emergency
– Most of Rx is supportive / directed towards
medical complications
– Never forget to search for other causes of
“intoxication”
Summary

Toxic Alcohols
– Can be difficult to detect
– Have significant direct toxicity (highly lethal)
– Main Rx is directed towards ADH inhibition
and serum clearance
The End

Any questions?