ALCOHOL TOXICITY AND
WITHDRAWAL SYNDROME
03/29/2021
Objective
2
By the end of this seminar, you will be able to:
Identify, assess, & diagnose pts with alcohol toxicity &
withdrawal syndrome.
Determine the best setting for conducting management of
alcohol toxicity & withdrawal syndrome.
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3 Outline
Introduction
Ethanol
Isopropanol
Methanol
Ethyl Glycol
Alcohol withdrawal syndrome
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4 Introduction
2/3rd of US consume beverages containing ethanol.
Moderate ethanol intake(1-2 drinks/day for men & one drink/day for
women)-appears to reduce the risk of MI.
Associated complications includes:
RTA, domestic violence, homicide, & suicide.
Uncomplicated ethanol intoxication is ~ over 600,000 ED visits each
year in the US alone.
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5 Cont..
Alcohol withdrawal syndrome is a common condition
~ 8 million alcohol dependent people in the US alone.
~ 500,000 episodes of withdrawal severe enough to require
pharmacologic Rx occur each yr.
Deaths from delirium tremens among pts. receiving early
aggressive Rx have declined from 35% in the early 20th century to
<5%.
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6 Cont..
All alcohols cause clinical inebriation,
the inebriating effects is directly proportional to the alcohol’s
molecular weight.
Primary toxicity can be due to:
the parent cpd (ethanol & isopropanol) or
toxic metabolites (ethylene glycol & methanol).
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7 Cont..
Chemical structures of the common alcohols.
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8 Cont..
Ethanol & isopropanol:
the most common alcohols ingested;
their principal effects are GI irritation & intoxication.
they do not in themselves produce a clinically relevant metabolic
acidosis.
Methanol & ethylene glycol:
toxic alcohols b/se they cause serious multisystem damage &
metabolic acidosis.
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Ethanol
9
Is a colorless, volatile liquid.
The most frequently used and abused drug in the world.
15 grams of ethanol (1 standard drink)~
12 oz (355 mL) of beer (2% to 6% ethanol)
5 oz (148 mL) of wine (10% to 20% ethanol)
1.5 oz (44 mL) of 80-proof spirits (40% ethanol).
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10 Pathophysiology
Ethanol is rapidly absorbed after oral administration.
Blood levels peak at 30 to 60 mins after ingestion.
Rates of elimination:
20mg/dL/h (4 mmol/L /h) in non habituated indiv’ls.
30mg/dL/h (6 mmol/L/h) in indiv’ls with chronic alcoholism.
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11 Cont..
Some ethanol is broken down by gastric ADH, w/c lowers the
amount available for absorption.
ADH level: men > women, w/c account higher blood ethanol level
in women.
Predominantly eliminated by hepatic metabolism, with about 10%
excreted in the urine, exhaled breath, & sweat.
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12 Cont..
Metabolism of ethanol NAD+ = oxidized form of nicotinamide adenine dinucleotide; NADH = reduced
form of nicotinamide adenine dinucleotide.
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13 Cont..
Intoxication may occur with levels as low as 50mg/dL (11 mmol/L).
Death from respiratory depression may occur at concentrations of
400-500 mg/dL (87-109 mmol/L).
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14 Cont..
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15 Cont..
Ethanol is CNS depressant that enhances the inhibitory
neurotransmitter GABA receptors.
Blockade of excitatory neurotransmitter NMDA receptors.
Modulation of these systems leads to the dev’t of:
tolerance, dependence, & a withdrawal syndrome when ethanol intake
ceases.
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16 Clinical Features
The hallmark of ethanol toxicity is clinical inebriation. Includes:
euphoria or agitation, combativeness.
slurred speech, nystagmus, ataxia.
Nausea & vomiting, hypothermia, orthostatic hypotension, reflex
tachycardia.
Severe intoxication may cause resp. depression & coma.
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17 Severity of ethanol toxicity
Mild ethanol intoxication:
intoxication, without signs of volume depletion.
Moderate ethanol intoxication:
signs of volume depletion, altered level of consciousness.
Severe ethanol intoxication
inadequate respiration, hypotension, coma.
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Diagnosis
18
Ethanol
Detail Hx & P/E.
Look for other disease processes, such as infections &
traumatic injuries.
Ethanol levels: required in the pt. with unclear cause, but not
necessarily required in cases of mild or mod. Intoxication.
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19 Cont..
In isolated ethanol intoxication, the presence of horizontal gaze
nystagmus has a sensitivity of :
70% to 80% for a blood ethanol level of 80 mg/dL &
80% to 90% for blood ethanol levels >100 mg/dL.
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Treatment
20
Observation until sobriety.
Activated charcoal is not useful.
Treat hypoglycemia with IV dextrose 0.5 - 1g/kg.
Acute Wernicke’s encephalopathy can be ppted by prolonged
sustained administration of IV carbohydrate.
There is no evidence that a single dose of IV glucose can cause this
syndrome.
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21 Cont..
Wernicke’s encephalopathy is triad of by abnormal mental status,
ataxia, and nystagmus.
Treat with thiamine,100mg/d, until normal diet is resumed.
Chronic drinkers may be vitamin deficient.
Treat with IV fluids containing magnesium, folate, thiamine, &
multivitamin. (banana bag)
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22 Cont..
Fluid administration does not hasten alcohol elimination.
Metadoxine, enhances the metabolism of ethanol & accelerates
recovery.
Metadoxine 900 milligrams IV
is reported to double the rate at which ethanol blood levels decreased
with time compared with the pt’s own metabolism.
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23 Isopropanol
Is a colorless, volatile liquid with a bitter, burning taste & an
aromatic odor.
It is found in rubbing alcohol, disinfectant & is a component of a
variety of skin and hair products, jewelry cleaners, detergents, paint
thinners, & deicers.
Poisoning may results from ingestion, inhalation or dermal
exposure.
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24 Cont..
Isopropanol is ~
twice as potent as ethanol in causing CNS depression.
its duration of action is 2-4x of ethanol.
As a result, it is often used as a substitute intoxicant by alcoholics as
well as in suicide attempts.
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25 Path.
Isopropanol is :
rapidly absorbed from the GI tract.
Its peak blood levels occur 30 to 120 min after ingestion.
the metabolized in the liver by ADH(50% to 80%), with the remainder
excreted unchanged in the urine.
Isopropanol is metabolized to a ketone, not an acid.
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26 Cont..
Metabolism of isopropanol. NAD+ = oxidized form of nicotinamide adenine dinucleotide;
NADH = reduced form of nicotinamide adenine dinucleotide.
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27 Cont..
Ketosis & an osmolar gap without acidosis are the hallmarks of
isopropanol toxicity.
high levels of acetone contribute to CNS depression.
Acetone is excreted primarily by the kidneys,
with some excretion through the lungs.
Takes 30 - 60 min after isopropanol ingestion for acetone to appear
in the serum.
~ 3 hrs for it to be detectable in the urine. 03/29/2021
28 Cont..
The half-life of :
isopropanol is 6 -7 hrs.
acetone is 17 - 27 hrs leads to the prolonged CNS
depression.
The toxic dose of 70% isopropanol is ~ 0.5 -1mL/kg.
The minimum lethal dose for an adult ~ 2 - 4 mL/kg.
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29 Cont..
Loss of consciousness is associated with respiratory depression,
hypoxia, and aspiration pneumonitis.
Hypotension and hypothermia can occur with very large ingestions.
Hypotension signifies severe poisoning with increased mortality
risk.
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30 Diagnosis
Obtain point-of-care glucose testing.
Other testing as directed by the Hx & P/E.
Other signs are elevated osmolar gap, ketonuria,& ketonemia
without acidosis.
Serum isopropanol & acetone levels.
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31 Treatment
Monitor for respiratory depression.
Intubate and ventilate as needed.
Hypotension usually responds to IV fluids.
Consider hemodialysis:
refractory hypotension
Isopropanol level >400mg/dL.
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Hemodialysis eliminates both isopropanol & acetone.
32 Disposition
Pts with lethargy or prolonged CNS depression should be admitted
to the hospital.
Those who remain asymptomatic for 4 to 6 hrs after ingestion may
be discharged.
Referral for substance abuse counseling or mental health evaluation
as indicated.
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33 Methanol
The simplest alcohol, is a colorless, volatile liquid with a distinctive
“alcohol” odor.
Found in:
automotive windshield cleaning solution, solid fuel for stoves,
chafing dishes, model airplane fuel, carburetor cleaner, gas line
antifreeze, photocopying fluid, and solvents.
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34 Cont..
Methanol poisoning occur by ingestion, inhalation or dermal
exposure.
The elimination half-life of:
methanol is nearly 24 hrs.
formic acid is nearly 20 hrs.
With concurrent consumption of ethanol or administration of
fomepizole, more than 50 hrs.
With dialysis~ 200 min.
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35 Cont..
Metabolism of methanol. NAD+ = oxidized form of nicotinamide adenine dinucleotide; NADH = reduced
form of nicotinamide adenine dinucleotide.
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36 Cont..
Characterized by CNS depression, metabolic acidosis, and visual
changes.
Coma, seizure, and severe metabolic acidosis on presentation
predict a poor outcome.
Head CT may demonstrate bilateral putamen necrosis, subcortical
white matter damage, ICH, and other patterns of brain injury.
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Features of Methanol Toxicity and Treatment
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38 Prognosis
correlates with the degree of acidosis, time to presentation, &
initiation of treatment.
The strongest predictor of morbidity & mortality is the degree of
acidosis, with high mortality rates at a pH < 7.
permanent complications, including:
blindness & neurologic deficits.
Parkinson-like extrapyramidal syndrome, with bradykinesia, tremor, &
dementia,
polyneuropathy, encephalopathy, ataxia, & cognitive deficits. 03/29/2021
39 Ethylene glycol
Is a colorless, odorless, sweet-tasting liquid.
Uses as :
glycerin substitute, preservative, component of hydraulic brake
fluid, foam stabilizer, automotive coolant.
Toxicity results from ingestion, b/se the chemical has a low vapor
pressure and does not penetrate skin well.
characterized by CNS depression, metabolic acidosis, & renal
failure. 03/29/2021
40 Cont..
Metabolism of ethylene glycol. NAD+ = oxidized form of nicotinamide adenine
dinucleotide; NADH = reduced form of nicotinamide adenine dinucleotide.
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Clinical poisoning has historically been divided into three stages
41
The first or “neurologic” stage
30 min to 12 hrs after ingestion.
Range from mild depression to seizure and coma.
CNS tissue effects of glycolic acid & calcium oxalate crystals include
cerebral edema, basal ganglia hemorrhagic infarction, &
meningoencephalitis.
Hypocalcaemia, which occurs when calcium combines with oxalate,
may contribute to seizures. 03/29/2021
42 Cont..
The second or “cardiopulmonary” stage
Begins 12 to 24 hrs after ingestion.
Tachypnea, tachycardia and HTN.
Glycolate & oxalate crystal deposition in tissues leads to MOF,
including HF, ALI & myositis.
Hypocalcaemia, cause prolongation of the QT interval myocardial
depression, & dysrhythmias.
Most deaths occur during this stage. 03/29/2021
43 Cont..
The third or “renal” stage
24 to 72 hrs after ingestion.
Renal failure due to calcium oxalate crystal deposition in the proximal
tubules.
Short-term hemodialysis is often required, and it may take wks to
months for the kidneys to recover.
Delayed neuropathies may occur 5 to 20 days.
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44 Prognosis
Glycolate concentrations >10 mmol/L associated with severe CNS
toxicity & mortality and have 100% sensitivity for predicting ARF.
Poor prognostic factors at admission include hyperkalemia, severe
metabolic acidosis, renal failure, seizures, coma, & delays in
treatment.
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Features of Ethylene Glycol Toxicity and Treatment
45
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46 Indications for Hemodialysis After Methanol or Ethylene Glycol Ingestion
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47 Cont..
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48 Disposition
Pt with suspected methanol ingestion should be observed for 12 hrs.
Pts seen at facilities unable to provide hemodialysis or ICU should
be transferred.
Suicidal pts should receive a psychiatric evaluation prior to
discharge.
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Alcohol withdrawal symptoms
49
Definition:-develop in ind’ls with a hx of heavy & prolonged consumption
of alcohol who abruptly stop or reduce their drinking characterized by;
hand tremors, headache, diaphoresis, insomnia, tachycardia, HTN,
fever
loss of appetite, nausea & vomiting,
psychomotor agitation, hyper arousal, craving, anxiety, seizures,
hallucinations, & delirium.
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50 Clinical features
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51 Cont..
Withdrawal hallucinosis
transient alterations in perception or illusions,
such as tactile, visual or auditory illusions.
Alcohol withdrawal seizures
may be brief, with a short or no postictal period.
diffuse tonic-clonic seizures- can occur 6 - 48 hrs.
Diagnosis requires the exclusion of TBI, hypoxia, hypoglycemia,
structural lesions, infections, idiopathic epilepsy. 03/29/2021
52 Cont..
Delirium tremens
is a life-threatening manifestation of alcohol withdrawal
syndrome consists of :
gross tremor, frightening visual hallucinations, profound confusion,
agitation, & a hyperadrenergic syndrome.
Pts often develop life-threatening fluid, metabolic & electrolyte
imbalances.
Risk factors: past withdrawal seizure & delirium tremens,
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severe dependence, older age & Hx detoxification.
53 Dx:
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54 Cont..
Alcohol-induced Psychotic Disorder
a persecutory nature psychosis, paranoia, & agitation may
last from days to wks.
symptoms start within 2wks of alcohol consumption &
persist for >=48hrs after withdrawal.
Rx may require short- or long-term use of antipsychotics.
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Clinical Institute Withdrawal Assessment for Alcohol–Revised Scale*
55
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56 Cont..
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57 Cont..
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58 Investigation
Blood drug level
Urine Drug Screen Other studies (if clinically
Blood chemistries indicated)
CBC CX-ray
U/A CT scan
Liver function tests ECG
PT/PTT
B12 & folate assays
Amylase /Lipase
59
Treatment
The goals of therapy for alcohol withdrawal are:
to alleviate autonomic hyperactivity & agitation.
halt progression to delirium tremens.
promote long-term abstinence.
Initial therapy is usually with benzodiazepines;
no specific agent is superior to the others
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Treatment of Alcohol Withdrawal Syndromes
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61 Indications for admission
advanced age
mild or mod. withdrawal that does not respond well to ED treatment.
presence of active medical comorbidities,
a prior history of delirium tremens, &
alcohol withdrawal seizures.
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62 Cont..
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63
Cont..
Discharge Criteria
Neurologically stable for last 24hrs.
No withdrawal symptoms; CIWA scores < 8 for last 24hrs.
Vital signs are stable & within normal limits.
No suicidal/homicidal thoughts or behavior.
Reference
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65
THANK U!!
03/29/2021
