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

37

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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

60

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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!!
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