ALCOHOL AND ACUTE

AGITATION
Presenter : Dr Deepak raj R ,EMD resident
Moderator : Dr Santhosh K B , AP of EMD ,SUIMS
● Ethanol

● Isopropanol

● Methanol

● Ethylene glycol
INTRODUCTION
• Primary toxicity can be due to the parent compound (ethanol and
isopropanol) or to toxic metabolites (ethylene glycol and
methanol).

• Alcohols cause clinical inebriation, with effects directly

proportional to the alcohol’s molecular weight.
 ETHANOL
• Ethanol is a colorless, volatile liquid.
• It is the most frequently used and abused drug in the world.
• Molecular weight – 46 g/mol
• Intoxication most commonly occurs from ingestion, inhalation or
percutaneous exposure.
• Beer - 2% to 6% ethanol by volume
• Wine - 10% to 20% ethanol by volume
• Proof spirits - 40% ethanol by volume
 Alcohol is most commonly abused drug worldwide

One standard drink = 10 grams of pure alcohol

• Ethanol is found in high concentrations in many common
household products.
 Mouthwash - up to 75%
 Colognes and perfumes - up to 40% to 60%
Diluent or solvent for medications - concentration between 0.4%
and 65%.

• These products are often flavored or brightly colored —>

attractive to children.
 PATHOPHYSIOLOGY
• Alcohol dehydrogenase is the major enzyme involved in the
metabolism of ethanol, producing acetaldehyde.

• At low ethanol concentrations- first-order kinetics, but as

concentrations rise metabolism switches to zero-order kinetics a
fixed amount is metabolized per unit of time.

• Hepatic microsomal oxidizing system ( cytochrome P450 2E1

[CYP2E1]) plays an important role in metabolism.
• Blood peak level-after 30-60 minutes
• Food in stomach prolongs absorption
• Causes pylorospasm , delayed emptying
• Gastric alcohol dehydrogenase (decrease absorption)
• Enzyme more in males
• CNS depressant(enhance GABA , block NMDA receptors)
• Death by respiratory depression- 400 to 500 mg/dl (non habituated)
• Limit for driving- 80 mg/dl(US,Canada,Mexico)
- 30 mg/dl (India)
• Elimination - 90 % hepatic metabolism
- 10% urine,breath,sweat
 CLINICAL FEATURES
• The hallmark of ethanol toxicity is clinical inebriation.
• Behavioral disinhibition - euphoria , agitation and combativeness.
• Severe intoxication- slurred speech , nystagmus, ataxia, decreased
motor coordination, respiratory depression and coma.
• Nausea and vomiting often occur in conjunction with neurologic
depression.
• Peripheral vasodilation - flushed, warm skin, hypothermia ,
Orthostatic hypotension and reflex tachycardia.
• Hypoglycemia
• Ketoacidosis
Differential Diagnosis:
• Trauma
• Sepsis
• CNS infections
• Seizure
• Nonalcoholic toxin ingestion
• Hypo- or hyperthermia
• Hypo- or hyperthyroidism
• Hypoxia
• Metabolic derangements.
 Diagnosis:
• Blood alcohol levels
• Blood alcohol level less than 25 mg/dl- sense of warmth and well being
• 25-50mg/dl- Euphoria and decreased judgement
• 50-100mg/dl- Incoordination,decreased reflexes and ataxia
• 100-250mg/dl- Cerebellar dysfunction
• More than 250 mg/dl- Respiratory depression and coma

• Blood glucose, CBC, Electrolyte panel, LFT, RFT.

• ABG - mild metabolic acidosis
• Ethanol-intoxicated patients often have other disease such as infections
and traumatic injuries —> perform a detailed physical examination.
• Uncomplicated ethanol intoxication improves over a few hours.
 TREATMENT
• History itself points to a diagnosis of acute alcohol intoxication
• Co-ingestion of other substances should be ruled out
• Rapid bedside blood glucose determination
• Assessment for occult traumatic injury and NCCT(Head)
• Urine toxicology screen
Mild intoxication
• Observation and serial
Moderate Intoxication Severe intoxication
• Signs of volume • Primary survey
examination until clinical soberity is
depletion,hypotension or • Aggressive supportive care
achieved
malnutrition • Gastric lavage with activated
• Chemical sedation for violent and
• IV catheter insertion and fluid charcoal not helpful
agitated patients
hydration • Frequent assessment of airway
• Disposition based on blood alcohol
• Alteration in mental status not and breathing
concentration and serial clinical
improving after initial • Endotracheal intubation and
assessment
stabilization and serial clinical mechanical ventilation
• Discharged when no longer
examination • IV hydration with isotonic
clinically intoxicated and no danger
• Obtain NCCT(Head) and serum crystalloid,IV Thiamine
to
electrolytes administration
themselves or others.
• Disposition based on blood • Requires admission for close
alcohol concentration and serial monitoring until clinical sobriety
clinical assessment is achieved
• “Holiday heart syndrome” —> characterized by new-onset
arrhythmias following acute ingestion of alcohol and can include new-
onset atrial fibrillation.
 TREATMENT
• Airway protection - in presence of respiratory depression.
• Observation until sobriety.
• Activated charcoal is not useful since ethanol is rapidly absorbed.
• Treat hypoglycemia with IV dextrose 0.5 to 1 gram/kg.

• Long term drinkers are vitamin deficient —>IV fluids containing

magnesium,folate, thiamine, and multivitamins ( banana bag because of
the yellow color imparted by the multivitamin mixture).
• Wernicke’s encephalopathy - abnormal mental status, ataxia, and
nystagmus
—> Inj. Thiamine 500 milligrams IV , 100mg daily until normal diet is resumed.

• Metadoxine ( 900 milligrams IV ) enhances the metabolism of ethanol and

accelerates recovery —> doubles the rate at which ethanol blood levels
decrease with time compared with the patient’s own metabolism.

• Agitated or violent—> sedatives like droperidol or haloperidol

• Many intoxicated patients have suicidal thoughts —> psychiatric evaluation

should be performed and have to be repeated as the patient becomes lucid.
 Complications:

● Trauma-related injuries
● Infections
● Alcoholic liver disease - Acute or Chronic
● Alcoholic hepatitis and acute on chronic liver failure
● Dysrhythmias - atrial fibrillation, supraventricular tachycardia, ventricular
tachycardia —> myocardial infarction and increased risk of cardiac death.
● Heart failure
● Stroke
 Wernicke encephalopathy
• Characterized by the triad of ataxia, oculomotor abnormalities and global
confusion.
• Occur in any disorder leading to a thiamine deficiency.
• It develops over days to weeks.
• Neurobehavioral findings —> decreased attention, impaired memory , and
disorientation.
• Severe form can lead to coma.
• Untreated Wernicke encephalopathy can progress to Korsakoff syndrome
characterized by anterograde and retrograde amnesia without impaired
alertness and attention or extraocular movement findings.
• Treatment - Inj. Thiamine 500 mg IV TID
 Disposition :
• Patients with acute ethanol intoxication as the only clinical problem require
ED observation until sober.

• Prior to discharge reassess for any underlying mental health disorder —>
such as suicidal or homicidal ideation —> Psychiatry consultation.

• Clinical judgment rather than a serum ethanol level, determines the

appropriateness of discharge.

• Discharge the patient in the care of a responsible companion. Patients

treated for alcohol intoxication should not be responsible for their own
transportation home.
 Alcohol withdrawal syndrome
• Commonly encountered in the ED settings
• Most people with alcohol use disorder do not experience significant withdrawal
when they stop or reduce drinking
• Alcohol withdrawal is usually mild
• 20% patients experience hallucinosis, seizures and delirium tremens

• Clinical Manifestation
 Minor withdrawal
 Alcoholic hallucinosis
 Alcohol Withdrawal Seizure
 Delirium Tremens
 Refractory delirium tremens
 Severe alcohol withdrawal
Minor withdrawal Alcoholic hallucinosis
• Onset after last drink 6-36 hrs • Begins 12-24 hours after last drink and
• Mild anxiety, diaphoresis, palpitations, GI resolves in another 24-48
upset, normal mentation hours
• Physical sings include tachycardia, • Usually Visual hallucinations
hypertension, hyperactive reflexes • auditory and tactile hallucinations
and tremor • Intact orientation and normal vital signs

Delirium Tremens
Alcohol Withdrawal Seizure • Onset after last drink 48-96hrs
• Begins 6-48 hours after last drink • Rapid onset fluctuating disturbance of attention and
cognition
• Occurs in 10-30% of patients in alcohol withdrawal
• Occurs in 5% patients hospitalized for alcohol withdrawal
• Risk of seizure increases with repeated withdrawals • Delirium, agitation, tachycardia, hypertension, fever,
• Single or brief episode of generalized tonic-clonic diaphoresis
seizures with short post-ictal period • With appropriate medical management mortality rate is
between1-4%
Severe Alcohol
Refractory delirium
withdrawal
Tremens
•Withdrawal seizure and withdrawal
• Non response of delirium tremens to
delirium grouped together as severe
benzodiazepines
alcohol withdrawal syndrome
• High requirement of IV Diazepam
• Risk factors of severe alcohol
• More than 50mg in first hour or 200
withdrawal
mg or more within the first three
• Old age
hours
• Comorbid medical or surgical illness
• Poor control of withdrwal symptoms
• Past history of delirium tremens or
withdrawal seizure
• Dehydration
• Hyponatremia
 CIWA-Ar Scale
• Clinical institutes withdrawal assessment scale for alcohol
• 10 item scale for clinical assessment of alcohol withdrawal syndrome and its
management
• Score less than or equal to 9- very mild withdrawal
• Score between 10-15- mild withdrawalScore16-20-moderate withdrawal
• Score more than 20- severe withdrawal
• It shortens the duration of therapy and amount of benzodiazepines needed
• Should not be used to diagnose alcohol withdrawal
• When patient cannot communicate symptoms and alcohol use history is absent
 Treatment
• Minor withdrawal
- Ambulatory management
- Supportive Care: Multi-vitamin containing thiamine and folate
-Benzodiazepines:
Fixed dose regime: Chlordiazepoxide
Day 1: 50mg every 6-12 hours
Day 2: 25mg every 6 hours
Day 3: 25mg twice a day
Day 4: 25mg at night
Symptom triggered regime: Chlordiazepoxide
 Day 1: 50 mg every 6-12 hours
 Day 2-5: 25mg every 6 hours as needed
 • Patient should be placed in a quiet and protective
environment
Moderate and
• Supportive care
severe • Psychomotor agitation: Benzodiazepines
withdrawal
 Fixed dose regime: fixed daily doses of benzodiazepines is administered in four
divided doses 60 mg diazepam or 125 mg chlordiazepoxide/day
 Symptom triggered regime: Diazepam 5-10 mg IV
 Intubated patients : Richmand Agitation Sedation Scale (0 to -2)

Refractory • Phenobarbital:130-260 mg IV repeated every 15-20 minutes

Delirium Tremens till symptoms are controlled
• Propofol (0.3-1.25mg/kg/hr) is another alternative.
DISPOSITION
• Patients with moderate and severe withdrawal require ICU admission
• Criteria for ICU admission
 Age > 40years
 Hemodynamic instability, Cardiac disease
 Severe electrolyte abnormalities, Persistent hyperthermia
 Respiratory insufficiency, Rhabdomyolysis
 History of prior alcohol withdrawal complications
 ISOPROPANOL
• Isopropanol (CH3CHOCH3) —> also known as isopropyl alcohol and 2-
propanol.

• It is a colorless, volatile liquid with a bitter, burning taste and an aromatic

odor.

• Molecular weight 60 g/mol.

• Found in many common household products such as rubbing alcohol (70%

isopropanol).
• It is widely used in industry as a solvent and disinfectant and is a
component of a variety of skin and hair products, jewelry cleaners,
detergents, paint thinners.

• Poisoning results from ingestion, inhalation or dermal exposure in poorly

ventilated areas or during alcohol sponge bathing.

• Isopropanol is approximately twice as potent as ethanol in causing CNS

depression, and its duration of action is two to four times that of ethanol.

• Hence it is often as a substitute intoxicant by alcoholics as well as in

suicide attempts.
 PATHOPHYSIOLOGY
• Isopropanol is rapidly absorbed from the GI tract.

• Peak blood levels - 30 to 120 minutes after ingestion.

• The major metabolism of isopropanol is in the liver by alcohol

dehydrogenase (50% to 80%),LUNGS and remainder excreted unchanged
in the urine.

• Ketosis and 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.
• It takes about 30 to 60 minutes after isopropanol ingestion for
acetone to appear in the serum and about 3 hours for it to be
detectable in the urine.
• Isopropanol metabolism follows first-order kinetics.

• The elimination half-life of isopropanol in the absence of ethanol is 6

to 7 hours and the elimination half-life of acetone is 17 to 27 hours.

• The long half-life of acetone may contribute to the prolonged mental

status depression associated with isopropanol poisoning.
• The toxic dose of 70% isopropanol - 1 mL/kg

• The minimum lethal dose for an adult - 2 to 4 mL/kg.

• Children are susceptible to toxic effects and develop symptoms after

as little as three swallows of 70% isopropanol.
 CLINICAL FEATURES
• CNS depression
• Hypoglycemia.
• GI symptoms - nausea, vomiting, abdominal pain, acute pancreatitis,
hemorrhagic gastritis , upper GI bleeding.
• Severe poisoning - early onset of coma, respiratory depression, and
hypotension, rhabdomyolysis and renal failure.
• Massive ingestion - hypotension secondary to peripheral vasodilation.
• Infants and small children—> if isopropanol is used to clean the skin—>
chemical burns and systemic symptoms can occur from dermal
absorption.
 DIAGNOSIS
• Point-of-care glucose
• Assess for upper and lower GI bleeding.
• Fruity odor of acetone or the smell of rubbing alcohol present in
breath. Elevated osmolar gap, ketonuria, and ketonemia without
acidosis.
• Increase in serum creatinine —> acetone’s interference with the
colorimetric creatinine assay.
• Serum isopropanol and acetone levels —> Isopropanol levels of 50
milligrams/dL (8 mmol/L) are often associated with intoxication in
individuals who are not habituated to ethanol.
 TREATMENT

• Treatment is supportive.

• # Do not administer activated charcoal or perform gastric lavage unless

indicated by co-ingestion of an additional toxic substance.
• # Do not administer fomepizole or ethanol—> the metabolite acetone is
less toxic than isopropanol itself.

• Monitor for respiratory depression—> intubate and ventilate as

needed.

• Hypotension —> IV fluids.

• Obtain blood grouping and cross-matching —>transfusion if needed
to treat GI bleeding.

• Hemodialysis eliminates both isopropanol and acetone.

• Consider hemodialysis if :
• Hypotension is refractory to conventional therapy
• Isopropanol level is >400 milligrams/dL (>66 mmol/L).
 DISPOSITION AND FOLLOW-
UP
• Patients with lethargy or prolonged CNS depression —> admitted.

• Asymptomatic for 4 to 6 hours after ingestion —> discharged with

referral for substance abuse counseling or mental health evaluation.
METHANOL AND ETHYLENE GLYCOL
• Methanol is the simplest alcohol (CH3OH,) —> colorless, volatile liquid
with a distinctive “alcohol” odor.
• Molecular weight 32gm/mol .
• Most cases of methanol poisoning occur by ingestion.

• Worldwide there are outbreaks of poisoning from contaminated alcoholic

beverages —> Persons who wish to consume ethanol but have no access to
it for financial or other reasons consume methanol as an alternative, either
intentionally or unintentionally.

• Methanol may be systemically absorbed after inhalation or dermal

exposure,but rarely causes significant clinical toxicity—> extensive
evaluation is not required after minor skin or inhalational exposures.
• Methanol is rapidly absorbed and
metabolized in the liver

• Low dose - First order kinetics

• High dose - Zero order kinetics

(8.5 milligrams/dL per hour)
 Clinical features
• CNS depression, metabolic acidosis, visual changes
• Coma ,seizure
• Delay of 12-24 hours(metabolism of formic acid is required for tissue damage)
• Delayed symptoms if ethanol coingestion
• Mild inebriant,headache,vertigo
• Photophobia/blurred/snowfield vision
• Papilloedema, nystagmus, nonreactive mydriasis (if permanent damage)
• Head CT-bilateral putamen necrosis subcortical white matter damage intracranial
hemorrhage
• Delayed parkinsonism,polyneuropathies
• Tachycardia,hypotension,shock
• Tachypnoea(compensation),respiratory failure
• Ethylene glycol [CH2CH2(OH)2] is a colorless, odorless, sweet-
tasting liquid.

• Molecular weight 62mg/mol.

• All ethylene glycol toxicity results from ingestion.

• Its sweet taste renders ethylene glycol an attractive ingestant for children.

• Other common exposure —> ingestion as an ethanol substitute when

ethanol is unavailable and intentional suicidal ingestions.
• End-organ damage from ethylene
glycol poisoning is due to direct
cytotoxicity of glycolic acid and tissue
damage from precipitation of calcium
oxalate crystals.
• Rate limiting step-glycolic to glyoxylic
acid

• Glycolic acid-main cause of metabolic

acidosis, end organ damage
 CLINICAL FEATURES

1-Neurologic stage 2-Cardiopulmonary 3-Renal stage

* begin 30 minutes to 12 hour after stage • 24-72 hours after ingestion
intake * begins 12-24 hours after ingestion • renal failure (crystals in PCT)
* due to parent compound * tachycardia,hypertension • short term hemodialysis
*depression,seizure,coma,ataxia,co * tachypnoea(compensation) • recovery after weeks to
nfusion * glycolate,oxalate crystals months
• slurred speech(but no ethanol deposition • delayed neuropathies
odour) * heart failure,acute lung
• nausea,vomiting,abdominal pain injury,myositis
• Cerebral * QT prolongation(hypocalcemia)
edema,meningoencephalitis • myocardial
• basal ganglia hemorrhagic depression,arrhythmias
infarction
• hypocalcemic seizures
 Metabolic blockade
• Fomepizole - (4-methyl-1H-pyrazole)
• Higher affinity for enzyme than methanol/ethylene glycol
• Fomepizole –better(less dosing error)
• Ethanol-CNS depression , GI irritation , hypoglycemia
• Fomepizole-increased cost
• Fomepizole until toxic alcohol level <20 mg/dl and acidosis resolve
 Induce its own metabolism
 Fomepizole 15 mg/kg IV over 30 minutes
 Then 10 mg/kg IV(over 30 min) 12 hourly
 If treatment last for >48 hours, 15 mg/kg IV every 12 hours
 4 hourly dosing during hemodialysis
Serum level monitoring not needed .
 Metabolic blockade-ethanol

Oral or IV
• If fomepizole not available or contraindicated
• Target-100-150 mg/dl ethanol level(>150 if high toxic alcohol levels)
• If IV not available, 1.5-2 ml/kg of 80-proof liquor PO/ via nasogastric
tube(loading)
• Maintainence – 0.2-0.5 ml/kg/hr
• Don’t use oral preparations IV
• IV loading dose- 800 mg/kg(10 ml/kg of10% iv solution)
• IV maintainence dose-100 mg/kg/hr(1.2ml/kg/hr of 10% iv solution)
• Serum ethanol concentration 1-2 hourly
• Double all maintainence dose if undergoing hemodialysis
• Treat until toxic alcohol level<20 mg/dl and acidosis resolve
 DISPOSITION AND FOLLOW-UP

• Symptoms of methanol or ethylene glycol intoxication are delayed if

ethanol has been co-ingested.

• A patient with suspected ethylene glycol ingestion should be observed

and monitored for 6 hours.

• If no ethanol is present, the patient remains completely asymptomatic,

there is no osmolar gap, and no metabolic acidosis develops, the
patient can be discharged.
• A patient with suspected methanol ingestion should be observed for 12 hours
using the same criteria.

• Patients with significant signs and symptoms should be admitted to an

intensive care setting.

• Patients seen at facilities unable to provide hemodialysis or intensive care

should be transferred as soon as possible to institutions capable of providing
such care.

• Suicidal patients should receive a psychiatric evaluation when their condition

improves and prior to discharge.
Case scenario
• A 47 year-old male with a history of substance use disorder and bipolar
disorder along with morbid obesity, DM and COPD presents to the ED at
0200 after calling to nearby hospital and reporting chest pain.
• He is cooperative in the ED, but observed to be mumbling to himself
and staring at staff suspiciously. He is given lorazepam 1mg PO to calm
him.
• Since arriving to the floor to rule out MI, he has become increasingly
restless, irritable, and confrontational. He is increasingly uncooperative
with medical care, then becomes verbally and physically threatening to
the staff.
• Agitation
• Excessive motor or verbal activity
• “an emergent situation that is temporary, breaks the therapeutic alliance, and
is in need of a prompt and immediate intervention” (Garriga et al. 2016)
Component Behaviors of Agitation
• Nonaggressive behaviors
• Restlessness (akathisia, fidgeting)
• Wandering
• Loud, excited speech
• Pacing or frequently changing body positions
• Inappropriate behavior (disrobing, intrusive, repetitive questioning)
• Aggressive behaviors
• Physical
• Combativeness, punching walls
• Throwing or grabbing objects, destroying items
• Clenching hands into fists, posturing
• Self-injury (repeatedly banging one’s head)
• Verbal
• Cursing
• Screaming
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Etiology of Agitation: Medical
Causes
• Head trauma  Hypoxia
• Encephalitis, meningitis, other  Thyroid disease
infection  Seizure (including post-ictal state)
 Toxic levels of medications
• Encephalopathy (e.g., liver or
renal failure)
• Environmental toxins
• Metabolic abnormalities
(sodium, calcium, glucose)

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Etiology of Agitation:
Substances
• Substance intoxication –
• Alcohol, cocaine, amphetamines, cannabis, ketamine, ecstasy, bath salts,
inhalants

• Substance withdrawal –
• Alcohol withdrawal delirium/DTs

• CNS effects of non-psychiatric medications (steroids)

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Etiology of Agitation: Primary Psychiatric disorders

 Schizophrenia
 Bipolar Disorder
 Neurocognitive Disorder (Dementia)
 Personality Disorders
 Agitated depression
 Anxiety disorder
 Autism spectrum disorder

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 Agitation Management
• Medical evaluation and triage
• Psychiatric evaluation
• Verbal de-escalation
• Environmental intervetions
• Psychopharmacologic interventions
• Use of seclusion/restraint

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Assessment of Agitation
For patients with atypical features additional diagnostic tests may be
required
• Atypical presentations
• Delirium
• History of trauma
• Overdose
• Headache
• Fever
• Diagnostic tests to consider
• Toxicology screens
• CT of brain
• BMP, CBC, and LFTs
• Urinalysis
• Endocrine tests
• Lumbar puncture

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Communication/Behavioral Interventions
• Nonverbal
• Maintain a safe distance
• Maintain a neutral posture
• Do not stare; eye contact should convey sincerity
• Do not touch the patient
• Stay at the same height as the patient
• Avoid sudden movements
• Verbal
• Speak in calm, clear tone
• Personalize yourself
• Avoid confrontation; offer to solve the problem

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 Environmental Interventions
• Examples of effective non-pharmacological treatments
• Clearing the room
• Removing dangerous objects
• Having staff available as a “show of force”
• Close observation
• Calm conversation
• Decreasing sensorial stimulation

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Thank you