Alcohol intoxication & withdrawal

ALCOHOL INTOXICATION AND
WITHDRAWAL
DR. PREM MOHAN JHA
JR3,
P.G. DEPTT. OF MEDICINE.
S.N.M.C., AGRA

INTRODUCTION
• The harmful use of alcohol results in 2.5 million
deaths each year.
• 320,000 young people between the age of 15 and
29 die from alcohol-related causes, resulting in 9%
of all deaths in that age group.
Global Status Report On Alcohol 2004, Geneva, WHO.

ACUTE ETHANOL
INTOXICATION
• Legal limit for intoxication - 80mg/dL
• Odor threshold - 10 ppm

ABSORPTION
 Stomach (70%),
 Duodenum (25%)
 Mouth and Esophagus (small amounts)
European journal of internal medicine 19 (2008) 561-567.

DISTRIBUTION& ELIMINATION
 Distributed to almost every tissue. Vd=0.5 l/kg.
 Half life = 2 – 6 hr .
Ethanol Acetadehyde+NADH
+NAD
Acetate
CO2+H2O Acetyl coA
Clin J Am Soc Nephrol 3 (2008) 208-225

CLEARANCE
 15 – 18 mg/ 100 ml blood/ hr.
 Zeero order kinetics.
 Independent of alcohol conc.
 2 – 10 % is excreted directly through the lungs, urine, or sweat,
but
 The greater part (90 – 95%) is metabolized (oxidised) to
acetaldehyde, primarily in the liver.
 Blood levels of ethanol are expressed as milligrams or grams of
ethanol per deciliter (e.g., 100 mg/dL = 0.10 g/dL)
 Values of 0.02 g/dL resulting from the ingestion of one typical
drink.
Harrisons principles of internal medicine, 18th ed, vol.2

ALCOHOLCONTENTOFVARIOUSBEVERAGES
BEVERAGE ALCOHOLCONTENT SERVINGSIZE AMOUNTOFALCOHOL
Beer 5% 12oz 13.85g
Wine 12% 4oz 10.7g
Fortifiedwine 20% 4oz 17.8g
Hardliquor 40% 1.5oz 13.4g
SleisengerandFordtran'sGastrointestinalandLiverDisease,9th
ed,vol.2.

PATHOPHYSIOLOGY
• Stimulate GABAA recepto
• ↑NAD/NAD ratio.
• ↑ketogenesis.
• ↓gluconeogenesis
• ↑glycogenolysis
• Fluid & electrolyte imbalance.

Effects of Blood Alcohol Levels in the Absence of
Tolerance
Blood Level, g/dL USUAL EFFECT
O.O2 Decreased inhibitions, a slight feeling of intoxication
0.08 Decrease in complex cognitive functions and motor
performance
0.20 Obvious slurred speech, motor incoordination, irritability, and
poor judgment
0.30 Light coma and depressed vital signs
0.40 Death

SIGNS THAT IMMEDIATE MEDICAL
ATTENTION IS NEEDED
 Nervous system depression (sleepiness, coma, lethargy, and
decreased response to pain)
 Withdrawal accompanied by pain
 Digestive problems that include vomiting, bleeding, and dehydration
 Slow or absent breathing
 Grand mal seizures
 Delirium tremens
 Disturbances of vision, mental confusion, and muscular incoordination
 Disinterested behavior and loss of memory

ASSCOCIATED ACUTE PROBLEMS
• Alcoholic ketoacidosis.
• Alcoholic hypoglycemia.
• Fluid & electrolyte imbalance.
• Wernicke’s encephalopathy.
• Acute effects on heart.
• Acute GI efects.
• Acute alcoholic myopathy.
• Trauma
• Associated other substance poisoining.

Alcoholic ketoacidosis:
• High anion gap acidosis
• Normal or low glucose level
• Chronic alcoholics
• Binge drinking weeks before symptoms
• Dehydration, starvation due to vomiting ,gastritis

• Alcohol Poor food intake Dehydration
↓ ↓ ↓
Acetaldehyde glycogenolysis ↑counter
regulatory
↓ hormones
Acetate ↓ ↓
↓
↑NADH/NAD ↑Glucagon
ratio ↓Insulin
↓gluconeogenesis
KETOGENESIS

• Altered mental status
• Kussumal breathing
• Ketotic breath
• Lab finding
high anion gap acidosis
↑beta hydroxybutyrate:acetoacetate
↓insulin level
• Exclude other causes of ↑metabolic acidosis.
Alcoholic ketoacidosis:

ALCOHOLIC HYPOGLYCEMIA
• Chronic “street alcoholic” found unresponsive
• Symptoms
Neuroglycopenic →confusion,fatigue,seizure,
Loss of consciousness→death
Autonomic responses → palpitation ,tremor ,
sweating
• Signs
Pallor ,diaphoresis
Tachycardia,raised systolic B.P
Transient focal neurological signs

• “all alcoholics are dehydrated” is false.
• Immediate ↑ in urine volume followed by ↑ADH.
• Hydration also depends on
-diet,nonalcoholic fluids,type of drinks
-vomiting, diarrhea,infection
• Water intoxication & hyponatremia in severe chronic
alcoholics→seizure& altered sensorium
• Central pontine mylenolysis
WATER AND ELECTROLYTES DISORDERS

Other electrolytes abnormalities
• Hypomagnesemia
• Hypophosphatemia
• Hpokalemia
• Hypocalcemia
WATER AND ELECTROLYTES DISORDERS

• As high as 12.5% in alcoholics.
• Major reversible cause of death.
• If untreated 10-20% mortality rate.
• Thiamine deficiency is the root cause.
• Magnesium deficiency in thiamin resistant cases.
• Clinical features
 Global confusion
 Ocular abnormalities
 Ataxia
WERNICKE-KORSAKOFF’S SYNDROME

ACUTE EFFECT ON HEART
• Direct negative inotropic effect & vasodilation.
• PR & QT prolongation
• Both supraventricular & venntricular arrythmia.
• “holiday heart syndrome”
• Various degree of heart block.
• +ve correlation between and sudden cardiac death.

ACUTE ALCOHOLIC MYOPATHY
• Acute muscle necrosis mainly in binge drinkers
• Alcoholism is the most common cause of
rhabdomyelisis
• Raised CKMM,myoglobinuria,
• Acute tubular necrosis→↑urea ,creatinine
• Conservative management

ACUTE GASTROINTESTINAL EFFECT
• Acute gastritis & esophagitis.
• Epigastric distress and gastrointesinal bleeding.
• Mallory-weiss tear.
• Acute hepatitis & pancreatitis.

 Toxic
 Metabolic
 Infectious diseases
 Neurologic
 Trauma
 Miscellaneous.
DIFFERENTIAL DIAGNOSIS
IN ACUTELY INTOXICATED PATIENT.

DIAGNOSIS
HISTORY
 Quantity of alcohol consumed
 Type of beverage
 Time course of symptoms
 Circumstances
 Eventual injuries
PHYSICAL EXAMINATION
 Vital signs
 Nutritional status
 Hydration
 Alcoholism related signs e.g. capillary prominence,spider naevi,
telengiectasias, palmar erythema, muscular atrophy

LAB INVESTIGATIONS
1. BAC (blood alcohol conc.) –
most imp.
2. Serum osmolality – increases
3. Sodium, potassium, calcium
4. B. urea nitrogen,
5. B. sugar,
6. Amylase,
7. LFT,
8. ABG,
9. Urine/blood ketones,
10. ECG,
11. CXR-PA,
12. CT Head when head trauma
suspected

TREATMENT
• Airway assessment
• Breathing
• Circulation
• IV assess
• Rules tube, Propped Up Position – to avoid aspiration.
• Foleys catheterisation
• Thiamin 100 mg im/ iv stat.
• Mechanical ventilation if required.

 IV solution containing : 1 ltr 0.45% DEXTROSE
NORMAL SALINE,2 gm MAGNESIUM SULPHATE, 1
mg FOLATE, 100 mg THIAMINE.
 Antiemetic drugs
 Sedatives – agitated, violent pt
 Droperidol, haloperidol
 Physical restrains- used only in extreme conditions
 Mechanical ventilation & intensive care
TREATMENT contd…

 METADOXINE is the one specific drug that is useful in tt of acute
alcohol intoxication
 It fascilitate atp synthesis and prevent decrease in atp in both
brain and liver
 Single iv injection of 900 mg significantly decreases half life of
ethanol in blood.
 Medial time of recovery is around 1 hr.
TREATMENT contd…

TOXICOKINETICS
ABSORPTION
o Most of the cases of methyl alcohol intoxication occur
through oral ingestion intentionally or accidently (half
life – 5 mints). Peak absorption occuring b/w 30 – 60
mints.
o Other routes of absorption are through intact skin,
inhalation etc.
DISTRIBUTION
o Rapid distribution results in peak plasma conc within 30
– 60 mints.
American Academy Of Clinical Toxicology,40(4), 415-446, (2002

METABOLISM
Methanol + NAD+ Formaldehyde + NADH
( alcohol dehydrogenase)
Formic acid
(folate)
CO2 + H2O

CLINICAL FEATURES
• Inebriated but lack of euphoria.
• 40 minutes --- 72 hrs of latent period.
• Fatal dose 60-240 ml.
• Signs and symptoms are mainly limited to CNS, EYE
& GIT.
• Vertigo, light headedness, dyspnea , agitation.
• Nausea, vomiting, diarrhea, abdominal pain (d/t
developement of acute pancreatitis),
• Blurred vision, photophobia, ↓ visual acuity.
American Academy Of Clinical Toxicology,40(4), 415-446, (2002)

CLINICAL FEATURES contd…
• Blurred vision with relatively clear sensorium strongly suggest
methanol intoxication, but
• Absense of symptoms and clear sensorium does not rule out serious
toxicity.
• CO-ingestion of ethanol typically delays symptoms beyond 24 hrs.
• BRADYCARDIA, BLINDNESS, SEIZURES, PROLONGED COMA, SHOCK,
PERSISTANT ACIDOSIS & ANURIA ARE SERIOUS PROGNOSTIC SIGNS.

Physical examination
 Constricted visual field,
 Fixed & dilated pupils,
 Retinal edema &hyperemia of disk
 Opisthotonus
 Respiratory failure / arrest is the main
cause of death.
CLINICAL EFFECTS contd…

LAB FINDING
 High anion gap
Metabolic acidosis
High osmolar gap
 Strongly suggest methanol toxicity.

ROUTINE LAB FINDING
1. S. methanol & ethanol conc.
2. S. Electrolytes including calcium.
3. S. BUN
4. S. creatinine
5. CBC
6. URINE- routine, microscopy and for ketones.
7. SGOT / SGPT
8. S. Amylase
9. ABG

IMAGING STUDIES
 B/L NECROSIS OF PUTAMEN is the most consistent
radiographic finding following severe methanol
toxicity.
 Marked cerebral edema
 Persistant of occipital lesions in cerebral cortex on
repeat MRI after 1 month suggests that visual
impairement is permanent.

AmericanAcademyOfClinicalToxicology,40(4),415-446,(2002)

TREATMENT contd….
 Aggressive tt of acidosis by sodabicarbonate.
 Ethanol
Achieve BAC of 100- 150mg /100ml
Loading 0.8gm/ kg of 5 – 10% ethanol
Followed by 130mg/kg/hr.
Oral loading if no iv preparation
If dialysis,250-350 mg/kg/hr.

• Folic acid : 30 mg iv every 4 hrly
• Leucovorin : 1-2mg/kg iv
• Fomepizole : 15-20 mg/kg iv
• Haemodialysis (not haemoperfusion)
• HAEMODIALYSIS INDICATIONS:
 Methanol>20-50mg/100ml
 Acidosis not responsive to bicarbonate
 Formate levels > 20 mg/100ml
 Visual impairment
 Renal impairement
• Dialysis till methanol level≈0mg/100ml and acidosis clears.

WITHDRAWAL SYNDROME
Results from Ethanol intake reduction
NOT necessarily result of complete withdrawal

INTRODUCTION
Usual time from last drink is about 5 days
but can last upto 14 days.
Do not treat alcohol withdrawal with more
alcohol.
American family physician .march (2004), vol . 69 (6),1448.

Australia government deptt of health and aging guidelines

Americanfamilyphysician.march(2004),vol.69(6),1448.

ASSESSMENT OF SEVERITY
SIWA-Ar scale
Score <9 - Mild
9 – 15 - Moderate
>15 - Severe withdrawal

Alcohol intoxication & withdrawal

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