1. Toxic Alcohol
Thitisak Kitthaweesin, M.D.
Department of Medicine
Phramongkutklao Hospital and
College of Medicine

2. Osmolal Gap
 Osmolal Gap = Measured Serum Osmol –
Calculated Serum Osmol
 Normal Osmolal gap < 10 mOsm/L
 High Osmolal gap > 20 mOsm/L

3. Alcohol
 Ethanol
 Isopropanol
 Methanol
 Ethylene glycol

4. Ethanol Isopropanol Ethylene glycol Methanol
COMMON
SEVERITY
Ethanol Isopropanol Ethylene glycol Methanol

5. Ethanol Methanol Isopropanol Ethylene glycol
COMMON
SEVERITY
Ethanol Isopropanol Ethylene glycol Methanol

6. Effect of Alcohol on Serum
Osmolality
Compound Molecular Weight ∆Sosm(mOsm/L) per
10 mg/dL ∆Serum
Alcohol Concentration
Methanol 32.04 3.09
Ethanol 46.07 2.12
Isopropanol 60.02 1.66
Ethylene glycol 62.07 1.60
Propylene glycol 76.09 1.31
Diethylene glycol 106.12 0.90

7. Kinetics of Major Alcohols
Alcohol Vd (L/kg) Half-Life (h) Route of Elimination (%)
Alone With Liver Lung Renal
Ethanol
Ethanol 0.5 2-6 95 2 3
Methanol 0.6-0.7 14-30 43-96 97 2.5 1
Ethylene 0.5-0.8 3-8 17-18 80 - 20
glycol
Diethylen 0.5 4-6 ?> 30-50 - 50-70
e glycol
Propylen 0.5 1.4-3.3 17 55-5 - 25-45
e glycol
Isopropa 0.5 2.5-6.4 ? 80-90 - 10-20
nol

8. Ethanol
Most commonly ingested alcohol

9. Ethanol Sources
 Alcoholicdrinking
 Mouthwashes
 Colognes
 Medical preparations

10. Pathophysiology
 CNS depression : inhibit neuronal activity
 Cross-tolerance exists : ethanol + sedative
drugs (benzodiazopine, barbiturates)
 Absorption : Proximal small bowel >
stomach, large bowel > mouth, esophagus
 Gender-relate differences
 Excretion : lungs, urine, sweat

11. Ethanol Metabolism

12. Ethanol Intoxication
 Slurred speech
 Disinhibited behavior
 CNS depression
 Decreased motor coordination and control
 Hypotension

13. Ethanol level > 50 mg/dL

14. The maximum blood alcohol
level limit for drivers

15. Symptoms
• depend on both the serum concentration and individual ethanol metabolism
Serum ethanol level Symptoms
less than 25 mg/dL warmth and well-being.
25-50 mg/dL. Euphoria and decreased
judgment
50-100 mg/dL. Incoordination, decreased
reaction time/reflexes
100-250 mg/dL Cerebellar dysfunction (ie,
ataxia, slurred speech,
nystagmus)
greater than 250 mg/dL Coma
greater than 400 mg/dL respiratory depression, loss of
protective reflexes, and death

18. Ethanol Withdrawal
 Palpitation
 Autonomic hyperactivity
 Sinus tachycardia
 Seizure
 Maximal symptom occur in 48 hrs.

19. Treatment
 Observation
 Hypoglycemia should be excluded
 Thiamine
 Activated charcoal (ineffective)

20. Alcoholic Ketoacidosis
(AKA)

21. Epidemiology
 Uncommon in patients with acute ethanol
intoxication
 Most frequent in patients who have long term
ethanol intake, liver disease and develop
syndrome after period of a binge drinking
 Associated with reduced food intake,
vomiting
 Mortality is low 1%

22. Pathophysiology
 Precursor of ketone
 Ketogenesis attributed to
lipolysis, FFA generation from low
insulin level and increased level
of epinephrine, cortisol, glucagon
 Excess production of acetoacetic
acid and β-hydroxybutyric acid

23. Clinical Findings
 Abdominal pain
 Nausea, vomiting
 Altered mental status

24. Laboratory Findings
 Metabolic acidosis ,usually wide AG
 Mixed acid-base disorders
 HCMA is uncommon
 Hyponatremia, hypokalemia, hypophosphatemia
 Serum osmolality often normal
 Elevated sOsm from elevated serum ethanol or
ketone
 Serum ethanol level often undetectable
 Blood glucose low, normal or high

25. Treatment
 Resolution of AKA occurs after administration
of dextrose and/or saline
 Restore volume deficit and provide glucose to
prevent hypoglycemia

26. Isopropanol
Isopropanol ( CH3CHOHCH3)
Isopropyl
2-propanol

27. Isopropanol
(Isopropyl Alcohol)
 Second most commonly ingested alcohol
 Severity : methanol, ethylene glycol >
isopropanal > ethanol

28. Sources
 Industry solvent
 Disinfectant
 Skin and hair products
 Jewelry cleaners
 Detergents
 Paint thinners
 Antifreeze

29. Pathophysiology
 Clear, burning taste and aromatic odor
 Rapidly absorb within 30 minutes
 Complete absorption within 2 hrs.
 Excretion : kidney 20- 50%
 Metabolism pathway

30. Isopropanol Metabolism
NAD+ NADH+H+
Isopropanol Acetone

31. Toxic dose
 70% isopropanol
 0.5 ml/kg : Symptom
 1.0 ml/kg : Toxic dose
 2-4ml/kg : Lethal dose
 (Report 1 liter survival)
 Children swallow 3 times : Symptom

32. Clinical Features
 Symptoms familiar with ethanol
 But occur in long duration toxication and CNS
depression
 Nystagmus, coma, respiratory depression
and hypotension

33. Lab
 High osmolal gap
 Ketosis
 Without wide AG metabolic acidosis

34. Laboratory Facts
 Serum level 60 mg/dL increase serum osmolarity 10
mOsm/kg
 Acidosis is rare : parent and metabolite are not
organic aicd
 High serum or urine acetone level without acidosis is
suggestive of recent isopropanol ingestion
 Renal failure in setting of significant hypotension
 Hypoglycemia : result from interference of
gluconeogenesis by isopropanol

35. Treatment
 Supportive treatment
 Inhibition of alcohol dehydrogenase is not indicated
because acetone is less toxic than isopropanol
 Hemodialysis
 Isopropanol level > 400 mg/dL
 Significant CNS depression, renal failure or
hypotension
 If acidosis is significant  investigate for other
cause

36. Methanol
Methanol (CH3OH) or Methylalcohol
Wood spirits
Wood alcohol

37. Sources
 Shellacs, varnishes, paint removers
 Windshield washing fluids and antifreeze
formulations
 Contaminated whiskey
 Accidental ingestion
 Suicidal

38. Character
 Colorless
 Volatile liquid
 Distinctive odor
 Rapid absorption
 Minimum lethal dose for adults is 10 mL

39. Pharmacokinetics
 MW 32 g/mol
 Vd 0.6 L/kg
 Rapid absorption after ingestion Peak 30-90 min
 Highest concentration at kidney, liver and G.I. tract
 Vitreous humor, optic nerve : high level
 Elimination half-life 14-18 hr without treatment
 Excretion : 90-95% by liver
2-5% by renal
Other by respiratory system

40. Metabolism of Methanol

41. Clinical Features
 Onset may be delayed
 Early: mucosal irritation, N/V, abdominal pain
 Late : CNS depression, No early phase of
elation
 Visual disturbances (looking into snow
field)
 Wide anion gap metabolic acidosis

42. Symptomatology
 Early period
 CNS depression
 Effect of methanol before metabolized
 Latent period
 Accumulation of formate
 Last 14-18 hr
 Followed by systemic findings

43. Diagnosis of methanol poisoning
 History
 Wide anion gap metabolic acidosis and
osmolar gap
 DDx.
 Ethylene glycol, DKA, Paraldehyde, Isoniazid,
Salicylates, Iron, Lactic acidosis, Phenformin,
Uremia

44. Methanol blood concentration
 mg/dL  normal methanol blood
concentation from endogenous sources
 mg/dL  Asymptomatic
 mg/dL  Serious poisoning
 - mg/dL  Risk of fatality

45. Systemic Findings
 Metabolic acidosis
 CNS effects
 Ocular findings
 Other

46. Systemic Findings
 Metabolic acidosis
 pH < 7.0 strongest predictor of mortality
 Mortality increased 20 times pH <7.0 Vs >7.0
 CNS effects
 Headache
 Lethargy, delirium
 Convulsion, coma…increased mortality 10 times

47. Systemic Findings
 Ocular findings
 Direct cytotoxic effect of formate on retina
 Photophobia
 Central scotoma
 Visual field defects
 Fixed pupils and difficulty with light adaptation
 Pupillary dysfunction : strong predictor of mortality
 Fundoscopic signs : hyperemia, disk edema,
possible optic atrophy

48. Systemic Findings
 Other findings
 Nausea, vomiting
 Diaphoresis
 Abdominal pain
 Pancreatitis

49. Diagnosis of methanol poisoning
 History
 Wide anion gap metabolic acidosis and
osmolar gap
 DDx.
 Ethylene glycol, DKA, Paraldehyde, Isoniazid,
Salicylates, Iron, Lactic acidosis, Phenformin,
Uremia

50. Anion Gap
 High anion gap metabolic acidosis
 Formate accumulation
 Lactate production
 Early or later after co-ingestion with MetOH+EtOH
may have little or no acidosis

51. Osmolar Gap
 Methanol produce osmolar gap
 Serum level 32 mg/dL increased measured serum
osmolarity 10 mOsm/kg
 Normal osmolar gap <10 mOsm/kg
 Present later after ingestion and methanol
converted to formate
 Formate not contribute to serum osmolarity
because it is balanced by sodium

53. Methanol blood concentration
 mg/dL  normal methanol blood
concentation from endogenous sources
 mg/dL  Asymptomatic
 mg/dL  Serious poisoning
 - mg/dL  Risk of fatality

54. Treatment
 Take BS, BUN, Cr, methanol, ethanol level
 Glucose + Thiamine + Naloxone
 Supportive care
 Correction of acidosis : NaHCO
 Administration of fomepizole or ethanol
 Dialysis

55. Ethanol
 Indication
 Plasma level > 20 mg/dL
 Recent history of methanol ingestion with
serum osmolal gap > 10 mOsm/L
 Strong clinical suspicion of methanol
poisoning with at least two of the following
 Arterial pH < 7.3
 Serum HCO3- <20 mEq/L
 Osmolal gap > 20 mOsm/L
AACT Recommendation, 2002

56. Management
Loading dose : . - . g/kg
oral or I.V.
( Alcoholism 
mg/kg )
Maintenance : . g/kg/hr.
( Hemodialysis  .
g/kg/hr.)

60. Hemodialysis
 Indication
 50 mg/dL
Methanol level
 Methanol consumed 30 mL
 Severe metabolic acidosis or high
formate level
 Visual, fundoscopic or CNS
disturbance

61. Ethylene glycol

62. Source
 Coolant (antifreeze)
 Preservative
 Glycerine substitute

63. Character
 Colorless, odorless, sweet taste
 Rapidly absorbed : ingestion
 Not by lungs, skin

64. Metabolism
ADH ALDH Folate
Methanol Formaldehyde Formic acid CO2+H2O
ADH ALDH
Ethylene glycol Glycoaldehyde Glycolic acid
Thiamine Glyoxylic acid
Pyridoxine,
Mg++
Glycine+Benzoic acid
α-hydroxy-β-ketoadipic acid Oxalic acid
Hippuric acid

65. Clinical features
 3 Phases
 Phase 1: - hrs.
 Slurred speech and ataxia. But without the odor of
ethanol on their breath
 Phase 2: - hrs.
 Cardiopulmonary, CHF, ARDS
 Phase 3 : - hrs.
 Nephrotoxicity, oligulic renal failure, ATN

66. Renal Toxicity
 Direct toxic effect from metabolites of
ethylene glycol
 Hydronephrosis and obstruction from calcium
oxalate crystal
 Most renal damage is reversible
 Renal recovery may take a few month

67. Laboratory
 Wide AG metabolic acidosis
 Calcium oxalate crystalluria
 Acute renal failure
 Hypocalcemia
 High osmolal gap*

68. Calcium oxalate crystal
 Monohydrate form  Dihydrate form
 Dumbbell shape  Octahedral shape
 More common  More specific
 Ingestion of high  Require higher
vitamin C and high oxalate concentration
urate-containing food for its formation
 More indicative of
intoxication

69. Calcium oxalate crystal

70. Treatment
 Supportive treatment
 Airway protection
 Circulatory support
 Correction of metabolic abnormalities
 Control seizure

71. Treatment
 No role for activated charcoal, cathartics or
gastric lavage
 Asymptomatic hypocalcemia
 Risk of ↑ formation of calcium oxalate crystal
 Alcoholic persons and malnourished should
be given thiamine and pyridoxine

72. Antidote
 Indication
 Plasma concentration > 20 mg/dL
 Recent ingestion and Osmolar gap > 10
mOsm/kg or high clinical suspicion
 AND 2 of the followings
 pH < 7.3
 Serum bicarbonate < 20 mmol/L
 Osmolar gap > 10 mOsm/kg
 Urinary oxalate crystals

73. Antidote
 Ethanol
 FDA not approved
 Loading dose 0.6 g ethanol/kg
 Constant infusion to keep blood alcohol
level 100-200 mg/dL
 Average maintenance dose 100 mg/kg/hr
 Blood alcohol checked every 1-2 hr until
steady state then 2-4 hr

74. Antidote
 Fomepizole
 FDA approved
 Loading dose 15 mg/kg
 Followed bt 10 mg/kg every 12 hr for 48 hrs
 After 48 hrs, 15 mg/kg every 12 hr
 Continued until serum ethylene glycol level
< 20 mg/dL, asymptomatic and normal pH
 In dialysis, fomepizole need to be dosed
every 4 hr

75. Hemodialysis
 Indication
 pH < 7.3
 Respiratory failure or hypotension
 ARF unresponsive to standard therapy
 Ethylene glycol level > 50 mg/dL*
* May be treated with fomepizole without hemodialysis

79. Substance Metabolites WGMA High Ketosis CNS Findings
Osmol depression
Gap
Ethanol Acetaldehyde Alcohol
acetic acid + + + + intoxication
Ethylene Oxalic acid, Renal failure
glycol glycolic acid ++ + - + Hypocalcemia
CalciumOxalate
crystalluria
Isopropyl Acetone Ketosis without
alcohol
- ++ + ++ acidosis,
Hemorrhagic
tracheobronchitis
Methanol Formaldehyde Blindness, pale
formic acid ++ + - + edematous optic
disc

80. Organ Ethylene Glycol Isopropanol Methanol
System
CVS Tachycardia Tachycardia Tachycardia
Hypertension Hypotension Hypotension
Hypotension Myocardial
Dysrhythmias depression
Myocarditis
CNS Ataxia Areflexia CNS depression
Meningoencephalitis Ataxia Convulsions
Convulsions CNS depression Dizziness
CNS depression Dizziness Headache
Inebriation Headache Hypothermia
Myoclonus Inebriation Inebriation
Muscle weakness
Hypothermia

81. Organ Ethylene Glycol Isopropanol Methanol
system
GI Nausea, Vomiting Abdominal pain Abdominal pain
Cramping Anorexia
Gastritis Gastritis
Hematemesis Nausea,vomiting
Nausea,vomiting Pancreatitis
Eye Ophthalmologic “Snow field”
Nystagmus Blurred vision
Hyperemic optic discs
Mydriasis
Papilledema, blindness
Pulmonary Hyperventilation Odor of acetone
Tachypnea Respiratory depression
Pneumonitis Hemorrhagic
Respiratory tracheobronchitis
depression
Renal Calcium oxalate Renal tubular acidosis
crystalluria Rhabdomyolysis

83. Thank You