Methanol Toxicity with a Normal Osmolal Gap
Christiane Mbianda, MD; Maria Herrera, MD; Amit Taneja, MD
Department of Medicine, Division of Pulmonary & Critical Care Medicine, Medical College of Wisconsin, Milwaukee, WI
DISCUSSION:
OBJECTIVES
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•
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Define osmolal gap
Discuss causes of high osmolal gap
Normal osmolal gap does not rule out methanol toxicity
CASE PRESENTATION
A 48-year-old male with history of depression admitted to the intensive care
unit (ICU) after ingesting > 500 tablets of extra-strength Acetaminophen. NAcetylcysteine infusion was initiated and patient mechanically ventilated
due to impending respiratory failure.
Physical Exam:
Intubated, sedated
Afebrile , HR 94, BP 135/65, RR 20 , Pox 95% on 40% FiO2
Cardiovascular, Abdominal, Rectal Exams: normal
Labs:
Acetaminophen level: 800 mg/L, Lactic Acid: 10.8 mmol/L
Serum Osmolality: 296 mOsmol/Kg; Osmolal Gap: 0 mOsm/Kg
Anion Gap: 16 mmol/L
On day 1, patient was maintained on NAC infusion. He required volume
resuscitation and initiation of vasopressor infusion to maintain effective
circulation. Over next several hours, lactate level decreased and yet patient
developed worsening anion gap metabolic acidosis. Other usual culprits for
presence of anion gap (salicylates, ketones, uremia) were absent. He had
to be deeply sedated and transiently paralyzed to promote patient-ventilator
synchrony. Even though he had no osmolal gap, illicit alcohol screen was
checked and was positive for methanol. Patient was initiated on fomepizole
and CRRT.
Figure 1: Esophageal erosion
Anion Gap Acidosis: presence of
Osmolal gap: presence of unmeasured
unmeasured anion
osmole
AG = (Na) – (Cl +bicarb)
Methanol
Osmolar Gap = Calculated Posm -Measured Posm
Uremia
Diabetic (and other) ketoacidosis Calculated Posm = 2 * Na + Glu + BUN
Paraldehyde (and other poisons)
18
2.8
INH
Ketones
Lactate (type A, B and D)
Alcohols (ethanol, methanol, isopropyl
Ethylene glycol (ilicit alcohols)
alcohol, ethylene glycol)
Salicylate
Note that normal osmolal gap ranges from -14 to + 10
TREATMENT of Methanol Poisoning
Fomepizole or
Ethanol
Figure 2: Duodenum with circumferential
erythema and inflammation
HOSPITAL COURSE
 Day 1: NAC infusion, unexplained worsening AGMA with normal osmolal gap,
. surprisingly positive for methanol.
 Day 2:, CRRT continued
 Day 3: worsening liver injury, cerebral edema
 Day 4: hypothermia protocol
 Day 5: Upper GI bleed, EGD, suggestive of caustic ingestion
 Day 6: Cerebral edema improved, rewarming process
 Day 7: stable hemodynamics
 Day 11: Extubated
 Day 12: normal mental status, normal MRI brain; Psychiatry evaluation
 Day 13: Transfer to medical floor
 Day 18: Discharged from the hospital
Chemistry:
Methanol is an alcohol which is sequentially metabolized by alcohol
dehydrogenase to formaldehyde and then formic acid. Osmolal gap is caused by
presence of alcohol, as it is an unmeasured osmole. Toxicity however is caused
by formic acid, which exists at physiologic pH as formate. Formate causes anion
gap. Early in the toxicity, patients have osmolal gap; however when presenting
late, most of methanol is now metabolized to formate; and they may have no
osmolar gap, only unexplained anion gap.
ANION GAP V/S OSMOLAR GAP
Figure 3: Head CT Cerebral Edema
 Endotracheal intubation, supportive care
 Administration of ethanol or fomepizole (blocks Alcohol Dehydrogenase)
 Initiation of renal replacement therapy
Supplementation
Physical Findings:
Latent period corresponds to conversion of methanol to formate
Symptoms develop 12-24 hours after ingestion
Kussmaul respirations, weakness, headache, nausea, severe epigastric pain,
visual disturbances, blindness
Memory loss, confusion, agitation
Stupor, coma
Laboratory Findings:
 Elevated Anion Gap Metabolic Acidosis
 Increased formic acid (this is not routinely measured)
 Elevated Osmolal Gap
 Elevated lactic acid
 Positive serum methanol assay
Pathology Findings:
 Cerebral edema
 Pulmonary edema
 Hemorrhagic gastritis
 Lesions in optic nerve and basal ganglia
TAKE HOME POINTS
 The gold standard for diagnosing methanol toxicity is gas chromatography.
 Results can take up to days and many hospitals are not equipped to provide this test.
 Clinicians must rely on the clinical presentation and other laboratory tests such
osmolal gap (OG) to make a diagnosis.
 Normal osmolal gap does not rule out methanol toxicity
 If suspicion of methanol toxicity is high, treatment with fomepizole or ethanol should
be initiated promptly pending methanol levels.
 Often times, toxidromes and ingestions co-exist. Thus high index of suspicion is
warranted in unexplained anion gap metabolic acidosis.
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