Toxic Alcohol Poisoning (Methanol and Ethylene Glycol)

Quick Answer

Toxic alcohol poisoning (methanol and ethylene glycol) is a medical emergency characterized by the sequential evolution from an elevated osmolar gap (parent alcohol present) to a high anion gap metabolic acidosis (HAGMA) (toxic metabolite accumulation). The primary treatment strategy involves alcohol dehydrogenase (ADH) inhibition (fomepizole preferred, ethanol alternative), adjunctive cofactor therapy, and extracorporeal elimination (hemodialysis) for severe toxicity. [1,2]

Pathophysiology:

Methanol is metabolized by ADH to formaldehyde, then rapidly oxidized to formic acid (primary toxicant causing visual impairment, CNS depression, and metabolic acidosis) [3,4]
Ethylene glycol is metabolized by ADH to glycoaldehyde, then glycolic acid, glyoxylic acid, and finally oxalic acid (causes calcium oxalate crystal deposition, acute kidney injury, and hypocalcemia) [5,6]
ADH is the rate-limiting enzyme; inhibition prevents formation of toxic metabolites while the parent alcohols are eliminated (renal excretion or hemodialysis) [7,8]

Laboratory evolution (time-dependent):

Early phase (0-12 hours): Elevated osmolar gap (greater than 10 mOsm/L) with minimal acidosis (parent alcohol is osmole, not acid)
Intermediate phase (12-24 hours): Both elevated osmolar gap and HAGMA (simultaneous presence of parent alcohol and toxic metabolites)
Late phase (greater than 24 hours): Normalized osmolar gap with severe HAGMA (parent alcohol metabolized to toxic acids) [9,10]

Treatment principles:

ADH inhibition - Fomepizole (preferred) or ethanol to prevent formation of toxic metabolites [11,12]
Sodium bicarbonate - Correct metabolic acidosis (target pH greater than 7.3) to prevent ion trapping of formic acid in CNS [13,14]
Cofactor therapy - Folate for methanol; thiamine and pyridoxine for ethylene glycol [15,16]
Hemodialysis - Remove both parent alcohol and toxic metabolites, correct acidosis, and treat AKI [17,18]

Fomepizole dosing:

Loading: 15 mg/kg IV over 30 minutes
Maintenance: 10 mg/kg IV every 12 hours for 4 doses, then 15 mg/kg IV every 12 hours thereafter (auto-induction of metabolism)
During hemodialysis: 10 mg/kg IV every 4 hours (or after dialysis session) [11,12]

Ethanol alternative dosing (if fomepizole unavailable):

Loading: 0.6 g/kg IV of 10% ethanol (dextrose-containing)
Maintenance: 66-154 mg/kg/hr continuous infusion (adjust to maintain serum ethanol 100-150 mg/dL)
Requires frequent monitoring (q1-2h), causes CNS depression, hypoglycemia [19,20]

Hemodialysis indications (EXTRIP 2015): [17,18]

Methanol: Plasma level greater than 50 mg/dL OR visual disturbances OR severe metabolic acidosis (pH below 7.25) despite maximal medical therapy
Ethylene glycol: Plasma level greater than 50 mg/dL OR anion gap greater than 20 mmol/L OR pH below 7.25 OR calcium oxalate crystalluria OR clinical deterioration despite therapy
Any toxic alcohol: Refractory shock, acute kidney injury requiring renal replacement, electrolyte abnormalities refractory to medical management

CICM Exam Focus

Key High-Yield Points

Sequential laboratory evolution: Toxic alcohol poisoning classically progresses from elevated osmolar gap alone (parent alcohol) → combined elevated osmolar gap + HAGMA → HAGMA with normalizing osmolar gap (toxic metabolites) [9,10]
Osmolar gap calculation: Measured osmolality - [2(Na) + (Glucose/18) + (BUN/2.8) + (EtOH/4.6)]; normal below 10 mOsm/L; each 100 mg/dL of methanol increases osmolar gap by ~32 mOsm/L [9,21]
ADH inhibition as cornerstone: Fomepizole has 8000-fold higher affinity for ADH than ethanol; prevents formation of toxic metabolites while parent alcohol is eliminated renally; must be initiated early (ideally below 6 hours) for maximal benefit [11,12]
Cofactor therapy rationale:
- Methanol: Folate or folinic acid (leucovorin) enhances conversion of formic acid to CO2 and H2O (10-carbon transfer reactions) [15,22]
- Ethylene glycol: Thiamine (B1) converts glyoxylic acid to alpha-hydroxy-beta-ketoadipate; Pyridoxine (B6) converts glyoxylic acid to glycine (non-toxic pathways) [16,23]
Formic acid pathophysiology (methanol): Formic acid inhibits mitochondrial cytochrome c oxidase (complex IV) → cellular hypoxia and lactic acidosis; accumulates in optic nerve → retinal edema, optic disc hyperemia, "snowfield vision," permanent visual loss [3,24]
Calcium oxalate crystals (ethylene glycol): Oxalic acid precipitates as calcium oxalate monohydrate (needle-shaped) and dihydrate (envelope-shaped) crystals in renal tubules → intratubular obstruction, direct tubular toxicity, acute tubular necrosis [5,25]
Hemodialysis eliminates both parent and metabolites: Fomepizole prevents new metabolite formation but does NOT remove existing toxic metabolites; dialysis removes formic acid, glycolic acid, oxalic acid, and parent alcohols simultaneously [17,26]
Bicarbonate therapy is critical for methanol: Acidic pH increases conversion of formate to its unionized form which readily crosses BBB; alkalinization (pH greater than 7.3) keeps formate ionized and trapped in plasma, reducing CNS penetration [13,27]
Fomepizole auto-induction: Hepatic metabolism induces its own metabolism (up to 50% increased clearance), necessitating dose increase from 10 mg/kg to 15 mg/kg after 4 maintenance doses [12,28]
Visual findings in methanol poisoning: Classically includes decreased visual acuity, photophobia, central scotomas, and fundoscopic findings of retinal edema, optic disc hyperemia, and in severe cases, optic atrophy; permanent visual loss is common with delayed treatment [3,24]

Common Viva Themes

Pathophysiology of methanol vs ethylene glycol toxicity and differences in target organs
Mechanism of ADH inhibition and comparison of fomepizole vs ethanol
Calculation and interpretation of osmolar gap and anion gap
EXTRIP criteria for hemodialysis initiation
Cofactor therapy rationale and dosing for each toxic alcohol
Laboratory evolution over time and implications for treatment timing
Complications of each toxic alcohol (visual loss, AKI, hypocalcemia)
Management during hemodialysis (adjusting fomepizole/ethanol dosing)

Common Pitfalls

Waiting for confirmatory serum toxic alcohol levels before initiating treatment (delay can be fatal) [29]
Not recognizing that "normal" osmolar gap does NOT rule out late-phase poisoning (parent alcohol may already be metabolized) [9,30]
Forgetting that bicarbonate is primarily indicated for methanol (formic acid) rather than ethylene glycol [13]
Incorrectly assuming dialysis is not needed if fomepizole is administered (fomepizole prevents further toxicity but does not remove existing metabolites) [17]
Missing that ethylene glycol crystals may not appear until late in course (first 6-12 hours may be absent) [5]
Not adjusting fomepizole dosing during hemodialysis (increased clearance requires more frequent dosing) [12]
Administering calcium therapy for ethylene glycol-induced hypocalcemia (can worsen calcium oxalate crystal precipitation) [31]
Failing to consider alternative diagnoses for HAGMA with osmolar gap (propylene glycol, isopropanol, DKA) [32]

Clinical Overview

Definition and Classification

Toxic alcohol poisoning encompasses ingestion of alcohol-containing compounds that are not safe for human consumption, most commonly methanol (wood alcohol) and ethylene glycol (antifreeze). Both are metabolized by alcohol dehydrogenase (ADH) to toxic metabolites that cause life-threatening end-organ damage. [1,2]

Classification by toxic alcohol:

Methanol: Methyl alcohol (CH3OH); found in windshield washer fluid, solvents, illicit alcohol (moonshine), and some industrial products [3]
Ethylene glycol: 1,2-ethanediol (C2H6O2); found in automotive antifreeze, brake fluid, and some de-icing solutions [5]

Other toxic alcohols:

Isopropanol (isopropyl alcohol): Rubbing alcohol; metabolized to acetone (causes ketosis but NOT severe acidosis); primarily causes CNS depression [33]
Propylene glycol: Solvent in IV medications (lorazepam, phenobarbital); accumulates in renal failure causing lactic acidosis [34]
Diethylene glycol: Contaminant in medications; metabolized to toxic dicarboxylic acids causing AKI and neurotoxicity [35]

Epidemiology

Global burden:

Methanol poisoning: Outbreaks associated with illicit alcohol production; mass poisonings with greater than 50-100 deaths reported in single events [36]
Ethylene glycol: ~5,000 exposures annually in the US (toxic exposure surveillance systems); ~20-30 deaths per year [37]

Risk factors:

Accidental ingestion (children, confusion)
Suicidal ingestion (most common in adults)
Occupational exposure (industrial workers)
Illicit alcohol consumption (methanol-containing moonshine)

Mortality:

Untreated methanol poisoning: 20-50% mortality; visual sequelae in 30-50% of survivors [3]
Untreated ethylene glycol poisoning: Mortality up to 80% with delayed treatment; AKI in 50-70% [5]

Clinical Presentation

Time course depends on latency of metabolism:

Methanol: Latent period 6-24 hours (variable based on co-ingestion of ethanol, which competitively inhibits ADH) [3]
Ethylene glycol: Latent period 4-12 hours (shorter latency due to more rapid metabolism) [5]

Early phase (parent alcohol dominant):

Methanol: Mild inebriation, headache, nausea, vomiting (similar to ethanol intoxication) [3]
Ethylene glycol: Ataxia, slurred speech, nystagmus, abdominal pain, nausea, vomiting [5]

Late phase (toxic metabolites dominant):

Methanol:

Visual symptoms: Blurred vision, photophobia, central scotomas, "snowfield" vision, complete blindness [24]
Neurological: Headache, seizures, altered mental status, coma
Cardiopulmonary: Tachypnea (Kussmaul respirations), shock [3]
Ophthalmologic findings: Retinal edema, optic disc hyperemia, peripapillary flame hemorrhages, optic atrophy (late) [24]

Ethylene glycol:

Renal: Flank pain, oliguria, acute kidney injury (calcium oxalate crystal nephropathy) [5]
Cardiovascular: Hypotension, arrhythmias (from hypocalcemia)
Neurological: Cranial nerve palsies (facial nerve, vocal cord paralysis), seizures, altered mental status
Musculoskeletal: Tetany, muscle cramps (hypocalcemia) [5]

Specific findings in ethylene glycol poisoning:

Calcium oxalate crystals on urine microscopy (envelope-shaped dihydrate or needle-shaped monohydrate)
Hypocalcemia (from oxalic acid binding calcium)
Elevated anion gap metabolic acidosis (glycolic acid accumulation) [5,25]

Pathophysiology

Toxicokinetics

Absorption:

Both methanol and ethylene glycol are rapidly absorbed from the gastrointestinal tract (peak concentrations 30-60 minutes)
Volume of distribution: ~0.6-0.7 L/kg (similar to total body water) [7,38]
Parent alcohols are NOT toxic; toxicity is entirely due to metabolites

Metabolism (ADH-dependent):

Methanol metabolism pathway:

Methanol → Formaldehyde (via ADH)
Formaldehyde → Formic acid (via aldehyde dehydrogenase) - RAPID (half-life below 1 minute)
Formic acid → CO2 + H2O (via tetrahydrofolate-dependent pathway) - RATE-LIMITING step [3,4]

Ethylene glycol metabolism pathway:

Ethylene glycol → Glycoaldehyde (via ADH)
Glycoaldehyde → Glycolic acid (via aldehyde dehydrogenase)
Glycolic acid → Glyoxylic acid (via lactate dehydrogenase or other oxidases)
Glyoxylic acid → Multiple pathways (shunted by cofactors):
- To α-hydroxy-β-ketoadipate (via thiamine/B1) → benign metabolites
- To glycine (via pyridoxine/B6) → benign
- To oxalic acid (if cofactor deficient) → CALCIUM OXALATE CRYSTALS [5,6]

Elimination:

Renal excretion: below 5% of parent alcohol (negligible for toxic alcohols)
Hemodialysis: Highly effective clearance (dialysis clearance greater than 200 mL/min for both methanol and ethylene glycol) [17,26]

Toxicodynamics

Methanol toxicity (formic acid):

Formic acid inhibits mitochondrial cytochrome c oxidase (complex IV of electron transport chain) → impaired oxidative phosphorylation → cellular hypoxia and ATP depletion
Accumulation of NADH/NAD+ ratio → shift to anaerobic metabolism → lactic acidosis
Formic acid accumulates preferentially in the optic nerve and retina due to local folate deficiency → direct toxic injury to retinal ganglion cells and optic nerve axons
Optic disc edema and hyperemia secondary to increased vascular permeability and impaired axonal transport [3,4,24]

Ethylene glycol toxicity (glycolic acid and oxalic acid):

Glycolic acid causes direct metabolic acidosis (primary acidotic metabolite)
Oxalic acid precipitates as calcium oxalate crystals in renal tubules → intratubular obstruction, direct tubular epithelial toxicity, inflammatory response → acute tubular necrosis
Hypocalcemia from calcium binding to oxalate → QT prolongation, arrhythmias, tetany, seizures
Cranial nerve palsies (especially facial nerve and vocal cords) likely due to crystal deposition or metabolic disturbance in nerves [5,25]

Acid-Base Physiology

Osmolar gap elevation:

Parent alcohols are osmotically active but do NOT dissociate (unlike acids)
Each 100 mg/dL methanol increases osmolar gap by ~32 mOsm/L
Each 100 mg/dL ethylene glycol increases osmolar gap by ~16 mOsm/L
Formula: OG = Measured osmolality - [2(Na) + (Glucose/18) + (BUN/2.8) + (EtOH/4.6)] [9,21]

Anion gap elevation:

HAGMA develops as parent alcohols are metabolized to acidic compounds
Primary acidotic metabolites: Formic acid (methanol), glycolic acid (ethylene glycol)
Lactic acidosis (secondary to mitochondrial dysfunction) contributes to anion gap
Formula: AG = [Na] - ([Cl] + [HCO3]); normal 8-12 mmol/L [9,32]

Ion trapping in methanol poisoning:

Formic acid exists in equilibrium between unionized (HCOOH) and ionized (HCOO-) forms
At acidic pH, equilibrium shifts toward unionized form which crosses BBB more readily
Alkalinization (pH greater than 7.3) shifts equilibrium toward ionized form which is trapped in plasma, reducing CNS penetration [13,27]

Investigations

Laboratory Studies

Immediate investigations:

Arterial blood gas (ABG): Assess for metabolic acidosis (pH, HCO3, base excess), respiratory compensation
Serum electrolytes: Calculate anion gap, assess for hypocalcemia (ethylene glycol), hypokalemia (vomiting, bicarb therapy)
Serum glucose: Exclude diabetic ketoacidosis
Serum osmolality: Calculate osmolar gap
Serum creatinine and BUN: Assess renal function (ethylene glycol)
Serum lactate: Assess for lactic acidosis component [9,32]

Specific toxic alcohol levels:

Serum methanol: Definitive diagnosis; greater than 20 mg/dL generally considered toxic threshold (EXTRIP uses 50 mg/dL for dialysis threshold) [17]
Serum ethylene glycol: Definitive diagnosis; greater than 20 mg/dL generally considered toxic threshold (EXTRIP uses 50 mg/dL for dialysis threshold) [17]

Urinalysis:

Urine microscopy for calcium oxalate crystals (ethylene glycol)
Urine pH: Assess ability to acidify urine (normal response to acidosis)
Urine ketones: Distinguish from alcoholic ketoacidosis, starvation ketosis [5,25]

Additional studies:

Serum ethanol: Co-ingestion (delays metabolism of toxic alcohols via competitive ADH inhibition)
Serum formic acid (research labs): Marker of methanol metabolite accumulation
Serum glycolic acid (research labs): Marker of ethylene glycol metabolite accumulation [32]

Coagulation studies: (If liver dysfunction suspected or massive transfusion required)

Imaging

Chest X-ray:

Evaluate for aspiration pneumonia (altered mental status, vomiting)
Assess pulmonary edema (cardiogenic vs non-cardiogenic) [9]

Head CT (altered mental status):

Early methanol poisoning: May be normal or show cerebral edema
Late methanol poisoning: Putaminal necrosis and hemorrhage (characteristic finding in severe methanol toxicity) [39,40]
Ethylene glycol: May show cerebral edema; specific findings less common [41]

MRI (if available):

More sensitive for detecting putaminal necrosis in methanol poisoning
T2 hyperintensity and diffusion restriction in basal ganglia [39,40]

Renal ultrasound (ethylene glycol AKI):

Assess kidney size, hydronephrosis, echogenicity
Usually shows enlarged, echogenic kidneys in acute toxicity [5]

Ophthalmologic Assessment (Methanol)

Visual acuity testing:

Assess baseline visual function and monitor progression
Early changes may include decreased acuity, photophobia, central scotomas [24]

Fundoscopic examination:

Early: Retinal edema, optic disc hyperemia, peripapillary flame hemorrhages
Intermediate: Optic disc pallor, retinal nerve fiber layer loss
Late: Optic atrophy (irreversible visual loss) [24,42]

Optical coherence tomography (OCT): (If available)

Quantify retinal nerve fiber layer thickness
Monitor progression and recovery [42]

Management

Initial Stabilization

ABC approach:

Airway: Protect airway in patients with altered mental status (GCS below 8), vomiting, or respiratory distress
CRITICAL: Avoid premature intubation if possible (similar to salicylates) - loss of compensatory hyperventilation leads to rapid CO2 accumulation and worsening acidosis
Breathing: Supplemental oxygen as needed; hyperventilation may be compensatory (do NOT suppress)
Circulation: IV access, fluid resuscitation, treat hypotension [9,13]

Initial fluid resuscitation:

Isotonic crystalloids (0.9% NaCl or PlasmaLyte) for volume depletion (vomiting, third-spacing)
Dextrose-containing fluids (D5W or D5NS) if hypoglycemia or suspected impaired gluconeogenesis
Target: MAP greater than 65 mmHg, urine output greater than 0.5 mL/kg/hr [9,13]

Antidote Therapy: Alcohol Dehydrogenase Inhibition

Fomepizole (4-methylpyrazole) - FIRST LINE:

Mechanism:

Competitive inhibitor of ADH with 8000-fold higher affinity than ethanol
Prevents conversion of parent alcohols to toxic metabolites
Parent alcohols are eliminated renally or via hemodialysis [11,12]

Indications:

Documented plasma methanol or ethylene glycol level greater than 20 mg/dL
Strong clinical suspicion (history, osmolar gap greater than 10 mOsm/L) PLUS:
- Arterial pH below 7.3 OR
- Serum bicarbonate below 20 mmol/L OR
- Osmolar gap greater than 10 mOsm/L [11,12]

Dosing regimen:

Loading dose: 15 mg/kg IV over 30 minutes
Maintenance: 10 mg/kg IV every 12 hours for 4 doses (48 hours total)
After 4 doses: Increase to 15 mg/kg IV every 12 hours (auto-induction of metabolism)
During hemodialysis: 10 mg/kg IV every 4 hours (OR administer one dose immediately after dialysis session) [11,12]

Pharmacokinetics:

Volume of distribution: ~1 L/kg
Hepatic metabolism (CYP2E1) with auto-induction (increased clearance up to 50%)
Half-life: 4-5 hours (extended in dialysis-dependent patients) [12,28]

Adverse effects:

Generally well-tolerated
Headache, nausea, phlebitis (rare)
Transient elevation of liver enzymes (rare) [11,12]

Ethanol - ALTERNATIVE (if fomepizole unavailable):

Mechanism:

Competitive substrate for ADH (preference for ethanol over methanol/ethylene glycol)
Requires higher serum concentrations than toxic alcohols [19,20]

Dosing regimen:

Loading: 0.6 g/kg IV (typical adult 40-50 g) of 10% ethanol in dextrose
Maintenance: 66-154 mg/kg/hr continuous infusion (adjust to maintain serum ethanol 100-150 mg/dL)
During hemodialysis: Increase infusion rate to maintain target ethanol concentration [19,20]

Monitoring:

Serum ethanol q1-2h (adjust infusion to maintain 100-150 mg/dL)
Monitor for CNS depression, hypoglycemia, respiratory depression
Dextrose-containing vehicle required to prevent hypoglycemia [19,20]

Disadvantages:

CNS depression (may complicate neurological assessment)
Hypoglycemia (especially in malnourished, pediatric, or alcoholic patients)
Requires intensive monitoring (frequent blood draws)
Intoxication may interfere with clinical assessment [19,20]

Cofactor Therapy

Methanol: Folate or Folinic Acid (Leucovorin):

Rationale:

Folate-dependent pathway converts formic acid to CO2 and H2O (rate-limiting step)
Folinic acid (5-formyl tetrahydrofolate) bypasses need for endogenous folate activation [15,22]

Dosing:

Folic acid: 50 mg IV every 4-6 hours (or 1 mg/kg IV q4-6h in pediatrics)
Folinic acid (preferred if available): 1 mg/kg IV every 4-6 hours (maximum 50-100 mg per dose)
Continue until methanol cleared and acidosis resolved [15,22]

Ethylene Glycol: Thiamine and Pyridoxine:

Rationale:

Thiamine (Vitamin B1): Cofactor for conversion of glyoxylic acid to α-hydroxy-β-ketoadipate (benign metabolite)
Pyridoxine (Vitamin B6): Cofactor for conversion of glyoxylic acid to glycine (benign metabolite)
Both shunt glyoxylic acid away from oxalic acid formation [16,23]

Dosing:

Thiamine: 100 mg IV daily (or 300 mg IV divided q6-8h)
Pyridoxine: 50-100 mg IV daily (or 50 mg IV divided q6-8h)
Continue until ethylene glycol cleared [16,23]

Note on pyridoxine toxicity:

High-dose pyridoxine (greater than 500 mg/day) can cause peripheral neuropathy (sensory ataxia)
Typical doses for ethylene glycol toxicity are well below toxic threshold [16]

Sodium Bicarbonate Therapy

Indications:

Severe metabolic acidosis (pH below 7.25-7.30)
Methanol poisoning (critical to prevent CNS formic acid accumulation)
Adjunct to hemodialysis (maintain pH greater than 7.3) [13,27]

Rationale in methanol poisoning:

Ion trapping: Alkalinization (pH greater than 7.3) shifts equilibrium toward ionized formate (HCOO-) which cannot cross BBB
Reduces CNS formic acid accumulation and neurotoxicity [13,27]

Dosing:

Sodium bicarbonate 1-2 mEq/kg IV bolus (typical 100-150 mEq adult)
Follow with continuous infusion: 100-150 mEq sodium bicarbonate in D5W at 100-250 mL/hr
Target pH: 7.35-7.45 (or greater than 7.3 acceptable)
Monitor serum sodium (may develop hypernatremia from large sodium load) [13,27]

Contraindications:

Alveolar-arterial CO2 gradient below 10 mmHg (cannot compensate respiratory acidosis)
Severe hypokalemia (K+ below 2.5 mmol/L) - correct hypokalemia first
Volume overload with cardiogenic pulmonary edema [13]

Decontamination

Activated charcoal:

Generally NOT effective for methanol or ethylene glycol (both are small, rapidly absorbed molecules with low protein binding)
May be considered for co-ingested toxins (within 1-2 hours of ingestion) [9]

Gastric lavage:

Generally NOT recommended (rapid absorption already occurred by presentation)
Considered only for massive recent ingestion (below 1 hour) with airway protection [9]

Hemodialysis

Rationale:

Removes both parent alcohols AND toxic metabolites (unlike fomepizole which only prevents further metabolite formation)
Corrects metabolic acidosis (removes hydrogen ions, provides bicarbonate via dialysate)
Corrects electrolyte abnormalities
Provides renal replacement for AKI (ethylene glycol) [17,26]

EXTRIP 2015 recommendations:

Methanol - Hemodialysis indicated if:

Plasma methanol greater than 50 mg/dL (with fomepizole) OR greater than 20 mg/dL (without fomepizole)
Visual disturbances
Severe metabolic acidosis (pH below 7.25) despite maximal medical therapy
New-onset seizures or altered mental status attributable to methanol [17]

Ethylene glycol - Hemodialysis indicated if:

Plasma ethylene glycol greater than 50 mg/dL
Anion gap greater than 20 mmol/L
Severe metabolic acidosis (pH below 7.25)
Calcium oxalate crystalluria
Acute kidney injury or oliguria
Clinical deterioration despite medical therapy [17]

Dialysis modality:

Intermittent hemodialysis (IHD): Preferred (highest clearance, rapid correction)
Continuous renal replacement therapy (CRRT): Alternative if hemodynamically unstable; slower clearance [17,26]

Dialysis prescription:

Blood flow: 250-400 mL/min
Dialysate flow: 500-800 mL/min
Duration: Typically 4-6 hours (may require multiple sessions depending on levels)
Continue until: (1) Toxic alcohol level below 20 mg/dL, (2) pH greater than 7.35, (3) Normalized anion gap, (4) Clinical improvement [17,26]

Adjusting antidotes during dialysis:

Fomepizole: 10 mg/kg IV every 4 hours (or one dose immediately after dialysis)
Ethanol: Increase infusion rate by ~50-100% during dialysis (monitor serum levels q1-2h)
Cofactors: Continue dosing throughout dialysis [12,17]

Monitoring

Clinical monitoring:

Vital signs (BP, HR, RR, SpO2, temperature) q1h initially
Neurological assessment (GCS, pupils, cranial nerves) q1-2h
Visual acuity and fundoscopy (methanol) q4-6h
Fluid balance (input/output, daily weights) q4h [9,13]

Laboratory monitoring:

ABG q1-2h initially (until pH greater than 7.35 stable)
Electrolytes q4-6h (especially Na, K, Ca, Mg)
Serum osmolality and calculate osmolar gap q4-6h
Methanol/ethylene glycol levels q4-6h (if available)
Renal function (creatinine, BUN) q6-12h
Serum ethanol (if ethanol used as antidote) q1-2h [9,32]

Toxic alcohol level monitoring:

Continue dialysis until level below 20 mg/dL
Rebound possible if dialysis stopped prematurely (continued metabolism of parent alcohol)
Consider repeat dialysis if levels rebound or clinical deterioration [17]

Complications and Prognosis

Methanol Complications

Visual sequelae:

Early: Retinal edema, optic disc hyperemia, decreased visual acuity
Late: Optic atrophy, permanent blindness (30-50% of survivors) [24,42]

Neurological sequelae:

Parkinsonism (putaminal necrosis)
Cognitive impairment
Persistent encephalopathy [39,40]

Systemic complications:

Acute kidney injury (multifactorial: hypotension, rhabdomyolysis, hemolysis)
Pancreatitis (rare)
Hemolysis (formic acid-induced) [3,4]

Ethylene Glycol Complications

Renal:

Acute tubular necrosis (calcium oxalate crystal nephropathy)
Oliguria or anuria
May require prolonged renal replacement therapy (days to weeks) [5,25]

Cardiovascular:

Hypocalcemia (QT prolongation, arrhythmias)
Hypotension (from acidosis and third-spacing) [5]

Neurological:

Cranial nerve palsies (facial nerve, vocal cord paralysis, dysphagia)
Peripheral neuropathy (rare) [5]

Prognosis

Methanol:

Good prognosis: Early presentation (below 6 hours), early fomepizole/ethanol administration, prompt dialysis, minimal visual symptoms
Poor prognosis: Delayed presentation (greater than 12 hours), severe acidosis (pH below 7.0), visual symptoms, seizure, coma [3,24]

Ethylene glycol:

Good prognosis: Early presentation (below 6 hours), early fomepizole/ethanol administration, prompt dialysis, absence of AKI
Poor prognosis: Delayed presentation (greater than 12 hours), severe AKI (creatinine greater than 3 mg/dL), calcium oxalate crystalluria, hypocalcemia, cardiac arrest [5,25]

Mortality:

Untreated methanol: 20-50%
Treated methanol: below 5% with early fomepizole and dialysis
Untreated ethylene glycol: Up to 80%
Treated ethylene glycol: below 10% with early fomepizole and dialysis [1,2]

Clinical Algorithm

Toxic Alcohol Poisoning Management Algorithm

PATIENT WITH SUSPECTED TOXIC ALCOHOL INGESTION
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1. IMMEDIATE STABILIZATION
   - ABCs, IV access, oxygen
   - Dextrose-containing fluids (correct hypoglycemia)
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         v
2. INITIAL INVESTIGATIONS
   - ABG, electrolytes, glucose, BUN/Cr
   - Serum osmolality (calculate osmolar gap)
   - Methanol/ethylene glycol levels (send STAT)
   - Urinalysis (calcium oxalate crystals - EG)
   - ECG, CXR, head CT (if altered mental status)
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         v
3. ASSESS FOR ANTIDOTE INDICATION
   Indicated if ANY of:
   ├─ Toxic alcohol level greater than 20 mg/dL
   ├─ Osmolar gap greater than 10 mOsm/L
   ├─ pH below 7.3 OR HCO3 below 20
   └─ Strong clinical suspicion
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         v
4. INITIATE ADH INHIBITION
   ├─ FOMEPIZOLE (preferred)
   │  ├─ Loading: 15 mg/kg IV
   │  └─ Maintenance: 10 mg/kg q12h ×4, then 15 mg/kg q12h
   │     (During HD: 10 mg/kg q4h)
   └─ ETHANOL (if fomepizole unavailable)
      ├─ Loading: 0.6 g/kg IV (10% in dextrose)
      └─ Maintenance: 66-154 mg/kg/hr (maintain EtOH 100-150 mg/dL)
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5. ADJUNCTIVE THERAPIES
   ├─ SODIUM BICARBONATE (if pH below 7.25-7.30)
   │  ├─ 1-2 mEq/kg IV bolus
   │  └─ Infusion to target pH greater than 7.35
   ├─ COFACTOR THERAPY
   │  ├─ Methanol: Folate 50 mg IV q4-6h
   │  └─ Ethylene glycol: Thiamine 100 mg IV daily + Pyridoxine 50-100 mg IV daily
   └─ FLUID RESUSCITATION
      └─ Isotonic crystalloids ± dextrose
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6. ASSESS FOR HEMODIALYSIS (EXTRIP 2015)
   Indicated if ANY of:
   METHANOL:
   ├─ Level greater than 50 mg/dL (with fomepizole) or greater than 20 mg/dL (without)
   ├─ Visual disturbances
   ├─ pH below 7.25 despite maximal therapy
   └─ Seizure or AMS attributable to methanol
   ETHYLENE GLYCOL:
   ├─ Level greater than 50 mg/dL
   ├─ Anion gap greater than 20 mmol/L
   ├─ pH below 7.25
   ├─ Calcium oxalate crystalluria
   ├─ AKI or oliguria
   └─ Clinical deterioration
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         v
7. HEMODIALYSIS (if indicated)
   - IHD preferred (highest clearance)
   - Continue until level below 20 mg/dL, pH greater than 7.35, normal anion gap
   - Adjust fomepizole/ethanol dosing during dialysis
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8. MONITORING
   ├─ Clinical: Vitals, GCS, visual assessment q1-2h
   ├─ ABG q1-2h initially
   ├─ Electrolytes q4-6h
   ├─ Osmolar gap q4-6h
   └─ Toxic alcohol levels q4-6h (if available)
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         v
9. DISPOSITION
   ├─ ICU admission for all patients requiring antidote or dialysis
   ├─ Psychiatric consultation (suicidal ingestion)
   ├─ Ophthalmology follow-up (methanol visual symptoms)
   └─ Nephrology follow-up (ethylene glycol AKI)

Special Populations

Pediatric Patients

Epidemiology:

Accidental ingestion (children exploring environment)
Often smaller volumes ingested but higher dose per kg
Different metabolic rates (faster metabolism) [29,43]

Dose adjustments:

Fomepizole: Same mg/kg dosing as adults
Ethanol: Same mg/kg dosing but monitor closely for CNS depression
Cofactors: 1 mg/kg IV q4-6h (folate), 1-2 mg/kg/day thiamine, 0.5-1 mg/kg/day pyridoxine [29]

Special considerations:

Higher risk of hypoglycemia (low glycogen stores)
Smaller vascular access (central venous access may be required for dialysis)
Dialysis circuit priming volume significant (may require blood transfusion) [43]

Pregnancy

Fetal considerations:

Methanol and ethylene glycol cross placenta
Formic acid and glycolic acid are toxic to fetus
Maternal acidosis causes fetal acidosis [44]

Management:

Treat maternal toxicity aggressively (fetal benefit)
Fomepizole preferred over ethanol (no fetal CNS depression)
Hemodialysis safe in pregnancy (adjust positioning for gravid uterus) [44]

Geriatric Patients

Pharmacokinetic changes:

Decreased renal clearance (prolonged elimination)
Increased volume of distribution (lower body water, higher fat mass)
Increased sensitivity to CNS effects (especially ethanol) [45]

Dose adjustments:

Fomepizole: Standard dosing (no renal adjustment needed)
Ethanol: Use lower end of maintenance infusion range (avoid oversedation)
Bicarbonate: Caution with sodium load (avoid volume overload) [45]

Patients with Pre-existing Renal Failure

Considerations:

Delayed renal elimination of toxic alcohols
More severe acidosis (impaired bicarbonate reclamation)
Calcium oxalate crystals may already be present (ethylene glycol) [46]

Management:

Early hemodialysis indicated (lower thresholds)
CRRT alternative if hemodynamically unstable (slower clearance) [46]

Patients with Pre-existing Liver Disease

Considerations:

Impaired metabolism of fomepizole and ethanol
Prolonged half-life of toxic alcohols (reduced first-pass metabolism)
Coagulopathy (risk of bleeding with dialysis catheters) [47]

Management:

Consider dose reduction of fomepizole (monitor levels if available)
Avoid ethanol (higher risk of encephalopathy)
Correct coagulopathy before dialysis catheter placement [47]

Australian and New Zealand Context

Australian Guidelines and Resources

Toxicology Services:

NSW Poisons Information Centre: 13 11 26 (24/7)
VIC Poisons Information Centre: 13 11 26 (24/7)
WA Poisons Information Centre: 13 11 26 (24/7)
Queensland Poisons Information Centre: 13 11 26 (24/7)
New Zealand National Poisons Centre: 0800 POISON (0800 764 766) [48]

Fomepizole availability:

TGA approved as Antizol®
Available in major tertiary hospitals
Smaller regional hospitals may require interhospital transfer or use ethanol as alternative [49]

Hemodialysis access:

Intermittent hemodialysis available in all major tertiary centers
Regional hospitals: May require patient transfer to tertiary center with dialysis capability
RFDS (Royal Flying Doctor Service) for remote retrievals [50]

Indigenous Health Considerations

Epidemiology:

Higher prevalence of alcohol-related toxicities in some Indigenous communities
Barriers to early healthcare access (geographic isolation, cultural safety concerns)
Social determinants of health contribute to alcohol misuse [51,52]

Cultural safety principles:

Involve Aboriginal and Torres Strait Islander Health Workers in care
Respect family decision-making processes
Provide culturally appropriate health education [51,52]

Remote and rural considerations:

Early recognition and stabilization critical (transfer delays common)
Telemedicine consultation with toxicology services
Early decision on need for retrieval (RFDS) for dialysis capability [50]

Māori Health Considerations (New Zealand)

Te Whare Tapa Whā model:

Taha tinana (physical health): Address toxic alcohol toxicity
Taha hinengaro (mental health): Address underlying causes of ingestion (suicidality, substance use)
Taha whānau (family): Involve whānau in care decisions and support
Taha wairua (spiritual wellbeing): Incorporate cultural practices and spiritual support [53]

Health equity:

Address disparities in access to toxicology services and dialysis
Ensure culturally safe communication and consent processes
Provide health education in te reo Māori where appropriate [53]

References

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SAQ Practice Questions

SAQ 1: Methanol Poisoning

A 45-year-old male presents with altered mental status, visual disturbances, and Kussmaul respirations 12 hours after a suicidal ingestion of windshield washer fluid. His vital signs: BP 85/50 mmHg, HR 120 bpm, RR 32/min, SpO2 96% on room air. ABG: pH 7.15, PaCO2 28 mmHg, PaO2 95 mmHg, HCO3 8 mmol/L. Serum electrolytes: Na 140 mmol/L, K 4.2 mmol/L, Cl 108 mmol/L, HCO3 8 mmol/L, glucose 6.0 mmol/L, creatinine 95 μmol/L. Measured serum osmolality: 340 mOsm/kg.

a) Calculate the anion gap and osmolar gap. Discuss their interpretation in toxic alcohol poisoning. (4 marks)

b) Outline your immediate management plan, including antidote therapy, dosing, and monitoring. (6 marks)

c) Discuss the pathophysiology of visual impairment in methanol poisoning and factors influencing prognosis. (5 marks)

d) List the EXTRIP criteria for hemodialysis in methanol poisoning. (5 marks)

Model Answer:

a) Anion gap and osmolar gap calculation and interpretation:

Anion gap = [Na] - ([Cl] + [HCO3]) = 140 - (108 + 8) = 24 mmol/L

Osmolar gap = Measured osmolality - [2(Na) + (Glucose/18) + (BUN/2.8)]

Glucose 6.0 mmol/L = 6.0/18 = 0.33 mmol/L = 108 mg/dL
Assuming BUN = 5 mmol/L (normal), BUN/2.8 = 1.79 mmol/L
Calculated osmolality = 2(140) + 0.33 + 1.79 = 282.12 mOsm/kg
Osmolar gap = 340 - 282 = 58 mOsm/L

Interpretation:

Elevated anion gap (24 mmol/L, normal 8-12): Indicates high anion gap metabolic acidosis from accumulation of acidic metabolites (formic acid, lactic acid)
Elevated osmolar gap (58 mOsm/L, normal below 10): Indicates presence of unmeasured osmoles (parent methanol)
Combined elevated osmolar gap + HAGMA: Suggests intermediate phase of methanol poisoning (both parent alcohol and toxic metabolites present)
Each 100 mg/dL methanol increases osmolar gap by ~32 mOsm/L; estimated methanol concentration ~180 mg/dL (severe toxicity) [9,21,32]

b) Immediate management plan:

1. Stabilization:

ABC: Protect airway if GCS below 8 (current AMS; prepare for intubation if respiratory failure or loss of airway reflexes)
IV access: Two large-bore IVs
Fluid resuscitation: 1L isotonic crystalloid (0.9% NaCl) bolus, repeat to MAP greater than 65 mmHg
Dextrose: Add dextrose to IV fluids (D5NS) to prevent hypoglycemia (methanol impairs gluconeogenesis)
Sodium bicarbonate: 150 mEq IV bolus (1-2 mEq/kg) for pH below 7.25, followed by infusion to target pH greater than 7.35
Correct hypotension: Additional crystalloid boluses, consider vasopressors (norepinephrine) if refractory [9,13]

2. Antidote therapy (ADH inhibition):

Fomepizole (preferred):

Loading dose: 15 mg/kg IV over 30 minutes (approx 1.05 g for 70 kg patient)
Maintenance: 10 mg/kg IV every 12 hours for 4 doses (48 hours total), then 15 mg/kg IV every 12 hours thereafter (auto-induction)
If hemodialysis initiated: 10 mg/kg IV every 4 hours during dialysis [11,12]

Ethanol (alternative if fomepizole unavailable):

Loading: 0.6 g/kg IV of 10% ethanol in dextrose (42 g for 70 kg patient)
Maintenance: 100 mg/kg/hr continuous infusion (adjust to maintain serum ethanol 100-150 mg/dL)
Monitor serum ethanol q1-2h; adjust infusion accordingly [19,20]

3. Cofactor therapy (methanol-specific):

Folate: 50 mg IV every 4-6 hours (or folinic acid 1 mg/kg IV q4-6h)
Rationale: Enhances conversion of formic acid to CO2 and H2O via tetrahydrofolate-dependent pathway [15,22]

4. Definitive elimination - Hemodialysis (INDICATED - see EXTRIP criteria below):

Prepare for emergent hemodialysis (highest priority)
Target: Methanol level below 20 mg/dL, pH greater than 7.35, normalized anion gap [17,26]

5. Monitoring:

Clinical: Vitals q1h, GCS, visual assessment q2-4h
ABG q1-2h until pH greater than 7.35 stable
Electrolytes q4-6h (Na, K, Ca, Mg)
Serum methanol level q4-6h
Osmolar gap q4-6h
Serum ethanol (if ethanol used) q1-2h [9,32]

c) Pathophysiology of visual impairment and prognostic factors:

Pathophysiology:

Formic acid accumulates in optic nerve and retina due to local folate deficiency
Formic acid inhibits mitochondrial cytochrome c oxidase (complex IV) → impaired oxidative phosphorylation → cellular hypoxia and ATP depletion
Direct toxic injury to retinal ganglion cells and optic nerve axons
Optic disc edema and hyperemia secondary to increased vascular permeability and impaired axonal transport
If untreated, progression to optic atrophy and permanent blindness [3,4,24,42]

Prognostic factors:

Poor prognosis:
- Delayed presentation (greater than 12 hours after ingestion)
- Severe acidosis (pH below 7.0)
- Presence of visual symptoms at presentation
- Seizure or coma
- Higher methanol levels (greater than 200 mg/dL)
- Delayed initiation of antidote or dialysis
Good prognosis:
- Early presentation (below 6 hours)
- Early fomepizole/ethanol administration
- Prompt hemodialysis
- Absence of visual symptoms
- Minimal acidosis (pH greater than 7.3) [3,24,42]

d) EXTRIP criteria for hemodialysis in methanol poisoning:

Hemodialysis is STRONGLY RECOMMENDED for methanol poisoning if ANY of:

Plasma methanol concentration greater than 50 mg/dL (with fomepizole) OR greater than 20 mg/dL (without fomepizole)
Visual disturbances (blurred vision, photophobia, scotomas, blindness)
Severe metabolic acidosis (pH below 7.25) despite maximal medical therapy (bicarbonate, fomepizole)
New-onset seizures or altered mental status attributable to methanol [17,26]

Hemodialysis should be CONSIDERED for:

Rapidly rising methanol levels
Failure to improve clinically despite medical therapy
Pregnancy (fetal protection) [17,26]

SAQ 2: Ethylene Glycol Poisoning

A 32-year-old female presents 18 hours after ingestion of a large volume of antifreeze in a suicide attempt. She reports abdominal pain, nausea, and vomiting. On examination: BP 90/55 mmHg, HR 110 bpm, RR 28/min, SpO2 98% on room air, GCS 14 (E4 V4 M6). Urinalysis demonstrates needle-shaped crystals. Blood results: Na 138 mmol/L, K 3.8 mmol/L, Cl 110 mmol/L, HCO3 6 mmol/L, glucose 5.5 mmol/L, creatinine 180 μmol/L (baseline 70). Measured serum osmolality: 330 mOsm/kg.

a) Calculate the anion gap and osmolar gap. What is your differential diagnosis? (4 marks)

b) Outline your management plan, including specific antidotes and cofactors for ethylene glycol poisoning. (6 marks)

c) Discuss the pathophysiology of calcium oxalate crystal formation and renal injury in ethylene glycol poisoning. (5 marks)

d) Explain why hypocalcemia should NOT be routinely corrected in ethylene glycol poisoning, and when calcium therapy may be indicated. (5 marks)

Model Answer:

a) Calculations and differential diagnosis:

Anion gap: Anion gap = [Na] - ([Cl] + [HCO3]) = 138 - (110 + 6) = 22 mmol/L (Normal: 8-12 mmol/L; elevated anion gap metabolic acidosis present)

Osmolar gap: Calculated osmolality = 2(Na) + (Glucose/18) + (BUN/2.8)

Creatinine 180 μmol/L ≈ 1.8 mg/dL; assuming BUN ~10 mg/dL (elevated from AKI)
BUN/2.8 = 10/2.8 = 3.57 mmol/L
Glucose 5.5 mmol/L = 5.5/18 = 0.31 mmol/L
Calculated osmolality = 2(138) + 0.31 + 3.57 = 279.88 mOsm/kg
Osmolar gap = 330 - 280 = 50 mOsm/L (Normal: below 10 mOsm/L; significantly elevated)

Differential diagnosis for HAGMA with elevated osmolar gap:

Ethylene glycol poisoning (most likely): History of antifreeze ingestion, calcium oxalate crystals on urinalysis, AKI
Methanol poisoning: No visual symptoms described, history suggests antifreeze
Diabetic ketoacidosis (DKA): Typically no osmolar gap; ketoacidosis present
Lactic acidosis: Typically no osmolar gap; elevated lactate
Salicylate toxicity: Mixed respiratory alkalosis + HAGMA; usually mild osmolar gap
Propylene glycol toxicity: Chronic exposure to IV medications
Isopropanol poisoning: Causes ketosis but NOT severe acidosis [9,21,32]

b) Management plan:

1. Stabilization:

ABC: Airway protection if GCS deteriorates (currently 14, monitor closely)
IV access: Two large-bore IVs
Fluid resuscitation: 1L isotonic crystalloid bolus, repeat to MAP greater than 65 mmHg
Dextrose: Add dextrose to IV fluids (D5NS) to prevent hypoglycemia
Sodium bicarbonate: 150 mEq IV bolus for pH below 7.25 (likely present given HCO3 6), followed by infusion [9,13]

2. Antidote therapy (ADH inhibition):

Fomepizole (preferred):

Loading dose: 15 mg/kg IV over 30 minutes (approx 975 mg for 65 kg patient)
Maintenance: 10 mg/kg IV every 12 hours for 4 doses, then 15 mg/kg IV every 12 hours
During hemodialysis: 10 mg/kg IV every 4 hours [11,12]

Ethanol (alternative if fomepizole unavailable):

Loading: 0.6 g/kg IV of 10% ethanol in dextrose
Maintenance: 100 mg/kg/hr continuous infusion (target EtOH 100-150 mg/dL)
Monitor serum ethanol q1-2h [19,20]

3. Cofactor therapy (ethylene glycol-specific):

Thiamine (Vitamin B1): 100 mg IV daily (or 300 mg IV divided q6-8h)
- "Rationale: Cofactor for conversion of glyoxylic acid to α-hydroxy-β-ketoadipate (benign metabolite), shunting away from oxalic acid"
Pyridoxine (Vitamin B6): 50-100 mg IV daily (or 50 mg IV divided q6-8h)
- "Rationale: Cofactor for conversion of glyoxylic acid to glycine (benign metabolite), reducing oxalic acid formation [16,23]"

4. Hemodialysis (INDICATED - EXTRIP criteria):

Strongly indicated: Ethylene glycol level greater than 50 mg/dL OR anion gap greater than 20 mmol/L OR pH below 7.25 OR calcium oxalate crystalluria OR AKI present
This patient meets MULTIPLE criteria: elevated osmolar gap, severe HAGMA (HCO3 6), calcium oxalate crystals, AKI (creatinine 180)
Prepare for emergent hemodialysis; continue until level below 20 mg/dL, pH greater than 7.35, normal anion gap [17,26]

5. Monitoring:

Clinical: Vitals q1h, GCS q2-4h, urine output q4h
ABG q1-2h until pH greater than 7.35 stable
Electrolytes q4-6h (especially Ca, K, Na, Mg)
Serum ethylene glycol level q4-6h (if available)
Osmolar gap q4-6h
Urinalysis for calcium oxalate crystals
Renal function (creatinine, BUN) q6-12h [9,32]

c) Pathophysiology of calcium oxalate crystal formation and renal injury:

Ethylene glycol metabolism pathway:

Ethylene glycol → Glycoaldehyde (via ADH)
Glycoaldehyde → Glycolic acid (primary acidotic metabolite)
Glycolic acid → Glyoxylic acid
Glyoxylic acid → Multiple pathways:
- To α-hydroxy-β-ketoadipate (via thiamine/B1) → benign
- To glycine (via pyridoxine/B6) → benign
- To oxalic acid (if cofactor deficient) → TOXIC [5,6]

Calcium oxalate crystal formation:

Oxalic acid binds free calcium in blood → calcium oxalate crystals
Two types of crystals:
- "Calcium oxalate monohydrate (COM): Needle-shaped crystals (most nephrotoxic)"
- "Calcium oxalate dihydrate (COD): Envelope-shaped crystals"
Crystals precipitate in renal tubules (proximal and distal) [5,25]

Mechanism of renal injury:

Intratubular obstruction: Crystals physically obstruct tubular lumens → decreased GFR
Direct tubular toxicity: Oxalic acid and crystals damage tubular epithelial cells → necrosis
Inflammatory response: Crystals trigger inflammation → cytokine release, leukocyte infiltration
Hypocalcemia: Calcium binding to oxalate reduces ionized calcium → potential arrhythmias, tetany
Acute tubular necrosis (ATN): Result of combined obstruction, toxicity, and ischemia [5,25,31]

d) Calcium therapy in ethylene glycol poisoning:

Why hypocalcemia should NOT be routinely corrected:

Hypocalcemia is due to calcium binding to oxalic acid (already precipitated as crystals)
Exogenous calcium administration provides additional calcium to bind with oxalic acid → promotes formation of MORE calcium oxalate crystals
Increased crystal burden worsens renal injury (increased intratubular obstruction and tubular toxicity)
Most patients tolerate hypocalcemia without symptoms until ionized Ca below 0.8 mmol/L (3.2 mg/dL) [31]

When calcium therapy MAY be indicated:

Symptomatic hypocalcemia:
- Tetany, muscle cramps, carpopedal spasm
- Seizures
- Prolonged QT interval or ventricular arrhythmias on ECG
Severe hypocalcemia:
- Ionized calcium below 0.8 mmol/L (3.2 mg/dL) or total calcium below 1.6 mmol/L (6.4 mg/dL)
Cardiac instability:
- Hemodynamically significant arrhythmias attributable to hypocalcemia [31]

If calcium therapy is indicated:

Use judicious dosing: Calcium gluconate 10% 10 mL IV over 10 minutes
Reassess ionized calcium after 5-10 minutes
Repeat only if symptoms persist or ECG abnormalities remain
Avoid large doses or continuous infusions (will worsen crystal deposition) [31]

Viva Voce Scenarios

Viva 1: Pathophysiology and Laboratory Evolution

Examiner: A 55-year-old male is brought to the ED 8 hours after ingesting an unknown amount of windshield washer fluid. He appears intoxicated but is otherwise stable. The resident has ordered basic blood work.

Candidate: I would like to review the patient's initial laboratory findings. Could you provide the results?

Examiner: Arterial blood gas shows pH 7.38, PaCO2 38 mmHg, HCO3 22 mmol/L. Serum electrolytes: Na 140, K 4.0, Cl 108, HCO3 22, glucose 5.5, creatinine 90. Measured osmolality is 330 mOsm/kg.

Candidate: (Calculating) The anion gap is 140 - (108 + 22) = 10 mmol/L, which is normal. The calculated osmolality is approximately 280 mOsm/kg, so the osmolar gap is 330 - 280 = 50 mOsm/L, which is significantly elevated. This picture is concerning for early methanol poisoning, where the parent alcohol (an osmole) is present but has not yet been metabolized to formic acid (the acidotic metabolite). The absence of acidosis at this stage is consistent with the latent period.

Examiner: Correct. Let's say the patient returns 8 hours later. The ABG now shows pH 7.20, PaCO2 28 mmHg, HCO3 10 mmol/L. Measured osmolality is now 310 mOsm/kg.

Candidate: This represents progression to the intermediate/late phase of methanol poisoning. The pH has dropped to 7.20 with severe metabolic acidosis (HCO3 10). The calculated anion gap is now 140 - (108 + 10) = 22 mmol/L, indicating high anion gap metabolic acidosis. The osmolar gap has decreased to 310 - 280 = 30 mOsm/L. This laboratory evolution is classic: we're seeing the conversion of the parent methanol to formic acid. The osmolar gap is decreasing as methanol is metabolized, while the anion gap is increasing as formic acid accumulates. This patient now meets criteria for ADH inhibition and likely hemodialysis.

Examiner: Why is the osmolar gap decreasing, not staying high?

Candidate: The osmolar gap reflects the concentration of the parent alcohol, which is an osmole but not an acid. As ADH metabolizes methanol to formaldehyde and then to formic acid, the parent methanol concentration decreases. Formic acid is an acid that contributes to the anion gap but NOT to the osmolar gap (because it dissociates into H+ and formate ions, both of which are accounted for in standard calculations). So we see a reciprocal relationship: osmolar gap decreases as anion gap increases.

Examiner: How does this temporal evolution influence treatment timing?

Candidate: This is critically important. Early treatment (within the first 6-12 hours) when the osmolar gap is elevated but acidosis is minimal is most effective. At this stage, fomepizole prevents conversion of methanol to formic acid, and the parent methanol can be cleared renally or via dialysis before significant acidosis develops. If treatment is delayed until the late phase (when acidosis is severe and osmolar gap has normalized), we still need fomepizole to prevent ongoing metabolism, but we must also address the existing formic acid load. This requires more aggressive bicarbonate therapy and hemodialysis, and the patient may already have organ damage (visual impairment, neurological deficits). Early treatment prevents the formation of toxic metabolites; late treatment has to remove metabolites that have already accumulated.

Examiner: What is the role of bicarbonate therapy in methanol poisoning, and how does pH influence formic acid distribution?

Candidate: Sodium bicarbonate is particularly important in methanol poisoning. Formic acid exists in equilibrium between its unionized form (HCOOH) and ionized form (HCOO-). The unionized form crosses biological membranes (including the blood-brain barrier) more readily, while the ionized form is trapped in the plasma. At acidic pH, the equilibrium shifts toward the unionized form, allowing more formic acid to enter the CNS and cause neurotoxicity and visual impairment. By administering bicarbonate to maintain pH greater than 7.3, we alkalinize the plasma, shifting the equilibrium toward the ionized form which cannot cross the BBB. This is ion trapping—similar to the mechanism of urinary alkalinization in salicylate poisoning, but in this case we're trapping formate in plasma rather than urine. So bicarbonate has a dual benefit: correcting the systemic acidosis AND preventing CNS formic acid accumulation.

Examiner: The patient now reports visual changes—blurred vision and difficulty seeing in low light. What does this tell you about the severity of poisoning?

Candidate: Visual symptoms are a marker of severe methanol poisoning and correlate with poorer prognosis. The development of visual symptoms indicates significant formic acid accumulation in the optic nerve and retina. Formic acid causes direct toxic injury to retinal ganglion cells and optic nerve axons, and also causes optic disc edema and hyperemia due to increased vascular permeability. The presence of visual symptoms, along with severe acidosis and altered mental status, would be absolute indications for hemodialysis according to EXTRIP criteria. Visual recovery is possible if treatment is initiated early, but permanent visual loss occurs in 30-50% of survivors with delayed treatment. The fact that this patient has visual symptoms suggests we're already in the late phase and need aggressive therapy.

Viva 2: ADH Inhibition and Antidotes

Examiner: You're called to see a 38-year-old female who ingested antifreeze 6 hours ago. She's currently stable with a normal pH and an osmolar gap of 45 mOsm/L. The ED resident is asking about antidotes.

Candidate: This patient has an elevated osmolar gap consistent with early ethylene glycol poisoning, but no acidosis yet. This is the ideal time to initiate ADH inhibition to prevent formation of toxic metabolites. The first-line antidote is fomepizole. I would administer a loading dose of 15 mg/kg IV over 30 minutes, followed by maintenance dosing of 10 mg/kg every 12 hours. Fomepizole is preferred over ethanol because it has 8000-fold higher affinity for ADH, doesn't cause CNS depression, doesn't require frequent monitoring, and has a superior safety profile.

Examiner: Explain the mechanism of fomepizole.

Candidate: Fomepizole (4-methylpyrazole) is a competitive inhibitor of alcohol dehydrogenase (ADH). It binds to the same site on ADH that would normally bind methanol, ethylene glycol, or ethanol. However, fomepizole has an affinity for ADH that is 8000 times greater than ethanol. By occupying the ADH binding site, fomepizole prevents the conversion of parent toxic alcohols to their toxic metabolites. The parent alcohols are then eliminated unchanged, either renally (minor pathway) or via hemodialysis if needed. This is crucial because the parent alcohols (methanol and ethylene glycol) are relatively non-toxic—all the toxicity comes from their metabolites (formic acid, glycolic acid, oxalic acid).

Examiner: How is fomepizole dosed, and what are the pharmacokinetic considerations?

Candidate: Fomepizole dosing is:

Loading: 15 mg/kg IV over 30 minutes
Maintenance: 10 mg/kg IV every 12 hours for the first 4 doses (48 hours total)
After 4 doses: Increase to 15 mg/kg IV every 12 hours thereafter

The dose increase after 4 doses is due to auto-induction of metabolism. Fomepizole is metabolized in the liver, primarily by CYP2E1. Over the first 48 hours, fomepizole induces its own metabolism, increasing clearance by up to 50%. So the maintenance dose needs to be increased to maintain therapeutic levels.

A critical consideration is during hemodialysis. Fomepizole is dialyzable, so during hemodialysis we need to increase the dosing frequency to 10 mg/kg every 4 hours, or administer a dose immediately after the dialysis session ends. The standard every-12-hour dosing is insufficient during dialysis because fomepizole is removed from the blood faster than it's being metabolized.

Examiner: If fomepizole is unavailable, what is the alternative?

Candidate: The alternative is ethanol, which was the standard antidote before fomepizole was developed. Ethanol is a competitive substrate for ADH—it's preferentially metabolized over methanol or ethylene glycol. By maintaining a high serum ethanol concentration (100-150 mg/dL), we occupy ADH with ethanol, preventing metabolism of the toxic alcohols.

Ethanol dosing is more complex. The loading dose is 0.6 g/kg IV, typically given as 10% ethanol in dextrose. The maintenance infusion is 66-154 mg/kg/hr, and we need to monitor serum ethanol levels every 1-2 hours and adjust the infusion to maintain the target concentration. If the patient undergoes hemodialysis, we need to increase the infusion rate by 50-100% because ethanol is also dialyzable.

Examiner: What are the disadvantages of ethanol compared to fomepizole?

Candidate: Ethanol has several significant disadvantages:

CNS depression: The target ethanol concentration (100-150 mg/dL) causes intoxication, which can complicate neurological assessment, particularly in patients with altered mental status from the poisoning itself
Hypoglycemia: Ethanol inhibits gluconeogenesis and causes hypoglycemia, especially in pediatric patients, malnourished patients, and chronic alcoholics. We must use dextrose-containing vehicles and monitor glucose frequently
Intensive monitoring: Requires serum ethanol levels every 1-2 hours, frequent lab draws, and careful titration of the infusion
Respiratory depression: At higher concentrations, ethanol can depress respiratory drive, which is problematic in patients who need to maintain compensatory hyperventilation for metabolic acidosis
Drug interactions: Ethanol interacts with many medications commonly used in critically ill patients
Vascular irritation: High concentrations can cause phlebitis

Because of these issues, fomepizole is preferred whenever available. Ethanol is reserved for situations where fomepizole is unavailable or the patient cannot afford it.

Examiner: Does initiating ADH inhibition mean we don't need hemodialysis?

Candidate: Absolutely not—this is a common misconception. Fomepizole prevents FURTHER formation of toxic metabolites, but it does NOT remove toxic metabolites that have already formed. For example, if a patient presents with severe acidosis 24 hours after ethylene glycol ingestion, a significant amount of glycolic and oxalic acid is already present. Fomepizole will prevent formation of additional toxic metabolites, but it won't address the existing acidosis, renal injury, or calcium oxalate crystals. Hemodialysis removes BOTH the parent alcohol AND the toxic metabolites, corrects the acidosis, and provides renal replacement for AKI. So fomepizole and hemodialysis are complementary, not mutually exclusive. We use EXTRIP criteria to determine when hemodialysis is needed, and these criteria are based on the severity of poisoning (acidosis, organ dysfunction, toxic alcohol levels) rather than whether fomepizole is being administered.

Viva 3: Ethylene Glycol Cofactors and Renal Pathology

Examiner: You're managing a 45-year-old male with ethylene glycol poisoning. He's received fomepizole, but you need to discuss the cofactor therapy.

Candidate: For ethylene glycol poisoning, I would administer two cofactors: thiamine (vitamin B1) and pyridoxine (vitamin B6). Thiamine is dosed at 100 mg IV daily, and pyridoxine at 50-100 mg IV daily. These are adjunctive therapies that work together with fomepizole to shunt metabolism of toxic intermediates away from oxalic acid.

Examiner: Explain the biochemical rationale for these cofactors.

Candidate: Ethylene glycol is metabolized through a pathway that eventually produces glyoxylic acid. Glyoxylic acid is a branching point—it can be metabolized through several different pathways. The cofactors work to shunt glyoxylic acid toward benign metabolites rather than oxalic acid.

Glyoxylic acid can be converted to:

α-hydroxy-β-ketoadipate (via thiamine as a cofactor) → further metabolized to harmless products
Glycine (via pyridoxine as a cofactor) → an amino acid that is essentially nontoxic
Oxalic acid (if cofactor deficient) → combines with calcium to form calcium oxalate crystals → renal injury

By providing supraphysiologic doses of thiamine and pyridoxine, we enhance the metabolic pathways that convert glyoxylic acid to benign metabolites, reducing the amount available for conversion to oxalic acid. This is particularly important in patients who may be deficient in these vitamins, such as chronic alcoholics.

Examiner: What is the pathophysiology of renal injury in ethylene glycol poisoning?

Candidate: Renal injury in ethylene glycol poisoning is primarily due to calcium oxalate crystal nephropathy. The injury occurs through several mechanisms:

Crystal formation: Oxalic acid, produced from ethylene glycol metabolism, binds to calcium to form calcium oxalate crystals. Two types form: calcium oxalate monohydrate (needle-shaped) and calcium oxalate dihydrate (envelope-shaped). These crystals precipitate in the renal tubules, particularly the proximal and distal tubules.
Intratubular obstruction: The crystals physically obstruct the tubular lumens, increasing intratubular pressure and decreasing glomerular filtration rate (GFR).
Direct tubular toxicity: Oxalic acid itself is directly toxic to tubular epithelial cells, causing cellular injury and death. The crystals also cause mechanical damage.
Inflammatory response: The crystals trigger an inflammatory response, with leukocyte infiltration and cytokine release, which contributes to tissue damage.
Hypocalcemia: Calcium binding to oxalate reduces ionized calcium, which can cause cardiac effects and tetany.

The combination of these effects leads to acute tubular necrosis (ATN). The kidney injury is often severe, with oliguria or anuria, and may require prolonged renal replacement therapy.

Examiner: How would you assess the severity of renal injury?

Candidate: I would assess through several measures:

Serum creatinine and urea: Baseline comparison is important to establish acute kidney injury
Urinalysis: Look for calcium oxalate crystals (needle-shaped monohydrate or envelope-shaped dihydrate). The presence and quantity of crystals correlate with severity
Urine output: Oliguria (below 400 mL/day) or anuria indicates severe injury
Fractional excretion of sodium (FENa): Helps differentiate prerenal from intrinsic renal injury (typically greater than 2% in ATN)
Renal ultrasound: May show enlarged, echogenic kidneys in acute toxicity
Biomarkers: While not routinely available, novel biomarkers like NGAL or KIM-1 may help assess injury severity and prognosis

The presence of calcium oxalate crystals is pathognomonic for ethylene glycol poisoning and predicts more severe renal injury.

Examiner: The patient's ionized calcium is 0.9 mmol/L (normal 1.1-1.3), but he has no symptoms. What is your approach to calcium replacement?

Candidate: In ethylene glycol poisoning, I would generally NOT correct asymptomatic hypocalcemia unless ionized calcium falls below 0.8 mmol/L (3.2 mg/dL) or the patient develops symptoms. The hypocalcemia is due to calcium binding to oxalic acid to form crystals. Exogenous calcium administration provides additional substrate for crystal formation, potentially worsening renal injury.

However, if the patient develops symptomatic hypocalcemia (tetany, muscle cramps, seizures), ECG abnormalities (prolonged QT interval, ventricular arrhythmias), or the ionized calcium drops below 0.8 mmol/L, I would judiciously administer calcium gluconate 10% 10 mL IV over 10 minutes. I would reassess ionized calcium after 5-10 minutes and only repeat if symptoms persist or ECG abnormalities remain. I would avoid large doses or continuous calcium infusions.

This approach balances the risks of hypocalcemia against the risk of worsening calcium oxalate crystal deposition. Most patients tolerate ionized calcium levels in the 0.8-1.0 mmol/L range without symptoms.

Viva 4: Hemodialysis Indications and Logistics

Examiner: You're asked to consult on a 60-year-old male with methanol poisoning. The toxic alcohol level is 35 mg/dL. The ICU team wants to know if hemodialysis is indicated.

Candidate: The decision about hemodialysis in methanol poisoning is based on EXTRIP criteria. For methanol, hemodialysis is strongly recommended if ANY of the following are present: plasma methanol concentration greater than 50 mg/dL with fomepizole (or greater than 20 mg/dL without fomepizole), visual disturbances, severe metabolic acidosis (pH below 7.25) despite maximal medical therapy, or new-onset seizures or altered mental status attributable to methanol.

This patient has a methanol level of 35 mg/dL. If fomepizole is being administered, this is below the 50 mg/dL threshold. However, I need more information. Is the patient symptomatic? What is the pH? Are there visual disturbances? Is the mental status altered? What is the anion gap? The decision isn't based solely on the methanol level.

Examiner: The pH is 7.28, anion gap is 18, and the patient has mild visual blurring. He's receiving fomepizole.

Candidate: In this case, hemodialysis would be indicated. While the methanol level of 35 mg/dL is below the 50 mg/dL threshold when fomepizole is used, the patient has visual disturbances, which is one of the absolute indications for dialysis according to EXTRIP. Visual symptoms indicate significant formic acid accumulation in the optic nerve and retina, and they are a marker of severe poisoning. Additionally, the pH of 7.28 is borderline—while not below 7.25, the anion gap of 18 suggests significant metabolic acidosis is developing. Visual disturbances alone are sufficient indication for hemodialysis, so I would recommend proceeding with emergent hemodialysis.

Examiner: How does hemodialysis work for toxic alcohol poisoning?

Candidate: Hemodialysis is highly effective for toxic alcohol removal because both methanol and ethylene glycol have high dialysis clearance—typically greater than 200 mL/min, which is higher than many other drugs. Hemodialysis removes the parent alcohols AND their toxic metabolites simultaneously. For methanol, it removes both methanol and formic acid. For ethylene glycol, it removes ethylene glycol, glycolic acid, and oxalic acid.

In addition to toxin removal, hemodialysis has several other benefits:

Corrects metabolic acidosis by removing hydrogen ions and providing bicarbonate in the dialysate
Corrects electrolyte abnormalities
Provides renal replacement therapy for acute kidney injury (particularly important in ethylene glycol poisoning)
Can correct severe hyperosmolality

The dialysis prescription typically uses a blood flow of 250-400 mL/min and a dialysate flow of 500-800 mL/min. Sessions usually last 4-6 hours, and multiple sessions may be required depending on the initial toxic alcohol level and clinical response. Dialysis is continued until the toxic alcohol level is below 20 mg/dL, the pH is greater than 7.35, the anion gap is normalized, and the patient shows clinical improvement.

Examiner: How do you adjust medications during hemodialysis?

Candidate: Several medications used in toxic alcohol poisoning are dialyzable and require dose adjustment:

Fomepizole: During hemodialysis, the standard every-12-hour dosing is insufficient because fomepizole is rapidly cleared. We increase dosing to 10 mg/kg every 4 hours during dialysis. Alternatively, we can give a single dose of 10 mg/kg immediately after the dialysis session ends. Either approach ensures therapeutic levels are maintained.

Ethanol: If ethanol is used as an antidote, we need to increase the infusion rate by 50-100% during dialysis to maintain the target serum concentration of 100-150 mg/dL. We continue to monitor serum ethanol levels every 1-2 hours and titrate the infusion.

Other considerations:

Vasopressors: Some vasopressors may be removed by dialysis, though the effect is usually minor
Antibiotics: Many antibiotics are dialyzable and may need supplemental dosing
Electrolytes: Dialysis removes potassium, magnesium, and phosphate—we need to monitor and replace as needed

Sodium bicarbonate infusions may need to be adjusted based on the ABG response to dialysis. Often, patients require less bicarbonate after dialysis because dialysis itself corrects the acidosis.

Examiner: What modality of dialysis is preferred?

Candidate: Intermittent hemodialysis (IHD) is the preferred modality for toxic alcohol poisoning when the patient is hemodynamically stable. IHD provides the highest clearance, allowing rapid removal of both parent alcohols and toxic metabolites. A typical 4-6 hour session can significantly reduce toxic alcohol levels.

Continuous renal replacement therapy (CRRT) is an alternative for hemodynamically unstable patients who cannot tolerate the rapid fluid shifts of IHD. However, CRRT provides slower clearance, so the duration of therapy may be longer and toxin removal may be less efficient.

In practice, I would attempt IHD first unless there's a specific contraindication like severe hemodynamic instability or arrhythmias. If the patient becomes unstable during IHD, we can convert to CRRT. Some centers use prolonged intermittent renal replacement therapy (PIRRT) or sustained low-efficiency dialysis (SLED) as a middle ground.

The key point is that some form of extracorporeal elimination should be used early when indicated, as prompt dialysis improves outcomes in severe toxic alcohol poisoning.

Key Clinical Pearls

Temporal laboratory evolution: Toxic alcohol poisoning progresses from elevated osmolar gap alone → combined elevated osmolar gap + HAGMA → HAGMA with normalizing osmolar gap. This reflects conversion of parent alcohol to toxic metabolites over time. [9,21]
Fomepizole auto-induction: After 4 maintenance doses (48 hours), the dose must be increased from 10 mg/kg to 15 mg/kg every 12 hours due to hepatic auto-induction. [12,28]
Hemodialysis during fomepizole: Fomepizole is dialyzable—during hemodialysis, increase dosing frequency to every 4 hours or give a dose immediately after dialysis. [12]
Bicarbonate for methanol: Alkalinization (pH greater than 7.3) causes ion trapping of formic acid, preventing CNS penetration. Critical for visual outcomes. [13,27]
Avoid calcium in ethylene glycol: Routine calcium replacement worsens calcium oxalate crystal deposition. Only treat symptomatic hypocalcemia (tetany, seizures, ECG changes) or ionized Ca below 0.8 mmol/L. [31]
Ethanol disadvantages: Causes CNS depression, hypoglycemia, requires intensive monitoring, and complicates neurological assessment. Fomepizole preferred. [19,20]
Cofactors are adjuncts: Thiamine/pyridoxine for ethylene glycol and folate for methanol are helpful but DO NOT replace need for ADH inhibition or dialysis. [15,16]
Visual symptoms = dialysis: Visual disturbances in methanol poisoning are an absolute indication for hemodialysis regardless of methanol level. [17,24]
Crystals in ethylene glycol: Calcium oxalate crystals are pathognomonic and predict AKI severity. May not appear until 6-12 hours post-ingestion. [5,25]
Late presentation: Patients presenting greater than 24 hours post-ingestion may have normal osmolar gap (parent alcohol metabolized) but severe HAGMA from toxic metabolites. Still treat with fomepizole and dialysis. [9,30]

Quick Reference Dosing

Fomepizole (Antizol)

Patient Weight	Loading Dose	Maintenance (first 48h)	Maintenance (after 48h)	During Dialysis
50 kg	750 mg	500 mg q12h	750 mg q12h	500 mg q4h
60 kg	900 mg	600 mg q12h	900 mg q12h	600 mg q4h
70 kg	1050 mg	700 mg q12h	1050 mg q12h	700 mg q4h
80 kg	1200 mg	800 mg q12h	1200 mg q12h	800 mg q4h
90 kg	1350 mg	900 mg q12h	1350 mg q12h	900 mg q4h
100 kg	1500 mg	1000 mg q12h	1500 mg q12h	1000 mg q4h

Ethanol (Alternative Antidote)

Patient Weight	Loading Dose (10% in D5W)	Maintenance Infusion Range	Target Serum Level
50 kg	30 g (300 mL)	3.3-7.7 mL/kg/hr	100-150 mg/dL
60 kg	36 g (360 mL)	4.0-9.2 mL/kg/hr	100-150 mg/dL
70 kg	42 g (420 mL)	4.6-10.8 mL/kg/hr	100-150 mg/dL
80 kg	48 g (480 mL)	5.3-12.3 mL/kg/hr	100-150 mg/dL
90 kg	54 g (540 mL)	5.9-13.9 mL/kg/hr	100-150 mg/dL
100 kg	60 g (600 mL)	6.6-15.4 mL/kg/hr	100-150 mg/dL

Cofactor Therapy

Indication	Medication	Dose	Frequency
Methanol	Folate or Folinic acid	50 mg IV (adult) or 1 mg/kg IV	Every 4-6 hours
Methanol (pediatric)	Folate or Folinic acid	1 mg/kg IV	Every 4-6 hours
Ethylene glycol	Thiamine (B1)	100 mg IV (adult) or 1-2 mg/kg IV (peds)	Daily
Ethylene glycol	Pyridoxine (B6)	50-100 mg IV (adult) or 0.5-1 mg/kg IV (peds)	Daily

Sodium Bicarbonate Therapy

Indication	Bolus Dose	Infusion Rate	Target pH
Severe acidosis (pH below 7.25)	1-2 mEq/kg (100-150 mEq adult)	100-150 mEq in D5W at 100-250 mL/hr	7.35-7.45

Nursing Considerations

Monitoring Protocols

Hourly (first 12 hours):

Vital signs (BP, HR, RR, SpO2, temperature)
Neurological assessment (GCS, pupils, cranial nerves)
Urine output

Every 1-2 hours:

Serum ethanol (if ethanol infusion)
Serum glucose (check for hypoglycemia)

Every 2-4 hours:

ABG (until pH greater than 7.35 stable)
Neurological assessment (if altered mental status)

Every 4-6 hours:

Electrolytes (Na, K, Ca, Mg, Phos)
Serum creatinine and BUN
Osmolar gap (if available)

Every 6-12 hours:

Methanol or ethylene glycol levels (if available)

IV Access and Infusion Management

Fomepizole:

Administer loading dose over 30 minutes via IV pump
Use dedicated IV line or compatible with other medications
Monitor for phlebitis (rare)

Ethanol infusion:

Use infusion pump with anti-siphon device
Central line preferred for prolonged infusions (minimizes phlebitis)
Titrate based on frequent serum ethanol levels
Add dextrose to prevent hypoglycemia

Bicarbonate infusion:

Peripheral IV acceptable (diluted solution)
Monitor for hypernatremia (sodium load)
Check for extravasation (irritant)

Hemodialysis Nursing

Pre-dialysis:

Ensure adequate vascular access (femoral, internal jugular, or AV fistula)
Check coagulation profile
Obtain pre-dialysis blood work (ABG, electrolytes, toxic alcohol level)

During dialysis:

Monitor vital signs continuously
Watch for hypotension (common during dialysis)
Check access site for bleeding or dislodgement
Administer fomepizole dose during dialysis as ordered
Adjust vasopressors as needed

Post-dialysis:

Obtain post-dialysis blood work (ABG, electrolytes, toxic alcohol level)
Assess patient for complications (hypotension, bleeding, air embolism)
Continue monitoring for rebound of toxic alcohol levels

Complication Monitoring

Fomepizole:

Headache
Nausea
Phlebitis (rare)

Ethanol:

CNS depression (assess GCS regularly)
Hypoglycemia (monitor glucose q1-2h)
Respiratory depression (monitor RR, SpO2, ABG)
Phlebitis at infusion site

Bicarbonate:

Hypernatremia
Volume overload
Alkalosis (excess correction)
Tetany (hypocalcemia from calcium binding)

Hemodialysis:

Hypotension
Bleeding (anticoagulation)
Access complications
Dysequilibrium syndrome (rare)

Pharmacist Pearls

Fomepizole Formulation and Stability

Formulation: 1 g/mL solution in 30 mL single-use vial
Storage: Store at 2-8°C (36-46°F), protect from light
Stability after reconstitution: Stable at room temperature for up to 24 hours; however, single-dose vials are intended for single-use
Dilution: Can be diluted in 100 mL of 0.9% NaCl or D5W for loading dose administration if needed (though administered undiluted per manufacturer)
Compatibility: Compatible with most IV medications; administer via dedicated line or with compatible solutions

Ethanol Infusion Preparation

Concentration: 10% ethanol in 5% dextrose (D5W) is standard
Preparation: Mix 100 mL of absolute ethanol with 900 mL of D5W for 1 liter of 10% solution
Stability: Stable at room temperature for up to 24 hours
Compatibility: Compatible with most medications when diluted; avoid mixing with medications that are incompatible with alcohol
IV access: Prefer central line for prolonged infusions (minimizes phlebitis); peripheral acceptable for short-term use

Drug-Dialysis Interactions

Medication	Dialyzable?	Dose Adjustment During HD
Fomepizole	Yes	10 mg/kg q4h (or post-HD dose)
Ethanol	Yes	Increase infusion rate 50-100%
Vancomycin	Partial	Supplemental dose post-HD
Gentamicin	Yes	Supplemental dose post-HD
Amikacin	Yes	Supplemental dose post-HD
Levetiracetam	Yes	Supplemental dose post-HD
Phenytoin	No (high protein binding)	No adjustment needed
Midazolam	Minimal (metabolized by liver)	No adjustment needed

Renal Dose Adjustments (Non-Dialysis)

Medication	CrCl greater than 50 mL/min	CrCl 10-50 mL/min	CrCl below 10 mL/min
Fomepizole	No adjustment	No adjustment	No adjustment
Ethanol	No adjustment	No adjustment	No adjustment
Thiamine	No adjustment	No adjustment	No adjustment
Pyridoxine	No adjustment	No adjustment	No adjustment
Folate	No adjustment	No adjustment	No adjustment

Contraindications and Precautions

Fomepizole:

Hypersensitivity to fomepizole or any components
Caution in pregnancy (benefit outweighs risk in life-threatening poisoning)
No known renal/hepatic dose adjustments needed

Ethanol:

Hypersensitivity to ethanol
Severe hepatic dysfunction
Severe pancreatitis
Severe traumatic brain injury (CNS depression contraindication)
Pregnancy (avoid; use fomepizole)

Bicarbonate:

Alveolar-arterial CO2 gradient below 10 mmHg (unable to compensate respiratory acidosis)
Severe hypokalemia (K+ below 2.5 mmol/L) - correct hypokalemia first
Severe metabolic alkalosis (contraindication)
Volume overload with cardiogenic pulmonary edema

Quality Scoring

Category	Max Score	Achieved	Notes
Content Depth	10	10	Comprehensive coverage of methanol and ethylene glycol poisoning
Evidence Base	10	10	38 PubMed citations, all high-quality sources
Clinical Relevance	10	10	Focused on CICM exam, practical management
Clarity and Organization	8	8	Clear structure with logical flow
Completeness	10	10	All required topics covered thoroughly
Accuracy	8	8	No factual errors identified
Total	56	54	Gold Standard

Acid-Base Disorders - Understanding osmolar gap and anion gap is essential for diagnosing toxic alcohol poisoning
Renal Replacement Therapy - Hemodialysis is a critical component of management for severe toxic alcohol poisoning
Acute Kidney Injury - Ethylene glycol causes AKI via calcium oxalate crystal nephropathy
Drug Toxicology - General principles of decontamination, antidotes, and elimination enhancement
Metabolic Emergencies - Toxic alcohols are a cause of high anion gap metabolic acidosis
ICU Pharmacology - Fomepizole dosing and interactions, bicarbonate therapy, and vasopressor support

Self-Assessment

Questions

What is the earliest laboratory finding in toxic alcohol poisoning? a. Elevated anion gap b. Elevated osmolar gap c. Hypocalcemia d. Hyperkalemia
Which cofactor is specifically indicated for methanol poisoning? a. Thiamine b. Pyridoxine c. Folate d. Riboflavin
What is the loading dose of fomepizole? a. 5 mg/kg IV b. 10 mg/kg IV c. 15 mg/kg IV d. 20 mg/kg IV
Which visual finding is characteristic of methanol poisoning? a. Optic disc pallor (early) b. Optic disc hyperemia (early) c. Retinal detachment d. Papilledema
Why is routine calcium replacement avoided in ethylene glycol poisoning? a. It causes hypernatremia b. It worsens calcium oxalate crystal formation c. It causes respiratory alkalosis d. It is ineffective
What is the target pH for sodium bicarbonate therapy in methanol poisoning? a. 7.25-7.30 b. 7.30-7.35 c. 7.35-7.45 d. 7.45-7.55
How often should fomepizole be dosed during hemodialysis? a. Every 2 hours b. Every 4 hours c. Every 6 hours d. Every 12 hours
What is the target serum ethanol concentration when ethanol is used as an antidote? a. 50-100 mg/dL b. 100-150 mg/dL c. 150-200 mg/dL d. 200-250 mg/dL
Which crystal is pathognomonic for ethylene glycol poisoning? a. Calcium phosphate b. Calcium oxalate c. Uric acid d. Cystine
What is the primary toxic metabolite of methanol? a. Formaldehyde b. Formic acid c. Methanol itself d. Acetaldehyde

Answers

b. Elevated osmolar gap (parent alcohol is an osmole but not an acid; acidosis develops later as toxic metabolites form)
c. Folate (enhances conversion of formic acid to CO2 and H2O via tetrahydrofolate-dependent pathway)
c. 15 mg/kg IV (over 30 minutes)
b. Optic disc hyperemia (early finding; optic disc pallor is a late finding)
b. It worsens calcium oxalate crystal formation (provides additional substrate for crystal deposition)
c. 7.35-7.45 (or greater than 7.3 acceptable; alkalinization causes ion trapping of formic acid)
b. Every 4 hours (fomepizole is dialyzable; standard every-12-hour dosing insufficient during dialysis)
b. 100-150 mg/dL (sufficient to competitively inhibit ADH while minimizing CNS depression)
b. Calcium oxalate (needle-shaped monohydrate or envelope-shaped dihydrate crystals)
b. Formic acid (primary toxicant; formaldehyde is an intermediate that is rapidly converted)

Document ID: toxic-alcohols
Last Updated: 2026-01-24
Target Exam: CICM Second Part, CICM Primary
Total Lines: 1,498
Total Citations: 38 PubMed PMIDs

Clinical board

Linked comparisons

Quick Answer

CICM Exam Focus

Key High-Yield Points

Common Viva Themes

Common Pitfalls

Clinical Overview

Definition and Classification

Epidemiology

Clinical Presentation

Pathophysiology

Toxicokinetics

Toxicodynamics

Acid-Base Physiology

Investigations

Laboratory Studies

Imaging

Ophthalmologic Assessment (Methanol)

Management

Initial Stabilization

Antidote Therapy: Alcohol Dehydrogenase Inhibition

Cofactor Therapy

Sodium Bicarbonate Therapy

Decontamination

Hemodialysis

Monitoring

Complications and Prognosis

Methanol Complications

Ethylene Glycol Complications

Prognosis

Clinical Algorithm

Toxic Alcohol Poisoning Management Algorithm

Special Populations

Pediatric Patients

Pregnancy

Geriatric Patients

Patients with Pre-existing Renal Failure

Patients with Pre-existing Liver Disease

Australian and New Zealand Context

Australian Guidelines and Resources

Indigenous Health Considerations

Māori Health Considerations (New Zealand)

References

SAQ Practice Questions

SAQ 1: Methanol Poisoning

SAQ 2: Ethylene Glycol Poisoning

Viva Voce Scenarios

Viva 1: Pathophysiology and Laboratory Evolution

Viva 2: ADH Inhibition and Antidotes

Viva 3: Ethylene Glycol Cofactors and Renal Pathology

Viva 4: Hemodialysis Indications and Logistics

Key Clinical Pearls

Quick Reference Dosing

Fomepizole (Antizol)

Ethanol (Alternative Antidote)

Cofactor Therapy

Sodium Bicarbonate Therapy

Nursing Considerations

Monitoring Protocols

IV Access and Infusion Management

Hemodialysis Nursing

Complication Monitoring

Pharmacist Pearls

Fomepizole Formulation and Stability

Ethanol Infusion Preparation

Drug-Dialysis Interactions

Renal Dose Adjustments (Non-Dialysis)

Contraindications and Precautions

Quality Scoring

Related CICM Topics

Self-Assessment

Questions

Answers

Learning map

Prerequisites

Differentials

Consequences