01Approach to the Critical Patient/attcp70

Immediate priorities

›Airway and CNS threats

›Altered mental status ranging from inebriation to coma

›GCS trending down signals imminent airway loss

›Seizure risk in severe poisoning

›If GCS < 8 or airway unprotected, proceed to rapid sequence intubation

›Pre-oxygenate fully before attempt

›Ketamine or etomidate as induction agent

›Seizure management

›Benzodiazepines first line

›Avoid phenytoin as renal failure may develop

›Hemodynamic stabilization

›Shock physiology (late or severe presentation)

›SBP < 90 mmHg

›MAP < 65 mmHg

›IV access and fluid resuscitation

›Maintain urine output 1–2 mL/kg/h to promote renal EG clearance

›Avoid fluid overload in AKI

›Cardiovascular monitoring

›Tachycardia from hypocalcemia or acidosis

›Dysrhythmia risk with severe hypocalcemia

›Metabolic crisis management

›Severe high anion gap metabolic acidosis

›pH < 7.1 threshold for aggressive intervention

›Bicarbonate < 5 mmol/L as marker of critical severity

›Sodium bicarbonate IV for pH < 7.1

›Titrate to maintain pH > 7.2 while hemodialysis arranged

›Monitor for hypernatremia and fluid overload

02History/hx66

Ingestion details

›Substance characterization

›Antifreeze or engine coolant (typically 95% EG)

›Sweet taste — palatability increases pediatric and accidental risk

›Bright green or orange color

›Industrial solvents or hydraulic fluids

›Occupational exposure context

›Variable EG concentration

›Amount ingested

›Minimum lethal dose approximately 100 mL (1.6 g/kg) in adults

›Toxicity with as little as 10–30 mL of concentrated solution

›Timing of ingestion

›Time from ingestion to presentation

›Early (< 6 hours): inebriation without acidosis

›6–12 hours: metabolic acidosis developing

›> 12 hours: renal failure and crystalluria

›Coingestant timing effect

›Ethanol coingestion delays metabolism 12–72 hours

›Present in 10–60% of cases

Symptom progression

›Early phase (0–6 hours)

›CNS inebriation

›Slurred speech, ataxia, nausea, vomiting

›Resembles ethanol intoxication

›Nausea and vomiting

›May limit total absorbed dose

›GI symptoms from EG itself

›Late phase (6–24+ hours)

03Physical Exam/exam58

Vitals

›Vital sign pattern

›Respiratory rate

›Tachypnea with deep breaths (Kussmaul pattern)

›Compensatory response to metabolic acidosis

›Heart rate

›Tachycardia from hypocalcemia or acidosis

›Bradycardia is ominous — severe myocardial depression

›Blood pressure

›Hypotension in late or severe poisoning

›Fluid-responsive initially; vasopressor requirement signals severity

›Temperature

›Hypothermia possible (exposure, CNS depression)

›Fever not typical — consider coingestant or infection

Neurological exam

›Mental status

›Inebriation state (early)

›Slurred speech

›Ataxia

›Obtundation to coma (late)

›GCS < 13 triggers immediate CT head

›Seizures indicate severe CNS toxicity

›Nystagmus

›Common in early phase

›Resembles acute ethanol intoxication

›Cranial nerve assessment

›Delayed cranial nerve palsies (days after exposure)

›Facial nerve, abducens palsy reported

04Differential Diagnosis/ddx59

Toxic alcohol mimics

›Methanol poisoning

›ICD-10 T51.1X

›Similar elevated osmolal and anion gap pattern

›Key distinguishing feature: visual disturbances (blurry vision, blindness)

›Formate accumulation (not oxalate)

›Papilledema and optic disc hyperemia

›No calcium oxalate crystalluria

›Isopropanol poisoning

›ICD-10 T51.2X

›Elevated osmolal gap WITHOUT anion gap acidosis

›Ketonemia and ketonuria without acidosis

›Acetone odor on breath

›Metabolized to acetone (ketone), not acid

›Supportive care only; no antidote needed

›Propylene glycol toxicity

›ICD-10 T51.8X

›Elevated osmolal gap with lactic acidosis

›Iatrogenic — IV lorazepam, phenobarbital, or esmolol infusions

›Elevated lactate with normal anion gap reconciliation

›POC and lab lactate gap less prominent

›EG history absent

High anion gap metabolic acidosis differential

›Diabetic ketoacidosis

›ICD-10 E13.10

›Ketonemia and hyperglycemia

›No osmolal gap (unless concurrent ethanol use)

›Insulin deficiency context

05Laboratory Tests/lt74

Core metabolic panel

›Basic metabolic panel

›Serum sodium for anion gap calculation

›Anion gap = Na − (Cl + HCO3); normal 8–12 mmol/L

›Anion gap > 20 mmol/L high suspicion for toxic alcohol

›Serum bicarbonate

›< 5 mmol/L indicates critical severity

›Serial values track treatment response

›Serum creatinine and BUN

›Rising creatinine signals AKI onset

›Rapid creatinine rise over hours distinguishes from CKD

›Ionized calcium

›Hypocalcemia from calcium oxalate precipitation

›Target ≥ 1.0 mmol/L with therapy

Osmolal gap calculations

›Serum osmolality by freezing-point depression

›Measured osmolality minus calculated osmolality

›Calculated = (2 × Na) + (BUN/2.8) + (glucose/18) + (ethanol/3.7)

›All values in mmol/L for SI calculation

›Osmolal gap normal < 10–20 mOsm/kg

›Elevated gap early in ingestion before metabolism

›Gap narrows as EG metabolized (anion gap rises)

›Osmolal gap can be normal with late presentation

›EG fully converted to acidic metabolites

›Do not use normal gap to exclude EG toxicity

Blood gas and lactate

›Arterial or venous blood gas

›pH

›< 7.1 threshold for emergent intervention

›< 7.25 hemodialysis consideration

›pCO2 (mmHg)

›Low with compensatory Kussmaul breathing

›Rising pCO2 despite acidosis indicates ventilatory failure

›Bicarbonate trend

›Serial values q2–4h to monitor treatment response

›Target pH > 7.35 with therapy

›Lactate — dual measurement strategy

›POC lactate (immediately)

›Glycolate cross-reacts with some analyzers — falsely elevated

›Apparent lactate gap is a diagnostic clue

›Laboratory lactate (simultaneous)

›True lactate measured by enzymatic method

›Discrepancy POC minus lab > 4 mmol/L = lactate gap sign

Confirmatory and prognostic labs

›Serum EG level

›> 3.2 mmol/L (20 mg/dL) — treat with antidote

›Often delayed result; do not withhold treatment

›> 8 mmol/L (50 mg/dL) — hemodialysis indication

›Serum glycolate level (if available)

›> 12 mmol/L correlates with anion gap > 28 mmol/L and worse outcome

›< 8 mmol/L has 100% negative predictive value for mortality

›Serum ethanol level

›Assess for coingestion

›Present in 10–60% of cases

›Delays metabolism and symptom onset

›Guides ethanol antidote dosing if fomepizole unavailable

›Target ethanol 22 mmol/L (100 mg/dL)

›Complete blood count and hepatic enzymes

›Leukocytosis from stress response or infection

›Baseline prior to fomepizole

›Hepatic transaminases

›Fomepizole can cause transient elevation and eosinophilia

›Serial monitoring during therapy

Urinalysis

›Urine microscopy

›Calcium oxalate dihydrate crystals (envelope-shaped)

›Appear within 4–6 hours of ingestion

›Highly specific finding for EG toxicity

›Calcium oxalate monohydrate crystals (needle-shaped)

›Appear later (> 6 hours)

›Monohydrate form predominates with severe exposure

›Hematuria

›Tubular injury from crystal deposition

›Pyuria may be absent (not infectious)

›Urine Wood lamp fluorescence

›Fluorescein added to many antifreeze products

›Urine glows green under Wood lamp

›Positive early, negative with late presentation or non-fluorescein product

›Not reliable to rule out ingestion

06Diagnostic Tests/dt69

Scoring Systems

›Toxicity severity classification

›Mild toxicity

›Alert and oriented

›pH > 7.3

›Osmolal gap elevated without anion gap

›Moderate toxicity

›Altered mental status

›pH 7.1–7.3

›Anion gap > 20 mmol/L

›Severe toxicity

›Coma or seizures

›pH < 7.1

›Bicarbonate < 5 mmol/L

›Overall treated mortality approximately 18.7%

›Anion gap as prognostic marker

›Anion gap > 28 mmol/L

›Correlates with glycolate > 12 mmol/L

›Significantly worse outcomes

›Emergency hemodialysis indication

›Anion gap trend used to guide treatment endpoint

›Normalizing gap signals metabolite clearance

›Continue antidote until gap and EG level normal

MRI

›Brain MRI role in EG toxicity

›Limited acute utility

›Osmolal and anion gap assessment is primary diagnostic tool

›CT head faster and more available

07Disposition/dispo41

ICU and inpatient criteria

›ICU admission indications

›All confirmed or high-suspicion EG ingestions require minimum monitored bed

›Rapid deterioration possible within hours

›Antidote and dialysis coordination

›ICU-level criteria

›Altered mental status (GCS < 14)

›pH < 7.25

›Hemodynamic instability

›Seizures

›AKI with oliguria or anuria

›Hemodialysis requirement

›Nephrology and ICU coordination

›Continuous renal replacement therapy if hemodynamically unstable

›Transfer criteria

›Transfer to tertiary center if hemodialysis not available

›Do not delay antidote while arranging transfer

›Start fomepizole and bicarbonate before departure

›Stabilize airway before transfer if altered mental status

›Intubate if GCS < 8 or airway concern

›Transfer with ICU-capable team

Discharge criteria

›Criteria to consider discharge (very limited cases)

›Very small ingestion with no symptoms at 6 hours

›Normal metabolic panel

›Normal osmolal gap

›No acidosis

›Poison control guidance supporting outpatient management

08Treatment/t94

Antidote therapy

›Fomepizole (4-methylpyrazole) — first-line antidote

›Loading dose

›15 mg/kg IV over 30 minutes

›Do NOT use polycarbonate syringes or needles

›Maintenance dosing

›10 mg/kg IV q12h for 4 doses (48 hours)

›Then 15 mg/kg IV q12h until EG level < 3.2 mmol/L and pH normal

›Dose adjustment during hemodialysis

›Increase to q4h during dialysis sessions

›Hemodialysis clears fomepizole and EG

›Administration precautions

›Dilute in 100 mL NS or D5W

›Infuse over 30 minutes to prevent phlebosclerosis

›Monitoring during fomepizole

›Transient transaminase elevation expected

›Eosinophilia possible

›Class I recommendation for toxic alcohol ADH inhibition

›Ethanol — alternative if fomepizole unavailable

›Target serum ethanol 22 mmol/L (100 mg/dL)

›Competitive ADH inhibitor at this concentration

›Requires continuous monitoring

›IV ethanol infusion

›10% ethanol in D5W — loading dose 7.6–10 mL/kg over 30–60 minutes

›Maintenance 0.83–1.0 mL/kg/h (higher in chronic drinkers)

›Oral ethanol as last resort

›50% ethanol (spirits) — 1 mL/kg loading dose

›Difficult to control levels; IV preferred

›Monitoring requirements

›Serum ethanol q1–2h to maintain target

›Glucose monitoring (hypoglycemia risk)

›ICU monitoring mandatory

Hemodialysis

›Indications for hemodialysis

›pH < 7.25 despite bicarbonate therapy

›Emergent nephrology consult

›Do not delay for EG confirmation

›EG level > 8 mmol/L (50 mg/dL)

›Even without acidosis if level critically elevated

›Hemodialysis most efficient EG removal

›AKI with oliguria unresponsive to fluids

›Fluid management failure

›Uremic complications developing

›Refractory hypocalcemia or hyperkalemia

›Hyperkalemia with poor prognosis association

›Dialysis corrects both electrolyte abnormalities

›Hemodialysis parameters

›Intermittent hemodialysis preferred

›More efficient EG clearance than CRRT

›Session duration 4–8 hours depending on response

›CRRT for hemodynamically unstable patients

›Slower clearance but tolerated in shock

›Fomepizole dose q4h during CRRT also

›Treatment endpoint

›EG level < 3.2 mmol/L

›pH > 7.35

›Anion gap normalized

›Osmolal gap normalized

Metabolic correction

›Sodium bicarbonate

›Indications

›pH < 7.1 or bicarbonate < 10 mmol/L

›Bridge to hemodialysis

›Dosing

›1–2 mEq/kg IV bolus

›Continuous infusion: 3 ampules in 1 L D5W at 150 mL/h

›Targets and monitoring

›pH > 7.2 goal while awaiting dialysis

›Monitor sodium (hypernatremia risk)

›Ionized calcium may drop further with alkalinization

›Calcium supplementation

›Calcium gluconate IV for symptomatic hypocalcemia

›1–2 g IV over 10–20 minutes

›Repeat as needed for symptomatic tetany or QTc prolongation

›Calcium chloride in cardiac arrest setting

›1 g IV via central line preferred

›Faster ionized calcium rise

›Caution with aggressive calcium supplementation

›Excess calcium may worsen oxalate deposition

›Treat symptomatic hypocalcemia; do not over-correct

Cofactor and supportive therapy

›Thiamine supplementation

›100 mg IV

›Cofactor shunting EG metabolism toward non-toxic pathways

›Empiric — limited evidence but low risk

›Prevents Wernicke encephalopathy in alcohol use disorder context

›Pyridoxine supplementation

›50–100 mg IV

›Cofactor shunting glycolate metabolism toward glycine (less toxic)

›Empiric use standard of practice

›Limited clinical evidence for efficacy

›IV fluids

›Maintain urine output 1–2 mL/kg/h

›Promotes renal EG excretion when ADH blocked

›EG renal elimination half-life ~17 hours with ADH inhibition

›Avoid fluid overload with AKI

›Monitor fluid balance closely

›Dialysis for volume overload if AKI established

09Special Populations/sp79

Pregnancy

›EG toxicity in pregnancy

›Teratogenicity

›EG is teratogenic in animal models

›Limited human data; treat mother aggressively as priority

›Fetal monitoring

›Continuous fetal heart rate monitoring when viable (> 24 weeks)

›Obstetrics consultation immediately

›Metabolic effects on fetus

›Maternal acidosis causes fetal acidosis

›Correct maternal pH urgently

›Antidote safety in pregnancy

›Fomepizole in pregnancy

›Limited safety data but generally preferred over ethanol

›Ethanol is a known teratogen — avoid if fomepizole available

›Risk-benefit favors fomepizole given EG teratogenicity

›Hemodialysis in pregnancy

›Safe and effective — required for same indications

›Obstetrics team at bedside during dialysis

›Monitor uterine contractions

›Sodium bicarbonate in pregnancy

›Generally safe for maternal acidosis correction

›Monitor fetal response to pH correction

›Hypernatremia risk with large doses

Geriatric

›Physiologic vulnerability

›Reduced renal reserve

›AKI develops faster and is more severe

›Baseline creatinine may mask early AKI

›Reduced volume of distribution

›Same ingested dose achieves higher EG level

›Lower threshold for antidote initiation

›Polypharmacy interactions

›Ethanol antidote increases risk of CNS depression from other medications

›Fomepizole preferred

›Presentation differences

›Atypical presentation

›Delirium may be attributed to dementia or psychiatric disease

›Low threshold for toxic alcohol screen in unexplained HAGMA

›Accidental ingestion more common

›Vision or cognitive impairment mislabeling containers

›Safe storage counseling for caregivers

›Hemodialysis considerations in older adults

›Same indications; age not a contraindication

›Vascular access challenges possible

›Hemodynamic monitoring intensified

›Post-AKI recovery slower

›Prolonged dialysis dependence risk

›Nephrology follow-up essential

Pediatrics

›Pediatric exposure characteristics

›Accidental ingestion predominates

›EG sweet taste is attractive to children

›Relatively small volumes cause toxicity (weight-based)

›Minimum toxic dose is weight-based

›0.1 mL/kg of concentrated EG can cause toxicity

›100 mL would be lethal for a 10 kg child

›Fomepizole dosing in children

›Loading dose 15 mg/kg IV (same as adult)

›Infuse over 30 minutes

›Do not exceed adult dosing

›Maintenance dosing

›10 mg/kg q12h × 4 doses

›Then 15 mg/kg q12h until EG level < 3.2 mmol/L

›Ethanol alternative in children

›Avoid ethanol if fomepizole available

›Ethanol causes more severe CNS depression in children

›Hypoglycemia risk significantly higher in pediatric patients

›Hemodialysis in children

›Pediatric nephrology consultation required

›Same indications as adults (pH < 7.25, AKI, high EG level)

›CRRT more commonly used in small children (< 10 kg)

›Vascular access

›Pediatric hemodialysis catheters required

›Femoral or internal jugular approach

›Child safety considerations

›Safe storage of EG-containing products

›Child-resistant containers

›Locked storage mandatory after ingestion event

›Poison control notification

›All pediatric EG exposures require consultation

›Follow-up call recommended

10Background/b78

Epidemiology

›Incidence and burden

›EG ingestion reported to US Poison Control Centers annually in thousands of cases

›Most cases are accidental or intentional adult ingestions

›Pediatric cases typically accidental and less severe volume-wise

›Overall mortality in treated cases approximately 18.7%

›Higher in delayed presentation

›Higher with suicidal intent (larger volumes)

›Geographic patterns

›Common in colder climates where antifreeze widely used

›Occupational exposure in automotive and industrial settings

›Demographics

›Adults (intentional) — most fatalities

›Alcohol use disorder as risk factor

›Psychiatric comorbidity in most intentional cases

›Children (accidental) — typically small volume

›Peak under 5 years old

›Sweet taste and bright color increase palatability

Pathophysiology

›Metabolic pathway

›Ethylene glycol absorbed rapidly from GI tract

›Peak serum level 1–4 hours post-ingestion

›Elimination half-life ~17 hours with ADH inhibition

›Metabolism via alcohol dehydrogenase (ADH)

›EG → glycolaldehyde → glycolate → glyoxylate → oxalate

›Glycolate accumulates and drives anion gap acidosis

›Oxalate combines with calcium → calcium oxalate crystals

›Temporal relationship of gaps

›Osmolal gap elevated early (unmetabolized EG)

›Anion gap rises as metabolites accumulate

›Late presentation: low osmolal gap + high anion gap

›Organ toxicity mechanisms

›Renal toxicity

›Calcium oxalate crystal deposition in tubules

›Direct tubular epithelial cell injury

›Oliguric AKI onset 24–72 hours post-ingestion

›CNS toxicity

›Direct EG effect — inebriation phase

›Acidosis-mediated CNS depression

›Calcium oxalate deposition in cerebral vessels (severe/delayed)

›Cardiovascular toxicity

›Hypocalcemia — dysrhythmia and cardiac depression

›Severe acidosis — myocardial dysfunction

›Pulmonary edema in severe cases

›Inverse gap relationship

›Early ingestion: high osmolal gap, low anion gap

›Parent compound EG generates osmolal gap

›Not yet metabolized to acidic metabolites

›Late ingestion: low osmolal gap, high anion gap

›EG fully converted to glycolate and oxalate

›Normal osmolal gap does not exclude late EG toxicity

Therapeutic Considerations

›ADH inhibition strategy

›Blocking ADH prevents formation of toxic metabolites

›Fomepizole has 8000x greater affinity for ADH than ethanol

›Ethanol competes with EG for ADH binding

›With ADH inhibition, EG excreted unchanged by kidneys

›Elimination half-life ~17 hours with antidote and normal renal function

›Hemodialysis dramatically shortens clearance time

›Hemodialysis rationale

›Removes EG, glycolate, and oxalate directly

›Corrects acidosis and electrolyte abnormalities simultaneously

›Most efficient intervention for severe toxicity

›Does not replace antidote

›Continue fomepizole throughout dialysis at increased frequency

›Dialysis removes fomepizole requiring dose adjustment

›Antidote selection rationale

›Fomepizole advantages over ethanol

›Predictable pharmacokinetics

›No CNS depression

›No hypoglycemia

›No need for frequent serum level monitoring

›Fomepizole cost consideration

›High cost in some settings

›Ethanol acceptable substitute with appropriate monitoring

›Treatment endpoint criteria

›EG level < 3.2 mmol/L (20 mg/dL)

›pH > 7.35

›Osmolal gap normalized

›Anion gap normalized

›Asymptomatic for > 12 hours

11Patient Discharge Instructions/pdi33

copy discharge instructions

›Ethylene glycol poisoning home care

›Recovery instructions

›Complete all prescribed medications including antidotes if outpatient

›Drink adequate fluids as instructed by your doctor

›Do not drive or operate machinery until fully cleared by your doctor

›Kidney monitoring

›Kidney function must be checked at your follow-up appointment

›Report any decrease in urine output immediately

›Report swelling in legs or face (sign of kidney problems)

›Warning signs — return to emergency room immediately

›Severe symptoms requiring immediate return

›Confusion, drowsiness, or difficulty staying awake

›Seizure or shaking episode

›Unable to urinate for more than 8 hours

›Severe nausea or vomiting preventing fluid intake

›Muscle cramps, spasms, or tetany

›Chest pain or palpitations

›Rapid or difficult breathing

›Worsening weakness

›Mental health and safety

›If poisoning was intentional

›Follow-up with mental health provider is mandatory

›Crisis line available 24 hours: 988 (Suicide and Crisis Lifeline)

›Remove or secure all toxic substances from home

›Antifreeze and ethylene glycol safety

›Store antifreeze in original labeled containers, locked away

›Keep out of reach of children and pets

12References/r25

Guidelines and key sources

›Toxicology guidelines

›American College of Medical Toxicology (ACMT) — Fomepizole for ethylene glycol poisoning position statement

›Fomepizole first-line antidote recommendation

›Hemodialysis indications outlined

›Extrip Workgroup — Extracorporeal Treatment for Ethylene Glycol Poisoning

›Evidence-based hemodialysis indications

›pH < 7.25, EG > 8 mmol/L, AKI criteria

›ACEP Clinical Policy on toxic alcohol poisoning

›Osmolal gap and anion gap diagnostic framework

›Level B/C recommendations for antidote use

›Key literature

›Brent J et al. Fomepizole for the treatment of ethylene glycol poisoning (NEJM 1999)

›Landmark trial establishing fomepizole safety and efficacy

›Basis for current dosing protocol

›Hovda KE et al. Anion gap and glycolate as prognostic markers in ethylene glycol poisoning

›Anion gap > 28 mmol/L correlated with glycolate > 12 mmol/L and mortality

›Glycolate < 8 mmol/L — 100% negative predictive value for death

›Mégarbane B et al. Overall mortality approximately 18.7% in treated EG poisoning

›Suicidal intent, coma, and hyperkalemia as poor prognostic factors

›Coding and classification

›ICD-10 T57.3X — Toxic effects of ethylene glycol

›Accidental: T57.3X1A

›Intentional self-harm: T57.3X2A

›SNOMED CT: Ethylene glycol poisoning (disorder)

›Concept aligns with toxic alcohol ingestion category

Evidence & Review