At a Glance

Why It's Ordered
Did the patient ingest a drug or toxin, how much, and how severe is the toxicity? Answers ED, ICU and transport questions for overdose and toxic exposure.
Check First
Acetaminophen and salicylate for every intentional overdose, the anion and osmolar gaps, and the ECG (QRS, QTc). Check K⁺ and Mg²⁺ with digoxin or lithium concerns.
Critical Values
APAP >150 µg/mL at 4 hr · Salicylate >30 mg/dL · Digoxin >2.0 ng/mL · Lithium >1.5 mEq/L · COHb >25 % · Osmolar gap >10 mOsm/kg
Don't Miss
A normal APAP level drawn before 4 hr is not interpretable. A negative drug screen does not exclude fentanyl, nitazenes or xylazine: test for the specific agent.
Field & Transport
Field SpCO and SpMet are screening only. Obtain the sending facility's levels with draw times, ingestion history and antidotes given. Repeat salicylate every 2 hr and lithium every 2–4 hr en route when feasible.

Panel Overview

The toxicology panel is a set of serum levels for drugs and toxins, plus the gaps and co-oximetry used to recognize poisoning in emergency and critical care. Most overdoses need acetaminophen and salicylate levels, ECG, and electrolytes. Toxic alcohols, digoxin and lithium are ordered when the history or the anion gap points to them.

The core measured levels are acetaminophen, salicylate, ethanol, toxic alcohols, digoxin, lithium, carboxyhemoglobin and methemoglobin. Serum osmolality, anion gap, serum iron, cholinesterase, creatine kinase and lactate are add-ons and calculated values.

When to Order:
  • Intentional overdose: acetaminophen and salicylate for every case
  • Altered mental status: ethanol, glucose, gaps, ECG, co-ingestants
  • Weakness or arrhythmia: digoxin, potassium, magnesium, ECG
  • High anion-gap acidosis: lactate, ketones, osmolar gap, toxic alcohols
  • Fire or enclosed-space exposure: carboxyhemoglobin, methemoglobin, lactate
  • Tremor or confusion on lithium: serial lithium levels, kidney function

Analgesic Levels

Acetaminophen

Therapeutic: 10–30 µg/mL

Plotted on the revised Rumack-Matthew nomogram only at 4 hr or later after a single acute ingestion of known timing. Treatment line 150 µg/mL at 4 hr.

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Salicylate

Expected on therapy: lab-specific; toxic above 30 mg/dL

Toxicity begins above 30 mg/dL; chronic toxicity can occur at lower levels. Mixed respiratory alkalosis and anion-gap acidosis is typical. Repeat until falling; levels can rise after extended-release ingestion.

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Alcohols & Osmolality

Ethanol Level

Expected: none detected

Ethanol level does not predict mental status reliably because tolerance varies widely. Consider other causes when the level and clinical picture do not match.

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Toxic Alcohols

Methanol / ethylene glycol: undetectable

Methanol and ethylene glycol cause high anion-gap acidosis and a raised osmolar gap. Start fomepizole on suspicion; do not wait for the level.

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Serum Osmolality

Expected: 275–295 mOsm/kg

Calculated osmolality is 2Na⁺ + glucose/18 + BUN/2.8 + ethanol (mg/dL) ÷ 3.7. Osmolar gap above 10 is abnormal and suggests toxic alcohols, especially with an anion-gap acidosis; ethanol and isopropanol raise the gap without major acidosis.

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Narrow Therapeutic Index Drugs

Digoxin

Target (heart failure): 0.5–0.9 ng/mL

Toxicity causes ventricular arrhythmias, bradycardia and AV block. Check K⁺ and Mg²⁺ at once; hypokalemia raises toxicity risk. Draw at least 6 hr after a dose.

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Lithium

Therapeutic: 0.6–1.2 mEq/L

Toxicity causes neurologic signs. Chronic toxicity can occur at levels near the therapeutic range. Serial levels are needed; a single level does not show the trend.

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Anticonvulsant Levels

Therapeutic: phenytoin 10–20 µg/mL

Total levels. Toxicity causes nystagmus, ataxia and altered mental status. Free levels and interpretation depend on albumin and kidney function.

Hemoglobin & Specific Poisons

Carboxyhemoglobin

Non-smoker: <3% | Smoker: up to 10%

Co-oximetry confirms CO exposure. Pulse-oximetry SpO₂ does not detect COHb, so a normal SpO₂ does not exclude CO poisoning.

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Methemoglobin

Expected: below 1% of total hemoglobin

Methemoglobinemia holds SpO₂ near 85% regardless of PaO₂, so a fixed low SpO₂ with normal PaO₂ and chocolate-brown blood is the clue. Co-oximetry is required. Treat symptomatic patients per protocol; methylene blue 1–2 mg/kg IV is the usual antidote, with caution in G6PD deficiency and with serotonergic drugs (serotonin syndrome).

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Serum Iron

Expected: lab-specific (about 60–170 µg/dL)

Serum iron above about 500 µg/dL is a typical concern threshold, not a validated cutoff. Check the time of ingestion; serum iron falls as iron distributes.

Cholinesterase

Expected: lab-specific; compare with baseline

RBC and plasma cholinesterase fall with organophosphate and carbamate exposure. Use a baseline when one exists; reference intervals differ between labs.

Screening, Calculated Values & Add-Ons

Urine Drug Screen

Qualitative: positive / negative

Immunoassays detect drug classes, not individual drugs. Fentanyl, nitazenes and xylazine are often missed. False positives and negatives are common; confirm with a specific assay.

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Anion Gap

Expected: 8–12 mEq/L (without K⁺; analyzer-dependent)

Calculated as Na⁺ − (Cl⁻ + HCO₃⁻). Above 12 mEq/L indicates an anion-gap acidosis; check lactate, ketones, uremia, toxic alcohols, salicylate.

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Lactate

Expected: 0.5–1.5 mmol/L; raised above 2

Elevated in shock, seizures and some toxins. A lactate of 10 mmol/L or more is in the US smoke-inhalation cyanide label criteria.

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Creatine Kinase

Expected: lab-specific

Rises with rhabdomyolysis from sedatives, stimulants, serotonergic and anticholinergic toxins. Check urine myoglobin and renal function if CK is rising.

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Reference Ranges & Critical Values
Toxic levels and thresholds (typical; institution-dependent)
TestTherapeutic or ExpectedToxic or CriticalSI UnitsNotes
Acetaminophen
10–30 µg/mL
150 µg/mL at 4 hr (treatment line)
150 µg/mL ≈ 990 µmol/L
Single acute ingestion, timed; line falls over time
Salicylate
No universal therapeutic range (lab-specific)
>30 mg/dL (2.2 mmol/L) in acute ingestion; chronic toxicity can occur at lower levels. EXTRIP dialysis (recommended): >100 mg/dL (>90 with impaired kidney function), altered mental status, ARDS requiring supplemental oxygen, or failure of standard therapy. Suggested: above 90 mg/dL (above 80 with impaired kidney function); pH 7.20 or lower without other indications
10 mg/dL ≈ 0.72 mmol/L
Repeat every 2 hr until falling
Ethanol
None detected
—
80 mg/dL ≈ 17.4 mmol/L
Legal limit is not a normal value
Methanol / Ethylene Glycol
Undetectable
Detectable with osmolar gap or acidosis
—
Treat on suspicion
Osmolar Gap
<10 mOsm/kg
>10 mOsm/kg
mOsm/kg = mmol/kg
Measured minus calculated osmolality
Digoxin
0.5–0.9 ng/mL (heart failure target)
>2.0 ng/mL; toxicity possible at lower levels with hypokalemia
2.0 ng/mL ≈ 2.6 nmol/L
Draw at least 6 hr after a dose
Lithium
0.6–1.2 mEq/L
>1.5 mEq/L
1 mEq/L = 1 mmol/L
Chronic toxicity can occur below 1.5
Phenytoin
10–20 µg/mL (total)
>20 µg/mL
—
Lab-specific; albumin affects interpretation
Carboxyhemoglobin
Non-smoker <3%; smoker up to 10%
Symptomatic or high COHb (typical >25%); pregnancy: lower threshold
%
SpO₂ does not detect COHb
Methemoglobin
Below 1%
Symptomatic; treatment threshold is protocol-dependent
%
Pulse oximetry unreliable
Serum Iron
Lab-specific (about 60–170 µg/dL)
>500 µg/dL (typical; not a validated cutoff)
1 µg/dL ≈ 0.18 µmol/L
Interpret with time since ingestion
Anion Gap
8–12 mEq/L
>12 mEq/L (acidosis)
mEq/L = mmol/L
Analyzer-dependent; without K⁺
Lactate
0.5–1.5 mmol/L
≥4 mmol/L
mmol/L
Repeat at 2–4 hr if initial above 2 mmol/L
Every lab sets its own intervals and critical values. They shift with the analyzer and the assay. Use your lab's reported interval and its critical-call policy. Doses vary by protocol; follow local protocols and medical direction.

Systematic Interpretation
  1. Timing and ingestion history: record the time of each ingestion, the agent, the amount and whether it was extended-release. Every intentional overdose gets an acetaminophen and a salicylate level.
  2. Acetaminophen: plot the level on the revised nomogram when it was drawn at 4 hr or later after a single acute ingestion of known time. Drawn before 4 hr, you can't read it yet.
  3. Salicylate: measure the level, then repeat it every 2 hr until it's falling. Get an arterial blood gas to look for a mixed acid-base disorder.
  4. Gaps: calculate the anion gap and the osmolar gap (formulas below). An anion-gap acidosis with a raised osmolar gap points you at toxic alcohols.
  5. ECG: measure the QRS duration (sodium-channel blockade above 100 ms), QTc, heart rate and AV conduction (digoxin). Any digoxin or lithium concern means K⁺ and Mg²⁺ get checked too.
  6. Specific agent levels: digoxin at 6 hr or later after a dose. Lithium serially. Ethanol, but don't assume it explains the mental status.
  7. Co-oximetry: measure COHb and methemoglobin when CO or an oxidant is possible. CO can leave SpO₂ reading falsely normal. MetHb pins SpO₂ near 85% whatever the PaO₂ is, and oxygen won't push it up.
Anion gap
Na⁺ − (Cl⁻ + HCO₃⁻); normal 8–12 mEq/L
Osmolar gap
Measured osmolality − [2Na⁺ + glucose/18 + BUN/2.8 + ethanol (mg/dL) ÷ 3.7]; abnormal above 10 mOsm/kg

HAGMA Work-Up

  1. Confirm the acidosis: check pH, HCO₃⁻ and PaCO₂. Winter's formula gives the expected PaCO₂ = 1.5 × HCO₃⁻ + 8 ± 2.
  2. Calculate the anion gap: above 12 mEq/L confirms an anion-gap acidosis.
  3. Check lactate and ketones: lactate for shock, seizures and some toxins. Beta-hydroxybutyrate and glucose for ketoacidosis.
  4. Check uremia and salicylate: BUN and creatinine; salicylate level.
  5. Check the osmolar gap: a raised gap with the acidosis calls for fomepizole on suspicion, plus toxic-alcohol levels.

ED Toxicology Bundle

  • Acetaminophen and salicylate: both, every time there's an intentional overdose.
  • Ethanol: the level, plus the bedside mental status and when any co-ingestant went in.
  • ECG: the QRS, the QTc and the rhythm.
  • Gaps: both the anion gap and the osmolar gap.
  • CK: the check for rhabdomyolysis, with urine myoglobin if it's rising.
  • Serum hCG: for women of reproductive age, before imaging and before any fetal-risk treatment.
Worked Example: A 34-year-old with altered mental status after an estimated acetaminophen and aspirin ingestion, at a reported time. APAP is 180 µg/mL, drawn 6 hr after that time. The treatment line at 6 hr is about 106 µg/mL (150 halved every 4 hr), so the level sits above it and NAC starts. Salicylate is 42 mg/dL. pH is 7.28, HCO₃⁻ 12 mEq/L, Na⁺ 138, Cl⁻ 100, glucose 110, BUN 14. That gives an anion gap of 26 (above 12). Winter's formula predicts a PaCO₂ of about 26 mmHg. A measured PaCO₂ near 26 fits appropriate compensation, so measure it before you call a second disorder. Salicylate gets treated and repeated every 2 hr.

Patterns & Differential

Each row below is a prompt to chase, not a diagnosis. Find the pattern first, then find the cause.

PatternKey FindingsCommon CausesNext Step
Anion-gap acidosis with raised osmolar gap
Gap above 12, osmolar gap above 10, visual changes
Methanol, ethylene glycol
Fomepizole on suspicion; toxic-alcohol levels; toxicology consult
Raised osmolar gap without major acidosis
Osmolar gap above 10; anion gap normal or modestly raised
Isopropanol (ketosis); ethanol
Ethanol level; acetone; repeat gaps; toxicology consult
Anion-gap acidosis with normal osmolar gap
Gap above 12, lactate raised or ketones positive
Shock, seizures, ketoacidosis, uremia, some toxins
Lactate, ketones, BUN and creatinine
Mixed respiratory alkalosis and anion-gap acidosis
Tachypnea, high salicylate level
Salicylate toxicity
Repeat salicylate every 2 hr; alkalinize; dialysis per criteria
Acetaminophen level below the line at 4 hr or later
Normal AST/ALT, no symptoms
Adequate time from a single ingestion
Continue monitoring; repeat AST/ALT if symptoms or extended-release
Digoxin toxicity with normal level
Arrhythmia, hypokalemia
Hypokalemia, hypomagnesemia, interacting drugs
Correct K⁺ and Mg²⁺; consider digoxin-immune Fab on clinical grounds
Lithium toxicity at a level near therapeutic
Tremor, confusion, seizures in chronic use
Dehydration, NSAIDs, ACE inhibitors, kidney injury
Serial levels; fluid and drug review; nephrology for dialysis criteria
SpO₂ discordant with PaO₂ or symptoms
Headache, confusion, dyspnea; SpO₂ normal (CO) or fixed near 85% and not rising with oxygen (MetHb)
Carbon monoxide, methemoglobinemia
Co-oximetry (COHb, MetHb)
Negative urine drug screen with toxicity
Opioid toxidrome not explained by screen
Fentanyl, nitazenes, xylazine not on standard screens
Specific-agent testing; toxicology consult

Serial Testing & Kinetics
AnalyteTiming RuleRepeat IntervalMonitoring Target
Acetaminophen
First level at 4 hr or later after a single acute ingestion
Repeat 4–6 hr after the first level when extended-release is possible, or when the level was drawn 4–12 hr after ingestion, is below the line and is above 10 µg/mL
Level against the treatment line; AST/ALT
Salicylate
Level at presentation
Every 2 hr until falling
Falling level, pH, mental status
Digoxin
At least 6 hr after a dose
Repeat if the first is equivocal or symptoms persist
Level with K⁺ and ECG
Lithium
Serial from presentation
Every 2–4 hr after acute ingestion until falling
Level, neurologic status, kidney function
Carboxyhemoglobin
At presentation
After oxygen therapy starts; repeat per response
Falling COHb with clinical improvement
Methemoglobin
At presentation
Repeat if symptoms persist after treatment
Level and SpO₂ discordance
Creatine kinase
At presentation
Serially if the first is elevated
Rising CK, urine myoglobin, creatinine

Critical Findings & Emergency Actions

Acetaminophen above the treatment line

Recognize: APAP at or above 150 µg/mL at 4 hr or later, or unknown-time ingestion with a level that cannot be plotted.

  1. Start NAC without waiting for the result if the ingestion is possibly toxic or the time is unknown (RN, Paramedic transport). If the level cannot be obtained in time to avoid starting treatment more than 8 hr after ingestion, start NAC before the result returns when there is strong concern (dose above 200 mg/kg or 10 g).
  2. Verify dose Acetylcysteine: three-bag IV, 150 mg/kg over 1 hr, then 50 mg/kg over 4 hr, then 100 mg/kg over 16 hr (dosing weight capped at 100 kg). Two-bag regimens exist per local protocol.
  3. Continue until stopping criteria are met, not for a fixed time; monitor AST/ALT, INR and creatinine during therapy. Watch for anaphylactoid reactions (rash, wheeze, hypotension) during IV NAC: pause the infusion and treat per protocol.
  4. Refer to a toxicologist or poison center for high-risk ingestion (30 g or more, or a level above the high-risk line).

Salicylate toxicity

Recognize: salicylate above 30 mg/dL (any level with symptoms in chronic use), tachypnea, altered mental status, mixed acid-base disorder.

  1. Alkalinize with sodium bicarbonate per protocol: 1–2 mEq/kg IV bolus, then infusion (Paramedic, RN). Target urine pH 7.5–8 and serum pH not above 7.55. Replace potassium, since hypokalemia blunts urinary alkalinization. Give dextrose for altered mental status even when serum glucose is normal. Check electrolytes, calcium and glucose during therapy.
  2. Protect the airway with care: avoid intubation and sedation where possible, because both can remove respiratory compensation for the acidosis, lower pH and raise CNS salicylate. If intubation cannot be avoided, give bicarbonate first and set the ventilator to match the patient's pre-intubation minute ventilation. Confirm with a blood gas.
  3. Repeat salicylate every 2 hr until falling.
  4. Hemodialysis per EXTRIP (recommended): salicylate above 100 mg/dL (above 90 with impaired kidney function); altered mental status; acute respiratory distress syndrome requiring supplemental oxygen; or failure of standard therapy at any level. Suggested: salicylate above 90 mg/dL (above 80 mg/dL with impaired kidney function); pH 7.20 or lower without other indications. Confirm with toxicology/nephrology.

Toxic alcohol: methanol or ethylene glycol

Recognize: anion-gap acidosis with a raised osmolar gap, visual changes or urinary crystals.

  1. Verify dose Fomepizole: 15 mg/kg IV over 30 min, started on suspicion (Paramedic, RN).
  2. Maintenance: 10 mg/kg IV every 12 hr for 4 doses, then 15 mg/kg every 12 hr until the level is below 20 mg/dL or undetectable. During hemodialysis, give every 4 hr (fomepizole is dialyzed; label). Ethanol is the alternative antidote where fomepizole is unavailable.
  3. Dialysis per EXTRIP methanol and ethylene glycol recommendations, with a toxicology consult.

Digoxin toxicity with arrhythmia or hyperkalemia

Recognize: life-threatening toxicity: ventricular arrhythmia, progressive bradycardia or AV block not responsive to atropine, or potassium above 5.5 mEq/L in adults (above 6 mEq/L in children) with rapidly progressive signs.

  1. Check K⁺ and Mg²⁺ at once. Correct hypokalemia cautiously.
  2. Verify dose Digoxin-immune Fab: for life-threatening arrhythmia, AV block or bradycardia unresponsive to atropine, potassium above 5.5 mEq/L in adults (above 6 mEq/L in children) with rapidly progressive signs, or hemodynamic instability.
  3. Dose for chronic toxicity with a serum level: vials = (serum digoxin ng/mL × kg) ÷ 100. Without a level: 6 vials (adults and children 20 kg or more) or 1 vial (under 20 kg). Acute unknown amount: 10 vials IV, then 10 more if needed (label maximum 20 vials). Do not use digoxin levels drawn after Fab to guide further dosing; total digoxin rises and free digoxin falls, so dose by clinical response.

Lithium toxicity with neurologic signs

Recognize: lithium above 1.5 mEq/L with confusion, coarse tremor, seizures, or ataxia. Chronic toxicity may appear at lower levels.

  1. Stop lithium and any interacting drug (NSAIDs, ACE inhibitors, thiazides). Activated charcoal does not bind lithium; for sustained-release products, consider whole-bowel irrigation with toxicology.
  2. Replace volume with isotonic saline if depleted, per protocol.
  3. Hemodialysis per EXTRIP: level above 4 mEq/L with impaired kidney function, or decreased consciousness, seizures or life-threatening dysrhythmia. Suggested above 5 mEq/L or with confusion. Confirm with nephrology or toxicology.

Carbon monoxide poisoning

Recognize: headache, confusion, syncope, or cardiac ischemia after fire or enclosed-space exposure. SpO₂ can read normal.

  1. Give 100% oxygen by non-rebreather mask immediately (Paramedic, RN, CCT).
  2. Measure COHb by co-oximetry. Consider a cyanide source in smoke exposure; hydroxocobalamin interferes with co-oximetry, so draw COHb before giving it.
  3. Hyperbaric oxygen: consider after consulting a hyperbaric service for loss of consciousness, neurologic deficit, cardiac ischemia or dysrhythmia, pregnancy, or a high COHb. ACEP (2017) treats HBO as an option rather than a standard; COHb cutoffs vary by source, so confirm against the UHMS chapter and local policy.

Sodium-channel blockade with QRS widening

Recognize: QRS above 100 ms, ventricular arrhythmia or hypotension after tricyclic, class I antiarrhythmic or similar exposure.

  1. Verify dose Sodium bicarbonate: 1–2 mEq/kg IV bolus of 8.4%; repeat for persistent QRS widening (Paramedic, RN). Stop boluses when pH reaches about 7.50–7.55.
  2. Treat hypotension and arrhythmia per ACLS/PALS; avoid class Ia and Ic antiarrhythmics. Lidocaine (class Ib) is second-line after bicarbonate for TCA-related ventricular arrhythmia.
Pitfall: A single normal APAP level before 4 hr is not interpretable. Draw the level at 4 hr or later, and treat empirically when timing is unknown.

Prehospital & Transport Considerations

Point-of-Care Testing

Device or MethodAnalytesLimitations
Blood gas and chemistry cartridges
Electrolytes, glucose, lactate, pH (cartridge-dependent)
No ethanol, salicylate, APAP or digoxin; check cartridge temperature and storage
Glucometer
Glucose
Unreliable with hypoperfusion or hematocrit extremes
Pulse CO-oximetry (SpCO) and SpMet
Screening COHb and MetHb
Screening only; use laboratory co-oximetry for treatment decisions
Urine drug screen (point of care)
Drug classes
Presumptive only; misses fentanyl, nitazenes and xylazine

Interfacility Transfer & Handoff

  • Obtain from the sending facility: each level with the time drawn, time of ingestion, agents, amounts, and any NAC, fomepizole, digoxin-immune Fab or bicarbonate given.
  • Repeat en route: salicylate every 2 hr and lithium every 2–4 hr after acute ingestion, when a repeat is due and the transport allows it.
  • Flight specimens: altitude and temperature can throw off cartridge results. Label each tube with its draw time.

Scope Notes

  • EMS: recognize the toxidrome. For opioid toxidrome, give naloxone and support ventilation. For organophosphate or carbamate exposure, give atropine per protocol. For salicylate, give bicarbonate per protocol, avoid sedation and intubation where you can, and give oxygen and airway support per protocol. Call the poison center early (1-800-222-1222). Get the ingestion history and send it with the patient.
  • Transport (CCT): manage fomepizole and digoxin-immune Fab infusions per local protocol and medical direction.
  • ED/ICU: confirm antidote stock and dialysis access before transfer when a critical threshold is likely.

Special Populations

Pediatrics

  • Acetylcysteine: 150 mg/kg IV in 3 mL/kg over 1 hr for children 5–20 kg (bag 1). Bags 2 and 3 use weight-band diluent volumes from the label table, which differ from adult volumes. Pediatric NAC carries a free-water risk: watch for fluid overload and hyponatremia. Check the calculation with weight-based dosing.
  • Fomepizole: 15 mg/kg IV loading dose over 30 min, the same mg/kg as adults. The label states safety and effectiveness are not established in children.
  • Digoxin-immune Fab: acute unknown amount 10–20 vials IV, not weight-based; watch for volume overload in children under 20 kg. Known amount uses the same body-load formula as adults. Without a serum level for chronic toxicity: 1 vial for children under 20 kg. Potassium threshold: above 6 mEq/L in children with rapidly progressive toxicity (adults: above 5.5 mEq/L), per the DigiFab label.
  • Sodium bicarbonate: 1–2 mEq/kg IV (1–2 mL/kg of 8.4%); 8.4% is hyperosmolar, so neonates and infants receive a 1:1 dilution to 4.2% per protocol.
  • Digoxin level: judge toxicity against the 2.0 ng/mL threshold above, and read the level alongside the ECG and potassium. Don't use post-Fab digoxin levels to guide further dosing.

Pregnancy

  • Carboxyhemoglobin: fetal hemoglobin binds CO more tightly. Bring up hyperbaric oxygen at a lower threshold.
  • Serum hCG: get it before imaging and before any fetal-risk treatment. A positive test changes the plan.

Older Adults

  • Digoxin and lithium: both build up when kidney clearance drops. A normal creatinine can hide a reduced GFR.
  • Salicylate: the picture is often atypical in older adults. Expect confusion, hypoglycemia or pulmonary edema, even at lower levels.

CKD and Dialysis

  • Lithium and salicylate: with impaired kidney function, EXTRIP dialysis thresholds drop. Bring nephrology in early.

Specimen Collection & Interfering Factors
  • Specimen and tube: serum or plasma for APAP, salicylate, digoxin and lithium. Gray-top (fluoride) for ethanol. Tube colors depend on the institution.
  • Lithium: do not draw from a lithium-heparin tube; use serum or a non-lithium-heparin tube.
  • Ethanol: use a non-alcohol skin prep; alcohol swabs can falsely raise the level.
  • Co-oximetry: arterial or venous sample; avoid drawing above an IV line with dextrose or saline running.
  • Handling: get it analyzed promptly. Send lactate on ice when the lab requires it.
Error or InterferentEffect on ResultsPrevention
Lithium-heparin tube
Falsely high lithium
Use serum or non-lithium-heparin tube
Alcohol skin prep
Falsely high ethanol
Use a non-alcohol antiseptic; allow to dry
IV line contamination
Dilution; dextrose or saline artifact
Draw from the opposite arm or stop the infusion and waste
Immunoassay cross-reactivity
False-positive or false-negative drug screen
Confirm with a specific assay
Hemolysis
Falsely high K⁺ and some drug assays
Avoid fist clenching and prolonged tourniquet

Clinical Pearls
Nomogram limits: the revised Rumack-Matthew nomogram only fits a single acute ingestion of known timing, within 24 hr. Repeated supratherapeutic ingestion falls outside it.
Salicylate rises: extended-release products and co-ingestants can keep salicylate climbing for hours. Keep repeating the level until it falls.
Ethanol does not explain everything: tolerance varies, so the ethanol level won't reliably predict mental status. Consider co-ingestants and hypoglycemia.
Field tip: a normal SpO₂ doesn't rule out carbon monoxide. An SpO₂ stuck near 85% that won't climb with oxygen suggests methemoglobinemia. Use co-oximetry or SpCO screening, and treat on clinical suspicion.
Nursing tip: digoxin toxicity tracks potassium shifts. Check K⁺ and Mg²⁺ before and after each dose.
Critical care tip: send lithium as serial levels. A falling level doesn't close the question when neurologic signs are present, and dialysis still needs review.
Pitfall: a negative urine drug screen can't rule out fentanyl, nitazenes or xylazine. When the opioid toxidrome isn't explained, test for the specific agent.
Pitfall: the osmolar gap shrinks as methanol and ethylene glycol get metabolized. A normal gap late in presentation doesn't rule out toxic alcohol poisoning.

Related

References
  1. Dart RC, Mullins ME, Matoushek T, et al. Management of acetaminophen poisoning in the US and Canada: a consensus statement. JAMA Netw Open. 2023;6(8):e2327739. https://doi.org/10.1001/jamanetworkopen.2023.27739
  2. Juurlink DN, et al. Extracorporeal treatment for salicylate poisoning: EXTRIP recommendations . Ann Emerg Med. 2015. https://doi.org/10.1016/j.annemergmed.2015.03.031
  3. Decker BS, et al. Extracorporeal treatment for lithium poisoning: EXTRIP recommendations . Clin J Am Soc Nephrol. 2015. https://doi.org/10.2215/CJN.10021014
  4. Weaver LK. Carbon monoxide poisoning. Undersea Hyperb Med. 2024;51(3):253–276. https://www.uhms.org/uhm-search/uhm-journal-volume-51-2024/number-3/indications-chapter.html
  5. Fomepizole injection (Mylan Institutional), US prescribing information. DailyMed; current label, accessed 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=911312e2-3a7c-4c97-88a8-b8d92cd12923
  6. DigiFab (digoxin immune fab) US prescribing information. DailyMed; current label, accessed 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c05ee6a5-c98b-45f4-83fd-40781639d653
  7. American Heart Association. 2025 American Heart Association Guidelines for CPR and ECC, Part 10: Special Circumstances of Resuscitation. Circulation. 2025. https://doi.org/10.1161/CIR.0000000000001380
  8. American College of Medical Toxicology. Interpretation of urine opiate and opioid tests: position statement. 2021. https://www.acmt.net/wp-content/uploads/2022/06/PRS_210913_Interpretation-of-Urine-Opiate-and-Opioid-Tests.pdf

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