Toxicology Antidotes

Toxidrome DDx — recognition guide

Patient weight (kg)

≈ 154.3 lb

Acetaminophen

N-Acetylcysteine (NAC)(Acetadote)

APAP toxicity above tx line, or unknown ingestion

First-line

Dose

Adult

Enter weight

150 mg/kg → 50 → 100 mg/kg

🧪 Initial labs / studies

4-hour post-ingestion serum acetaminophen level (plot on Rumack-Matthew)
AST, ALT, total bilirubin, INR/PT
BMP (HCO3, anion gap), glucose, lactate, lipase
Salicylate level + UDS (rule out co-ingestion)
βhCG in women of childbearing age
ABG/VBG if AMS or shock

⏱ ED observation

Min 24 h on NAC; ≥21 h infusion. Extend if AST/ALT rising or APAP still detectable.

👁 Symptoms to watch

Stage 1 (0–24 h): N/V, malaise, often asymptomatic
Stage 2 (24–72 h): RUQ pain, ↑ AST/ALT, ↑ INR
Stage 3 (72–96 h): fulminant hepatic failure, AMS, hypoglycemia, lactic acidosis
Stage 4 (>96 h): recovery or death — transplant criteria (King's College)

Route: IV (21-h) or PO (72-h)

Onset: Hepatoprotective if started <8 h

Anaphylactoid rxn common in load — slow infusion, give diphenhydramine, do NOT stop NAC.
Continue beyond 21 h if AST/ALT still rising or APAP detectable.

Opioid / Sedative

Naloxone(Narcan)

Opioid-induced respiratory depression

First-line

Dose

Adult

0.04–0.4 mg IV; titrate to RR/airway

Peds: 0.1 mg/kg (max 2 mg)

🧪 Initial labs / studies

Fingerstick glucose, BMP, ABG/VBG
EtOH, salicylate, acetaminophen levels (co-ingestion)
ECG (QT prolongation w/ methadone, propoxyphene)
CXR (aspiration, opioid-induced pulmonary edema)
CK if down-time prolonged (rhabdo)
UDS (confirmatory, not for triage)

⏱ ED observation

Short-acting opioid: ≥4–6 h after last naloxone dose. Long-acting (methadone, ER, fentanyl analogs): ≥12–24 h or admit.

👁 Symptoms to watch

Triad: ↓RR/apnea, pinpoint pupils, ↓LOC
Hypoxia, cyanosis, hypotension, bradycardia
Non-cardiogenic pulmonary edema (esp. after reversal)
Re-sedation as naloxone wears off
Withdrawal post-naloxone: agitation, vomiting, diarrhea, lacrimation

Route: IV / IM / IN

Onset: 1–2 min IV

Start LOW (0.04 mg) in chronic users to avoid withdrawal/agitation.
Re-dose q2–3 min; consider drip 2/3 of waking dose/hr if long-acting opioid.

Benzodiazepine

Supportive Care (Benzodiazepine OD)

Pure benzodiazepine overdose — mainstay is airway/breathing support, NOT routine flumazenil

First-line

Dose

Adult

ABCs · supplemental O2 · IV access · cardiac monitor

NPO, aspiration precautions, frequent neuro/RR checks. Bolus NS 500–1000 mL for hypotension.

🧪 Initial labs / studies

Fingerstick glucose, BMP, ABG/VBG, lactate
Acetaminophen + salicylate levels, EtOH, UDS
ECG (rule out TCA / Na-channel co-ingestion → wide QRS, terminal R in aVR)
CXR (aspiration pneumonitis), CK (rhabdo if down-time)
βhCG in women of childbearing age
Specific benzo levels NOT clinically useful — UDS misses clonazepam, lorazepam, midazolam, alprazolam

⏱ ED observation

Asymptomatic + normal vitals: 4–6 h. Symptomatic: until clinically sober (usually 6–12 h). Long-acting (diazepam, clonazepam) or sustained-release: ≥12–24 h.

👁 Symptoms to watch

CNS depression: drowsiness, slurred speech, ataxia, nystagmus, coma
Respiratory: hypoventilation, hypoxia (worse with opioid/EtOH co-ingestion)
Cardiovascular: mild hypotension, bradycardia (usually well-tolerated)
Paradoxical agitation (esp. peds, elderly, midazolam)
Red flags suggesting co-ingestion: wide QRS, seizures, anticholinergic toxidrome, severe hypotension

Route: Airway, O2, IV fluids, monitoring

Onset: Immediate

Most pure benzo ODs do well with airway support alone — coma rarely needs intubation if RR adequate.
Co-ingestion (EtOH, opioids, TCA) is the rule — assume mixed OD until proven otherwise.
Activated charcoal 1 g/kg PO if <1 h, intact airway, cooperative patient (rarely indicated).
Hemodialysis NOT effective (high protein binding, large Vd).

Flumazenil(Romazicon)⚠ High-risk

Iatrogenic / procedural benzo over-sedation in a benzo-naive patient. AVOID in chronic users, unknown OD, or suspected co-ingestion.

Rescue

⛔ Contraindications

• Chronic benzodiazepine use / dependence
• Suspected TCA, bupropion, or other proconvulsant co-ingestion
• Benzos given for status epilepticus or ↑ICP control
• Unknown / undifferentiated overdose
• Seizure disorder on benzo therapy

Dose

Adult

🧪 Initial labs / studies

Fingerstick glucose, BMP, ABG/VBG
Acetaminophen + salicylate levels, EtOH
ECG (rule out TCA / Na-channel co-ingestion → wide QRS) BEFORE giving flumazenil
UDS (often misses clonazepam, lorazepam, midazolam, alprazolam)
CK if prolonged down-time, βhCG

⏱ ED observation

Iatrogenic over-sedation: ≥2 h post-flumazenil. Pure benzo OD without reversal: 4–6 h after return to baseline. Long-acting benzo: ≥12 h (re-sedation risk).

👁 Symptoms to watch

Sedation, ataxia, dysarthria, respiratory depression (usually mild in pure OD)
Post-flumazenil adverse effects: seizures, agitation, arrhythmias if co-ingestion
Withdrawal in chronic users: tremor, anxiety, autonomic instability, seizures
Watch for re-sedation (flumazenil t½ ≈ 1 h, shorter than most benzos)

Route: IV

Onset: 1–2 min (peak 6–10 min)

Seizure risk if TCA / bupropion / chronic benzo use — can be REFRACTORY (no benzos to abort).
Routine use in undifferentiated OD is NOT recommended (AAEM, ACMT, ToxIC consensus).
Best candidates: iatrogenic procedural sedation, pediatric accidental ingestion of single benzo, reversal of conscious sedation.
If seizure occurs post-flumazenil: barbiturates or propofol (benzos won't work — receptor blocked).

Cardiac (Na-channel / TCA)

Sodium Bicarbonate

Wide QRS (>100 ms) from TCA/Na-channel blocker; salicylate alkalinization

First-line

Dose

Adult

1–2 mEq/kg IV bolus

Then 150 mEq in 1 L D5W @ 150–250 mL/hr

🧪 Initial labs / studies

ECG STAT (QRS width, terminal R in aVR, QTc)
BMP (Na, K, HCO3, anion gap), ABG/VBG (pH)
Ionized Ca, Mg, phos
Acetaminophen, salicylate, EtOH, UDS
TCA level only if specific (not actionable acutely)
Lactate, CK, troponin

⏱ ED observation

TCA: ≥6 h asymptomatic with normal ECG & normal mental status. Symptomatic: ICU 24 h after QRS normalizes & off bicarb drip.

👁 Symptoms to watch

Wide QRS >100 ms, RBBB-like terminal R in aVR, ventricular dysrhythmias
Hypotension, AMS, seizures, anticholinergic toxidrome (TCA)
Salicylate: tinnitus, tachypnea, mixed acid-base, hyperthermia, AMS
Watch for hypokalemia, hypocalcemia, alkalosis from therapy

Route: IV bolus + drip

Onset: Minutes

Re-bolus until QRS narrows; monitor K+ (will drop), ionized Ca, pH.
Salicylate goal urine pH ≥7.5; do NOT intubate without aggressive bicarb plan.

β-blocker / CCB

High-dose Insulin Euglycemia (HIE)⚠ High-risk

Refractory shock from β-blocker or CCB toxicity

First-line

Dose

Adult

🧪 Initial labs / studies

ECG continuous (HR, blocks, QRS, QTc)
BMP, glucose q15–30 min, K+ q1h, Mg, phos
Lactate, ABG/VBG
Echo (bedside) — LV function
Drug level if available (digoxin co-ingestion, etc.)
Acetaminophen, salicylate, EtOH screen

⏱ ED observation

Sustained-release CCB/BB: ≥24 h on monitor even if asymptomatic. Symptomatic: ICU with HIE drip + frequent glucose/K checks.

👁 Symptoms to watch

Bradycardia, AV blocks, hypotension, cardiogenic shock
CCB: hyperglycemia; BB: hypoglycemia (esp. propranolol, peds)
AMS, seizures (propranolol — Na-channel effect), bronchospasm
Watch for hypoglycemia & hypokalemia during HIE therapy

Route: IV

Onset: 15–60 min

Co-infuse D10 or D25; monitor glucose q15–30 min, K+ q1h.
Add Ca-gluconate, glucagon, IV lipid as adjuncts. Pressors (norepi/epi) for MAP.

Calcium gluconate / chloride

CCB toxicity, hyperkalemia, Mg toxicity, hydrofluoric acid

First-line

⛔ Contraindications

• Digoxin toxicity (controversial — may worsen) unless using DigiFab concurrently

Dose

Adult

Ca-gluconate 1–3 g IV (60 mg/kg) over 10 min

Or CaCl 1 g IV via central line. Repeat q10–20 min.

🧪 Initial labs / studies

ECG (peaked T, wide QRS, blocks)
BMP, ionized Ca, Mg, phos
Digoxin level if dig possible
ABG/VBG, lactate
CK, UA (rhabdo, HF exposure)

⏱ ED observation

Per underlying toxin (CCB ≥24 h SR; hyperK until K<5.5 & ECG normal; HF exposure ≥24 h for delayed hypoCa/hypoMg).

👁 Symptoms to watch

CCB: brady, AV block, hypotension, hyperglycemia
HyperK: peaked T → wide QRS → sine wave → asystole
Hydrofluoric acid: pain out of proportion, hypoCa/hypoMg, hyperK, arrhythmias
Watch for hypercalcemia, tissue necrosis from extravasation

Route: IV

Onset: Minutes

CaCl 3× more elemental Ca than gluconate; central line preferred (extravasation = necrosis).

Glucagon

β-blocker toxicity (also CCB adjunct)

Adjunct

Dose

Adult

3–10 mg IV bolus over 3–5 min

Then 1–5 mg/hr infusion; antiemetic prophylaxis (frequent vomiting).

🧪 Initial labs / studies

ECG (brady, AV block, QRS)
BMP, glucose, Mg
Lactate, ABG/VBG
Acetaminophen, salicylate, UDS

⏱ ED observation

Immediate-release BB: ≥6 h. Sustained-release or sotalol: ≥24 h on monitor.

👁 Symptoms to watch

Bradycardia, hypotension, AV block
Hypoglycemia (esp. propranolol, peds)
AMS, seizures (propranolol — Na-channel/lipophilic)
Bronchospasm; sotalol → QT prolongation, torsades
Vomiting from glucagon — protect airway

Route: IV

Onset: 5–10 min

Often vomits — protect airway. Limited supply at most hospitals.

Toxic alcohol

Fomepizole(Antizol)

Methanol or ethylene glycol ingestion (level >20 or anion-gap acidosis)

First-line

Dose

Adult

15 mg/kg IV load → 10 mg/kg q12h × 4

Then 15 mg/kg q12h

🧪 Initial labs / studies

Methanol & ethylene glycol levels (send-out — do NOT wait)
BMP (anion gap), ABG/VBG, lactate
Serum osmolality + calculated osm gap
EtOH, acetaminophen, salicylate
UA (calcium oxalate crystals — EG), urine fluorescence (antifreeze)
Lipase, CK; visual acuity & fundoscopy (methanol)

⏱ ED observation

Admit ICU. Continue fomepizole + HD until level <20 mg/dL, AG closed, asymptomatic.

👁 Symptoms to watch

Early: inebriation w/o EtOH smell, N/V, abd pain
Methanol: blurred/snowfield vision, blindness, putaminal hemorrhage, AGMA
Ethylene glycol: AKI/oliguria, hypoCa, tetany, CN palsies, AGMA
Late: coma, seizures, cardiovascular collapse

Route: IV

Onset: Blocks ADH within minutes

Double dosing during HD (or give q4h).
Folinic acid for methanol; pyridoxine + thiamine for ethylene glycol.

CO / Cyanide

Hydroxocobalamin(Cyanokit)

Suspected cyanide (smoke inhalation + AMS + lactate >8)

First-line

Dose

Adult

5 g IV over 15 min (70 mg/kg, max 5 g)

May repeat 5 g for severe toxicity.

🧪 Initial labs / studies

Lactate (>8 suggests CN in smoke inhalation)
ABG/VBG with co-oximetry (COHb, MetHb)
BMP, troponin, ECG
CXR, fiberoptic airway eval if smoke
Cyanide level (send-out, do NOT wait)

⏱ ED observation

ICU ≥24 h. Repeat lactate, ABG; monitor for delayed neuro sequelae.

👁 Symptoms to watch

AMS, seizures, coma; cherry-red skin (late, unreliable)
Tachypnea → bradypnea/apnea, hypotension, arrhythmias
Severe lactic acidosis (>10) with normal SpO2
Smoke inhalation: stridor, soot, singed nares — secure airway early

Route: IV

Onset: Minutes

Turns urine/skin/serum red — interferes w/ co-oximetry & some labs.
Avoid mixing in same line w/ NaHCO3.

Methemoglobinemia

Methylene Blue⚠ High-risk

Symptomatic methemoglobinemia (MetHb >25%, or >15% with sx/comorbidities)

First-line

⛔ Contraindications

• Known G6PD deficiency (hemolysis risk)
• Concurrent serotonergic agents (SSRIs/SNRIs/MAOIs) — serotonin syndrome

Dose

Adult

🧪 Initial labs / studies

Co-oximetry: MetHb % (pulse ox unreliable, ~85%)
CBC (hemolysis), haptoglobin, LDH, retic, smear
G6PD level (do not delay tx if life-threat)
BMP, ABG, lactate
Chocolate-brown blood on draw is classic

⏱ ED observation

≥6 h after MetHb <10% and asymptomatic. Sustained-release agent (dapsone): admit 24+ h, may need repeat dosing.

👁 Symptoms to watch

Cyanosis unresponsive to O2, SpO2 plateau ~85%
HA, dizziness, fatigue (MetHb 20–30%)
Dyspnea, tachycardia, AMS (30–50%); coma, seizures, death (>50%)
Watch for hemolysis (esp. G6PD); rebound MetHb with dapsone

Route: IV

Onset: 30–60 min

Contraindicated in G6PD deficiency (causes hemolysis) — use ascorbic acid + exchange transfusion.
Will falsely lower SpO2 transiently.

Anticholinergic / Cholinergic

Atropine + Pralidoxime (2-PAM)

Organophosphate / carbamate poisoning (SLUDGE, bronchorrhea)

First-line

Dose

Adult

Atropine 1–6 mg IV, DOUBLE q5 min until secretions dry

2-PAM 1–2 g IV over 30 min, then 8 mg/kg/hr infusion

🧪 Initial labs / studies

RBC & plasma cholinesterase (confirmatory, send-out)
BMP, glucose, lipase, troponin
ABG, lactate; ECG (QT, AV blocks)
CXR (pulmonary edema, aspiration)
CK, UA (rhabdo)

⏱ ED observation

Min 12 h asymptomatic off atropine. Severe / fat-soluble agent (parathion, fenthion): admit ICU days — relapse common.

👁 Symptoms to watch

SLUDGE: Salivation, Lacrimation, Urination, Defecation, GI, Emesis
Killer Bs: Bronchorrhea, Bronchospasm, Bradycardia
Miosis, fasciculations, weakness, seizures, coma
Intermediate syndrome 24–96 h: proximal weakness, respiratory failure

Route: IV

Onset: Minutes

Endpoint = drying of pulmonary secretions, NOT pupils or HR.
Decontaminate (remove clothing, copious irrigation) — staff PPE.

Physostigmine⚠ High-risk

PURE anticholinergic toxidrome with severe agitation/delirium (NOT TCA)

Rescue

⛔ Contraindications

• Wide QRS / TCA or Na-channel blocker poisoning
• AV block, bradycardia
• Reactive airways / asthma
• Mechanical bowel obstruction

Dose

Adult

🧪 Initial labs / studies

ECG (rule out wide QRS → TCA — contraindication)
BMP, glucose, CK (rhabdo from hyperthermia)
Acetaminophen, salicylate, UDS
Bladder scan (urinary retention)
Lactate, ABG if severe

⏱ ED observation

≥6 h after resolution of delirium. Diphenhydramine / sustained-release: ≥12–24 h (long t½).

👁 Symptoms to watch

“Hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter”
Hyperthermia, mydriasis, dry skin/mucosa, flushing, urinary retention
Agitated delirium, picking, mumbling, seizures
Tachycardia; wide QRS suggests Na-channel toxicity — STOP, do NOT give physostigmine

Route: IV slow push

Onset: 5 min

AVOID with wide QRS, TCA, asthma, AV block, mechanical bowel obstruction.
Risk: bradyasystole, seizures, cholinergic crisis.

Local anesthetic (LAST)

Intralipid 20% (Lipid Emulsion)

LAST (bupivacaine arrest), refractory cardiotox from lipophilic drugs

First-line

Dose

Adult

1.5 mL/kg bolus → 0.25 mL/kg/min

Repeat bolus ×2 PRN; ↑ infusion 0.5 mL/kg/min if hypotensive

🧪 Initial labs / studies

ECG continuous, troponin
BMP, lactate, ABG
CK, lipase (pancreatitis risk from lipid)
Lipid panel (interferes with subsequent labs ~12 h)
Drug level if available (bupivacaine, propranolol, etc.)

⏱ ED observation

Post-LAST arrest: ICU 24–48 h. Lipid interferes with chem labs for ~12 h — alert lab.

👁 Symptoms to watch

LAST early: perioral numbness, tinnitus, metallic taste, agitation
Progression: seizures → coma → wide QRS → VT/VF → asystole
Hypotension, bradycardia refractory to standard ACLS
Watch for re-sedation/relapse as drug redistributes

Route: IV

Onset: Seconds–minutes

Use REDUCED-dose epi (≤1 mcg/kg) in LAST; avoid vasopressin, CCBs, β-blockers.
Continue infusion ≥10 min after hemodynamic stability.

Sulfonylurea / Insulin

Octreotide

Sulfonylurea-induced refractory hypoglycemia

First-line

Dose

Adult

50–100 mcg SQ q6h (1–2 mcg/kg)

Continue 24 h after last hypoglycemic episode + glucose stable on D5.

🧪 Initial labs / studies

Fingerstick glucose q1h (q15–30 min during hypoglycemia)
BMP, Mg, phos
Sulfonylurea level (send-out, confirmatory)
Insulin & C-peptide (rule out exogenous insulin)
Acetaminophen, salicylate, UDS

⏱ ED observation

Admit ALL sulfonylurea OD ≥24 h. Pediatric ingestion: admit even if single tab. Continue octreotide 24 h after last hypoglycemic episode off dextrose.

👁 Symptoms to watch

Hypoglycemia: diaphoresis, tremor, palpitations, AMS, seizures, coma
Onset may be delayed 8–24 h (esp. glipizide, glyburide)
Recurrent hypoglycemia despite D50 boluses — hallmark
Watch for QT prolongation, mild hyperglycemia rebound with octreotide

Route: SQ or IV

Onset: 30 min

Admit ALL sulfonylurea overdoses (pediatric: even 1 tab can kill).

Digoxin

Digoxin Immune Fab(DigiFab)

Dig toxicity w/ life-threatening arrhythmia, K+ >5, level >10 ng/mL, or known massive ingestion

First-line

Dose

Adult

Acute: 10–20 vials empiric IV over 30 min

Chronic: 3–6 vials. Calc: vials = (level × wt kg) / 100, or mg ingested × 0.8 / 0.5

🧪 Initial labs / studies

Digoxin level (pre-Fab; uninterpretable for ~1 week after)
BMP — K+ critical (>5 = severe)
Mg, ionized Ca, BUN/Cr
ECG (any arrhythmia — brady, AV block, VT, bidirectional VT)
TSH if chronic

⏱ ED observation

ICU ≥24 h post-Fab. Renal failure: longer (rebound toxicity). Re-dose Fab for recurrent arrhythmia/hyperK.

👁 Symptoms to watch

Acute: N/V, AMS, hyperK, brady or any arrhythmia (esp. bidirectional VT)
Chronic: vague — anorexia, fatigue, visual changes (yellow/green halos), confusion
Watch post-Fab: hypokalemia, worsening CHF, AFib RVR (rate control returns)

Route: IV

Onset: 20–30 min

Post-Fab digoxin levels are uninterpretable for ~1 week.
Watch for hypokalemia and worsening CHF after binding.

Iron / Heavy metal

Deferoxamine

Iron level >500 mcg/dL, AGMA, shock, or symptomatic ingestion

First-line

Dose

Adult

15 mg/kg/hr IV continuous

Max 6 g/day. Stop when AGMA resolves & urine clears (vin-rosé color).

🧪 Initial labs / studies

Serum iron level at 4–6 h post-ingestion (peak)
BMP (AGMA), ABG, lactate, glucose
AST/ALT, INR, lipase
CBC, type & screen (GI bleed)
Abdominal X-ray (radiopaque tablets)
βhCG (prenatal vitamins common source)

⏱ ED observation

Asymptomatic w/ <20 mg/kg ingested & normal AXR: 6 h. Symptomatic or level >500: ICU ≥24 h, often longer through stage 4–5.

👁 Symptoms to watch

Stage 1 (0–6 h): N/V, hematemesis, diarrhea, abd pain
Stage 2 (6–24 h): apparent recovery — DO NOT discharge
Stage 3 (12–48 h): shock, AGMA, hepatic failure, AKI, coagulopathy
Stage 4 (2–5 d): hepatic necrosis; Stage 5 (4–6 wk): pyloric/bowel stricture

Route: IV

Onset: Hours

Hypotension if infused too fast. ARDS risk with infusion >24 h.

INH / Hydrazine

Pyridoxine (B6)

INH overdose with seizures (or hydrazine, gyromitra mushroom)

First-line

Dose

Adult

1 g pyridoxine per 1 g INH ingested

If unknown: 5 g IV over 5 min; repeat for ongoing seizures (max 70 mg/kg)

🧪 Initial labs / studies

Fingerstick glucose, BMP (AGMA), ABG, lactate
AST/ALT, INR, ammonia
CK (rhabdo from seizures)
Acetaminophen, salicylate, EtOH, UDS
EEG if persistent AMS

⏱ ED observation

INH OD: admit ≥24 h after seizure control. Massive ingestion / hepatotoxicity: longer.

👁 Symptoms to watch

Triad: refractory seizures, AGMA (lactate), coma
N/V, slurred speech, ataxia early; seizures within 30–120 min
Hepatotoxicity (delayed days); hyperthermia, rhabdo from seizures
Benzos alone often fail — pyridoxine is definitive

Route: IV

Onset: Minutes

Benzos are second-line for INH seizures — give B6 first.

Anticoagulant

Vitamin K1 (phytonadione)

Warfarin / superwarfarin (rodenticide) coagulopathy

First-line

Dose

Adult

10 mg IV over 30 min (major bleed) or 1–5 mg PO

Superwarfarin: high-dose 50–100 mg PO daily for weeks–months.

🧪 Initial labs / studies

PT/INR (baseline + serial q6–12 h × 48 h for superwarfarin)
CBC, type & screen, fibrinogen
BMP, LFTs
UA (hematuria), stool guaiac
CT head if any AMS or trauma

⏱ ED observation

Single warfarin OD: PT/INR at 24 & 48 h. Superwarfarin (brodifacoum): admit / close f/u, recheck INR for weeks–months (t½ wks).

👁 Symptoms to watch

Often asymptomatic initially — coagulopathy delayed 24–48 h
Bleeding: epistaxis, gum/GI bleeding, hematuria, bruising
Severe: intracranial hemorrhage, retroperitoneal bleed, hemorrhagic shock
Superwarfarin: prolonged coagulopathy lasting weeks to months

Route: IV (slow) / PO

Onset: 6–12 h (IV); 24 h (PO)

Anaphylactoid risk with IV — slow infusion, dilute. Co-administer 4F-PCC for bleeding.

Protamine sulfate⚠ High-risk

Heparin reversal; partial LMWH reversal

First-line

⛔ Contraindications

• Known fish hypersensitivity (severe)
• Prior anaphylaxis to protamine

Dose

Adult

🧪 Initial labs / studies

aPTT (heparin), anti-Xa (LMWH), ACT if periop
CBC, platelets (HIT), fibrinogen
BMP, type & screen
ECG, troponin if hemodynamic instability

⏱ ED observation

Per bleeding source & anticoagulant t½. UFH: ~4–6 h post-reversal. LMWH: 12–24 h (partial reversal).

👁 Symptoms to watch

Bleeding from any site; hypotension, tachycardia
Protamine reaction: flushing, hypotension, bradycardia, bronchospasm, anaphylaxis
Higher risk: prior protamine exposure, NPH insulin users, fish allergy, post-vasectomy

Route: IV slow

Onset: 5 min

Hypotension, brady, anaphylaxis (esp. fish allergy, NPH insulin, vasectomy). Push slowly.

Methotrexate

(Wellcovorin)⚠ High-risk

Leucovorin rescue for MTX toxicity: (1) HD-MTX (≥500 mg/m²) — start 24–42 h post-infusion per protocol; (2) Acute accidental / intentional MTX overdose; (3) Delayed MTX clearance — MTX >5 µmol/L at 24 h, or >0.9 µmol/L at 42 h, or >0.2 µmol/L at 48 h; (4) AKI or rising Cr on MTX; (5) Severe mucositis / cytopenias while on MTX; (6) Accidental intrathecal MTX overdose.

First-line

⛔ Contraindications

• Pernicious anemia / B12-deficient megaloblastic anemia (masks deficiency without treating it)

Dose

Adult

🧪 Initial labs / studies

Serum methotrexate level (STAT, then q24h until <0.05 µmol/L)
BMP / CMP — creatinine, BUN (AKI is hallmark), LFTs, albumin
CBC w/ diff + platelets (nadir day 7–10: pancytopenia, mucositis)
Urine pH (goal ≥7.0–7.5), urinalysis
ABG/VBG, lactate, LDH
DIC panel if septic / bleeding (PT/INR, aPTT, fibrinogen, D-dimer)
Type & screen; blood cultures if febrile neutropenia
βhCG (MTX is teratogenic / abortifacient)
If intrathecal exposure: CSF MTX level, CSF cell count/protein

⏱ ED observation

Admit all symptomatic / HD-MTX / supratherapeutic level. Monitor q24h MTX level, daily CBC + BMP × ≥10 days (nadir 7–10 d). Discharge only when MTX <0.05 µmol/L, AKI resolving, ANC recovering, mucositis healing.

👁 Symptoms to watch

Early (hours–days): N/V, mucositis, stomatitis, diarrhea, AKI (oliguria, ↑Cr), transaminitis
Day 4–10: pancytopenia (neutropenia → febrile neutropenia, thrombocytopenia, anemia), severe mucositis, GI bleeding
Pulmonary: MTX pneumonitis (cough, dyspnea, hypoxia, bilateral infiltrates) — can occur at any dose
CNS (esp. intrathecal / HD-MTX): seizures, encephalopathy, stroke-like syndrome, leukoencephalopathy
Dermatologic: photosensitivity, rash, radiation recall, rarely SJS/TEN
Chronic / accidental daily dosing (gout/RA confusion with weekly regimen): insidious pancytopenia + mucositis 1–6 wk in

Route: IV preferred in acute toxicity • PO acceptable when Poison Control orders it AND patient tolerates PO, no significant N/V or mucositis, MTX level <1 µmol/L, no AKI, and dose ≤25 mg (PO absorption saturates >25 mg — give IV if higher) • IM rarely used

Onset: Minutes (IV)

Give leucovorin EARLY — efficacy drops sharply if delayed >24–42 h after MTX.
Dose must be ≥ molar MTX concentration. Never substitute folic acid (does not bypass DHFR block).
Add IV hydration 2.5–3 L/m²/day + urinary alkalinization (NaHCO3 drip) to keep urine pH ≥7.0–7.5 → MTX is 10× more soluble.
AVOID nephrotoxins (NSAIDs, contrast, aminoglycosides), TMP-SMX, PPIs, salicylates, probenecid — all ↑ MTX levels.
Glucarpidase (Voraxaze) 50 U/kg IV ×1 for refractory toxicity: MTX >1 µmol/L at 42 h + AKI, or life-threatening level. Hydrolyzes MTX in <15 min; leucovorin must continue (avoid leucovorin within 2 h of glucarpidase).
Hemodialysis: limited benefit (high protein binding, rebound) — high-flux HD only as adjunct in severe AKI; not a substitute for glucarpidase.
Intrathecal MTX overdose: STAT CSF drainage, intrathecal carboxypeptidase G2, dexamethasone, systemic leucovorin — do NOT give intrathecal leucovorin.

📋 Leucovorin dosing by MTX level & timepoint

Time	MTX Level	Leucovorin Dose	Pearl
24 h	< 5 µmol/L	15 mg/m² PO/IM/IV q6h	Standard rescue
24 h	5–10 µmol/L	15 mg/m² IV q6h	Escalate if rising
24 h	> 10–50 µmol/L	100 mg/m² IV q6h	Monitor MTX q24h
24 h	> 50–100 µmol/L	200 mg/m² IV q6h	Aggressive hydration + alkalinization
24 h	> 100 µmol/L	1000 mg/m² IV q6h	Consider glucarpidase early
48 h	< 1 µmol/L	Continue 15 mg/m²	Taper toward discharge
48 h	1–5 µmol/L	100 mg/m² IV q6h	Escalate monitoring
48 h	> 5 µmol/L	200–1000 mg/m² IV q6h	Glucarpidase if AKI / life-threatening
72 h	> 0.2 µmol/L	Continue until <0.05	Do not stop until target reached

Route: IV preferred in toxicity (faster, bypasses GI mucositis, no absorption ceiling).

PO indicated when: Poison Control specifically orders PO • patient tolerates PO (no vomiting/mucositis) • MTX level <1 µmol/L • no AKI • single dose ≤25 mg (PO bioavailability saturates above 25 mg — split larger doses or switch to IV).

Duration: Continue until serum MTX <0.05 µmol/L (or <0.1 if no end-organ injury).

Toxin	Antidote	Adult Dose
Acetaminophen Dx: 4-h serum APAP level + AST/ALT, INR		150 mg/kg load → 50 → 100
Opioids Dx: Clinical (RR, miosis, response to naloxone) ± UDS		0.04–0.4 mg IV q2–3 min (max 10 mg)
Benzodiazepines Dx: Clinical; UDS often false-negative for clonaz/lorazepam		0.2 mg IV over 15 s, repeat to 1 mg
β-blocker / CCB Dx: ECG (brady/AVB), glucose (CCB→hyper, BB→hypo), lactate	/ /	Glucagon 5–10 mg; Ca-gluc 1–3 g; HIE 1 U/kg
TCA (wide QRS) Dx: ECG: QRS >100 ms, terminal R in aVR >3 mm		1–2 mEq/kg IV bolus
Iron Dx: Serum iron 4–6 h post-ingestion + AXR (radiopaque tabs)		15 mg/kg/h IV
Methemoglobin Dx: Co-oximetry MetHb % (SpO₂ ~85%, chocolate-brown blood)		1–2 mg/kg IV
Cyanide Dx: Lactate >8 + AGMA + smoke/exposure hx; whole-blood CN level		5 g IV over 15 min
Organophosphate Dx: Plasma/RBC cholinesterase activity; clinical SLUDGE	+	Atropine 1–3 mg IV, double q3–5 min
Sulfonylurea Dx: Serial POC glucose; C-peptide ↑ (vs exogenous insulin ↓)		50 mcg SQ q6h
Salicylate (ASA) Dx: Serial salicylate q2h, ABG (mixed resp alk + AGMA)	+	Alkalinize urine pH >7.5; HD if >100 mg/dL
Digoxin Dx: Serum digoxin level + K⁺ + ECG (any dysrhythmia)		Acute: 10–20 vials; chronic: 3–6 vials
Methanol / Ethylene glycol Dx: Osm gap + AGMA; serum MeOH/EG level; urine Ca-oxalate		15 mg/kg IV load → 10 mg/kg q12h ×4
Warfarin / superwarfarin Dx: INR/PT (peak 24–48 h); repeat at 48 h if normal early	+	10 mg IV K1; PCC 25–50 U/kg if major bleed
Heparin Dx: aPTT (UFH) or anti-Xa (LMWH)		1 mg per 100 U heparin (max 50 mg)
Isoniazid (INH) Dx: Clinical (refractory seizures + AGMA); INH level rarely available		1 g per g INH (empiric 5 g IV)
Carbon monoxide Dx: Co-oximetry COHb % (pulse ox unreliable)	100% O₂ ± HBO	NRB until COHb <5%; HBO if AMS / COHb >25%
Local anesthetic (LAST) Dx: Clinical (CV collapse/seizure during regional block)		1.5 mL/kg bolus → 0.25 mL/kg/min
Anticholinergic Dx: Clinical toxidrome (hot/dry/red/mad); ECG for QRS		1–2 mg IV slow (pure anticholinergic only)
Lead / arsenic / mercury Dx: Whole-blood lead; 24-h urine As/Hg; CBC (basophilic stippling)	DMSA / BAL / EDTA	Chelation per heavy-metal protocol

Substance	Key Concern	ER Action
Acetaminophen (Tylenol) Dx: 4-h serum APAP + AST/ALT + INR ()	Hepatotoxicity (>150 mg/kg or >7.5 g)	4-h level → Rumack-Matthew nomogram → NAC
Ibuprofen / NSAIDs Dx: BMP, ABG (AGMA), CBC; ibuprofen level rarely useful	GI bleed, AKI, AG acidosis at >400 mg/kg	Supportive; activated charcoal if <1 h
Aspirin / salicylates Dx: Serial salicylate q2h, ABG, BMP (mixed acid-base)	Tachypnea, tinnitus, mixed acid-base	Serial salicylate, K+ repletion, alkalinize, HD
Diphenhydramine (Benadryl) Dx: ECG (QRS, QT); clinical anticholinergic toxidrome	Anticholinergic, wide QRS, seizures	NaHCO₃ if QRS >100; benzos for seizures
Dextromethorphan (DXM) Dx: Clinical; check APAP level (combo products)	Serotonin syndrome, dissociation	Benzos, cooling, supportive
Pseudoephedrine / decongestants Dx: ECG, troponin if chest pain; clinical	HTN, tachy, MI, stroke	Benzos, BP control (avoid pure β-block)
Loperamide (Imodium) abuse Dx: ECG (QRS, QTc); Mg, K+	QT/QRS prolongation, torsades	Mg, NaHCO₃ for QRS, overdrive pace
Caffeine / energy drinks Dx: BMP (hypoK), ECG, lactate; caffeine level if available	Tachydysrhythmia, seizures, hypoK	Benzos, K+ replete, esmolol for SVT
Iron supplements Dx: Serum Fe @ 4–6 h + AXR (radiopaque tabs) + ABG	>40 mg/kg elemental → shock, AGMA	AXR, serum Fe @ 4–6 h, deferoxamine
Vitamin D / multivitamins Dx: Serum Ca, 25-OH vit D, PTH, BMP	Hypercalcemia (chronic)	IVF, calcitonin, bisphosphonate
Melatonin (peds) Dx: Clinical observation; no specific test	Sedation, usually mild	Observe; airway support if large dose
Alcohol (ethanol) Dx: Serum ethanol level + glucose (peds)	CNS depression, hypoglycemia (peds)	Glucose, thiamine, airway
Marijuana / THC edibles Dx: Clinical; UDS confirms THC	Peds: lethargy, ataxia; adults: anxiety, vomiting	Supportive, antiemetics, benzos
Cannabinoid hyperemesis Dx: Clinical (chronic use + relief w/ hot showers); UDS	Cyclic vomiting in chronic users	Haloperidol or droperidol, capsaicin cream
Bleach / household cleaners Dx: Clinical; CXR if aspiration suspected	Mucosal irritation; mixing → chlorine gas	Dilute with water/milk; humidified O₂
Drain / oven cleaner (alkali) Dx: Endoscopy 12–24 h; CXR for perforation	Caustic burns, esophageal injury	NPO, no charcoal/no induced emesis, GI consult
Button battery Dx: CXR (double-ring/halo sign on AP, step-off lateral)	Esophageal necrosis <2 h	Honey if <12 y & <12 h; emergent endoscopy
Magnets (multiple) Dx: Serial AXR; surgical eval	Bowel perforation	XR; surgical/GI consult if >1 or with metal
Laundry pods Dx: Clinical; CXR if aspiration; airway assessment	Caustic burns, CNS depression, aspiration	Airway, dilute, observe
Hand sanitizer (ethanol/methanol) Dx: Ethanol + methanol levels; osm gap, ABG	Intoxication; methanol blindness	Check ethanol/methanol levels, fomepizole if MeOH
Antifreeze (ethylene glycol) Dx: Osm gap + AGMA + EG level + urine Ca-oxalate crystals	AGMA, Ca-oxalate crystals, AKI	Fomepizole + HD; Ca repletion
Windshield washer (methanol) Dx: Osm gap + AGMA + serum methanol level	Blindness, AGMA	Fomepizole + HD; folinic acid
Rat poison (superwarfarin) Dx: INR/PT at 24 & 48 h; repeat over weeks	Delayed coagulopathy (days–weeks)	Vitamin K1 (high-dose, prolonged); PCC if bleeding
Organophosphate pesticides Dx: Plasma/RBC cholinesterase activity; clinical SLUDGE	SLUDGE, bradycardia, fasciculations	Atropine to dry secretions; 2-PAM
Mushrooms (Amanita) Dx: LFTs, INR (delayed >24 h); urinary α-amanitin if available	Delayed hepatic failure (>6 h sx)	NAC, silibinin, transplant center
Plants (oleander, foxglove) Dx: Digoxin level (cross-reactive) + K+ + ECG	Cardiac glycoside toxicity	Treat as digoxin; DigiFab
Essential oils (eucalyptus, camphor) Dx: Clinical; no specific level	Seizures, CNS depression	Benzos, airway
Nicotine (vape liquid, gum) Dx: Clinical; ECG; cotinine if forensic	N/V, seizures, bradycardia	Atropine, benzos, supportive
ADHD stimulants (amphetamine) Dx: ECG, troponin, CK, temp; UDS	Sympathomimetic, hyperthermia	Benzos, cooling, IVF
SSRIs / SNRIs Dx: Clinical (Hunter criteria: clonus, hyperreflexia); CK, BMP	Serotonin syndrome, seizures	Benzos, cyproheptadine, cooling
Bupropion Dx: ECG (QRS, QTc); observe ≥24 h for delayed seizure	Seizures, wide QRS, status	Benzos, NaHCO₃, intralipid for refractory
Quetiapine / antipsychotics Dx: ECG (QTc); BMP; CK if rigidity (NMS)	Sedation, hypotension, QT	IVF, pressors, ECG monitoring
Lithium Dx: Serum lithium level (timing matters), BMP, TSH	Tremor, AMS, renal failure	IVF, hold drug, HD if level >4 or symptomatic
Metformin Dx: ABG/lactate, BMP, glucose	Lactic acidosis	HD if pH <7.1 or lactate >20
Insulin / sulfonylurea Dx: Serial POC glucose; C-peptide differentiates source	Prolonged hypoglycemia	D10 infusion, octreotide for sulfonylurea
Statins / fibrates Dx: CK, BMP, urinalysis (myoglobinuria)	Rhabdomyolysis	IVF, monitor CK, renal
Kratom (mitragynine / 7-OH-mitragynine) Dx: Clinical Dx — NOT on UDS; ECG (QTc/Brugada), LFTs, APAP/ASA level, lactate	Mixed opioid + stimulant; seizures, QTc/Brugada, hepatotoxicity, frequent co-ingestion	Naloxone (partial, may need repeat), benzos, ECG, screen co-ingestants
Synthetic cannabinoids (K2/Spice) Dx: Clinical; CK, BMP (AKI); UDS does NOT detect	Agitation, seizures, AKI	Benzos, cooling, IVF

US Poison Control1-800-222-1222

Tap any row for pediatric dosing & full ER approach. Always confirm with poison control.

Reference only. Always confirm with your local poison control center: 1-800-222-1222 (US). Verify weight-based caps and renal/hepatic adjustment before administration.