Toxic Ingestion — Antidotes and Medications — Clinical Pathway: Emergency Department, ICU and Inpatient

Toxic Ingestion Clinical Pathway — Emergency Department, ICU and Inpatient

Antidotes and Medications

Use as clinically indicated to treat complications from poisonings.
Poison Control Center consultation is recommended.

Antidotes and Medications by Urgent Indications

  • Indications
    • Known/suspected opioid toxicity
    • Unexplained severe respiratory depression
    • Depressed mental status consistent w/opioid toxidrome
  • Dosing
    • Infants and Children < 20 kg
      • 0.1 mg/kg IV, IM, intratracheal, or subQ, Repeat every 2-3 minutes as needed
      • Max 2 mg/dose, Max total dose 10 mg
    • Children > 20 kg
      • 2 mg/dose IV, IM, intratracheal, or subQ, Repeat every 2-3 minutes as needed
      • Max total dose 10 mg
    • Adolescents, Adults, or Concern for Opioid Dependence
      • 0.4 mg IV, IM, intratracheal, or subQ
      • Severe respiratory depression, unresponsive to 0.4mg, consider subsequent 2 mg doses
      • May repeat every 2-3 minutes as needed
      • Max total dose 10 mg
      • Use lower initial dose (0.1 mg) if opioid dependence to avoid acute withdrawal
    • Continuous Infusion
      • Naloxone infusions at CHOP are in mg/kg/hr
      • To calculate initial infusion rate:
        • Calculate the total effective reversing dose of naloxone in mg
          • (e.g., if child required three 2 mg doses for effect, the total reversing dose = 6 mg)
        • Apply this formula:
          • (2/3) x (total reversing effective dose in mg)/(child’s weight in kg)
    • Example
      • A 25 kg child received 6 mg total of naloxone with effective reversal
      • Calculate starting infusion rate as:
        • (2/3) x (6 mg total reversing dose) / (25kg child) = 0.16mg/kg/hr
  • Comments
    • Dose escalation and/or continuous infusion may be necessary for certain situations
      • (e.g., buprenorphine, clonidine, or synthetic opioid toxicity)
  • Indications/Dosing
    • Severe bradycardia
    • Children and Adolescents
      • Initial dose: 0.02 mg/kg/dose IV, Max 0.5 mg/dose
      • Repeat in 3 to 5 minutes intervals for persistent bradycardia
      • Max total dose 0.04 mg/kg or 2 mg
    • Adults
      • 1 mg IV every 3 to 5 minutes
      • Max total dose 3 mg or 0.04 mg/kg
  • Indications/Dosing
    • Anticholinesterase toxicity
    • Organophosphates
    • Nerve agents
    • Infants and Children
      • Initial dose: 0.03 to 0.05 mg/kg IV
      • Subsequent dosing: Double dose every 5 minutes as needed
      • Titrate based on life-threatening cholinergic symptoms
    • Adolescents and adults
      • Initial dose: 2 mg IV
      • Subsequent dosing: Double dose every 5 minutes as needed
      • Titrate based on life-threatening cholinergic symptoms
  • Comments
    • Dose required varies considerably with the severity/type of poisoning. Poison Control consultation is recommended.
  • Indications
    • Calcium channel blocker toxicity
    • Hyperkalemia
  • Dosing
    • Infants and Children
      • 100 mg/kg/dose IV
      • Max 3,000 mg/dose
    • Adolescents and adults
      • 1,500-3,000 mg/dose IV
  • Comments
    • Max peripheral concentration: 50 mg/mL
    • Max central concentration: 100 mg/mL
  • Indications
    • Hypoglycemia
  • Dosing
    • Infants ≤ 6 months
      • 0.25-0.5 g/kg/dose IV
      • Given as IV push:
        • 2.5-5 mL/kg of 10% solution
        • 1-2 mL/kg/dose of 25% solution
      • Max: 25 g/dose
    • Infants > 6 months and children
      • 0.5-1 g/kg/dose IV
      • Given as IV push:
        • 5-10 mL/kg of 10% solution
        • 2-4 mL/kg/dose of 25% solution
      • Max: 25 g/dose
    • Adolescents and adults
      • 10-25 g IV
      • Given as IV push:
        • 40-100 mL of 25% solution
  • Indications
    • Fluid refractory shock
  • Dosing
    • IV infusion initial dose
      • 0.01-0.05 mcg/kg/minute, titrate to desired effect
  • Indications
    • Fluid refractory shock
  • Dosing
    • IV infusion initial dose
      • 0.05-0.1 mcg/kg/minute; titrate to desired effect
  • Indications
    • Prolonged QT
    • Torsades de pointes
  • Dosing
    • 25-50 mg/kg/dose IV
    • Max: 2,000 mg/dose
  • Indications
    • Prolonged QRS (> 100 ms) from sodium channel blockade
      • (e.g., severe tricyclic antidepressant overdose)
  • Dosing
    • Children
      • 1-2 mEq/kg/dose IV, may repeat as needed
    • Adolescents and adults
      • 1 mEq/kg/dose IV, may repeat as needed

Toxic Substances and Specific Time-Sensitive Antidotes and Medications

Poison Control Center consultation is recommended when considering the administration of antidotes or medication from this list.

Initiate supportive care measures before considering the following antidotes and medications.

  • Antidote
    • Acetyl Cysteine (NAC)
  • Indications
    • Indicated for measured or anticipated toxicity from serum acetaminophen
  • Dosing
    • Loading Dose
      • 150 mg/kg IV over 60 mins (150 mg/kg/hr)
      • Max 15,000 mg/dose
    • Second Infusion: to be administered immediately following completion of loading dose
      • 50 mg/kg IV over 4 hrs (12.5 mg/kg/hr)
      • Max 5,000 mg/dose
    • Third Infusion: To be administered immediately following completion of second dose
      • 100 mg/kg IV over 16 hrs (6.25 mg/kg/hr)
      • Max 10,000 mg/dose
      • The third infusion rate of 6.25 mg/kg/hr should be continued past 16 hrs, until the following criteria are met:
        • Serum acetaminophen concentration is < 10 mcg/mL (< 10 mg/L)
        • and
        • Serum AST concentration is normal, or definitively returning to normal
        • and
        • Liver synthetic function is normal
  • Comments
    • Poison Control Center consult encouraged for guidance on NAC therapy
      (PCC: 1-800-222-1222 or 4-2100)
    • RN or FLOC can contact PCC for clarification of next steps for the patient’s plan of care
    • Duration of therapy may extend > 21 hours if hepatocellular injury is present
  • Adjunctive Antidote
    • Fomepizole
      • Initial loading dose (dose 1)
        • 15 mg/kg IV
      • Subsequent doses, as needed, for up to four additional doses (doses 2-5)
        • 10 mg/kg IV every 12 hrs
      • If further doses are required (doses ≥ 6)
        • 15 mg/kg IV every 12 hrs
  • Indications
    • Consider for massive overdose with high likelihood of hepatotoxicity
    • Use only in consultation with Poison Control Center only
    • Dosing may require adjustment if on hemodialysis
  • Dosing
    • Children and adults
      • Initial loading dose
        • 15 mg/kg IV
        • Followed by 10 mg/kg IV every 12 hrs for 4 doses
      • Subsequent doses
        • 15 mg/kg IV every 12 hrs
  • Antidote
    • Glucagon
  • Dosing
    • IV Bolus
      • 0.05 mg/kg
      • Max 5 mg/dose
    • Typical Initial Infusion Rate
      • 0.05 mg/kg/hr, titrate to effect
      • Max starting rate 5 mg/hr
  • General Management Considerations
    • Continuous cardiac monitoring
    • Fluid resuscitation with attention to fluid overload and drug-induced inotropic failure
    • Early Poison Control Center consultation for decontamination, WBI, and antidote/medication treatment
    • Cardiology consultation pacing, ventricular assist for severe overdose
  • Antidote – Option 1
    • Calcium Gluconate
  • Dosing
    • Infants and children
      • 100 mg/kg/dose IV, Max 3,000 mg/dose
    • Adults
      • 1,500-3,000 mg/dose IV
  • Antidote – Option 2
    • High-Dose Insulin (and Dextrose)
  • Dosing
    • Starting Bolus Doses
      • Insulin: 1 unit/kg IV
      • Dextrose (if starting blood glucose < 200 mg/dL): 0.25g/kg IV
    • Followed by Continuous Insulin AND Dextrose infusions
      • Insulin: 1 unit/kg/hour, titrate to effect
      • Max 10 units/kg/hr
      • Dextrose (as D10 or D15 crystalloid): 0.25g dextrose/kg/hr
    • Note
      • Insulin dosing for management of CCB ingestion is higher than for other indications
  • Comments
    • Correct hypokalemia prior to insulin administration.
    • Serum blood glucose monitoring:
      • Goal > 100 mg/dL
      • Monitor every 20 minutes for one hour after initiation of therapy and after any changes to insulin dose, then hourly thereafter
  • Antidote – Option 3
    • Lipid Emulsion Therapy (20% Lipid Emulsion)
  • Dosing
    • First Bolus
      • 1.5 mL/kg IV over 1 min
      • Max 100 mL
    • Second Bolus
      • 0.75 mL/kg IV over 3-5 mins
      • Max 50 mL
    • Initial Infusion
      • 0.025 mL/kg/min
      • Consult Poison Control Center for titration recommendations
  • Comments
    • If hemodynamic instability re-occurs/worsens shortly after cessation of infusion, may consider repeating boluses and infusion
  • Antidote – Option 4
    • Vasopressin
  • Dosing
    • Infants and children/adolescents < 50 kg
    • Infant Infusion
      • 12 milliunits/kg/hr IV
      • Increase dose 12 milliunits/kg/hr every 10-15 minutes as needed based on response
      • Max 240 milliunits/kg/hr
    • Adolescents ≥ 50 kg and Adults
      • 0.01-0.04 units/minute IV infusion
  • Comments
    • Dosing units may vary across institutions
  • Antidote
    • Sodium Bicarbonate and Dextrose
  • Dosing
    • Sodium Bicarbonate
      • 1-2 mEq/kg/dose initial IV bolus
      • Followed by, continuous infusion of
        • D5W with 130-150 mEq sodium bicarbonate per liter
        • Administer at 1.5-2 times maintenance fluid rate
  • Comments
    • Monitor serum potassium level
    • Consider supplementation as needed to prevent/correct hypokalemia
  • Antidote
    • Sodium Bicarbonate
  • Dosing
    • Sodium Bicarbonate
      • 1-2 mEq/kg/dose initial IV bolus
      • Followed by, continuous infusion of
        • D5W with 130-150 mEq sodium bicarbonate per liter
        • Administer at 1.5-2 times maintenance fluid rate
    • Administer IV sodium bicarbonate to achieve
      • Blood pH of 7.45-7.5 and urine pH of 7.5-8
  • Comments
    • Monitor serum potassium level

Toxic Substances and Antidotes and Medications Requiring Caution/Poison Control Consultation

Consultation with Poison Control required to discuss the risk versus benefits of using the following antidotes and medications.

  • Antidote
    • Physostigmine
  • Dosing
    • Children and adolescents
      • 0.01-0.03 mg/kg/dose IV
      • Max single dose 0.5 mg
      • Repeat after 15-20 minutes
      • Max total dose 2 mg
    • Adults
      • Initial dose: 0.5-2 mg IM, IV, SubQ
    • Repeat every 20 minutes until response or adverse effect occurs
  • Comments
    • Use is generally reserved for severely affected children
    • Monitor for signs of cholinergic toxicity
    • Continuous cardiac monitoring recommended
  • Antidote
    • Flumazenil
  • Dosing
    • Children and adolescents
      • Initial dose: 0.01 or 0.02 mg/kg IV (max 0.2 mg)
      • Repeat doses: 0.01 mg/kg (max 0.2 mg/dose) every minute
      • Max total dose: 1 mg
    • Adults
      • Initial dose 0.2 mg IV over 30 seconds
      • May give 0.3 mg dose after 30 seconds if desired level of consciousness is not obtained
    • Additional doses
      • 0.5 mg can be given over 30 seconds at 1 minute intervals up to a cumulative dose of 3 mg
  • Comments
    • Do no use to reverse benzodiazepine toxicity in any child on chronic benzodiazepine therapy or in poly-pharmacy overdose
    • It may be of value for reversal of iatrogenic parenteral benzodiazepine overdose
  • Antidote
    • Atropine, pralidoxime
  • Dosing
    • Atropine
    • Pralidoxime
      • Infants, children, adolescents ≤ 16 yrs
        • 20-50 mg/kg/dose, Max 2,000 mg/dose
        • Repeat in 1-2 hours if muscle weakness is not relieved
        • Then at 10-12 hour intervals if cholinergic signs recur
      • Adolescent > 16 yrs, Adults
        • 1,000-2,000 mg
        • Repeat 250 mg every 5 min as needed
  • Antidote
    • Digoxin Immune fab
  • Dosing
  • Comments
    • Can interfere with digoxin assay and cause false elevations in repeat digoxin levels
  • Antidote
    • Deferoxamine
  • Dosing
    • Children, adolescents, and adults
      • Infusion Rate: 5-15 mg/kg/hr IV
      • Max cumulative dose: 6 g/day
  • Comments
    • Rarely, higher infusion rates early in the clinical course might be warranted for life-threatening toxicity
    • Continue infusion until clinical and laboratory manifestations have waned in consultation with Poison Control Center
  • Antidote
    • BAL, EDTA, DMSA
  • Dosing
    • Consult Poison Control Center or toxicology service regarding dosing and agent selection
  • Antidote
    • Pyridoxine
  • Dosing
    • Acute ingestion of KNOWN amount
      • Give a total dose of pyridoxine = to the amount of isoniazid ingested
        • I.V., I.M., SubQ
      • (e.g., 3 g dose of isoniazid ingested = administer 3 g pyridoxine)
    • Acute ingestion of UNKNOWN amount
      • 70 mg/kg, max 5 g IV, IM, SubQ
      • Administer at a rate of 0.5-1 g/minute
      • Repeat doses every 5-10 minutes may be needed for persistent seizure activity or CNS toxicity
  • Antidote
    • Dextrose and Octreotide
  • Dosing
    • Octreotide
      • Initial dose
      • 1 mcg/kg/dose SubQ, Max 50 mcg/dose
      • May be repeated every 6 hrs in consultation with Poison Control Center
  • Comments
    • Ensure dextrose infusion with octreotide administration
    • Rebound hypoglycemia can occur with dextrose boluses
  • Antidote
    • Fomepizole
      • Initial loading dose (dose 1)
        • 15 mg/kg IV
      • Subsequent doses, as needed, for up to four additional doses (doses 2-5)
        • 10 mg/kg IV every 12 hrs
      • If further doses are required (doses ≥ 6)
        • 15 mg/kg IV every 12 hrs
  • Dosing
    • Children and adults NOT requiring hemodialysis
      • Initial loading dose
        • 15 mg/kg IV followed by 10 mg/kg IV every 12 hrs for 4 doses
      • Subsequent doses
        • 15 mg/kg IV every 12 hrs until toxic alcohol levels are acceptable in consultation with Poison Control Center
  • Comments
    • Ensure dextrose infusion with octreotide administration
    • Rebound hypoglycemia can occur with dextrose boluses