The Agent / Antidote Game Show

Acetaminophen Overdose

Acetaminophen is metabolized by glucuronidation and sulfuration
Metabolized to NAQPI
- NAQPI is reduced by glutathione to non toxic compounds that are renally excreted
Toxicity develops at 140 mg/kg
Centrilobular necrosis
- Elevated levels of NAQPI. Depletes the Glutathione stores
NAC repletes glutathione and prevents NAQPI from binding to hepatic macromolecules
Rumack-Matthew Nomogram
- guides indication for NAC usage
- Used ONLY in acute toxicity
- measured 4hrs after ingestion

Iron Toxicity

Very common and deadly among children
Failure to recognize and appropriately treat → multi organ failure, death
Amount ingested depends on the formulation
- For example: 325 mg ferrous sulfate tablets are 20% elemental iron
  - 0.20 x 325 mg = 65 mg of Iron
Direct caustic injury to GI tract.
- Hemorrhagic necrosis can occur
Impairs cellular metabolism in multiple organs
Free radical formation → cell death
Treatment:
- Asymptomatic: supportive care
- Mild symptoms, but hemodynamically stable: observation
- Unstable + symptomatic → Deferoxamine + ICU admission

Digoxin Toxicity

Cardiac Glycoside derived from foxglove
Inotropic effects helpful for CHF
AV nodal blocker helpful for atrial tachydysrhythmias
Toxicity presents w/ hyperkalemia, GI symptoms, visual disturbances, ECG changes

Carbon Monoxide Poisoning

CO binds to Hgb with affinity 250x that of O2 → reduced Hgb O2 saturation and inability to carry oxygen rich blood to tissues
The O2 dissociation curve displaced leftwards making it hard for Hgb to offload O2 to peripheral tissue
Vague symptoms.
- Whole family comes in w/ same symptoms
- Pet fatality
Obtain Carboxyhemoglobin level
- Normal < 5%
- Abnormal in non smokers: > 5%
- Abnormal in smoker: > 10%
O2 Half lives
- Room air ~6hrs
- 100% FiO2 ~1hr
- Hyperbaric O2 ~30m

Hyperbaric O2 indications:

RAPID FIRE:

Aspirin

Sodium Bicarbonate
- 3 amps (150 Meqs) of Bicarb in 1000cc D5W
- Alkalinizes urine and creates ionic trapping for aspirin
- Need to keep potassium at adequate numbers as this is used for ionic exchange
Hemodialysis indications
- Altered mental status
- pH < 7.2 despite bicarb therapy
- Salicylate level > 100mg/dL in acute overdoses
- Salicylate level > 90mg/dL in acute overdoses with renal dysfunction OR despite fluid resuscitation / alkalinization
- Salicylate level > 80mg/dL in acute overdoses with renal dysfunction AND despite fluid resuscitation / alkalinization
- Salicylate level >40-50mg/dL in chronic overdoses (considerable amount of levels within tissue not circulating in blood)
- Consider hemodialysis in conjunction with Nephrology AND Toxicology

Tricyclic Antidepressants

Methanol

Fomepizole
- 15mg/kg IV, then
- 10mg/kg IV q12hrs x4 doses, then
- 15mg/kg IV q12hrs
- EXPENSIVE (~$1500 / dose)
Ethanol
- Target blood alcohol 100-150mg/dL
- Oral dosing
  - Loading dose: 0.8g/kg ethanol
    - volume = loading dose / ABV
  - Maintenance dose
    - ~66-130mg/kg/hr, may be higher for regular drinkers (100-150mg/kg/hr)
    - equates to ~7g/hr (equates to approximately 1/2 of a "standard drink" per hr)
Dialysis indications
- consult Nephrology AND toxicology
- Acidosis pH < 7.15
- Anion gap >24
- End organ damage
- Methanol level
  - >50mg/dL in absence of EtOH or fomepizole therapy
  - >60mg/dL in contenxt of ethanol therapy
  - >70mg/dL in context of fomepizole therapy

Isoniazid

References

Farkas J. Sodium Channel Blocker Toxicity (including tricyclic antidepressants). Published April 26, 2021. EMCrit Project. https://emcrit.org/ibcc/nacb/
Farkas J. Salicylate intoxication. Published October 1, 2021. EMCrit Project. https://emcrit.org/ibcc/salicylates/
Farkas J. Ethylene glycol & methanol poisoning. Published January 23, 2020. EMCrit Project. https://emcrit.org/ibcc/alcohols/
Farkas J. Status Epilepticus. Published July 6, 2022 EMCrit Project. https://emcrit.org/ibcc/sz/#pyridoxine

Darshak Vekaria, MD

THE MORNING REPORT