Organophosphate Toxicity

Patho
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Rapidly absorbed everywhere

Delayed tox, fat distribution
Muscarinic
Diarrhea
Urination
Miosis
Bronchorrhea
Bradycardia
Emesis
Lacrimation
Salivation
Nicotinic
↑BP, HR, BG
Sweating
Priapism
Muscular weakness/paralysis
Cramps
Fasciculations
Bind/deactivate AChE → ACh accumulation
Presentation

Onset within 12hr, duration up to several months post exposure/treatment
CNS
Seizure
Coma
Respiratory depression
Labs/Diagnostics
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RBC cholinesterase: 120 days to recover
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Pseudocholinesterase: days-2 wks to recover, use to monitor treatment efficacy
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Tox seen at 50%↓ from baseline
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1 mg atropine, likely tox if pulse increase, unlikely if pupils dilate
Treatment (all get decon + atropine initially)
Decontamination
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Gastric lavage/charcoal if recent ingestion
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Remove clothes/shower/ethyl alcohol wash if topical
Atropine (muscarinic >> CNS)
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Blocks effects of ACh
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2-5 mg IV (adult) or 0.05 mg/kg (peds) q10-30min until complete clearing rales and
bronchorrhea
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HR, pupil size not good endpoints, nicotinic effects
Pralidoxime (nictonic > muscarinic > CNS)
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Reactivate AChE via dephosphorylation (antidote)
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Most effective within 48 hr, AChE-phos becomes irreversible over time
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Indications: muscle weakness, fasciculations, coma, seizure, lower doses of atropine
APAP Toxicity
Patho
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APAP metabolized to reactive NAPQI via 2E1 (one of many paths)→ glutathione
depletion→ hepatocellular necrosis
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Acute tox→ ingestion 10g or 200 mg/kg
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2E1 inducers, liver disease, AUD ↑risk
Presentation
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< 24 hr: asymptomatic, N/V, lethargy, diaphoresis
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24-48 hr: LFT start↑, mainly asymptomatic
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3-4 d: LFT spike/peak, hepatic encephalopathy, RUQ pain, jaundice
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5 d: LFTs normalize
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3 mo: liver normalizes
Labs/Diagnostics
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Rumack-Matthew Nomogram
o Based on IR, acute, one time ingestion in adults→ still use for SR with repeat
levels
o 4-24 hr post ingestion; must wait 4 hr

LFTs (ALT/LFT, Alb, Bili, PT/INR) q24h
Treatment
Activated charcoal < 4 hours
NAC – IV for shorter stay, PO if expected to admit
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Replenishes glutathione with surrogate sulfhydryl groups; d/c if concentration under
line, and labs improving
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72hr PO→ 140 mg/kg LD + 70 mg/kg q4h x 17 doses
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20 hr IV→ 150 mg/kg/15min + 50 mg/kg/4 hr + 100 mg/kg/16 hr
Opioid Toxicity
Presentation
respiratory depression (< 12 bpm), lethargy, coma, seizure, pinpoint pupils, hypoxia
Treatment

Whole bowel irrigation for ER formulations if stabilized
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Naloxone – competitive antagonist, multiple formulations
o 0.04-2mg mg IV q1-3; maintenance 70% (2/3 in her notes) wake-up dose/hr
o Higher doses for methadone/fentanyl might be needed
Methanol/Ethylene Glycol Toxicity
Patho
methanol→ formic acid
Ethylene Glycol→ glycolic acid→ oxalic acid
*alcohol dehydrogenase initiates metabolism in both*
Treatment
Gut Decontamination with lavage within 30 min, no charcoal
Presentation

MeOH: Vertigo, N/V, confusion, lethargy, coma, seizure, blurred vision, photophobia,
pancreatitis, snowfield, smell of alcohol
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EG: N/V, hematemesis, seizure, coma, tachycardia, HTN, pulmonary edema, CHF,
oliguria, flank pain, crystalluria
Labs/Diagnostics
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MeOH or EG > 20 mg/dl
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PMH or suspicion with at least 2 of: pH < 7.3, osmolar gap > 10, bicarb < 20, urine
oxalate crystals (EG)
Antidotes
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Fomepizole: inhibits alcohol dehydrogenase
o 15 mg/kg over 30 min
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Ethanol: binds/saturates alcohol dehydrogenase
o 7.6-10 ml/kg in 30 min to BAL 100-130 mg/dl
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d/c when levels of either < 10 mg/dl + no symptoms
Cofactors
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MeOH = leucovorin + folic acid; enhance formic acid metabolism
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EG = pyridoxine + thiamine; prevent oxalate deposits in tissue
Dialysis
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If either ≥ 50 mg/dl
Salicylate Toxicity
Patho

ASA, Bengay, Excedrin, Pepto-Bismol, Oil of Wintergreen (most toxic)

Saturable metabolism pathways leads to increased free drug→ uncouples oxidative
phosphorylation→ CO2 production, heat, glucose utilization, acidic accumulationj
Presentation

Metabolic acidosis and respiratory alkalosis*, fever, N/V, hematemesis, hypoglycemia,
irritation, disorientation/hallucination, non-cardiogenic pulmonary edema,
hepatotoxicity

hyperpyrexia→lethargy→seizure/coma→death (progression based on levels)
Labs

electrolytes, ABG, glucose, ASA level
Treatment
Gut decontamination if acute overdose
Alkalinization of urine

bicarb + KCl to produce U/O 2-3 ml/kg/hr with urine pH 7.5-8; add more K+ if not
working
Dialysis
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> 80 mg/dl in acute tox
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> 50 mg/dl in chronic tox
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Renal failure
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Deterioration after treatment
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Refractory acidosis
Digoxin Toxicity


Inhibition of Na/K/ATPase pump→ ↑K/↓K and Ca, ↑vagal tone, ↓conduction velo, ↑automaticity
Risk factors that increase dig sensitivity
o hypokalemia, hypomagnesemia, hypercalcemia
o macrolides (gut flora), amio, spironolactone, CCB, quinidine
o renal failure, CHF, hypothyroid, COPD, hypoxia, elderyly, acid/base disturbances
Presentation
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Chronic→ Any arrhythmia, brady/tachycardia, flu symptoms, visual problems, AMS/hallucination/delirium, hypokalemia

Acute→ N/V, bradycardia, heart block (high grade, 2/3), atrial arrhythmias, hyperkalemia
Labs/Tests

Dig level > 15, electrolytes, EKG

Don’t use dig level after fab administration
Treatment
Acute Tox

Stabilize arrhythmia
o Lidocaine 1st for ventricular→ phenytoin, Mg→ amio
o No class 1a (procainamide, quinidine) exacerbate
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Bradycardia and heart blocks
o Atropine, pacemakers

Fab
o Vtach/fib, HR < 40, hypotensive, AMS/coma, K > 5 if not renal insufficient, > 10 mg adult/4 mg child, 2/3 deg heart block

Gut decontamination with multidose activated charcoal even if chronic tox
Chronic tox

d/c

look for precipitating factors

treat symptoms