6.2 Acute Toxicology, Overdoses & Environmental Emergencies

6.2 Acute Toxicology, Overdoses & Environmental Emergencies

Clinical Scenario: A 22-year-old male arrives obtunded after an ingestion. Vital signs: BP 86/50 mmHg, HR 46 bpm, RR 7 breaths/min, SpO2 86% on room air, core temperature 34.4°C. Examination reveals 1 mm pinpoint pupils, shallow respirations, and absent bowel sounds. Capillary glucose is 88 mg/dL. He transiently awakens following 0.4 mg IV naloxone, but relapses into stupor 40 minutes later. Empty containers of diltiazem CD, clonazepam, and acetaminophen were discovered.

Clinical Toxidromes: Diagnostic Differentiation & Management

Toxidromes are clinical symptom clusters identifying toxic drug classes:

Acetaminophen (APAP) Overdose & Hepatoprotective Protocols

Acetaminophen toxicity is a leading cause of acute liver failure:

• Pathophysiology: Overdose saturates glucuronidation and sulfation pathways, shunting APAP to CYP2E1 to generate N-acetyl-p-benzoquinone imine (NAPQI). NAPQI depletes glutathione. When glutathione falls below 30%, NAPQI binds hepatic macromolecules, causing centrilobular necrosis.
• Rumack-Matthew Nomogram: Use the nomogram for a timed acute ingestion with a concentration drawn 4–24 hours after ingestion. The treatment line starts at 150 mcg/mL at 4 hours.
• IV N-Acetylcysteine (NAC) 3-Bag Protocol: Replenishes glutathione. The listed diluent volumes are for adults weighing 41–99 kg. Use weight-specific volumes and dose caps per protocol:
  1. Loading Dose: 150 mg/kg IV in 200 mL D5W over 60 minutes.
  2. Second Bag: 50 mg/kg IV in 500 mL D5W over 4 hours.
  3. Third Bag: 100 mg/kg IV in 1000 mL D5W over 16 hours. Continuation: Do not stop by elapsed time alone. Continue until APAP <10 mcg/mL, AST/ALT are at baseline or have fallen 25–50% from peak, INR <2, and prognostic markers (e.g., creatinine, lactate, pH) are improving; consult toxicology for individualized treatment.
• King's College Criteria for Liver Transplantation: Arterial pH <7.30 after fluid resuscitation, OR all three present within 24 hours: Grade III/IV encephalopathy, serum creatinine >3.4 mg/dL (300 mcmol/L), and INR >6.5 (PT >100 seconds).

Salicylate Toxicity & Urinary Alkalinization

Salicylate poisoning induces characteristic biphasic metabolic derangements:

1. Direct Medullary Stimulation: Causes primary respiratory alkalosis with hyperventilation.
2. Mitochondrial Uncoupling: Uncouples oxidative phosphorylation, accumulating lactic acid and ketones to generate a high anion gap metabolic acidosis.
3. Urinary Alkalinization: Infuse IV sodium bicarbonate (100–150 mEq in 1 L D5W with 20–40 mEq KCl) targeting urine pH 7.5–8.0 and systemic pH 7.50–7.55. Alkalinization ionizes salicylate to its charged conjugate base, trapping it in renal tubules for excretion. Maintain serum potassium 4.0–4.5 mEq/L; hypokalemia forces distal tubular H+ excretion, impairing alkalinization.
4. Hemodialysis Indications: Obtain urgent toxicology/nephrology input for altered mental status, new oxygen-requiring hypoxemia or failed standard therapy, regardless of level. EXTRIP recommends dialysis at >100 mg/dL, or >90 with impaired kidney function, and suggests it for pH <=7.20. Chronic toxicity may require dialysis at much lower levels; judge clinical severity.

Refractory Beta-Blocker & Calcium Channel Blocker Toxicity

Overdoses cause severe cardiogenic shock and bradycardia. CCBs cause hyperglycemia (blocking pancreatic islet L-type calcium channels, halting insulin release), whereas beta-blockers cause euglycemia or hypoglycemia.

• Treatment Priorities: Contact a poison center/toxicologist and support airway, ventilation and perfusion. Treat the observed cardiogenic/vasodilatory physiology rather than following a fixed antidote ladder.
  1. Vasopressors and HIET: Give vasopressors for hypotension. Start high-dose insulin early for life-threatening CCB hypotension; in BB poisoning, use it when hypotension is refractory to vasopressors. Regular insulin 1 unit/kg IV, then 1–2 units/kg/hr, may be titrated up to 10 units/kg/hr under protocol. Monitor glucose and potassium frequently; give dextrose and potassium as needed.
  2. IV Calcium: Reasonable for CCB toxicity: calcium chloride 1–2 g IV centrally, or gluconate 3–6 g IV peripherally, with response/ionized-calcium monitoring.
  3. Glucagon: Reasonable for symptomatic BB bradycardia/hypotension: 5–10 mg IV, then 2–5 mg/hr if effective. Benefit in CCB poisoning is uncertain; monitor for vomiting.
  4. Rescue Support: Consider VA-ECMO for refractory cardiogenic shock. 20% lipid emulsion is not routine BB/CCB treatment; its role after failure of other therapies is uncertain and requires expert consultation.

Substance Use Disorder and Ongoing Treatment

Acute overdose treatment should lead to assessment for substance use disorder: a harmful pattern of use with impaired control, continued use despite consequences or functional impairment. Physiologic dependence during appropriate prescribed treatment alone does not establish addiction. Ask nonjudgmentally about substances, withdrawal, prior treatment and the patient's goals. For opioid use disorder, offer evidence-based medication treatment such as buprenorphine or methadone, with an ongoing-care handoff and overdose-prevention naloxone. Standard buprenorphine initiation requires objective withdrawal to reduce precipitated-withdrawal risk; fentanyl exposure may require an individualized induction strategy. Withdrawal management alone is not adequate ongoing OUD treatment. Continue appropriate medication treatment during hospitalization and coordinate access at discharge.

Accidental Hypothermia & Rewarming Protocols

Accidental hypothermia is a core temperature <35°C. Measure core temperature and assess consciousness/vital signs. The revised Swiss system stages risk clinically: I alert; II responds to voice; III responds only to pain or is unresponsive but has vital signs; IV no detectable vital signs. Temperature bands alone do not determine stage or arrest.

• Rewarming: Protect from further heat loss and use active external rewarming, warmed fluids and selected internal methods. ECLS is appropriate for hypothermic arrest and may be considered in severe hypothermia without arrest.
• Hypothermic Arrest: Start CPR and rewarm concurrently unless obvious lethal injury is present. Under AHA 2025, it may be reasonable to give one shock, then defer further shocks if unsuccessful until core temperature is >=30°C; epinephrine may also be deferred until >=30°C. These treatments are not categorically ineffective below 30°C. Use the overall clinical context and validated prognostication, not a temperature alone, for ECLS and continuation decisions.

Malignant Hyperthermia: Recognition & Emergency Management

Malignant hyperthermia (MH) is a pharmacogenetic crisis involving abnormal skeletal muscle calcium release. Susceptibility is usually autosomal dominant and often involves RYR1.

• Triggers: Volatile anesthetics (sevoflurane, isoflurane, desflurane) and succinylcholine.
• Clinical Presentation: Uncontrolled sarcoplasmic calcium release produces sustained rigidity and hypermetabolism. An early warning sign is an unexplained rise in end-tidal CO2 despite adequate ventilation. Masseter spasm, generalized rigidity, tachycardia, mixed acidosis, hyperkalemia and rhabdomyolysis may occur. Hyperthermia may appear later.
• Immediate Management:
  1. Cease Triggers: Immediately discontinue volatile agents and succinylcholine; hyperventilate with 100% O2 at >10 L/min flow.
  2. Dantrolene Sodium: 2.5 mg/kg rapid IV bolus, repeated as needed until hypercarbia, rigidity and tachycardia improve. Doses >10 mg/kg may be required; reassess the diagnosis if large doses do not resolve the crisis. Blocks ryanodine calcium channels.
  3. Active Cooling: Use cooled IV fluids and surface cooling if temperature exceeds 39°C or is rising rapidly. Stop active cooling at about 38°C.
  4. Treat Hyperkalemia: Calcium, insulin with dextrose, bicarbonate. Avoid calcium channel blockers with dantrolene (causes cardiovascular collapse).