This chapter will review the pharmacotherapy for management of acute alcohol and drug poisoning according to the current practice guidelines by The American Academy of Clinical Toxicology and other expert panel.
Introduction
The primary treatment strategy for acute poisoning should focus on stabilizing the patient, with an emphasis on airway, breathing, and circulation.
Management after patient stabilization
Gastrointestinal (GI) decontamination
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To prevent the absorption of an ingested toxin from the GI tract
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Methods, indications, and contraindications ( Table 18.1 )
Table 18.1
METHODS
INDICATIONS
CONTRAINDICATIONS
DOSING
Activated charcoal
(preferred)
Use within 1 h of ingestion of drug poisoning
Decreased level of consciousness or inability to protect airway
Increased risk of gastrointestinal bleeding or perforation
Recent bowel surgery
Ingestion of acids, alkali, alcohols, carbamates, cyanide, organic solvents, hydrocarbons, metals, and organophosphates
Oral/NG:
Single dose: 25–100 g
Multidose: 50 g ×1 then 25–50 g q4h
Gastric lavage
Reserve for extraordinary situations involving life-threatening overdoses
Unprotected airway
Increased risk of and severity for aspiration
Ingestion of strong acid or alkali
Increased risk of gastrointestinal bleeding or perforation
Lavage via large-bore OG tube with 200–300 mL of warm saline or water; continue until fluid is free of pills or pill fragments
Cathartics
Not recommended
Conflicting data on decreased transit time in the GI track of drugs that are sustained-release, enteric coated, or poorly absorbed by activated charcoal
Bowel obstruction or perforation
Absent bowel sounds
Recent bowel surgery
Volume depletion
Electrolyte disturbances
Renal insufficiency for magnesium citrate
Hypotension
Sorbitol 70% solution 1–2 mL/kg or
Magnesium citrate 10% solution 240 mL
Whole bowel irrigation
Not recommended for routine use
May consider in potentially life-threatening ingestion of drugs with long half-lives, sustained-release, enteric coated drugs, or drugs that are poorly absorbed by activated charcoal (e.g., lithium, iron)
May be useful in persons who ingest large quantities of illicit drugs for the purpose of smuggling (body packers)
Unprotected airway
Ileus
Recent bowel surgery
Bowel obstruction or perforation
Intractable vomiting
Hemodynamic instability
Polyethylene glycol electrolyte solution 500–2000 mL/h until rectal effluent is clear
Acute drug poisoning
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Toxic syndromes (toxidromes) and specific therapies ( Table 18.2 )
Table 18.2
DRUG
TOXIC SYNDROMES
TREATMENT
Acetaminophen
Anorexia; elevated liver enzymes; jaundice; pallor; lethargy; liver failure; N/V
Treatment based on Rumack-Matthew nomogram (see Fig. 18.1 )
N -acetylcysteine dosage:
Oral (72 h): 140 mg/kg (LD), then 70 mg/kg q4h × 17 doses (MD)
IV (21 h): 150 mg/kg (max 15 g) in 200 mL D5W infused over 60 min (LD), then 50 mg/kg (max 5 g) in 500 mL D5W over 4 h then 100 mg/kg (max 10 g) in 1L D5W over 16 h (MD); reduce volume if weight <40 kg
Limitations to using the Rumack-Matthew nomogram: presentation >24 h postingestion, unclear history of ingestion, overdose with extended-release formulations, chronic or repeated overdoses, preexisting hepatic disease, chronic alcohol use, or concurrent medications metabolized by the CYP system
Anticholinergics (antihistamines, antipsychotics, tricyclic antidepressants, skeletal muscle relaxants)
Agitation, hallucinations, abnormal movements, tachycardia, mydriasis, dry membranes, flushed/dry skin, hyperthermia, urinary retention, decreased bowel sounds
Physostigmine IV: 0.5–2 mg over 2–4 min, may repeat q0.5–1h PRN
Benzodiazepines for seizures and agitation: lorazepam 1–4 mg IV push
Avoid phenothiazines (e.g., chlorpromazine) and butyrophenones (e.g., haloperidol)
Benzodiazepines
Anterograde amnesia; ataxia; coma; confusion; drowsiness; lethargy; sedation
Flumazenil: 0.5 mg IV push; repeat 0.5 mg q1min PRN
If no response 5 min after a cumulative dose of 5 mg, consider other causes of sedation
CI: history of seizures, chronic benzodiazepine use, co-ingestion that could induce seizures (e.g., tricyclic antidepressants, cocaine)
Propylene glycol toxicity from lorazepam or diazepam: characterized by hyperosmolarity and anion gap metabolic acidosis. Dialysis may be required for severe cases
β -Blockers (BBs)
Acidosis, bradycardia, bronchospasm, coma, hyper/hypoglycemia, hyperkalemia, hypotension, respiratory depression, seizures, prolonged AV conduction
Same treatment for BB and CCB:
Atropine 0.5 mg IV push
Glucagon 5–10 mg IV push; continuous infusion if symptom response achieved with bolus
Calcium chloride 1–2 g or calcium gluconate 3–6 g IVPB; continuous infusion 0.3–0.7 mEq/kg/h if symptoms persist
Norepinephrine 2–5 mcg/min, titrated to response
Dopamine 5–10 mcg/kg/min, titrated to response
Phenylephrine 20–40 mcg/min, titrated to response
Hyperinsulinemic euglycemic therapy: Regular insulin 1 unit/kg IVP bolus (with dextrose bolus of 1 g/kg), then 0.5 unit/kg/h (with dextrose 0.5 g/kg/h) titrated until hypotension resolved or a maximum of 10 units/kg/h reached (keep serum glucose level at 100–250 mg/dL)
Replete potassium PRN
Sodium bicarbonate for QRS widening, severe acidosis, or dysrhythmia: 1–2 mEq/kg bolus; continuous infusion if symptoms persist
Calcium channel blockers (CCBs)
Non-dihydropyridine CCB: hypotension, prolonged AV conduction, bradycardia, lethargy, hyperglycemia, and depressed consciousness
Dihydropyridine CCB: vasodilation, hypotension, and reflex tachycardia
Clonidine
Apnea; bradycardia; coma; hyper- or hypotension; hypothermia; mental status change; pinpoint pupils
Naloxone: IV bolus: 0.04 mg then increase q2–3min to 0.5 mg, 2 mg, 4 mg, 10 mg, then 15 mg
IV infusion: two-thirds the effective bolus dose per hour (0.04–4 mg/h) for patients requiring subsequent naloxone doses to sustain effect
IV preferred, but can be given via endotracheal, intramuscular, intranasal, inhalational, intraosseous, or intrapulmonary route
Atropine: 0.5–1 mg IV push
Dopamine: 5–20 mcg/kg/min
Cholinergics (organophosphates, nerve agent exposure, physostigmine)
Hypersalivation, lacrimation, urinary/fecal incontinence, GI cramping, emesis, bradycardia, miosis, diaphoresis, pulmonary edema, weakness, muscle fasciculations, paralysis, bronchoconstriction
Atropine: 1–2 mg IV push ×1 then doubled dose q3–5min PRN until pulmonary muscarinic signs and symptoms are alleviated
Pralidoxime (in addition to atropine): IV bolus: 30 mg/kg (max 2000 mg) over 30 min, then IV infusion: 8–10 mg/kg/h (max 650 mg/h)
Digoxin
Heart block, tachyarrhythmias, bradyarrhythmias, N/V, lethargy, headaches, confusion, and visual disturbances
Correct electrolyte abnormalities: K, Mg, Ca
Treat symptomatic bradyarrhythmias: atropine 0.5 mg IV push
Digoxin immune antigen-binding fragments (Fab) for life-threatening arrhythmias; asystole, VF/VT, complete heart block, symptomatic bradycardia, end-organ damage, hyperkalemia
Dosing:
If amount of digoxin ingested is unknown: 10–20 vials for acute toxicity or 6 vials for chronic toxicity
If amount of digoxin ingested is known: dose (vials) = [serum digoxin conc (ng/mL) × weight (kg)] / 100
Monitoring: serum digoxin concentrations are not recommended after the administration of Fab as a rapid rise in serum concentrations expected from the Fab-digoxin complex
Iron
N/V/D, hypovolemia, metabolic acidosis, seizures, hepatic/kidney failure, and GI tract scarring/strictures
Deferoxamine IV infusion: 5 mg/kg/h, titrate to 15 mg/kg/h as tolerated, max dose 6 g/day
Opioids
CNS depression, including coma, lethargy, or stupor; constipation, N/V; flushing and pruritus; hypotension; meiosis; pulmonary edema; respiratory depression; seizures
Naloxone: a competitive antagonist at the opioid receptor
IV onset: 2 min; IV duration: 30–120 min
IV bolus: 0.04 mg then increase q2–3min to 0.5 mg, 2 mg, 4 mg, 10 mg, then 15 mg
IV infusion: two-thirds the effective bolus dose per hour (0.04–4 mg/h) for patients requiring subsequent naloxone doses to sustain effect
IV preferred, but can be give via endotracheal, intramuscular, intranasal, inhalational, intraosseous, or intrapulmonary route
Salicylates
If serum concentration:
<30 mg/dL: asymptomatic
15–30 mg/dL: therapeutic
30–50 mg/dL: hyperventilation, N/V, tinnitus, dizziness
50–70 mg/dL: tachypnea, fever, sweating, listlessness, dehydration
>70 mg/dL: coma, seizures, stupor, hallucinations, cerebral edema, oliguria, dysrhythmias, hypotension, renal failure
No antidote for salicylate poisoning
Gastric decontamination with activated charcoal for acute ingestions if the patient is alert without vomiting
IV crystalloids to maintain BP
IV glucose for hypoglycemia or significant neurologic symptoms
Urine alkalinization to enhance renal elimination: 250 mL of sodium bicarbonate 8.4% over 1 h then 50 mL boluses PRN to maintain urine pH 7.5–8.5 or 150 mL of sodium bicarbonate 8.4% in 1L D5W at 2–3 mL/kg/h to maintain urine output 1–2 mL/kg/h to maintain urine pH ≥7.4
Replete serum potassium as necessary
Consider hemodialysis if acute renal insufficiency, end-organ damage, altered mental status, deterioration of clinical status, or severe acid-base abnormalities
Sulfonylureas
Coma, decreased appetite, dizziness, hypoglycemia, lethargy, seizures, weakness
Conscious patients: 8 oz of oral carbohydrate (juice, non-diet sodas, or milk) or oral glucose tablet/gel PRN BG <60 mg/dL
Unconscious patients: IV dextrose 0.5–1 g/kg q15min PRN BG <60 mg/dL
Octreotide: 50 mcg subcutaneous or IV q6h ×4
Glucagon: 1 mg IM, IV, or SubQ q15min PRN
Tricyclic antidepressants
Coma; confusion; delirium; dilated pupils; dry mouth; seizure; hypotension; tachycardia; urinary incontinence
Benzodiazepines for seizures (avoid barbiturates and phenytoin): lorazepam 2–4 mg IV push
Sodium bicarbonate 1 mEq/kg IV push q15min until ECG stabilized or arterial pH goal (7.45–7.55) achieved
Dopamine 5–10 mcg/kg/min, titrated to response
Norepinephrine 2–5 mcg/min, titrated to response
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