Management of Specific Overdoses

Central inhibition of norepinephrine release → ↓ noradrenergic activity

early/transient HTN, attenuated sympathetic response (decreased HR, BP), opioid-like toxidrome (pinpoint pupils, CNS depression, respiratory depression)

None associated w/ overdose

Sinus bradycardia

• IVF and high dose naloxone 10mg IVP followed by 5 mg/hr if there is no response.
• Vasopressors such as norepinephrine/epinephrine are second line.

Competitively block catecholamines at beta-adrenergic receptors →

• ↓ inotropy and chronotropy
• Impaired gluconeogenesis and glycogenolysis

Lipophilic BB's (propranolol, metoprolol)

• Cross the blood brain barrier → CNS depression, seizures

Membrane stabilizing BB's/Cardiac sodium channel blockade (propranolol, carvedilol):

• QRS prolongation, dysrhythmias (monomorphic VT), Brugada pattern

Cardiac potassium channel blockade (sotalol)

• QTc prolongation and dysrhythmias, torsades de pointes

CNS depression, seizures, myocardial depression, respiratory depression

Hypoglycemia or normoglycemia

Sinus bradycardia, AV block, QRS widening (sodium channel blocking, propranolol), QTc prolongation (potassium channel blocking, sotalol)

• IVF
• Calcium gluconate 3g - Can repeat q10-20 min PRN for max dose of 9 grams of Ca gluconate
• Glucagon 10 mg over 10 min and infusion 3-5 mg/hr (needs infusion since half-life is 6 min)
• Vomiting can occur if administered too fast, consider aspiration risk
• Epinephrine or norepinephrine: first line vasopressors
• Norepinephrine helps if significant vasodilation (carvedilol, labetalol)
• Atropine 0.5-1mg q3-5min
• Intralipid infusion if pt arrests from a lipophilic BB (e.g. propranolol)
• Intralipid (Lipid Emulsion) 20% infusions: 1.5 cc/kg bolus followed by 0.25 cc/kg/min for 60 minutes (for 70 kg adult: 1 liter over 1 hour) for refractory hypotension or if pt codes, max dose: 10 ml/kg or 1200 ml whichever is greater. If using lipid emulsion therapy, please call Toxicology or Poison Control immediately
• BB induced arrhythmias: sodium bicarbonate (adjunct QRS widening) and Mg for QTc prolongation induced Torsades de pointes (TdP)
• Significant atenolol or sotalol toxicity: hemodialysis

DHP: arterial vasodilation

Non-DHP: peripheral vasodilation, decreased inotropy, bradycardia; calcium mediated insulin inhibition in the pancreas → hyperglycemia

DHP (amlodipine, nifedipine): peripheral > central channels, selectivity is lost in overdose

Non-DHP (diltiazem, verapamil): primarily cardiac calcium channels

Markedly preserved mental status until rapid deterioration.

• DHP:
  • Lower doses → vasodilatory shock → hypotension and reflex tachycardia
  • Higher doses → lost selectivity and effect on heart → hypotension and bradycardia

hyperglycemia (associated with severe overdose and sequelae)

bradyarrhythmia, high-degree heart block (3rd degree)

• IVF, vasopressors if needed
• Bradycardia: atropine 0.5-1mg q3-5min (not effective for second- or third-degree block), calcium gluconate 3g, and glucagon 10 mg over 10 min followed by infusion 3-5 mg/h (see beta-blocker management for more info)
• Hypotension + bradycardia: High dose insulin/euglycemic therapy (HIE)
• High-dose insulin 0.5-1 unit/kg bolus followed by 0.5-1 unit/kg/hour infusion titrated up to 10 units/kg/hour. Call Toxicology immediately if considering use since it may be less helpful for dihydropyridines
• Give with dextrose. Titrate insulin like a pressor. Blood pressure may take up to 20 minutes to change
• Must be started early as takes 15-60 min to take effect
• May increase contractility through increasing the cardiac utilization of glucose. Not likely to help with vasodilation or bradycardia
• Vasopressors (norepinephrine or epinephrine): levophed useful for vasodilatory shock such as with DHP-CCBs, may consider phenylephrine for DHP induced vasoplegic shock with tachycardia
• Intralipid should be used in code/peri-arrest for lipophilic CCB's (verapamil, amlodipine, diltiazem)
• 20% infusions: 1.5 cc/kg bolus followed by 0.25 cc/kg/min for 60 minutes (for 70 kg adult: 1 liter over 1 hour) for refractory hypotension or if pt codes, max dose is 10 ml/kg or 1200 ml whichever is greater however, there is limited guidance on a max dose - if using lipid emulsion therapy, please call Toxicology or Poison Control immediately
• Methylene blue for refractory distributive shock for DHP's can be considered, but consult Toxicology prior to using

Blockade of Na/K ATPase → ↑ intracellular Ca → ↑ contractility and may delay afterdepolarizations/shorten repolarization of the atria and ventricles → arrhythmias;

• Acute toxicity: Generally GI symptoms → neuro symptoms later.
• Chronic toxicity: insidious neuro symptoms > GI

lethargy, nausea, vomiting, reported increased vagal tone, yellow halos in visual fields (chronic)

• Hyperkalemia (marker of acute toxicity but not the cause; correlates with mortality)
• Digoxin level: (doesn't always correlate well with clinical toxicity and must be obtained before giving antibody)
• Acute intoxication: >10 ng/ml (>12.8 nM/L). Repeat level 6h post ingestion
• Chronic intoxication: >4 ng/ml (>5.1 nM/L). Repeat level not needed

any abnormality (though Afib RVR is unlikely, more likely to have a regular pulse due to 3rd degree block in the setting of Afib), bidirectional ventricular tachycardia is classic but rarely seen

• Consider activated charcoal if within one hour of acute ingestion.
• Digoxin antibody fragments (dose: # of vials) = [(serum level times the weight of the pt)/100] rounded up. Empiric treatment is 10 vials.
• In acute on chronic toxicity or chronic toxicity, please contact the Poison Center + Toxicology for guidance as less vials may be recommended to avoid adverse events from worsening heart failure or atrial fibrillation
• Unclear dosing for natural toxins (often empirically 10 vials)
• Indications: hemodynamic instability, significant unstable arrhythmia, end organ damage secondary to hypoperfusion (renal failure), or potassium ≥5.0 mEq/L
• Can be used in asymptomatic patients with high level of distribution (Please contact Poison Control/Toxicology for guidance).
• May need to delay if patient hypokalemic (similar to insulin); hypokalemia worsens digoxin cardiotoxicity.
• Atropine 0.5-1mg q3-5min: severe symptomatic bradycardia when digoxin fab fragments are not available
• Given the sensitivity of the myocardium with digoxin, pacers can trigger significant dysrhythmias and only recommended if no access to digoxin fab fragments or fab fragment failure

Inhibition of the breakdown of acetylcholine → ↑ acetylcholine → stimulation of muscarinic and nicotinic receptors

Muscarinic (DUMBBELS): Diarrhea/Diaphoresis, Urination, Miosis, Bronchorrhea/Bronchospasm, Bradycardia, Miosis, Emesis, Lacrimation, Salivation

Nicotinic: fasciculations, muscle weakness, and/or muscle paralysis, sympathetic effects

Intermediate syndrome: neurologic syndrome after resolution of cholinergic excess, decreased DTR, proximal muscle weakness, respiratory insufficiency, neck flexion weakness, CN abnormalities

NA

sinus bradycardia, QTc prolongation

• Ensure decontamination if insecticide.
• Atropine:
  • 1-2 mg (mild-moderate symptoms) vs 3-5mg (severe) IV repeated every 2-20 minutes or 1mg followed by doubling doses every 5 minutes until bronchorrhea is no longer present followed by an infusion 10-20% of the loading dose per hour (max 2 mg/hour)
• Pralidoxime: (Only for organophosphates)
  • 30mg/kg (max 2g) loading dose followed by 8-10 mg/kg/hr (max 650mg/hr)
  • WHO dosing is 2000 mg bolus followed by 500 mg/hr infusion. Consult Poison Control/Medical Toxicology for acetylcholinesterase inhibitor use.
• Seizures: Benzodiazepines
• Secretions: Titrate atropine to dry secretions (can require large amounts i.e. 50 mg).
• Bronchorrhea: Atropine as above

• One standard drink = 12oz regular beer = 5oz wine = 1.5oz 80% distilled spirit
• Absorption is primarily in duodenum/small intestine (80%) with 80-90% of absorption in <60 min in ideal conditions (i.e. empty stomach)
• Metabolized via alcohol dehydrogenase.

PE: Slurred speech, disinhibition, incoordination, unsteady gait, memory impairment, nystagmus, stupor, coma, hypotension, tachycardia

Lab Abnormalities: EtOH, Peth, UDS, hypoglycemia, hyperlactatemia, hypoK, hypoMg, hypoCa, hypophos, LFTs, PT/INR

Symptoms typically begin within 6-24 hours of stopping or significantly decreasing chronic heavy alcohol use.

Classes:

• Natural opiates (morphine, codeine)
• Semi-synthetic (hydrocodone, hydromorphone, oxycodone, oxymorphone, heroin, buprenorphine)
• Synthetic (fentanyl, meperidine, tramadol)

Mechanism: Multiple receptors with wide range of clinical effects including sedation, analgesia, respiratory depression, GI dysmotility, bradycardia, miosis, anxiolysis

PE: AMS, miosis, hypoventilation, decreased bowel sounds, seizures, coma

Laboratory abnormalities: None specific to opioid toxicity

EKG: QT prolongation (loperamide, methadone, very large doses of oxycodone), QRS widening (loperamide)

PE: Irritability, tachycardia, mydriasis, yawning, piloerection, diaphoresis, rhinorrhea, increased BS.

Note: The patient should not have fever or delirium from opioid withdrawal.

Examples: class I antiarrhythmics, tricyclic antidepressants (amitriptyline, imipramine), anticonvulsants (carbamazepine, lamotrigine), cocaine, antihistamines, insecticides.

Mechanism: ↓ depolarization of non-nodal cardiac myocytes.

PE:

• Pure Na channel blockade: bradycardia classically, but can be anticholinergic.
• TCAs: typically tachycardia, cardiogenic shock, hypotension, AMS, seizures, respiratory depression, anticholinergic symptoms

Laboratory abnormalities: NA

EKG: QRS widening with a tall R wave in AVR, QTc prolongation, ventricular dysrhythmia, new right axis deviation. Can appear similar to VT.