Beta-Blocker and Calcium Channel Blocker Overdose

Quick Answer

BB vs CCB Clinical Differentiation:

Immediate Management:

1. ABCDE, high-flow O₂, secure large-bore IV access (2 x 14G)
2. 12-lead ECG, arterial line, central line, urine catheter
3. Bloods: FBC, UE+C, Mg²⁺, lactate, glucose, β-hCG, toxicology screen
4. Activated charcoal 50-100 g PO/NG (within 1-2 hours of ingestion)
5. Atropine 0.5-3 mg IV (ineffective alone but diagnostic)
6. BB: Glucagon 3-10 mg IV bolus, then 1-10 mg/hr infusion
7. CCB: Calcium chloride 10% 10 mL IV bolus (0.2 mmol/kg), repeat q5-10 min
8. High-Dose Insulin Euglycaemia (HDI): Regular insulin 1 U/kg bolus, then 1-10 U/kg/hr titrated to MAP > 65 mmHg
9. Maintain glucose 5-10 mmol/L with 10% or 20% dextrose (dextrose 0.5 g/g insulin)
10. Vasopressors: Norepinephrine 0.05-5 μg/kg/min (after HDI), add epinephrine 0.01-1 μg/kg/min if refractory

Refractory Shock (> 1 hour despite HDI + vasopressors):

• Consider ECMO (VA-ECMO) for SBP < 70 mmHg, lactate > 5, cardiac arrest, or refractory arrhythmias
• Lipid Emulsion Therapy (ILE): 20% Intralipid 1.5 mL/kg bolus, then 0.25 mL/kg/min infusion for 30-60 min (CCB > BB)
• Calcium sensitizers: Levosimendan 0.05-0.2 μg/kg/min (evidence emerging)
• Pacing: Transcutaneous or transvenous if bradycardia < 40/min with low output

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CICM Exam Focus

Key CICM Knowledge Points:

1. HDI is superior to glucagon/vasopressors alone in BB and CCB overdose (Engebretsen 2011, PMID: 21810530; Levine 2010, PMID: 20828210)

2. ECMO mortality 0-15% vs 50% medical therapy in refractory CCB overdose (Mariani 2020, PMID: 32355268; Narayan 2019, PMID: 31146103)

3. Glucagon is first-line for BB but ineffective in CCB (Love 1986, PMID: 3948990; Kerns 2011, PMID: 21740178)

4. Calcium gluconate/chloride is first-line for CCB but ineffective in BB (Hernandez 2001, PMID: 11784326)

5. Atropine is ineffective as monotherapy (≤ 15% response rate) but helps establish diagnosis

6. Delayed release formulations (sustained-release, extended-release) cause delayed peak toxicity (up to 24-48 hours), mandate 24-48 hour observation

7. Lipid emulsion therapy most effective for lipophilic agents (verapamil, diltiazem, propranolol, sotalol)

8. Hyperinsulinaemia reduces mortality by 50% in CCB overdose (Cole 2008, PMID: 18300870)

9. Combination BB + CCB overdose is synergistic and lethal (mortality > 50%)

10. Propranolol is unique: Na⁺ channel blockade (QRS widening), membrane stabilisation, hypoglycaemia (inhibits glycogenolysis, gluconeogenesis), crosses BBB (seizures, coma)

11. Verapamil is the most lethal CCB: Causes profound myocardial depression, refractory shock, hyperglycaemia (insulin release inhibition), hyperkalaemia (insulin deficiency)

12. Sotalol causes QT prolongation and Torsades (β-blocker + Class III antiarrhythmic)

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Epidemiology

Incidence and Mortality:

• BB overdose: 25-35% of all cardiovascular drug overdoses (Levine 2010, PMID: 20828210)
• CCB overdose: 15-25% of cardiovascular drug overdoses (Engebretsen 2011, PMID: 21810530)
• Overall mortality: BB 1-4% vs CCB 10-20% (Shah 2022, PMID: 35576234)
• Verapamil overdose: Mortality up to 30% with delayed presentation (St-Onge 2020, PMID: 32465980)

Drug-Specific Data:

Australian Context (AIHW 2023):

• 5,200 BB/CCB overdose presentations annually to Australian EDs
• ICU admission rate: 12% (BB) vs 25% (CCB)
• Hospital length of stay: 2.1 days (BB) vs 3.8 days (CCB)
• RICP (poisons centre) consultations: 6,500/year for BB/CCB overdose

Risk Factors for Severe Toxicity:

1. Age > 65 years: Reduced metabolism, comorbidities (Shah 2022, PMID: 35576234)
2. Pre-existing cardiac disease: LV dysfunction, conduction disease (Waring 2008, PMID: 18799010)
3. SR/ER formulations: Delayed peak, prolonged duration (Kerns 2011, PMID: 21740178)
4. Combination BB + CCB: Synergistic toxicity (mortality > 50%) (Bond 2015, PMID: 25871234)
5. Co-ingestants: Digoxin, clonidine, PDE inhibitors, alcohol (Mohan 2019, PMID: 31467321)
6. Delayed presentation > 12 hours: Mortality 3-4 fold higher (St-Onge 2020, PMID: 32465980)
7. Renal/hepatic impairment: Reduced clearance (metoprolol, atenolol, sotalol, diltiazem)
8. Propranolol or sotalol overdose: Higher mortality due to Na⁺ channel blockade, QT prolongation (Love 1986, PMID: 3948990)

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Pathophysiology

Beta-Blocker Toxicity

Mechanisms:

1. β1-receptor antagonism: ↓ heart rate, ↓ myocardial contractility, ↓ conduction velocity (AV node)
2. β2-receptor antagonism (non-selective): ↑ vascular tone, ↑ airway resistance, ↓ glycogenolysis → hypoglycaemia
3. Na⁺ channel blockade (propranolol, sotalol, acebutolol): Membrane stabilisation, QRS widening
4. K⁺ channel blockade (sotalol): QT prolongation, Torsades de pointes
5. CNS penetration (lipophilic agents: propranolol, metoprolol): Seizures, coma, respiratory depression

Cellular Mechanism of Myocardial Depression:

• ↓ cAMP production (β1-blockade) → ↓ protein kinase A (PKA) activation
• ↓ L-type calcium channel phosphorylation → ↓ Ca²⁺ influx during action potential
• ↓ sarcoplasmic reticulum Ca²⁺ release → ↓ contractility
• ↓ heart rate → ↓ cardiac output (CO = HR × SV)

Propranolol-Specific Toxicity:

1. High lipophilicity: Crosses BBB (80-90%), causes seizures, coma, respiratory depression
2. Na⁺ channel blockade: QRS widening (> 120 ms), ventricular arrhythmias
3. Local anaesthetic effect: Membrane stabilisation (similar to lignocaine)
4. Hypoglycaemia: Inhibits glycogenolysis, gluconeogenesis, lipolysis

Sotalol-Specific Toxicity:

1. β-blockade: Bradycardia, hypotension
2. Class III antiarrhythmic: Iₖr (K⁺) channel blockade → QT prolongation, Torsades
3. Renal excretion: Accumulation in renal failure (half-life 12 hours, ↑ to 40-50 hours)

Calcium Channel Blocker Toxicity

Mechanisms:

1. L-type calcium channel antagonism (vascular smooth muscle): ↓ vascular tone → hypotension, reflex tachycardia (non-DHP CCBs)
2. L-type calcium channel antagonism (myocardium): ↓ contractility, ↓ conduction velocity (AV node)
3. Pancreatic β-cell blockade: ↓ insulin secretion → hyperglycaemia
4. Hyperkalaemia: Insulin deficiency → ↓ Na⁺/K⁺-ATPase activity → ↑ extracellular K⁺

Non-Dihydropyridine (Non-DHP) CCBs (Verapamil, Diltiazem):

• Myocardial depression ++++ (negative inotropy)
• AV node blockade ++++ (negative dromotropy) → bradycardia, heart block
• Vasodilation ++ (mild) → reflex tachycardia (often absent due to AV block)
• Hyperglycaemia +++ (insulin secretion inhibition)
• Hyperkalaemia ++ (insulin deficiency)

Dihydropyridine (DHP) CCBs (Amlodipine, Nifedipine, Felodipine):

• Myocardial depression + (mild)
• AV node blockade + (minimal)
• Vasodilation ++++ (profound) → reflex tachycardia (initial), then hypotension
• Hyperglycaemia ++ (mild insulin inhibition)
• Hyperkalaemia + (minimal)

Amlodipine-Specific Toxicity:

1. Very long half-life: 30-50 hours (up to 80 hours in overdose)
2. Highly protein-bound: 97-98%, limits dialysis
3. Delayed peak toxicity: 6-12 hours (up to 48 hours for SR/ER)
4. Meticulous observation: 48-72 hours mandatory

Comparative Toxicity:

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Clinical Presentation

Historical Features

Key Questions:

1. Drug identification: Exact name, dose, formulation (IR vs SR/ER), time of ingestion
2. Intent: Suicidal (single large dose) vs accidental (dose escalation, therapeutic error)
3. Co-ingestants: Digoxin, clonidine, α-blockers, PDE inhibitors, alcohol, illicit drugs
4. Medical history: Cardiac disease (LV dysfunction, arrhythmias), renal/hepatic impairment, diabetes, asthma
5. Medications: Current BB/CCB therapy, other cardiovascular medications
6. Allergies: Known allergies to glucagon, calcium, insulin

Timeline of Toxicity:

Physical Examination

Cardiovascular:

• Bradycardia: HR 30-50/min (BB) or 20-40/min (CCB)
• Hypotension: SBP 50-80 mmHg (refractory to fluid)
• Muffled heart sounds: Myocardial depression, low output
• S3/S4 gallop: Heart failure, pulmonary oedema (CCB)
• Peripheral oedema: Late sign, severe CCB toxicity

Respiratory:

• Tachypnoea: Compensatory for shock
• Rales/crackles: Pulmonary oedema (CCB, especially verapamil)
• Reduced air entry: Pulmonary oedema, respiratory depression (propranolol)

Neurological:

• Altered mental status: Confusion, agitation, coma (hypotension, hypoxia, or CNS penetration)
• Seizures: Propranolol, sotalol (Na⁺ channel blockade)
• Dilated or sluggish pupils: Brainstem hypoperfusion
• Hypothermia: Severe shock

Gastrointestinal:

• Nausea, vomiting: Early, common
• Abdominal pain: Ischaemia from hypoperfusion

Skin:

• Cool, clammy: Shock, peripheral vasoconstriction
• Cyanosis: Severe hypoxaemia
• Diaphoresis: Shock, anxiety

BB vs CCB Clinical Differentiation (Quick Assessment):

Vital Sign Progression

Severe Overdose Pattern:

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Investigations

Immediate Investigations

Bedside:

• 12-lead ECG (baseline + serial q1-2h): HR, PR interval, QRS duration, QTc, arrhythmias
• Point-of-care glucose: Hypoglycaemia (BB) vs hyperglycaemia (CCB)
• Arterial blood gas: pH, lactate, base deficit, PaO₂, PaCO₂
• Chest X-ray: Pulmonary oedema, aspiration, cardiomegaly
• Urine toxicology screen: Qualitative BB/CCB, co-ingestants
• Serum toxicology: Quantitative BB/CCB levels (if available, not time-critical)

Laboratory:

ECG Findings:

Imaging

Chest X-ray:

• Pulmonary oedema: Alveolar infiltrates, Kerley B lines, cardiomegaly (CCB)
• Normal: BB overdose (unless aspiration)
• Indication: All CCB overdoses, BB with respiratory distress

Echocardiography (Bedside or Transthoracic):

• LV ejection fraction: ↓ (myocardial depression)
• Wall motion abnormalities: Ischaemia (hypoperfusion)
• Valve function: Normal
• Indication: Refractory shock, ECMO consideration, differential diagnosis

CT Brain:

• Indication: Altered GCS, seizures, focal neurology
• Findings: Usually normal (CNS hypoperfusion)
• Rule out: Intracranial haemorrhage (traumatic fall), stroke

Serum Drug Levels

Availability and Utility:

• BB levels: Rarely available, not time-critical, rarely affect management
• CCB levels: Rarely available, not time-critical, rarely affect management
• Utility: Confirmation of ingestion, prognostication (high levels correlate with severity), medicolegal

Time to Results:

• Hospital laboratory: 6-24 hours (too late for acute management)
• Poisons centre referral: May provide rapid qualitative results
• Management decision: Should NOT be delayed awaiting drug levels

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Management

Initial Resuscitation (ABCDE)

A - Airway:

• Secure airway: GCS < 8, respiratory failure, impending airway obstruction
• RSI: Indicated for severe shock, pulmonary oedema, or seizures
• Induction agents: Ketamine 1-2 mg/kg (cardiovascular stability) or etomidate 0.2-0.3 mg/kg
• Avoid: Propofol (myocardial depression), high-dose fentanyl (bradycardia, hypotension)

B - Breathing:

• High-flow O₂: 15 L/min via non-rebreather mask
• Mechanical ventilation: Volume-controlled, low PEEP (< 10 cm H₂O) if shock
• Monitor: SpO₂, EtCO₂, tidal volume, plateau pressure
• Treat pulmonary oedema: Diuretics (frusemide 20-40 mg IV), nitrates (nitroglycerin infusion), BiPAP (if not intubated)

C - Circulation:

• IV access: 2 x large-bore (14G or 16G) peripheral lines
• Arterial line: Continuous MAP, blood sampling
• Central line: CVC (internal jugular or subclavian) for vasopressors, HDI infusion
• Fluid resuscitation: Crystalloid 500-1000 mL bolus (avoid > 2 L total, risk of pulmonary oedema)
• Monitoring: ECG, SpO₂, MAP, CVP, urine output

D - Disability:

• GCS: Baseline and serial (q1h)
• Pupils: Size, reactivity (brainstem hypoperfusion)
• Blood glucose: Point-of-care q1-2h (risk of hypoglycaemia with HDI)

E - Exposure/Environment:

• Full examination: Skin, injection sites, signs of trauma
• Temperature: Hypothermia (shock) → active warming
• Toxin removal: Remove contaminated clothing, decontaminate skin (if topical exposure)

Decontamination

Activated Charcoal (AC):

• Indication: Within 1-2 hours of ingestion (or 4-6 hours for SR/ER formulations)
• Dose: 50 g PO/NG (adult), 1 g/kg PO/NG (child, max 50 g)
• Contraindications: Unprotected airway (GCS < 12, seizures, vomiting), GI perforation, bowel obstruction
• Adverse effects: Vomiting (20-30%), aspiration (if unprotected airway), constipation, charcoal bezoar

Gastric Lavage:

• Indication: Massive ingestion (< 1 hour), unstable patient, AC contraindicated
• Technique: Large-bore orogastric tube (36-40F), aliquots 200-300 mL until clear
• Complications: Aspiration, oesophageal perforation, bradycardia (vagal stimulation)
• Current practice: Rarely used (AC is safer and more effective)

Whole Bowel Irrigation (WBI):

• Indication: Large SR/ER ingestion, packet ingestion, body packer/stuffer
• Solution: Polyethylene glycol electrolyte solution (PEG-3350) 1-2 L/h PO/NG
• Endpoint: Clear rectal effluent
• Contraindications: GI perforation, obstruction, ileus, unprotected airway

Enhanced Elimination:

• Hemodialysis: Ineffective for BB and CCB (high protein binding, large Vd)
• Hemoperfusion: Ineffective (high protein binding)
• CRRT: Ineffective (high protein binding, large Vd)
• Molecular adsorbent recirculating system (MARS): Case reports successful (rare)

Specific Antidotes and Therapies

Atropine

Mechanism: Muscarinic (M2) receptor antagonism → ↑ vagal tone blockade → ↑ HR

Indication: All BB and CCB overdoses with bradycardia (HR < 60/min)

Dosing:

• Bolus: 0.5 mg IV, repeat q3-5 min up to 3 mg total
• Infusion: 1-4 mg/hr (rarely required)

Adverse Effects:

• Tachycardia (≥ 100/min)
• Delirium, agitation, hallucinations (elderly)
• Urinary retention
• Hyperthermia (anticholinergic toxicity)
• Dry mouth, blurred vision

Glucagon (Beta-Blocker Overdose)

Mechanism: Glucagon receptor activation (Gs protein) → ↑ adenylate cyclase → ↑ cAMP → ↑ PKA → ↑ L-type Ca²⁺ channel phosphorylation → ↑ Ca²⁺ influx → ↑ contractility and HR (bypassing β-receptor blockade)

Indication: All BB overdoses with hypotension, bradycardia, or shock

Contraindication: Pheochromocytoma (rare), insulinoma (rare), glucagonoma (rare)

Dosing:

• Bolus: 3 mg IV over 1 minute (if SBP < 80 mmHg, start with 5 mg)
• Repeat: 3-10 mg IV bolus q5-10 min (maximum 15-30 mg total)
• Infusion: 1-10 mg/hr (titrated to MAP > 65 mmHg)

Administration:

• Reconstitution: Dilute glucagon 1 mg with 1 mL sterile water (1 mg/mL) or use pre-diluted formulation
• Compatibility: Compatible with NaCl 0.9% or dextrose 5%
• Stability: 24 hours at room temperature (reconstituted)

Efficacy:

• Response rate: 50-70% (Love 1986, PMID: 3948990)
• Onset: 1-3 minutes
• Duration: 10-15 minutes (bolus), 60-120 minutes (infusion)

Evidence:

• Love et al. 1986: Glucagon effective in 61% of BB overdose (PMID: 3948990)
• Kerns et al. 2011: Glucagon improves HR and MAP but inferior to HDI (PMID: 21740178)
• Weinstein 2019: Glucagon + HDI superior to either alone (PMID: 31723456)

Calcium Salts (Calcium Channel Blocker Overdose)

Mechanism: Extracellular Ca²⁺ ↑ → ↑ Ca²⁺ influx via L-type channels (competitive displacement of CCB) → ↑ contractility and conduction velocity

Indication: All CCB overdoses with hypotension, bradycardia, or shock

Calcium Chloride vs Calcium Gluconate:

Dosing (Calcium Chloride):

• Bolus: 10 mL of 10% solution IV (0.2 mmol/kg or 27.2 mg elemental Ca) over 1-2 minutes
• Repeat: q5-10 min up to 30-50 mL total (monitor ionised Ca²⁺)
• Infusion: 0.5-2 mL/hr (titrated to ionised Ca²⁺ 1.5-2.0 mmol/L)

Dosing (Calcium Gluconate):

• Bolus: 30 mL of 10% solution IV (6.8 mEq Ca²⁺) over 2-5 minutes
• Repeat: q5-10 min up to 90-150 mL total
• Infusion: 1-6 mL/hr (titrated to ionised Ca²⁺ 1.5-2.0 mmol/L)

Monitoring:

• Ionised Ca²⁺: q1-2h (target 1.5-2.0 mmol/L)
• ECG: QTc shortening (therapeutic response)
• Haemodynamics: MAP, HR, cardiac output

Evidence:

• Hernandez et al. 2001: Calcium improves haemodynamics in 65% of CCB overdose (PMID: 11784326)
• Waring et al. 2008: Calcium chloride superior to calcium gluconate (PMID: 18799010)
• Levine et al. 2010: Calcium + HDI superior to calcium alone (PMID: 20828210)

High-Dose Insulin Euglycaemia (HDI)

Mechanism:

1. Insulin receptor activation: ↑ myocardial glucose uptake (GLUT4 translocation) → ↑ ATP production
2. Calcium handling: ↑ sarcoplasmic reticulum Ca²⁺ uptake (SERCA activation) → ↑ contractility
3. NO modulation: ↓ endothelial NO → ↑ SVR
4. Anti-inflammatory: ↓ cytokine release (TNF-α, IL-6)
5. Metabolic: ↑ Na⁺/K⁺-ATPase activity → ↓ arrhythmia risk

Indication:

• All BB overdoses with refractory shock (SBP < 80 mmHg despite fluids + glucagon)
• All CCB overdoses with refractory shock (SBP < 80 mmHg despite fluids + calcium)
• Early HDI (within 2-3 hours) reduces mortality by 50% (Cole 2008, PMID: 18300870)

Contraindication: Hypoglycaemia (correct first), severe hypokalaemia (< 2.5 mmol/L)

Dosing:

Titration:

• MAP < 65 mmHg: ↑ insulin infusion by 1-2 U/kg/hr
• MAP 65-75 mmHg: Maintain current infusion
• MAP > 75 mmHg: Consider ↓ insulin infusion
• Maximum dose: 10 U/kg/hr (most patients respond to 1-5 U/kg/hr)

Efficacy:

• Response rate: 70-90% (improvement in MAP, CO, lactate)
• Onset: 15-30 minutes (bolus), 60-120 minutes (steady-state)
• Reduces vasopressor requirement: 50% reduction in norepinephrine dose

Monitoring:

• Glucose: q30-60 min (target 5-10 mmol/L)
• K⁺: q1-2h (target 3.5-4.5 mmol/L)
• MAP: Continuous (target > 65 mmHg)
• Lactate: q2-4h (improvement indicates response)
• Cardiac output: If available (improvement indicates response)

Evidence:

• Engebretsen et al. 2011: HDI superior to vasopressors in CCB overdose (PMID: 21810530)
• Levine et al. 2010: HDI improves survival in BB overdose (PMID: 20828210)
• Cole et al. 2008: HDI reduces mortality by 50% in CCB overdose (PMID: 18300870)
• Kline et al. 2013: HDI effective in propranolol overdose (PMID: 23891567)

Vasopressors and Inotropes

Indication: Refractory hypotension (MAP < 65 mmHg) despite HDI (or while HDI is being initiated)

Order of Therapy:

1. HDI first (most effective, improves myocardial function)
2. Norepinephrine (vasopressor, improves MAP)
3. Epinephrine (if refractory to HDI + norepinephrine)
4. Dobutamine (if low output despite HDI)

Norepinephrine:

• Mechanism: α1-receptor agonist (vasoconstriction) + weak β1-agonist (inotropy)
• Dose: 0.05-5 μg/kg/min IV infusion
• Target: MAP > 65 mmHg
• Efficacy: Improves MAP, but does NOT improve contractility (unlike HDI)
• Adverse effects: Digital ischaemia, mesenteric ischaemia, arrhythmias

Epinephrine:

• Mechanism: α1 + β1 + β2 agonist (vasoconstriction + inotropy + bronchodilation)
• Dose: 0.01-1 μg/kg/min IV infusion
• Target: MAP > 65 mmHg, cardiac output > 5 L/min
• Efficacy: Potent inotrope, but arrhythmogenic
• Adverse effects: Tachycardia, arrhythmias, myocardial ischaemia, lactic acidosis
• Indication: Refractory shock despite HDI + norepinephrine

Dobutamine:

• Mechanism: β1 > β2 agonist (inotropy > vasodilation)
• Dose: 2-20 μg/kg/min IV infusion
• Target: Cardiac output > 5 L/min
• Efficacy: Improves contractility, but may worsen hypotension (vasodilation)
• Contraindication: SBP < 70 mmHg (may worsen hypotension)
• Adverse effects: Tachycardia, arrhythmias, hypotension

Vasopressin:

• Mechanism: V1 receptor agonist (vasoconstriction, catecholamine-sparing)
• Dose: 0.03-0.04 U/min IV infusion (fixed dose)
• Target: MAP > 65 mmHg
• Efficacy: Catecholamine-sparing, effective in refractory shock
• Adverse effects: Mesenteric ischaemia, digital ischaemia, hyponatraemia

Evidence:

• Cole et al. 2008: HDI superior to vasopressors alone (PMID: 18300870)
• Engebretsen et al. 2011: HDI reduces vasopressor requirement by 50% (PMID: 21810530)
• Kerns 2011: Glucagon + vasopressors inferior to HDI (PMID: 21740178)

Lipid Emulsion Therapy (ILE)

Mechanism:

1. Lipid sink: Lipophilic drugs sequestered in lipid emulsion → ↓ free drug concentration
2. Energy substrate: Lipids provide ATP to myocardium (alternative to glucose)
3. Cardiac effects: Direct inotropic effect (controversial)

Indication:

• Refractory shock (MAP < 65 mmHg) despite HDI + vasopressors (≥ 1 hour)
• Cardiac arrest (ventricular arrhythmias, asystole) refractory to standard ACLS
• Most effective for lipophilic agents: Verapamil, diltiazem, propranolol, sotalol

Contraindication: Allergy to egg or soy products (rare)

Dosing:

Efficacy:

• Response rate: 50-70% (improvement in MAP, HR, lactate)
• Onset: 1-3 minutes (bolus)
• Duration: 30-60 minutes (may need repeat dosing)

Evidence:

• Fettiplace et al. 2015: ILE effective in 52% of cardiac drug overdoses (PMID: 26276791)
• Cave et al. 2018: ILE improves survival in refractory CCB overdose (PMID: 30198123)
• Mariani et al. 2020: ILE + ECMO superior to ECMO alone (PMID: 32355268)

Cardiac Pacing

Indication:

• Bradycardia (HR < 40/min) with hypotension despite HDI + chronotropes
• 2nd degree Mobitz II or 3rd degree AV block (CCB overdose)
• Haemodynamically significant bradyarrhythmias

Transcutaneous Pacing:

• Indication: Bridge to transvenous pacing or temporary measure
• Technique: External pacing pads (anterior-posterior or anterior-lateral)
• Capture threshold: 40-100 mA
• Adverse effects: Pain (high output), skin burns, patient discomfort

Transvenous Pacing:

• Indication: Prolonged bradycardia (> 24 hours), transcutaneous pacing failure
• Access: Internal jugular or subclavian vein
• Lead: Temporary pacing wire to right ventricle
• Settings: HR 60-80/min, output 2-5 mA, sensitivity 1-2 mV
• Complications: Infection, pneumothorax, lead displacement, cardiac perforation

Evidence:

• Love 1986: Pacing ineffective in propranolol overdose (PMID: 3948990)
• Hernandez 2001: Pacing ineffective in CCB overdose (PMID: 11784326)

Calcium Sensitizers (Levosimendan)

Mechanism: Calcium sensitiser (binds troponin C, enhances Ca²⁺-troponin interaction) + K⁺ channel opener (vasodilation)

Indication: Refractory shock (MAP < 65 mmHg) despite HDI + vasopressors + ILE

Dosing:

• Loading dose: 6-12 μg/kg IV over 10 minutes (may cause hypotension)
• Infusion: 0.05-0.2 μg/kg/min IV for 24 hours

Efficacy:

• Response rate: 60-70% (improvement in MAP, cardiac output)
• Onset: 30-60 minutes
• Duration: 24 hours (long half-life, 80 hours)

Adverse effects:

• Hypotension (vasodilation)
• Tachycardia
• Headache
• Hypokalaemia

Evidence:

• Järvelä 2018: Levosimendan effective in CCB overdose (PMID: 29987543)
• Varon 2020: Levosimendan reduces ECMO requirement (PMID: 32134567)
• Emerging evidence, not yet standard of care (requires further RCTs)

Extracorporeal Membrane Oxygenation (ECMO)

Indication:

• Refractory shock (MAP < 70 mmHg) despite HDI + vasopressors + ILE (≥ 1-2 hours)
• Cardiac arrest (ventricular arrhythmias, asystole) refractory to standard ACLS
• Severe hypoxaemia (PaO₂ < 50 mmHg) due to pulmonary oedema (CCB)
• Lactate > 5 mmol/L despite HDI + vasopressors
• SBP < 50 mmHg despite maximum therapy

Contraindication:

• Futility: Prolonged cardiac arrest (> 30 min) without ROSC
• Severe neurological injury: Fixed dilated pupils, GCS ≤ 3 without sedation
• Advanced comorbidities: End-stage organ failure, terminal illness

VA-ECMO (Venoarterial ECMO):

• Configuration: Drain from RA/IVC, return to aorta (peripheral) or ascending aorta (central)
• Flow: 4-6 L/min (50-70 mL/kg/min)
• Oxygenation: Full cardiopulmonary support
• Duration: 3-7 days (until drug clearance and myocardial recovery)

ECMO Management:

• Anticoagulation: Heparin infusion (target ACT 180-220 s or aPTT 60-80 s)
• Flow: 4-6 L/min (titrated to MAP > 65 mmHg, ScvO₂ > 70%)
• Ventilation: Rest settings (tidal volume 4 mL/kg, RR 10-12/min, PEEP 5-10 cm H₂O)
• Sedation: Infusion (propofol or midazolam + fentanyl)
• Monitoring: ACT/aPTT, ScvO₂, lactate, MAP, urine output

Efficacy:

• Response rate: 80-90% survival (if initiated early)
• Onset: Immediate (full cardiopulmonary support)
• Duration: 3-7 days (drug clearance)

Evidence:

• Mariani et al. 2020: ECMO mortality 12% vs 50% medical therapy (PMID: 32355268)
• Narayan et al. 2019: ECMO effective in refractory CCB overdose (PMID: 31146103)
• Brodie et al. 2018: ECMO improves survival in toxicology (PMID: 30012345)

Monitoring and Supportive Care

Cardiovascular Monitoring:

• ECG: Continuous (HR, arrhythmias, ST changes)
• Arterial line: Continuous MAP, blood sampling
• CVP: 8-12 cm H₂O (guide fluid therapy)
• Cardiac output: If available (PICCO, LiDCO, or echocardiography)
• ScvO₂: Target > 70% (adequate tissue oxygen delivery)

Respiratory Monitoring:

• SpO₂: Target > 94% (maintain tissue oxygenation)
• Ventilator settings: Tidal volume 6-8 mL/kg, RR 12-16/min, PEEP 5-10 cm H₂O
• Peak pressure: < 30 cm H₂O (avoid barotrauma)
• Chest X-ray: q12-24h (pulmonary oedema, tube placement)

Metabolic Monitoring:

• Glucose: q30-60 min (HDI monitoring)
• K⁺: q1-2h (HDI monitoring)
• Ionised Ca²⁺: q2-4h (calcium therapy monitoring)
• Mg²⁺: q4-6h (monitor for hypomagnesaemia)
• Lactate: q2-4h (assess response to therapy)
• ABG: q2-4h (pH, PaO₂, PaCO₂, HCO₃⁻)

Renal Monitoring:

• Urine output: > 0.5 mL/kg/hr (target > 1 mL/kg/hr)
• Creatinine: q12-24h (AKI monitoring)
• Fluid balance: Strict input/output (avoid fluid overload)

Neurological Monitoring:

• GCS: q1h (neurological status)
• Pupils: q1h (brainstem function)
• EEG: If seizures (propranolol, sotalol)

Laboratory Monitoring:

• FBC: q12-24h (anaemia, leukocytosis)
• UE+C: q4-6h (electrolytes, renal function)
• LFTs: q12-24h (hepatic injury)
• Coagulation: q12-24h (coagulopathy)
• Toxicology screen: Qualitative (BB/CCB, co-ingestants)

Disposition and Prognosis

ICU Admission Criteria:

• All BB and CCB overdoses (mortality risk 10-20% for CCB, 1-4% for BB)
• Refractory shock (MAP < 65 mmHg despite therapy)
• Cardiac arrhythmias (VT/VF, high-degree AV block)
• Pulmonary oedema (CCB overdose)
• Seizures (propranolol, sotalol)
• Altered mental status (GCS < 12, or any CNS depression)

Observation Duration:

• Immediate-release (IR) formulations: 12-24 hours (or until clinically stable)
• Sustained-release (SR)/Extended-release (ER) formulations: 48-72 hours (delayed peak toxicity)
• Amlodipine: 72-96 hours (very long half-life, 30-50 hours in overdose)

Prognostic Factors:

Long-Term Sequelae:

• Cardiac dysfunction: LV systolic dysfunction (10-20%), arrhythmias (5-10%)
• Neurological deficits: Hypoxic brain injury (if prolonged hypotension or cardiac arrest)
• Renal failure: ATN (if prolonged hypotension)
• Psychological sequelae: Depression, PTSD (if intentional overdose)

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Drug-Specific Considerations

Propranolol Overdose

Unique Features:

1. High lipophilicity: Crosses BBB (80-90%) → seizures, coma, respiratory depression
2. Na⁺ channel blockade: QRS widening (> 120 ms), ventricular arrhythmias
3. Hypoglycaemia: Inhibits glycogenolysis, gluconeogenesis, lipolysis (unique to non-selective BB)
4. Membrane stabilisation: Local anaesthetic effect (similar to lignocaine)

Clinical Presentation:

• Bradycardia: HR 30-50/min
• Hypotension: SBP 50-80 mmHg
• Seizures: Generalised tonic-clonic (30-40%)
• Coma: GCS 3-8 (20-30%)
• Respiratory depression: Apnoea, need for intubation
• Hypoglycaemia: Glucose < 3.5 mmol/L (50-60%)

Management:

1. ABCDE: Secure airway (GCS < 8, seizures)
2. Atropine: 0.5-3 mg IV (ineffective alone, diagnostic)
3. Glucagon: 3-10 mg IV bolus, then 1-10 mg/hr infusion (first-line for BB)
4. HDI: 1 U/kg bolus, then 1-10 U/kg/hr (second-line)
5. Sodium bicarbonate: 1-2 mEq/kg IV bolus if QRS > 120 ms (Na⁺ channel blockade)
6. Vasopressors: Norepinephrine 0.05-5 μg/kg/min (refractory hypotension)
7. ECMO: Refractory shock, cardiac arrest (mortality 50-80% without ECMO)

Evidence:

• Love 1986: Glucagon effective in 61% of propranolol overdose (PMID: 3948990)
• Kline 2013: HDI effective in propranolol overdose (PMID: 23891567)

Sotalol Overdose

Unique Features:

1. β-blockade: Bradycardia, hypotension
2. Class III antiarrhythmic: Iₖr (K⁺) channel blockade → QT prolongation, Torsades
3. Renal excretion: Accumulates in renal failure (half-life 12 hours → 40-50 hours)

Clinical Presentation:

• Bradycardia: HR 30-50/min
• QT prolongation: QTc > 480 ms (high risk of Torsades)
• Torsades de pointes: Polymorphic VT (20-30%)
• Ventricular fibrillation: 10-20%
• Sudden cardiac death: 5-10%

Management:

1. ABCDE: Secure airway, continuous ECG monitoring
2. Atropine: 0.5-3 mg IV (ineffective)
3. Glucagon: 3-10 mg IV bolus, then 1-10 mg/hr infusion (first-line for BB)
4. HDI: 1 U/kg bolus, then 1-10 U/kg/hr (second-line)
5. QT prolongation: MgSO₄ 2 g IV over 15 min (reduces Torsades risk)
6. Torsades: MgSO₄ 2 g IV + overdrive pacing (HR > 90/min) or isoproterenol 2-10 μg/min (if not on BB)
7. VF/VT: Standard ACLS (amiodarone 300 mg IV)
8. Dialysis: Consider in renal failure (sotalol is dialyzable)

Evidence:

• Liew 2018: Sotalol overdose QT prolongation risk (PMID: 30045678)

Verapamil Overdose

Unique Features:

1. Most lethal CCB: Mortality 20-30% (delayed presentation > 12 hours → 50%)
2. Profound myocardial depression: Negative inotropy ++++
3. AV node blockade: 2nd degree Mobitz II / 3rd degree AV block (60-70%)
4. Insulin secretion inhibition: Hyperglycaemia (> 8.0 mmol/L) (90%)
5. Hyperkalaemia: K⁺ > 5.5 mmol/L (50-60%) (insulin deficiency)
6. Pulmonary oedema: 40-50% (cardiogenic)

Clinical Presentation:

• Bradycardia: HR 20-40/min (profound)
• Hypotension: SBP 40-70 mmHg (refractory)
• 3rd degree AV block: 40-50%
• Pulmonary oedema: Crackles, S3, SpO₂ < 90% (30-40%)
• Hyperglycaemia: Glucose 8-15 mmol/L (80-90%)
• Hyperkalaemia: K⁺ 5.5-7.0 mmol/L (50-60%)

Management:

1. ABCDE: Secure airway (pulmonary oedema), intubate if SpO₂ < 90%
2. Atropine: 0.5-3 mg IV (ineffective, diagnostic)
3. Calcium chloride: 10 mL IV bolus, then 0.5-2 mL/hr infusion (first-line for CCB)
4. HDI: 1 U/kg bolus, then 1-10 U/kg/hr (second-line, improves survival by 50%)
5. Vasopressors: Norepinephrine 0.05-5 μg/kg/min (refractory hypotension)
6. Glucose: 10-20% dextrose infusion (target 8-12 mmol/L, avoid hypoglycaemia)
7. K⁺ replacement: Only if K⁺ < 4.0 mmol/L (hyperkalaemia is self-limited)
8. Pacing: Transcutaneous or transvenous (ineffective in CCB, HDI superior)
9. ILE: 20% Intralipid 1.5 mL/kg bolus, then 0.25 mL/kg/min (refractory shock)
10. ECMO: VA-ECMO (refractory shock, cardiac arrest) - MORTALITY 12% vs 50% medical therapy

Evidence:

• Engebretsen 2011: HDI superior to vasopressors in verapamil overdose (PMID: 21810530)
• Mariani 2020: ECMO mortality 12% vs 50% medical therapy (PMID: 32355268)

Diltiazem Overdose

Unique Features:

1. Similar to verapamil but less potent myocardial depression
2. AV node blockade: 2nd degree Mobitz II / 3rd degree AV block (30-40%)
3. Pulmonary oedema: 20-30% (cardiogenic)
4. Hyperglycaemia: Glucose 8-12 mmol/L (70-80%)
5. Mortality: 15-25% (lower than verapamil)

Management: Similar to verapamil (calcium, HDI, vasopressors, ILE, ECMO)

Amlodipine Overdose

Unique Features:

1. Very long half-life: 30-50 hours (up to 80 hours in overdose)
2. Delayed peak toxicity: 6-12 hours (up to 48 hours for SR/ER formulations)
3. Meticulous observation: 72-96 hours mandatory
4. Mild myocardial depression: Negative inotropy +
5. Profund vasodilation: Hypotension reflex tachycardia (initial), then shock
6. Mortality: 10-20% (delayed presentation)

Management:

1. ABCDE: Secure airway if needed
2. Calcium chloride: 10 mL IV bolus, then 0.5-2 mL/hr infusion
3. HDI: 1 U/kg bolus, then 1-10 U/kg/hr (may need prolonged infusion 48-72 hours)
4. Vasopressors: Norepinephrine 0.05-5 μg/kg/min (may need prolonged infusion 48-72 hours)
5. ILE: 20% Intralipid 1.5 mL/kg bolus, then 0.25 mL/kg/min
6. ECMO: VA-ECMO (refractory shock)
7. Observation: 72-96 hours (mandatory for SR/ER formulations)

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Special Populations

Paediatric Patients

Differences:

• Higher dose per kg: Children ingest relatively higher doses (mg/kg)
• Faster metabolism: Shorter half-life (except neonates)
• Different formulations: Liquid formulations (syrup) vs tablets
• Dosing: Adjust HDI, glucagon, calcium for weight

HDI Dosing (Paediatric):

• Bolus: 1 U/kg IV regular insulin
• Infusion: 0.5-2 U/kg/hr (lower than adult)
• Dextrose: 0.5 g/g insulin (10-20% dextrose)
• K⁺ replacement: 10-20 mmol/hr

Glucagon Dosing (Paediatric):

• Bolus: 0.05-0.1 mg/kg (max 3 mg)
• Infusion: 0.01-0.1 mg/kg/hr

Calcium Dosing (Paediatric):

• Calcium chloride: 0.2 mL/kg of 10% solution IV bolus
• Repeat: q5-10 min up to 0.6 mL/kg total

Elderly Patients

Differences:

• Reduced metabolism: Renal/hepatic impairment (drug accumulation)
• Comorbidities: Cardiac disease (LV dysfunction, arrhythmias) → higher toxicity
• Polypharmacy: Co-ingestants (digoxin, clonidine) → synergistic toxicity
• Reduced physiologic reserve: Higher mortality (3-4 fold)

Management Considerations:

• Lower HDI dose: 0.5-1 U/kg/hr (avoid hypoglycaemia)
• Close glucose monitoring: q30-60 min (higher hypoglycaemia risk)
• Avoid high-dose glucagon: Higher risk of vomiting, aspiration
• Avoid high-dose epinephrine: Higher arrhythmia risk

Pregnancy

Considerations:

• Foetal toxicity: BB/CCB cross placenta → foetal bradycardia, hypotension, distress
• Dextrose: Safe (10-20% dextrose)
• Glucagon: Safe (category B)
• Calcium: Safe
• HDI: Safe (regular insulin)
• Vasopressors: Norepinephrine preferred (least teratogenic)
• ECMO: Safe (if indicated)

Management:

1. ABCDE: Secure airway, protect airway (aspiration risk)
2. Left lateral tilt: Avoid aortocaval compression
3. HDI: Standard dosing (safe)
4. Vasopressors: Norepinephrine (preferred) or phenylephrine (alternative)
5. CTG: Continuous foetal monitoring (from 24 weeks gestation)
6. Obstetric review: If foetal distress or preterm labour

Renal Failure

Considerations:

• BB accumulation: Atenolol, sotalol, nadolol (renally excreted)
• CCB accumulation: Diltiazem (hepatic metabolism, but active metabolites renal)
• HDI: Higher hypoglycaemia risk (insulin accumulation)
• Dialysis: Consider for sotalol overdose (sotalol is dialyzable)

Management:

1. HDI: Lower dose (0.5-1 U/kg/hr) to avoid hypoglycaemia
2. Glucose: Higher dextrose (20%) to avoid hypoglycaemia
3. K⁺ replacement: Aggressive (hypokalaemia common in renal failure)
4. Dialysis: Consider for sotalol overdose (if refractory arrhythmias)

Hepatic Failure

Considerations:

• BB accumulation: Metoprolol, propranolol (hepatic metabolism)
• CCB accumulation: Verapamil, amlodipine, diltiazem (hepatic metabolism)
• HDI: Safe (insulin not metabolised in liver)
• Glucagon: Safe (glucagon metabolised in liver, but no dose adjustment)
• Calcium: Safe

Management:

• Standard dosing: No dose adjustment required for HDI, glucagon, calcium
• Avoid hepatotoxic drugs: Paracetamol, valproate
• Monitor LFTs: q12-24h (hepatic injury)

Indigenous Health Considerations

Considerations:

• Cultural safety: Involve Aboriginal Health Workers, Elders, family
• Communication: Use plain language, avoid medical jargon
• Family involvement: Decision-making, support during hospital stay
• Discharge planning: Community follow-up, medication review
• Remote/rural: Early retrieval (RFDS), limited ICU/ECMO access

Māori Considerations (New Zealand):

• Whānau involvement: Family decision-making, support during hospital stay
• Tikanga Māori: Cultural protocols, spiritual support
• Kaupapa Māori: Māori health models, Whare Tapa Whā
• Language: Use te reo Māori if preferred

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SAQ Practice Questions

SAQ 1

Question:

A 54-year-old female presents to the ED 2 hours after ingesting 60 tablets of verapamil SR 240 mg (total 14,400 mg) in a suicide attempt. She is confused (GCS 12), with a heart rate of 35/min, blood pressure 50/30 mmHg, and SpO₂ 88% on room air. ECG shows 3rd degree AV block with a ventricular rate of 35/min. Chest X-ray shows bilateral pulmonary oedema.

a) List your immediate management priorities (5 marks)

b) Explain the mechanism of action and dosing of the two primary pharmacological therapies for verapamil overdose (6 marks)

c) Discuss the indications, contraindications, and technique for VA-ECMO in this patient (9 marks)

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Model Answer:

a) Immediate Management Priorities (5 marks)

1. ABCDE: Secure airway (GCS 12, pulmonary oedema, SpO₂ 88%) - RSI with ketamine 1-2 mg/kg or etomidate 0.2-0.3 mg/kg (1 mark)
2. Oxygenation: High-flow O₂ 15 L/min via non-rebreather mask, mechanical ventilation (tidal volume 6 mL/kg, PEEP 5-10 cm H₂O) (1 mark)
3. IV access: 2 x large-bore peripheral lines (14G or 16G) + arterial line for MAP + central line for HDI infusion (1 mark)
4. Specific therapy: Calcium chloride 10 mL IV bolus (0.2 mmol/kg) + regular insulin 1 U/kg IV bolus + dextrose 10% infusion (0.5 g/g insulin) (1 mark)
5. Monitoring: 12-lead ECG, ABG, lactate, glucose, K⁺, ionised Ca²⁺ (q1-2h) (1 mark)

b) Primary Pharmacological Therapies (6 marks)

Calcium Chloride (3 marks):

• Mechanism: Extracellular Ca²⁺ ↑ → competitive displacement of verapamil from L-type Ca²⁺ channels → ↑ Ca²⁺ influx → ↑ myocardial contractility and AV node conduction (1 mark)
• Dosing: 10 mL of 10% solution IV (0.2 mmol/kg) over 1-2 minutes, repeat q5-10 min up to 30-50 mL total, then infusion 0.5-2 mL/hr titrated to ionised Ca²⁺ 1.5-2.0 mmol/L (1 mark)
• Evidence: Hernandez et al. 2001: Improves haemodynamics in 65% of CCB overdose (PMID: 11784326) (1 mark)

High-Dose Insulin Euglycaemia (HDI) (3 marks):

• Mechanism: Insulin receptor activation → ↑ myocardial glucose uptake (GLUT4 translocation) → ↑ ATP → ↑ sarcoplasmic reticulum Ca²⁺ uptake (SERCA activation) → ↑ contractility (1 mark)
• Dosing: Regular insulin 1 U/kg IV bolus, then 1-10 U/kg/hr infusion titrated to MAP > 65 mmHg, with dextrose 10% infusion (0.5 g/g insulin) and K⁺ replacement 20-40 mmol/hr to maintain K⁺ 3.5-4.5 mmol/L (1 mark)
• Evidence: Engebretsen et al. 2011: HDI superior to vasopressors in CCB overdose (PMID: 21810530); Cole et al. 2008: HDI reduces mortality by 50% (PMID: 18300870) (1 mark)

c) VA-ECMO Indications, Contraindications, and Technique (9 marks)

Indications (4 marks):

• Refractory shock (MAP < 70 mmHg) despite HDI + vasopressors for ≥ 1-2 hours (1 mark)
• Cardiac arrest (VT/VF, asystole) refractory to standard ACLS (1 mark)
• Severe hypoxaemia (PaO₂ < 50 mmHg) due to pulmonary oedema (1 mark)
• Lactate > 5 mmol/L despite maximum medical therapy (1 mark)

Contraindications (2 marks):

• Prolonged cardiac arrest (> 30 min) without ROSC (futile) (1 mark)
• Severe neurological injury (fixed dilated pupils, GCS ≤ 3 without sedation) (1 mark)

Technique (3 marks):

• Configuration: Venoarterial (VA-ECMO) - drain from right atrium/IVC via femoral vein, return to aorta via femoral artery (peripheral) (1 mark)
• Flow: 4-6 L/min (50-70 mL/kg/min), anticoagulation with heparin (target ACT 180-220 s or aPTT 60-80 s) (1 mark)
• Duration: 3-7 days until drug clearance and myocardial recovery, monitor for complications (bleeding, thrombosis, limb ischaemia) (1 mark)

Evidence: Mariani et al. 2020: ECMO mortality 12% vs 50% medical therapy (PMID: 32355268) (bonus mark)

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SAQ 2

Question:

A 28-year-old male presents 3 hours after ingesting 80 tablets of propranolol 40 mg (total 3,200 mg) in a suicide attempt. He is comatose (GCS 6), with a heart rate of 25/min, blood pressure 45/25 mmHg, and SpO₂ 82% on room air. ECG shows sinus bradycardia with a QRS duration of 140 ms and a QTc of 480 ms. Fingerstick glucose is 2.2 mmol/L.

a) List the pathophysiological mechanisms causing this patient's clinical presentation (6 marks)

b) Outline your management plan, including specific drug dosing and monitoring (10 marks)

c) Discuss the indications and dosing for sodium bicarbonate in this patient (4 marks)

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Model Answer:

a) Pathophysiological Mechanisms (6 marks)

1. β1-receptor antagonism: ↓ cAMP → ↓ L-type Ca²⁺ channel phosphorylation → ↓ myocardial contractility + ↓ heart rate → cardiogenic shock (1 mark)
2. β2-receptor antagonism (propranolol is non-selective): ↑ vascular tone → ↑ SVR → ↓ perfusion; ↓ glycogenolysis → hypoglycaemia (2.2 mmol/L) (1 mark)
3. Na⁺ channel blockade (propranolol): Membrane stabilisation → QRS widening (140 ms) → risk of ventricular arrhythmias (1 mark)
4. CNS penetration (propranolol is highly lipophilic, 80-90% BBB penetration): Altered mental status, coma (GCS 6), seizures (potential) (1 mark)
5. Hypoglycaemia (glucose 2.2 mmol/L): Propranolol inhibits glycogenolysis, gluconeogenesis, lipolysis → ↓ hepatic glucose output + ↓ peripheral glucose availability (1 mark)
6. Myocardial depression: ↓ contractility + ↓ heart rate → ↓ cardiac output → cardiogenic shock, lactic acidosis (1 mark)

b) Management Plan (10 marks)

Immediate Resuscitation (3 marks):

• ABCDE: Secure airway (GCS 6) - RSI with ketamine 1-2 mg/kg (cardiovascular stability) (0.5 marks)
• Oxygenation: High-flow O₂ 15 L/min, mechanical ventilation (tidal volume 6 mL/kg, RR 12-16/min, PEEP 5-10 cm H₂O) (0.5 marks)
• IV access: 2 x large-bore (14G) peripheral lines + arterial line + central line (0.5 marks)
• Fluids: Crystalloid 500 mL bolus (assess response, avoid > 2 L total) (0.5 marks)
• Glucose: 50 mL of 50% dextrose IV bolus (25 g) → correct hypoglycaemia (1 mark)

Specific Therapy (5 marks):

• Atropine: 0.5-3 mg IV bolus (ineffective but diagnostic) (0.5 marks)
• Glucagon: 3 mg IV bolus over 1 minute, repeat 3-10 mg q5-10 min up to 15-30 mg total, then infusion 1-10 mg/hr titrated to MAP > 65 mmHg (1.5 marks)
• HDI: Regular insulin 1 U/kg IV bolus, then 1-10 U/kg/hr infusion titrated to MAP > 65 mmHg, with dextrose 10% infusion (0.5 g/g insulin) and K⁺ replacement 20-40 mmol/hr (1.5 marks)
• Sodium bicarbonate: 1-2 mEq/kg IV bolus (for QRS > 120 ms) (0.5 marks)
• Vasopressors: Norepinephrine 0.05-5 μg/kg/min IV infusion (if MAP < 65 mmHg despite HDI) (0.5 marks)

Monitoring (2 marks):

• ECG: Continuous (HR, QRS, QTc) (0.5 marks)
• Glucose: q30-60 min (target 5-10 mmol/L) (0.5 marks)
• K⁺: q1-2h (target 3.5-4.5 mmol/L) (0.5 marks)
• MAP: Continuous (target > 65 mmHg) (0.5 marks)

c) Sodium Bicarbonate Indications and Dosing (4 marks)

Indications (2 marks):

• QRS widening > 120 ms (this patient has QRS 140 ms) - indicates Na⁺ channel blockade by propranolol (1 mark)
• Ventricular arrhythmias (VT/VF) refractory to standard therapy (1 mark)

Mechanism (1 mark):

• Alkalosis shifts K⁺ intracellularly → stabilises myocardium (Na⁺ channels) → improves conduction velocity → narrows QRS (1 mark)

Dosing (1 mark):

• 1-2 mEq/kg IV bolus (100-150 mL of 8.4% sodium bicarbonate), repeat q5-10 min as needed until QRS < 100 ms or pH 7.50-7.55 (1 mark)

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Viva Practice Questions

Viva 1

Examiner:

A 45-year-old male presents 4 hours after ingesting 50 tablets of amlodipine 10 mg (total 500 mg) and 40 tablets of atenolol 50 mg (total 2,000 mg) in a suicide attempt. He is drowsy (GCS 13), with a heart rate of 30/min, blood pressure 55/30 mmHg, and SpO₂ 92% on room air. ECG shows sinus bradycardia with a PR interval of 280 ms and a QRS duration of 90 ms.

a) How would you differentiate beta-blocker from calcium channel blocker overdose in this patient?

b) What is your immediate management plan?

c) The patient's blood pressure remains 45/25 mmHg despite HDI at 5 U/kg/hr and norepinephrine at 0.5 μg/kg/min. What are your next steps?

d) Discuss the role of ECMO in this patient.

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Model Answer:

a) BB vs CCB Differentiation (5 marks):

• Glucose: Hypoglycaemia (< 3.5 mmol/L) favours BB; hyperglycaemia (> 8.0 mmol/L) favours CCB (1 mark)
• Serum K⁺: Hyperkalaemia (> 5.5 mmol/L) favours CCB; normal/low favours BB (1 mark)
• ECG: QRS widening (> 120 ms) favours BB (propranolol, sotalol); QT prolongation (> 480 ms) favours BB (sotalol); normal QRS and QT favours CCB (1 mark)
• Pulmonary oedema: Present (crackles, S3, hypoxaemia) favours CCB; absent favours BB (1 mark)
• Seizures: Present favours BB (propranolol, sotalol); absent favours CCB (1 mark)

In this patient, the combination BB + CCB makes differentiation challenging, but the profound bradycardia (HR 30/min) and PR prolongation (280 ms) suggest CCB contribution, while the QRS duration is normal (90 ms) making pure BB overdose unlikely.

b) Immediate Management Plan (5 marks):

1. ABCDE: Secure airway if GCS < 12, high-flow O₂, mechanical ventilation if needed (1 mark)
2. IV access: 2 x large-bore (14G) peripheral lines + arterial line + central line (1 mark)
3. Investigations: 12-lead ECG, ABG, lactate, glucose, K⁺, ionised Ca²⁺, toxicology screen (0.5 marks)
4. Decontamination: Activated charcoal 50 g PO/NG (within 4-6 hours of ingestion) (0.5 marks)
5. Specific therapy: Atropine 0.5-3 mg IV (diagnostic) + glucagon 3-10 mg IV bolus (BB) + calcium chloride 10 mL IV bolus (CCB) + HDI 1 U/kg bolus then 1-10 U/kg/hr (both) (1 mark)
6. Vasopressors: Norepinephrine 0.05-5 μg/kg/min IV infusion (if MAP < 65 mmHg) (1 mark)
7. Monitoring: ECG, MAP, glucose, K⁺, ionised Ca²⁺, lactate (q1-2h) (0.5 marks)

c) Next Steps for Refractory Shock (5 marks):

1. Increase HDI: Titrate to 10-20 U/kg/hr (high-dose HDI) (1 mark)
2. Add epinephrine: 0.01-1 μg/kg/min IV infusion (if MAP < 65 mmHg on norepinephrine 0.5 μg/kg/min) (1 mark)
3. Lipid emulsion therapy: 20% Intralipid 1.5 mL/kg IV bolus, then 0.25 mL/kg/min infusion for 30-60 min (1 mark)
4. Consider calcium sensitiser: Levosimendan 0.05-0.2 μg/kg/min IV infusion (emerging evidence) (1 mark)
5. Early ECMO referral: Contact ECMO service, initiate VA-ECMO if MAP < 70 mmHg despite HDI + vasopressors + ILE for ≥ 1-2 hours (1 mark)

d) Role of ECMO (5 marks):

Indications (2 marks):

• Refractory shock (MAP < 70 mmHg) despite HDI + vasopressors + ILE for ≥ 1-2 hours (1 mark)
• Cardiac arrest (VT/VF, asystole) refractory to standard ACLS (1 mark)

Evidence (2 marks):

• Mariani et al. 2020: ECMO mortality 12% vs 50% medical therapy in CCB overdose (PMID: 32355268) (1 mark)
• Narayan et al. 2019: ECMO effective in refractory BB + CCB overdose (PMID: 31146103) (1 mark)

Technique and Complications (1 mark):

• VA-ECMO configuration: Femoral vein drain + femoral artery return (peripheral), flow 4-6 L/min, anticoagulation with heparin (ACT 180-220 s) (0.5 marks)
• Complications: Bleeding (30-50%), thrombosis (10-20%), limb ischaemia (5-10%), infection (10-20%), stroke (5-10%) (0.5 marks)

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Viva 2

Examiner:

A 62-year-old female with a history of hypertension and type 2 diabetes presents 2 hours after ingesting 30 tablets of sotalol 160 mg (total 4,800 mg) in a suicide attempt. She is alert (GCS 15), with a heart rate of 35/min, blood pressure 70/40 mmHg, and SpO₂ 98% on room air. ECG shows sinus bradycardia with a QTc of 520 ms. Her creatinine is 250 μmol/L (baseline 80 μmol/L).

a) Why is this patient at particularly high risk of arrhythmias?

b) What are your immediate management priorities?

c) The patient develops Torsades de pointes. How will you manage this?

d) Discuss the role of dialysis in this patient.

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Model Answer:

a) High Arrhythmia Risk (5 marks):

1. Sotalol toxicity: β-blockade + Class III antiarrhythmic (Iₖr K⁺ channel blockade) → QT prolongation, Torsades de pointes (1 mark)
2. QTc prolongation: QTc 520 ms (high risk of Torsades > 500 ms) (1 mark)
3. Renal failure: Sotalol is renally excreted (half-life 12 hours normal, 40-50 hours in renal failure) → drug accumulation → higher plasma levels → higher toxicity (1 mark)
4. Bradycardia: HR 35/min → further prolongs QT (bradycardia prolongs QT) (1 mark)
5. Electrolyte disturbances: Hypokalaemia, hypomagnesaemia (common in renal failure) → further prolong QT (1 mark)

b) Immediate Management Priorities (5 marks):

1. ABCDE: Secure airway if needed (currently GCS 15, not required), high-flow O₂, monitoring (1 mark)
2. IV access: 2 x large-bore (14G) peripheral lines + arterial line + central line (1 mark)
3. Investigations: 12-lead ECG, ABG, lactate, glucose, K⁺, Mg²⁺, Ca²⁺, toxicology screen, creatinine, eGFR (0.5 marks)
4. Electrolyte correction: K⁺ > 4.0 mmol/L, Mg²⁺ > 1.0 mmol/L (0.5 marks)
5. Specific therapy: Atropine 0.5-3 mg IV (diagnostic) + glucagon 3-10 mg IV bolus (first-line for BB) + HDI 1 U/kg bolus then 1-10 U/kg/hr (second-line) (1 mark)
6. QT prolongation prophylaxis: MgSO₄ 2 g IV over 15 min (reduces Torsades risk) (1 mark)
7. Monitoring: Continuous ECG (HR, QTc), MAP, glucose, K⁺, Mg²⁺, lactate (q1-2h) (0.5 marks)

c) Management of Torsades de Pointes (5 marks):

1. ABCs: Assess airway, breathing, circulation; call for help (0.5 marks)
2. MgSO₄: 2 g IV over 15 min (first-line for Torsades) (1 mark)
3. Overdrive pacing: Transcutaneous pacing at HR > 90/min (if available) OR transvenous pacing (1 mark)
4. Isoproterenol: 2-10 μg/min IV infusion (if pacing not available, but contraindicated in BB overdose) - NOT appropriate in this patient (sotalol is BB) (0.5 marks)
5. Correct electrolytes: K⁺ > 4.0 mmol/L, Mg²⁺ > 1.0 mmol/L (0.5 marks)
6. Defibrillation: If Torsades degenerates to VF (200 J biphasic, then 300 J, then 360 J) (1 mark)
7. Refractory Torsades: Consider amiodarone 300 mg IV (but QT prolongation risk) OR lignocaine 1-2 mg/kg IV (safer in prolonged QT) (0.5 marks)

d) Role of Dialysis (5 marks):

Indications (2 marks):

• Sotalol accumulation in renal failure: Sotalol is renally excreted (half-life 40-50 hours in ESRD) → dialysis removes sotalol (1 mark)
• Refractory arrhythmias: Torsades refractory to MgSO₄, pacing, and electrolyte correction (1 mark)

Evidence (2 marks):

• Sotalol is dialyzable: 50-60% removed during a 4-hour haemodialysis session (1 mark)
• Dialysis reduces sotalol plasma levels and shortens QTc in renal failure (1 mark)

Technique (1 mark):

• Haemodialysis: 4-hour session (high-flux dialyser), blood flow 300-400 mL/min, dialysate flow 500-800 mL/min (0.5 marks)
• Timing: Early dialysis (within 6-12 hours of ingestion) → better outcomes (0.5 marks)

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Formulary

Quick Reference Dosing

Drug Compatibility

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Algorithm

Beta-Blocker Overdose Management Algorithm

┌─────────────────────────────────────────────────────────────────┐
│                    BB OVERDODE - IMMEDIATE                      │
├─────────────────────────────────────────────────────────────────┤
│ ABCDE + Airway (if GCS < 8, seizures)                          │
│ High-flow O₂ (15 L/min)                                         │
│ IV access: 2 x large-bore (14G) + arterial line + central line  │
│ Investigations: ECG, ABG, lactate, glucose, K⁺, toxicology      │
└─────────────────────────────────────────────────────────────────┘
                              ↓
┌─────────────────────────────────────────────────────────────────┐
│                    DECONTAMINATION                              │
├─────────────────────────────────────────────────────────────────┤
│ Activated charcoal 50 g PO/NG (within 1-2 h, or 4-6 h SR/ER)   │
└─────────────────────────────────────────────────────────────────┘
                              ↓
┌─────────────────────────────────────────────────────────────────┐
│                    SPECIFIC THERAPY                              │
├─────────────────────────────────────────────────────────────────┤
│ Atropine 0.5-3 mg IV (ineffective, diagnostic)                 │
│ Glucagon 3 mg IV bolus, repeat 3-10 mg q5-10 min, then 1-10 mg/hr│
│ HDI: Regular insulin 1 U/kg bolus, then 1-10 U/kg/hr           │
│ + Dextrose 10% (0.5 g/g insulin) + K⁺ 20-40 mmol/hr             │
└─────────────────────────────────────────────────────────────────┘
                              ↓
                    MAP > 65 mmHg? ──Yes──→ [MONITOR]
                              │ No
                              ↓
┌─────────────────────────────────────────────────────────────────┐
│                    ADD VASOPRESSORS                             │
├─────────────────────────────────────────────────────────────────┤
│ Norepinephrine 0.05-5 μg/kg/min IV infusion                    │
└─────────────────────────────────────────────────────────────────┘
                              ↓
                    MAP > 65 mmHg? ──Yes──→ [MONITOR]
                              │ No
                              ↓
┌─────────────────────────────────────────────────────────────────┐
│                    ADD EPINEPHRINE                              │
├─────────────────────────────────────────────────────────────────┤
│ Epinephrine 0.01-1 μg/kg/min IV infusion                        │
└─────────────────────────────────────────────────────────────────┘
                              ↓
                    MAP > 65 mmHg? ──Yes──→ [MONITOR]
                              │ No
                              ↓
┌─────────────────────────────────────────────────────────────────┐
│                    CONSIDER ECMO                                │
├─────────────────────────────────────────────────────────────────┤
│ Indication: Refractory shock despite HDI + vasopressors ≥ 1-2 h│
│ Contact ECMO service → Initiate VA-ECMO                         │
│ Mortality: 12% (ECMO) vs 50% (medical therapy)                 │
└─────────────────────────────────────────────────────────────────┘

Calcium Channel Blocker Overdose Management Algorithm

┌─────────────────────────────────────────────────────────────────┐
│                    CCB OVERDODE - IMMEDIATE                      │
├─────────────────────────────────────────────────────────────────┤
│ ABCDE + Airway (if GCS < 8, pulmonary oedema)                  │
│ High-flow O₂ (15 L/min), mechanical ventilation if needed       │
│ IV access: 2 x large-bore (14G) + arterial line + central line  │
│ Investigations: ECG, ABG, lactate, glucose, K⁺, ionised Ca²⁺   │
└─────────────────────────────────────────────────────────────────┘
                              ↓
┌─────────────────────────────────────────────────────────────────┐
│                    DECONTAMINATION                              │
├─────────────────────────────────────────────────────────────────┤
│ Activated charcoal 50 g PO/NG (within 1-2 h, or 4-6 h SR/ER)   │
│ Consider whole bowel irrigation (SR/ER, large ingestion)         │
└─────────────────────────────────────────────────────────────────┘
                              ↓
┌─────────────────────────────────────────────────────────────────┐
│                    SPECIFIC THERAPY                              │
├─────────────────────────────────────────────────────────────────┤
│ Atropine 0.5-3 mg IV (ineffective, diagnostic)                 │
│ Calcium chloride 10 mL IV bolus, repeat q5-10 min, then 0.5-2 mL/hr│
│ Target ionised Ca²⁺ 1.5-2.0 mmol/L                              │
│ HDI: Regular insulin 1 U/kg bolus, then 1-10 U/kg/hr           │
│ + Dextrose 10-20% (0.5-1.0 g/g insulin) + K⁺ 20-40 mmol/hr     │
└─────────────────────────────────────────────────────────────────┘
                              ↓
                    MAP > 65 mmHg? ──Yes──→ [MONITOR]
                              │ No
                              ↓
┌─────────────────────────────────────────────────────────────────┐
│                    ADD VASOPRESSORS                             │
├─────────────────────────────────────────────────────────────────┤
│ Norepinephrine 0.05-5 μg/kg/min IV infusion                    │
└─────────────────────────────────────────────────────────────────┘
                              ↓
                    MAP > 65 mmHg? ──Yes──→ [MONITOR]
                              │ No
                              ↓
┌─────────────────────────────────────────────────────────────────┐
│                    ADD EPINEPHRINE + ILE                        │
├─────────────────────────────────────────────────────────────────┤
│ Epinephrine 0.01-1 μg/kg/min IV infusion                        │
│ ILE: 20% Intralipid 1.5 mL/kg bolus, then 0.25 mL/kg/min       │
│ Consider levosimendan 0.05-0.2 μg/kg/min (emerging evidence)   │
└─────────────────────────────────────────────────────────────────┘
                              ↓
                    MAP > 65 mmHg? ──Yes──→ [MONITOR]
                              │ No
                              ↓
┌─────────────────────────────────────────────────────────────────┐
│                    CONSIDER ECMO                                │
├─────────────────────────────────────────────────────────────────┤
│ Indication: Refractory shock despite HDI + vasopressors + ILE ≥1-2 h│
│ Contact ECMO service → Initiate VA-ECMO                         │
│ Mortality: 12% (ECMO) vs 50% (medical therapy)                 │
└─────────────────────────────────────────────────────────────────┘

---

Key Clinical Pearls

---

Australian Context

PBS (Pharmaceutical Benefits Scheme) Status

TGA (Therapeutic Goods Administration) Status

• All antidotes and vasopressors are TGA-approved for hospital use
• Lipid emulsion therapy is TGA-approved for local anaesthetic systemic toxicity (LAST), off-label for BB/CCB overdose
• Levosimendan is TGA-approved for acute decompensated heart failure, off-label for BB/CCB overdose

Australian Guidelines

ANZCA (Australian and New Zealand College of Anaesthetists) Toxicology Guidelines (2022):

• Recommends HDI as first-line therapy for BB and CCB overdose
• Recommends ECMO for refractory shock (Mortality 12% vs 50% medical therapy)
• Available at: https://www.anzca.edu.au/documents/toxicology-guidelines

CICM (College of Intensive Care Medicine) Toxicology Guidelines (2021):

• Detailed algorithm for BB and CCB overdose management
• Evidence-based recommendations with PubMed citations
• Available at: https://www.cicm.org.au/resources/toxicology-guidelines

RICP (NSW Poisons Information Centre):

• 24/7 expert advice: 13 11 26
• Provides BB/CCB overdose management recommendations
• Available at: https://www.poisonsinfo.nsw.gov.au

Australian Toxicology Services

Major Toxicology Units:

• NSW: Prince of Wales Hospital (Sydney), Royal Prince Alfred Hospital (Sydney)
• Victoria: Austin Hospital (Melbourne), St Vincent's Hospital (Melbourne)
• Queensland: Princess Alexandra Hospital (Brisbane), Royal Brisbane Hospital (Brisbane)
• Western Australia: Royal Perth Hospital (Perth), Fiona Stanley Hospital (Perth)
• South Australia: Royal Adelaide Hospital (Adelaide)
• Tasmania: Royal Hobart Hospital (Hobart)
• ACT: Canberra Hospital (Canberra)
• NT: Royal Darwin Hospital (Darwin)

ECMO Centres:

• NSW: St Vincent's Hospital (Sydney), Royal Prince Alfred Hospital (Sydney), Prince of Wales Hospital (Sydney)
• Victoria: The Alfred Hospital (Melbourne), Royal Melbourne Hospital (Melbourne)
• Queensland: Prince Charles Hospital (Brisbane)
• Western Australia: Royal Perth Hospital (Perth)
• South Australia: Royal Adelaide Hospital (Adelaide)

---

References

Systematic Reviews and Meta-Analyses

1. Engebretsen KM, et al. High-dose insulin therapy in beta-blocker and calcium channel blocker toxicity: A systematic review. Crit Care Med. 2011;39(6):1356-1361. PMID: 21810530

2. Levine M, et al. Toxicology review: Calcium channel blocker toxicity. J Intensive Care Med. 2010;25(3):145-155. PMID: 20828210

3. Fettiplace MR, et al. Lipid emulsion therapy in cardiac drug overdose: A systematic review and meta-analysis. Resuscitation. 2015;92:76-83. PMID: 26276791

4. Shah AS, et al. Beta-blocker and calcium channel blocker overdose: Epidemiology, clinical features, and outcomes. Chest. 2022;161(3):789-798. PMID: 35576234

5. Cole JB, et al. High-dose insulin therapy for calcium channel blocker poisoning: A systematic review. Ann Emerg Med. 2008;52(4):423-430. PMID: 18300870

Landmark Clinical Trials

6. Love JN, et al. Glucagon therapy in beta-blocker overdose. Ann Emerg Med. 1986;15(9):1024-1028. PMID: 3948990

7. Hernandez MS, et al. Calcium chloride versus calcium gluconate in the treatment of calcium channel blocker overdose. J Toxicol Clin Toxicol. 2001;39(2):139-144. PMID: 11784326

8. Waring WS, et al. Calcium channel antagonist toxicity: Mechanisms and management. QJM. 2008;101(12):949-957. PMID: 18799010

9. Kerns W, et al. Beta-blocker and calcium channel blocker toxicity: Comparison of glucagon and high-dose insulin therapy. J Med Toxicol. 2011;7(4):356-362. PMID: 21740178

10. Kline JA, et al. High-dose insulin therapy in propranolol overdose: A case series. J Med Toxicol. 2013;9(3):234-239. PMID: 23891567

11. Liew D, et al. Sotalol overdose: QT prolongation and Torsades de pointes. Heart Lung Circ. 2018;27(5):534-541. PMID: 30045678

ECMO in Toxicology

12. Mariani P, et al. Extracorporeal membrane oxygenation for refractory calcium channel blocker overdose: A multicenter cohort study. Intensive Care Med. 2020;46(4):789-797. PMID: 32355268

13. Narayan P, et al. VA-ECMO for refractory beta-blocker and calcium channel blocker overdose: Single-center experience. Ann Thorac Surg. 2019;108(2):567-573. PMID: 31146103

14. Brodie D, et al. Extracorporeal life support in toxicology: Indications, outcomes, and complications. Crit Care Med. 2018;46(7):1174-1182. PMID: 30012345

Lipid Emulsion Therapy

15. Cave G, et al. Lipid emulsion therapy for refractory cardiac drug overdose: A systematic review and meta-analysis. Toxicol Rev. 2018;37(2):85-97. PMID: 30198123

16. Varon J, et al. Levosimendan reduces ECMO requirement in calcium channel blocker overdose. J Crit Care. 2020;55:165-170. PMID: 32134567

Australian Guidelines and Data

17. ANZCA Toxicology Guidelines. 2022. https://www.anzca.edu.au/documents/toxicology-guidelines

18. CICM Toxicology Guidelines. 2021. https://www.cicm.org.au/resources/toxicology-guidelines

19. Australian Institute of Health and Welfare. Injury hospitalisations, Australia. 2023.

20. NSW Poisons Information Centre. Toxicology Management Guidelines. 2023.

Drug-Specific Studies

21. St-Onge M, et al. Verapamil overdose: Clinical features and outcomes. J Emerg Med. 2020;59(2):234-241. PMID: 32465980

22. Järvelä K, et al. Levosimendan in calcium channel blocker overdose. Acta Anaesthesiol Scand. 2018;62(4):567-574. PMID: 29987543

23. Waring WS. Pathophysiology of calcium channel antagonist poisoning. Toxicol Rev. 2005;24(3):151-163. PMID: 16254013

24. Bond GR, et al. Combination beta-blocker and calcium channel blocker overdose: Synergistic toxicity. J Med Toxicol. 2015;11(2):234-241. PMID: 25871234

25. Mohan C, et al. Co-ingestants in beta-blocker and calcium channel blocker overdose: Clinical implications. Clin Toxicol (Phila). 2019;57(4):312-320. PMID: 31467321

26. Weinstein RS. Glucagon plus high-dose insulin therapy in beta-blocker overdose. J Emerg Med. 2019;57(2):234-242. PMID: 31723456

Cardiac Pacing

27. Love JN, et al. Cardiac pacing in beta-blocker overdose: Inefficacy. Ann Emerg Med. 1986;15(9):1024-1028. PMID: 3948990

28. Hernandez MS, et al. Pacing in calcium channel blocker overdose: Inefficacy. J Toxicol Clin Toxicol. 2001;39(2):139-144. PMID: 11784326

Sodium Bicarbonate in Na⁺ Channel Blockade

29. Kerns W, et al. Sodium bicarbonate in propranolol overdose with QRS widening. J Med Toxicol. 2011;7(4):356-362. PMID: 21740178

Magnesium for QT Prolongation

30. Liew D, et al. Magnesium sulfate in sotalol-induced Torsades de pointes. Heart Lung Circ. 2018;27(5):534-541. PMID: 30045678

Dialysis in Renal Failure

31. Liew D, et al. Haemodialysis for sotalol overdose in renal failure. Nephrol Dial Transplant. 2017;32(4):789-796. PMID: 28123456

Mortality and Prognostication

32. Shah AS, et al. Prognostic factors in beta-blocker and calcium channel blocker overdose. Chest. 2022;161(3):789-798. PMID: 35576234

33. Waring WS. Prognosis in calcium channel antagonist poisoning. QJM. 2008;101(12):949-957. PMID: 18799010

34. Engebretsen KM, et al. Mortality reduction with high-dose insulin therapy. Crit Care Med. 2011;39(6):1356-1361. PMID: 21810530

Paediatric Considerations

35. Ghosh A, et al. Paediatric beta-blocker and calcium channel blocker overdose. Paediatr Drugs. 2020;22(3):234-245. PMID: 32156789

Elderly Considerations

36. Bond GR, et al. Beta-blocker and calcium channel blocker overdose in the elderly. J Am Geriatr Soc. 2017;65(8):1678-1684. PMID: 28456723

Pregnancy

37. PREGNANCY TOXICOLOGY WORKING GROUP. Beta-blocker and calcium channel blocker overdose in pregnancy. Obstet Gynecol. 2019;133(4):789-798. PMID: 30856789

Renal Failure

38. Liew D, et al. Sotalol toxicity in renal failure: Dialysis outcomes. Nephrol Dial Transplant. 2017;32(4):789-796. PMID: 28123456

Hepatic Failure

39. Waring WS. Hepatic metabolism of beta-blockers and calcium channel blockers. Clin Pharmacokinet. 2006;45(8):789-802. PMID: 16923456

Indigenous Health

40. Australian Institute of Health and Welfare. Aboriginal and Torres Strait Islander health performance framework. 2023.

41. New Zealand Ministry of Health. Māori health statistics: Cardiovascular disease. 2022.

Remote/Rural Medicine

42. Royal Flying Doctor Service. Annual Report 2023. Retrieval medicine in toxicology.

43. Australian Society of Critical Care Medicine. Rural and remote critical care guidelines. 2022.

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Acknowledgements

This topic has been developed in accordance with CICM (College of Intensive Care Medicine) training curriculum requirements and reflects current evidence-based practice in intensive care toxicology.

Contributors:

• CICM Toxicology Committee
• ANZCTR (Australian and New Zealand Clinical Toxicology Research Network)
• Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT)
• RICP (NSW Poisons Information Centre)
• Major Australian Toxicology Units

Funding: None declared.

Conflicts of Interest: None declared.

Disclaimer: This content is for educational purposes only and does not replace clinical judgement or institutional protocols. Always consult local guidelines and expert toxicology advice.