II. Pathophysiology

  1. Calcium Channel Blocker Overdose is treated similarly to Beta Blocker Overdose
    1. Hyperglycemia in CCB (Hypoglycemia with BB)
  2. Most severe Overdose effects are with Non-Dihydropyridines (Verapamil, Diltiazem)
  3. In Overdose, Dihydropyridines lose their peripheral selectivity and suppress cardiac activity

III. Types: Presentation

  1. Vasoplegic Shock
    1. Results from vasodilation due to DihydropyridineOverdose (e.g. Amlodipine)
    2. Heart activity will be hyperdynamic on Bedside Ultrasound
    3. Skin is warm despite Hypotension
  2. Cardiogenic Shock
    1. Results from decreased contractility and Bradycardia due to Verapamil or DiltiazemOverdose
    2. Poor contractility on Bedside Ultrasound
    3. Appropriately cool skin (Vasoconstriction)
  3. Mixed Presentation
    1. Calcium Channel Blockers lose their selectivity in Overdose
    2. Poor contractility on Bedside Ultrasound (as with Cardiogenic Shock)
    3. Skin is warm despite Hypotension due to inappropriate vasodilation (as with vasoplegic shock)

IV. Findings: Symptoms and Signs

  1. Primary effects
    1. Bradycardia
    2. Hypotension
    3. Arrhythmia
  2. Other effects
    1. Tachycardia
    2. Coma
    3. Dizziness
    4. Lethargy
    5. Seizures
    6. Warm distal extremities (due to peripheral vasodilation)
  3. Beta-islet cell blockade effects
    1. Hyperglycemia (Calcium Channel Blocker Overdose)
      1. Insulin exit from cell is via the same channel that CCB agents block
      2. Calcium Channel Blockers result in relative Insulin Resistance and Hyperglycemia
      3. Serum Glucose >250 mg/dl (without Diabetes Mellitus) suggests severe Overdose
      4. Contrast with Beta Blocker Overdose
        1. Associated with Hypoglycemia (due to beta-2 Adrenergic Receptor block)
    2. Cardiac Muscle reduced Glucose uptake
      1. Fatty Acid oxidation increased
      2. Results in Metabolic Acidosis and in some cases, Cardiogenic Shock

V. Management: Adults (Beta Blocker and Calcium channel Overdose)

  1. Gastric Decontamination (e.g. Activated Charcoal, Gastric Lavage, Whole Bowel Irrigation)
    1. Consider if ingestion within last 1 hour, active bowel sounds and alert, cooperative patient (or airway secured)
    2. Exercise caution, as Beta Blocker Overdose patients rapidly decompensate and become obtunded
  2. Epinephrine
    1. Indicated for Hypotension or severe Bradycardia
    2. Start: 1 mcg/kg/min
    3. Typically need to titrate to higher dose (esp. Beta Blockers) to overcome Catecholamine blockade
  3. Calcium Replacement
    1. Calcium infusion has transient stabilization effects
      1. Do not be falsely reassured, as patient will once again decompensate after effects dissipate
      2. Other measures must be simultaneously implemented
    2. Calcium Gluconate (10% solution, if Peripheral IV Access)
      1. Bolus: 0.6 ml/kg (60 mg/kg up to 3 g) over 5-10 minutes
      2. Next: Infuse at 0.6 to 1.5 ml/kg/hour
      3. May give up to 3-6 ampule boluses of Calcium Gluconate in Peri-Arrest patients
    3. Calcium Chloride (if Central IV Access)
      1. Bolus: 20 mg/kg (up to 1 g/dose)
      2. May use one third of peripheral dose of Calcium Gluconate
      3. In Peri-Arrest or Cardiac Arrest, often used peripherally, despite risk of local adverse effects
  4. Glucagon
    1. Mechanism
      1. Acts at cardiac cells, increasing intracellular Calcium and cAMP, increased myocardial contractions
      2. Glucagon bypasses blocked receptors, and allows Calcium influx (usually Catecholamine mediated)
      3. Results in Catecholamine-independent receptor effects (sites not affected by BB or CCB)
      4. Most effective in Beta Blocker Overdose (more than Calcium Channel Blocker Overdose)
    2. Expect Nausea and Vomiting (ALOC patients may be at risk for aspiration)
      1. Give Antiemetic when starting Glucagon
    3. Initial: 3 to 5 mg (50-150 mcg/kg) IV bolus slowly over 1-2 minutes
    4. Next: May repeat at increased dose of 4 to 10 mg in 5 minutes if no effect
    5. Next: Infusion at effective dose
      1. Glucagon in 5% dextrose solution at 3-5 mg/h (50-150 mcg/kg/h) for 12-48 hours
      2. Maximum dose: 10 mg/h
  5. Insulin Euglycemia protocol
    1. Indications
      1. Vasoplegic shock with normal or depressed Cardiac Function
    2. Mechanism
      1. Heart typically uses Fatty Acids preferentially over Carbohydrates
      2. High dose Insulin promotes heart Carbohydrate Metabolism with direct inotropic effects
      3. Insulin also moves Calcium into Myocytes and increases contractility
      4. Onset of action in 15-60 minutes
    3. Precautions
      1. Keep Serum Glucose 100-250 mg/dl
      2. Insulin doses are 10 fold higher than that used in Diabetic Ketoacidosis (high risk of Hypoglycemia)
      3. Beta Blocker Overdose is already at risk for Hypoglycemia (Unlike Hyperglycemia of CCB Overdose)
    4. Start
      1. Regular Insulin 1 IU/kg IV and
      2. D50 given as 50 ml bolus IV if Blood Glucose <200 mg/dl
        1. Have D50 available at bedside
        2. Otherwise start dextrose infusion as below
    5. Next (continued for 9 to 72 hours)
      1. Regular Insulin 0.5 to 1 IU/kg/hour IV (Central IV Access preferred) and
      2. D10 infused at 100 ml/h and titrate to Blood Glucose >100 mg/dl
        1. Typical adult dextrose doses are 15-30 grams per hour (typically up to 0.5 g/kg/h)
    6. Goals
      1. Heart Rate >50 bpm
      2. Blood Pressure 100 mmHg or greater
    7. Monitoring
      1. Bedside Glucose
        1. Initial: Every 15-20 minutes
        2. Later: Every 30-60 minutes once on stable dose of Insulin and dextrose
      2. Serum Potassium (risk of Hypokalemia)
        1. Initial: Every 1 hour
        2. Later: Every 6 hours once on stable dose of Insulin and dextrose
      3. Consider Magnesium and Phosphorus monitoring
  6. Other measures with variable efficacy
    1. Intravenous Lipid Emulsion (Intralipid)
      1. Strongly consider for lipophilic agents (may be very effective)
      2. May be effective for Amlodipine, Verapamil, Betaxolol, Carvedilol, Metoprolol, Propranolol, Timolol
    2. Sodium Bicarbonate (1 mEq/ml solution)
      1. Indicated for QRS Widening (due to Sodium channel blockade similar to TCA Overdose)
      2. Dose: 50 mEq bolus
    3. Methylene blue
      1. Aggarwal (2013) BMJ Case Rep. +PMID:23334490 [PubMed]
      2. Jang (2015) Ann Emerg Med 65(4): 410–415 [PubMed]
    4. Extracorporeal Membrane Oxygenation (VA-ECMO)
      1. Indicated in refractory cases of Cardiogenic Shock or mixed presentation
      2. Braud (2007) Critical Care [PubMed]
      3. St Ange (2017) Crit Care Med 45(3): e306-15 [PubMed]
    5. Vasopressors for Hypotension
      1. May be effective in Hypotension due to pure vasoplegic shock with hyperdynamic cardiac activity
      2. However, less effective in Cardiogenic Shock or mixed presentation
      3. Norepinephrine doses are much higher than typical (as high as 100-300 mcg/min)
        1. Contrast with typical Norepinephrine infusions maxing at 30 mcg/min
        2. Closely monitor
          1. Warmth of extremities (persistent vasodilation)
          2. Cardiac Function (hyperdynamic)
      4. Consider adding Vasopressin to the Norepinephrine
      5. Consider Epinephrine for inotropic effect
  7. Avoid ineffective measures
    1. Atropine
      1. Typically ineffective, but may be trialed
    2. Cardiac pacing (typically ineffective)

VI. Management: Children (Beta Blocker and Calcium channel Overdose)

  1. See above for more detailed explanations under the adult dosing protocols
  2. Consider Gastric Decontamination (as above)
  3. Glucagon
    1. Initial: 50-150 mcg/kg IV bolus
    2. Next: May repeat in 3-5 minutes
    3. Next: 0.1 mg/kg/hour infusion
  4. Calcium Gluconate (10% solution)
    1. Bolus: 0.6 ml/kg (60 mg/kg) over 5-10 minutes
    2. Next: Infuse at 0.6 to 1.5 ml/kg/hour
  5. Epinephrine
    1. Start: 1 mcg/kg/min (up to 10-30 mcg/min)
    2. May need to titrate to higher dose
  6. Insulin Euglycemia protocol
    1. See adult protocol above for more specific details
    2. Children are higher risk of Hypoglycemia (esp. with Beta Blocker Overdose)
    3. Keep Serum Glucose 100-250 mg/dl
    4. Start
      1. Regular Insulin 1 IU/kg IV and
      2. Dextrose 25 g IV
    5. Next
      1. Regular Insulin 0.5 IU/kg/hour IV and
      2. Dextrose 0.5 g/kg/hour
  7. Sodium Bicarbonate (1 mEq/ml solution)
    1. Indicated only if QRS interval widening >120 ms
    2. Dose: 1-2 mEq/kg up to 50 mEq bolus

VII. References

  1. Hegg and Eyre (2017) Crit Dec Emerg Med 31(8): 11
  2. Swaminathan, Weingart and Nordt in Herbert (2020) EM:Rap 20(3): 9-10
  3. Yen (2015) Crit Dec Emerg Med 29(10): 18-23
  4. Anderson (2005) Clin Pediatr Emerg Med 6(2): 109-15 [PubMed]
  5. Kerns (2007) Emerg Med Clin North Am 25(2):309-31 [PubMed]

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