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. 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 which is associated with Hypoglycemia
    2. Cardiac muscle reduced Glucose uptake
      1. Fatty Acid oxidation increased
      2. Results in Metabolic Acidosis and in some cases, Cardiogenic Shock

IV. Management: Adults (Beta Blocker and calcium channel Overdose)

  1. Gastric Decontamination (e.g. Activated Charcoal)
    1. Consider if ingestion within last 1 hour, active bowel sounds and alert, cooperative patient
    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 over 5-10 minutes
      2. Next: Infuse at 0.6 to 1.5 ml/kg/hour
    3. Calcium Chloride (if Central IV Access)
      1. May use one third of peripheral dose
  4. Glucagon
    1. Mechanism
      1. Acts at cardiac cells, increasing intracellular calcium, 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 4-10 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. Mechanism
      1. Heart typically uses Fatty Acids preferentially over carbohydrates
      2. High dose Insulin promotes heart carbohydrate metabolism with direct inotropic effects
      3. Onset of action in 15-60 minutes
    2. 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)
    3. Start
      1. Regular Insulin 1 IU/kg IV and
      2. D50 given as 50 ml bolus IV if Blood Glucose <200 mg/dl
        1. Otherwise start dextrose infusion as below
    4. 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)
    5. Goals
      1. Heart Rate >50 bpm
      2. Blood Pressure 100 mmHg or greater
    6. 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. ECMO
      1. Braud (2007) Critical Care [PubMed]
      2. St Ange (2017) Crit Care Med 45(3): e306-15 [PubMed]
  7. Avoid ineffective measures
    1. Atropine (typically ineffective)
    2. Cardiac pacing (typically ineffective)

V. Management: Children (Beta Blocker and calcium channel Overdose)

  1. See above for more detailed explanations under the adult dosing protocols
  2. 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
  3. Calcium Gluconate (10% solution)
    1. Bolus: 0.6 ml/kg over 5-10 minutes
    2. Next: Infuse at 0.6 to 1.5 ml/kg/hour
  4. Epinephrine
    1. Start: 1 mcg/kg/min (up to 10-30 mcg/min)
    2. May need to titrate to higher dose
  5. 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
  6. 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

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Ontology: Overdose of calcium-channel blockers (C0573229)

Concepts Injury or Poisoning (T037)
SnomedCT 296355001
English OD of calcium-channel blockers, blockers calcium channel overdose, calcium channel blocker overdose, overdose of calcium-channel blockers, Overdose of calcium-channel blockers, Overdose of calcium-channel blockers (disorder)
Spanish sobredosis de fármacos bloqueantes de los canales del calcio (trastorno), sobredosis de fármacos bloqueantes de los canales del calcio