Basics
Description
- 3 classes of calcium channel blockers (CCBs):
- Phenylalkylamines (verapamil):
- Vasodilation resulting in a decrease in BP
- Negative chronotropic and inotropic effects: Reflex tachycardia not seen with a drop in BP.
- Dihydropyridine (nifedipine):
- Decreased vascular resistance resulting in a drop in BP
- Little negative inotropic effect: Reflex tachycardia occurs
- Benzothiazepine (diltiazem):
- Decreased peripheral vascular resistance leading to a decrease in BP
- Heart rate (HR) and cardiac output initially increased
- Direct negative chronotropic effect, which leads to a fall in HR
- Effects of calcium channel blockade
- Calcium plays key role in cardiac and smooth muscle contractility
- CCBs prevent
- the entry of calcium, resulting in a lack of muscle contraction
- the normal release of insulin from pancreatic islet cells, resulting in hyperglycemia
Diagnosis
Signs and Symptoms
- Cardiovascular:
- Hypotension
- Bradycardia
- Reflex tachycardia (dihydropyridine)
- Conduction abnormalities/heart blocks
- Neurologic:
- CNS depression
- Coma
- Seizures
- Agitation
- Confusion
- Metabolic:
History
- Inquire about risk of medication error.
- Inquire about risk of suicidal ideation with intent.
- Inquire about possible exposure to medications with a pediatric patient.
Physical Exam
- Hypotension
- Bradycardia
- Skin may be warm instead of cool and clammy.
Essential Workup
ECG:
- Bradycardia (reflex tachycardia with nifedipine)
- Conduction delays: QRS complex prolongation
- Heart blocks
Diagnosis Tests & Interpretation
Lab
- Ionized calcium level when administering calcium
- Digoxin level if patient taking digoxin (dictate safety of calcium administration)
- CBC
- Electrolytes, BUN, creatinine, glucose
- Strongly consider CCB overdose in the setting of bradycardia, hypotension, and hyperglycemia
- Degree of hyperglycemia may correlate with severity of CCB poisoning in nondiabetics
- Toxicology screen if coingestants suspected
Differential Diagnosis
- β-Blocker toxicity
- Clonidine toxicity
- Digitalis toxicity
- Acute myocardial infarction with heart block
Treatment
Pre-Hospital
- Transport pill/pill bottles to ED
- Calcium for bradycardic/unstable patient with confirmed CCB overdose
Initial Stabilization/Therapy
- ABCs:
- Airway protection, as indicated
- Supplemental oxygen, as needed
- 0.9% NS IV access
- Hemodynamic monitoring
Ed Treatment/Procedures
Goals
- HR >60 beats/min
- Systolic BP >90 mm Hg
- Adequate urine output
- Improving level of consciousness
GI-Decontamination
- Syrup of ipecac: Contraindicated in the pre-hospital and ED setting
- Activated charcoal:
- May be helpful, especially in the presence of coingestants
Calcium
- Usually only transiently effective
- Calcium gluconate (10%):
- Contains 0.45 mEq Ca2+/mL
- Does not cause tissue necrosis as calcium chloride does
- Calcium gluconate: Preferred agent in an acidemic patient
- Calcium chloride (10%):
- Contains 1.36 mEq Ca2+/mL (3 times more calcium than calcium gluconate)
- Can cause tissue necrosis and sloughing with extravasation
- Very irritating to veins
- Follow serum calcium levels if repeated doses of calcium administered.
- Contraindicated in known digoxin toxicity because calcium may cause serious adverse effects in this setting
Bradycardia/Hypotension
- IV fluids:
- Administer cautiously in the hypotensive patient.
- Swan-Ganz catheter or central venous pressure (CVP) monitoring to help follow volume status
- Atropine usually ineffective
- High-dose insulin (HDI):
- CCBs cause myocardial insulin resistance and inhibit insulin release from pancreatic islet cells
- Results in inefficient fatty acid metabolism
- HDI promotes more efficient myocardial carbohydrate metabolism and has been shown to improve hemodynamic function
- Vasopressor agents:
- No clear evidence that 1 agent is more effective than another
- Institute invasive monitoring to help guide treatment.
- Dopamine:
- β1-Receptor agonist at low doses, which causes a positive inotropic effect on the myocardium
- α-Receptor agonist at higher doses, which leads to vasoconstriction
- Epinephrine:
- Potent α- and β-receptor agonist
- Amrinone:
- Selective phosphodiesterase inhibitor
- Indirectly increases cAMP leading to increased inotropy
- Electrical pacing: When other treatment options have failed
- Potential future therapies:
- Hypertonic sodium bicarbonate
- IV fat emulsion (20% intralipid)
Medication
- Amrinone: Loading dose 0.75 mg/kg; maintenance drip 2-20 μg/kg/min; titrate for effect
- Atropine: 0.5 mg (peds: 0.02 mg/kg) IV; repeat 0.5-1 mg IV (peds: 0.04 mg/kg)
- Calcium chloride: 5-10 mL of 10% solution slow IVP (peds: 0.2-0.25 mL/kg; repeat in 10 min if necessary) followed by infusion 20-50 mg/kg/h
- Calcium gluconate: 10-20 mL of 10% solution slow IVP (peds: 1 mL/kg; may repeat in 10 min if necessary)
- Dextrose: 50 mL of 50% solution (peds: 0.25 g/kg of 25% solution)
- Dopamine: 2-20 μg/kg/min; titrate to effect
- Epinephrine: 1-2 μg/min (peds: 0.01 mg/kg or 0.1 mL/kg 1:10,000); titrate to effect
- Norepinephrine: Start 2-4 μg/min IV; titrate up to 1-2 μg/kg/min IV
- Potassium: 40 mEq PO or IV
High-dose Insulin Treatment Protocol
- Should be considered if response to fluid resuscitation is inadequate
- Insulin (regular insulin): 1 IU/kg bolus IV followed by 0.5-1 IU/kg/h titrated up to clinical response
- Administer dextrose if blood glucose <200 mg/dL
- Administer potassium if serum potassium <2.5 mEq/L
- Monitor serum glucose and potassium concentrations every 30 min for the 1st 4 hr
- Approximate 24-hr insulin requirement: 1,500 U of regular insulin for adult patient
First Line
- IV fluids
- Calcium
- HDI
- Vasopressor agents
Second Line
Follow-Up
Disposition
Admission Criteria
- Admit symptomatic patients to a monitored bed for hemodynamic monitoring.
- Admit all patients who ingested sustained-release CCBs for 24-hr observation and monitoring owing to the potential delay in symptoms.
Discharge Criteria
Discharge asymptomatic patients 8 hr after ingestion of immediate-release preparation.
Follow-Up Recommendations
- Psychiatric evaluation for all suicidal patients
- Poison prevention guidance for parents of pediatric accidental ingestion
Pearls and Pitfalls
- Consider CCB toxicity in patients presenting hypotensive and bradycardic.
- Consider suicidal gesture in patients presenting with CCB toxicity.
- Consider HDI with dextrose and potassium if fluid resuscitation not rapidly effective.
Additional Reading
- Greene SL, Gawarammana I, Wood DM, et al. Relative safety of hyperinsulinaemia/euglycaemia therapy in the management of calcium channel blocker overdose: A prospective observational study. Intensive Care Med. 2007;33:2019-2024.
- Levine M, Boyer EW, Pozner CN, et al. Assessment of hyperglycemia after calcium channel blocker overdoses involving diltiazem or verapamil. Crit Care Med. 2007;35:2071-2075.
- Shepherd G. Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers. Am J Health Syst Pharm. 2006;63:1828-1835.
- Shepherd G, Klein-Schwartz W. High-dose insulin therapy for calcium-channel blocker overdose. Ann Pharmacother. 2005;39:923-930.
See Also (Topic, Algorithm, Electronic Media Element)
β-Blocker, Poisoning
Codes
ICD9
972.9 Poisoning by other and unspecified agents primarily affecting the cardiovascular system
ICD10
- T46.1X1A Poisoning by calcium-channel blockers, accidental, init
- T46.1X2A Poisoning by calcium-channel blockers, self-harm, init
- T46.1X4A Poisoning by calcium-channel blockers, undetermined, init
SNOMED
- 212715006 Poisoning by calcium-channel blockers
- 291287004 Accidental poisoning by calcium-channel blockers
- 291288009 Intentional poisoning by calcium-channel blockers (event)
- 291289001 Poisoning by calcium-channel blockers of undetermined intent (disorder)