Doctor123.org

Calcium Channel Blocker Poisoning, Emergency Medicine

Basics

Description

- 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

- 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

- ABCs: - Airway protection, as indicated - Supplemental oxygen, as needed - 0.9% NS IV access

- 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

- 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

- Amrinone: - Selective phosphodiesterase inhibitor - Indirectly increases cAMP leading to increased inotropy

  • 3 classes of calcium channel blockers (CCBs):Phenylalkylamines (verapamil):Vasodilation resulting in a decrease in BPNegative chronotropic and inotropic effects: Reflex tachycardia not seen with a drop in BP.Dihydropyridine (nifedipine):Decreased vascular resistance resulting in a drop in BPLittle negative inotropic effect: Reflex tachycardia occursBenzothiazepine (diltiazem):Decreased peripheral vascular resistance leading to a decrease in BPHeart rate (HR) and cardiac output initially increasedDirect negative chronotropic effect, which leads to a fall in HR
  • Effects of calcium channel blockadeCalcium plays key role in cardiac and smooth muscle contractilityCCBs preventthe entry of calcium, resulting in a lack of muscle contractionthe normal release of insulin from pancreatic islet cells, resulting in hyperglycemia

Diagnosis

Signs and Symptoms

  • Cardiovascular:HypotensionBradycardiaReflex tachycardia (dihydropyridine)Conduction abnormalities/heart blocks
  • Neurologic:CNS depressionComaSeizuresAgitationConfusion
  • 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, glucoseStrongly consider CCB overdose in the setting of bradycardia, hypotension, and hyperglycemiaDegree 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 indicatedSupplemental oxygen, as needed0.9% 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+/mLDoes not cause tissue necrosis as calcium chloride doesCalcium 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 extravasationVery 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 cellsResults in inefficient fatty acid metabolismHDI 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 anotherInstitute invasive monitoring to help guide treatment.Dopamine:β1-Receptor agonist at low doses, which causes a positive inotropic effect on the myocardiumα-Receptor agonist at higher doses, which leads to vasoconstrictionEpinephrine:Potent α- and β-receptor agonist
  • Amrinone:Selective phosphodiesterase inhibitorIndirectly increases cAMP leading to increased inotropy
  • Electrical pacing: When other treatment options have failed
  • Potential future therapies:Hypertonic sodium bicarbonateIV 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)