Physiology and Pathophysiology
Block slow calcium channels in the myocardium and vascular smooth muscle leading to varying degrees of negative ionotropy, conduction blockade, and vasodilation depending upon the CCB ingested
force of myocardial contractility and vascular tone is proportional to the amount of intracellular calcium which is required to bind to actin-myosin
calcium enters cells during Phase 2 of the action potential via slow calcium channels
Clinical
severe toxicity affects multiple systems, but the CV toxicity is responsible for most of the morbidity and mortality
CV - hypotension, sinus brady, sinus arrest, AV block, junctional rhythm, asystole
Resp - respiratory depression, apnea, pulmonary edema, ARDS
GI - nausea, vomiting, bowel infarction
Neurologic - lethargy, confusion, coma, seizures, infarction
Metabolic - lactic acidosis, hyperglycemia, hyperkalemia
Toxicity can be delayed for 24-36 hours with sustained release preparations
Treatment
Fluids
crystalloids to correct relative intravascular depletion secondary to vasodilation
improves contractility by increasing preload
Calcium Chloride
excess extracellular calcium may overcome some of the CC blockade, however the failure rate is greater than 50% in severe toxicity, more effective at improving contractility thambradycardia or vasodilation
CaCl has 14.6mEq/10cc vs 4.3mEq/10 cc of calcium gluconate
Must exclude the possibility of digoxin toxicity as calcium could lead to systolic tetany and asystolic cardiac arrest.
The optimal dose is not known. Up to 8 g of CaCl has been given without adverse effects. However hypercalcemia could cause lethargy, AMS, hyporelexia, weakness, ataxia, decreased GI motility, nausea, anorexia, vomiting, abdominal pain, constipation, pancreatitis. At high levels hypercalcemia can lead to heart blocks and cardiac depression.
In view of low success rate and potential for toxicity, the general recommendations are for 2 to 3 amps ( 20 -30 cc) of 10% CaCl, then monitor serum calcium levels and start a constant infusion at 5 -10 ml/hr if necessary
Glucagon
increases intracellular cAMP by specific noncatecholamine receptors leading to increased release of calcium from sarcoplasmic reticulum stores
Swan-Ganz catheter directed ionotropes
need to distinguish between negative ionotropic effects and vasodilation
any increase in afterload in the face of a poorly functioning ventricle may further decrease cardiac output (caution with Epi, NE, phenylephrine)
since peripheral vasodilation with a low SVR seems to be the predominant hemodynamic derangement in the majority of CCB overdoses a drug with strong alpha agonists activity would appear to be the best choice and multiple case reports with NE supoort this. However, this should not be given without a Swan-Ganz catheter as an increase in afterload with poor myocardial contractility can be detrimental
Amrinone/milrinone -phosphodiesterase inhibitors which increase ionotropy via non-catecholamine mechanisms, may act synergidstically with glucagon
Atropine, Isuprel
have been used for bradycardia with disappointing results
Temporary pacer - TCP or TVP
Intra-aortic ballon pump or cardiopulmonary bypass - case reports demonstrate utility as temporizing supportive measures while waiting for drug elimination