Week #48: Calcium Channel Blocker, Beta-Blocker, and Digoxin Overdoses

The ECG demonstrates atrial fibrillation. Patients with atrial fibrillation are usually on medication for rate control.Digoxin is used therapeutically for two reasons: 1) to improve the contractility of the heart and 2) to suppress conduction through the AV node (rate control). Digoxin acts on the Na⁺/K⁺ ATPase on the surface of the cell, making it inactive leading to an accumulation of sodium inside the cell and potassium outside the cell. This impairs the ability of the Na⁺/Ca²⁺ exchanger to remove calcium from the cell leading to higher levels of intracellular calcium. In terms of rate control, digoxin increases the vagal tone at the AV node when it is at therapeutic levels in the serum. It also slows conduction through the AV node. Through its alteration in membrane potentials and transport of ions, it also changes repolarization of the myocardium. On ECG, a downsloping ST segment is seen with a flattened, inverted or biphasic T wave. Both the atrial and ventricular refractory periods are shortened leading to the repolarization abnormalities seen in the ST segments. These changes are the expected effect of digoxin therapy and not associated with toxic serum levels.

This patient presents with signs and symptoms of a beta-blocker overdose, which may be treated with high-dose insulin therapy. Beta-blockers are a commonly used group of medications that can have effect on inotropy (cardiac contractility), dromotropy (cardiac conduction) and chronotropy (heart rate). Additionally, they may have beta-2 effects leading to vascular smooth muscle relaxation and vasodilation. These agents are rapidly absorbed after ingestion and their peak effect (in normal-release preparations) is in the 1 to 4 hour range. The most common sign of beta-blocker overdose is bradycardia followed by hypotension and altered level of consciousness. Bradycardia results from blocking conduction through the AV node. In larger overdoses, respiratory depression and apnea may occur. More liphophilic agents (i.e. propranolol) can cause delirium in the absence of cardiovascular manifestations. Treatment for these patients aims at reversing hypotension caused by negative inotropy and peripheral vasodilation. In awake patients soon after an overdose, activated charcoal may be beneficial but the rapid absorption in the gastrointestinal tract limits its effectiveness. Atropine is often ineffective as the drug decreases vagal tone but does not reverse global myocardial depression. Increasing extracellular calcium with calcium chloride or calcium gluconate promotes intracellular calcium flux and may be beneficial. Glucagon bypasses the beta-receptors and activates adenyl cyclase leading to improved contraction. When these interventions don’t work, high-dose insulin (HDI) may be life saving. Although the exact mechanism of action is not known, HDI is a powerful inotrope. Therapy starts with a bolus of 1 unit/kg of regular insulin followed by a drip of 1 – 10 units/kg/hr. This must be paired with an infusion of dextrose to prevent hypoglycemia.

The patient exhibits signs and symptoms of a sympathomimetic toxidrome, with hyperthermia, hypertension, tachycardia, diaphoresis, and dilated pupils. In addition, he has cardiac ischemia induced by cocaine, evidenced by the ECG changes and elevated troponin. The mainstay of management of cocaine toxicity includes cooling for hyperthermia and benzodiazepines like lorazepam and diazepam for sedation and anxiety symptoms. Cooling methods include infusion of saline, packing with ice, and use of wet sheets and large fans to induce evaporative cooling. Cocaine can cause chest pain via multiple mechanisms, including noncardiac causes like pneumothorax, pneumomediastinum, and aortic dissection. In terms of cardiac causes of chest pain, cocaine induces coronary vasoconstriction while simultaneously increasing myocardial oxygen demand, which can result in cardiac ischemia or infarction. This patient has evidence of cardiac ischemia and should be treated with aspirin and nitrates. Heparin and antiplatelet agents may also be given if myocardial infarction is suspected. If hypertension persists despite nitrate use, phentolamine or hydralazine may be used. Beta-blockers like metoprolol are contraindicated with cocaine use because of the risk ofunopposed alpha-stimulation which can worsen coronary vasoconstriction.

Digoxin is used therapeutically as an inotropic agent to increase myocardial contractility and also as a rate control agent to decrease conduction through the AV node. The drug inhibits the surface Na⁺/K⁺ ATPase which alters the Na⁺gradient of the Na⁺/Ca⁺⁺ exchanger leading to increased levels of intracellular calcium. Additionally, digoxin increases the vagal activity at the SA and AV nodes. At toxic levels, digoxin can cause almost any dysrhythmia or conduction block. However, certain dysrhythmias are more specific for digoxin toxicity including: slow and regular atrial fibrillation, junctional tachycardia, atrial tachycardia with a block and bidirectional ventricular tachycardia. In acute toxicity, patients experience a variety of noncardiac symptoms although nausea and vomiting are almost always present. Hyperkalemia is the most severe electrolyte abnormality associated with digoxin toxicity and prognosis is correlated with serum potassium levels. Patients do not typically survive when the serum potassium level exceeds 5.5 mEq/dL.

The patient presents with digoxin toxicity and should be given digibind as soon as possible. Digoxin is a cardioactive steroid that leads to increased cardiac contractility and decreased AV conduction. The drug acts by inhibiting the sodium-potassium-ATPase (Na+-K+-ATPase) leading to increased intracellular sodium concentration. Digoxin can present with acute or chronic overdose. In acute overdose, nausea and vomiting occur early. Patients may also experience confusion and lethargy. Poisoning the Na+-K+-ATPase can lead to hyperkalemia. The ECG will show the digitalis effect of scooped ST segments (Salvador Dali mustache) and PR prolongation. Digoxin can cause nearly any type of dysrhythmia with the exception of supraventricular tachydysrhyhtmias (as a result of AV nodal blockade). The most common ECG finding in digoxin toxicity is PVCs. In patients with digoxin overdose, the serum potassium level is a key predictor of mortality and helps to guide therapy. Patients with a serum potassium <5.0 mEq/dl almost always survive. Prior to the availability of digoxin-specific Fab patients with a potassium between 5.0 and 5.5 mEq/dl had a 50% survival and those with a potassium >5.5 mEq/dl always died. In an acute overdose, digoxin-specific Fab should be given to patients with an elevated digoxin level of 10-15 nanograms/ml, a serum potassium >5.0 mEq/dl or in the presence of severe conduction disturbances (any ventricular dysrhythmia, bradydysrhythmias unresponsive to atropine). In a chronic overdose, serum concentrations are often lower and administration of digoxin-specific Fab is typically based on the presence or absence of conduction abnormalities and serum potassium.

The correct answer is calcium channel blocker. Both calcium channel blockers and beta blockers present very similarly, with the major difference being that calcium channel blockers prevent insulin release and thus result in hyperglycemia. Treatment for both is atropine, glucagon, and epinephrine as needed. Calcium can be attempted but doesn’t usually work very well. Recommendations are also to give high dose insulin and maintain blood sugar with dextrose. Intralipid can also be given. For acute ingestions, activated charcoal and whole bowel irrigation are recommended. For severe cases, pacing, intra-aortic balloon pumps, and ECMO can be used.

The correct answer is benzodiazepines. For sympathomimetic toxidromes, the most efficacious medicines to reduce blood pressure/tachycardia/hyperthermia are benzos. Betablockers are contraindicated as they lead to unopposed alpha activity. Phentolamine is a difficult medicine to titrate.

The correct answer is benzodiazepines. For sympathomimetic toxidromes, the most efficacious medicines to reduce blood pressure/tachycardia/hyperthermia are benzos. Betablockers are contraindicated as they lead to unopposed alpha activity. Phentolamine is a difficult medicine to titrate.

The ECG (http://www.ncbi.nlm.nih.gov/pubmed/16490826) demonstrates bidirectional ventricular tachycardia that is most commonly associated and nearly diagnostic for digoxin toxicity. Bidirectional ventricular tachycardia is diagnosed with beat-to-beat alteration of the frontal QRS axis (or alternating LBBB and RBBB)

Interestingly, digoxin toxicity can result in almost any dysrhythmia (except rapidly-conducted supraventricular tachydysrhythmia because digoxin has a prominent depressive effect on the AV node). In 10% of cases, the first ECG sign of digoxin toxicity is ectopic premature ventricular beats, while AV junctional blocks with increased ventricular automaticity is one of the most common ECG findings (30-40%).

Hyperkalemia is common in acute digoxin toxicity, and once digoxin-specific antibody fragments (Fab fragments) are administered, the hyperkalemia is rapidly corrected. Aggressive treatment with potassium-lowering agents could lead to profound hypokalemia after Fab fragment administration. If Fab fragments are unavailable or not readily available, then an attempt at gently lowering potassium is recommended (to avoid profound hypokalemia after Fab administration)

Clonidine is a centrally acting alpha-2-adrenergic agonist. Because of its action on these receptors, large ingestions cause bradycardia and hypotension. Initially there may be hypertension with bradycardia. The hypertension occurs through activation of peripheral alpha-2 receptors which causes the release of norepinephrine. This effect is transient and typically resolves by the time the patient reaches the hospital. Clonidine overdose also mimics opiate ingestions with small pupils, somnolence and a decreased respiratory rate. Patients with a clonidine overdose may have periods of apnea as well.