BETA BLOKERS Tintinalli's Emergency Medicine 2010 BY DR. TAYEBEH SALEHI

Epidemiology  common medications used in the treatment of various cardiovascular, neurologic, endocrine, ophthalmologic, and psychiatric disorders  accidental and intentional toxicity is common

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 The beta -blockers by decreasing calcium entry into the cell modulate the activity of myocyte and vascular smooth muscle contraction  excessive beta -blockade may lead to profound pump failure, with bradycardia, decreased contractility, and hypotension.

 selectivity is often lost following large overdoses.  Sotalol is unique among beta-blockers in its ability to block potassium channels  Sotalol is class III antiarrhythmic drugs.

 Under normal conditions, the heart uses free fatty acids as its primary energy source,  but during times of stress, it switches to using carbohydrates to maintain metabolism

 Inhibition of glycogenolysis and gluconeogenesis reduces the availability of carbohydrates for use by cells  hypoglycemia occurs as a consequence of beta -blocker toxicity, it is actually very rare. In the presence of adequate glucose stores, euglycemia and hyperglycemia are more common than hypoglycemia.

Clinical Presentation

 Absorption of regular-release beta -blockers occurs rapidly, often with peak effects within 1 to 4 hours  sustained-release cardiac drugs, it is assumed that symptoms may be delayed >6 hours after ingestion  Coingestants that alter gut function, such as opioids and anticholinergics, may affect absorption of beta -blockers and subsequent onset of symptoms.

 The primary organ system affected by beta-blocker toxicity is the cardiovascular system, and the hallmark of severe toxicity is bradycardia and shock.  The beta -blockers with sodium channel antagonism can cause a wide-complex bradycardia, and may contribute to development of seizures (especially when the QRS interval is >100 milliseconds).

 sotalol ability to block potassium channels and prolong the QT interval  sotalol is more often associated with ventricular dysrhythmias, includin :  premature ventricular contractions  bigeminy  ventricular tachycardia  ventricular fibrillation  torsades de pointes

 Neurologic manifestations include depressed mental status, coma, and seizures.  More lipophilic beta-blockers, such as propranolol, cause greater neurologic toxicity than the less lipophilic agents.  Seizures can occur but are generally brief, and status epilepticus is rare.

Diagnosis  including patient history, physical examination findings, and results of basic diagnostic testing.  exposures to other drugs and toxins can present with bradycardia and hypotension

 The 12-lead ECG and Bedside echocardiography are useful to evaluate myocardial performance in cases of undifferentiated shock.  Invasive monitoring with central venous or pulmonary artery catheters may be necessary to help direct resuscitation.  renal function, glucose level, oxygenation, and acid-base status

Treatment  General Management  should be evaluated in a critical-care area of the ED with appropriate monitoring  protect air way

 GI Decontamination  ingestion of a significant quantity of beta -blockers decontamination should be considered.  Activated charcoal may be of benefit if it can be given within 1 to 2 hours after ingestion. Multiple dose of activated charcoal therapy following ingestion of sustained-release - blockers

 Use of ipecac syrup is not recommended  Gastric lavage is not routinely used, but may be considered for life-threatening ingestions when the airway is adequately protected from aspiration.  Whole-bowel irrigation may be beneficial after ingestion of a sustained-release product, If whole-bowel irrigation is used, adequate airway protection and normal GI function are important.

Pharmacologic Treatment

Glucagon  Glucagon is a first-line agent in the treatment of acute beta – blocker induced bradycardia and hypotension.  Effects from an IV bolus of glucagon are seen within 1 to 2 minutes, reach a peak in 5 to 7 minutes duration of action of 10 to 15 minutes.  Due to the short duration of effect, a continuous infusion is often necessary after bolus administration.

 The bolus dose of glucagon is 0.05 to 0.15 milligram/kg (3 to 10 milligrams for the average 70-kg ( and can be repeated as needed.  If a beneficial effect is seen from bolus, a continuous infusion 1 to 10 milligrams/h

 the positive inotropic and chronotropic effects of glucagon may not be maintained for a prolonged period due to possible tachyphylaxis.  side effects of high-dose glucagon therapy : Nausea and vomiting esophageal sphincter relaxation  Intubation prior to glucagon administration may be warranted in any patient with altered mental status to limit the risk of aspiration.

Adrenergic Receptor Agonists  The beta -adrenergic receptor agonists—such as norepinephrine, dopamine, epinephrine, and isoproterenol  The most effective adrenergic receptor agonist may be norepinephrine due to its ability to increase heart rate and blood pressure.

Hyperinsulinemia-Euglycemia Therapy  insulin facilitates myocardial utilization of glucose, the desired substrate during stress  This is in contrast to glucagon, epinephrine, and calcium, which promote free fatty acid utilization

 The initial dose is regular insulin 1 unit/kg IV bolus followed by 0.5 to 1.0 unit/kg/h continuous infusion.

 adverse effects from hyperinsulinemia-euglycemia therapy are hypoglycemia and hypokalemia  0.5 gram/kg bolus of glucose should accompany the initial insulin bolus in a patient whose serum glucose level is <400 milligrams/dL.  Serum glucose levels should be monitored regularly: every 20 to 30 minutes until stable euglycemia is achieved, and then every 1 to 2 hours thereafter.

 Serum potassium levels may fall during hyperinsulinemia-euglycemia therapy.  Serum potassium level should be monitored,  replacement is not required unless it falls to <2.5 mEq/L (<2.5 mmol/L) or the patient has other sources of true potassium loss

Atropine  a muscarinic blocker, is unlikely to be effective in the management of beta blocker–induced bradycardia and hypotension,  although its use is unlikely to cause harm.

Calcium  calcium administration is not routinely recommended in beta -blocker overdose, it may be worth considering in patients with refractory shock unresponsive to other therapies.  Calcium for IV administration is available in two forms, gluconate and chloride, both in a 10% solution. Calcium chloride solution contains three times more elemental calcium than calcium gluconate solution

 10% calcium gluconate 0.6 mL/kg given over 5 to 10 minutes followed by a continuous infusion of 0.6 to 1.5 mL/kg/h  10% calcium chloride 0.2 mL/kg given via central line over 5 to 10 minutes followed by a continuous infusion of 0.2 to 0.5 mL/kg/h.  Ionized calcium levels should be checked every 30 minutes initially and then every 2 hours to achieve an ionized calcium level of twice the normal value.

Phosphodiesterase Inhibitors  such as inamrinone (formerly known as amrinone), milrinone, and enoximone  These agents inhibit the breakdown of cAMP thereby maintaining intracellular calcium levels  In animal models, phosphodiesterase inhibitors produce positive inotropic effects without increasing myocardial oxygen demand, but have no appreciable effect on heart rate.

 In the setting of a beta -blocker overdose, phosphodiesterase inhibitors are administrated as a continuous IV infusion, starting at 5 micrograms/kg/min for inamrinone 0.5 microgram/kg/min for milrinone 0.75 microgram/kg/min for enoximone

Sodium Bicarbonate  In a patient demonstrating a QRS interval longer than 120 to 140 milliseconds, it is reasonable to administer sodium bicarbonate  The suggested dose is a rapid bolus of 2 to 3 mEq/kg, Thus, a 70-kg adult receives a bolus of 140 to 210 mEq of sodium bicarbonate, or three to four ampules (50 mL each) of 8.4% sodium bicarbonate  Repeat boluses may be required to maintain the QRS interval at <120 milliseconds.

Cardiac Pacing  Electrical capture and restoration of blood pressure is not always successful  Cardiac pacing may be most beneficial in treating torsades de pointes associated with sotalol toxaicity.

Extracorporeal Elimination (Hemodialysis)  acebutolol  atenolol  nadolol  sotalol their lower protein binding, water solubility, and lower volume of distribution

Extracorporeal Circulation  extreme of resuscitation, intra-aortic balloon pumps have been successful when pharmacologic measures have failed to reverse cardiogenic shock

Treatment of Sotalol Toxicity  Inhibition of K channel and prolang QT  magnesium supplementation  lidocaine  cardiac overdrive pacing

 The goal of resuscitation is to improve hemodynamics and organ perfusion  cardiac ejection fraction of 50%,  reduction of the QRS interval to <120 milliseconds,  heart rate of >60 beats/min,  systolic blood pressure of >90 mm Hg in an adult  urine output of 1 to 2 mL/kg/h  improved mentation

Disposition and Follow-Up  Patients with altered mental status, bradycardia, conduction delays, or hypotension are often managed in an intensive care unit.  any patient who ingests a sustained-released beta -blocker product warrants admission and monitoring for the development of delayed toxicity

 Patients ingesting an overdose of regular beta -blocker tablets who remain asymptomatic and have normal vital signs for 6 hours after ingestion safe for discharge

THANKS FOR YOUR ATTENTION