BETA BLOKERS Tintinalli's Emergency Medicine 2010

1. BETA BLOKERSTintinalli's Emergency Medicine 2010 BY dr. Tayebeh salehi

2. 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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5. 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.

9. 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.

10. 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

11. 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.

12. Clinical Presentation

13. 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.

14. 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).

15. 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

16. 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.

17. 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

19. 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

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

21. 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

22. 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.

23. Pharmacologic Treatment

24. 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.

25. 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

26. 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.

27. 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.

28. 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

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

30. 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.

31. 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

32. 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.

33. 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

34. 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.

35. 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.

36. 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

37. 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.

38. 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.

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

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

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

42. 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

43. 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

44. 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

45. THANKS FOR YOUR ATTENTION