1. Cardiovascular Meds Intoxication
Zohair Al Aseri MD,FRCPC EM & CCM

2. Cardiovascular BB & CCB Intoxication
Zohair Al Aseri MD,FRCPC EM & CCM

3. Introduction
a 64-year-old man in the critical bay who took an overdose of his medications.
Zohair Al Aseri MD,FRCPC EM & CCM

4. has a history of hypertension, atrial fibrillation, and depression.
lethargic but arousable
reports he took about 40 tablets of immediate- release metoprolol three hours ago in an attempt to “end it all.”
Zohair Al Aseri MD,FRCPC EM & CCM

5. “Is it too late for gastric decontamination?
If he is symptomatic, which therapy will you try first, and what are your options?”
Zohair Al Aseri MD,FRCPC EM & CCM

6. The grandmother thinks that at most there are three tablets missing.
a 2-year-old child in the pediatric area who was found playing with grandma’s bottle of verapamil controlled release 15 minutes ago.
The grandmother thinks that at most there are three tablets missing.
Zohair Al Aseri MD,FRCPC EM & CCM

7. “Are three tablets a big deal?
Child looks great
“Are three tablets a big deal?
Can we just watch the child for a couple of hours?
Do we need an IV and blood work?
Zohair Al Aseri MD,FRCPC EM & CCM

8. Principles of Disease Pathophysiology
inhibit endogenous catecholamines such as epinephrine at the beta-receptor.
Zohair Al Aseri MD,FRCPC EM & CCM

9. Selected Characteristics of Common Beta-Blockers
Zohair Al Aseri MD,FRCPC EM & CCM

10. Principles of Disease Pathophysiology
Beta-blockers are rapidly absorbed after oral ingestion, and the peak effect of normal-release preparations occurs in 1 to 4 hours. 
Hepatic metabolism on first pass results in significantly less bioavailability after oral dosing than with IV injection (1 : 40 for propranolol).
Volume of distribution for various beta-blockers generally exceeds 1 L/kg, meaning tissue concentrations exceed those of serum.
Zohair Al Aseri MD,FRCPC EM & CCM

11. Principles of Disease Pathophysiology
Therefore, hemodialysis is not efficacious for most beta-blockers.
Protein binding varies from 0% for sotalol to 93% for propranolol.
Elimination half-lives vary from 8 to 9 minutes for esmolol to as long as 24 hours for nadolol and others 
Zohair Al Aseri MD,FRCPC EM & CCM

12. MANIFESTATIONS AND COMPLICATIONS OF BETA-BLOCKER OVERDOSEIN ORDER OF DECREASING FREQUENCY
Zohair Al Aseri MD,FRCPC EM & CCM

13. Diagnostic Strategies
Diagnosis and management depend on the clinical picture
Hypoglycemia is common in children
Zohair Al Aseri MD,FRCPC EM & CCM

14. Management IV fluids Oxygen
Monitoring of card for rhythm and respirations.
Activated charcoal is unproven treatment.
Multiple-dose charcoal without supporting evidence for an improvement in outcome.
Zohair Al Aseri MD,FRCPC EM & CCM

15. Management
Onset of toxicity is so uniformly early that absence of symptoms 4 hours after ingestion implies a low risk for subsequent morbidity unless a delayed-release preparation is involved.
Zohair Al Aseri MD,FRCPC EM & CCM

16. Management Hypotension, Bradycardia, and Atrioventricular Block
Catecholamines with chronotropic and dromotropic as well as inotropic and vasopressor effects should be chosen.
Zohair Al Aseri MD,FRCPC EM & CCM

17. Management
It is rare for one catecholamine to be equally effective against all four toxic effects, so combinations of drugs are often used in severe cases.
Zohair Al Aseri MD,FRCPC EM & CCM

18. Management The first step in the treatment of beta-blocker overdose is
Atropine
Glucagon
Crystalloid fluids.
Zohair Al Aseri MD,FRCPC EM & CCM

19. Management
A dose of atropine may quickly wear off or be ineffective, so infusion of more potent drugs or cardiac pacing is usually necessary.
Atropine (0.5 mg for adults, 0.02 mg/kg for children, minimum 0.10 mg) should be given before vagal stimuli such as tracheal or gastric intubation.
Zohair Al Aseri MD,FRCPC EM & CCM

20. Management
Glucagon
Does not depend on beta-receptors for its action, has both inotropic and chronotropic effects.
it helps to counteract the hypoglycemia induced by beta-blocker overdose.
is given as a 5- to 10-mg IV bolus
Zohair Al Aseri MD,FRCPC EM & CCM

21. Management
Glucagon
Because of its short (20-minute) half-life, an infusion of 2 to 5 mg/hr (or for children, 0.05– 0.1 mg/kg bolus, then 0.05–0.1 mg/kg/hr) should be started immediately after the bolus.
With cumulative large doses, glucagon should be diluted in 5% glucose in water for constant infusion.
Zohair Al Aseri MD,FRCPC EM & CCM

22. Management
Glucagon
Side effects include nausea and vomiting in most patients, mild hyperglycemia, hypokalemia, and allergic reactions.
The response to glucagon alone is often inadequate.
Zohair Al Aseri MD,FRCPC EM & CCM

23. Management sodium bicarbonate
Sodium channel blockade, manifested by QRS widening, occasionally occurs with beta-blocker intoxication and may respond to infusion of sodium bicarbonate.
Zohair Al Aseri MD,FRCPC EM & CCM

24. Management
In hypotensive patients, 20 to 40 mL/kg of normal saline or Ringer's lactate solution can be infused and repeated.
If hypotension or bradycardia persists, other cardioactive drugs are indicated.
dopamine, or epinephrine.
Zohair Al Aseri MD,FRCPC EM & CCM

25. Management
Other catecholamines include norepinephrine, dobutamine, and phenylephrine.
Often, norepinephrine or dopamine is added to beta-agonists such as isoproterenol that lack vasopressor activity.
Zohair Al Aseri MD,FRCPC EM & CCM

26. Treatment High-Dose Insulin Euglycemia (HDIE) Therapy
There are no randomized controlled human trials.
There are multiple case reports of the hemodynamic improvement after institution of HDIE.
Stellpflug SJ, Harris CR, Engebretsen KM, et al. Intentional overdose with cardiac arrest treated with intravenous fat emulsion and high-dose insulin. Clin Toxicol 2010;48:
Zohair Al Aseri MD,FRCPC EM & CCM

27. Management
Insulin
High-dose (0.5–1 unit/kg/hr) insulin infusion for hemodynamically significant toxicity is often given before traditional pressors.
Beta-blocker toxicity shifts myocardial energy preferences from free fatty acids to carbohydrates, and insulin increases myocardial carbohydrate uptake.
Recent canine and porcine models showed the benefit of insulin infusion up to 10 units/kg/hr.
Zohair Al Aseri MD,FRCPC EM & CCM

28. Management
Insulin
Glucose, usually in 5 to 10% solutions, is infused to maintain a serum glucose of approximately 100 mg/dL.
The combination of glucose and high-dose insulin augments myocardial contraction independent of beta-receptors.
Glucose and potassium should be monitored frequently during infusion and supplemented as needed to maintain euglycemia and eukalemia.
Zohair Al Aseri MD,FRCPC EM & CCM

29. Management
Refractory cases of bradycardia may respond to an external or transvenous pacemaker.
Zohair Al Aseri MD,FRCPC EM & CCM

30. Management
Calcium
Because deleterious effects on calcium transport may contribute to beta-blocker toxicity, IV calcium salts have been suggested for treating hypotension.
calcium should be given cautiously and less aggressively than for cases of calcium channel blocker overdose.
Constant infusions are safer than boluses.
Give 1 to 2 g over 5 to 10 minutes, monitoring closely for effect.
Zohair Al Aseri MD,FRCPC EM & CCM

31. Ventricular Dysrhythmias
Management
Ventricular Dysrhythmias
Although uncharacteristic, ventricular tachydysrhythmias do occur sometimes.
Cardioversion and defibrillation are indicated for ventricular tachycardia and ventricular fibrillation, respectively, following American Heart Association guidelines.
Pulsatile ventricular tachycardia or frequent ventricular ectopy can most safely be treated with lidocaine.
Zohair Al Aseri MD,FRCPC EM & CCM

32. Extracorporeal Elimination and Circulatory Assistance
Management
Extracorporeal Elimination and Circulatory Assistance
Hemodialysis or hemoperfusion may be beneficial for atenolol, nadolol, sotalol, and timolol, the beta-blockers with lower Vd, lower protein binding, and greater hydrophilicity.
Zohair Al Aseri MD,FRCPC EM & CCM

33. Extracorporeal Elimination and Circulatory Assistance
Management
Extracorporeal Elimination and Circulatory Assistance
can be lifesaving in cases of refractory hypotension. 
To be successful, such heroic measures must be taken before prolonged hypotension leads to multiorgan ischemic injury.
Zohair Al Aseri MD,FRCPC EM & CCM

34. TREATMENT OF BETA-BLOCKER POISONING
Zohair Al Aseri MD,FRCPC EM & CCM

35. Zohair Al Aseri MD,FRCPC EM & CCM

36. Disposition
Patients who remain completely asymptomatic for 6 hours after an oral overdose of normal-release preparations can be safely referred for psychiatric evaluation, with medical consultation for the first 24 hours.
Zohair Al Aseri MD,FRCPC EM & CCM

37. CALCIUM CHANNEL BLOCKERS
Perspective
Most fatalities occur with verapamil, but severe toxicity and death have been reported for most drugs of this class.
Zohair Al Aseri MD,FRCPC EM & CCM

38. Pathophysiology Calcium channel antagonists
block the slow calcium channels in the myocardium and vascular smooth muscle, leading to coronary and peripheral vasodilation.
reduce cardiac contractility
depress SA nodal activity
slow AV conduction.
Zohair Al Aseri MD,FRCPC EM & CCM

39. Pathophysiology
Both verapamil and diltiazem act on the heart and blood vessels, whereas nifedipine causes primarily vasodilation.
In the pancreas, calcium channel blockade inhibits insulin release, resulting in hyperglycemia.
As with beta-blockers, selectivity is lost in cases of overdose
Zohair Al Aseri MD,FRCPC EM & CCM

40. Pathophysiology All calcium channel blockers are rapidly absorbed
Onset of action and toxicity ranges from less than 30 minutes to 60 minutes
Peak effect of nifedipine can occur as early as 20 minutes after ingestion,
Zohair Al Aseri MD,FRCPC EM & CCM

41. Pathophysiology
Peak effect of sustained-release verapamil can be delayed for many hours.
High protein binding and Vd greater than 1 to 2 L/kg make hemodialysis or hemoperfusion ineffective.
Fortunately (except with sustained-release preparations), their half-lives are relatively short, limiting toxicity to 24 to 36 hours.
Zohair Al Aseri MD,FRCPC EM & CCM

42. Selected Characteristics of Some Calcium Channel Blockers
Zohair Al Aseri MD,FRCPC EM & CCM

43. MANIFESTATIONS AND COMPLICATIONS OF CALCIUM CHANNEL BLOCKER POISONING
Zohair Al Aseri MD,FRCPC EM & CCM

44. Diagnostic Strategies
Serum levels of calcium antagonists are not available
Glucose and Electrolytes (including calcium and magnesium). Hyperglycemia secondary to insulin inhibition occurs occasionally, but mild and short-lived requires no treatment.
Lactic acidosis occurs with hypotension and hypoperfusion.
Zohair Al Aseri MD,FRCPC EM & CCM

45. Diagnostic Strategies
ECG
A prolonged QRS or QT interval suggests bepridil or a co-ingested cardiac toxin such as a TCA.
Zohair Al Aseri MD,FRCPC EM & CCM

46. Management IV O2 Cardiac monitoring
Vomiting is a powerful vagal stimulus that can exacerbate bradycardia and heart block.
No evidence for activated charcoal
Zohair Al Aseri MD,FRCPC EM & CCM

47. Hypotension and Bradycardia
Atropine (0.5–1 mg, up to 3 mg for adults, and 0.02 mg/kg for children, minimum 0.1 mg).
Atropine's effect is short-lived
If symptomatic bradycardia or heart block persists, the next step is a pacemaker or chronotrope such as isoproterenol.
Zohair Al Aseri MD,FRCPC EM & CCM

48. Hypotension and Bradycardia Intravenous calcium
have considerable effect on contractility but their effect on bradycardia, AV block, and peripheral vasodilation is often poor.
Zohair Al Aseri MD,FRCPC EM & CCM

49. Hypotension and Bradycardia
Epinephrine, norepinephrine, and dobutamine have also led to successful outcomes.
Zohair Al Aseri MD,FRCPC EM & CCM

50. Hypotension and Bradycardia
Glucagon has also been used for its inotropic and chronotropic effects.
Zohair Al Aseri MD,FRCPC EM & CCM

51. Hypotension and Bradycardia Insulin
(0.5–1 iu/kg/hr) infusion has been effective in both animal trials and human cases.
Glucose (5–10% solutions usually suffice) is infused concurrently to maintain serum glucose at 100 mg/dL (usually 10–30 g/hr).
Insulin euglycemia is thought to act by improving myocardial carbohydrate metabolism, thereby augmenting myocardial contraction.
Zohair Al Aseri MD,FRCPC EM & CCM

52. Hypotension and Bradycardia Insulin
Serum glucose and potassium levels should be checked frequently to ensure that normal levels are maintained.
Zohair Al Aseri MD,FRCPC EM & CCM

53. Treatment High-Dose Insulin Euglycemia (HDIE) Therapy
may be administered to increase inotropy.
Its proposed mechanism of action is by improving calcium use in the myocytes, although the exact mechanism is unclear.
Megarbane B, Karyo S, Baud FJ. The role of insulin and glucose (hyperinsulinaemie/ euglycaemia) therapy in acute calcium channel antagonist and beta-blocker poisoning. Toxicol Rev 2004;23: Kline JA, Leonova E, Raymond R. Beneficial myocardial metabolic effects of insuin during verapamil toxicity in the anesthetized canine. Crit Care Med 1995;3: Tune JD, Mallet RT, Downey HF. Insulin improves contractile function during moderate ischemia in canine left ventricle. Am J Physiol 1998;274:
Zohair Al Aseri MD,FRCPC EM & CCM

54. TREATMENT OF CALCIUM CHANNEL BLOCKER INTOXICATION
Zohair Al Aseri MD,FRCPC EM & CCM

55. Zohair Al Aseri MD,FRCPC EM & CCM

56. Disposition
Because the peak effect occurs in 90 minutes to 6 hours, patients who are totally asymptomatic for 6 hours can be safely discharged
For delayed-release preparations should be admitted for at least 24 hours of continuous cardiac monitoring.
Zohair Al Aseri MD,FRCPC EM & CCM

57. NITRATES AND NITRITES
Widely used as vasodilators in the treatment of heart failure and ischemic heart disease.
augment coronary blood flow as well as reduce myocardial oxygen consumption by reducing afterload.
At lower doses nitrates primarily dilate veins
At higher doses they also dilate arteries.
Zohair Al Aseri MD,FRCPC EM & CCM

58. NITRATES AND NITRITES
Hypotension is a common complication, but usually responds to supine positioning, IV fluids, and reduction of dose.
Hypotension is usually transient.
Low-dose pressors are occasionally needed, but it is best to avoid them in the setting of acute coronary syndromes.
Zohair Al Aseri MD,FRCPC EM & CCM

59. NITRATES AND NITRITES
Nitrites are also oxidizing agents that convert hemoglobin to methemoglobin, impairing oxygen delivery.
Zohair Al Aseri MD,FRCPC EM & CCM

60. NITRATES AND NITRITES
When methemoglobin levels exceed 15%, a venous blood sample appears chocolate brown, and the skin appears blue even while patients look remarkably comfortable.
Unlike most cases of cyanosis, supplemental oxygen does not improve the patient's color.
Zohair Al Aseri MD,FRCPC EM & CCM

61. NITRATES AND NITRITES Pulse oximetry is not reliable, Treatment
IV methylene blue, but this antidote is usually not needed unless methemoglobinemia approaches 30%
The usual dose of methylene blue in adults is 1 to 2 mg IV over 5 minutes.
Zohair Al Aseri MD,FRCPC EM & CCM

62. Digitalis Intoxication
Zohair Al Aseri MD,FRCPC EM & CCM

63. DIGITALIS Perspective
The foxglove plant, from which digitalis is derived.
DIGITALIS
Perspective
Zohair Al Aseri MD,FRCPC EM & CCM

64. Principles of Disease Pathophysiology
In therapeutic doses, digitalis has two effects:
(1) increasing the force of myocardial contraction to increase cardiac output in patients with heart failure.
(2) decreasing atrioventricular (AV) conduction to slow the ventricular rate in atrial fibrillation.
Zohair Al Aseri MD,FRCPC EM & CCM

65. Principles of Disease Pathophysiology
It inhibits membrane sodium-potassium adenosine triphosphatase (ATPase), which increases intracellular sodium and calcium and increases extracellular potassium.
At therapeutic doses, the effects on serum electrolyte levels are minimal.
Zohair Al Aseri MD,FRCPC EM & CCM

66. Principles of Disease Pathophysiology
With toxic levels, digitalis paralyzes the Na-K pump, potassium cannot be transported into cells, and serum potassium can rise as high as 13.5 mEq/L.
Zohair Al Aseri MD,FRCPC EM & CCM

67. Principles of Disease Pathophysiology
At therapeutic levels, digitalis indirectly increases vagal activity and decreases sympathetic activity.
At toxic levels, digitalis can directly halt the generation of impulses in the SA node, depress conduction through the AV node, and increase the sensitivity of the SA and AV nodes to catecholamines.
Zohair Al Aseri MD,FRCPC EM & CCM

68. Principles of Disease Pathophysiology
Digitalis can produce virtually any dysrhythmia or conduction block, and bradycardias are as common as tachycardias.
Zohair Al Aseri MD,FRCPC EM & CCM

69. DYSRHYTHMIAS ASSOCIATED WITH DIGITALIS TOXICITY
Zohair Al Aseri MD,FRCPC EM & CCM

70. Principles of Disease Pathophysiology
The significant protein binding and large volume of distribution suggest that hemodialysis, hemoperfusion, and exchange transfusion are ineffective.
Zohair Al Aseri MD,FRCPC EM & CCM

71. FACTORS ASSOCIATED WITH INCREASED RISK OF DIGITALIS TOXICITY
Zohair Al Aseri MD,FRCPC EM & CCM

72. NONCARDIAC SYMPTOMS OF DIGITALIS INTOXICATION IN ADULTS AND CHILDREN
Zohair Al Aseri MD,FRCPC EM & CCM

73. Diagnostic Strategies
Serum digoxin levels.
It is the steady state, rather than peak level, that correlates with tissue toxicity and is used to calculate antidote dosages.
Zohair Al Aseri MD,FRCPC EM & CCM

74. Diagnostic Strategies
Peak levels after an oral dose of digoxin occur in 1.5 to 2 hours, with a range of 0.5 to 6 hours. 
Steady-state serum concentrations are not achieved until after distribution, or 6 to 8 hours after a dose or overdose, and may be only one fourth to one fifth of the peak level.
Zohair Al Aseri MD,FRCPC EM & CCM

75. Diagnostic Strategies
The ideal serum digoxin concentration for patients with heart failure is considered to be 0.7 to 1.1 ng/mL. 
Zohair Al Aseri MD,FRCPC EM & CCM

76. Diagnostic Strategies
After an acute massive overdose in a patient who is rapidly becoming symptomatic, however, it may be impractical to wait 6 to 8 hours for the first reading. 
It is unlikely that early levels exceeding 10 to 20 ng/mL will fade to clinical insignificance at 6 to 8 hours after ingestion.
Zohair Al Aseri MD,FRCPC EM & CCM

77. Diagnostic Strategies
Patients taking digitalis therapeutically often take diuretics as well, and they often have low serum and total body potassium levels.
The acutely poisoned patient, in contrast, may have life-threatening hyperkalemia.
Zohair Al Aseri MD,FRCPC EM & CCM

78. Management
There is no evidence to support gastric emptying for the treatment of digoxin overdose.
Activated charcoal, no improvement in outcome has been established.
Multidose charcoal has no proven benefit
Zohair Al Aseri MD,FRCPC EM & CCM

79. Electrolyte Correction K
In cases of chronic intoxication, often exacerbated by hypokalemia, raising the serum potassium level to 3.5 to 4 mEq/L is an important early treatment.
Potassium can be administered orally (which is safer) or intravenously (IV) although a rate more rapid than 10 to 40 mEq/hour is dangerous.
Zohair Al Aseri MD,FRCPC EM & CCM

80. Electrolyte Correction K
In acute poisoning, serum potassium may begin to rise rapidly within 1 to 2 hours of ingestion, potassium should be withheld, even if mild hypokalemia is measured initially.
Zohair Al Aseri MD,FRCPC EM & CCM

81. Electrolyte Correction K
A serum potassium level greater than 5 mEq/L warrants consideration of digitalis antibody (ovine Fab fragment) treatment.
If digitalis antibodies are not immediately available, severe hyperkalemia should be treated with IV glucose, insulin, and sodium bicarbonate.
Zohair Al Aseri MD,FRCPC EM & CCM

82. Electrolyte Correction Mg
Many patients on diuretic therapy are also magnesium-depleted, even when the measured serum magnesium level is normal.
If significant magnesium depletion is suggested, 1 to 2 g of magnesium sulfate can be given over 10 to 20 minutes (child: 25 mg/kg), followed by a constant infusion of 1 to 2 g/hour.
Zohair Al Aseri MD,FRCPC EM & CCM

83. Atropine
Atropine is generally used for severe bradycardia and advanced AV block, with mixed results.
Generally, an external or transvenous pacemaker should be prepared when bradycardia or AV block appears.
Zohair Al Aseri MD,FRCPC EM & CCM

84. Pacing
It may be safer to temporize with an external rather than a transvenous pacemaker while waiting for Fab fragments to take effect.
Cardioversion and defibrillation can cause asystole after attempts to treat tachydysrhythmias.
Lower energy settings, such as 25 to 50 J, may be less hazardous.
Zohair Al Aseri MD,FRCPC EM & CCM

85. Fab Fragments (Digibind or Digifab)
Digitalis antibodies are derived from sheep immunized with digoxin.
Side Effect
Reactions have included erythema, urticaria, and facial edema, all of which are responsive to the usual treatment.
Hypokalemia
Exacerbation of congestive heart failure
Increase in ventricular rate with atrial fibrillation.
Zohair Al Aseri MD,FRCPC EM & CCM

86. Fab Fragments (Digibind or Digifab)
Indicated for serious cardiovascular toxicity
Not for prophylactic administration of higher than expected serum levels.
The primary indication for antibody treatment in cases of acute poisoning is hyperkalemia with a serum potassium level greater than 5.5 mEq/L or ECG changes.
Zohair Al Aseri MD,FRCPC EM & CCM

87. Fab Fragments (Digibind or Digifab)
Fab fragment therapy should be used before transvenous pacing, which carries significant risk.
Zohair Al Aseri MD,FRCPC EM & CCM

88. RECOMMENDATIONS FOR ADMINISTRATION OF DIGITALIS ANTIBODY FRAGMENTS
Zohair Al Aseri MD,FRCPC EM & CCM

89. Disposition and Summary
All patients who are symptomatic for digitalis intoxication with hyperkalemia, dysrhythmia, AV block, or significant comorbidity should be admitted to the hospital or the emergency department observation unit for at least 12 hours of continuous cardiac monitoring.
All patients treated with antibodies require admission to an intensive care unit.
Zohair Al Aseri MD,FRCPC EM & CCM

90. Important to know: ED Evaluation time of ingestion
specific name of the medication
number of pills ingested
formulation
(i.e., immediate release vs. sustained release)
dose per tablet
co-ingestants
chronic medications taken as prescribed
alcohol, or illicit drugs.
Zohair Al Aseri MD,FRCPC EM & CCM

91. Zohair Al Aseri MD,FRCPC EM & CCM

92. Thank you Main reference is Rosen Text book of EM
Zohair Al Aseri MD,FRCPC EM & CCM