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

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

 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

 “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

 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

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

 Overdose of propranolol is the most deadly, followed by acebutolol, oxprenolol, and alprenolol Zohair Al Aseri MD,FRCPC EM & CCM Perspective BETA-ADRENERGIC BLOCKERS

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

 Equally important properties, which vary from one beta-blocker to another, include cardioselectivity, membrane-stabilizing effect, lipophilicity, and intrinsic sympathomimetic activity.  Although cardioselectivity is lost in overdose, cardioselective beta-blockers such as atenolol, metoprolol, and esmolol are associated with a lower mortality rate than propranolol, the oldest beta-blocker. Zohair Al Aseri MD,FRCPC EM & CCM Principles of Disease Pathophysiology

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

 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 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 Principles of Disease Pathophysiology

 Bradycardia the most common  Hypotension and unconsciousness are the second and third most common signs.  Much of propranolol's toxicity derives from its lipophilic nature and membrane-stabilizing effect that allow it to penetrate the CNS, leading to obtundation, respiratory depression, and seizures. Other beta-blockers do not have these effects. Zohair Al Aseri MD,FRCPC EM & CCM Clinical Features

 Seizures probably result from a combination of hypotension, hypoglycemia, hypoxia, and direct CNS toxicity.  Surprisingly, bronchospasm is not problematic in cases of beta-blocker overdose, even with nonselective beta-blockers. Zohair Al Aseri MD,FRCPC EM & CCM Clinical Features

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

 Propranolol's membrane-stabilizing effect impairs SA and AV node function and leads to bradycardia and AV block.  Ventricular conduction is also depressed, leading to QRS widening and occasional ventricular dysrhythmias.  Nadolol and acebutolol also have a significant membrane-stabilizing effect.  These BB, like the TCA, can cause ventricular dysrhythmias such as VT, VF and torsades de pointes as well as the bradydysrhythmias more characteristic of beta-blockers in general. Zohair Al Aseri MD,FRCPC EM & CCM Clinical Features

 The intrinsic sympathomimetic activity of some beta-blockers such as pindolol and carteolol has led to some unusual manifestations such as sinus tachycardia instead of bradycardia and ventricular dysrhythmias.  Labetalol is unique in that it also blocks alpha- adrenergic receptors, yielding an additional mechanism for hypotension.  However, labetalol's beta-blockade is three to seven times more potent than its alpha-blockade. Zohair Al Aseri MD,FRCPC EM & CCM Clinical Features

 In contrast to digitalis, beta-blocker toxicity has a more rapid onset: life-threatening CNS and cardiovascular effects can occur 30 minutes after oral overdose.  Patients ingesting delayed-release preparations may remain asymptomatic for several hours, affording a valuable therapeutic window. Zohair Al Aseri MD,FRCPC EM & CCM Clinical Features

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

 Known access of the patient to a beta-blocker and consistent clinical features such as obtundation, seizures, bradydysrhythmias, and occasionally tachydysrhythmias should lead the clinician to consider beta-blocker intoxication. Zohair Al Aseri MD,FRCPC EM & CCM Diagnostic Strategies

 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 Management

 Evidence for improved outcome is also lacking but whole-bowel irrigation has been advocated for sustained-release preparations with a polyethylene glycol solution (OCL, GoLytely, CoLyte), administered orally or via nasogastric tube at 1 to 2 L/hour in adults or 20 mL/kg initially in children. Zohair Al Aseri MD,FRCPC EM & CCM 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 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 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 Management

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

 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 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 Management Glucagon

 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 Management sodium bicarbonate

 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 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 Management

 Because patients are resistant to these drugs, the initial dose should be high and the infusion rates should be rapidly titrated to effect.  A common mistake with cases of beta-blocker overdose is to timidly titrate catecholamine infusions within previously familiar ranges. In the setting of massive beta-blockade, much higher doses are usually needed and the drug is titrated to effect. Zohair Al Aseri MD,FRCPC EM & CCM Management

 There are no randomized controlled human trials.  There are multiple case reports of the hemodynamic improvement after institution of HDIE. Zohair Al Aseri MD,FRCPC EM & CCM 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: Treatment High-Dose Insulin Euglycemia (HDIE) Therapy

Kerns W. Antidotes in Depth: Insulin- Euglycemia Therapy. In: Nelson LS, et al eds. Goldfrank’s Toxicologic Emergencies 9 th ed. New York: McGraw Hill; 2010:  It can take up to 60 minutes to see improvement.  It is given along with a dextrose infusion of 0.5 g/kg/hr.  It is important to follow glucose and potassium levels closely during HDIE and avoid hypoglycemia and hypokalemia. Zohair Al Aseri MD,FRCPC EM & CCM Treatment High-Dose Insulin Euglycemia (HDIE) Therapy

 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 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 Management Insulin

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

 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 Calcium Management

 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 Ventricular Dysrhythmias Management

 Other antidysrhythmic drugs, especially of classes IA and IC, should be avoided because they may potentiate AV block or be prodysrhythmic because of an additive membrane stabilizing effect. Zohair Al Aseri MD,FRCPC EM & CCM Ventricular Dysrhythmias Management

 Sotalol, unlike other beta-blockers, has class III as well as class II effects; that is, it prolongs the QT interval and can cause torsades de pointes and other ventricular dysrhythmias.  Overdrive pacing with isoproterenol or a pacemaker and magnesium sulfate are specific therapies for torsades de pointes. Zohair Al Aseri MD,FRCPC EM & CCM Ventricular Dysrhythmias Management

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

 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 Management Extracorporeal Elimination and Circulatory Assistance

 Because most patients recover with just supportive care, these expensive and invasive interventions should be reserved for drugs and circumstances, such as propranolol, verapamil, and mixed cardiotoxic overdoses, that are associated with higher rates of mortality. Zohair Al Aseri MD,FRCPC EM & CCM Management Extracorporeal Elimination and Circulatory Assistance

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

 At this time, given the potential benefit and despite no human randomized controlled trials performed to date, IFE may be considered for patients who are failing other modalities or during cardiac arrest. Zohair Al Aseri MD,FRCPC EM & CCM Intravenous Fat Emulsion Rescue Therapy.

 Reported adverse effects include acute reactions such as an anaphylactoid reaction, and subacute reactions or the “fat overload syndrome” (i.e., coagulopathy, jaundice, lipid accumulation in the liver). Zohair Al Aseri MD,FRCPC EM & CCM Driscoll DF. Lipid injectable emulsions: Pharmacopeial and safety issues. Pharm Res 2006;23: Intravenous Fat Emulsion Rescue Therapy.

Weinberg GL. Treatment of Local Anesthetic Systemic Toxicity (LAST). Reg Anesth Pain Med 2010;35:  Based on previous use of intralipid for local anesthetic toxicity, the accepted dosing for IFE is a 20% lipid emulsion given as a 1.5 mL/ kg bolus, followed by an infusion of 0.25 mL/kg/min for 30 minutes (not to exceed 8 mL/kg total initial dose). Zohair Al Aseri MD,FRCPC EM & CCM Intravenous Fat Emulsion Rescue Therapy.

 may be useful in severe cases of atenolol overdoses because atenolol is less than 5% protein bound and 40-50% is excreted unchanged in urine.  Nadolol, sotalol, and atenolol, which have low lipid solubility and low protein binding, reportedly are removed by hemodialysis. Acebutolol is dialyzable.  Propranolol, metoprolol, and timolol are not removed by hemodialysis.  Consider hemodialysis or hemoperfusion only when treatment with glucagon and other pharmacotherapy fails.  Zohair Al Aseri MD,FRCPC EM & CCM Hemodialysis

Zohair Al Aseri MD,FRCPC EM & CCM

 symptomatic hypoglycemia is much more common in children, especially in those who have been fasting, and occurs even after therapeutic doses. Zohair Al Aseri MD,FRCPC EM & CCM Pediatric Considerations

 Obtunded children should receive empirical glucose, 1 to 2 mL/kg of 25% glucose IV. Generally, 5% glucose infusions have been sufficient to maintain euglycemia, especially with concomitant use of glucagon and catecholamines, which stimulate glucose release.  Because glycogen mobilization is a beta 2 effect, hypoglycemia may be less common with the cardioselective (beta 1 ) blockers. Zohair Al Aseri MD,FRCPC EM & CCM Pediatric Considerations

 Seizures also occur in cases of pediatric beta- blocker overdose, but hypoglycemia is probably an important contributing factor.  Diazepam is effective. Zohair Al Aseri MD,FRCPC EM & CCM Pediatric Considerations

 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 Disposition

 Patients ingesting sustained-release preparations should be admitted to a monitored bed, but those who remain asymptomatic 8 hours after ingestion are very unlikely to develop toxicity.  Those who have been hypotensive, who have more than first-degree heart block, or who have hemodynamically significant dysrhythmias should be admitted to the intensive care unit. Zohair Al Aseri MD,FRCPC EM & CCM Disposition

 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 CALCIUM CHANNEL BLOCKERS Perspective

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 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 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 Pathophysiology

 Peak effect of sustained-release verapamil can be delayed for many hours.  High protein binding and V d 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 Pathophysiology

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

 Cardiovascular toxicity is primarily responsible for morbidity and mortality.  Hypotension and bradycardia occur early  AV block  Sinus arrest  Junctional rhythm  Asystole.  Reflex sinus tachycardia mainly by nifedipine overdose Zohair Al Aseri MD,FRCPC EM & CCM Clinical Features

 Calcium channel blockade has little effect on ventricular conduction, so QRS widening is not seen commonly.  Ventricular dysrhythmias are also uncommon except  Bepridil, which has class I antidysrhythmic properties and prolongs the QT with increased risk of ventricular tachycardia, especially torsades de pointes Zohair Al Aseri MD,FRCPC EM & CCM Clinical Features

 Unlike beta-blockers, calcium antagonists seldom induce seizures.  Pulmonary effects include noncardiogenic pulmonary edema and apnea can also occur.  As with digitalis and beta-blocker overdose, nausea and vomiting are common. Zohair Al Aseri MD,FRCPC EM & CCM Clinical Features

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

 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 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 Diagnostic Strategies

 IV  O2  Cardiac monitoring  Vomiting is a powerful vagal stimulus that can exacerbate bradycardia and heart block. Zohair Al Aseri MD,FRCPC EM & CCM Management

 No evidence for activated charcoal.  Sorbitol should be avoided because hypotension frequently causes an ileus where residual sorbitol is metabolized to cause abdominal distension. Zohair Al Aseri MD,FRCPC EM & CCM Management

 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 Hypotension and Bradycardia

 A bolus of crystalloid fluid (20 mL/kg or more) should also be infused early. Zohair Al Aseri MD,FRCPC EM & CCM Hypotension and Bradycardia

 have considerable effect on contractility but their effect on bradycardia, AV block, and peripheral vasodilation is often poor.  A reasonable dose is 6 g of calcium chloride, but some have given much higher calcium infusions, administering up to 30 g and raising the total serum calcium level to as high as 23.8 mg/dL. Zohair Al Aseri MD,FRCPC EM & CCM Hypotension and Bradycardia Intravenous calcium

 With rapid IV injection bradycardia, AV block, AV dissociation, junctional tachycardia, ventricular ectopy, and VF have been reported.  Extravasation can cause severe tissue necrosis.  Administration through a central venous catheter is safer.  Infiltration of calcium gluconate is less destructive than calcium chloride, but larger doses are necessary Zohair Al Aseri MD,FRCPC EM & CCM Hypotension and Bradycardia Intravenous calcium

 It is prudent to raise the total serum calcium level no higher than 14 mg/dL, which the endocrine and oncology literature define as the threshold of “severe” hypercalcemia.  If ionized calcium levels are followed, it is probably wise not to exceed twice-normal levels. Zohair Al Aseri MD,FRCPC EM & CCM Hypotension and Bradycardia Intravenous calcium

 Adults should receive 10 to 20 mL of 10% calcium chloride slowly over 5 to 10 minutes, followed by a constant infusion of 5 to 10 mL/hour.  Children can receive 10 to 30 mg/kg (0.1– 0.3 mL/kg) of 10% calcium chloride initially.  calcium level can be as high as 18.2 mg/dL within 15 minutes after a bolus of just 5 mL of 10% calcium chloride, so levels should be measured later during the constant infusion. Zohair Al Aseri MD,FRCPC EM & CCM Hypotension and Bradycardia

 Most severely poisoned patients require addition of catecholamines to accelerate the heart rate (chronotropy), enhance AV conduction (dromotropy), and restore tone to peripheral vessels (vasotropy).  Most experience and success have been reported with isoproterenol and dopamine, often in combination.  Isoproterenol infusion can begin at 2 to 10 ?g/min (0.1 ?g/kg/min in children), but much higher rates may be needed. Zohair Al Aseri MD,FRCPC EM & CCM Hypotension and Bradycardia

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

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

 (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 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 Hypotension and Bradycardia Insulin

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: 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. Zohair Al Aseri MD,FRCPC EM & CCM Treatment

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

Zohair Al Aseri MD,FRCPC EM & CCM

 Nifedipine, can kill a child with ingestion of a single tablet.  Seizures may be more common in children than adults and should be treated with diazepam, lorazepam, or calcium.  Recommendations for calcium chloride administration in children range from 10 to 30 mg/kg (0.1–0.3 mL/kg of 10% calcium chloride) over 5 to 10 minutes, followed by an infusion. Zohair Al Aseri MD,FRCPC EM & CCM Pediatric Considerations

 Overall, death following calcium antagonist ingestion in children is rare. Zohair Al Aseri MD,FRCPC EM & CCM Pediatric Considerations

 Hyperglycemia occasionally occurs in children, but the elevation is usually short-lived.  Insulin it is generally not necessary, because the hyperglycemia usually resolves spontaneously within 24 to 36 hours. Zohair Al Aseri MD,FRCPC EM & CCM Pediatric Considerations

 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 Disposition

 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 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 NITRATES AND NITRITES

 Intravenous nitroglycerin infusions are being used commonly in patients with acute pulmonary edema for afterload reduction.  Infusions are usually initiated at 5 to 10 micg/min, but rates as high as 200 to 300 micg/min may be used.  hypotension may develop suddenly Zohair Al Aseri MD,FRCPC EM & CCM NITRATES AND NITRITES

 Excessive fall in blood pressure usually responds to reducing or terminating the infusion.  Use of nitrates is contraindicated in patients who have recently taken sildenafil (Viagra). Zohair Al Aseri MD,FRCPC EM & CCM NITRATES AND NITRITES

 Sildenafil and related drugs (vardenafil/Levitra and tadalafil/Cialis) inhibit type-5 phosphodiesterase, thereby relaxing vascular smooth muscle.  These agents can prolong and intensify the vasodilating effects of nitrates, resulting in severe hypotension.  If blood pressure does not rise with IV fluids, dopamine should be cautiously titrated, beginning at 5 micg/kg/min. Zohair Al Aseri MD,FRCPC EM & CCM NITRATES AND NITRITES

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

 Patients with g6pd deficiency are especially susceptible to the oxidative stress of nitrite exposure, and they may even develop hemolysis.  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 NITRATES AND NITRITES

 Pulse oximetry is not reliable, and the partial pressure of oxygen remains normal in mild to moderate cases.  This rare complication can be treated with IV methylene blue, but this antidote is usually not needed unless methemoglobinemia approaches 30% or the patient develops more reliable signs of distress, such as tachypnea, tachycardia, acidosis, and hypotension.  The usual dose of methylene blue in adults is 1 to 2 mg IV over 5 minutes. Zohair Al Aseri MD,FRCPC EM & CCM NITRATES AND NITRITES

Zohair Al Aseri MD,FRCPC EM & CCM

 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 ED Evaluation Important to know:

 Intravenous Fat Emulsion Rescue Therapy.  its use has been reported in betablocker and calcium channel blocker toxicity. Zohair Al Aseri MD,FRCPC EM & CCM Controversies

 No human randomized control trials regarding treatment with IFE are available.  A few animal studies of IFE in beta-blocker and calcium channel blocker toxicity show hemodynamic benefit. Zohair Al Aseri MD,FRCPC EM & CCM Jamaty C, Bailey B, Laroque A, et al. Lipid emulsions in the treatment of acute poisoning: A systematic review of human and animal studies. Clin Toxicol 2010;48:1-27 Tebbutt S, Harvey M, Nicholson T, et al. Intralipid prolongssurvival in a rat model of Verapamil Toxicity. Acad Emerg Med 2006;13: Cave, G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: A systematic review. Acad Emerg Med 2009;16: Cave G, Harvey M, Castle C. The role of fat emulsion therapy in a rodent model of propranolol toxicity: A preliminary study. J Med Toxicol 2006;2:4-7  Intravenous Fat Emulsion Rescue Therapy.

 There are multiple human case reports in which IFE appears to have contributed to recovery from cardiogenic shock or arrest. Zohair Al Aseri MD,FRCPC EM & CCM 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: Jamaty C, Bailey B, Laroque A, et al. Lipid emulsions in the treatment of acute poisoning: A systematic review of human and animal studies. Clin Toxicol 2010;48:1-27 Cave, G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: A systematic review. Acad Emerg Med 2009;16: Cave G, Harvey M, Castle C. The role of fat emulsion therapy in a rodent model of propranolol toxicity: A preliminary study. J Med Toxicol 2006;2:4-7 Dolcourt BA, Aaron CK. Intravenous fat emulsion for refractory verapamil and atenolol induced shock: A human case report. Clin Toxicol 2008;46:619 Young AC, Velez LI, Kleinschmidt KC. Intravenous fat emulsion therapy for intentional sustained-release verapamil overdose. Resuscitation 2009;80:591-3  Intravenous Fat Emulsion Rescue Therapy.

 As these are case reports, and there may exist a bias against reporting or publishing negative outcomes, human case-control studies are needed to further elucidate the efficacy of IFE in beta-blocker and calcium channel blocker overdose. Zohair Al Aseri MD,FRCPC EM & CCM  Intravenous Fat Emulsion Rescue Therapy.

 At this time, given the potential benefit and despite no human randomized controlled trials performed to date, IFE may be considered for patients who are failing other modalities or during cardiac arrest. Zohair Al Aseri MD,FRCPC EM & CCM Intravenous Fat Emulsion Rescue Therapy.

 Reported adverse effects include acute reactions such as an anaphylactoid reaction, and subacute reactions or the “fat overload syndrome” (i.e., coagulopathy, jaundice, lipid accumulation in the liver). Zohair Al Aseri MD,FRCPC EM & CCM Driscoll DF. Lipid injectable emulsions: Pharmacopeial and safety issues. Pharm Res 2006;23: Intravenous Fat Emulsion Rescue Therapy.

West P, McKeown NJ, Hendrickson RG. Iatrogenic lipid emulsion overdose in a case of amlodipine poisoning. Clin Toxicol 2010;48:393-6  One case report of iatrogenic IFE overdose describes interference with laboratory studies, but otherwise no other attributable adverse effects were noted. Zohair Al Aseri MD,FRCPC EM & CCM Intravenous Fat Emulsion Rescue Therapy.

Weinberg GL. Treatment of Local Anesthetic Systemic Toxicity (LAST). Reg Anesth Pain Med 2010;35:  Based on previous use of intralipid for local anesthetic toxicity, the accepted dosing for IFE is a 20% lipid emulsion given as a 1.5 mL/ kg bolus, followed by an infusion of 0.25 mL/kg/min for 30 minutes (not to exceed 8 mL/kg total initial dose). Zohair Al Aseri MD,FRCPC EM & CCM Intravenous Fat Emulsion Rescue Therapy.

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