Initially, all b-blocker exposures should be evaluated in a high-acuity area of the emergency department. For serious cases, treatment begins by establishing adequate airway patency, ventilation, and oxygenation. Multiple intravenous access sites, as well as central venous access, may be required.

The goal of specific cardiovascular drug therapy is to restore perfusion to critical organ systems by improving myocardial contractility, increasing heart rate, or both. Current therapy is derived principally from reports of case studies and includes glucagon, adrenergic agonists, atropine, and phosphodiesterase inhibitors. Overall, these therapies have met with variable success. Figure 169-1 is an algorithm for use of these drugs based on review of available human cases and limited experimental studies.

Glucagon is widely accepted as first-line therapy. It enhances myocardial performance by increasing cAMP concentrations in a manner identical to that of catecholamines but is thought to act via its own receptor.8 Thus, glucagon may bypass the blocked b receptor. Clinical experience with this antidote has generally produced favorable results, often after other treatments have failed. However, only two cases report glucagon as the sole pharmacologic agent to resuscitate severely toxic propranolol overdoses.9 In several instances, glucagon failed to reverse toxicity. —II A limited number of animal models directly comparing glucagon to other therapies support the use of glucagon.12

The initial glucagon dose is 50 to 150 Mg/kg intravenous bolus. For a 70-kg patient, this represents 3.5 to 10 mg. The bolus may be repeated as needed. Because the duration of action of glucagon is 15 min, a constant infusion of 1 to 10 mg/h may be necessary to sustain its effect. There is no defined maximum therapeutic dose of glucagon. Cumulative bolus doses ranged from 1 to 30 mg.1 I4 Infusions have been continued for up to 26 h.15

Compared to the potential benefits of increasing heart rate and blood pressure, the adverse effects of glucagon are minimal. Nausea and vomiting may occur due to esophageal sphincter relaxation. Mild, transient hyperglycemia may develop. When using large amounts of glucagon, excessive exposure to phenol, the manufacturer's diluent, may occur, resulting in seizures, hypotension, or dysrhythmias.16 To avoid these unwanted effects, discard the supplied diluent and reconstitute glucagon with normal saline solution.

Unfortunately, sufficient amounts of glucagon are frequently unavailable in hospital pharmacies. 17 If glucagon is not available or fails to restore organ perfusion, the next step is to add a catecholamine.

b-adrenergic receptor agonists (catecholamines) are a logical therapy for b-blocker toxicity. Nevertheless, their use has met with disappointing results, restoring heart rate in only two-thirds of cases and blood pressure in only half. Results may not have been optimal because of inadequate dosing. For example, in humans, the dose of isoproterenol required to maintain heart rate and blood pressure had to be increased 26-fold following an infusion of labetolol. 18 In canines, isoproterenol and dopamine had to be increased 15 and 5 times, respectively, to overcome the depressant effects of propranolol. 19

When faced with significant b-blocker toxicity, dopamine or norepinephrine are the catecholamines of choice. These agents may be preferable to epinephrine for two reasons. First, in animal models of propranolol toxicity, epinephrine had no effect on mortality rates. 20 Second, in similar calcium channel blocker toxicity models, epinephrine failed to provide optimal myocardial energy substrates needed during shock. 21 Dopamine or norepinephrine is administered as a constant infusion. Dopamine is more likely to work for mildy toxic cases. For severe toxicity, one may need to start with norepinephrine. Potential adverse effects of catecholamines include dysrhythmia, tissue necrosis, and increased myocardial oxygen demand.

Phosphodiesterase inhibitors have been used to treat b-blocker toxicity. In theory, they inhibit cAMP breakdown, thereby facilitating maintenance of intracellular calcium levels. In propranolol-induced heart failure, amrinone demonstrated positive inotropic effects without increasing myocardial oxygen demands. 22 However, other animal studies are not encouraging. Amrinone and milrinone increased cardiac output but had no appreciable effect on heart rate. 12 When administered with glucagon, neither amrinone or milrinone provided any additional benefit over that of glucagon. 23 Thus, phosphodiesterase inhibitors have no advantage over glucagon. However, if glucagon is not available, phosphodiesterase inhibitors can be reasonable alternatives.

Atropine is unlikely to be effective in the management of bradycardia and hypotension.

Treatment of ventricular dysrhythmias due to sotalol requires pharmacologic measures different from those required for other b blockers. Isoproterenol, lidocaine, and overdrive pacing have been successfully used. Magnesium may also be of benefit. 24

Extrinsic pacing may be required to maintain heart rate. However, electrical capture is not always successful, and, if capture does occur, blood pressure is not always restored. Cardiac pacing may be most beneficial in treating torsades de pointes associated with sotalol. 24

Occasionally, extreme means of resuscitation, including extracorporeal circulation 25 and aortic balloon pump,26 have been successful. Insulin-dextrose was superior to standard antidotes in animals19 and was used successfully in a combined amlodipine and atenolol overdose. 27

Gastrointestinal decontamination with 1.0 g/kg plain activated charcoal should be initiated unless oral intake is contraindicated. Gastric lavage may be beneficial prior to instillation of charcoal if it can be accomplished within 1 to 2 h of ingestion. Syrup of ipecac is contraindicated, since b-blocker intoxicated patients may experience a rapid decline in mental status, with risk of aspiration during vomiting.

Based on previously described pharmacokinetic properties, hemodialysis would not be expected to effectively remove lipophilic b-blocker drugs that have a large volume of distribution or extensive protein binding. Hemodialysis may be useful for atenolol, nadolol, and sotalol overdose because these drugs have a lower volume of distribution and less protein binding than do other b blockers.

Spiritual Weight Loss Mentality

Spiritual Weight Loss Mentality

Awesome Ways To Get Over Your Mentality That Keeps you Overweight! This Book Is One Of The Most Valuable Resources In The World When It Comes To Results In Your Slim-down and Health Efforts! Day in day out we keep ourselves absorbed with those matters that matter the most to us. A lot of times, it might be just to survive and bring in some money. In doing so we at times disregard or forget about the extra matters that are essential to balance our lives. They’re even more essential to supply real meaning to our world. You have to pay attention to your wellness.

Get My Free Ebook

Post a comment