BETA BLOKERSTintinalli's Emergency Medicine 2010BY 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