Toxicology 6: Beta Blocker Toxicity Portal
Overview
Beta blockers act as competitive inhibitors of catecholamines, exerting their effects at both central and peripheral receptors. Blockade of beta-receptors results in decreased production of intracellular cyclic adenosine monophosphate (cAMP) with a resultant blunting of multiple metabolic and cardiovascular effects of circulating catecholamines. Beta1-blockers reduce heart rate, blood pressure, myocardial contractility, and myocardial oxygen consumption. Beta2-receptor blockade inhibits relaxation of smooth muscle in blood vessels, bronchi, the gastrointestinal system, and the genitourinary tract. In addition, beta-adrenergic receptor antagonism inhibits both glycogenolysis and gluconeogenesis, which may result in hypoglycemia.
Signs and Symptoms:
Bradycardia:
Hypotension:
Seizures:
EKG changes:
- Sinus or nodal bradycardia
- First-degree AV block
- QRS prolongation (slight)
- QT Prolongation
Hypothermia, hypoglycemia can occur but are less common.
Bradycardia, by itself, is not necessarily helpful as a warning sign because slowing of the heart rate and damping of tachycardia in response to stress is observed with therapeutic doses. If a patient is bradycardic and hypotensive consider a beta-blocker or calcium blocker overdose.
Severe beta blocker toxicity consists of bradycardia with
associated hypotension and shock (systolic BP <80 mm Hg, HR
<60 bpm).
Intermediate toxicity results in a moderate drop in blood pressure
(systolic BP >80 mm Hg) and/or bradycardia (heart rate
<60 bpm).
The first critical signs of overdose can appear 20 minutes postingestion but are more commonly observed within 1-2 hours. All clinically significant beta blocker overdoses develop symptoms within 6 hours. While the half-life of these compounds is usually short (2-12 h), half-lives in the overdose patient may be prolonged because of a depressed cardiac output reducing blood flow to the liver and kidneys or because of the formation of active metabolites.
A depressed level of consciousness and seizures may occur as a result of cellular hypoxia from poor cardiac output, a direct CNS effect caused by sodium channel blocking, or even hypoglycemia. The lipid-soluble agents have increased distribution into the brain and these agents are associated with severe CNS toxicity. Lipid soluble beta blockers, such as propranolol, frequently present with seizures after an overdose. Coma may be prolonged, depending on the half-life of the agent involved and the coexisting morbidity.
Treatment
The goal of therapy in beta blocker toxicity is to restore perfusion to critical organ systems by increasing cardiac output. This may be accomplished by improving myocardial contractility, increasing heart rate, or both. If possible determine the specific type of beta blocker, quantity, and time of the overdose. Information regarding the patient's underlying medical condition may clue the clinician to the possibility of an overdose.
Gastric decontamination: Gastric lavage may be beneficial in a severe overdose if the patient presents to the ED within 1-2 hours of ingestion.
Crystalloid: If hypotensive, administer 20 mL/kg of isotonic intravenous fluids and place the patient in Trendelenburg position. If the patient is unresponsive to these measures, administer pharmacologic therapies.
Epinephrine is especially useful in beta blocker overdoses. Give an epinephrine infusion of 2 to 100 µg/min IV or a combination of epinephrine and dopamine. Isoproterenol, dobutamine, and/or norepinephrine may be administered to patients who do not regain hemodynamic stability with epinephrine.
Glucagon: Is losing favor as an antidote but can still be used safely. Because a glucagon bolus can be diagnostic and therapeutic, administer glucagon and check for a response. Give an initial dose of 3mg (0.05 mg/kg) IV bolus then and IV infusion of 5mg/hr (0.07 mg/kg/hr), then titrate to maximum of 10 mg/h (use BP, HR, OR both as parameters).
Consider pretreating with an antiemetic as nausea can be a side effect. Monitor the potassium levels frequently due to the potassium shift caused by the glucagon. The blood glucose rise is usually not of clinical significance in a non diabetic patient. Monitor the glucose following glucagon therapy as rebound hypoglycemia can occur.
Use pacing, either TCP or TVP, for bradycardia that is unresponsive to the preceding therapies. Cardiac pacing may be effective in increasing the rate of myocardial contraction. Electrical capture is not always successful and, if capture does occur, blood pressure is not always restored. Atropine is rarely effective in beta blocker-induced bradycardia or for reversing symptomatic heart block
High-dose Insulin: In case reports and animal models, high-dose insulin infusion (in combination with glucose administration to maintain serum glucose levels) has been reported to improve outcomes. The exact mechanism is not known but it appears to promote the uptake and utilization of carbohydrates as and energy source.
If you are not familiar with the use of high-dose insulin for the treatment of beta blocker toxicity we suggest you first consult your poison control center before beginning treatment.
One suggested protocol for the use of high-dose insulin for the treatment of beta blocker toxicity (which is not suggested for use if the initial blood glucose level is > 200 mg/dl) is to begin with an initial bolus of regular insulin of 0.1 units/kg IV followed with a continuous infusion of IV regular insulin starting at 0.1 units/kg/hour and rapidly increasing the continuous infusion of insulin to a goal of at least 1.0 units/kg/hour. (Infusion rates much higher than 1.0 units/kg/hour has been used by some providers.) The IV insulin needs to be combined with IV dextrose to maintain a euglycemic state with a blood glucose value being kept at or above 100 mg/dl. Give an initial bolus of IV dextrose of 25 to 50 grams, followed by a continuous infusion of 0.5 to 1.0 grams of glucose/kg/hour. Carefully monitor the serum glucose level, initially every 10 to 15 minutes, while titrating the insulin dose. Once the infusion of insulin is stabilized, monitor the glucose every 30 minutes x four hours and then every hour. Intermittent boluses of IV dextrose may be necessary. The response to the IV insulin infusion is typically delayed for 15 to 60 minutes and lasts approximately one hour after the insulin has been shut off. The insulin infusion may be necessary for 12 to 36 hours or more. Note: a similar use of high-dose insulin has been used to treatment calcium channel blocker toxicity.
References
- Harris CR. The Toxicology Handbook for Clinicians. Philadelphia, Pa: Mosby Elsevier, 2006.
- Lemkin E, Barrueto F, et al. Use of high-dose insulin for treatment of beta blocker toxicity. UpToDate, Version 16.1, January 2008.