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Beta blocker poisoning

Author: Fermin Barrueto, Jr, MD, FACEP, FAAEM, FACMT

Section Editor: Stephen J Traub, MD
Deputy Editor: Jonathan Grayzel, MD, FAAEM

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2017. | This topic last updated: Apr 11, 2017.

INTRODUCTION — Beta adrenergic antagonists (beta blockers) have been in clinical use for more than 30 years, and are
employed in the management of a range of disorders, including hypertension, ischemic heart disease, heart failure,
arrhythmias, migraine headache, tremor, portal hypertension, and aortic dissection. Although safe for most patients when
taken as prescribed, beta blocker toxicity is associated with significant morbidity and mortality. In 2006, there were 9041
single beta blocker exposures reported to poison centers in the United States. Of these, there were 613 moderate or major
adverse outcomes and four deaths [1].

Complications following beta blocker overdose are related to excessive beta adrenergic blockade, and occasionally the
proarrhythmic (membrane-stabilizing) activity of these agents on cardiac conduction [2]. Ingestion of other cardioactive
agents in association with beta blockers increases mortality following overdose [2,3]. Common and potentially dangerous
coingestions include calcium channel blockers, cyclic antidepressants, and neuroleptics [2].

An overview of beta blocker intoxication will be presented here. A summary table to facilitate emergent management is
provided (table 1). A general approach to an adult patient with possible drug intoxication, and an overview of adverse effects
of beta blockade, are discussed separately. (See "General approach to drug poisoning in adults" and "Major side effects of
beta blockers".)

PHARMACOLOGY

Receptor types and general mechanism — There are at least three distinct types of beta receptors:

● Beta 1, which are found primarily in heart muscle. Activation of these receptors results in an increase in heart rate,
contractility, atrioventricular (AV) conduction, and a decrease in AV node refractoriness.

● Beta 2, which are present in heart muscle but are more prominent in bronchial and peripheral vascular smooth muscle.
Activation of these receptors results in vasodilation and bronchodilation.

● Beta 3, which are found in adipose tissue and the heart. Activation of these receptors may mediate catecholamine-
induced thermogenesis and may reduce cardiac contractility.

Competitive antagonism of the beta receptor decreases cellular levels of cyclic adenosine monophosphate (cAMP). Beta-1
selective blockade results in depressed myocardial contractility, decreased automaticity in pacemaker cells, and decreased
conduction velocity through the atrioventricular node [3]. The lungs, peripheral blood vessels, glucose metabolism, and
central nervous system are all affected by beta blockade. Nonselective beta blockade results in systemic effects including
bronchoconstriction, impaired gluconeogenesis, and decreased insulin release. (See "Major side effects of beta blockers".)

CELLULAR TOXICOLOGY — There are many beta blockers available for clinical use, and although they all inhibit the
beta-adrenoreceptor, there are several characteristics that differ among these agents. Following overdose, manifestations of
toxicity are observed in varying degrees, depending on the specific agent and dose involved [3,4]. In addition to beta-
adrenoreceptor blockade, three properties that affect toxicity include the membrane stabilizing activity (MSA), lipophilicity,
and intrinsic sympathomimetic activity (ISA) of the ingested agent (table 2).

● Membrane stabilizing activity (MSA) – Membrane stabilizing agents (eg, propranolol, acebutolol) inhibit myocardial fast
 sodium channels, which can result in a widened QRS interval and may potentiate other dysrhythmias.

● Lipophilicity – Beta blockers with high lipid solubility (eg, propranolol) rapidly cross the blood brain barrier into the
central nervous system, predisposing to neurologic sequelae such as seizures and delirium. Beta Blockers with this
characteristic are more amenable to treatment with 20 percent lipid emulsion therapy in the setting of a clinically
significant overdose [5].

● Intrinsic sympathomimetic activity (ISA) – Many agents demonstrate a partial agonist effect at the beta receptor site,
resulting in less bradycardia and hypotension in therapeutic and supratherapeutic doses. Bronchoconstriction is also
less likely to occur with compounds that possess intrinsic sympathomimetic activity (ISA), or beta-1 selectivity.
However, the protective effects of ISA do not completely prevent cardiovascular toxicity following intentional or
accidental overdose.

TOXICITY OF SPECIFIC AGENTS — Of all the variables contributing to toxicity, membrane stabilizing activity (MSA)
appears to have the greatest influence on adverse cardiovascular effects (table 2). Agents with significant MSA include
propranolol, acebutolol, betaxolol, and oxprenolol. The effect of MSA is thought to be negligible at therapeutic doses, but in
overdose can cause significant cardiovascular morbidity. In one retrospective study, 94 percent (15 out of 16) of patients
with cardiovascular toxicity had a history of ingesting beta blockers with MSA [2].

Acebutolol, a cardioselective agent with partial agonist activity and significant MSA, is one of the most toxic beta blockers in
overdose [6]. Acebutolol toxicity may predispose the patient to ventricular repolarization resulting in arrhythmias [6].

Sotalol combines class III antidysrhythmic properties with beta adrenergic antagonism. Sotalol prolongs the action potential
duration and increases the refractory period by blocking delayed potassium channels. This leads to prolongation of the QTc
interval, and can contribute to the development of Torsades de Pointes [7]. (See "Therapeutic use and major side effects of
sotalol" and "Acquired long QT syndrome", section on 'Drug-induced TdP'.)

Carvedilol has been associated with toxic epidermal necrolysis at therapeutic levels [8].

PHARMACOKINETICS — In therapeutic use, most beta blockers have half-lives ranging from two to eight hours, but
kinetics can change in overdose (table 2). Ingestion of sustained release preparations can delay the onset of symptoms and
substantially prolong the duration of toxicity.

Many beta blockers are metabolized via the liver. Esmolol is metabolized by erythrocyte esterases. Atenolol, bisoprolol,
labetalol, and sotalol are eliminated by the kidney.

CLINICAL FEATURES OF OVERDOSE — Diagnosis of beta blocker intoxication is made on the basis of history and
clinical presentation.

History — Data obtained should include the specific agent, amount ingested, time of ingestion, and any coingestions.
Historical features that suggest increased risk for severe toxicity include:

● Coingestion of other cardioactive agents

● Underlying cardiac disease (eg, heart failure)
● Ingestion of sotalol or another agent with membrane-stabilizing activity (eg, propranolol or acebutolol) (see 'Toxicity of
specific agents' above)

Any possible witnesses and emergency medical services (EMS) personnel who may have recovered pill bottles at the
scene should be contacted. The patient's pharmacy may provide valuable information regarding prescribed medications, the
date of the most recent refill, and the total number of pills dispensed.

Physical findings — Most patients who overdose on beta blockers become symptomatic within two hours following
ingestion, and nearly all develop symptoms within six hours [2,9]. Exceptions to this general rule include ingestions of
sustained release medications and sotalol [10]. In these cases, delayed toxicity up to 24 hours after ingestion can occur.

Bradycardia and hypotension are the most common effects, and in severe overdoses can result in profound myocardial
depression and cardiogenic shock. Ventricular dysrhythmias are seen more frequently following propranolol and acebutolol
exposures, probably because of the increased membrane-stabilizing activity (MSA) of these agents (table 2) [2,11]. Other
potential effects of severe toxicity include mental status change, seizure, hypoglycemia, and bronchospasm.
Mental status changes, including delirium, coma, and seizures, occur most frequently in patients with severe hypotension,
but can occur in those with normal blood pressure [12]. Similarly, respiratory depression usually occurs in hypotensive,
comatose patients, but has been reported in awake patients. Specific agents, particularly propranolol, are associated with
neurologic effects in the absence of cerebral hypoperfusion. This was demonstrated in a report comparing the clinical
course of patients following overdose with either propranolol or other beta blockers [9]. Although the minimum pulse and
systolic and diastolic ranges were not significantly different between groups, 29 percent of the propranolol group
experienced seizures versus none in the non-propranolol group. This difference is probably due to the increased lipophilicity
of propranolol, allowing rapid diffusion into the central nervous system.

In addition to the cardiovascular and neurologic manifestations, bronchospasm and hypoglycemia can complicate acute
beta blocker intoxication. Early recognition and prompt treatment of hypoglycemia is critical. (See 'Management' below.)

LABORATORY EVALUATION

Laboratory studies — Although serum concentrations of most beta blockers can be measured, they cannot be obtained in
time to be clinically useful and are generally performed only for academic or forensic purposes.

In patients with beta blocker overdose, we generally obtain the following studies: an electrocardiogram (ECG), a fingerstick
glucose, serum electrolytes including calcium, and blood urea nitrogen and creatinine levels. If calcium is administered
repeatedly, levels should be measured every four to six hours. If an insulin/glucose treatment regimen is used, glucose and
potassium levels must be measured every 30 to 60 minutes. (See 'Insulin and glucose' below and 'Calcium' below.)

Routine laboratory evaluation of any poisoned patient should include acetaminophen and salicylate levels, to rule out these
common coingestions, and a pregnancy test in women of childbearing age.

A serum lactate concentration above 3 mmol/L is used to predict life-threatening overdose of some medications. However,
this may be an insensitive finding with beta blocker overdose. In one retrospective study, four of nine deaths associated with
beta blocker poisoning were associated with serum lactate concentrations below 3 mmol/L [13].

Additional tests are obtained based upon clinical findings. As an example, a plain chest radiograph is obtained in patients
with signs of pulmonary edema.

Electrocardiogram — Beta blockers decrease conduction velocity across the atrioventricular (AV) node, resulting in PR
prolongation; they also slow automaticity within the sinoatrial (SA) node, causing bradycardia [14].

QRS prolongation occurs more commonly when beta blockers with membrane stabilizing activity (MSA) are ingested.
Significant QTc prolongation can develop following sotalol overdose as a result of its independent Class III antiarrhythmic
activity. In severe poisoning, the electrocardiogram (ECG) can show ANY bradydysrhythmia, and can progress to asystole.
(See "Advanced cardiac life support (ACLS) in adults", section on 'Asystole and pulseless electrical activity'.)

A Brugada-like ECG pattern has been reported in the setting of propranolol poisoning, suggesting that other beta blockers
that are lipophilic or possess membrane stabilizing activity might have similar effects [15].

DIAGNOSIS — The diagnosis of beta blocker poisoning is made clinically on the basis of the history and clinical
presentation. Typically there is a history of overdose combined with findings of bradycardia and hypotension, which can be
profound in severe overdose, resulting in cardiogenic shock. Other findings can include ventricular dysrhythmia, altered
mental status, seizure, hypoglycemia, and bronchospasm. Although serum concentrations of most beta blockers can be
measured, such measurements cannot be obtained in time to be clinically useful.

DIFFERENTIAL DIAGNOSIS — Many drugs can cause profound hypotension or bradydysrhythmia in overdose. Calcium
channel blockers, digoxin, clonidine, and cholinergic agents must be considered when evaluating bradydysrhythmia
potentially caused by a toxic ingestion.

Calcium channel blockers are less likely than beta blockers to produce alterations in mental status, and frequently do not do
so unless the patient is in profound shock. Hyperglycemia occurs more often with calcium channel blocker toxicity, while
beta blockers are associated with hypoglycemia. (See "Calcium channel blocker poisoning".)

Nausea and vomiting occur more often with digoxin toxicity than beta blocker toxicity. Digoxin may cause characteristic
changes in an electrocardiogram, such as scooped ST segment depressions. Digoxin is more likely to produce rhythms of
increased automaticity, such as atrial tachycardia with atrioventricular block, premature ventricular contractions, or
ventricular arrhythmias. (See "Digitalis (cardiac glycoside) poisoning".)

Clonidine produces a constellation of signs that can resemble opioid overdose, including somnolence and miosis, but are
accompanied by hypotension and bradycardia.

Overdose of a cholinergic agent can present with bradycardia but also includes other characteristic features (salivation,
lacrimation, urination, defecation, GI upset, and muscle excitability).

MANAGEMENT

Acute stabilization and overview of therapy — First, secure the airway and provide advanced cardiac life support as
necessary (table 1). Atropine should be given early in bradycardic patients and as a pretreatment agent when rapid
sequence intubation is required [16]. Establish intravenous access and provide continuous cardiac monitoring. A summary
table to facilitate emergent management is provided (table 1). (See "Rapid sequence intubation for adults outside the
operating room" and "Advanced cardiac life support (ACLS) in adults".)

Treat hypotension with intravenous (IV) boluses of isotonic fluid; treat symptomatic bradycardia with atropine. Atropine is
given in a dose of 0.5 to 1 mg every three to five minutes up to a total of 0.03 to 0.04 mg/kg. Sodium bicarbonate and
magnesium may be needed to treat some arrhythmias. (See 'Other therapies' below.)

Treat symptomatic hypoglycemia with IV dextrose. For adults, administer boluses of 50 percent dextrose in water (D50W);
for children administer an appropriate IV bolus of dextrose (0.25 g/kg body weight). In infants and young children this is
usually given as 2.5 mL/kg of 10 percent dextrose solution. Multiple doses of dextrose may be necessary. Treatment of
hypoglycemia in children is discussed in detail separately. (See "Approach to hypoglycemia in infants and children".)

Treat seizures with benzodiazepines (eg, lorazepam). (See "Convulsive status epilepticus in adults: Classification, clinical
features, and diagnosis".)

IV fluid and atropine often do not completely reverse the cardiotoxic effects of beta blocker overdose. In such cases, we
give additional treatments based upon the severity of the presentation. These treatments may include:

● IV glucagon
● IV calcium salts
● Vasopressor
● High dose insulin and glucose infusions
● Lipid emulsion therapy

These therapeutic options are discussed below. (See 'Approach to the selection of specific therapies' below.)

Hemodialysis may be needed in specific circumstances, although this is uncommon. In such cases a nephrologist should be
contacted early in the patient’s course. (See 'Other therapies' below.)

Many patients with isolated beta blocker overdose remain asymptomatic and can be discharged after a period of
observation. (See 'Disposition' below.)

Approach to the selection of specific therapies — Although it is ideal to institute treatments individually to assess their
success or failure, this is often not possible in patients who are severely ill from a beta blocker poisoning. Our suggested
approaches to therapy based upon the severity of the clinical presentation are described here; a summary table to facilitate
emergent management is provided (table 1).

Severely symptomatic patients — Our suggested approach to patients manifesting signs of severe beta blocker
poisoning (profound hypotension and/or severe bradycardia, depressed mental status) consists of multiple simultaneous
interventions, including all of the following treatments [17,18]:

● Stabilization of the airway as necessary (avoid induction agents that exacerbate hypotension)

● Additional IV boluses of isotonic crystalloid

● IV glucagon
 ● IV calcium salts

● IV vasopressor (eg, epinephrine)

● IV high-dose insulin and glucose

● IV lipid emulsion therapy

Dosing for each of these therapies is provided below. (See 'Specific therapies' below.)

Mildly symptomatic patients — Our suggested approach to patients with mild hypotension or bradycardia begins with
IV boluses of isotonic crystalloid and atropine respectively. However, these therapies often do not completely reverse the
cardiotoxic effects of beta blocker poisoning. In such cases, we add the following treatments in succession based upon
patient response. As an example, we begin treatment with glucagon if IV crystalloid does not adequately improve the
patient’s blood pressure, but if hypotension resolves following treatment with glucagon, we do not proceed to IV calcium
salts or any other treatment specifically for the overdose.

● IV glucagon

● IV calcium salts

● IV vasopressor (eg, epinephrine)

● IV high-dose insulin and glucose

● IV lipid emulsion therapy

A period of 15 minutes is reasonable to determine the effectiveness of a specific therapy before proceeding to the next
treatment. Dosing for each of these therapies is provided below. (See 'Specific therapies' below.)

Asymptomatic patients — Many patients with an isolated beta blocker overdose remain asymptomatic and may be
discharged after a period of observation, unless the overdose was intentional. (See 'Disposition' below.)

Specific therapies

Glucagon — Despite limited data, glucagon is considered first-line, antidotal treatment for beta blocker overdose
[19,20]. Glucagon may be effective initially for a brief period, but prolonged treatment may become ineffective due to
tachyphylaxis. Intravenous (IV) glucagon is given as a slow bolus dose followed by continuous infusion. An initial bolus of 5
mg intravenously is administered over one minute; if there is no increase in pulse or blood pressure after 10 to 15 minutes,
a second bolus should be administered. The initial pediatric dose is 50 mcg/kg. An effect should be observed within one to
three minutes, with a peak response at five to seven minutes. If there is no observed effect after 10 minutes following a
second dose, it is unlikely an infusion will provide benefit.

If there is an increase in pulse or blood pressure, an infusion is started at a rate of 2 to 5 mg/hour (pediatric dose 70
mcg/kg/hour). The goal is to maintain a mean arterial pressure of 60 mmHg. If this cannot be achieved, additional therapies
are implemented in a sequential manner, beginning with calcium salts. When used as a sole agent in humans, glucagon has
been associated with treatment failures.

Vomiting is common following administration of glucagon. We suggest prophylactic or concurrent administration of a

serotonin antagonist antiemetic (eg, ondansetron). (See "Characteristics of antiemetic drugs".)

Glucagon activates adenylate cyclase at a site independent from beta-adrenergic agents, causing an increase in adenosine
3'-5'-cyclic monophosphate (cAMP). Elevations in cAMP increase the intracellular pool of calcium available for release
during depolarization, augmenting contractility. The successful use of glucagon to manage beta blocker toxicity has been
documented in many case reports, but no controlled trials involving humans have been conducted [21]. One review of the
available controlled trials in animal models found that glucagon increased heart rate (HR), at least transiently, but had
minimal effect on mean arterial pressure (MAP) [19].

In 2006, a trial comparing vasopressin with glucagon in a swine model of propranolol overdose found no difference in
survival at four hours [22]. No difference was detected in HR, MAP, systolic BP, or cardiac output, except in the first hour,
when vasopressin caused a marked increase in MAP and systolic BP. Notably, cardiac output did not improve following
glucagon administration.

Calcium — A number of case reports demonstrate the efficacy of IV calcium salts in treating beta blocker toxicity [23,24].
Either calcium chloride or calcium gluconate may be given.

Calcium chloride, 1 g of a 10 percent solution (10 mL), is given as a slow push, and should be administered via a central
venous catheter. The dose may be repeated up to a total of 3 g. The pediatric dose is 20 mg/kg (maximum dose is 1 g); up
to 60 mg/kg may be given.

Calcium gluconate should be given if only peripheral IV access is available. The percentage of elemental calcium in calcium
gluconate is one-third that of the calcium chloride salt, so 30 mL of a 10 percent solution should be administered as an initial
dose. In children, give 60 mg/kg per dose (maximum dose is 3 g).

Clinicians must monitor serum calcium concentrations if treatment with an IV calcium salt is given. Lethal iatrogenic
overdose has been reported [25].

IV calcium salts may improve hemodynamic parameters by increasing inotropy. Animal models suggest that calcium salts
increase blood pressure and cardiac output, but do not increase heart rate, following combined calcium channel blocker and
beta blocker overdose [26].

Vasopressor (catecholamine) — In animal models and human case reports, treatment of beta blocker overdose with
catecholamine infusion alone has resulted in poor outcomes [27-29]. Catecholamine infusions may be added if the
combination of atropine, IV fluids, glucagon, and IV calcium salts are unsuccessful in improving cardiovascular
performance, or as a temporizing measure until high dose insulin therapy starts to take effect. The vasopressor can then be
titrated downward as tolerated. (See "Use of vasopressors and inotropes".)

An infusion of epinephrine at 1 mcg/minute can be started and titrated upwards to maintain a MAP of 60 mmHg. Pediatric
dosing starts at 0.1 mcg/kg/minute and is titrated upwards based upon the patient's MAP. High infusion rates may be
necessary to overcome competitive inhibition. An arterial line may be needed to monitor blood pressure.

Catecholamines exert positive inotropic and chronotropic activity on the myocardium by stimulating adrenergic receptors
and increasing the concentration of cAMP. One possible explanation for the lack of effectiveness of catecholamines in beta
blocker overdose is that high doses are often required to achieve a therapeutic effect, and such doses may increase the risk
of arrhythmia. In addition, some speculate that unopposed alpha constriction increases the cardiac workload, diminishing
stroke volume and cardiac output.

Insulin and glucose — High-dose insulin is being used with greater frequency to treat beta-blocker overdose. In
patients who manifest hemodynamic instability refractory to the other therapies described above, we suggest that a trial of
high-dose insulin and glucose be administered, possibly in combination with other agents depending on the clinical
scenario, and titrated upward until blood pressure stabilizes. (See 'Approach to the selection of specific therapies' above.)

The dosing regimen for high-dose insulin is described in detail separately. (See "Calcium channel blocker poisoning",
section on 'Insulin and glucose'.)

Of note, hypoglycemia is a possible complication of this treatment since the dose of insulin is much higher (approximately
10-fold) than that typically given for diabetic ketoacidosis. When necessary, euglycemia can be maintained by means of a
continuous IV infusion of 5 to 10 percent dextrose. A hemodynamic response to high-dose insulin therapy is delayed for 30
to 60 minutes, therefore simultaneous implementation of other therapies to support the patient's pulse and blood pressure
are generally required. Repletion of potassium and magnesium may be needed.

Animal studies and case reports of both isolated beta blocker overdose and combined calcium channel blocker and beta
blocker overdose suggest that treatment with high dose insulin and glucose is effective [26,30,31]. However, the role for this
therapy in pure beta blocker overdose remains unsettled, despite an increasing number of case reports describing
successful treatment of patients with severe beta-blocker and mixed beta-blocker overdoses [32]. Often, such cases involve
patients treated with multiple therapies (eg, calcium, atropine, glucagon, vasopressors) before treatment with high dose
insulin, making it difficult to determine which therapy was most effective. High dose insulin has been well tolerated in
patients, and has been administered for prolonged periods, up to 116 hours in one case [32].

One animal study of insulin therapy in propranolol toxicity was terminated early when every pig in the insulin and glucose
treatment group achieved the study goal of four hour survival, while those treated with vasopressin and epinephrine died
within 90 minutes [27]. Cardiac output (CO) in animals treated with insulin and glucose increased steadily and consistently,
while CO in animals treated with vasopressin and epinephrine decreased until death.

It appears that insulin exhibits a steady dose response curve, and may be titrated upwards until blood pressure improves.
One study using a pig model of propranolol overdose, compared treatments with placebo and insulin at doses of 1 unit/kg
per hour, 5 units/kg per hour, and 10 units/kg per hour [33]. For each one unit/kg per hour increase of insulin, there was a
statistically significant increase in cardiac output, and no ceiling effect was noted.

The pathophysiology of beta blocker intoxication is similar in many respects to that of calcium channel blocker (CCB)
intoxication, for which high dose insulin and glucose therapy has been more extensively studied. Although the mechanism is
not completely understood, both CCB and beta blocker poisoning appear to interfere with myocyte metabolism. In addition,
beta blockers inhibit pancreatic insulin release further reducing available glucose and diminishing CO. Insulin appears to
improve inotropy by providing substrate for aerobic metabolism within the myocyte. (See "Calcium channel blocker
poisoning", section on 'Pathophysiology'.)

Lipid emulsion therapy — Lipid emulsions are the fats used in total parenteral nutrition (TPN). Initially used to treat
overdoses of local anesthetics such as bupivacaine, intravenous lipid emulsion (ILE) has been used to treat poisonings
involving a number of other lipophilic medications. A more complete discussion of ILE, including suggested dosing, is found
separately; we suggest consultation with a medical toxicologist or poison control center to determine whether ILE therapy is
appropriate [5]. (See "Calcium channel blocker poisoning", section on 'Lipid emulsion therapy'.)

Studies of ILE therapy are preliminary and limited. ILE may have a useful role in the treatment of patients who are
hemodynamically unstable from particular poisonings, including beta blockers, after more traditional therapies (eg, in the
case of beta blocker poisoning: IV fluids, atropine, glucagon, high dose insulin and glucose, and vasopressors) have failed
to restore hemodynamic stability. ILE has been used successfully in documented cases of severe beta blocker overdose
[34,35]. Several case reports describe patients treated with both high dose insulin and ILE with good results [36]. ILE may
be used early in the treatment of an overdose of a highly lipophilic agent (eg, propranolol), or as an adjunct to other
treatments as described above. (See 'Approach to the selection of specific therapies' above.)

Gastrointestinal (GI) decontamination — GI decontamination may involve activated charcoal (AC), whole bowel
irrigation, or gastric lavage; therapy is based upon clinical circumstance. (See "Gastrointestinal decontamination of the
poisoned patient".)

We suggest treatment with activated charcoal (AC), 1 g/kg by mouth or nasogastric tube, in all patients who present within
one to two hours of a known or suspected beta blocker ingestion, unless there are contraindications to its administration.
Charcoal should be withheld in patients who are sedated and may not be able to protect their airway, unless endotracheal
intubation is performed first. However, endotracheal intubation should not be performed solely for the purpose of giving
charcoal.

Asymptomatic patients who present more than two hours after a reported ingestion are unlikely to benefit from AC, and we
do not recommend routine treatment in these patients.

The role of activated charcoal in symptomatic patients who present several hours after ingestion is more controversial. We
suggest the administration of AC (1 g/kg by mouth or nasogastric tube) if there are no contraindications to charcoal
administration. Although there are no data to suggest improved outcomes with AC in such patients, we believe that AC is a
relatively safe intervention whose potential benefits in this situation outweigh its risks.

Gastric lavage should not be routinely performed, but may be considered for patients who present within one hour following
ingestion of a large quantity of medication. Large sustained or controlled release tablets may not pass through the oral
gastric tube.

Whole bowel irrigation is reserved for patients who have ingested sustained release or enteric coated preparations, or have
suspected drug concretions (pharmacobezoars) in the GI tract.

Other therapies

● Sodium bicarbonate – Sodium bicarbonate has been used successfully in the treatment of beta blocker induced
 arrhythmia [37,38]. Because it is a relatively safe intervention, we suggest giving it as an adjunct for patients with QRS
widening.

The dose of sodium bicarbonate is 1 to 2 mEq/kg given as an IV push, which may be repeated. If treatment is effective,
an infusion can be started. We mix 132 mEq of sodium bicarbonate in 1 L of D5W and infuse at 250 mL/hour in adults,
and at twice the maintenance fluid rate in children. The infusion is tapered once the arrhythmia resolves. (See "Tricyclic
antidepressant poisoning".)

● Magnesium – Magnesium may be administered when ventricular arrhythmias are present or hypomagnesemia is
suspected. Sotalol has a high propensity to induce ventricular arrhythmias and will often require magnesium,
administered as a 2 g IV bolus or as a continuous infusion.

● Intravenous pacing – Ventricular pacing may be effective in patients with profound bradycardia, or in patients with
combined beta blocker and calcium channel blocker intoxication [39]. However, ventricular pacing frequently fails to
capture, or increases the heart rate without a corresponding increase in perfusion [40]. IV pacing can be implemented if
there is no response to pharmacologic therapies, and the patient remains bradycardic and hypotensive. Some authors
note a decrease in blood pressure with pacing [4]. (See "Temporary cardiac pacing".)

● Intraaortic balloon pump – The intraaortic balloon pump has been used successfully after failure of pharmacologic
management in severe cases of propranolol and atenolol overdose [41,42] and in combined verapamil-SR (sustained
release) and atenolol overdose [43]. (See "Intraaortic balloon pump counterpulsation".)

● Hemodialysis – Hemodialysis has a minimal role in the treatment of beta blocker overdose and is effective only with
hydrophilic, minimally protein-bound beta blockers such as atenolol [44]. Nadolol, sotalol, acebutolol, and atenolol are
reportedly removed by hemodialysis, but metoprolol, propranolol, and timolol are not.

Hemodialysis is reserved for patients who have not improved despite aggressive medical intervention, have ingested a
significant amount of a beta blocker that can be removed using dialysis (eg, acebutolol), or have ingested other
cardioactive medications that may exacerbate toxicity. In such cases, the emergency clinician should contact a
nephrologist early in the patient's course to avoid delays in preparing for hemodialysis.

Continuous venovenous hemodialysis (VVHD) can be used if the patient is not able to tolerate traditional hemodialysis due
to pronounced hypotension. The decision to initiate hemodialysis and the selection of the appropriate type is made in
consultation with the nephrologist. (See "Enhanced elimination of poisons".)

Pediatric considerations — Although hypoglycemia is seen more often in pediatric patients than adults, overall
management does not differ significantly in children.

We recommend 24 hours of observation in a monitored setting for any initially asymptomatic child who has ingested an
extended release preparation, sotalol, or multiple cardioactive agents. Outside of such cases, the great majority of isolated
ingestions by young children are uneventful and they can be discharged after a six hour period of observation [45,46].

Children may be observed safely at home after the witnessed ingestion of a single beta blocker tablet and Poison Control
Centers typically manage these exposures via telephone follow-up [47,48]. Should the patient's family call the Emergency
Department (ED) for advice, it is prudent to advise them to bring the child to the ED for evaluation since follow-up can be
problematic.

Disposition — Patients who have ingested a beta blocker and who manifest hemodynamic instability or an altered mental
status should be admitted to a critical care unit for cardiac monitoring and further management.

Sotalol has a long half-life and toxicity may result in ventricular dysrhythmias. Thus, patients require 24 hours of inpatient
cardiac monitoring following sotalol overdose, even if they are asymptomatic.

Any person who has taken an overdose of a beta blocker with membrane stabilizing activity (table 2) or multiple cardioactive
medications is at increased risk of severe toxicity and should be observed in the emergency department for six hours.
Patients who remain asymptomatic without need of intervention can be safely discharged. Patients who are asymptomatic
at presentation after ingestion of a sustained release beta blocker should be observed for at least six hours to insure that
symptoms do not develop [2].
Asymptomatic adults who have inadvertently ingested an amount of beta blocking agent no greater than their total daily
dose (excluding sotalol) may be observed safely at home [2].

ADDITIONAL RESOURCES — Regional poison control centers in the United States are available at all times for
consultation on patients who are critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222).
In addition, some hospitals have clinical and/or medical toxicologists available for bedside consultation and/or inpatient
care. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or
overdoses. The World Health Organization provides a listing of international poison centers at its website:
www.who.int/gho/phe/chemical_safety/poisons_centres/en/index.html

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and
regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning
treatment" and "Society guideline links: Treatment of acute poisoning caused by specific agents other than drugs of abuse".)

SUMMARY AND RECOMMENDATIONS

● Although beta blocker overdose generally follows a benign clinical course, patients with significant toxicity require
aggressive medical management. A summary table to facilitate emergent management is provided (table 1).

● Toxicity increases greatly when an agent has membrane stabilizing activity (MSA) (table 2) or when other cardioactive
agents are ingested concomitantly. Lipophilic agents cross the blood brain barrier and can cause neurologic
dysfunction even in the absence of systemic hypotension (table 2). (See 'Cellular toxicology' above and 'Toxicity of
specific agents' above.)

● Sotalol is a unique agent with an extended half-life that can cause QTc interval prolongation and severe ventricular
arrhythmias in overdose. Propranolol and acebutolol possess properties that increase their potential toxicity. (See
'Toxicity of specific agents' above and 'History' above.)

● Most patients who develop toxicity from beta blocker overdose do so within two hours of ingestion, and virtually all do
so within six hours. Bradycardia and hypotension are the most common effects. Cardiogenic shock and ventricular
dysrhythmias can occur with severe overdose. Other potential effects of severe toxicity include mental status change,
seizure, hypoglycemia, and bronchospasm. Hypoglycemia is seen more often in children. (See 'Physical findings'
above and 'Pediatric considerations' above.)

● Obtain the following studies in patients with beta blocker poisoning: an electrocardiogram (ECG), a fingerstick glucose,
serum electrolytes including calcium, and blood urea nitrogen and creatinine levels. Cardiac conduction delays can
occur, most often a prolonged PR interval. In severe poisoning, ANY bradydysrhythmia can develop, and may progress
to asystole. (See 'Laboratory studies' above and 'Electrocardiogram' above.)

● For patients with severely symptomatic beta blocker poisoning (eg, profound persistent hypotension or bradycardia),
we suggest simultaneous treatment with all of the following therapies (Grade 2C). Dosing is provided in the text and
the rapid overview table (table 1). Severe beta blocker poisoning can be difficult to manage and consultation with a
medical toxicologist or regional poison control center is prudent. (See 'Acute stabilization and overview of therapy'
above and 'Severely symptomatic patients' above.):

• Stabilization of the airway as necessary (avoid induction agents that exacerbate hypotension)

• Additional IV boluses of isotonic crystalloid

• IV glucagon

• IV calcium salts

• Vasopressor (eg, epinephrine)

• IV high-dose insulin and glucose

• IV lipid emulsion therapy

● For patients who are mildly symptomatic from beta blocker poisoning, and in whom IV fluids, atropine, and glucagon
 prove ineffective at reversing signs of cardiotoxicity, we suggest a stepwise treatment approach (Grade 2C). Give the
following treatments, in succession, based upon patient response: IV calcium salts, lipid emulsion therapy,
vasopressors, and high-dose insulin and glucose. The implementation of each therapeutic option is discussed in the
text. (See 'Acute stabilization and overview of therapy' above and 'Specific therapies' above.)

● Sodium bicarbonate and magnesium may be needed to treat some arrhythmias. Hemodialysis may rarely be needed,
in which case a nephrologist should be contacted early. (See 'Other therapies' above.)

● The length of observation following inadvertent overdose varies according to the type and number of medications
ingested. (See 'Disposition' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Ellen Lemkin, MD, PharmD, who
contributed to an earlier version of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

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Topic 330 Version 18.0

GRAPHICS

Beta blocker poisoning: Rapid overview

To obtain emergent consultation with a medical toxicologist, call the United States Poison Control Network at 1-800-222-1222,
or access the World Health Organization's list of international poison centers
(www.who.int/gho/phe/chemical_safety/poisons_centres/en/index.html).

Clinical and laboratory features

Prominent features include hypotension and bradycardia

Electrocardiogram can show PR prolongation or any bradydysrhythmia

Beta-blockers with membrane-stabilizing activity may cause QRS prolongation

Mild hyperkalemia and hypoglycemia may also be present

Diagnostic evaluation
Diagnosis depends on history and clinical presentation

Assays for beta-blockers are not routinely available

Toxicologic differential diagnosis for unexplained bradycardia includes beta blockers, calcium channel blockers, digoxin, and
cholinergic agents

Management
Stabilize airway, breathing, and circulation

Give boluses of isotonic IV fluids: give atropine 1 mg IV (up to 3 doses) for initial treatment of hypotension and bradycardia

For severe poisoning (eg, profound hypotension), give following treatments simultaneously (dosing given below): IV glucagon,
IV calcium salts, vasopressor, IV high-dose insulin (with glucose), and IV lipid emulsion therapy.
For mild symptoms, give treatments in succession, but only if prior treatment is ineffective.

Gastrointestinal decontamination: single dose activated charcoal; consider whole bowel irrigation if an extended-release
preparation has been ingested

Glucagon: give 5 mg IV bolus, if IV fluids and atropine ineffective; may be repeated if the initial bolus has no effect

Calcium chloride (via central venous access) 10 to 20 mL of 10 percent solution OR calcium gluconate IV 30 to 60 mL of 10
percent solution

Vasopressors (eg, epinephrine) can be used for hypotension

High-dose insulin and glucose:

Bolus of 1 unit/kg IV of regular, short-acting insulin, followed by

Continuous infusion of 0.5 units/kg per hour IV; titrate infusion upwards until hypotension corrected or dose reaches 2 units/kg per hour

Intravenous lipid emulsion (20 percent solution): give 1.5 mL/kg over 2 minutes, followed by 1.5 mL/kg infusion over 60
minutes

Other potential treatments include: sodium bicarbonate (eg, prolonged QRS), magnesium (ventricular dysrhythmia),
intraaortic balloon pump, temporary transvenous pacing, and hemodialysis

Graphic 82572 Version 15.0

Beta blocker properties

Alpha Beta-1 Usual Half life,

Drug ISA MSA Lipophilicity Elimination
blockade selectivity dose* hours ¶

Acebutolol No Yes Yes Yes Low 100 to 400 mg 3 to 4 Hepatic

twice per day (primary)
Renal
(secondary)

Atenolol No Yes No No Low 50 to 200 mg 6 to 9 Renal

once daily

Betaxolol No Yes No Yes Low 10 to 20 mg 14 to 22 Hepatic

once daily (primary)
Renal
(secondary)

Bisoprolol No Yes No No Moderate 2.5 to 20 mg 9 to 12 Renal and

once daily hepatic

Carteolol No No Yes No Low 2.5 to 5 mg 6 Renal

once daily

Carvedilol Yes No No Yes High 3.125 to 25 7 to 10 Biliary

mg twice per (primary)
day
Hepatic
(secondary)

Esmolol No Yes No No Low IV only 250 to 9 minutes Blood

500 esterases
micrograms/kg
over one
minute then
25 to 50
micrograms/kg
per minute as
IV infusion;
titrate
incrementally
up to
maximum of
300
microgram/kg
per minute Δ

Labetalol Yes No Yes Low Moderate IV 20 mg Δ 3 to 4 Hepatic

(Beta 2 )
Orally 100-400
mg two or
three times
per day

Metoprolol No Yes No Low Moderate IV 1.25 to 5 3 to 4 Hepatic via

tartrate mg Δ (7 to 9 hours CYP2D6
in poor (polymorphic)
Orally 25 to
metabolizers)
100 mg two or
three times
per day

Metoprolol No Yes No Low Moderate Orally 50 to Apparent Hepatic via

succinate 400 mg once half-life CYP2D6
(extended daily prolonged by (polymorphic)
release) continuous
osmotic
release over
~20 hours

Nadolol No No No No Low 40 to 160 mg 20 to 24 Renal

once daily

Nebivolol No Yes No No High 5 to 40 mg 10 to 12 Hepatic

 once daily (19 to 32
poor
metabolizers)

Oxprenolol ◊ No No Yes Yes Moderate 40 to 80 mg 1.5 Hepatic

three times
per day

Penbutolol No No Yes No High 10 to 40 mg 5 Hepatic

once daily

Pindolol No No Yes Low Moderate 5 to 30 mg 3 to 4 Hepatic

twice per day (primary)
Renal
(secondary)

Propranolol No No No Yes High IV 1 to 5 mg Δ 3 to 4 Hepatic

Orally 10 to 80
mg two to four
times daily

Sotalol § No No No No Low 80 to 160 mg 12 Renal

twice per day

Timolol No No No No Moderate 10 to 30 mg 4 to 5 Hepatic

twice per day (primary)
Renal
(secondary)

ISA: intrinsic sympathomimetic activity; MSA: membrane stabilizing activity; IV: intravenous.
* Range of usual, oral, anti-hypertensive dose, unless "IV" noted.
¶ Duration of hypotensive effect, in general, is longer than may be predicted by serum half-life.
Δ Usual initial IV dose. Subsequent dosing generally needed. See drug monograph for detail.
◊ Not available in US.
§ Sotalol has independent class III antiarrhythmic activity.

Prepared with data from:​

1. Frishman WH, Alwarshetty M. β-Adrenergic blockers in systemic hypertension pharmacokinetic considerations related to
current guidelines. Clin Pharmacokinet 2002; 41:505.
2. Brubacher JR. β-Adrenergic Antagonists. In: Goldfrank's Toxicologic Emergencies, 9th ed, Nelson LS (Ed), McGraw-Hill, New
York 2010.

Graphic 82571 Version 9.0

Contributor Disclosures
Fermin Barrueto, Jr, MD, FACEP, FAAEM, FACMT Nothing to disclose Stephen J Traub, MD Nothing to
disclose Jonathan Grayzel, MD, FAAEM Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by
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