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Revista Brasileira de Anestesiologia

Print version ISSN 0034-7094

Rev. Bras. Anestesiol. vol.51 no.5 Campinas Sept./Oct. 2001 



Beta-blockers in anesthesiology: clinical and pharmacological aspects*


Beta-bloqueadores en anestesiologia: aspectos farmacológicos y clínicos



Fabiana Aparecida Penachi Bosco, M.D.I; José Reinaldo Cerqueira Braz, TSA, M.D.II

IME2 do CET/SBA do Departamento de Anestesiologia da FMB da UNESP, SP
IIProfessor Titular do CET/SBA do Departamento de Anestesiologia da FMB da UNESP, SP





BACKGROUND AND OBJECTIVES: Experimental and clinical data have suggested b-blockers protective hemodynamic effects during anesthesia and surgery. This study aimed at reviewing pharmacological and clinical information needed to prescribe b-blockers in perioperative medicine.
CONTENTS: Selective b-blockers inhibit preferentially b1-receptors, decreasing heart rate and inotropism leading to less myocardial oxygen consumption. Non-selective b-blockers also inhibit b2-receptors, increasing bronchial and peripheral vascular resistance. Some b-blockers are also vasodilators. Prolonged treatment with b-blockers increases cell membrane b-receptors density, which may explain sympathetic hyperactivity observed during treatment interruption. In non-cardiac surgeries, beneficial effects of b-blockers have been observed in hypertensive patients and in patients with coronary artery disease, with a decrease in postoperative myocardial ischemia and overall two-year mortality.
CONCLUSIONS: Continued administration of b-blockers until anesthesia induction has been encouraged except in patients with signs of intolerance such as hypotension or significant bradycardia. b-blockers have been shown to have beneficial effects on postoperative outcomes in patients with cardiovascular disease or risk factors. Hence, their more widespread use in perioperative medicine is encouraged.

Key words: DRUGS, Interaction: beta-blockers


JUSTIFICATIVA Y OBJETIVOS: Informaciones experimentales y clínicas han sugerido que os b-bloqueadores presentan efectos hemodinámicos importantes y protectores durante el acto anestésico-cirúgico. El objetivo de este trabajo es revisar las Informaciones farmacológicas y clínicas de los b-bloqueadores para su utilización adecuada en la medicina per-operatoria.
CONTENIDO: Los b-bloqueadores selectivos inhiben preferencialmente los b1-receptores reduciendo la frecuencia e inotropismo cardíacos y determinando reducción en el consumo de oxígeno del miocardio. Los b-bloqueadores no selectivos inhiben también los b2-receptores, aumentando la resistencia bronquiolar y vascular periférica. Algunos b-bloqueadores son, también, vasodilatadores. El tratamiento prolongado con los b-bloqueadores aumenta la densidad de los b-receptores en la membrana celular, lo que puede explicar la hiperatividad simpática que puede ocurrir durante la parada del tratamiento de eses medicamentos. En cirugía no cardíaca, han sido demostrados los efectos benéficos de los b-bloqueadores en pacientes hipertensos o en los que presentan enfermedad coronariana, con reducción de la incidencia de isquemia miocárdica en el pós-operatorio y de la mortalidad durante el período de dos años que se siguen a la operación.
CONCLUSIONES: El tratamiento con b-bloqueadores debe ser mantenido hasta el período de la mañana de la operación, excepto en los pacientes con señales de intolerancia a la droga, como hipotensión o bradicardia importante. Los b-bloqueadores ejercen efecto benéfico en la recuperación pós-operatoria de pacientes con enfermedades cardiovasculares o en los que presentan factores de riesgo. Por eso, el empleo de esos medicamentos es importante en la medicina per-operatoria y debe ser ampliado.




Beta-adrenergic receptor antagonists (b-blockers) (Figure 1) have been studied by anesthesiologists for minimizing circulating catecholamine effects by blocking their binding to receptors. They are peri and postoperatively used for preventing or treating tachycardia, hypertensive crises, ischemic cardiopathy and arrhythmias, mainly supraventricular arrhythmias 1,2. Several studies have also shown the efficacy of such drugs in decreasing postoperative morbidity and mortality 3-5. Preanesthetic evaluations often reveal patients in chronic use of b-blockers.

The interest in b-blockers in Anesthesiology has increased with the recent introduction of a very short half-life molecule, namely esmolol. So, it is necessary to know the pharmacology of such agents to use them in perioperative medicine 1,6,7.



Action Mechanism

Norepinephrine is the neurotransmitter responsible for most sympathetic nervous system adrenergic activity. It is synthesized in the axoplasm and stored in post-ganglionary sympathetic fiber vesicles. Adrenergic receptors are often classified in three major groups: alpha and beta-adrenergics and dopaminergics (Chart I), which are divided in sub-types a1 and a2, b1 and b2, dopa1 and dopa2, respectively. Visceral membrane b-receptors are stimulated by catecholamines released by sympathetic post-ganglionary neurons and the medulla of the adrenal gland. Such stimulation results in the activation of stimulating proteins (protein Gs), which trigger adenylate cyclase activation promoting the conversion of adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cyclic-AMP).The latter phosphorilates the proteic component of voltage-dependent calcium channels increasing the number of open channels during depolarization and calcium transfer to cytoplasm, which is responsible for intracellular activation 8.

An opposite situation is observed when there is a decreased agonist stimulation or receptor blockade 6,9. The action mechanism may explain "rebound" events when beta-blockers are abruptly withdrawn.


The most important b1-receptors are located in post-synaptic heart membranes. Their stimulation results in increase atrioventricular stimulus conduction, myocardial contractility and heart rate.

b2-receptors are post-synaptic adrenoreceptors located in bronchi, vessels, uterus, bladder and intestine smooth muscles. Their stimulation causes bronchodilation, vasodilation and uterus, bladder and intestine relaxation, respectively. It also determines glucogenolysis, neoglucogenesis, insulin secretion stimulation and Na+/K+ pump activation and may lead to hypokalemia and cardiac arrhythmias 9,10.

Chart I shows major types, location and primary actions of adrenergic receptors.


Ahlquist's 11 hypothesis that catecholamine effects are mediated by the action of different a and b-adrenergic receptors has triggered b-blockers study, synthesis and pharmacological evaluation. Further efforts resulted in compounds with a relative differentiated affinity to b1 and b2 receptors, presence or not of intrinsic sympatheticomimetic activity and presence or absence of membrane stabilizing effects (Table I).

Beta-adrenergic receptor antagonists are classified as selective and non-selective, according to their affinity to b1 and b2 receptors. So, methoprolol is a very selective molecule for b1-receptors only being beaten by bisoprolol, while atenolol, esmolol and acebutolol are less selective. Propranolol, pindolol, sotalol and timolol, on the other hand, have equivalent affinity to b1 and b2 receptors. They are also classified as pure or partial antagonists, depending on the presence or absence of intrinsic sympatheticomimetic activity, which may be related only to b1 receptors, as it is the case of acebutolol, to b2 receptors, or even to both, as with pindolol 12. Intrinsic sympatheticomimetic activity antagonists are less effective in decreasing heart rate and cause less myocardial contractility depression. So, partial antagonists may be better tolerated by patients with poor left ventricular function.

Some beta-adrenergic antagonists, such as propranolol, may produce some degree of membrane stabilization, similar to quinidine or local anesthetics, which are anti-arrhythmic agents class I. However, such effect can only be observed when plasma concentrations above those needed for an adequate blockade are reached. So, myocardial depression and bradycardia produced by beta-blockers are due to sympathetic nervous system blockade and not to membrane stabilization 9,10.

Some beta-blockers, such as labetalol, are also vasodilators and prevent the increase in systemic vascular resistance by acting as alfa1-adrenergic antagonist in arterial circulation 14.

Beta-blockers are anti-arrhythmic agents class II, according to Vaughan-Williams' classification. They are effective in treating arrhythmias caused by increased sympathetic activity and myocardial ischemia 14. Catecholamines are important for conduction velocity during the refractory period and in fibrillation vulnerability. Beta-blockers decrease diastolic depolarization velocity (phase 4) and are effective in decreasing ectopic arrhythmias, especially in the atrium. In the presence of fibrillation or atrial flutter, the increase in refractory period and nodus atrioventricularis velocity controls the ventricular rate and may interrupt re-entry-induced tachi-arrhythmias 15.

Pharmacological Effects

Beta-blockers efficiency for coronary failure is attributed to the decrease in myocardial oxygen consumption (MVO2), which is preceded by negative chronotropic effects, especially when exercising, and negative inotropic effects. Before increasing total peripheral resistance by blocking vascular b2-receptors and decreasing cardiac output, propranolol decreases blood pressure by decreasing heart rate and myocardial contractility and, probably, plasma rennin activity 10.

On the other hand, beta-blockers do not act on coronary spasm and may even favor it 16. Beta blockers-induced bradycardia and decreased inotropism increase systolic ejection time and left ventricle end diastolic volume, which may increase MVO2, especially during exercise 10.

Local circulations are affected by beta-blockers in a different manner. So, systemic vascular resistance is increased by those lacking intrinsic sympatheticomimetic activity, mainly the non selective beta-blockers. The same is not true for those with such activity. The same is true for renal 17 and brain circulation. Propranolol decreases hepatic artery and portal vein blood flow in liver circulation. Most bronchioli have b2-adrenergic receptors which, when stimulated cause bronchodilation. Beta-blockers are bronchoconstrictors, especially in asthma patients. Beta1 selectivity and intrinsic sympatheticomimetic activity decrease beta-blockers bronchoconstrictor activity 18.

The action of beta-blockers on the renal function is a function of direct and indirect effects and may increase or decrease diuresis 17.

Beta-blockers decrease intraocular pressure in glaucoma patients 19 and also decrease angiotensin and aldosterone plasma levels, glucagon secretion in response to physiological hypoglycemia and to glucogenolysis. Beta1 selectivity and intrinsic sympatheticomimetic activity decrease such effects.


Hydrosoluble beta-blockers, such as atenolol and nadolol, are absorbed by the GI tract and are weakly or not metabolized and excreted by the urine. Conversely, liposoluble compounds, such as propranolol, pindolol and methoprolol, are almost totally absorbed by the GI tract and suffer the first liver passage effect because they are metabolized in the liver, sometimes giving origin to active metabolites, such as propranolol. The knowledge of their metabolic pathways allows for dose adjustments according to patients renal and liver function (Table II).

Some authors propose preoperative isoproterenol tests to determine an effective blockade with beta-blockers, since it seems not to be a satisfactory correlation between plasma concentration and therapeutic effects 20. Beta-blockers may also change the metabolism of other drugs by decreasing liver output and/or oxidative metabolism. As an example, propranolol decreases lidocaine clearance in 30% 21and diazepam in 17% 22.

Propranolol also decreases lung fentanyl clearance 23. This reflects the property of a basic lypophylic amine (propranolol) of inhibiting lung re-intake of a second lipophylic amine. As a result, two to four times more fentanyl enter circulation after injection.

On the other hand, drugs changing liver microsomal functions alter the metabolism of liposoluble beta-blockers. So, enzyme inducers, such as barbiturates, decrease propranolol, timolol and methoprolol plasma rates, while drugs decreasing microsomal activity, such as cimetidine, decrease liver extraction and increase b-blockers plasma levels 9,13.



There is a wide spectrum of beta-blockers available for daily use. In anesthesiology, cardioselectivity, action time and intravenous formulation are important factors to be considered (Table III).


Although with clinical relevance proven for several years, only recently is esmolol being more widely used in anesthesia. Due to its pharmacokinetics and short action time it is the best intravenous beta-blocker for continuous infusion.

Its short duration is due to the fast hydrolytic metabolism through plasma estearases, resulting in an inactive metabolite and negligible amounts of methanol. Plasma estearases responsible for its metabolization are different from plasma pseudocholinesterases 25. So, succinylcholine has no prolonged effect in patients treated with esmolol. Its distribution half-life is approximately two minutes, elimination half-life is nine minutes with 55% protein binding and high clearance rate of 20 Esmolol plasma concentrations are undetectable 15 minutes after withdrawal. Its low liposolubility limits its passage through the blood-brain or placental barrier.

Esmolol has been used during pheochromocytoma resection in association with alpha-blockers 26,27, to treat thyrotoxicosis-induced hypertension 28 and cardiovascular toxicity caused by epinephrine or cocaine. It can also be used as an alternative to cardioplegia in coronary surgery 29, in controlled hypotension 30, as an adjuvant for electroconvulsive therapy 31 and rigid bronchoscopy, and in controlling tachiarhythmias and arterial and intra-ocular hypertension, among others 6,10,13,32.


Methoprolol is a selective beta-adrenergic blocker without intrinsic sympatheticomimetic activity. In high doses it may act upon b1 and b2 receptors. It is available for intravenous administration and is perioperatively used to control hypertension and tachiarhytmias.

After intravenous administration, its peak of action occurs in approximately ten minutes and its elimination half-life is 3 to 4 hours. It has a high distribution volume of 5 to 6, suffers liver metabolization and its inactive metabolites are excreted by urine and feces. Hemodynamic effects are negative chronotropism and inotropism without significant vascular resistance changes 6. b1-blocker recovery pharmacodynamics is prolonged and may last more than 12 hours after excessive doses.


Propranolol interacts with b1 and b2 receptors, does not block a receptors and has no intrinsic sympatheticomimetic activity.

It is highly lipophylic and after oral absorption suffers an intense first passage effect; only 10% to 25% of the initial dose reach systemic circulation. In spite of its basic character, it has high protein binding (90%), especially acid a1-glucoproteins. Its liver biotransformation is by cytochrome P450 and most metabolites are excreted by the urine. Hydroxypropranolol, with antagonist activity, is one of its metabolites with an elimination half-life shorter than the original drug. Its plasma clearance depends on blood flow and liver function. Its elimination half-life is 3 to 6 hours 6,10,13,32.


Labetalol is seldom used in Brazil, but in other countries it is often used for acting on a1 and b-adrenergic receptors with beta blockade much more potent than alfa. The alfa1 blockade is selective and the beta blockade is non-selective. It is weakly lipophylic and 55% of the drug are bound to plasma proteins. It has a 5-minute onset, short distribution half-life and distribution volume from 9 to 16 It is conjugated to glucuronic acid in the liver and excreted by urine and feces. Its elimination half-life is 5 to 8 hours 33. It has minor effects on uterine and cerebral flows 34. Its anti-hypertensive effects result from systemic vascular resistance, heart rate and myocardial contractility decrease. It does not increase heart rate after vasodilation and blood pressure decrease 33 being widely used in pheochromocytoma surgeries.


Atenolol is a selective b1 blocker. This drug causes less side-effects than propranolol because it is less liposoluble. It is the most selective b1 blocker among all adrenergic agonists and is widely used in preventing recurrent supraventricular arrhythmias and in controlling hypertension and stable angina. Approximately 50% are orally absorbed with low binding to plasma proteins (10%). It suffers minor liver metabolization and 85% to 100% of the drug are excreted unaltered by the urine. It has a 2 clearance and a very low apparent distribution volume of 1

The prophylactic use of perioperative atenolol in cardiac patients submitted to non-cardiac surgeries has been recommended because it decreases medium and long term mortality and has few side-effects 35,36. So it is recommended for cardiac patients or patients at risk of coronary disease presenting two or more risk factors, more than 65 years of age, systemic hypertension, smokers, serum cholesterol above 240 mg.dl-1 or diabetes 37,38.

Atenolol does not exacerbate insulin-induced hypoglycemia and may be cautiously administered to diabetes patients whose hypertension was not controlled with other drugs. It administration requires heart rate to be equal to or higher than 55 bpm and systolic pressure to be equal to or higher than 100 mmHg, with no signs of heart failure or bronchospasm. It should be slowly injected in 5 mg intravenous bolus 30 minutes before surgery and the dose should be repeated immediately after surgery. Postoperatively, patients are maintained with oral 100 if heart rate is equal to or higher than 65 bpm, or 50 if it is equal to or higher than 55 bpm. If the patient is unable to receive oral medication, intravenous doses of 5 mg are administered every 12 hours for no longer than 7 days 6,36.



Several studies have shown that treating patients with beta-blockers until the day of the surgery, in addition to not significantly changing hemodynamic balance during general anesthesia, decreases heart rate, blood pressure and blocked pulmonary artery pressure increase and ischemia related to noxious stimuli of tracheal intubation and surgery 39-43.

Beta-blockers should also be maintained until the day of the surgery for spinal or epidural anesthesia. In these situations, however, all relative perioperative hypovolemia should be recognized and treated 44.

To control perioperative blood pressure and heart rate some authors propose the preanesthetic administration of beta-blockers in patients not using such drugs 41. In those cases, liposoluble beta-blockers, such as methoprolol, pindolol and labetalol, which are mostly metabolized during the first liver passage, should not be used and hydrosoluble beta blockers, such as atenolol and nadolol should be preferred.

Another possibility is to use esmolol and other intravenous beta-blockers immediately before anesthetic induction. In such situation, esmolol has shown to be useful in decreasing heart rate and blood pressure during tracheal intubation and anesthesia 45,46.

For preanesthetic medication, beta-blockers should only be used after assuring that the patient has a good left ventricular function at clinical evaluation and, if needed, at additional tests such as ecocardiography and angioscintigraphy which provide objective and reliable data on ventricular function 1.

Interactions of b-blockers with anesthetic agents do not favor perioperative hemodynamic complications. Several studies have shown that cardiac effects of b-blockers and opioids are additive without exacerbation 1.

Halothane and enflurane decrease sympathetic adrenergic activity. However, beta-blockers effect in decreasing sympathetic activity is a function of the baseline sympathetic tone level and their effects are limited in the absence of stimuli 1,10. Conversely, tachycardia, arrhythmias and hypertension during laryngoscopy, intubation and surgical painful stimuli may be prevented by beta-blockers 10,32, thus avoiding an increase in cardiac oxygen consumption, especially in patients with coronary artery disease.

Among halogenate agents, only enflurane and halothane seem to exacerbate negative chronotropic and inotropic effects of some beta-blockers, but only in concentrations higher than 1.5 times minimum alveolar concentration (MAC) 1. So, in patients adequately beta-blocked they should only be used in low concentrations 10. The same caveat is true for other halogenate agents, especially when there are high beta-blockers plasma levels, to decrease the risk for drug interaction 40.

Cardiovascular effects of neuromuscular blockers may also be changed by beta-blockers. In patients with coronary artery disease, preoperative propranolol (180 mg in 24 hours) may minimize pancuronium-induced heart rate, blood pressure and cardiac output increase 47. However, care must be taken during reversion of the neuromuscular block with neostigmine because there may be prolonged bradycardia 48.

Beta-blockers are well tolerated by anesthetized patients with acute hypovolemia 49.

Hypercabia has a negative inotropic effect, in general compensated by sympathetic hyper-reactivity. In the presence of beta-blockers, such compensation is impossible. It is recommended, then, to avoid hypercabia during anesthesia in beta-blockers users 50.

Bradycardia is frequent during regional blocks so prophylactic beta-blockers are, in general, not needed. It must be taken into consideration that during spinal or epidural blocks beta-blockers cardiovascular effects may add to the effects of sympathetic block and local anesthetics when there is an overdose of such agents. However, their perioperative use during regional blocks, such as isolated or combined thoracic epidural and general anesthesia is considered safe 7,51. Regional anesthesia in beta-blocked patients requires special attention for correcting hypovolemia and hypotension with vasoactive agents and bradycardia with atropine. One must bear in mind that after the test dose with epinephrine and local anesthetics for epidural anesthesia there may be no heart rate increase in patients under b-blockers although blood pressure increase may be seen 52.

Preanesthetic administration of beta-blockers or during anesthesia may limit cardiac output adaptation to metabolic demand, especially during postanesthetic recovery, when it is markedly increased. So, it is desirable to decrease postoperative metabolic demand in beta-blocked patients, such as maintaining artificial ventilation until the patient is warm 1.



Patients with coronary artery disease

Perioperative beta-blockers in coronary artery disease patients are administered whenever myocardial ischemia secondary to heart rate increase is to be avoided or treated. In the presence of tachycardia, two mechanisms are added to favor myocardial ischemia: oxygen consumption increase and myocardial oxygen uptake decrease due to a decrease in coronary diastolic filling time. Studies have shown that noxious effects of perioperative blood pressure decrease on the mechanism of the myocardial area where coronary stenosis is located will be more severe with high heart rates 53.

Mean blood pressure and heart rate ratio (MBP/HR) is a good index when the goal is to avoid perioperative ischemia and it seems to always occur myocardial ischemia when such ratio is lower than one, that is, blood pressure, expressed in mmHg is lower than heart rate in beats per minute 53.

So, intravenous peri or postoperative beta-blockers should be used in the following situations 1:

1. To re-establish myocardial energetic balance if myocardial ischemia secondary to heart rate increase but with no significant blood pressure decrease is detected by ECG;

2. In patients with overt or latent coronary failure to reduce heart rate increases during tracheal intubation, surgery or anesthetic recovery. Perioperatively, it is important that depth of anesthesia matches the intensity of the surgical stimulus.

Heart Rate and Blood Pressure Limitations to Tracheal Intubation

Since intubation-induced hemodynamic changes have a short duration, ultra-short duration intravenous beta-blockers, such as esmolol, are preferred 46,54. The benefit of beta-blockers for coronary artery disease patients before tracheal intubation is also result of a myocardial depressing effect of such drugs with potential to change ventricular function. Care must be taken with Prizmetal's angina patients because non-selective beta-blockers may cause myocardial ischemia 32. For those patients, calcium channel blockers and nitrates are the best indication.

Heart Rate Increase during Surgery

Inadequate anesthesia and/or analgesia are fundamental for the etiopathogeny of heart rate increases during surgery. So, whenever there is tachycardia during surgery after volume expansion, higher concentrations of halogenate anesthetics and/or opioids should be administered to deepen anesthesia. If after such measures heart rate is still high, intravenous beta-blockers are indicated.

Postoperative Heart Rate Increase

Heart rate increase favors postoperative myocardial ischemia. In a study by Mangano et al. (1990) 55 (Figure 2), the incidence of ischemia was significantly higher in the postoperative period. This is easily explained by the fact that the thorough blood pressure and heart rate control during surgery was very often impossible after surgery in such studies, either because tachycardia was not detected or because the postoperative follow-up did not provide for a specific tachycardia treatment. In addition, in most studies, myocardial ischemia episodes were collected retrospectively and long time after surgery, from continuous electrocardiographic records obtained by Holter's method.

Several studies have proven the efficacy of peri and postoperative beta-blockers in decreasing myocardial ischemia and necrosis 3,4,35,38,56,57. So, in patients under preoperative beta-blockers, the treatment must be restarted as soon as possible after surgery, in general in decreased doses for some days to prevent hypotension. Patients who received perioperative beta-blockers should continue to receive it after surgery and, when possible, orally. When using esmolol, it should be replaced, if possible, by other oral beta-blockers.

Treatment of Supraventricular Rhythm Changes

Perioperative paroxistic supraventricular rhythm changes are common. One may see atrial tachycardia (tachysystolis, tachyarrhythmias, atrial flutter) or junctional tachycardia.

In coronary patients or those with myocardial changes, it is important to decrease any ventricular rhythm increased by atrial rhythm changes. When stimulated at very fast rhythm, the ventricular myocardium often develops ventricular rhythm changes, such as extrasystole and tachycardia.

In the presence of atrial tachycardia, intravenous beta blockers drugs may rapidly and effectively control heart rate. They decrease nodal conduction, thus decreasing heart rate. Esmolol is the major short-duration beta blockers and is used in the doses of 50 to 150 µ In a clinical trial where esmolol was compared to verapamil, it was observed that both drugs decrease heart rate. However, blood pressure maintenance was better obtained with esmolol. Although the sinus rhythm return being not very frequent with both drugs, it was more frequent with esmolol (36% versus 12%). The efficacy of beta-receptors block should be first tested with esmolol and, after being proven, it might be replaced by other beta-blocker with longer half-life 2.


Surgery preparation and intervention are performed under alpha-adrenergic blockade. However, the use of beta-blockers provides better hemodynamic stability. Associated infusions of esmolol and phentolamine or labetalol may be used 26,27.

Controlled Hypotension

Labetalol is the most frequent beta-blocker used abroad for controlled hypotension because it determines blood pressure decrease by reducing systemic vascular resistance and prevents reflex tachycardia. This agent also promotes hypotension through a synergic effect with halogenate agents 58. In our country, the experience has been the association of a-blockers with droperidol, and b-blockers with methoprolol 59. Traditional beta-blockers still have an important role as adjuvants in controlled hypotension, but their medium and long half-life may limit the method. So, it is believed that esmolol, due to its short plasma half-life, will be more widely used for this technique 30.



Beta-blockers major adverse effects are hypotension, heart failure (counterindicated for patients class IV AHA) and bronchospasm.

Beta blocker-induced heart failure may be treated with diuretics and vasodilators, but frequently require inotropic support. In bronchial hyperactivity patients, non cardioselective beta-blockers may cause severe and even fatal bronch- spasms. Bronchospasm may be treated with sympatheticomimetic agents and aminophiline. In patients with chronic bronchial disease, there is a good respiratory tolerance for cardioselective beta-blockers 60. In diabetes patients they intensify insulin-induced hypoglycemia by decreasing glucagon secretion and liver glyconeogenesis. Such effects are not evident with atenolol.

Beta-blockers are also counterindicated for patients with 2nd and 3rd degree atrioventricular blockade or with major bradycardia. Atropine may reestablish an adequate heart rate. In atropine-resistant bradycardia, one should consider the use of transcutaneous pacemaker, dopamine, epinephrine or isoproterenol infusion. To correct hypotension without bradycardia calcium chloride may be used (7

Beta-blockers adverse effects may be exacerbated when associated to drugs with similar effects, such as calcium channel antagonists, anti-hypertensive and anti-arrhythmic agents.

Beta-blocker effects may be exacerbated in elderly patients, probably due to high baseline levels of plasma catecholamines 5. For this patients, lower doses should be prescribed.



In patients under chronic use of beta-blockers, interactions between such drugs and intraoperative cardiovascular changes are particularly beneficial. So, the treatment with beta-blockers should be maintained until the day of the surgery. This is critical for the maintenance of hemodynamic balance both peri and postoperatively, in addition to decreasing postoperative cardiovascular complications. Due to their negative chronotropic effects, intravenous beta-blockers during surgery favor the preventive and even curative treatment of myocardial ischemia caused by heart rate increase. Those agents also allow for heart rate control if there is a change in atrial rhythm. The introduction in our country of a very short plasma half-life beta-blocker - esmolol - will certainly extend the use of such agents during and after surgery.



01. Coriat P - Interação entre os Anti-Hipertensivos e a Anestesia: III. Beta-Bloqueadores, em: Braz JRC, Auler Jr JOC, Gomes do Amaral JL et al - O Sistema Cardiovascular e a Anestesia. São Paulo, Editoras UNESP & Artes Medicas, 1997;341-344.         [ Links ]

02. Balser JR, Martinez EH, Winters BD - Beta-adrenergic blockade accelerates conversion of postoperative supraventricular tachyarrhythmias. Anesthesiology, 1998;89:1052-1059.         [ Links ]

03. Mangano DT, Layug EL, Wallace A et al - Effect of atenolol on mortality and cardiovascular morbity after noncardiac surgery. N Engl J Med, 1996;335:1713-1720.         [ Links ]

04. Gottlieb SS, McCarter RJ, Vogel RA - Effect of beta-blockade on mortality among high-risk patients after myocardial infarction. N Engl J Med, 1998;339:489-497.         [ Links ]

05. Zaugg M, Tagliante T, Lucchinetti E et al - Beneficial effects from b-adrenergic blockade in elderly patients undergoing noncardiac surgery. Anesthesiology, 1999;91:1674-1686.         [ Links ]

06. Carmona MJC, Bernardes CES - Beta-Bloqueadores e Anestesia, em: Auler Jr JOC, Yamashita AM - Atualização em Anestesiologia. São Paulo, Office Editora, 2000;103-117.         [ Links ]

07. Dagnino J, Prys-Roberts C - Studies of anaesthesia in relation to hipertension. VI: cardiovascular reponses to extradural blockage of treated and untreated hypertensive patients. Br J Anaesth, 1984;56:1065-1074.         [ Links ]

08. Spedding M - Activators and inactivators of Ca++ channels: new perspectives. J Pharmacol (Paris), 1985;16:319-343.         [ Links ]

09. Hoffman BB, Lefkowitz RJ - Sympathomimetic Drugs and Adrenergic Receptor Antagonists, em: Goodman & Gilmans - The Pharmalogical Bosis of therapeutics. 9th Ed, New York, McGraw-Hill, 1996;199-182.         [ Links ]

10. Piriou V, Aouifi A, Lehot JJ - Interêt des beta-bloquants em médicine périopérative. Première partie: notions fondamentales. Can J Anesth, 2000;47:653-663.         [ Links ]

11. Ahlquist RP - A study of adrenotropic receptors. Am J Physiol, 1948;153:586-600.         [ Links ]

12. Aelling WH, Clark BJ - Is the ISA of pindolol beta2-adrenoceptor selective? Br J Clin Pharmacol, 1987;24:215-285.         [ Links ]

13. Moss J, Renz CL - The Autonomic Nervous System, em: Miller RD - Anesthesia. 5thEd, Philadelphia, Churchill Livingstone, 2000;523-577.         [ Links ]

14. Monopoli A, Forlani A, Bevilacqua M et al - Interaction of selected vasodilating beta-blockers with adrenergic receptors in human cardiovascular tissues. J Cardiovasc Pharmacol, 1989;14:114-120.         [ Links ]

15. Gregory FH - Disritmias Cardíacas e Anestesia. em: Braz JRC, Auler Jr JOC, Gomes do Amaral JL et al - O Sistema Cardiovascular e a Anestesia. São Paulo, UNESP & Artes Médicas, 1997;77-99.         [ Links ]

16. Kugiyama K, Yasue H, Horio Y et al - Effects of propranolol and nifedipine on exercice-induced attack in patients with variant angina: assessment by exercice thalium - 201 myocardial scintigraphy with quantitative rotational tomography. Circulation, 1986;74:374-380.         [ Links ]

17. Hollerberg NK, Adams DF, Mac Kinstry DN et al - Beta-adrenoceptor blocking agents and the kidney: effect of nadolol and propranolol on the renal circulation. Br J Clin Pharmacol, 1979;7:219S-225S.         [ Links ]

18. Oh VMS, Kaye CM, Warrington SJ et al - Studies of cardioselectivity and partial agonist activity in beta-adrenoceptor blockade comparing effects on heart rate and peak expiratory flow rate during exercice. Br J Clin Pharmacol, 1978;5:107-120.         [ Links ]

19. De Dieuleveut C, Queinnee MC, Pinoud M et al - Beta-adrenoceptor blockade with metipranolol or betaxolol. Comparative study after ocular instillation in healty volunteers. Ann Fr Anesth Réanim, 1989;8:46-50.         [ Links ]

20. Dagnino J, Prys-Roberts C - Assessment of beta-adrenoceptor blockade during anesthesia in humans: use of isoproterenol dose-response curves. Anesth Analg, 1985;64:305-311.         [ Links ]

21. Naguib M, Magboul MM, Samakandi AH et al - Adverse effects and drug interactions associated with local and regional anesthesia. Drug Saf, 1998;18:221-250.         [ Links ]

22. Ochs HR, Greenblatt DJ, Verburg-Ochs B - Propranolol interactions with diazepam, lorazepam, and alprazolam. Clin Pharmacol Ther, 1984;36:451-455.         [ Links ]

23. Tumber PS, Cullen BF - Drug interactions for the anesthesiologist. ASA Refresher Courses in Anesthesiology, 2000;28: 215-228.         [ Links ]

24. Stoelting RK - Alpha and Beta-Adrenergic Receptor Antagonists, em: Pharmacology & Physiology in Anesthetic Practice. 3rd Ed, Philadelphia, Lippincott, Raven, 1999;288-301.         [ Links ]

25. McCammon RL, Hilgenberg JC, Sandage BW et al - The effect of esmolol on the onset and duration of succinylcholine-induced neuromuscular blockade. Anesthesiology, 1995;63:A317.         [ Links ]

26. Gabrielson GV, Griffin AV, Kaplan JA et al - Continuous intravenous infusions of phentolamine and esmolol for preoperative and intraoperative blockade in patients with pheocromocytoma. J Cardiothorac Anesth, 1987;1:554-558.         [ Links ]

27. Nicholas E, Deutschman CS, Allo M et al - Use of esmolol in the intraoperative management of pheochromocytoma. Anesth Analg, 1988;67:1114-1117.         [ Links ]

28. Knighton JD, Crosse MM - Anaesthetic management of childhood thyrotoxicoses and the use of esmolol. Anaesthesia, 1997;52:67-70.         [ Links ]

29. Mehlhorne U, Sudkam M - Beta-blockade as an alternative to cardioplegia. Thorac Cardiovasc Surg, 1998;46:302-307.         [ Links ]

30. Pilli G, Güzeldemir ME, Bayhan N - Esmolol for hypotensive anesthesia in middle ear sugery. Acta Anaesthesiol Belg, 1996;47:85-91.         [ Links ]

31. Castelloni I, Steainer LA, Kaufmann MA et al - Comparative effects of esmolol and labetalol to attenuate hyperdynamic states after eletroconvulsive therapy. Anesth Analg, 1995;80:557-661.         [ Links ]

32. Piriou V, Aouifi A, Lehot JJ - Beta-bloquants en médecine périopératoire. Deuxième partie: indications thérapeutiques. Can J Anesth, 2000;47:653-663.         [ Links ]

33. MacCarthy EP, Bloomfield SS - Labetalol: a review of its pharmacology, pharmacokinetics, clinical uses and adverse effects. Pharmacotherapy, 1983;3:193-219.         [ Links ]

34. Jouppilla P, Kirkinen P, Keivula A et al - Labetalol does not alter the placental and fetal blood flow or maternal prostanoids in preeclampsia. Br J Obstet Gynaecol, 1986;93:543-547.         [ Links ]

35. Mangano DT - Adverse outcomes after surgery in the year 2001 - a continuing odyssey. Anesthesiology, 1998;88:561-564.         [ Links ]

36. Wallace A, Layug B, Tateo I et al - Prophylatics atenolol reduces postoperative myocardial ischemia. Anesthesiology, 1998;88: 7-17.         [ Links ]

37. The American College of Physicians: Clinical Guideline. Part 1 Guidelines for assessing and mananging the perioperative risk from coronary artery disease associated with major noncardiac surgery. Ann Intern Med, 1997;309-312.         [ Links ]

38. Palda V, Detsky A - Clinical Guideline Part II. Perioperative assessment and management of risk from coronary artery disease. Ann Intern Med, 1997;127:313-328.         [ Links ]

39. Prys-Roberts C, Foex P, Biro GP et al - Studies of anaesthesia in relation to hypertension. V. Adrenergic. Anesthesiology, 1988;68:495-500.         [ Links ]

40. Still JC, Nugent M, Moyer TP et al - Plasma levels of beta-blocking drugs prior to coronary artery bypass surgery. Anesthesiology, 1985;62:67-70.         [ Links ]

41. Stone JG, Foëx P, Sear J et al - Myocardial ischemia in untreated hypertension patients: effect of single small oral dose of a beta-adrenergic blocking agent. Anesthesiology, 1988;68:495-500.         [ Links ]

42. Pasternack PF, Grossi EA. Baumann FG et al - Beta-blockade to decreased silent myocardial ischemia during peripheral vascular surgery. Am J Surg, 1989;158:113-116.         [ Links ]

43. Poldermans D, Boersma E, Bax JJ et al - The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. N Engl J Med, 1999;341:1789-1794.         [ Links ]

44. Ponten J, Biber B, Bjuro T et al - b-receptor blockade and spinal anaesthesia. Withdrawall versus continuation of long-therm therapy. Acta Anaesthesiol Scand, 1982;76:62-69.         [ Links ]

45. Gold MI, Sacks DJ, Grosnoff DB et al - Use of esmolol during anesthesia to treat tachycardia and hypertension. Anesth Analg, 1989;68:101-104.         [ Links ]

46. Liu PL, Gatt S, Gugino LD et al - Esmolol for control of increases in heart rate and blood pressure during tracheal intubation after thiopentone and succinylcholine. Can Anaesth Soc J, 1986;33:556-562.         [ Links ]

47. Pinoud MLJ, Souron RJ - Beta-adrenergic effect of pancuronium bromide: fact or fallacy? Anesthesiology, 1984;60:512-513.         [ Links ]

48. Eldar J, Hoffman B, Davidson JT - Prolonged bradycardia and hypotension after neostigmine administration in a patient received atenolol. Anaesthesia, 1987;42:1294-1297.         [ Links ]

49. Roberts JG, Prys-Roberts C, Foëx P et al - A comparison of the effects of practolol and propranolol on the response to haemorrhage in anaesthetized dog after myocardial infarction. Br J Anaesth, 1973;45:1230-1238.         [ Links ]

50. Foëx P, Prys-Roberts C - Interactions of beta receptor blockage and PCO2 levels in the anaesthetized dog. Br J Anaesth, 1974;46:397-401.         [ Links ]

51. Stenseth R, Berg EM, Bjella L et al - The influence of thoracic epidural analgesia alone and in combination with general anesthesia on cardiovascular function and myocardial metabolism in patients receiving b-adrenergic blockers. Anesth Analg, 1993;77:463-468.         [ Links ]

52. Garaud O, Samii K - Test injections before epidural anaesthesia in patients treated by beta-blockers. Ann Fr Anesth Réanim, 1987;6:125-126.         [ Links ]

53. Buffington CW - Hemodynamic determinants of ischemic myocardial disfunction in the presence of coronary stenosis in dogs. Anesthesiology, 1985;63:651-662.         [ Links ]

54. Cucchiara RF, Benefiel DJ, Matteo AS et al - Evaluation of esmolol in controlling increases in heart rates and blood pressure during endotracheal intubation in patients undergoing carotid endarterectomy. Anesthesiology, 1986;65:528-531.         [ Links ]

55. Mangano D, Browner WS, Hollenberg M et al - Association of perioperative myocardial ischemic with cardiac morbidity and mortality in undergoing non cardiac surgery. New Engl J Med, 1990;323:1781-1788.         [ Links ]

56. Olsson G - Long term treatment with metoprolol after miocardial infarctation: effect on 3 year mortality and morbity. J Am Coll Cardiol, 1985;5:1428-1437.         [ Links ]

57. Roby KE, Brull SJ, Timimi F et al - The effect of heart rate control on myocardial ischemia among high-risk patients after vascular surgery. Anesth Analg, 1999;88:477-482.         [ Links ]

58. Cope DHP, Crawford MC - Labetalol in controlled hypotension. Administration of labetalol when adequate hypotension is difficult to achieve. Br J Anaesth, 1979;51:359-365.         [ Links ]

59. Vieira JL, Katayama M - Hipotensão induzida com bloqueadores a e b1 e halogenados: comparação entre enflurano, halotano e isoflurano em rinoplastias. Rev Bras Anestesiol, 1992;42: 201-206.         [ Links ]

60. Guerin JM, Baillhart O, Segrestaa JM et al - Can the respiratory effects of beta-blockers be predicted? Presse Med, 1986;15: 2109-2112.         [ Links ]



Correspondence to:
Dr. José Reinaldo Cerqueira Braz
Deptº de Anestesiologia da FMB - UNESP
ZIP: 18618-970 City: Botucatu, Brazil

Submitted for publication January 19, 2001
Accepted for publication March 14, 2001



* Received from CET/SBA do Departamento de Anestesiologia da Faculdade de Medicina de Botucatu (FMB) da UNESP, SP

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