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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Any type of surgery will cause body stress and may lead to negative clinical outcomes&#44; including myocardial ischemia or infarction&#44; arrhythmias&#44; heart failure&#44; stroke and&#44; in some cases&#44; death&#46; This response is aggravated by any pre-existing cardiac morbidities&#44; such as coronary artery disease or heart failure&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Beta-blockers are well known for attenuating the stress response&#44; mainly by slowing heart rate and lowering blood pressure&#46; Over the last two decades a number of studies have investigated the use of beta-blockers in patients who are subject to severe surgical stress and are at significant risk of major adverse cardiac events &#40;MACE&#41; and death&#44; in the context of both cardiac and non-cardiac surgery&#46; While the effects of beta-blockers are desirable to fight the stress response&#44; the same effects &#8211; if too marked &#8211; may cause very low blood pressure and a very low pulse&#44; eventually leading to MACE&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The paper by Alegria et al&#46; in this issue of the <span class="elsevierStyleItalic">Journal</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">1</span></a> assesses the Cochrane systematic review by Blessberger et al&#46; on perioperative beta-blockers for preventing surgery-related mortality and morbidity&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">2</span></a> The review analyzes 88 randomized controlled clinical trials &#40;53 involving cardiac surgery and 35 non-cardiac surgery&#41; including 19 161 participants in terms of MACE and other outcomes following surgery&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The review found no evidence of any effect of beta-blockers on patients undergoing cardiac surgery regarding all-cause mortality&#44; acute myocardial infarction&#44; myocardial ischemia&#44; stroke&#44; hypotension&#44; bradycardia or heart failure&#44; but found a beneficial effect in reducing ventricular arrhythmias and supraventricular arrhythmia&#44; possibly leading to a slight reduction in hospital stay&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Regarding non-cardiac surgery&#44; the review found that beta-blockers increased the risk of hypotension and bradycardia and possibly also of all-cause mortality and stroke&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">It seems clear that the endpoints of myocardial ischemia&#44; infarction and supraventricular arrhythmias are reduced by the use of beta-blockers&#44; while the endpoints of ventricular arrhythmias&#44; heart failure and length of stay are largely unaffected&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Theoretically&#44; these well-demonstrated favorable effects of beta-blockers on myocardial ischemia and arrhythmias should protect both cardiac and non-cardiac surgical patients&#46; However&#44; these protective effects were offset by a potential increase in mortality and stroke seen in the non-cardiac surgery group&#44; while their use was favorable for cardiac surgical patients&#44; for whom it improved their clinical outcomes&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">While medicine should rely more and more on evidence &#8211; of the type that is generated mainly by large randomized trials&#44; such as those so thoroughly reviewed by Cochrane&#44; and that this paper echoes &#8211; one must be cautious due to the nature of these trials&#44; since they in fact analyze a case mix&#46; On the basis of this analysis&#44; they develop general rules that physicians are supposed to apply to individual cases and to particular patients&#46; Let me specify&#58;</p><p id="par0045" class="elsevierStylePara elsevierViewall">&#40;1&#41; Beta-blockers are competitive antagonists that block the receptor sites for the endogenous catecholamines epinephrine and norepinephrine on adrenergic beta receptors of the sympathetic nervous system&#44; which mediates the fight-or-flight response&#46; Some will block activation of all three known types of beta-adrenergic receptors&#44; while others are selective for one of the three organ-specific types&#46; Beta-blockers all differ in terms of power and action&#46; Furthermore&#44; drug dosages and treatment duration are important&#44; particularly if the patient was on chronic beta-blocker therapy prior to surgery&#44; as opposed to starting the drug the day before&#46; It is also relevant that in some cases&#44; beta-blocker dosage should be adjusted just prior to surgery&#44; which may reduce any possible negative drug-related action&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">All these variables are flattened in the present analysis&#44; by the number of cases and the case mix&#44; although it is uncertain to what extent this affects the final conclusions&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">&#40;2&#41;&#46; Not all patients are the same&#46; Cardiac surgery patients&#44; in whom beta-blockers appear to have a beneficial effect&#44; have a cardiac lesion that is to be corrected by surgery&#44; while non-cardiac patients may be healthy in cardiac terms&#44; or they have some cardiac comorbidity&#44; such as hypertension&#44; myocardial ischemia or infarction&#44; or heart failure&#44; or suffer from silent cerebrovascular disease&#46; The latter patients will tolerate the hypotensive effects of beta-blockers less well&#44; and thus see their stroke and mortality risk worsen&#44; as demonstrated in the Cochrane analysis&#46; So separating the analysis into cardiac versus non-cardiac surgery is in fact a gross simplification&#44; as the characteristics of these two patient groups are very different&#46; As an example&#44; a recent paper by Park et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">3</span></a> addressed non-cardiac surgery patients&#44; with successful myocardial revascularization and without systolic dysfunction&#44; and concluded that for these patients&#44; the use of perioperative beta-blockers was not associated with any negative clinical outcomes&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Once more&#44; analysis of a case mix will flatten the unbalanced nature of cohorts&#44; in a way that can distort the real tendencies&#46; Some trials are less robust than others in terms of the evidence generated&#44; possibly due to the uneven nature of patient populations&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">&#40;3&#41; Finally&#44; the types of surgery are different&#46; Cardiac surgery patients may be undergoing coronary or valvular procedures&#44; which have different potential for associated ischemia and arrhythmias&#44; and will therefore respond differently to beta-blockers&#44; while non-cardiac surgery patients undergo operations that may be more or less stressful&#44; with more or less blood loss and alterations in blood pressure&#46; Again&#44; these are all flattened in the case mix&#44; and this may also compromise the results of the analysis&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">We are living in a time of evidence-based medicine&#44; and we now practice according to guidelines&#46; That is positive&#44; but we must be careful when trying to apply these &#8216;rules&#8217; to individual patients&#46; In fact&#44; analysis of a case mix dilutes most of the variation&#44; but while this is true&#44; its significance is threatened by the Pareto principle&#44; which long ago established that 80&#37; of any variation is determined by 20&#37; of causes&#46; This could easily cast doubt on the evidence for the negative effects of beta-blockers in non-cardiac surgical patients as an absolute indication&#44; as they might in fact be extremely useful for the general population without myocardial ischemia&#44; by reducing stress on the heart and circulation&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">A good friend of mine&#44; who recently passed away&#44; used to allude to the advantages of &#8216;evidence based on medicine&#8217; as opposed to &#8216;evidence-based medicine&#8217;&#46; What was meant was medicine that would take into account the general rule but be personal and personalized to a particular patient&#59; in fact&#44; anticipating what is now called &#8216;precision medicine&#8217;&#46; Such medicine&#44; in line with the ideal combination of generalization plus particularization&#44; should always be preserved&#46; As for the mathematics&#44; to quote Sir Berkeley Moynihan&#44; &#8220;statistics will prove anything&#44; even the truth&#46;&#8221;</p><p id="par0080" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSmallCaps">I</span> truly enjoyed reading this useful paper&#44; <span class="elsevierStyleSmallCaps">I</span> congratulate the authors and <span class="elsevierStyleSmallCaps">I</span> strongly recommend it to the readers of the <span class="elsevierStyleItalic">Journal</span>&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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Editorial comment
Beta-blockers: Protective against perioperative stress, but not for all – as the evidence shows
Betabloqueantes, protetores de stress perioratório, mas não para todos… a evidência comprova
José Fragata
Serviço de Cirurgia Cardiotorácica, CHLC, Hospital de Santa Marta, Lisboa, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Any type of surgery will cause body stress and may lead to negative clinical outcomes&#44; including myocardial ischemia or infarction&#44; arrhythmias&#44; heart failure&#44; stroke and&#44; in some cases&#44; death&#46; This response is aggravated by any pre-existing cardiac morbidities&#44; such as coronary artery disease or heart failure&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Beta-blockers are well known for attenuating the stress response&#44; mainly by slowing heart rate and lowering blood pressure&#46; Over the last two decades a number of studies have investigated the use of beta-blockers in patients who are subject to severe surgical stress and are at significant risk of major adverse cardiac events &#40;MACE&#41; and death&#44; in the context of both cardiac and non-cardiac surgery&#46; While the effects of beta-blockers are desirable to fight the stress response&#44; the same effects &#8211; if too marked &#8211; may cause very low blood pressure and a very low pulse&#44; eventually leading to MACE&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The paper by Alegria et al&#46; in this issue of the <span class="elsevierStyleItalic">Journal</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">1</span></a> assesses the Cochrane systematic review by Blessberger et al&#46; on perioperative beta-blockers for preventing surgery-related mortality and morbidity&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">2</span></a> The review analyzes 88 randomized controlled clinical trials &#40;53 involving cardiac surgery and 35 non-cardiac surgery&#41; including 19 161 participants in terms of MACE and other outcomes following surgery&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The review found no evidence of any effect of beta-blockers on patients undergoing cardiac surgery regarding all-cause mortality&#44; acute myocardial infarction&#44; myocardial ischemia&#44; stroke&#44; hypotension&#44; bradycardia or heart failure&#44; but found a beneficial effect in reducing ventricular arrhythmias and supraventricular arrhythmia&#44; possibly leading to a slight reduction in hospital stay&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Regarding non-cardiac surgery&#44; the review found that beta-blockers increased the risk of hypotension and bradycardia and possibly also of all-cause mortality and stroke&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">It seems clear that the endpoints of myocardial ischemia&#44; infarction and supraventricular arrhythmias are reduced by the use of beta-blockers&#44; while the endpoints of ventricular arrhythmias&#44; heart failure and length of stay are largely unaffected&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Theoretically&#44; these well-demonstrated favorable effects of beta-blockers on myocardial ischemia and arrhythmias should protect both cardiac and non-cardiac surgical patients&#46; However&#44; these protective effects were offset by a potential increase in mortality and stroke seen in the non-cardiac surgery group&#44; while their use was favorable for cardiac surgical patients&#44; for whom it improved their clinical outcomes&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">While medicine should rely more and more on evidence &#8211; of the type that is generated mainly by large randomized trials&#44; such as those so thoroughly reviewed by Cochrane&#44; and that this paper echoes &#8211; one must be cautious due to the nature of these trials&#44; since they in fact analyze a case mix&#46; On the basis of this analysis&#44; they develop general rules that physicians are supposed to apply to individual cases and to particular patients&#46; Let me specify&#58;</p><p id="par0045" class="elsevierStylePara elsevierViewall">&#40;1&#41; Beta-blockers are competitive antagonists that block the receptor sites for the endogenous catecholamines epinephrine and norepinephrine on adrenergic beta receptors of the sympathetic nervous system&#44; which mediates the fight-or-flight response&#46; Some will block activation of all three known types of beta-adrenergic receptors&#44; while others are selective for one of the three organ-specific types&#46; Beta-blockers all differ in terms of power and action&#46; Furthermore&#44; drug dosages and treatment duration are important&#44; particularly if the patient was on chronic beta-blocker therapy prior to surgery&#44; as opposed to starting the drug the day before&#46; It is also relevant that in some cases&#44; beta-blocker dosage should be adjusted just prior to surgery&#44; which may reduce any possible negative drug-related action&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">All these variables are flattened in the present analysis&#44; by the number of cases and the case mix&#44; although it is uncertain to what extent this affects the final conclusions&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">&#40;2&#41;&#46; Not all patients are the same&#46; Cardiac surgery patients&#44; in whom beta-blockers appear to have a beneficial effect&#44; have a cardiac lesion that is to be corrected by surgery&#44; while non-cardiac patients may be healthy in cardiac terms&#44; or they have some cardiac comorbidity&#44; such as hypertension&#44; myocardial ischemia or infarction&#44; or heart failure&#44; or suffer from silent cerebrovascular disease&#46; The latter patients will tolerate the hypotensive effects of beta-blockers less well&#44; and thus see their stroke and mortality risk worsen&#44; as demonstrated in the Cochrane analysis&#46; So separating the analysis into cardiac versus non-cardiac surgery is in fact a gross simplification&#44; as the characteristics of these two patient groups are very different&#46; As an example&#44; a recent paper by Park et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">3</span></a> addressed non-cardiac surgery patients&#44; with successful myocardial revascularization and without systolic dysfunction&#44; and concluded that for these patients&#44; the use of perioperative beta-blockers was not associated with any negative clinical outcomes&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Once more&#44; analysis of a case mix will flatten the unbalanced nature of cohorts&#44; in a way that can distort the real tendencies&#46; Some trials are less robust than others in terms of the evidence generated&#44; possibly due to the uneven nature of patient populations&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">&#40;3&#41; Finally&#44; the types of surgery are different&#46; Cardiac surgery patients may be undergoing coronary or valvular procedures&#44; which have different potential for associated ischemia and arrhythmias&#44; and will therefore respond differently to beta-blockers&#44; while non-cardiac surgery patients undergo operations that may be more or less stressful&#44; with more or less blood loss and alterations in blood pressure&#46; Again&#44; these are all flattened in the case mix&#44; and this may also compromise the results of the analysis&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">We are living in a time of evidence-based medicine&#44; and we now practice according to guidelines&#46; That is positive&#44; but we must be careful when trying to apply these &#8216;rules&#8217; to individual patients&#46; In fact&#44; analysis of a case mix dilutes most of the variation&#44; but while this is true&#44; its significance is threatened by the Pareto principle&#44; which long ago established that 80&#37; of any variation is determined by 20&#37; of causes&#46; This could easily cast doubt on the evidence for the negative effects of beta-blockers in non-cardiac surgical patients as an absolute indication&#44; as they might in fact be extremely useful for the general population without myocardial ischemia&#44; by reducing stress on the heart and circulation&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">A good friend of mine&#44; who recently passed away&#44; used to allude to the advantages of &#8216;evidence based on medicine&#8217; as opposed to &#8216;evidence-based medicine&#8217;&#46; What was meant was medicine that would take into account the general rule but be personal and personalized to a particular patient&#59; in fact&#44; anticipating what is now called &#8216;precision medicine&#8217;&#46; Such medicine&#44; in line with the ideal combination of generalization plus particularization&#44; should always be preserved&#46; As for the mathematics&#44; to quote Sir Berkeley Moynihan&#44; &#8220;statistics will prove anything&#44; even the truth&#46;&#8221;</p><p id="par0080" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSmallCaps">I</span> truly enjoyed reading this useful paper&#44; <span class="elsevierStyleSmallCaps">I</span> congratulate the authors and <span class="elsevierStyleSmallCaps">I</span> strongly recommend it to the readers of the <span class="elsevierStyleItalic">Journal</span>&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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Revista Portuguesa de Cardiologia (English edition)
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