Abstract Background: Perioperative metoprolol increases postoperative stroke. Animal studies indicate that the mechanism may be related to attenuated β2-adrenoreceptor-mediated cerebral vasodilatation. The authors therefore conducted a cohort to study whether the highly β1-specific β-blocker (bisoprolol) was associated with a reduced risk of postoperative stroke compared with less selective β-blockers (metoprolol or atenolol). Methods: The authors conducted a single-center study on 44,092 consecutive patients with age 50 yr or more having noncardiac, nonneurologic surgery. The primary outcome was stroke within 7 days of surgery. The secondary outcome was a composite of all-cause mortality, postoperative myocardial injury, and stroke. A propensity score-matched cohort was created to assess the independent association between bisoprolol and less β1-selective agents metoprolol or atenolol. A secondary analysis using logistic regression, based on previously identified confounders, also compared selective β1-antagonism. Results: Twenty-four percent (10,756) of patients were exposed to in-hospital β-blockers. A total of 88 patients (0.2%) suffered a stroke within 7 days of surgery. The matched cohort consisted of 2,462 patients, and the pairs were well matched for all variables. Bisoprolol was associated with fewer postoperative strokes than the less selective agents (odds ratio = 0.20; 95% CI, 0.04–0.91). Multivariable risk-adjustment in the β-blockers-exposed patients comparing bisoprolol with the less selective agents was associated with a similarly reduced stroke rate. Conclusions: The use of metoprolol and atenolol is associated with increased risks of postoperative stroke, compared with bisoprolol. These findings warrant confirmation in a pragmatic randomized trial.
Ventricular dysfunction is associated with increased cardiovascular morbidity and mortality after both cardiac and non-cardiac surgery. Traditionally, invasive pressure monitoring has been used to make inferences regarding ventricular function. However, the relationship between pressure and organ perfusion may be affected by many variables in the dynamic intraoperative environment. TOE has the advantage of real-time visualization of ventricular filling, contractility and ischaemia. As such, TOE is now considered to be the ‘gold standard’ intraoperative monitor of ventricular function.
We wish to thank Drs. Wicker and Bronheim for their interest in our recent publication1 and welcome the opportunity to address their concerns. They question whether the impact of early initiation of β-blocker may have confounded our analysis. This is entirely appropriate because it is possible that metoprolol is preferentially used in acute administration, a population that has been shown to be associated with increased cardiovascular outcomes.First, we would point out that our recent article was not simply arrived at through a data-mining process but carried out to investigate a specific hypothesis: β-receptor selectivity increased stroke rates. Our hypothesis was firmly based on the physiologic changes that we had observed in several previous animal studies.2–4 These experimental investigations, started in 2005, were on the basis of several signals that we had observed in both animal models of stroke5 and a meta-analysis of noncardiac surgical patients.6 Thus, with publication of our recent article,1 there are now both physiologic rationale and human data supporting the THESIS that β selectivity is one of the several possible mechanisms mediating the increase in stroke rates with β receptor antagonists. It is also irrefutable that perioperative β-receptor antagonism is a major patient safety issue.Although we think that the issue of timing is an important component of β-blocker safety, we do not believe that it is the primary reason behind the increased incidence in β-blocker–mediated perioperative stroke. The issue of timing has been addressed now in at least five different articles, all using separate databases, and varied outcome measures, outcomes that are not equivalent. The first report, Flu et al.7 used data from Erasmus Medical Centre. This group and its data resources are currently the object of intense scrutiny. In this article, the only outcome that was different at 30 days was an increased rate of detectable troponin T.* Ellenberger et al.8 showed a difference in number of patients with detectable troponin I. Neither of these studies used the universal definition or screened for myocardial infarction. In addition, neither report show a difference in 30-day mortality rates. More recently, London et al.,9 using the Veteran Affairs Surgical database, could not show a difference in mortality based on the initiation within the 7 days compared with those initiated within 30 days of surgery (etable 15). Wijeysundera et al. have shown that early versus late initiation of β-blockers is associated with a 50% risk-adjusted increase in mortality. Neither myocardial infarction nor stroke rate (using International Statistical Classification of Diseases and Related Health Problems 10 coding) was shown to be different based on the timing of drug.10 Importantly, this analysis, using a large administrative database in more than 47,000 Medicare patients, found little difference in the proportion of patients initiating metoprolol or bisoprolol early versus those who were chronically β-blocked (table 2 in reference 1).1 Thus, our data do not support the idea that metoprolol is preferentially the drug used clinically in acutely starting perioperative β-blockers. In addition, the cumulative data, in these five reports, do not support the notion that timing is important to postoperative stroke.Third, we also agree that a discussion relating to the dosage of β-blockers is relevant. However, Drs. Wicker and Bronheim are mistaken, the dosages of the three major β-blockers were presented (see line 1 of table 1 in reference 1).1 The median outpatient dosages found in our population reflect the package insert instruction for use of these β-blockers as antihypertensive and antiangina medications. The variability in dose we present reflects what we consider to be the advantage of chronic dosing; that is, dose titration. Moreover, the doses in our study are identical to the outpatient dosages of metoprolol found in the Wallace study.11 We would also point out that the higher the dose of a β-blocker the less likely it would be for the drug will maintain a relative β1 selectivity.As we state in the original article, we agree entirely that this thesis should be subject to further investigation, preferably using a blinded randomized design. Our analysis was intended, and we think reconfirms the possibility that, the physiologic phenomena we demonstrated in animal models of stroke may be active in humans. We are actively seeking support for this proposed randomized trial and invite all interested parties to contact us to get involved in this important investigation.The authors declare no competing interests.
Pulmonary hypertension is associated with increased postoperative morbidity and mortality. Early diagnosis and echocardiographic detection of right ventricular (RV) dysfunction are paramount in perioperative management. The goal of this review is to provide an overview of the recent literature on this topic.Doppler interrogation of pulmonary artery flow may provide an insight into the severity and mechanism of pulmonary hypertension. Established echocardiographic techniques of RV assessment have multiple limitations. Newer echocardiographic technologies (strain and three-dimensional imaging) are promising, but require further validation in the perioperative setting before they are adopted.More pulmonary hypertension patients are presenting for noncardiac surgery, creating a challenge for the anesthesiologist. Echocardiographic detection of RV dysfunction can be difficult. Routine use of intraoperative transesophageal echocardiography in major thoracic surgery is not advocated yet, but the development of automated techniques may provide an objective assessment of RV function.
Young and mature adults living with CHD often regard themselves as normal persons that happen to have had a heart problem in the past. They frequently are followed by a pediatric cardiologist, who, for a variety of reasons, both patient and system related, has not transitioned their care to an adult cardiologist and a network of adult consultants. The number of adults living with congenital heart disease has exceeded the number of children living with congenital heart disease for over a decade, and the ratio continues to rise in favour of adult populations. Where and how to deliver services to this group of patients is a challenge for pediatric and adult institutions. The number of adults living past 18 years will mandate that many non-cardiac procedures will not occur in specialized tertiary care centers. Patients will explore care in their immediate community for convenience, occasional necessity and in the case of US patients, insurance. Cardiac anesthesiologists with competencies in congenital cardiac anesthesia will provide anesthetic and ICU care for these patients in cardiac surgery however they will also participate and advise colleagues in the management of their non-cardiac surgery. The challenges for the next decade are the increasing complexity of these patients and the organization of their care for elective, urgent, and emergent non-cardiac procedures.
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