Perioperative Beta-blocker Research Articles

Perioperative beta-blockers in noncardiac surgery: the evidence continues to evolve.

The effectiveness and safety of giving beta-blockers to patients undergoing noncardiac surgery remain controversial. The use of these drugs in this clinical scenario increased after the publication of two positive trials in the late 1990s and was encouraged by national organizations and clinical guidelines. However, when several subsequent studies failed to show a benefit, recommendations became more limited and use decreased. This paper reviews recent evidence for and against the perioperative use of beta-blockers.

Perioperative beta-blocker use and survival in lung cancer patients

Study ObjectiveTo assess the effect of perioperative beta blockers on recurrence and overall survival after non-small cell lung cancer surgery. DesignRetrospective study. SettingAcademic medical center. MeasurementsThe medical records of patients with stage 1, 2, and 3a non-small cell lung cancer were divided into three different groups: those patients who never received beta blockers perioperatively, those receiving nonselective beta blockers within 60 days of surgery, and those taking selective beta blockers within 60 days of surgery.Recurrence-free survival and overall survival were the main clinical endpoints. Univariate log-rank tests and multivariate Cox proportional hazards models were used to assess the effects of selective beta blockers, nonselective beta blockers, or no beta blockers on recurrence-free survival and overall survival. Main ResultsThe analysis included records of 435 patients. Univariate analyses showed that the use of both selective and nonselective beta blockers was associated with decreased recurrence-free survival (P = 0.014) and overall survival (P = 0.009). However, these findings were not sustained after adjusting for possible confounding variables in the multivariate analysis. The hazard ratios for recurrence-free survival (selective beta blockers vs no beta blocker use were: 1.304; 95% confidence intervals [CI] 0.973 - 1.747; P = 0.075; for nonselective beta blockers vs no beta blockers: 0.989; 95% CI 0.639 - 1.532; P = 0.962. The hazard ratios for overall survival were: selective beta blocker use vs no beta blockers: 1.335; 95% CI 0.966 - 1.846; P = 0.080; nonselective beta blocker use vs no beta blocker use: 1.108; 95% CI 0.678 - 1.812; P = 0.682. ConclusionAdministration of beta blockers during the perioperative period did not improve recurrence-free or overall survival in patients undergoing resection of non-small cell lung cancer.

International RCT-based guidelines for use of preoperative stress testing and perioperative beta-blockers and statins in non-cardiac surgery

BackgroundCardiologists frequently advise on perioperative care for non-cardiac surgery and require guidance based on randomised controlled trials that are not discredited by misconduct or misreporting. Regional political bodies currently do not provide this. We therefore examined the credible randomised controlled trial (RCT) evidence on key cardiac perioperative questions which currently have 14 recommendations. MethodsThree aspects of perioperative measures were considered: perioperative statins, preoperative stress-testing and perioperative beta-blockade. One author searched PubMed for RCTs considering these topics. All authors independently assessed the RCTs and then collaboratively composed guidelines. ResultsPerioperative statin therapy has been examined by three RCTs, DECREASE III and IV, which are discredited and a third containing serious inconsistencies undermining its validity.Preoperative stress testing has been examined by two RCTs: one discredited trial, DECREASE II, and a second which found no benefit.Perioperative beta-blockade has been examined by eleven RCTs, two of which are discredited. The nine remaining trials together suggest that perioperative beta-blockade increases mortality. ConclusionsWhen the non-credible RCTs are omitted, the evidence base on these three subjects is much smaller than previously believed: 14 recommendations can be replaced by 3.Current guideline arrangements collectively paralyse the numerous signatories from making urgent amendments after initial publication, even when important new information comes to light. Clinicians simply have to wait for the routine five-year expiry.We present a concise scientifically based guideline and commit to updating it responsibly.

Perioperative Beta-blocker and Statin use in Patients with Coronary Artery Disease Undergoing Orthotopic Liver Transplantation

Background: In patients that undergo Orthotopic Liver Transplantation (OLT), the presence of Coronary Artery Disease (CAD) is associated with worse short- and long-term outcomes. With reported 3-year mortality rates up to 50%, recent efforts have focused on ways to reduce perioperative cardiovascular risk in this population. While continuation of Beta-Blocker (BB) and statin therapy has been shown to benefit patients with known CAD undergoing intermediate or high-risk noncardiac surgery, it is unknown whether these therapies benefit patients with CAD undergoing OLT. Methods: We retrospectively identified 45 patients that underwent OLT between 2002 and 2010 with known CAD. Records were reviewed and patterns of BB (uninterrupted therapy, interrupted therapy no therapy, at hospital discharge) and statin (preoperative, at hospital discharge) use were categorized as indicated. Chi-square, Fisher's exact test, and ANOVA were employed to compare patterns of use with Length of Stay (LOS), as well as the incidence of death, Myocardial Infarction (MI), and composite death and Myocardial Infarction (MI) at both 30 days and 12 months post-OLT. Results: Thirty-three patients (73%) were on a BB at admission, and of these 20 (61%) had BB therapy withheld for > 48 hours. Twenty-seven (60%) patients were discharged on a BB. Eight patients out of 45 (18%) were on statin therapy chronically and had the drug continued till the time of OLT. Following transplantation, 1 patient (2%) was discharged on a statin. Overall there were 5 (11%) in-hospital MI in the cohort. Of these, none occurred in patients given continuous BB therapy, while 4 occurred in patients that had BB therapy withdrawn (p = 0.118) and 1 in a patient never administered BB. On univariate analysis, mean LOS differed with respect to BB use and was longer in those that had interrupted (20.3 ± 13.9 days) compared with uninterrupted BB therapy (11.5 ± 7.1; p = 0.020). Composite 1-year mortality and MI was 22% and did not differ with regard to BB or statin prescription at the time of discharge. Conclusions: In patients with CAD undergoing OLT there is a high rate of perioperative BB withdrawal. In addition, few patients are on statin therapy at the time of OLT, and most are not administered a statin postoperatively. BB withdrawal in this population was associated with a non-significant increase in 30-day MI and a significant increase in LOS. This observation, from the largest CAD-OLT cohort yet reported, calls for identifying reasons for BB withdrawal and provides support for increased vigilance with respect to BB provision in this population.

New data on peri-operative beta-blockers suggest benefits for some patients

New data on peri-operative beta-blockers suggest benefits for some patients

Prevention of Post–Coronary Artery Bypass Grafting (CABG) Atrial Fibrillation: Efficacy of Prophylactic Beta‐Blockers in the Modern Era

Atrial fibrillation/flutter (AF) is a common complication of open heart surgery and ACC/AHA guidelines strongly recommend the use of prophylactic beta-blockers (BB) for its prevention. Several recent studies, however, have failed to show the desired protective effects of BB against post-coronary artery bypass grafting (CABG) AF. As the protocols of CABG, medical management of CAD (coronary artery disease) and demographic features of the patients undergoing open heart surgery have evolved significantly over the last two decades, we decided to perform a review of evidence from latest randomized controlled trials (RCTs) to confirm the efficacy of prophylactic BB. We searched for RCTs comparing the efficacy of prophylactic BB versus placebo/control against post-CABG AF. We limited our search to 1995 till present to reflect ongoing advancements in the protocols of CABG and the medical management of CAD. Initially, 34 trials were selected; however after certain exclusions only 10 RCTs were included in the final analysis. Prophylactic BB decreased the incidence of post-CABG AF from 32.8% in the control group to 20% in the prophylactic group with risk ratio (RR) of 0.50 with 95% CI of 0.36-0.69, P value < 0.001. In a subgroup analysis, carvedilol appears to be superior to metoprolol for the prevention of postoperative AF. Despite several limitations, this analysis confirms the efficacy of prophylactic BB against post-CABG AF in this era. We recommend continuing perioperative BB in the open heart surgery patients in the absence of contraindications.

Perioperative processes and outcomes after implementation of a hospitalist‐run preoperative clinic

A structured, medical preoperative evaluation may positively impact the perioperative course of medically complex patients. Hospitalists are in a unique position to assist in preoperative evaluations, given their expertise with inpatient medicine and postoperative surgical consultation. To evaluate specific outcomes after addition of a Hospitalist-run, medical Preoperative clinic to the standard Anesthesia preoperative evaluation. A pre/post retrospective, comparative review of outcomes of 5223 noncardiac surgical patients at a tertiary care Veterans Administration (VA) medical center. Length of stay was reduced for inpatients with an American Society of Anesthesia (ASA) score of 3 or higher (P < 0.0001). There was a trend towards a reduction in same-day, medically avoidable surgical cancellations (8.5% vs 4.9%, P = 0.065). More perioperative beta blockers were used (P < 0.0001) and more stress tests were ordered (P = 0.012). Inpatient mortality rates were reduced (1.27% vs 0.36%, P = 0.0158). A structured medical preoperative evaluation may benefit medically complex patients and improve perioperative processes and outcomes.

Associations between perioperative beta-blocker use and surgical outcomes

Associations between perioperative beta-blocker use and surgical outcomes

Improving Documentation of a Beta-Blocker Quality Measure Through an Anesthesia Information Management System and Real-Time Notification of Documentation Errors

Continuation of perioperative beta-blockers for surgical patients who are receiving beta-blockers prior to arrival for surgery is an important quality measure (SCIP-Card-2). For this measure to be considered successful, name, date, and time of the perioperative beta-blocker must be documented. Alternately, if the beta-blocker is not given, the medical reason for not administering must be documented. Before the study was conducted, the institution lacked a highly reliable process to document the date and time of self-administration of beta-blockers prior to hospital admission. Because of this, compliance with the beta-blocker quality measure was poor (-65%). To improve this measure, the anesthesia care team was made responsible for documenting perioperative beta-blockade. Clear documentation guidelines were outlined, and an electronic Anesthesia Information Management System (AIMS) was configured to facilitate complete documentation of the beta-blocker quality measure. In addition, real-time electronic alerts were generated using Smart Anesthesia Messenger (SAM), an internally developed decision-support system, to notify users concerning incomplete beta-blocker documentation. Weekly compliance for perioperative beta-blocker documentation before the study was 65.8 +/- 16.6%, which served as the baseline value. When the anesthesia care team started documenting perioperative beta-blocker in AIMS, compliance was 60.5 +/- 8.6% (p = .677 as compared with baseline). Electronic alerts with SAM improved documentation compliance to 94.6 +/- 3.5% (p < .001 as compared with baseline). To achieve high compliance for the beta-blocker measure, it is essential to (1) clearly assign a medical team to perform beta-blocker documentation and (2) enhance features in the electronic medical systems to alert the user concerning incomplete documentation.

Cardiac events after vascular surgery: risk factors and the role of perioperative beta-blockers

Cardiac events after vascular surgery: risk factors and the role of perioperative beta-blockers

Beta-Blocker management in High-Risk Patients Presenting for Non-Cardiac Surgery: Before and after the POISE Trial

The POISE Trial was a randomised, placebo-controlled, double-blind study of the effectiveness of perioperative beta-blockade in preventing cardiac events including death in 8351 patients. Our hypothesis was that knowledge of the results of the POISE Trial would either increase or decrease the use of effective perioperative beta-blockade, depending on the result. Patients presenting for non-cardiac surgery and at risk of perioperative cardiac events were recruited in two cohorts before and after the release of the POISE Trial results. Effective perioperative beta-blockade was defined as heart rate <65 beats per minute for at least 80% of the perioperative period in patients prescribed beta-blockers. Effective perioperative beta-blockade was achieved in 22 (11.5%) of 191 patients prescribed perioperative beta-blockade in the first cohort (n=392) and seven (6%) of 118 patients in the second cohort (n=241) (P=0.10). Effective heart rate control was achieved in 29 (9%) patients prescribed perioperative beta-blockers compared with 10 (3%) patients not prescribed perioperative beta-blockers (P=0.001). The rate of implementation of effective beta-blockade was low before POISE and this did not change significantly after publication. Our finding does not provide reliable evidence of a change in practice as a result of the POISE Trial.

Whatʼs New in Adult Reconstructive Knee Surgery

The purpose of this review is to summarize studies on various topics in adult knee reconstruction that were published during the year 2010. The keywords “knee” and “arthroplasty” and “prospective” and “randomized” were used to perform a search of the National Library of Medicine’s PubMed database; the search was limited to studies that were published in The Journal of Bone and Joint Surgery (American Volume) or The Journal of Arthroplasty in 2010. The resulting seventeen studies are included in this review of adult reconstruction of the knee and are included in the complete bibliography at the end of the manuscript. In addition, other studies from 2010 were chosen for their specific relevance to the topics being discussed. Continuing research into the epidemiology and economics of adult hip and knee arthroplasty has improved our understanding of costs, processes of care, and outcomes. Data related to these topics are ever important in a time when standards and mandates of care are being generated by various administrative bodies. As health care protocols and recommended processes of care are generated, there is a clear need to validate decisions that affect entire populations of patients. Bozic et al.1 used the Perspective database to identify 182,146 patients managed with primary hip and knee arthroplasty in order to assess the independent effects of surgeon volume, hospital volume, and process standardization on short-term outcomes. The authors used adherence to antibiotic prophylaxis, the appropriate use of perioperative beta-blockers, and venous thromboembolism prophylaxis as a proxy for care that was provided with process standardization. As expected, both surgeon volume and hospital volume were associated with significant improvements in short-term outcomes, including reduced complication rates, reduced rates of reoperations and readmissions, reduced mortality, and reduced length of hospital stay. In addition, the authors found that process standardization was independently responsible …

Antinociceptive effects of intrathecal landiolol injection in a rat formalin pain model.

Perioperative beta-blocker administration has recently been recommended for patients undergoing cardiac or other surgery due to the beneficial cardiovascular effects of these agents. In addition, some studies have reported that perioperatively administered beta-blockers also have analgesic effects. In this study, to investigate the antinociceptive effects and the analgesic profile of landiolol, we examined the effects of intrathecal landiolol administration on nociceptive pain behavior and c-fos mRNA expression (a neural marker of pain) in the spinal cord using a rat formalin model. We found that pain-related behavior was inhibited by intrathecal landiolol administration. Moreover, the increase in c-fos mRNA expression on the formalin-injected side was less pronounced in rats administered landiolol than in saline administered controls. Thus, intrathecal administration of landiolol exhibited antinociceptive effects. Further investigation of the antinociceptive mechanism of landiolol is required.

Colchicine for the Prevention of Postoperative Atrial Fibrillation

Colchicine for the Prevention of Postoperative Atrial Fibrillation

Perioperative cardiac evaluation, monitoring, and risk reduction strategies in noncardiac surgery patients

Cardiac complications after noncardiac surgery cause significant morbidity and mortality. This review will discuss recent developments in risk stratification, monitoring, and risk reduction strategies. The addition of biomarkers for ischemia, left ventricular function, and atherosclerosis to classic cardiac risk factors improves the prediction of both short-term and long-term outcome after noncardiac surgery. Intraoperative monitoring, using continuous 12-lead ECG assessment and transesophageal echocardiography, may timely identify treatable myocardial ischemia and arrhythmias. A prudent perioperative beta-blocker and statin regimen can reduce cardiac complications and mortality without increasing the risk of stroke in intermediate to high-risk patients. The use of circulatory assist devices might improve outcomes after major surgery in patients with severely reduced left ventricular function. Systematic preoperative assessment can identify patients at high risk of cardiac complications and guide the application of appropriate risk reduction strategies.

The power of large clinical trials

The power of large clinical trials

Myocardial ischemia-reperfusion and cardioprotection: a study with microdialysis in a porcine model

The studies in this thesis are based on questions raised in the clinical setting. Perioperative myocardial ischemia occurs more often than recognized. This may lead to myocardial infarction, increased morbidity, mortality, and health care costs. In the first study, myocardial metabolism was investigated before, during, and after 30 min of regional coronary artery occlusion, utilizing the microdialysis technique, concomitantly with the monitoring of global circulation and local coronary artery flow in an open chest pig model. Myocardial interstitial metabolites demonstrated characteristic, significant, and reproducible changes as decreased glucose, increased glycerol, and increased lactate/pyruvate ratio during ischemia, normalizing after reperfusion. Of special interest was found that myocardial glycerol concentrations remained high initially at reperfusion, raising the hypothesis of this release corresponding to reperfusion injury. This model was used for the next two studies. In cardiac surgery, episodes of myocardial ischemia or decreased myocardial performance are highly expected to occur. Patients with poor cardiac function will have a double benefit of an inotropic drug with anti-ischemic properties. Levosimendan may have this potential. In the second study, it was demonstrated that an infusion of levosimendan started before the coronary artery occlusion, as compared to start during the ischemia, reduced the effect of ischemia on the myocardial metabolism, improved, and preserved cardiac performance during this period. In recent years, concerns with the use of perioperative beta-blockers have been debated. Beta-blockers may inhibit the pharmacological preconditioning elicited by volatile anaesthetics. In the third study, it was demonstrated that levosimendan, in the presence of beta-blockade, was still able to induce a cardioprotective effect on the myocardial ischemic metabolism. During cold cardioplegic storage, or in the future during preservation of donor hearts by perfusion, monitoring of the donor heart before transplantation may be of benefit. We hypothesized, that myocardial microdialysate glycerol will reflect progressive damage. As the first step in pursuing this, in the fourth study, the course of myocardial metabolites was investigated during ten hours of cold cardioplegic storage. An accelerating myocardial glycerol accumulation was demonstrated during storage, after an initial stable period, probably reflecting the acceptable storage time. (Less)

A regional quality improvement effort to increase beta blocker administration before vascular surgery

To determine if a regional quality improvement effort can increase beta-blocker utilization prior to vascular surgery and decrease the incidence of postoperative myocardial infarction (POMI). A quality improvement effort to increase perioperative beta blocker utilization was implemented in 2003 at centers participating in the Vascular Study Group of New England (VSGNE). A 90% target was set and feedback given at biannual meetings. Beta blocker utilization (<1 month preoperative versus chronic) and POMI rates were prospectively collected for patients undergoing open abdominal aortic aneurysm (AAA) repair (n = 926) and lower extremity bypass (LEB; n = 2,123) from 2003 through 2008. Predictors of POMI were determined using multivariate logistic regression. Rates of beta blocker administration and POMI were analyzed over time, and across strata of patient risk based on a multivariate model. Perioperative beta blocker treatment increased from 68% of patients in the first 3 months of 2005 to 88% by the last 3 months of 2008 (P < .001). In 2003, 44% of patients not on chronic beta blockers were treated with preoperative beta blockers; by 2008, 78% of patients not on chronic beta blockers were started perioperatively on these medications (P < .001). Beta blocker utilization increased across all centers and surgeons participating during the study period, and increased in patients of low, medium, and high cardiac risk. However, the rate of POMI did not change over time (5.2% in 2003, 5.5% in 2008; P = .876), although a trend towards lower POMI rate was seen in patients on preoperative beta blockers (4.4% in 2003-2005, 2.6% in 2006-2008; P = .43). In multivariable modeling we found that age >70 (odds ratio [OR], 2.1), positive stress test (OR, 2.2), congestive heart failure (CHF; OR, 1.7), chronic beta blocker administration (OR, 1.7), resting heart rate <70 (OR, 1.8), and diabetes (OR, 1.6) were associated with POMI. Resting heart rate was similar for patients on chronic (67), preoperative (70), and no beta blockers (70; P = .521). Our regional quality improvement effort successfully increased perioperative beta blocker utilization. However, this was not associated with reduced rates of POMI or resting heart rate. While this demonstrates the effectiveness of regional quality improvement efforts in changing practice patterns, further work is necessary to more precisely identify those patients who will benefit from beta blockade at the time of vascular surgery.

Is it possible to decrease the incidence of peri-operative stroke associated with acute peri-operative beta-blocker administration?

Is it possible to decrease the incidence of peri-operative stroke associated with acute peri-operative beta-blocker administration?

Other important applications for beta-blockers in high-risk patients.

Beta-blockers suppress the adverse effects of chronic activation of the sympathetic nervous system-which plays an important role in the progression of cardiovascular disease- and the drugs are also recommended as primary therapy in other diverse medical conditions that present treatment problems. For many patients with atrial fibrillation, a common condition that poses a high risk of stroke, heart rate control with beta-blockers is increasingly seen as a critical therapeutic component. Similarly, perioperative beta-blocker use provides clinical benefits in patients undergoing noncardiac surgery who are at risk of cardiac events. In migraine therapy, beta-blockers are well established as effective agents for prophylaxis, and beta-blockers may reduce levels of C-reactive protein, a sensitive marker of inflammation in cardiovascular disease. Reviewing the role of beta-blockers in several ancillary conditions should help illuminate various aspects of the complex progression of cardiovascular disease and clarify the drugs' various therapeutic benefits.