W. Scott Beattie

Aspirin "resistance" and risk of cardiovascular morbidity: systematic review and meta-analysis

Objective To determine if there is a relation between aspirin “resistance” and clinical outcomes in patients with cardiovascular disease. Design Systematic review and meta-analysis. Data source Electronic literature search without language restrictions of four databases and hand search of bibliographies for other relevant articles. Review methods Inclusion criteria included a test for platelet responsiveness and clinical outcomes. Aspirin resistance was assessed, using a variety of platelet function assays. Results 20 studies totalling 2930 patients with cardiovascular disease were identified. Most studies used aspirin regimens, ranging from 75-325 mg daily, and six studies included adjunct antiplatelet therapy. Compliance was confirmed directly in 14 studies and by telephone or interviews in three. Information was insufficient to assess compliance in three studies. Overall, 810 patients (28%) were classified as aspirin resistant. A cardiovascular related event occurred in 41% of patients (odds ratio 3.85, 95% confidence interval 3.08 to 4.80), death in 5.7% (5.99, 2.28 to 15.72), and an acute coronary syndrome in 39.4% (4.06, 2.96 to 5.56). Aspirin resistant patients did not benefit from other antiplatelet treatment. Conclusion Patients who are resistant to aspirin are at a greater risk of clinically important cardiovascular morbidity long term than patients who are sensitive to aspirin.

Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications:: A meta-analysis☆

PURPOSEnTo investigate the effects of alpha(2)-adrenergic agonists on perioperative mortality and cardiovascular complications in adults undergoing surgery.nnnMETHODSnMEDLINE (1966 to May 2002), EMBASE (1980 to May 2002), the Cochrane Clinical Trials Register, the Science Citation Index, and bibliographies of included articles were searched without language restriction. Randomized trials comparing preoperative, intraoperative, or postoperative (first 48 hours) administration of clonidine, dexmedetomidine, or mivazerol with controls were included. Studies had to report any of the following outcomes: mortality, myocardial infarction, ischemia, or supraventricular tachyarrhythmia. Treatment effects were calculated using the fixed-effects model. Heterogeneity was assessed using the Q test.nnnRESULTSnTwenty-three trials comprising 3395 patients were included. Overall, alpha(2)-adrenergic agonists reduced mortality (relative risk [RR] = 0.64; 95% confidence interval [CI]: 0.42 to 0.99; P = 0.05) and ischemia (RR = 0.76; 95% CI: 0.63 to 0.91; P = 0.003) significantly. They also reduced mortality (RR = 0.47; 95% CI: 0.25 to 0.90; P = 0.02) and myocardial infarction (RR = 0.66; 95% CI: 0.46 to 0.94; P = 0.02) during vascular surgery. During cardiac surgery, alpha(2)-adrenergic agonists reduced ischemia (RR = 0.71; 95% CI: 0.54 to 0.92; P = 0.01) and were associated with trends toward lower mortality (RR = 0.49; 95% CI: 0.12 to 1.98; P = 0.3) and a reduced risk of myocardial infarction (RR = 0.83; 95% CI: 0.35 to 1.96; P = 0.7).nnnCONCLUSIONnAlpha-2 adrenergic agonists reduce mortality and myocardial infarction following vascular surgery. During cardiac surgery, they reduce ischemia and may also have effects on mortality and myocardial infarction. Large randomized trials are needed to evaluate these agents during cardiac and vascular surgery.

A propensity score case‐control comparison of aprotinin and tranexamic acid in high‐transfusion‐risk cardiac surgery

BACKGROUND:u2002 Cardiac surgery with cardiopulmonary bypass may result in excessive fibrinolysis and platelet (PLT) dysfunction, resulting in impaired hemostasis and excessive blood loss. Prophylactic use of the antifibrinolytic drugs aprotinin and tranexamic acid is thought to prevent these hemostatic defects. Their relative clinical utility and safety in high‐transfusion‐risk cardiac surgery, however, is not known.

Risk Associated With Preoperative Anemia in Cardiac Surgery A Multicenter Cohort Study

Background— Preoperative anemia is an important risk factor for perioperative red blood cell transfusions, which are associated with postoperative morbidity and mortality. Whether preoperative anemia also is an independent risk factor for adverse outcomes after cardiac surgery, however, has not been fully elucidated. Methods and Results— In this multicenter cohort study, data were collected on 3500 consecutive patients who underwent cardiac surgery during 2004 at 7 academic hospitals. The prevalence of preoperative anemia, defined as hemoglobin <12.5 g/dL, and its unadjusted and adjusted relationships with the composite outcome of in-hospital death, stroke, or acute kidney injury were obtained. The overall prevalence of preoperative anemia was 26%, with values ranging from 22% to 30% at the participating hospitals. After the exclusion of patients who had severe preoperative anemia (hemoglobin <9.5 g/dL) or preoperative kidney failure and those who underwent emergency surgery, the composite outcome was observed in 7.5% of patients (247 of 3286). The unadjusted odds ratio for the composite outcome in anemic versus nonanemic patients was 3.6 (95% confidence interval, 2.7 to 4.7). The risk-adjusted odds ratios, obtained by multivariable logistic regression and propensity-score matching to control for important confounders (including comorbidities, institution, surgical factors, and blood transfusion), were 2.0 (95% confidence interval, 1.4 to 2.8) and 1.8 (95% confidence interval, 1.2 to 2.7), respectively. Conclusions— Preoperative anemia is independently associated with adverse outcomes after cardiac surgery. Future studies should determine whether therapies aimed at treating preoperative anemia would improve the outcomes of patients undergoing cardiac surgery.

Perioperative Myocardial Infarction

More than 230 million major surgeries are performed annually worldwide,1 and this number grows continuously. The 30-day mortality associated with moderate- to high-risk noncardiac surgery in recent large cohorts and population-based studies exceeds 2%2–4 and surpasses 5% in patients at high cardiac risk.5 Cardiac complications constitute the most common cause of postoperative morbidity and mortality,4,6 having considerable impact on the length and cost of hospitalization.7 As our population ages, more high-risk cardiac patients will undergo surgery, and perioperative myocardial infarction (PMI) can be an increasing problem.nnTraditionally, MI was defined by the World Health Organization criteria, ECG criteria, and cardiac enzymes. Defining PMI, however, is often difficult because most PMIs occur without symptoms in anesthetized or sedated patients, ECG changes are subtle and/or transient, and the creatine kinase-MB isoenzyme has limited sensitivity and specificity because of coexisting skeletal muscle injury.8 Consequently, PMI was often recognized late (postoperative day 3 to 5), resulting in high (30% to 70%9) mortality.nnCardiac troponin assays have changed this definition.10 The recent universal definition of MI11 is based on a rise and/or fall of cardiac biomarkers (preferably troponin) in the setting of myocardial ischemia: cardiac symptoms, ECG changes, or imaging findings. Studies using serial troponin measurements demonstrate that most PMIs start within 24 to 48 hours of surgery during the greatest postoperative stress.12–15 Le Manach et al15 observed early ( 24 hours) peaks in troponin in 1136 patients after abdominal aortic aneurysmectomy. Yet, 90% of troponin elevations began within <24 hours.nnTwo distinct mechanisms may lead to PMI: acute coronary syndrome and prolonged myocardial oxygen supply-demand imbalance in the presence of stable coronary artery disease (CAD), designated type 1 and type 2 by the universal definition of MI.11 This distinction …

The effects of volatile anesthetics on cardiac ischemic complications and mortality in CABG: a meta-analysis

PurposeCoronary artery bypass graft surgery (CABG) is associated with cardiac complications, including ischemia, acute myocardial infarction (AMI), and death. Volatile anesthetics have been shown to have a preconditioning-like effect. This systematic review assesses the effects of volatile anesthetics on cardiac ischemic complications and morbidity after CABG.MethodsData were obtained, without language restriction, from searches of MEDLINE, Science Citation Index, PubMed, and reference lists. We included only prospective randomized controlled trials evaluating volatile anesthetics during CABG. Two reviewers independently abstracted data on myocardial ischemia, acute myocardial infarction (AMI), and death. Treatment effects were calculated as odds ratio (OR) with 95% confidence intervals (CI) for binary data, and weighted mean difference (WMD) with 95% CI for continuous data.Principal findingsThirty-two studies (2,841 patients) were included. In comparison withiv anesthesia, volatile anesthetics were associated with reduced all-cause mortality (OR, 0.65; 95% CI, 0.36-1.18;P = 0.16). Enflurane was associated with increased AMI (OR, 1.34; 95% CI, 0.68–2.64;P = 0.40), whereas sevoflurane and desflurane reduced cardiac troponin I (cTnI) at six hours, 12 hr, 24 hr [WMD,-1.45; 95% CI (-1.73,-1.16);P < 0.00001 ], and 48 hr after operation.ConclusionThis meta-analysis demonstrates sevoflurane and desflurane reduce the postoperative rise in cTnI. Sevoflurane-mediated reduction in cardiac troponin was associated with improved long-term outcomes in one study. This meta-analysis was not able to show that these positive effects on troponin were translated into improved clinical outcomes. Well-designed large randomized control trials are needed to further elucidate the differential cardio-protective effects of volatile anesthetics.ObjectifLe pontage aortocoronarien (PAC) est associé à des complications cardiaques comme l’ischémie, l’infarctus aigu du myocarde (IAM) et la mort. Un effet semblable à celui du préconditionnement a été démontré avec les anesthésiques volatils. Dans la présente revue systématique, nous évaluons les effets des anesthésiques volatils sur les complications ischémiques et la morbidité cardiaques après un PAC.MéthodeLes données obtenues, sans restriction de langue, proviennent de MEDLINE, Science Citation Index, PubMed et des listes de références. Seules les études prospectives, randomisées et contrôlées qui évaluent les anesthésiques volatils pendant le PAC ont été retenues. Deux réviseurs indépendants ont résumé les données sur l’ischémie myocardique, l’IAM et la mort. Les effets ont été calculés par le risque relatif approché (RRA) avec un intervalle de confiance (IC) de 95 % pour les données binaires et la différence moyenne pondérée (DMP) avec un IC de 95 % pour les données en continu.Constatations principalesTrente-deux études, sur 2 841 patients, ont été retenues. Comparés aux anesthésiques iv, les anesthésiques volatils réduisent toutes les causes de mortalité (RRA de 0,65; IC de 95 %, 0,36 - 1,18; P = 0,16). L’enflurane augmente l’IAM (RRA de 1,34; IC de 95 %, 0,68 - 2,64;P = 0,40), tandis que le sévoflurane et le desflurane réduisent la troponine cardiaque I (cTnI) à six heures, 12 h, 24 h [DMP,-1,45; IC de 95 % (-1,73,-1,16);P < 0,00001] et 48 h après l’opération.ConclusionCette méta-analyse démontre que le sévoflurane et le desflurane réduisent la hausse postopératoire de cTnI. La réduction de troponine cardiaque induite par le sévoflurane est associée à une meilleure évolution à long terme dans l’une des études. La méta-analyse n’a pu montrer que ces effets positifs sur la troponine présentaient des avantages cliniques. De grandes études bien définies randomisées et contrôlées devront élucider les effets cardio-protecteurs différentiels des anesthésiques volatils.

Prediction of massive blood transfusion in cardiac surgery.

PurposeIn cardiac surgery with cardiopulmonary bypass (CPB), excessive blood loss requiring the transfusion of multiple red blood cell (RBC) units is a common complication that is associated with significant morbidity and mortality. The objective of this study was to develop a prediction rule for massive blood transfusion (MBT) that could be used to optimize the management of, and research on, at-risk patients.MethodsData were collected prospectively over the period from 2000 to 2005, on patients who underwent surgery with CPB at one hospital. Patients who received ≥ five units of RBC within one day of surgery were classified as MBT. Logistic regression was used to appropriately select and weigh perioperative variables in the prediction rule, which was developed on the initial 60% of the sample and validated on the remaining 40%.ResultsOf the 10,667 patients included, 925 (8.7%) had MBT. The clinical prediction rule included 12 variables (listed in order of predictive value: CPB duration, preoperative hemoglobin concentration, body surface area, nadir CPB hematocrit, previous sternotomy, preoperative shock, preoperative platelet count, urgency of surgery, age, surgeon, deep hypothermic circulatory arrest, and type of procedure) and was highly discriminative (c-index = 0.88). In the validation set, those classified as low-, moderate-, and high-risk by a simple risk score derived from the prediction rule had a 5%, 27%, and 58% chance of MBT, respectively.ConclusionA clinical prediction rule was developed that accurately identified patients at low-risk or high-risk for MBT. Studies are needed to determine the external generalizability and clinical utility of the prediction rule.RésuméObjectifEn cardiochirurgie avec circulation extracorporelle (CEC), une perte de sang excessive exigeant la transfusion de multiples unités de culots globulaires (CG) est une complication fréquente associée à une morbidité et à une mortalité significatives. L’objectifde notre étude était d’élaborer une règle de prédiction pour la transfusion massive (TM) qui pourrait être utilisée pour optimaliser la recherche sur les patients à risque, et leur traitement.MéthodeLes données prospectives ont été recueillies sur les patients qui ont subi une opération avec CEC dans un hôpital entre 2000 et 2005. Les patients ayant reçu ≥ cinq unités de CG en moins d’un jour postopératoire ont été classés comme TM. La régression logistique a permis de choisir et pondérer convenablement les variables périopératoires de la règle de prédiction qui a été élaborée d’après les premiers 60 % de l’échantillon et validée sur les 40 % restant.RésultatsDes 10 667 patients inclus, 925 (8,7 %) avaient eu une TM. La règle de prédiction clinique incluait 12 variables (présentées par ordre de valeur prédictive: durée de la CEC, concentration d’hémoglobine préopératoire, surface corporelle, hématocrite minimal de la CEC, sternotomie antérieure, choc

Comprehensive Canadian Review of the Off-Label Use of Recombinant Activated Factor VII in Cardiac Surgery

Background— This observational study sought to identify the off-label use pattern of recombinant activated factor VII (rFVIIa) in cardiac surgery and to identify predictors of its effectiveness and risk. Methods and Results— At 18 Canadian centers, 522 nonhemophiliac cardiac surgical patients received rFVIIa during the period 2003 through 2006; data were available, and retrospectively collected, on 503 patients. The median (quartile 1, quartile 3) units of red blood cells transfused from surgery to therapy and in the 24 hours after therapy were 8 (5, 12) and 2 (1, 5), respectively (P<0.0001). Mortality rate was 32%, and mortality or major morbidity rate was 44%. These rates were within expected ranges (mortality, 27% to 35%; mortality or morbidity, 39% to 48%), which were calculated with a separate cohort of cardiac surgical patients who did not receive rFVIIa used as reference. Independent predictors of complications included instability before therapy (multiple inotropes or intra-aortic balloon pump) and increasing red blood cell units transfused before and after therapy. Variables independently associated with nonresponse included abnormal coagulation parameters and >15 red blood cell units transfused before therapy. Conclusions— In Canada, rFVIIa is used primarily when standard interventions have failed to control bleeding. In this setting, rFVIIa is associated with reduced blood product transfusions and, after risk adjustment, does not appear to be associated with increased or decreased complication rates. The effectiveness of the drug may be enhanced if it is given early in the course of refractory blood loss in the setting of adequate amounts of circulating coagulation factors.

Platelet transfusions are not associated with increased morbidity or mortality in cardiac surgery.

PurposeTo determine the independent relationship between leukoreduced platelet transfusions and adverse events in cardiac surgery.MethodsIn this observational study, detailed baseline and perioperative data were prospectively collected on consecutive patients who underwent cardiac surgery at a single institution from 1999 to 2004. The independent associations of platelet transfusion with clinical outcomes (low output syndrome, myocardial infarction, stroke, renal failure, sepsis, and death) were determined by multivariable logistic regression analysis and propensity score case-control analysis.ResultsOf the 11,459 patients analyzed, 2,174 (19%) received (leukoreduced) platelets -1,408 received 5 U, 471 received 10 U, 140 received 15 U, and 155 received 20 or more units. Although all measured adverse event rates were higher in those who received platelets, in neither the logistic regression analyses nor the propensity score analyses was there any association between platelet transfusion and any of the adverse events.ConclusionsTransfusion of leukoreduced platelets in cardiac surgery is not associated with adverse clinical outcomes when adjustments are made for important confounders.RésuméObjectifDéterminer la relation indépendante entre la transfusion de plaquettes réduites en leucocytes et les événements indésirables en cardiochirurgie.MéthodeDans une étude par observation, la cueillette prospective des données initiales et périopératoires détaillées a été faite pour des patients successivement opérés en cardiochirurgie dans un seul établissement entre 1999 et 2004. Les associations indépendantes entre transfusion plaquettaire et résultat clinique (syndrome de bas débit, infarctus du myocarde, accident vasculaire, insuffisance rénale, septicémie et mort) ont été déterminées par une analyse multivariée de régression logistique et une analyse cas-témoins du score de propension.RésultatsDes 11 459 patients analysés, 2 174 (19 %) ont reçu des plaquettes réduites en leucocytes -1 408 ont eu 5 U, 471 ont eu 10 U, 140 ont eu 15 U et 155 ont eu 20 unités ou plus. Tous les taux ďévénements indésirables mesurés étaient plus élevés chez ceux qui avaient reçu des plaquettes, mais ni éanalyse de régression logistique ni éanalyse du score de propension n’ont montré ďassociation entre la transfusion de plaquettes et éun des événements indésirables.ConclusionEn cardiochirurgie, la transfusion de plaquettes réduites en leucocytes n’est pas associée à des complications cliniques quand ďimportants facteurs de confusion sont corrigés.Objectif nDeterminer la relation independante entre la transfusion de plaquettes reduites en leucocytes et les evenements indesirables en cardiochirurgie.

Alpha-2 adrenergic agonists for the prevention of cardiac complications among patients undergoing surgery

BACKGROUNDnThe surgical stress response plays an important role on the pathogenesis of perioperative cardiac complications. Alpha-2 adrenergic agonists attenuate this response and may thereby prevent cardiac complications.nnnOBJECTIVESnThis review assessed the efficacy and safety of preoperative (within 24 hours), intraoperative, and postoperative (first 48 hours) alpha-2 adrenergic agonists for preventing mortality and cardiac complications after surgery performed under either general or neuraxial anaesthesia, or both.nnnSEARCH STRATEGYnWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to August week 4 2008), EMBASE (1980 to week 36 2008), the Science Citation Index, and reference lists of articles.nnnSELECTION CRITERIAnWe included randomized controlled trials that compared alpha-2 adrenergic agonists (clonidine, dexmedetomidine, or mivazerol) against placebo or non-alpha-2 adrenergic agonists. Included studies had to report on mortality, myocardial infarction, myocardial ischaemia, or supraventricular tachyarrhythmia.nnnDATA COLLECTION AND ANALYSISnThree authors independently assessed trial quality and extracted data. Two authors independently performed computer entry of abstracted data. We contacted study authors for additional information. Adverse event data were gathered from the trials.nnnMAIN RESULTSnWe included 31 studies (4578 participants). Study quality was generally inadequate, with only six studies clearly reporting methods for blinding and allocation concealment. Overall, alpha-2 adrenergic agonists reduced mortality (relative risk (RR) 0.66; 95% CI 0.44 to 0.98; P = 0.04) and myocardial ischaemia (RR 0.68; 95% CI 0.57 to 0.81; P < 0.0001). However, their effects appeared to vary with the surgical procedure. The most encouraging data pertained to vascular surgery, where they reduced mortality (RR 0.47; 95% CI 0.25 to 0.90; P = 0.02), cardiac mortality (RR 0.36; 95% CI 0.16 to 0.79; P = 0.01), and myocardial infarction (RR 0.66; 95% CI 0.46 to 0.94; P = 0.02). With regard to adverse effects, alpha-2 adrenergic agonists significantly increased perioperative hypotension (RR 1.32; 95% CI 1.07 to 1.62; P = 0.009) and bradycardia (RR 1.66; 95% CI 1.14 to 2.41; P = 0.008).nnnAUTHORS CONCLUSIONSnOur study provides encouraging evidence that alpha-2 adrenergic agonists may reduce cardiac risk, especially during vascular surgery. Nonetheless, these data remain insufficient to make firm conclusions about their efficacy and safety. A large randomized trial of alpha-2 adrenergic agonists is therefore warranted. Additionally, future research must determine which specific alpha-2 adrenergic agonist should be used, and whether it is safe to combine them with other perioperative interventions (for example beta-adrenergic blockade).