Association between complications and death within 30 days after noncardiac surgery.

BACKGROUND: Among adults undergoing contemporary noncardiac surgery, little is known about the frequency and timing of death and the associations between perioperative complications and mortality. We aimed to establish the frequency and timing of death and its association with perioperative complications. METHODS: We conducted a prospective cohort study of patients aged 45 years and older who underwent inpatient noncardiac surgery at 28 centres in 14 countries. We monitored patients for complications until 30 days after surgery and determined the relation between these complications and 30-day mortality using a Cox proportional hazards model. RESULTS: We included 40 004 patients. Of those, 715 patients (1.8%) died within 30 days of surgery. Five deaths (0.7%) occurred in the operating room, 500 deaths (69.9%) occurred after surgery during the index admission to hospital and 210 deaths (29.4%) occurred after discharge from the hospital. Eight complications were independently associated with 30-day mortality. The 3 complications with the largest attributable fractions (AF; i.e., potential proportion of deaths attributable to these complications) were major bleeding (6238 patients, 15.6%; adjusted hazard ratio [HR] 2.6, 95% confidence interval [CI] 2.2-3.1; AF 17.0%); myocardial injury after noncardiac surgery [MINS] (5191 patients, 13.0%; adjusted HR 2.2, 95% CI 1.9-2.6; AF 15.9%); and sepsis (1783 patients, 4.5%; adjusted HR 5.6, 95% CI 4.6-6.8; AF 12.0%). INTERPRETATION: Among adults undergoing noncardiac surgery, 99.3% of deaths occurred after the procedure and 44.9% of deaths were associated with 3 complications: major bleeding, MINS and sepsis. Given these findings, focusing on the prevention, early identification and management of these 3 complications holds promise for reducing perioperative mortality. Study registration: ClinicalTrials.gov, no. NCT00512109.

Impact of renin-angiotensin system inhibitors continuation versus discontinuation on outcome after major surgery: protocol of a multicenter randomized, controlled trial (STOP-or-NOT trial).

BACKGROUND: Chronic treatment of hypertension or heart failure very often includes an angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) as renin-angiotensin system inhibitors (RASi) treatments. To stop or not to stop these medications before major surgery remains an unresolved issue. The lack of evidence leads to conflicting guidelines with respect to RASi management before major surgery. The purpose of this study is to evaluate the impact of a strategy of RASi continuation or discontinuation on perioperative complications in patients undergoing major non-cardiac surgery. METHODS: This is a multicenter, open-labeled randomized controlled trial in > 30 French centers. In the experimental group, RASi will be continued while the treatment will be stopped 48 h before the surgery in the control arm. The primary endpoint is a composite endpoint of major complications after surgery. An endpoint adjudication committee will review clinical data and adjudicate efficacy endpoints while blinded to the assigned study drug group. Main analysis will be by intention-to-treat comparing the composite outcome measure at 28 days in the two groups. A total of 2222 patients are planned to detect an absolute complications difference of 5%. DISCUSSION: The results of the trial should provide robust evidence to anesthesiologists and surgeons regarding management of RASi before major non-cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03374449 . Registered on 11 December 2017.

Perioperative management of patients with coronary artery disease undergoing non-cardiac surgery: Summary from the French Society of Anaesthesia and Intensive Care Medicine 2017 convention.

This review summarises the specific stakes of preoperative, intraoperative, and postoperative periods of patients with coronary artery disease undergoing non-cardiac surgery. All practitioners involved in the perioperative management of such high cardiac risk patients should be aware of the modern concepts expected to decrease major adverse cardiac events and improve short- and long-term outcomes. A multidisciplinary approach via a functional heart team including anaesthesiologists, cardiologists and surgeons must be encouraged. Rational and algorithm-guided management of those patients should be known and implemented from preoperative to postoperative period.

Risk factors for pulmonary complications after hepatic resection: role of intraoperative hemodynamic instability and hepatic ischemia.

BACKGROUND: Postoperative operative pulmonary complications (PPCs) after hepatic surgery are associated with increased length of hospital stays. Intraoperative blood transfusion, extensive resection and different comorbidities have been identified. Other parameters, like time of hepatic ischemia, have neither been clinically studied, though experimental studies show that hepatic ischemia can provide lung injury. The objective of this study was to determinate the risk factors of postoperative pulmonary complications (PPCs) after hepatic resection within 7 postoperative days. METHOD: Ninety-four patients consecutively who underwent elective hepatectomy between January and December 2013. Demographic data, pathological variables, and preoperative, intraoperative, and postoperative variables had been prospectively collected in a data base. The dependant variables studied were the occurrence of PPCs, defined before analysis of the data. RESULTS: PPCs occurred in 32 (34%) patients. A multivariate analysis allowed identifying the risk factors for PPCs. On multivariate analysis, preoperative gamma-glutamyltransferase (GGT) elevation OR =5,12 [1,85-15,69] p = 0,002, liver ischemia duration OR = 1,03 [1,01-1,06] p = 0,01 and the intraoperative use of vasopressor OR = 4,40 [1,58-13,36] p = 0,006 were independently associated with PPCs. For every 10 min added in ischemia duration, the OR of the risk of PPCs was estimated to be 1.37 (CI95% = [1.08-1.81], p = 0.01). CONCLUSION: Three risk factors for PPCs have been identified in a population undergoing liver resection: preoperative GGT elevation, ischemia duration and the intraoperative use of vasopressor. PPCs after liver surgery could be related to lung injury induced by liver ischemia reperfusion and not solely by direct infectious process. That could explain why factors influencing directly or indirectly liver ischemia were independently associated with PPCs.

Association of Postoperative High-Sensitivity Troponin Levels With Myocardial Injury and 30-Day Mortality Among Patients Undergoing Noncardiac Surgery.

IMPORTANCE: Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS). OBJECTIVE: To determine the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality). DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013. EXPOSURES: Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement. MAIN OUTCOMES AND MEASURES: A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality. RESULTS: Among 21 842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT <5 ng/L), peak postoperative hsTnT levels of 20 to less than 65 ng/L, 65 to less than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0% (123/4049; 95% CI, 2.6%-3.6%), 9.1% (102/1118; 95% CI, 7.6%-11.0%), and 29.6% (16/54; 95% CI, 19.1%-42.8%), with corresponding adjusted HRs of 23.63 (95% CI, 10.32-54.09), 70.34 (95% CI, 30.60-161.71), and 227.01 (95% CI, 87.35-589.92), respectively. An absolute hsTnT change of 5 ng/L or higher was associated with an increased risk of 30-day mortality (adjusted HR, 4.69; 95% CI, 3.52-6.25). An elevated postoperative hsTnT (ie, 20 to <65 ng/L with an absolute change ≥5 ng/L or hsTnT ≥65 ng/L) without an ischemic feature was associated with 30-day mortality (adjusted HR, 3.20; 95% CI, 2.37-4.32). Among the 3904 patients (17.9%; 95% CI, 17.4%-18.4%) with MINS, 3633 (93.1%; 95% CI, 92.2%-93.8%) did not experience an ischemic symptom. CONCLUSIONS AND RELEVANCE: Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.

Impact of aspirin and clopidogrel interruption on platelet function in patients undergoing major vascular surgery.

AIMS: To investigate functional platelet recovery after preoperative withdrawal of aspirin and clopidogrel and platelet function 5 days after treatment resumption. METHODS/RESULTS: We conducted an observational study, which prospectively included consecutive patients taking aspirin, taking clopidogrel, and untreated controls (15 patients in each group). The antiplatelet drugs were withdrawn five days before surgery (baseline) and were reintroduced two days after surgery. Platelet function was evaluated by optical aggregation in the presence of collagen, arachidonic acid (aspirin) and ADP (clopidogrel) and by VASP assay (clopidogrel). Platelet-leukocyte complex (PLC) level was quantified at each time-point. At baseline, platelet function was efficiently inhibited by aspirin and had recovered fully in most patients 5 days after drug withdrawal. PLC levels five days after aspirin reintroduction were similar to baseline (+4±10%; p = 0.16), in line with an effective platelet inhibition. Chronic clopidogrel treatment was associated with variable platelet inhibition and its withdrawal led to variable functional recovery. PLC levels were significantly increased five days after clopidogrel reintroduction (+10±15%; p = 0.02), compared to baseline. CONCLUSIONS: Aspirin withdrawal 5 days before high-bleeding-risk procedures was associated with functional platelet recovery, and its reintroduction two days after surgery restored antiplaletet efficacy five days later. This was not the case of clopidogrel, and further work is therefore needed to define its optimal perioperative management.

The long-term impact of early cardiovascular therapy intensification for postoperative troponin elevation after major vascular surgery.

BACKGROUND: Acute cardiac events are a frequent cause of morbidity after vascular surgery. The impact of early evidence-based treatment for patients with an acute cardiac event after vascular surgery on long-term postoperative outcomes has not been extensively studied. We hypothesized that providing appropriate evidence-based treatment to patients with elevated postoperative cardiac troponin levels may limit long-term mortality. METHODS: We conducted a study of 667 consecutive major vascular surgery patients with an elevated postoperative troponin I level. We then determined which of these patients received medical therapy as per the 2007 American College of Cardiology/American Heart Association recommendations for the medical management of patients with chronic stable angina. All patients with troponin elevation were then matched with 2 control patients without postoperative troponin elevation. Matching was done using logistic regression and nearest-neighbor matching methods. The primary study end point was 12 months survival without a major cardiac event (i.e., death, myocardial infarction, coronary revascularization, or pulmonary edema requiring hospitalization). RESULTS: Therapy was intensified in 43 of 66 patients (65%) who suffered a troponin I elevation after surgery. Patients with a troponin I elevation not receiving intensified cardiovascular treatment had a hazard ratio (HR) of 1.77 (95% confidence interval (CI), 1.13-2.42; P = 0.004) for the primary study outcome as compared with the control group. In contrast, patients with a troponin I elevation who received intensified cardiovascular treatment had an HR of 0.63 (95% CI, 0.10-1.19; P = 0.45) for the primary outcome as compared with the control group. Patients with a troponin I elevation not receiving treatment intensification likely were at higher risk for a major cardiac event (HR, 2.80; 95% CI, 1.05-24.2; P = 0.04) compared with patients who did receive treatment intensification. CONCLUSIONS: The main finding of this study was that in patients with elevated troponin I levels after noncardiac surgery, long-term adverse cardiac outcomes may likely be improved by following evidence-based recommendations for the medical management of acute coronary syndromes.

Impact of perioperative bleeding on the protective effect of ß-blockers during infrarenal aortic reconstruction.

BACKGROUND: The use of ß-blockers during the perioperative period remains controversial. Although some studies have demonstrated their protective effects regarding postoperative cardiac complications, others have demonstrated increased mortality when ß-blockers were introduced before surgery. METHODS: In this observational study involving 1,801 patients undergoing aortic reconstruction, we prospectively assessed ß-blocker therapy compared with no ß-blocker therapy, with regard to cardiac and noncardiac postoperative outcomes using a propensity score approach. The impact of ß-blockers was analyzed according to the intraoperative bleeding estimated by transfusion requirements. RESULTS: In-hospital mortality was 2.5% (n=45), ß-blocker use was associated with a reduced frequency of postoperative myocardial infarction (OR=0.46, 95% CI [0.26; 0.80]) and myocardial necrosis (OR=0.62, 95% CI [0.43; 0.88]) in all patients, but also with an increased frequency of multiple organ dysfunction syndromes (OR=2.78, 95% CI [1.71; 4.61]). In patients with severe bleeding (n=163; 9.1%), the frequency of in-hospital death (OR=6.65, 95% CI [1.09; 129]) and/or multiple organ dysfunction syndromes (OR=4.18, 95% CI [1.81; 10.38]) were markedly increased. Furthermore, no more than 28% of the patients who died presented with postoperative myocardial infarction, whereas 69% of the patient with a postoperative myocardial infarction also presented an excessive bleeding. CONCLUSIONS: Perioperative ß-blocker therapy was associated with an overall reduction in postoperative cardiac events. In the vast majority of patients with low perioperative bleeding, the global effect of ß-blockers was protective; in contrast, patients given ß-blockers who experienced severe bleeding had higher mortality and an increased frequency of multiorgan dysfunction syndrome.

Impact of preoperative statin therapy on adverse postoperative outcomes in patients undergoing vascular surgery.

BACKGROUND: Chronic statin therapy is associated with reduced postoperative mortality. Renal and cardiovascular benefits have been described, but the effect of chronic statin therapy on postoperative adverse events has not yet been explored. METHODS: In this observational study involving 1,674 patients undergoing aortic reconstruction, we prospectively assessed chronic statin therapy compared with no statin therapy, with regard to serious outcomes, by propensity score and multivariable methods. RESULTS: In propensity-adjusted multivariable logistic regression (c-index: 0.83), statins were associated with an almost threefold reduction in the risk of death in patients undergoing major vascular surgery (odds ratio: 0.40; 95% CI: 0.28-0.59) and an almost twofold reduction in the risk of postoperative myocardial infarction (odds ratio: 0.52; 95% CI: 0.38-0.71). Likewise, the use of chronic statin therapy was associated with a reduced risk of postoperative stroke and renal failure. Statins did not significantly reduce the risk of pneumonia, multiple organ dysfunction syndrome, and surgical complications; however, in the case of postoperative multiple organ dysfunction syndrome (odds ratio: 0.34; 95% CI: 0.12-0.94) and surgical complications (odds ratio: 0.39; 95% CI: 0.17-0.86), reduced mortality was observed. CONCLUSIONS: Chronic statin therapy was associated with a reduction in all cardiac and vascular outcomes after major vascular surgery. Furthermore, in major adverse events, such as multiple organ dysfunction syndrome and surgical complications, statins were also associated with decreased mortality.

Differential down-regulation of HLA-DR on monocyte subpopulations during systemic inflammation.

INTRODUCTION: Decreased expression of human leukocyte antigen class II (HLA-DR) on monocytes is a hallmark of altered immune status in patients with a systemic inflammatory response syndrome (SIRS). So far, the analyses were mainly performed without taking into account monocytes subpopulations. METHODS: We studied this modification on CD14HIGH and CD14LOW monocytes of 20 SIRS patients undergoing abdominal aortic surgery (AAS), 20 patients undergoing carotid artery surgery (CAS), and 9 healthy controls, and we investigated mediators and intracellular molecules that may be involved in this process. RESULTS: HLA-DR on CD14HIGH monocytes started to decrease during surgery, after blood reperfusion, and was further reduced post-surgery. In contrast, HLA-DR expression on CD14LOW cells only decreased after surgery, and to a lesser extent than on CD14HIGH monocytes. Negative correlations were found between the reduction of HLA-DR expression and the change in cortisol levels for both subpopulations, whereas a negative correlation between interleukin-10 (IL-10) levels and HLA-DR modulation was only observed for CD14HIGH cells. In accordance with these ex vivo results, HLA-DR on CD14HIGH and CD14LOW monocytes of healthy donors was reduced following incubation with hydrocortisone, whereas IL-10 only acted on CD14HIGH subpopulation. Furthermore, flow cytometry revealed that the expression of IL-10 receptor was higher on CD14HIGH versus CD14LOW monocytes. In addition, hydrocortisone, and to a lesser extent IL-10, reversed the up-regulation of HLA-DR induced by bacterial products. Finally, membrane-associated RING-CH-1 protein (MARCH1) mRNA, a negative regulator of MHC class II, was up-regulated in monocytes of AAS patients on Day 1 post-surgery, and in those of healthy subjects exposed to hydrocortisone. CONCLUSIONS: This study reveals that HLA-DR expression is modulated differently on CD14HIGH (classical) versus CD14LOW (inflammatory) monocytes after systemic inflammation.

Real-life management of dual antiplatelet therapy interruption: the REGINA survey.

BACKGROUND: Concern about procedure-related bleeding is a major reason for premature discontinuation of dual oral antiplatelet therapy (APT); treatment cessation is detrimental in patients with coronary artery disease (CAD), especially after drug-eluting stent (DES) placement. The nationwide REGINA survey was designed to evaluate how the interruption of dual APT is managed in the 'real world'. METHODS: Physicians (2700/4581) were randomly selected to participate in a computer-assisted telephone interview. Knowledge about DES and APT was appraised by multiple-choice questions. Strategies for temporary interruption of dual APT before an invasive or surgical procedure were evaluated using 21 scenarios, including high-risk (30 days after DES) and low-risk (18 months after DES) periods. RESULTS: Out of 2700 practitioners, 2515 completed the interview. Rates of correct answers to basic knowledge questions ranged from 0% (dentists) to 52% (cardiologists). Unjustified total interruption of dual APT was much more frequent than expected (22.0% vs. 11.8%). A strategy of total interruption was less frequently chosen in the period of high ischemic risk compared to the low-risk period (13.7% vs. 31.1%, p<0.0001). Dual APT interruption in patients who require additional invasive cardiac or surgical procedures depended on type of physician consulted (more frequent in specialists than general practitioners or dentists), and on the physician's age and practice type (rural/private vs. urban/hospital). Correct answers were more frequently given in situations bearing a major risk, either ischemic or bleeding risk, than in those with no risk (49.2% vs. 30.2%, p<0.0001). Low-molecular-weight heparin was the substitution therapy in over two-thirds of scenarios and was associated with longer periods of APT interruption. INTERPRETATION: Adequate management of APT in patients with intracoronary stents who undergo potentially haemorrhagic invasive procedures depends mainly on the type of physician involved and their practice rather than on a carefully weighted assessment of ischemic/bleeding risk. Our findings suggest a lack of scientific evidence, insufficient knowledge of guidelines, and poor communication between physicians managing these patients.

Translocation of bacterial NOD2 agonist and its link with inflammation.

INTRODUCTION: The gut is often considered as the motor of critical illness through bacterial translocation, which amplifies the inflammatory response and alters the immune status. However, systemic bacterial translocation was rarely proven and endotoxin measurement only reflects translocation of Gram-negative-derived products. The process could be more frequently identified if peptidoglycan, derived from both Gram-negative and Gram-positive bacteria, was measured. METHODS: We developed a new tool to detect circulating peptidoglycan-like structure using a NOD2-transfected cell line. We also measured plasma and cell-associated endotoxin and different plasma markers of inflammation. We studied 21 patients undergoing abdominal aortic surgery (AAS), and 21 patients undergoing carotid artery surgery (CAS) were included as negative controls. Patients were sampled during surgery until two days post-surgery. RESULTS: In 90.5% of the AAS patients, a NOD2 agonist peak was detected in plasma before aortic clamping, but after gut manipulation by the surgeon, and persisted after blood reperfusion. As expected, no peak was detected in plasma from CAS patients (P = 0.003). Leukocyte-bound endotoxin appeared after blood reperfusion in 71% of the AAS patients, and circulating endotoxin was detected for 57% of them. The levels of interleukin (IL)-6, IL-10 and of inflammatory markers (C-reactive protein, procalcitonin) were maximal at postoperative day 1 or 2 in AAS patients. The levels of circulating NOD2 agonist positively correlated with those of cortisol and IL-10. CONCLUSIONS: The measurement of circulating NOD2 agonist gives a higher informative tool than that of circulating endotoxin for early and sensitive detection of the translocation of bacterial products. The data suggest that circulating NOD2 agonist contributes to further enhance the stress response following surgery.

Perioperative statin therapy is associated with a significant and dose-dependent reduction of adverse cardiovascular outcomes after coronary artery bypass graft surgery.

OBJECTIVE: The aim of this study was to determine whether perioperative statin therapy was associated with a dose-dependent decrease in adverse cardiovascular events after coronary artery bypass graft (CABG) surgery. DESIGN: A prospective observational study. SETTING: A cardiovascular anesthesia unit in a university hospital. PARTICIPANTS: Four hundred eighteen consecutive patients undergoing CABG surgery between October 2004 and October 2005. INTERVENTIONS: Patients were divided in 2 groups depending on whether their preoperative treatment included statins or not. In patients receiving statins, high- and low-dose regimens were respectively defined as a regimen recognized to induce a theoretic reduction of low-density lipoprotein cholesterol level equal to 45% (n = 87) or <45% (n = 258). In treated patients, statin therapy was maintained until the day of surgery and was restarted soon thereafter. MEASUREMENTS AND MAIN RESULTS: The measured endpoint was adverse in-hospital cardiovascular outcomes including heart failure and/or malignant arrhythmia and/or cardiac death. Stepwise logistic regression and a multivariate analysis of propensity-matched cohort were used for analysis of the findings. After adjustment for propensity score, statin therapy was found to produce a significant reduction in cardiovascular outcomes (odds ratio = 0.56; 95% confidence interval [CI], 0.32-0.96, p < 0.05). By using multivariate analysis, the odds ratio for cardiovascular outcomes in patients receiving high-dose statins compared with those treated by low-dose statins was 0.62 (95% CI, 0.41-0.93; p < 0.05). CONCLUSION: Statin therapy is associated with a significant and dose-dependent reduction in adverse cardiovascular events after CABG surgery. However, further randomized trials still require confirming a causal association between statins and better postoperative outcomes and evaluating the tolerance of such perioperative therapy.

Influence of renal dysfunction on the accuracy of procalcitonin for the diagnosis of postoperative infection after vascular surgery.

OBJECTIVE: Procalcitonin has been advocated as a specific biomarker for bacterial infection. We performed this study to determine whether accuracy of procalcitonin for diagnosis of postoperative bacterial infection is affected by renal function after aortic surgery. DESIGN: Single-center prospective study. SETTING: University hospital. PATIENTS: Two hundred seventy-six patients scheduled for elective major aortic surgery. INTERVENTIONS: Blood samples were taken before surgery and each day over the 5-day postoperative period, and measurement of serum procalcitonin was performed. Diagnosis of infection was performed by a blinded expert panel. Renal function was assessed using an estimate of creatinine clearance with the Cockcroft formulas. Renal dysfunction was defined as a creatinine clearance <50 mL x min(-1). MEASUREMENTS AND MAIN RESULTS: Infection was diagnosed in 67 patients. Seventy five patients (27%) had postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, with a peak reached at the fourth postoperative day, but it was significantly higher in patients with impaired renal function in both control and infected patients. The optimal threshold of procalcitonin markedly differed in patients with renal dysfunction compared with patients without renal dysfunction (2.57 vs. 0.80 ng x mL(-1), p < .05). The diagnostic accuracy of procalcitonin significantly increased (0.74 vs. 0.70, p < .05) when the threshold of procalcitonin was adapted to the renal function. The elevation of procalcitonin occurred 2 days before the medical team was able to diagnose infection. CONCLUSIONS: Procalcitonin is a valuable marker of bacterial infections after major aortic surgery, but renal function is a major determinant of procalcitonin levels and thus different thresholds should be applied according to renal function impairment.

The impact of postoperative discontinuation or continuation of chronic statin therapy on cardiac outcome after major vascular surgery.

BACKGROUND: Statins reduce cardiac morbidity in nonsurgical populations, and may benefit surgical patients. We sought to examine cardiac outcome in patients who continued, compared with those who discontinued, statin therapy after major vascular surgery. METHODS: Prospectively collected data were examined for an association between statin therapy and perioperative cardiac morbidity in patients undergoing infrarenal aortic surgery. Between January 2001 and December 2003, there were no guidelines for perioperative continuation of statins (discontinuation group, n = 491). From January 2004, guidelines were instituted whereby statin therapy was continued starting as soon as possible after surgery (continuation group, n = 178). The occurrence of cardiac myonecrosis (defined as an increase of cardiac troponin I more than the 99th percentile or 0.2 ng/mL) was analyzed. Intra-cohort (propensity score) and extra-cohort (Lee score) adjustments of the risk were performed. RESULTS: The median delay between surgery and resumption of statin therapy was 4 days and 1 day in the discontinuation and continuation groups (P < 0.001), respectively. Using propensity score matching for likelihood of preoperative treatment, the odds ratio associated with chronic statin treatment to predict myonecrosis for patients with versus without early postoperative statin resumption (continuation versus discontinuation groups) was 0.38 and 2.1 (relative risk reduction of 5.4; 95% confidence interval: 1.2-25.3, P < 0.001), respectively. The odds ratio after adjustment for the Lee score was 0.38 in the continuation group and 2.1 in the discontinuation group (relative reduction of 5.5; 95% confidence interval: 1.2-26.0, P < 0.001). Postoperative statin withdrawal (>4 days) was an independent predictor of postoperative myonecrosis (OR 2.9, 95% confidence interval 1.6-5.5). CONCLUSIONS: Discontinuation of statin therapy after major vascular surgery is associated with an increased postoperative cardiac risk, suggesting that statin therapy should be resumed early after major vascular surgery.

Impact of aspirin with or without clopidogrel on postoperative bleeding and blood transfusion in coronary surgical patients treated prophylactically with a low-dose of aprotinin.

AIMS: Aspirin combined with clopidogrel is the treatment of choice for acute coronary syndromes. Although the maintenance of aspirin until surgery does not affect postoperative bleeding after coronary artery bypass graft (CABG) surgery, the latter may be dramatically increased when clopidogrel is continued over a period of 5 days preoperatively. METHODS AND RESULTS: This prospective observational study included 217 consecutive patients scheduled for first-time CABG. Postoperative bleeding and blood transfusion requirements were compared (equivalence) between patients pretreated during a period of 5 days prior surgery by either aspirin alone (n = 157) or combined with clopidogrel (n = 60). Aprotinin was systematically used in all these patients considered as high risk for bleeding. We found no significant difference between both groups concerning the preoperative characteristics except for unstable angina (33 vs. 19%, P = 0.02) and left main coronary artery stenosis (27 vs. 13%, P = 0.02), which were more frequent in patients receiving clopidogrel. The median chest tube output was similar in both groups 24 h postoperatively at 350 mL (95% CI 150-850) vs. 375 mL (95% CI 175-875), and the difference between groups (7%, 95% CI -9 to 22) did not encompass the predetermined margins of equivalence (25%). No significant difference was found on blood transfusion use (38 vs. 38%, P = 0.99). After adjustment by a propensity score, we found that clopidogrel was not associated with an increased risk of excessive bleeding. CONCLUSION: In patients undergoing first-time CABG and treated prophylactically with aprotinin, aspirin and clopidogrel may be continued until surgery without increasing postoperative bleeding or transfusion requirements.

Efficacy of zoniporide, an Na/H exchange ion inhibitor, for reducing perioperative cardiovascular events in vascular surgery patients.

OBJECTIVES: To determine whether a novel Na+/H+ exchange ion inhibitor, zoniporide, is associated with reduced perioperative myocardial ischemic injury in high-risk surgery patients. DESIGN: Randomized double-blind placebo-controlled multidose trial. SETTING: Multicenter worldwide (105 centers) trial. PARTICIPANTS: Patients with known or multiple risk factors for coronary artery disease undergoing noncardiac vascular surgery. INTERVENTIONS: Four parallel groups received 1 of 3 doses of zoniporide or placebo, delivered as a 60-minute loading dose immediately before surgery, and followed by a continuous intravenous infusion for up to 7 days. MEASUREMENTS AND MAIN RESULTS: A total of 824 subjects were randomized into the study from 105 centers worldwide. Of these, 784 subjects received study drug infusion in the 3-mg/kg/d, 6-mg/kg/d, and 12-mg/kg/d groups and the placebo group, and 769 satisfied the criteria for the primary efficacy analysis population. This is 68% of the planned sample size of 1125 subjects. Anesthetic management and perioperative cardiac medications were at the discretion of the attending anesthesiologists, surgeons, and cardiologists. The proportion of subjects who experienced the composite endpoint event (death, myocardial infarction, congestive heart failure, arrhythmia) by postsurgical day 30 was 18.5% in the 12-mg/kg/d group, compared with 15.7% in the placebo group, resulting in a relative risk (RR) of 1.17% (95% confidence interval [CI], 0.80-1.72; p = NS) favoring placebo. The proportions in the lower 2 zoniporide dose groups were slightly lower than in the placebo group, although the sample size is inadequate to reach any firm conclusions. CONCLUSIONS: The results fail to demonstrate the efficacy of zoniporide in reducing the proportion of patients at high risk undergoing noncardiac vascular surgery who experience a composite cardiovascular endpoint, which led the corporate sponsor to stop enrollment early on the basis of a futility analysis of the chance of demonstrating efficacy with a larger sample size.

Poor intraoperative blood glucose control is associated with a worsened hospital outcome after cardiac surgery in diabetic patients.

BACKGROUND: Tight perioperative control of blood glucose improves the outcome of diabetic patients undergoing cardiac surgery. Because stress response and cardiopulmonary bypass can induce profound hyperglycemia, intraoperative glycemic control may become difficult. The authors undertook a prospective cohort study to determine whether poor intraoperative glycemic control is associated with increased intrahospital morbidity. METHODS: Two hundred consecutive diabetic patients undergoing on-pump heart surgery were enrolled. A standard insulin protocol based on subcutaneous intermediary insulin was given the morning of the surgery. Intravenous insulin therapy was initiated intraoperatively from blood glucose concentrations of 180 mg/dl or greater and titrated according to a predefined protocol. Poor intraoperative glycemic control was defined as four consecutive blood glucose concentrations greater than 200 mg/dl without any decrease in despite insulin therapy. Postoperative blood glucose concentrations were maintained below 140 mg/dl by using aggressive insulin therapy. The main endpoints were severe cardiovascular, respiratory, infectious, neurologic, and renal in-hospital morbidity. RESULTS: Insulin therapy was required intraoperatively in 36% of patients, and poor intraoperative glycemic control was observed in 18% of patients. Poor intraoperative glycemic control was significantly more frequent in patients with severe postoperative morbidity (37% vs. 10%; P < 0.001). The adjusted odds ratio for severe postoperative morbidity among patients with a poor intraoperative glycemic control as compared with patients without was 7.2 (95% confidence interval, 2.7-19.0). CONCLUSION: Poor intraoperative control of blood glucose concentrations in diabetic patients undergoing cardiac surgery is associated with a worsened hospital outcome after surgery.