ArticleLiterature Review

Nonsurgical Strategies to Reduce Mortality in Patients Undergoing Cardiac Surgery: An Updated Consensus Process

Authors:
  • I.R.C.C.S. IRCCS Ospedale san Martino
  • Dante Pazzanese Institute of Cardiology - Fundação Adib Jatene
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Abstract

Objective: A careful choice of perioperative care strategies is pivotal to improve survival in cardiac surgery. However, there is no general agreement or particular attention to which nonsurgical interventions can reduce mortality in this setting. The authors sought to address this issue with a consensus-based approach. Design: A systematic review of the literature followed by a consensus-based voting process. Setting: A web-based international consensus conference. Participants: More than 400 physicians from 52 countries participated in this web-based consensus conference. Interventions: The authors identified all studies published in peer-reviewed journals that reported on interventions with a statistically significant effect on mortality in the setting of cardiac surgery through a systematic Medline/PubMed search and contacts with experts. These studies were discussed during a consensus meeting and those considered eligible for inclusion in this study were voted on by clinicians worldwide. Measurements and main results: Eleven interventions finally were selected: 10 were shown to reduce mortality (aspirin, glycemic control, high-volume surgeons, prophylactic intra-aortic balloon pump, levosimendan, leuko-depleted red blood cells transfusion, noninvasive ventilation, tranexamic acid, vacuum-assisted closure, and volatile agents), whereas 1 (aprotinin) increased mortality. A significant difference in the percentages of agreement among different countries and a variable gap between agreement and clinical practice were found for most of the interventions. Conclusions: This updated consensus process identified 11 nonsurgical interventions with possible survival implications for patients undergoing cardiac surgery. This list of interventions may help cardiac anesthesiologists and intensivists worldwide in their daily clinical practice and can contribute to direct future research in the field.

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... [11][12][13] However, there is growing evidence that also optimizing perioperative care may improve outcomes significantly. 2,14 The potential role of anesthesia (and of the anesthesiologist) in influencing outcome, particularly mortality, after cardiac surgery has been suggested since the mid-1980s. 15 Although the results of recent investigations 12,13 may lead to the opposite, and simplistic, conclusion that "the anesthesiologist makes no difference," there are plenty of reasons for the inability of such investigations to highlight a difference in outcome according to the individual attending cardiac anesthesiologist. ...
... 15,16 Actually, anesthesiologists make several decisions during a single cardiac surgery case, and for some of them (eg, concerning hemostasis and transfusion management, inotropic drugs, 1 fluid balance, monitoring, hemodynamic management, and mechanical ventilation), there is evidence of a significant effect on survival and other clinically relevant outcomes. 2,[17][18][19][20][21] The present review focuses on the aspects of perioperative care that are strictly related to the anesthesia regimen, including the anesthetics, opioids, and neuromuscular blocking agents (NMBAs) used for induction and maintenance of general anesthesia; the use of neuraxial anesthesia as an adjunct to general anesthesia; and intraoperative mechanical ventilation. Table 1 shows short-term mortality rates and the incidence of the most common and severe complications of cardiac surgery that are associated with increased mid-and long-term mortality, which, together with ICU/hospital length of stay (LOS), are among the outcomes that most likely could be affected by anesthetic drugs and techniques used intraoperatively and for which there is some evidence in this regard. ...
Article
Despite the improvements in surgical techniques and perioperative care, cardiac surgery is still burdened by relatively high mortality and frequent major postoperative complications, including myocardial dysfunction, pulmonary complications, neurologic injury, and acute kidney injury. Although the surgeon's skills and volume as well as patient-related and procedure-related risk factors play a major role in the success of cardiac surgery, there is growing evidence that also optimizing perioperative care may significantly improve outcomes. In this review, we focus on those aspects of perioperative care which are strictly related to the anesthesia regimen, with special reference to volatile anesthetics and neuraxial anesthesia, whose impact on outcome in adult cardiac surgery has been extensively investigated.
... To identify surgeries where TXA is not standard of care, we excluded surgeries with TXA utilization rates ≥50%, which included total hip and knee arthroplasty (Appendix C). This data was obtained from a multicenter retrospective study evaluating current TXA utilization rates, and is further supported by international consensus guidelines [16,[21][22][23][24]. Our intervention included intravenous prophylactic perioperative (within 1 hour of start of surgery) TXA regardless of dose, frequency and duration. ...
... TXA has been consistently shown to reduce RBC transfusion in cardiac surgery, trauma, and hip and knee arthroplasty, where it is now routinely incorporated into standard of care [16,23,[101][102][103][104]. Perioperative TXA use is supported by the American Society of Anesthesiologists (ASA) Practice Guidelines for Perioperative Blood Management to reduce transfusion for patients at increased risk for bleeding [105]. ...
Article
Tranexamic acid (TXA) reduces transfusion requirements in cardiac surgery and total hip and knee arthroplasty, where it has become standard of care. Our objective is to determine the efficacy and safety of TXA in other surgeries associated with a high risk for red blood cell (RBC) transfusion. We identified randomized controlled trials in Medline, Embase, CENTRAL, and CAB abstracts from inception to June 2019. We included trials evaluating intraoperative IV TXA in adult patients undergoing a non-cardiac and non-hip and knee arthroplasty surgeries at high-risk for RBC transfusion, defined as a baseline transfusion rate ≥5% in comparator arm. We assessed risk of bias using the Cochrane Risk of Bias tool. We used GRADE methodology to assess certainty of evidence. From 8565 citations identified, we included 69 unique trials, enrolling 6157 patients. TXA reduces both the proportion of patients transfused RBCs (relative risk (RR) 0.59; 95% confidence interval (CI) 0.48 to 0.72; low certainty evidence) and the volume of RBC transfused (MD -0.51 RBC units; 95%CI -0.13 to -0.9 units; low certainty evidence) when compared to placebo or usual care. TXA was not associated with differences in deep vein thrombosis, pulmonary embolism, all-cause mortality, hospital length of stay, need for re-operation due to hemorrhage, myocardial infarction, stroke or seizure. In patients undergoing a broad range of non-cardiac and non-hip and knee arthroplasty surgeries at high risk for RBC transfusion, perioperative TXA reduced exposure to RBC transfusion. No differences in thrombotic outcomes were identified; however, summary effect estimates were limited by lack of systemic screening and short duration of follow-up.
... Numerous studies suggest that halogenated volatile agents have cardioprotective proper-ties in patients undergoing cardiac surgery [5,6]. According to international consensus conferences, volatile anesthetics have been identified as non-surgical interventions that reduce mortality during cardiac surgery [7,8]. Current European and American guidelines recommend using volatile anesthetics to maintain general anesthesia during cardiac surgical procedures and cardiopulmonary bypass (CPB) [9,10]. ...
Article
Background: This study investigated the influence of volatile anesthesia (VA) on major complications and mortality in patients undergoing coronary artery bypass graft surgery (CABG). Methods: This post-hoc analysis included 1586 patients from the MYRIAD trial managed using the same perioperative protocol at a single institution. Patients were randomized to receive either volatile anesthesia (sevoflurane, isoflurane, or desflurane) or total intravenous anesthesia (TIVA). The assessed study outcomes were the rate of complications , including: myocardial infarction, stroke, acute kidney injury, prolonged ventilation (>24 h), receipt of high-dose inotropic support (inotropic score >10), and need for mechanical circulatory support. The duration of intensive care unit (ICU) stay, length of hospitalization , hospital readmission during follow-up, 30-days and 1-year mortality were also analyzed. Results: 1586 patients were enrolled between September 2014-September 2017 and randomly assigned to the volatile anesthesia group (n = 794) and the TIVA group (n = 792). The median patient age was 63 years, with a median ejection fraction of 60%. There were no significant differences in the rates of major complications, duration of ICU stay, and hospitalization between the groups. The median total dose of fentanyl was 12.0 mcg/kg in volatile group and 14.4 mcg/kg in TIVA group (p < 0.001). One-year mortality rates were 2.5% (n = 20) and 3.2% (n = 25) in the volatile and TIVA groups, respectively. Two patients were lost at the 30-day and 1-year follow-ups in the volatile group compared to four patients in TIVA group. Regression analysis showed that cardiopulmonary bypass (CPB) duration, fentanyl dose, and baseline serum creatinine level were associated with 30-days mortality, while ejection fraction was associated with 1-year mortality. Conclusions: The use of VA in patients undergoing CABG did not result in a reduction in major complications or mortality compared with TIVA. A higher dose of fentanyl was used in the TIVA group and was associated with an increase in the 30-days mortality. These findings warrant further investigation. Clinical Trial Registration: ClinicalTrials.gov (NCT02105610). Keywords: volatile anesthesia; cardiopulmonary bypass; cardioprotection; total intravenous anesthesia; cardiac anesthesia
... Therefore, the pharmacodynamic and pharmacokinetic features make levosimendan a promising drug in supporting patient cardiorespiratory function during the process of weaning from Va-eCMo. 15,16 Moreover, levosimendan is among the few interventions with documented improved survival in the perioperative period 17 and is already considered (or used) in the majority of centers worldwide in case of difficult cardiopulmonary bypass (CPB) separation. 18 The purpose of this systematic review and meta-analysis was to evaluate how effective levosimendan has been at weaning from support and reducing mortality in critically ill adult patients on Va-eCMo. ...
Article
Introduction: Patients with refractory cardiogenic shock can benefit from veno-arterial extracorporeal membrane oxygenation (VA-ECMO). The use of levosimendan in VA-ECMO patients may facilitate weaning and enhance survival. Evidence acquisition: MEDLINE, Scopus, Web of Science, and Cochrane were searched from inception to October 10th, 2021. Eligible clinical trials and observational studies reporting the use of levosimendan in VA-ECMO were searched. Two reviewers extracted data and independently assessed the risk of bias. To integrate the data, a random-effect model was applied. The success of weaning from VA-ECMO was the primary outcome. Evidence synthesis: Ten observational studies, including a total of 987 patients, were identified. Levosimendan was associated with successful weaning (362/448) compared with controls (328/539) (OR 2.37, 95% CI [1.71 - 3.28]; p = 0.01) and reduced mortality (144/433 vs 258/507) (nine studies, OR 0.53, 95% CI [0.36 - 0.78]; p = 0.01) compared with control. Conclusions: Levosimendan was associated with successful weaning and increased survival in VA-ECMO patients. Randomized trials should confirm these findings.
... Coronary artery bypass graft surgery (CABG) is one of the most common major surgical procedures performed worldwide, and is associated with a postoperative mortality rate of 2-3%, [1][2][3][4] almost two times higher as compared with non-cardiac surgery. 1 Therefore, strategies aimed at reducing perioperative mortality remain a key target for clinical research. 5,6 Several pre-clinical studies, using models of cardiac ischemia-reperfusion injury, demonstrated that volatile anesthetics exert a cardioprotective effect which limits infarct size. [7][8][9][10] In addition, several randomized controlled trials (RCTs) suggested that volatile anesthetics confer myocardial protection also in clinical practice. ...
Article
Objective: To investigate the effect of volatile anesthetics on rate of postoperative myocardial infarction (MI) and cardiac death following coronary artery bypass graft (CABG). Design: Post-hoc analysis of a randomized trial. Setting: Cardiac surgery theaters. Participants: Patients undergoing elective, isolated CABG. Interventions: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane or sevoflurane) or total intravenous anesthesia (TIVA). Primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48h from surgery. Secondary outcome was 1-year death due to cardiac causes. Measurements and Main Results: 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). Mean age was 62±8.4 years, and median baseline ejection fraction was 57 (50-67)%, without differences between the two groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14/2,530 [0.6%] versus 27/2,501 [1.1%] in the TIVA group; p=0.038) and as-treated analyses (16/2,708 [0.6%] versus 29/2,617 [1.1%] in the TIVA group; p=0.039), but not in the intention-to-treat analysis (17/2,663 (0.6%) versus 28/2,667 (1.0%) in the TIVA group; p=0.10). Overall, death due to cardiac causes was lower in the volatile group (23/2,685 [0.9%] versus 40/2,668 [1.5%] in the TIVA group; p=0.03). Conclusions: An anesthetic regimen including volatile agents may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality. Study registration: ClinicalTrials.gov, NCT02105610, Registered 7 April 2014, https://clinicaltrials.gov/ct2/show/NCT02105610.
... These qualifying remarks themselves must be put in context: a recent update of an online-assisted consensus process identified levosimendan as one of 10 non-surgical interventions that significantly reduce mortality in cardiac surgery and a majority opinion (55% of contributors) recommended its use in low ejection fraction (<35%) patients undergoing CABG to reduce mortality (Grade 1B) [116]. This is a useful illustration of the importance of careful subgroup analysis in reconceptualizing a drug with an intricate pharmacology to address specific, sometimes niche, treatment requirements for complex clinical scenarios. ...
Article
Full-text available
Introduction In the 20 years since its introduction to the palette of intravenous hemodynamic therapies, the inodilator levosimendan has established itself as a valuable asset for the management of acute decompensated heart failure. Its pharmacology is notable for delivering inotropy via calcium sensitization without an increase in myocardial oxygen consumption. Areas covered Experience with levosimendan has led to its applications expanding into perioperative hemodynamic support and various critical care settings, as well as an array of situations associated with acutely decompensated heart failure, such as right ventricular failure, cardiogenic shock with multi-organ dysfunction, and cardio-renal syndrome. Evidence suggests that levosimendan may be preferable to milrinone for patients in cardiogenic shock after cardiac surgery or for weaning from extracorporeal life support and may be superior to dobutamine in terms of short-term survival, especially in patients on beta-blockers. Positive effects on kidney function have been noted, further differentiating levosimendan from catecholamines and phosphodiesterase inhibitors. Expert opinion Levosimendan can be a valuable resource in the treatment of acute cardiac dysfunction, especially in the presence of beta-blockers or ischemic cardiomyopathy. When attention is given to avoiding or correcting hypovolemia and hypokalemia, an early use of the drug in the treatment algorithm is preferred.
... These qualifying remarks themselves must be put in context: a recent update of an online-assisted consensus process identified levosimendan as one of 10 non-surgical interventions that significantly reduce mortality in cardiac surgery and a majority opinion (55% of contributors) recommended its use in low ejection fraction (<35%) patients undergoing CABG to reduce mortality (Grade 1B) [116]. This is a useful illustration of the importance of careful subgroup analysis in reconceptualizing a drug with an intricate pharmacology to address specific, sometimes niche, treatment requirements for complex clinical scenarios. ...
Article
Full-text available
Introduction In the 20 years since its introduction to the palette of intravenous hemodynamic therapies, the inodilator levosimendan has established itself as a valuable asset for the management of acute decompensated heart failure. Its pharmacology is notable for delivering inotropy via calcium sensitization without an increase in myocardial oxygen consumption. Areas covered Experience with levosimendan has led to its applications expanding into perioperative hemodynamic support and various critical care settings, as well as an array of situations associated with acutely decompensated heart failure, such as right ventricular failure, cardiogenic shock with multi-organ dysfunction, and cardio-renal syndrome. Evidence suggests that levosimendan may be preferable to milrinone for patients in cardiogenic shock after cardiac surgery or for weaning from extracorporeal life support and may be superior to dobutamine in terms of short-term survival, especially in patients on beta-blockers. Positive effects on kidney function have been noted, further differentiating levosimendan from catecholamines and phosphodiesterase inhibitors. Expert opinion Levosimendan can be a valuable resource in the treatment of acute cardiac dysfunction, especially in the presence of beta-blockers or ischemic cardiomyopathy. When attention is given to avoiding or correcting hypovolemia and hypokalemia, an early use of the drug in the treatment algorithm is preferred.
... 8 Tranexamic acid has been shown to consistently reduce RBC transfusion in cardiac surgery, hip and knee arthroplasty, and trauma, where it is now incorporated into standard of care. 5,[9][10][11][12] Recent evidence syntheses suggest that TXA is effective in reducing transfusion in hip fracture surgery [13][14][15] and spine surgery. 16,17 In a recent meta-analysis evaluating a broader surgical population at high risk for RBC transfusion, TXA reduced the percentage of patients receiving transfused RBCs as well as the volume of transfused RBCs compared with placebo or usual care. ...
Article
Purpose: Tranexamic acid (TXA) reduces red blood cell transfusion in various orthopedic surgeries, yet the degree of practice variation in its use among anesthesiologists and surgeons has not been described. To target future knowledge transfer and implementation strategies, and to better understand determinants of variability in prophylactic TXA use, our primary objective was to evaluate the influence of surgical team members on the variability of prophylactic TXA administration. Methods: This was a retrospective cohort study of all adult patients undergoing primary total hip arthroplasty (THA), hip fracture surgery, and spine fusion ± vertebrectomy at two Canadian hospitals between January 2014 and December 2016. We used Canadian Classification of Health Interventions procedure codes within the Discharge Abstract Database which we linked to the Ottawa Data Warehouse. We described the percentage of patients that received TXA by individual surgery, the specifics of TXA dosing, and estimated the effect of anesthesiologists and surgeons on prophylactic TXA using multivariable mixed-effects logistic regression analyses. Results: In the 3,900 patients studied, TXA was most commonly used in primary THA (85%; n = 1,344/1,582), with lower use in hip fracture (23%; n = 342/1,506) and spine fusion surgery (23%; n = 186/812). The median [interquartile range] total TXA dose was 1,000 [1,000-1,000] mg, given as a bolus in 92% of cases. Anesthesiologists and surgeons added significant variability to the odds of receiving TXA in hip fracture surgery and spine fusion, but not primary THA. Most of the variability in TXA use was attributed to patient and other factors. Conclusion: We confirmed the routine use of TXA in primary THA, while observing lower utilization with more variability in hip fracture and spine fusion surgery. Further study is warranted to understand variations in use and the barriers to TXA implementation in a broader population of orthopedic surgical patients at high risk for transfusion.
... Many experts do not continue to acknowledge the potential utility of IABP use. An international consensus conference on mortality reduction in cardiac anesthesia and intensive care has recently published a consensus in this topic (25). Recognizing that there is a lack of general agreement regarding which nonsurgical interventions can reduce mortality in cardiac surgery, the authors sought to address this issue with a consensus-based approach identifying 11 nonsurgical interventions with possible survival implications for patients undergoing cardiac surgery, the prophylactic IABP placement as one of these interventions, suggesting its use in high-risk patients undergoing CABG might reduce mortality. ...
Preprint
Full-text available
The intra-aortic balloon pump (IABP) is used to prevent complications after coronary artery bypass grafting (CABG) surgery; although some results are controversial nowadays even contradictory. A new article on this field is published in this edition and shows that the risk factors for in-hospital mortality are the preoperative plasma creatinine level and cardiopulmonary bypass time in 177 patients. About the prophylactic use of the IABP regarding mortality the results reflected so far in meta-analyses have been highly contradictory between them, and the risk factors associated with it have been several and different. This lack of evidence has resulted in the continued variation of IABP use in these procedures. A large, multicenter RCT is certainly required to take the next step towards more definitive evidence, either for or against, the use of IABP in high-risk CABG. Until then, the unanswered questions regarding this topic will remain.
... More than 400 physicians from 52 countries investigated all studies published in peer-reviewed journals that discussed nonsurgical interventions with a statistically significant effect on mortality in the setting of cardiac surgery. The authors selected prophylactic IABP as among the ten techniques that reduced mortality, and recommended direct future research in that field [24]. ...
Article
Full-text available
Coronary artery bypass grafting (CABG) remains a routine operation despite major advancements in angioplastic procedures. Around 200,000 CABG procedures are performed annually in the U.S. Patients who are not candidates for angioplasty intervention often have advanced coronary disease and comorbidities that raise the risk of heart failure with decreased ejection fraction to around 25%. Over the years, significant developments in various preoperative interventions have occurred; in this paper, we suggest a multidisciplinary preoperative algorithm that can be included in a regularly scheduled multidisciplinary care plan.
... In recent report, almost 300,000 cardiac surgery procedures are performed each year in the United States [8]. But surgical mortality remains around 2%, even for the lowest-risk procedures, such as isolated coronary artery bypass graft or isolated aortic valve replacement [9,10]. In the last decades, the mortality rate was reduced as people improve surgical techniques and perioperative care, but cardiac surgery is still considered a high-risk procedure [11,12]. ...
... In recent years, this group developed a well-established method, also known as democracy-based medicine, 7,9-12 to provide clinicians with a rigorous and widely agreed-upon selection of published evidence by combining the features (and overcoming some limitations 10,13 ) of classical consensus conferences, international surveys, and systematic reviews. Using this method, the group performed 2 consensus processes aimed at identifying all nonsurgical interventions (drugs, techniques, strategies) with a significant effect on mortality in the perioperative period 9,14 and in critically ill patients, [11][12] respectively. ...
... In recent years, this group developed a well-established method, also known as democracy-based medicine, 7,[9][10][11][12] to provide clinicians with a rigorous and widely agreed-upon selection of published evidence by combining the features (and overcoming some limitations 10,13 ) of classical consensus conferences, international surveys, and systematic reviews. Using this method, the group performed 2 consensus processes aimed at identifying all nonsurgical interventions (drugs, techniques, strategies) with a significant effect on mortality in the perioperative period 9,14 and in critically ill patients, [11][12] respectively. ...
... The search for safe and efficacious drugs for hemodynamic support in the period of weaning from CPB is ongoing. [4][5][6][7][8] It is common practice among many cardiac anesthesiologists to use calcium during this period, but the rationale for its administration remains a matter of debate. [9][10][11] Several studies showed beneficial effects of calcium on blood pressure or cardiac index after CPB. ...
Article
The search for safe and effective patient management strategies during weaning from cardiopulmonary bypass is ongoing; intravenous calcium is occasionally used as a first-line drug. The physiologic role of calcium suggests that it can support the function of the cardiovascular system during this critical period. Patients may be mildly hypocalcemic after cardiopulmonary bypass; however, this degree of hypocalcemia does not significantly impair the cardiovascular system. The transient beneficial effects of calcium administration (increase in arterial blood pressure, systemic vascular resistance, cardiac index, stroke volume, and coronary perfusion pressure) might be helpful in cases of moderate contractility reduction or vasoplegia. Nonetheless, effects on clinically relevant endpoints are unknown, and possible systemic side effects, such as transient reduction in internal mammary artery graft flow, attenuation of the effects of β-sympathomimetics, "stone heart" phenomenon, and pancreatic cellular injury, may limit the use of calcium salts. Further studies are needed to expand the understanding of the effects of calcium administration on patient outcomes.
... An international consensus conference on mortality reduction in cardiac anesthesia and intensive care has recently published findings from its "democratic" consensus process. 10 Recognizing that there is a lack of general agreement regard- ing which nonsurgical interventions can reduce mortality in cardiac surgery, the authors sought to address this issue with a consensus-based approach. Utilizing a "novel approach to consensus building," all nonsurgical interventions (drugs, techniques, and strategies) with literature evidence of a significant effect on mortality were identified systematically, assessed, and described by a group of 458 clinicians from around the world. ...
... Recent evidence has suggested that levosimendan may improve outcomes after adult cardiac surgery, given the prognostic importance of the low cardiac output syndrome in this setting. [82][83][84] A multicenter, randomized, double-blind, placebo-controlled trial (n ¼ 506 [248 levosimendan, 258 placebo]) investigated the outcome effects of levosimendan in patients requiring hemodynamic support after cardiac surgery. 84 The primary trial outcome was mortality at 30 days. ...
Article
Background Randomized clinical trials (RCTs) represent the highest level of scientific evidence. The aim of this review was to map and summarize the main characteristics and publication trends of RCTs with a statistically significant effect on mortality in critically ill and perioperative patients. Methods A mapping review of RCTs published between January 1982 and January 2021. We searched PubMed/MEDLINE and EMBASE for RCTs reporting mortality data. A descriptive analysis was conducted, including general and methodological information of all these RCTs with a statistically significant difference (p<0.05) in mortality. Results We identified 340 studies published in 115 journals and from 42 countries. The most represented clinical areas were ventilatory support (n=58, 17%) and hemodynamics (n=56, 16%). Detrimental effect on survival was described in 47 (14%) RCTs. Denmark had the highest number of published trials per million inhabitants. A total of 40 (10%) RCTs were led by a female author. The intention to treat principle was applied overall in 60% of RCTs, though this percentage increased up to 75% when the study was published in journals with high IF. Conclusion In the largest contemporary RCT database of interventions significantly influencing mortality, we found an increase in scientific production. US, China, France, Italy, and the UK contributed with 172 (51%) RCTs over 40 years. Only 20% of the studies were multinational collaborations, though this percentage increased over time. The presence of women as first authors, was one out of 8 RCTs.
Article
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The objective: to evaluate the international practice of using calcium salts when weaning from cardiopulmonary bypass after cardiac surgery in adult patients. Design: a multiple-choice survey about the current practice of calcium salts use when weaning from cardiopulmonary bypass based on the SurveyMonkey platform. Participants: cardiac surgical hospitals around the world. Estimation and main results. Totally 112 emails were sent to Russian and foreign centers inviting them to participate in the survey. 100 centers from 32 countries replied to this request. Generally, the majority of centers (88%) administer calcium salts during surgery with cardiopulmonary bypass, and in 71 (71%) centers out of 100, calcium salts are used to improve hemodynamics. Among 88 centers that use calcium salts during surgery, 66% (58/88) of respondents use calcium chloride, 22% (19/88) use calcium gluconate, and 12% (11/88) use both drugs. Most centers (55 (77%) out of 71) use doses of 5 to 15 mg/kg as a bolus or infusion for 1 min. Conclusion: Our survey shows that the majority of cardiac surgery centers use calcium in adult cardiac surgery patients especially during weaning from cardiopulmonary bypass. There is variability in the type of drug, dose, and route of administration.
Chapter
Randomized controlled trials (RCTs) are the gold standard of evidence-based medicine.
Article
Background: Tranexamic acid (TXA) reduces transfusion in a wide range of surgical populations, although its real-world use in non-cardiac surgeries has not been well described. The objective of this study was to describe prophylactic TXA use in non-cardiac surgeries at high risk for transfusion. Methods: This is a retrospective cohort study of all adult patients undergoing major non-cardiac surgery at ≥5% risk of perioperative transfusion at five Canadian hospitals between January 2014 and December 2016. Canadian Classification of Health Interventions procedure codes within the Discharge Abstract Database were linked to transfusion and laboratory databases. TXA use was ascertained electronically from The Ottawa Hospital Data Warehouse and via manual chart review for Winnipeg hospitals. For each surgery, we evaluated the percentage of patients who received TXA as well as the specifics of TXA dosing and administration. Results: TXA use was evaluable in 14 300 patients. Overall, 17% of surgeries received TXA, ranging from 0% to 68% among individual surgeries. TXA use was more common in orthopaedic (n = 2043/4942; 41%) and spine surgeries (n = 239/1322; 18%) compared to other surgical domains (n = 109/8036; 1%). TXA was commonly administered as a bolus (n = 2097/2391; 88%). The median TXA dose was 1000 mg (IQR 1000-1000 mg). Conclusion: TXA is predominantly used in orthopaedic and spine surgeries, with little uptake in other non-cardiac surgeries at high risk for red blood cell transfusion. Further studies are needed to evaluate the effectiveness and safety of TXA and to understand the barriers to TXA administration in a broad range of non-cardiac surgeries.
Article
Background: Sevoflurane may reduce the occurrence of major adverse cardiovascular events (MACCEs) in surgical patients, although the mechanisms are poorly understood. We hypothesised that sevoflurane stabilises atherosclerotic plaques by inhibiting inflammation and enhancing prolyl-4-hydroxylase α1 (P4Hα1), the rate-limiting subunit for the P4H enzyme essential for collagen synthesis. Methods: We established a vulnerable arterial plaque model in apolipoprotein E-knockout mice (ApoE-/-) fed a high-fat diet that underwent daily restraint/noise stress, with/without a single prior exposure to sevoflurane for 6 h (1-3%; n=30 per group). In vitro, smooth muscle cells (SMCs) were incubated with tumour necrosis factor-alpha in the presence/absence of sevoflurane. Immunohistochemistry, immunoblots, and mRNA concentrations were used to quantify the effect of sevoflurane on plaque formation, expression of inflammatory cytokines, P4Hα1, and collagen subtypes in atherosclerotic plaques or isolated SMCs. Results: In ApoE-/- mice, inhalation of sevoflurane 1-3% for 6 h reduced the aortic plaque size by 8-29% in a dose-dependent manner, compared with control mice that underwent restraint stress alone (P<0.05); this was associated with reduced macrophage infiltration and lower lipid concentrations in plaques. Sevoflurane reduced gene transcription and protein expression levels of pro-inflammatory cytokines (≥69-75%; P<0.05) and matrix metalloproteinases (≥39-65%; P<0.05) at both gene transcription and protein levels, compared with controls. Sevoflurane dose dependently increased Types I and III collagen deposition through enhanced protein expression of P4Hα1, both in vivo and in vitro (0.7-3.3-fold change; P<0.05). Conclusions: Sevoflurane dose dependently promotes plaque stabilisation and decreases the incidence of plaque disruption in ApoE-/- mice by increasing collagen deposition and inhibiting inflammation. These mechanisms may contribute to sevoflurane reducing MACCE.
Article
In this study examined the effects of a multivalent protease inhibitor aprotininum on the state indicators of blood coagulation and antiproteinase potential during the development of experimental reperfusion syndrome, as well as the severity of morphological changes in liver tissue. It was found that with a 12-hour reperfusion syndrome in the background the development of an imbalance in the proteinase-inhibitor system occurs coagulopathy consumption and there are initial liver damage with development necrosis and plethora of blood vessels. Against the background of the use of aprotininum with experimental reperfusion syndrome is less marked severe liver damage decreases imbalance in condition of non-specific proteinases and their inhibitors without deeper disorders in the blood coagulation system.
Article
Objective To describe international practice on the use of calcium salts during cardiopulmonary bypass (CPB) weaning in adult cardiac surgery patients. Design Multiple-choice survey on current practice of CPB weaning. Setting On-line survey using the SurveyMonkey platform. Participants Departments of cardiac anesthesiology worldwide. Interventions None Measurements and main Results Out of 112 surveys sent, 100 centers from 32 countries replied. The majority of centers (88/100 = 88%) administer calcium salts intraoperatively: 71/100 (71%) are using these drugs for CPB weaning and 78/100 (78%) for correction of hypocalcemia. Among the 88 centers that use calcium salts intraoperatively, 66% (58/88) of respondents use calcium chloride, 22% (19/88) use calcium gluconate and 12% (11/88) use both drugs. Calcium salts are routinely used during normal (47/71 centers = 66%) and difficult (59/71 centers = 83%) weaning from CPB. Doses of 5-15 mg/kg during termination of CPB were used by 55/71 centers (77%) either by bolus (39/71, 55%) or over a time period longer than 1 min (32/71 = 45%). Norepinephrine is the most commonly used first line vasopressor or inotropic agent used to support hemodynamics during termination of CPB in 32 out of 100 centers (32%), while calcium is the second one, used by 23 out of 100 centers (23%). Conclusion Our survey demonstrates that the majority of cardiac centers uses calcium in adult patients undergoing cardiac surgery, especially during weaning from CPB. There is variability on the type of the drug, dose and modality of drug administration.
Article
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Purpose of Review Vasoactive therapy represents a pivotal yet debated topic in critically ill patients and in those with chronic heart failure. Levosimendan, a calcium sensitizer agent with inodilating properties, has been in the market for 27 years and new indications came out over time. The aim of the present review is to highlight what is actually proven and what is debated on the use of levosimendan in light of its pharmacologic features and the pathophysiological evidence. Recent Findings Levosimendan was firstly seen as an inodilator acting through calcium sensitization in myocytes both in the myocardium and in vascular smooth muscle. Over the years, its anti-inflammatory properties became clearer and a role in preconditioning and weaning from mechanical circulatory support was postulated. More recently, a possible action on other muscular fibers, namely, diaphragmatic myocytes, was observed, leading to a possible application in mechanical ventilation-related diaphragmatic dysfunction. Summary Preliminary data showed promising effects of levosimendan in patients with sepsis-related and stress-related (Takotsubo) myocardial dysfunction, in those difficult-to-wean from mechanical circulatory support and in ventilator-associated diaphragmatic dysfunction. Moreover, its vasodilating, anti-oxidant, and neuroendocrine properties pave the way to a number of additional possible applications. Larger studies yielding to more conclusive results on these indications are under way or need to be planned in the future.
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This is a narrative review of recent articles (mainly published in 2017 and 2018) related to the conduct of cardiopulmonary bypass (CPB) that should be of interest to the cardiac anesthesiologist. Some of the topics covered include recent guidelines on temperature management, anticoagulation, perfusion practice, use of transesophageal echocardiography during CPB, optimal mean arterial pressure, vasoplegia, bleeding, perioperative anemia, post-cardiac surgery transfusion, acute kidney injury, delirium and cognitive decline, CPB during pregnancy, lung management, radial-to-femoral artery pressure gradients during CPB, prophylactic perioperative intra-aortic balloon pump, del Nido cardioplegia, antibiotic prophylaxis, and use of levosimendan in cardiac surgery. The review concludes with a perspective on the effect of these development on the practice of cardiac anesthesia.
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Obstetric hemorrhage is one of the leading, as well as one of the most treatable, causes of maternal morbidity and mortality worldwide. As obstetric hemorrhage often occurs in patients without risk factors, there is virtually unanimous agreement from obstetric professional societies to establish obstetric hemorrhage protocols in anticipation of these emergencies. These protocols involve multidisciplinary teams in which the transfusion service plays an essential and vital role. This manuscript will examine the epidemiology of obstetric hemorrhage, risk factors that may be present, and recommendations for these protocols, with a focus on massive transfusion protocols, laboratory testing, cell salvage and use of pharmacologic adjuvant therapy including tranexamic acid and factor concentrates.
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Objective Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. Design Double-blind, placebo-controlled, multicenter randomized trial. Setting Tertiary care hospitals. Interventions Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours. Measurements and main results The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. From the
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Background: -Mitral valve (MV) repair is preferred over replacement in clinical guidelines and is an important determinant of the indication for surgery in degenerative mitral regurgitation (MR). Yet, the level of evidence supporting current recommendations is low, and recent data cast doubts on its validity in the current era. Accordingly, the aim of the present study was to analyze very long-term outcome after MV repair and replacement for degenerative MR with a flail leaflet. Methods: -MIDA is a multicenter registry enrolling patients with degenerative MR with a flail leaflet in 6 tertiary European and US centers. We analyzed the outcome after MV repair (n=1,709) and replacement (n= 213), overall, by propensity score matching and by inverse probability-of-treatment weighting. Results: -At baseline, patients undergoing MV repair were younger, had more comorbidities and were more likely to present with a posterior leaflet prolapse than those undergoing MV replacement. After propensity score matching as well as after inverse probability-of-treatment weighting, the 2 treatments groups were balanced and absolute standardized differences were usually below 10%, indicating adequate match. Operative mortality (defined as a death occurring within 30 days from surgery or during the same hospitalization) was lower after MV repair than after replacement, both in the entire (1.3 vs 4.7%; p<0.001) and in propensity-matched population (0.2% vs 4.4%; p<0.001). During a mean follow-up of 9.2 years, 552 deaths were observed, of which 207 were of cardiovascular origin. Twenty-year survival was better after MV repair than after MV replacement, both in the entire (46% vs 23%, p<0.001) and in matched population (41% vs 24%, p<0.001). Similar superiority of MV repair were obtained in patients' subsets based on age, sex or any stratification criteria (all p<0.001). MV repair was also associated with reduced incidence of reoperations and valve-related complications. Conclusions: -Among patients with degenerative MR with a flail leaflet, referred to mitral surgery, MV repair was associated with lower operative mortality, better long-term survival and fewer valve-related complications compared to MV replacement.
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Background In patients undergoing cardiac surgery, a reduced preoperative left ventricular ejection fraction (LVEF) is common and is associated with a worse outcome. Available outcome data for these patients address specific surgical procedures, mainly coronary artery bypass graft (CABG). Aim of our study was to investigate perioperative outcome of surgery on patients with low pre-operative LVEF undergoing a broad range of cardiac surgical procedures. Methods Data from patients with pre-operative LVEF ≤40 % undergoing cardiac surgery at a university hospital were reviewed and analyzed. A subgroup analysis on patients with pre-operative LVEF ≤30 % was also performed. ResultsA total of 7313 patients underwent cardiac surgery during the study period. Out of these, 781 patients (11 %) had a pre-operative LVEF ≤40 % and were included in the analysis. Mean pre-operative LVEF was 33.9 ± 6.1 % and in 290 patients (37 %) LVEF was ≤30 %. The most frequently performed operation was CABG (31 % of procedures), followed by mitral valve surgery (22 %) and aortic valve surgery (19 %). Overall perioperative mortality was 5.6 %. Mitral valve surgery was more frequent among patients who did not survive, while survivors underwent more frequently CABG. Post-operative myocardial infarction occurred in 19 (2.4 %) of patients, low cardiac output syndrome in 271 (35 %). Acute kidney injury occurred in 195 (25 %) of patients. Duration of mechanical ventilation was 18 (12–48) hours. Incidence of complications was higher in patients with LVEF ≤30 %. Stepwise multivariate analysis identified chronic obstructive pulmonary disease, pre-operative insertion of intra-aortic balloon pump, and pre-operative need for inotropes as independent predictors of mortality among patients with LVEF ≤40 %. Conclusions We confirmed that patients with low pre-operative LVEF undergoing cardiac surgery are at higher risk of post-operative complications. Cardiac surgery can be performed with acceptable mortality rates; however, mitral valve surgery, was found to be associated with higher mortality rates in this population. Accurate selection of patients, risk/benefit evaluation, and planning of surgical and anesthesiological management are mandatory to improve outcome.
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We aimed to identify all treatments that affect mortality in adult critically ill patients in multicenter randomized controlled trials. We also evaluated the methodological aspects of these studies, and we surveyed clinicians' opinion and usual practice for the selected interventions. MEDLINE/PubMed, Scopus, and Embase were searched. Further articles were suggested for inclusion from experts and cross-check of references. We selected the articles that fulfilled the following criteria: publication in a peer-reviewed journal; multicenter randomized controlled trial design; dealing with nonsurgical interventions in adult critically ill patients; and statistically significant effect in unadjusted landmark mortality. A consensus conference assessed all interventions and excluded those with lack of reproducibility, lack of generalizability, high probability of type I error, major baseline imbalances between intervention and control groups, major design flaws, contradiction by subsequent larger higher quality trials, modified intention to treat analysis, effect found only after adjustments, and lack of biological plausibility. For all selected studies, we recorded the intervention and its comparator, the setting, the sample size, whether enrollment was completed or interrupted, the presence of blinding, the effect size, and the duration of follow-up. We found 15 interventions that affected mortality in 24 multicenter randomized controlled trials. Median sample size was small (199 patients) as was median centers number (10). Blinded trials enrolled significantly more patients and involved more centers. Multicenter randomized controlled trials showing harm also involved significantly more centers and more patients (p = 0.016 and p = 0.04, respectively). Five hundred fifty-five clinicians from 61 countries showed variable agreement on perceived validity of such interventions. We identified 15 treatments that decreased/increased mortality in critically ill patients in 24 multicenter randomized controlled trials. However, design affected trial size and larger trials were more likely to show harm. Finally, clinicians view of such trials and their translation into practice varied.
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The elderly undergo cardiac surgery more and more frequently, often present multiple comorbidities, assume chronic therapies, and present a unique physiology. Aim of our study was to analyze the experience of a referral cardiac surgery center with all types of cardiac surgery interventions performed in patients ≥80 years old over a six years' period. A retrospective observational study performed in a university hospital. 260 patients were included in the study (3.5% of the patients undergoing cardiac surgery in the study period). Mean age was 82 ± 1.8 years. Eighty-five percent of patients underwent elective surgery, 15% unplanned surgery and 4.2% redo surgery. Intervention for aortic valve pathology and coronary artery bypass grafting were performed in 51% and 46% of the patients, respectively. Interventions involving the mitral valve were the 26% of the total, those on the tricuspid valve were 13% and those on the ascending aortic arch the 9.6%. Postoperative low output syndrome was identified in 44 patients (17%). Mortality was 3.9% and most of the patients (91%) were discharged from hospital in good clinical conditions. Hospital mortality was lower in planned vs unplanned surgery: 3.8% vs 14% respectively. Chronic obstructive pulmonary disease (OR 9.106, CI 2.275 - 36.450) was the unique independent predictor of mortality. Clinicians should be aware that cardiac surgery can be safely performed at all ages, that risk stratification is mandatory and that hemodynamic treatment to avoid complications is expected.
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Octogenarians (aged ≥ 80 years) are increasingly being referred for cardiac surgery. We aimed to describe the morbidity, mortality, and health services utilization of octogenarians undergoing elective cardiac surgery. Retrospective population-based cohort study of adult patients receiving elective cardiac surgery between January 1 2004 and December 31 2009. Primary exposure was age ≥80 years. Outcomes were 30-day, 1- and 5-year mortality, post-operative complications, and ICU/hospital lengths of stay. Multi-variable logistic and Cox regression analyses were used to explore the association between older age and outcome. Of 6,843 patients receiving cardiac surgery, 544 (7.9%) were octogenarians. There was an increasing trend in the proportion of octogenarians undergoing surgery during the study period (0.3% per year, P = 0.073). Octogenarians were more likely to have combined procedures (valve plus coronary artery bypass or multiple valves) compared with younger strata (p < 0.001). Crude 30-day, 1-year and 5-year mortality for octogenarians were 3.7%, 10.8% and 29.0%, respectively. Compared to younger strata, octogenarians had higher adjusted 30-day (OR 4.83, 95%CI 1.30-17.92; P = 0.018) and 1-year mortality (OR 4.92; 95% CI, 2.32-10.46. P<0.001). Post-operative complications were more likely among octogenarians. Octogenarians had longer post-operative stays in ICU and hospital, and higher rates of ICU readmission (P < 0.001 for all). After multi-variable adjustment, age ≧ 80 years was an independent predictor of death at 30-days and 1 year. Octogenarians are increasingly referred for elective cardiac surgery with more combined procedures. Compared to younger patients, octogenarians have a higher risk of post-operative complications, consume greater resources, and have worse but acceptable short and long-term survival.
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Background: Inodilators are commonly used in critically ill patients, but their effect on survival has not been properly studied to date. The objective of this work was to conduct a network meta-analysis on the effects of inodilators on survival in adult cardiac surgery patients, and to compare and rank drugs that have not been adequately compared in head-to-head trials. Methods: Relevant studies were independently searched in BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Central Register of clinical trials (updated on May 1, 2014). The criteria for inclusion were: random allocation to treatment with at least one group receiving dobutamine, enoximone, levosimendan, or milrinone and at least another group receiving the above inodilators or placebo, performed in cardiac surgical patients. The endpoint was to identify differences in mortality at longest follow-up available. Results: The 46 included trials were published between 1995 and 2014 and randomised 2647 patients. The Bayesian network meta-analysis found that only the use of levosimendan was associated with a decrease in mortality when compared with placebo (posterior mean of OR=0.48, 95% CrI 0.28 to 0.80). The posterior distribution of the probability for each inodilator to be the best and the worst drug showed that levosimendan is the best agent to improve survival after cardiac surgery. The sensitivity analyses performed did not produce different interpretative result. Conclusion: Levosimendan seems to be the most efficacious inodilator to improve survival in cardiac surgery.
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IntroductionThe intra-aortic balloon pump is routinely used in cardiac surgery; however its impact on outcome is yet matter of debate and randomized trials were recently published. We perform an updated meta-analysis of randomized controlled trials that investigated the use of preoperative intra-aortic balloon pump in adult patients undergoing coronary artery bypass grafting.Methods Potentially eligible trials were identified by searching the Medline, Embase, Scopus, ISI Web of Knowledge and The Cochrane Library. Searches were not restricted by language or publication status and were updated in August 2014. Randomised controlled trials on preoperative intra-aortic balloon pump in patients undergoing coronary artery bypass grafting either with or without cardiopulmonary bypass were identified. The primary endpoint was mortality at the longest follow up available and the secondary endpoint was 30-days mortality.ResultsThe eight included randomized clinical trials enrolled 625 patients (312 to intra-aortic balloon pump group and 313 to control). The use of intra-aortic balloon pump was associated with a significant reduction in the risk of mortality (11 of 312 (3.5%) versus 33 of 313 (11%), risk ratio¿=¿0.38 (0.20 to 0.73), P for effect¿=¿0.004, P for heterogeneity¿=¿0.7, I-square¿=¿0%, with eight studies included). The benefit on mortality reduction was confirmed restricting the analysis to trials with low risk of bias, to those reporting 30-days follow up and to patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass.Conclusions Preoperative intra-aortic balloon pump reduces perioperative and 30-days mortality in high-risk patients undergoing elective coronary artery bypass grafting.
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Although noninvasive positive pressure ventilation (NPPV) has been successfully used for various kinds of acute respiratory failure, the data are limited regarding its application in postoperative respiratory failure after cardiac surgery. Therefore, we conducted a prospective randomized control study in a university surgical intensive care unit to evaluate the efficacy and safety of NPPV in the treatment of acute respiratory failure after cardiac surgery, and explore the predicting factors of NPPV failure. From September 2011 to November 2012 patients with acute respiratory failure after cardiac surgery who had indication for the use of NPPV were randomly divided into a NPPV treatment group (NPPV group) and the conventional treatment group (control group). The between-group differences in the patients' baseline characteristics, re-intubation rate, tracheotomy rate, ventilator associated pneumonia (VAP) incidence, in-hospital mortality, mechanical ventilation time after enrollment (MV time), intensive care unit (ICU) and postoperative hospital stays were compared. The factors that predict NPPV failure were analyzed. During the study period, a total of 139 patients who had acute respiratory failure after cardiac surgery were recorded, and 95 of them met the inclusion criteria, which included 59 males and 36 females with a mean age of (61.5±11.2) years. Forty-three patients underwent coronary artery bypass grafting (CABG), 23 underwent valve surgery, 13 underwent CABG+valve surgery, 13 underwent major vascular surgery, and three underwent other surgeries. The NPPV group had 48 patients and the control group had 47 patients. In the NPPV group, the re-intubation rate was 18.8%, tracheotomy rate was 12.5%, VAP incidence was 0, and the in-hospital mortality was 18.8%, significantly lower than in the control group 80.9%, 29.8%, 17.0% and 38.3% respectively, P < 0.05 or P < 0.01. The MV time and ICU stay (expressed as the median (P25, P75)) were 18.0 (9.2, 35.0) hours and 4.0 (2.0, 5.0) days, which were significantly shorter than in the control group, 96.0 (26.0, 240.0) hours and 6.0 (4.0, 9.0) days respectively, P < 0.05 or P < 0.01. The postoperative hospital stays of the two groups were similar. The univariate analysis showed that the NPPV success subgroup had more patients with acute lung injury (ALI) (17 vs. 0, P = 0.038), fewer patients with pneumonia (2 vs. 7, P < 0.001) and lower acute physiology and chronic health evaluation II (APACHE II) scores (16.1±2.8 vs. 21.8±3.2, P < 0.001). Multivariate analysis showed that pneumonia (P = 0.027) and a high APACHE II score >20 (P = 0.002) were the independent risk factors of NPPV failure. We conclude that NPPV can be applied in selected patients with acute respiratory failure after cardiac surgery to reduce the need of re-intubation and improve clinical outcome as compared with conventional treatment. Pneumonia and a high APACHE II score >20 might be the independent risk factors of NPPV failure in this group of patients.
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To determine the impact of anesthesiologists, surgeons, and their monthly caseload volume on mortality after cardiac surgery. Ten-year audit of prospectively collected cardiac surgical data. Large adult cardiothoracic hospital. A total of 18,569 cardiac surgical patients in the decade from April 2002 through March 2012, plus 21 consultant surgeons and 29 consultant anesthesiologists. Major risk-stratified cardiac surgical operations. The primary outcome was in-hospital death. Random intercept models for the surgeon and anesthesiologist cluster, respectively, were fitted, achieving risk-adjustment through the logistic EuroSCORE. The intraclass correlation coefficient (ICC) subsequently was used to measure the amount of outcome variation due to clustering. After exclusions (duplicates, very-short-term appointments, and cases performed by more than one consultant), there were 18,426 patients with 581 (3.15%) in-hospital deaths. The overwhelming factor associated with outcome variation was the patient risk profile, accounting for 97.14% of the variation. The impact of the surgeon was small (ICC = 2.78%), and the impact of the anesthesiologist was negligible (ICC = 0.08%). Low monthly surgeon volume of surgery, adjusted for average case mix, was associated with higher risk-adjusted mortality (odds ratio = 0.93, 95% CI 0.87-0.98). Outcome was determined primarily by the patient. There were small but significant differences in outcome between surgeons. The attending anesthesiologist did not affect patient outcome in this institution. Low average monthly surgeon volume was a significant risk factor. In contrast, low average monthly anesthesiologist volume had no effect.
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To estimate the effect of non-invasive mechanical ventilation (NIV) on the rate of reintubation among patients undergoing cardiothoracic surgery. A meta-analysis of randomised trials. Medline, Embase, and the Cochrane Central Register of clinical trials were searched (April 2012) for pertinent studies by two trained investigators. International experts were contacted. Articles were assessed by two trained investigators, with divergences resolved by consensus. Inclusion criterion was random allocation to NIV versus standard treatment without restrictions on duration or modalities of the treatment delivered. Fourteen studies enrolling 1211 patients were included in the meta-analysis. NIV reduced the reintubation rate (risk ratio [RR], 0.29; 95% CI, 0.16-0.53; P for efficacy < 0.0001; I2 = 0), hospital length of stay and mortality. Subgroup analyses suggested that the benefits of NIV are more important in patients with ongoing acute respiratory failure (RR, 0.25; 95% CI, 0.07-0.89) and in those at high risk of developing postoperative pulmonary complications (RR, 0.19; 95% CI, 0.04-0.84). Analyses including prophylactic studies in patients at low risk did not show a significant effect of NIV on reintubation rate (RR = 0.42; 95% CI, 0.12-1.48) and on any of the outcomes considered except for oxygenation. NIV seems to be effective in reducing reintubation rate after cardiothoracic surgery. The results of this meta-analysis should be confirmed by large randomised controlled studies.
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/st>Many studies have compared desflurane, isoflurane, sevoflurane, total i.v. anaesthesia (TIVA), or all in cardiac surgery to assess their effects on patient survival. /st>We performed standard pairwise and Bayesian network meta-analyses; the latter allows indirect assessments if any of the anaesthetic agents were not compared in head-to-head trials. Pertinent studies were identified using BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Library (last updated in June 2012). /st>We identified 38 randomized trials with survival data published between 1991 and 2012, with most studies (63%) done in coronary artery bypass grafting (CABG) patients with standard cardiopulmonary bypass. Standard meta-analysis showed that the use of a volatile agent was associated with a reduction in mortality when compared with TIVA at the longest follow-up available [25/1994 (1.3%) in the volatile group vs 43/1648 (2.6%) in the TIVA arm, odds ratio (OR)=0.51, 95% confidence interval (CI) 0.33-0.81, P-value for effect=0.004, number needed to treat 74, I(2)=0%] with results confirmed in trials with low risk of bias, in large trials, and when including only CABG studies. Bayesian network meta-analysis showed that sevoflurane (OR=0.31, 95% credible interval 0.14-0.64) and desflurane (OR=0.43, 95% credible interval 0.21-0.82) were individually associated with a reduction in mortality when compared with TIVA. /st>Anaesthesia with volatile agents appears to reduce mortality after cardiac surgery when compared with TIVA, especially when sevoflurane or desflurane is used. A large, multicentre trial is warranted to confirm that long-term survival is significantly affected by the choice of anaesthetic.
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To examine the impact of VAC therapy on mortality of patients with sternal wound infections after cardiothoracic surgery. Controversial results regarding mortality of patients with sternal wound infections were published. We performed a systematic search in PubMed and Scopus. Mortality was the primary outcome of the meta-analysis. Recurrences, complications and length of stay were secondary outcomes. Twenty-two retrospective studies including 2467 patients were eligible for inclusion. Patients treated with VAC had significantly lower mortality compared to those treated without VAC [2233 patients, RR = 0.40, (95% CI 0.28, 0.57)]. This finding was consistent regardless of the study design, the exclusion of studies with positive findings, the criteria for establishment of the compared groups, the time of mortality assessment or the type of infections under study, provided that adequate data was available. VAC therapy was associated with fewer recurrences (RR = 0.34, 95% CI: 0.19-0.59). The meta-analysis did not show any difference in the length of stay (RR = -2.25, 95% CI: -7.52-3.02). VAC therapy was associated with lower mortality than other surgical techniques in retrospective cohorts of patients with DSWIs following cardiothoracic surgery.
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To compare the effect of aprotinin with the effect of lysine analogues (tranexamic acid and ε-aminocaproic acid) on early mortality in three subgroups of patients: low, intermediate and high risk of cardiac surgery. We performed a meta-analysis of randomised controlled trials and observational with the following data sources: Medline, Cochrane Library, and reference lists of identified articles. The primary outcome measure was early (in-hospital/30-day) mortality. The secondary outcome measures were any transfusion of packed red blood cells within 24 hours after surgery, any re-operation for bleeding or massive bleeding, and acute renal dysfunction or failure within the selected cited publications, respectively. Out of 328 search results, 31 studies (15 trials and 16 observational studies) included 33,501 patients. Early mortality was significantly increased after aprotinin vs. lysine analogues with a pooled risk ratio (95% CI) of 1.58 (1.13-2.21), p<0.001 in the low (n = 14,297) and in the intermediate risk subgroup (1.42 (1.09-1.84), p<0.001; n = 14,427), respectively. Contrarily, in the subgroup of high risk patients (n = 4,777), the risk for mortality did not differ significantly between aprotinin and lysine analogues (1.03 (0.67-1.58), p = 0.90). Aprotinin may be associated with an increased risk of mortality in low and intermediate risk cardiac surgery, but presumably may has no effect on early mortality in a subgroup of high risk cardiac surgery compared to lysine analogues. Thus, decisions to re-license aprotinin in lower risk patients should critically be debated. In contrast, aprotinin might probably be beneficial in high risk cardiac surgery as it reduces risk of transfusion and bleeding complications.
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There is no consensus on which drugs/techniques/strategies can affect mortality in the perioperative period of cardiac surgery. With the aim of identifying these measures, and suggesting measures for prioritized future investigation we performed the first international consensus conference on this topic. The consensus was a continuous international internet-based process with a final meeting on June 28th 2010 in Milan at the Vita-Salute University. Participants included 340 cardiac anesthesiologists, cardiac surgeons and cardiologists from 65 countries all over the world. A comprehensive literature review was performed to identify topics that subsequently generated position statements for discussion, voting and ranking. Of the 17 major topics with a documented mortality effect, seven were subsequently excluded after further evaluation due to concerns about clinical applicability and/or study methodology. The following topics are documented as reducing mortality: administration of insulin, levosimendan, volatile anesthetics, statins, chronic beta-blockade, early aspirin therapy, the use of preoperative intra-aortic balloon counterpulsation and referral to high-volume centers. The following are documented as increasing mortality: administration of aprotinin and aged red blood cell transfusion. These interventions were classified according to the level of evidence and effect on mortality and a position statement was generated. This international consensus conference has identified the non-surgical interventions that merit urgent study to achieve further reductions in mortality after cardiac surgery: insulin, intra-aortic balloon counterpulsation, levosimendan, volatile anesthetics, statins, chronic beta-blockade, early aspirin therapy, and referral to high-volume centers. The use of aprotinin and aged red blood cells may result in increased mortality.
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To estimate the relative risks of death, myocardial infarction, stroke, and renal failure or dysfunction between antifibrinolytics and no treatment following the suspension of aprotinin from the market in 2008 for safety reasons and its recent reintroduction in Europe and Canada. Systematic review and network meta-analysis. A Cochrane review of antifibrinolytic treatments was chosen as the starting point for this systematic review. Medline, Embase, and the Cochrane register of trials were searched with no date restrictions for observational evidence. Propensity matched or adjusted observational studies with two or more of the interventions of interest (aprotinin, tranexamic acid, epsilon-aminocaproic acid, and no treatment) that were carried out in patients undergoing cardiac surgery. Network meta-analysis was used to compare treatments, and odds ratios with 95% credible intervals were estimated. Meta-analyses were carried out for randomised controlled trials alone and for randomised controlled trials with observational studies. 106 randomised controlled trials and 11 observational studies (43 270 patients) were included. Based on the results from analysis of randomised controlled trials, tranexamic acid was associated on average with a reduced risk of death compared with aprotinin (odds ratio 0.64, 95% credible interval 0.41 to 0.99). When observational data were incorporated, comparisons showed an increased risk of mortality with aprotinin on average relative to tranexamic acid (odds ratio 0.71, 95% credible interval 0.50 to 0.98) and epsilon-aminocaproic acid (0.60, 0.43 to 0.87), and an increased risk of renal failure or dysfunction on average relative to all comparators: odds ratio 0.66 (95% credible interval 0.45 to 0.88) compared with no treatment, 0.66 (0.48 to 0.91) versus tranexamic acid, and 0.65 (0.45 to 0.88) versus epsilon-aminocaproic acid. Although meta-analyses of randomised controlled trials were largely inconclusive, inclusion of observational data suggest concerns remain about the safety of aprotinin. Tranexamic and epsilon-aminocaproic acid are effective alternatives that may be safer for patients.
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The aim of this study was to assess the efficacy of a prophylactic intra-aortic balloon pump (IABP) in high-risk patients undergoing coronary artery bypass graft surgery. MEDLINE, EMBASE, CENTRAL/CCTR, SciELO, LILACS, Google Scholar, and reference lists of relevant articles were searched. We included only randomized controlled trials. Assessments for eligibility, relevance, and study validity and data extraction were performed in duplicate using prespecified criteria. Meta-analysis was carried out using fixed-effect and random-effect models. Seven publications fulfilled our eligibility criteria. There was no important statistical heterogeneity or publication bias among included studies. In total, 177 patients received prophylactic IABP and 168 did not. Overall relative risk (RR) for hospital mortality in patients treated with prophylactic IABP was 0.255 [95% confidence interval (CI), 0.122-0.533; P<0.001; same results for both effect models]. Pooled RR for postoperative low cardiac output syndrome was 0.206 (95% CI, 0.109-0.389; P<0.001) for the fixed-effect model and 0.219 (95% CI, 0.095-0.504; P<0.001) for the random-effect model. Patients treated with prophylactic IABP presented an overall difference in means for length of intensive care unit stay and hospital stay, which was lower than that in the control group (P<0.001 for both effect models). Only 7.4% (13/177) of patients who received prophylactic IABP developed complications at an insertion site, with no IABP-related death. This meta-analysis supports the use of prophylactic IABP in high-risk patients to reduce hospital mortality.
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Objectives: To assess the effectiveness of preoperative intra-aortic balloon pump (IABP) placement in high-risk patients undergoing coronary bypass surgery (CABG). The primary outcome was hospital mortality and secondary outcomes were IABP-related complications (bleeding, leg ischemia, aortic dissection). Methods: MEDLINE, EMBASE, Cochrane registry of Controlled Trials, and reference lists of relevant articles were searched. We included randomized controlled trials (RCTs), and cohort studies that fulfilled our a priori inclusion criteria. Eligibility decisions, relevance, study validity, and data extraction were performed in duplicate using pre-specified criteria. Meta-analysis was conducted using a random effects model. Results: Ten publications fulfilled our eligibility criteria, of which four were RCTs and six were cohort studies with controls. There were statistical as well as clinical heterogeneity among included studies. A total of 1034 patients received preoperative IABP and 1329 did not receive preoperative IABP. The pooled odds ratio (OR) for hospital mortality in patients treated with preoperative IABP was 0.41 (95% CI, 0.21-0.82, p = 0.01). The number needed to treat was 17. The pooled OR for hospital mortality from randomized trials was 0.18 (95% CI, 0.06-0.57, p = 0.003) and from cohort studies was 0.54 (95% CI, 0.24-1.2, p = 0.13). Overall, 3.7% (13 of 349) of patients who received preoperative IABP developed either limb ischemia or haematoma at the IABP insertion site, and most of these complications improved after discontinuation of IABP. Conclusion: Evidence from this meta-analysis support the use of preoperative IABP in high-risk patients to reduce hospital mortality.
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Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known. We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter [4.4 and 6.1 mmol per liter]) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter [11.9 mmol per liter] and maintenance of glucose at a level between 180 and 200 mg per deciliter [10.0 and 11.1 mmol per liter]). At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P<0.04, with adjustment for sequential analyses). The benefit of intensive insulin therapy was attributable to its effect on mortality among patients who remained in the intensive care unit for more than five days (20.2 percent with conventional treatment, as compared with 10.6 percent with intensive insulin therapy, P=0.005). The greatest reduction in mortality involved deaths due to multiple-organ failure with a proven septic focus. Intensive insulin therapy also reduced overall in-hospital mortality by 34 percent, bloodstream infections by 46 percent, acute renal failure requiring dialysis or hemofiltration by 41 percent, the median number of red-cell transfusions by 50 percent, and critical-illness polyneuropathy by 44 percent, and patients receiving intensive therapy were less likely to require prolonged mechanical ventilation and intensive care. Intensive insulin therapy to maintain blood glucose at or below 110 mg per deciliter reduces morbidity and mortality among critically ill patients in the surgical intensive care unit.
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Patients undergoing coronary revascularization often require inotropic support that has been associated with an increased risk for death and morbidity. The purpose of this study was to evaluate the effect of levosimendan versus control on survival after coronary revascularization. A systemic review and meta-analysis of the literature was carried out on published randomized controlled clinical trials that investigated the efficacy of levosimendan compared to other therapy in patients having coronary revascularisaion. The databases searched were Pubmed, EMBASE, the Cochrane Registry of Clinical Trials and the metaRegister of Controlled Trials. Studies that compared levosimendan to any other therapy for coronary revascularisation in adult humans and reported at least one outcome of interest were considered for inclusion. Both percutaneous coronary intervention and cardiac surgery were included. Data extraction was performed independently by two reviewers using predefined criteria. Relevant outcomes included mortality, cardiac index, cardiac enzymes, length of stay and post-procedural atrial fibrillation. The meta-analysis included 729 patients from 17 studies. Levosimendan was associated with a mortality reduction after coronary revascularization, (19/386 in the levosimendan group vs 39/343 in the control arm) odds ratio (OR) 0.40 (95% confidence interval (CI) 0.21 to 0.76, P for overall effect 0.005, P for heterogeneity = 0.33, I2 = 12% with a total of 729 patients. Levosimendan also had a favourable effect on cardiac index (standardised mean difference 1.63, 95% CI 1.43 to 1.83, P for overall effect < 0.00001), length of intensive care stay (random effects model, mean difference - 26.18 hours 95% CI 46.20 to 6.16, P for heterogeneity < 0.00001, I2 = 95%, P for overall effect P = 0.01), reductions in the rate of atrial fibrillation (OR 0.54, 95% CI 0.36 to 0.82, P for effect = 0.004, P for heterogeneity 0.84, I2 = 0% for 465 patients) and troponin I levels group (mean difference -1.59, 95% CI 1.78 to 1.40, P for overall effect < 0.00001, P for heterogeneity < 0.00001, I2 = 95%). Limitations of this analysis are discussed. Levosimendan is associated with a significant improvement in mortality after coronary revascularization. There are also improvements in several secondary endpoints. A suitably powered randomised controlled trial is required to confirm these findings and to address the unresolved questions about the timing and dosing of levosimendan.
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The intra aortic balloon pump (IABP) is a mechanical assist device which improves cardiac function. The device has a well-established place in algorithms for managing low cardiac output following cardiac surgery. There is increasing evidence that certain cardiac surgery patients benefit from a period of preoperative augmentation with the intra aortic balloon pump. To determine the effect of the preoperative intra aortic balloon pump on mortality and morbidity in a number of different patients groups undergoing coronary artery bypass grafting. The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 3, 2009), MEDLINE (2000 to August 2009), EMBASE (1998 to August 2009), BIOSIS previews (1969 to August 2009) and ISI Proceedings (1990 to August 2009) were searched. References and ongoing registers of studies were checked. No language restrictions were applied. Randomised controlled trials (RCTs) of any size or length were included. Papers were assessed for inclusion by two authors independently and differences were settled by consensus with a third author. Date are presented in the form of odds ratios (OR) and 95% confidence intervals (CI). Six trials were included (five on-pump and one off-pump). This update adds the results of one further trial. Data from a total of 255 patients were included in the meta-analysis of mortality outcomes; all on-pump. Generally, the patients were considered as "high risk" and 132 were treated preoperatively with IABP and 123 served as controls. There were four hospital deaths in the intervention arm and 23 in the non-intervention arm (OR 0.18, 95% CI 0.08 to 0.41; P<0.0001). In a subgroup analysis, low cardiac index (<2.0 L/min/m(2)) was noted in 21 out of 105 patients in the treatment arm and 59 patients out of 88 in the non-treatment arm (OR 0.14, 95% CI: 0.08 to 0.25; P<0.00001). An off-pump versus on-pump analysis was not possible due to the limited number of off-pump studies. However a single well-conducted RCT suggested favourable effect of the preoperative IABP in off-pump patients. Evidence suggests that preoperative IABP may have a beneficial effect on mortality and morbidity in specific high risk patient groups undergoing coronary artery bypass grafting, however there are many problems with the quality, validity and generalisability of the trials. However, the available evidence is not robust enough to extend the use of IABP to truly elective, high risk patients. Defining more precisely which patient groups may benefit would be the challenge for the future.
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Hyperglycaemia is a common occurrence during cardiac surgery, however, there remains some uncertainty surrounding the role of tight glycaemic control (blood glucose <180 mg/dL) during and/or after surgery. The aim of this study was to systematically review the literature to determine the effects of tight versus normal glycaemic control, during and after cardiac surgery, on measures of morbidity and mortality. The literature was systematically reviewed, based on pre-determined search criteria, for clinical trials evaluating the effect of tight versus normal glycaemic control during and/or after cardiac surgery. Each paper was reviewed by two, independent reviewers and data extracted for statistical analysis. Data from identified studies was combined using meta-analysis (RevMan5®). The results are presented either as odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CIs). A total of seven randomised controlled trials (RCTs) were identified in the literature, although not all trials could be used in each analysis. Tight glycaemic control reduced the incidence of early mortality (death in ICU) (OR 0.52 [95% CI 0.30, 0.91]); of post-surgical atrial fibrillation (odds ratio (OR 0.76 [95%CI 0.58, 0.99]); the use of epicardial pacing (OR 0.28 [95%CI 0.15, 0.54]); the duration of mechanical ventilation (mean difference (MD) -3.69 [95% CI -3.85, -3.54]) and length of stay in the intensive care unit (ICU) (MD -0.57 [95%CI -0.60, -0.55]) days. Measures of the time spent on mechanical ventilation (I2 94%) and time spent in ICU (I2 99%) both had high degrees of heterogeneity in the data. The results from this study suggest that there may be some benefit to tight glycaemic control during and after cardiac surgery. However, due to the limited number of studies available and the significant variability in glucose levels; period of control; and the reporting of outcome measures, further research needs to be done to provide a definitive answer on the benefits of tight glycaemic control for cardiac surgery patients.
Article
Objective: Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. Design: Double-blind, placebo-controlled, multicenter randomized trial. Setting: Tertiary care hospitals. Interventions: Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours. Measurements and main results: The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. Conclusions: This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery.
Article
Background: Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. Methods: We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 μg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30-day mortality. Results: The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30-day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%], respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], -5.7 to 5.9; P=0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, -2 hours; 95% CI, -5 to 1; P=0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, -12 hours; 95% CI, -21 to 2; P=0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, -1 to 2; P=0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. Conclusions: In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825).
Article
Background Levosimendan is an inotropic agent that has been shown in small studies to prevent or treat the low cardiac output syndrome after cardiac surgery. Methods In a multicenter, randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of levosimendan in patients with a left ventricular ejection fraction of 35% or less who were undergoing cardiac surgery with the use of cardiopulmonary bypass. Patients were randomly assigned to receive either intravenous levosimendan (at a dose of 0.2 μg per kilogram of body weight per minute for 1 hour, followed by a dose of 0.1 μg per kilogram per minute for 23 hours) or placebo, with the infusion started before surgery. The two primary end points were a four-component composite of death through day 30, renal-replacement therapy through day 30, perioperative myocardial infarction through day 5, or use of a mechanical cardiac assist device through day 5; and a two-component composite of death through day 30 or use of a mechanical cardiac assist device through day 5. Results A total of 882 patients underwent randomization, 849 of whom received levosimendan or placebo and were included in the modified intention-to-treat population. The four-component primary end point occurred in 105 of 428 patients (24.5%) assigned to receive levosimendan and in 103 of 421 (24.5%) assigned to receive placebo (adjusted odds ratio, 1.00; 99% confidence interval [CI], 0.66 to 1.54; P=0.98). The two-component primary end point occurred in 56 patients (13.1%) assigned to receive levosimendan and in 48 (11.4%) assigned to receive placebo (adjusted odds ratio, 1.18; 96% CI, 0.76 to 1.82; P=0.45). The rate of adverse events did not differ significantly between the two groups. Conclusions Prophylactic levosimendan did not result in a rate of the short-term composite end point of death, renal-replacement therapy, perioperative myocardial infarction, or use of a mechanical cardiac assist device that was lower than the rate with placebo among patients with a reduced left ventricular ejection fraction who were undergoing cardiac surgery with the use of cardiopulmonary bypass. (Funded by Tenax Therapeutics; LEVO-CTS ClinicalTrials.gov number, NCT02025621.)
Article
Older adults make up an ever-increasing number of patients presenting for surgery, and a significant percentage of these patients will be frail. Frailty is a geriatric syndrome that has been conceptualized as decreased reserve when confronted with stressors, although the precise definition of frailty has not been easy to standardize. The 2 most popular approaches to define frailty are the phenotypic approach and the deficit accumulation approach, although at least 20 tools have been developed, which has made comparison across studies difficult. In epidemiologic studies, baseline frailty has been associated with poor outcomes in both community cohorts and hospitalized patients. Specifically in cardiac surgery (including transcatheter aortic valve implantation procedures), frailty has been strongly associated with postoperative mortality and morbidity, and thus frailty likely improves the identification of high-risk patients beyond known risk scores. For perioperative physicians then, the question arises of how to incorporate this information into perioperative care. To date, 2 thrusts of research and clinical practice have emerged: (1) preoperative identification of high-risk patients to guide both patient expectations and surgical decision-making; and (2) perioperative optimization strategies for frail patients. However, despite the strong association of frailty and poor outcomes, there is a lack of well-designed trials that have examined perioperative interventions with a specific focus on frail patients undergoing cardiac surgery. Thus, in many cases, principles of geriatric care may need to be applied. Further research is needed to standardize and implement the feasible definitions of frailty and examine perioperative interventions for frail patients undergoing cardiac surgery.
Article
Background: Low cardiac output syndrome is associated with increased mortality and occurs in 3% to 14% of patients undergoing cardiac surgery on cardiopulmonary bypass (CPB). Levosimendan, a novel calcium sensitizer and KATP channel activator with inotropic, vasodilatory, and cardioprotective properties, has shown significant promise in reducing the incidence of low cardiac output syndrome and related adverse outcomes in patients undergoing cardiac surgery on CPB. Methods: LEVO-CTS is a phase 3 randomized, controlled, multicenter study evaluating the efficacy, safety, and cost-effectiveness of levosimendan in reducing morbidity and mortality in high-risk patients with reduced left ventricular ejection fraction (≤35%) undergoing cardiac surgery on CPB. Patients will be randomly assigned to receive either intravenous levosimendan (0.2 μg kg(-1) min(-1) for the first hour followed by 0.1 μg/kg for 23hours) or matching placebo initiated within 8hours of surgery. The co-primary end points are (1) the composite of death or renal replacement therapy through day 30 or perioperative myocardial infarction, or mechanical assist device use through day 5 (quad end point tested at α<.01), and (2) the composite of death through postoperative day 30 or mechanical assist device use through day 5 (dual end point tested at α<.04). Safety end points include new atrial fibrillation and death through 90days. In addition, an economic analysis will address the cost-effectiveness of levosimendan compared with placebo in high-risk patients undergoing cardiac surgery on CPB. Approximately 880 patients will be enrolled at approximately 60 sites in the United States and Canada between July 2014 and September 2016, with results anticipated in January 2017. Conclusion: LEVO-CTS, a large randomized multicenter clinical trial, will evaluate the efficacy, safety, and cost-effectiveness of levosimendan in reducing adverse outcomes in high-risk patients undergoing cardiac surgery on CPB. Clinical trial registration: ClinicalTrials.gov (NCT02025621).
Article
Objective: To investigate the frequency and predictors of in-hospital complications among patients undergoing coronary artery bypass grafting (CABG) in the United States. Design: Retrospective national database analysis SETTINGS: United States hospitals. Participants: A weighted sample of 1,910,236 patients undergoing CABG surgery identified from the National (Nationwide) Inpatient Sample from 2008 to 2012. Interventions: CABG surgery MEASUREMENTS AND MAIN RESULTS: The number of CABG surgeries decreased from 436,275 in 2008 to 339,749 in 2012. The Deyo comorbidity index showed a steady increase from 2008 to 2012. The rate of in-hospital mortality decreased from 2.7% in 2008 to 2.2% in 2012 (p<0.001). The most common in-hospital complication was postoperative hemorrhage (30.4%), followed by cardiac (11.34%) and respiratory complications (2.3%). During the 5-year period, the rates of in-hospital cardiac, respiratory and infectious complications decreased (p<0.001), while the rate of postoperative hemorrhage showed a 35.8% relative increase in 2012 compared to 2008. Conclusion: The annual number of CABG surgeries is declining in the United States. While the burden of comorbidities is increasing, the rates of mortality and most in-hospital complications are improving. The increasing rate of postoperative bleeding necessitates the need to develop strategies to improve the risk of bleeding in this patient population.
Article
OBJECTIVE: Of the 230 million patients undergoing major surgical procedures every year, more than 1 million will die within 30 days. Thus, any nonsurgical interventions that help reduce perioperative mortality might save thousands of lives. The authors have updated a previous consensus process to identify all the nonsurgical interventions, supported by randomized evidence, that may help reduce perioperative mortality. DESIGN AND SETTING: A web-based international consensus conference. PARTICIPANTS: The study comprised 500 clinicians from 61 countries. INTERVENTIONS: A systematic literature search was performed to identify published literature about nonsurgical interventions, supported by randomized evidence, showing a statistically significant impact on mortality. A consensus conference of experts discussed eligible papers. The interventions identified by the conference then were submitted to colleagues worldwide through a web-based survey. MEASUREMENTS AND MAIN RESULTS: The authors identified 11 interventions contributing to increased survival (perioperative hemodynamic optimization, neuraxial anesthesia, noninvasive ventilation, tranexamic acid, selective decontamination of the gastrointestinal tract, insulin for tight glycemic control, preoperative intra-aortic balloon pump, leuko-depleted red blood cells transfusion, levosimendan, volatile agents, and remote ischemic preconditioning) and 2 interventions showing increased mortality (beta-blocker therapy and aprotinin). Interventions then were voted on by participating clinicians. Percentages of agreement among clinicians in different countries differed significantly for 6 interventions, and a variable gap between evidence and clinical practice was noted. CONCLUSIONS: The authors identified 13 nonsurgical interventions that may decrease or increase perioperative mortality, with variable agreement by clinicians. Such interventions may be optimal candidates for investigation in high-quality trials and discussion in international guidelines to reduce perioperative mortality.
Article
Purpose of review: Cardiac surgery is at high risk for the development of postoperative complications involving cardiovascular and respiratory system, as well as kidneys and central nervous system. The aim of this review is to provide an overview on the most recent findings concerning the type and incidence of different complications after cardiac surgery and to summarize the current recommendations. Recent findings: Despite an improvement of surgical and anaesthesia techniques that resulted in a significant decrease in mortality, postoperative complications play a major role in affecting morbidity, mortality, length of hospital stay and patients' quality of life. The most recent evidence suggests that fluid and inotropes administration should be targeted to maintain a cardiac index above 3 l/min/m throughout the perioperative period. Volatile anaesthesia and mechanical ventilation with low tidal volumes, low driving pressure and moderate-low positive end-expiratory pressure should be preferred. Preoperative steroids could reduce postoperative atrial fibrillation, whereas no drug has shown to effectively prevent kidney injury. Summary: Cardiac surgery is still at high risk for postoperative complications. The optimal type of anaesthesia, protective mechanical ventilation during and after surgery as well as haemodynamic management with vasoactive and inotropic drugs is still to be determined.
Article
Background Complications after cardiac surgery are common and lead to substantial increases in morbidity and mortality. Meta-analyses of small randomized trials have suggested that perioperative statin therapy can prevent some of these complications. Methods We randomly assigned 1922 patients in sinus rhythm who were scheduled for elective cardiac surgery to receive perioperative rosuvastatin (at a dose of 20 mg daily) or placebo. The primary outcomes were postoperative atrial fibrillation within 5 days after surgery, as assessed by Holter electrocardiographic monitoring, and myocardial injury within 120 hours after surgery, as assessed by serial measurements of the cardiac troponin I concentration. Secondary outcomes included major in-hospital adverse events, duration of stay in the hospital and intensive care unit, left ventricular and renal function, and blood biomarkers. Results The concentrations of low-density lipoprotein cholesterol and C-reactive protein after surgery were lower in patients assigned to rosuvastatin than in those assigned to placebo (P<0.001). However, the rate of postoperative atrial fibrillation did not differ significantly between the rosuvastatin group and the placebo group (21.1% and 20.5%, respectively; odds ratio 1.04; 95% confidence interval [CI], 0.84 to 1.30; P=0.72), nor did the area under the troponin I–release curve (102 ng×hour per milliliter and 100 ng×hour per milliliter, respectively; between-group difference, 1%; 95% CI, −9 to 13; P=0.80). Subgroup analyses did not indicate benefit in any category of patient. Rosuvastatin therapy did not result in beneficial effects on any of the secondary outcomes but was associated with a significant absolute (±SE) excess of 5.4±1.9 percentage points in the rate of postoperative acute kidney injury (P=0.005). Conclusions In this trial, perioperative statin therapy did not prevent postoperative atrial fibrillation or perioperative myocardial damage in patients undergoing elective cardiac surgery. Acute kidney injury was more common with rosuvastatin. (Funded by the British Heart Foundation and others; STICS ClinicalTrials.gov number, NCT01573143.)
Article
Importance: Statins affect several mechanisms underlying acute kidney injury (AKI). Objective: To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce AKI following cardiac surgery. Design, setting, and participants: Double-blinded, placebo-controlled, randomized clinical trial of adult cardiac surgery patients conducted from November 2009 to October 2014 at Vanderbilt University Medical Center. Interventions: Patients naive to statin treatment (n = 199) were randomly assigned 80 mg of atorvastatin the day before surgery, 40 mg of atorvastatin the morning of surgery, and 40 mg of atorvastatin daily following surgery (n = 102) or matching placebo (n = 97). Patients already taking a statin prior to study enrollment (n = 416) continued taking the preenrollment statin until the day of surgery, were randomly assigned 80 mg of atorvastatin the morning of surgery and 40 mg of atorvastatin the morning after (n = 206) or matching placebo (n = 210), and resumed taking the previously prescribed statin on postoperative day 2. Main outcomes and measures: Acute kidney injury defined as an increase of 0.3 mg/dL in serum creatinine concentration within 48 hours of surgery (Acute Kidney Injury Network criteria). Results: The data and safety monitoring board recommended stopping the group naive to statin treatment due to increased AKI among these participants with chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2) receiving atorvastatin. The board later recommended stopping for futility after 615 participants (median age, 67 years; 188 [30.6%] were women; 202 [32.8%] had diabetes) completed the study. Among all participants (n = 615), AKI occurred in 64 of 308 (20.8%) in the atorvastatin group vs 60 of 307 (19.5%) in the placebo group (relative risk [RR], 1.06 [95% CI, 0.78 to 1.46]; P = .75). Among patients naive to statin treatment (n = 199), AKI occurred in 22 of 102 (21.6%) in the atorvastatin group vs 13 of 97 (13.4%) in the placebo group (RR, 1.61 [0.86 to 3.01]; P = .15) and serum creatinine concentration increased by a median of 0.11 mg/dL (10th-90th percentile, -0.11 to 0.56 mg/dL) in the atorvastatin group vs by a median of 0.05 mg/dL (10th-90th percentile, -0.12 to 0.33 mg/dL) in the placebo group (mean difference, 0.08 mg/dL [95% CI, 0.01 to 0.15 mg/dL]; P = .007). Among patients already taking a statin (n = 416), AKI occurred in 42 of 206 (20.4%) in the atorvastatin group vs 47 of 210 (22.4%) in the placebo group (RR, 0.91 [0.63 to 1.32]; P = .63). Conclusions and relevance: Among patients undergoing cardiac surgery, high-dose perioperative atorvastatin treatment compared with placebo did not reduce the risk of AKI overall, among patients naive to treatment with statins, or in patients already taking a statin. These results do not support the initiation of statin therapy to prevent AKI following cardiac surgery. Trial registration: clinicaltrials.gov Identifier: NCT00791648.
Article
Background: Levosimendan has been shown to confer direct renoprotection in renal endotoxemic and ischemia-reperfusion injury and could increase renal blood flow in patients with low-cardiac-output heart failure. Results from clinical trials of levosimendan on acute kidney injury (AKI) following cardiac surgery are controversial. Study design: A random-effect meta-analysis was conducted based on evidence from PubMed, EMBASE, and Cochrane Library. Settings & population: Adult patients undergoing cardiac surgery. Selection criteria for studies: Randomized controlled trials comparing the renal effect of levosimendan versus placebo or other inotropic drugs during cardiac surgery. Intervention: Perioperative levosimendan continuous infusion at a rate of 0.1 to 0.2μg/kg/min following a loading dose (6-24μg/kg) for 24 hours or only 1 loading dose (24μg/kg) within 1 hour. Outcomes: AKI, need for renal replacement therapy, mechanical ventilation duration, intensive care unit stay during hospitalization, and postoperative mortality (in-hospital or within 30 days). Results: 13 trials with a total of 1,345 study patients were selected. Compared with controls, levosimendan reduced the incidence of postoperative AKI (40/460 vs 78/499; OR, 0.51; 95% CI, 0.34-0.76; P=0.001; I(2)=0.0%), renal replacement therapy (22/492 vs 49/491; OR, 0.43; 95% CI, 0.25-0.76; P=0.002; I(2)=0.0%), postoperative mortality (35/658 vs 94/657; OR, 0.41; 95% CI, 0.27-0.62; P<0.001; I(2)=0.0%), mechanical ventilation duration (in days; n=235; weighted mean difference, -0.34; 95% CI, -0.58 to -0.09; P=0.007], and intensive care unit stay (in days; n=500; weighted mean difference, -2.2; 95% CI, -4.21 to -0.13; P=0.04). Limitations: Different definitions for AKI among studies. Small sample size for some trials. Conclusions: Perioperative administration of levosimendan in patients undergoing cardiac surgery may reduce complications. Future trials are needed to determine the dose effect of levosimendan in improving outcomes, especially in patients with decreased baseline kidney function.
Article
High-quality evidence and derived guidelines, as typically published in major academic journals, are a major process that shapes physician decision-making worldwide. However, for many aspects of medical practice, there is a lack of High-quality evidence or an overload of somewhat contradictory low-quality information, which makes decision-making a difficult, uncertain, and unpredictable process. When the issues in question are important and evidence limited or controversial, the medical community seeks to establish common ground for "best practice" through consensus conferences and consensus statements or guidelines. Such consensus statements are seen as a useful tool to establish expert agreement, define the boundaries of acceptable practice, provide priorities for the research agenda, and obtain opinions from different countries and healthcare systems. This standard approach, however, can be criticized for being elitist, noninclusive, and poorly representative of the community of clinicians who will have to make decisions about the implementation of such recommendations. Accordingly, the authors propose a new model based on a combination of a local core meeting (detailed review and expert input) followed by a worldwide web-based network assessment (democracy-based consensus). The authors already have applied this approach to develop consensus on all nonsurgical interventions that increase or reduce perioperative mortality in critically ill patients and in those with acute kidney injury. The methodology was based on 5 sequential local and web-based steps. Both a panel of experts and a large number of professionals from all over the world were involved, giving birth to a new type of "democracy-based consensus." This new type of "democracy-based consensus" has the potential to increase grass-root clinician involvement, expand the reach to less-developed countries, provide a more global perspective on proposed interventions, and perhaps more importantly, increase awareness, ownership, and the statistical likelihood of subsequent implementation. Copyright © 2014 Elsevier Inc. All rights reserved.
Article
Purpose: Trends towards surgical sub-specialisation to improve patient-outcomes are well-documented and largely supported by evidence. However few studies have examined whether this benefit exists within adult-cardiac surgery. To answer whether sub-specialisation within adult-cardiac surgery improves patient-outcomes, this study assessed the relationship between procedure-specific and total-cardiac surgeon-volume and mortality and morbidity in cardiac-valve and coronary artery bypass grafting (CABG) surgery. Methods: Data came from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) registry from 2001 to 2010 and included 23 hospitals, 109 surgeons, 20,619 patients with isolated-CABG-surgery and 11,536 patients with a valve-procedure. Hierarchical logistic regression using generalised estimating equations was used to analyse outcomes. Measures included operative-mortality and occurrence of a complication (deep sternal wound infection, new stroke, acute kidney injury). Results: Crude operative mortality (and complication rates) were 1.7% (4.9%) and 4% (11%) in the isolated-CABG and valve-surgical populations respectively. A greater procedure-specific surgeon volume was associated with reduced mortality and complication rates in valve-surgery but not isolated-CABG. There was a 33% decrease in odds of dying for every additional 50 valve procedures performed [OR 0.67, p=0.003]. Conversely, greater total-cardiac surgical volume for individual surgeons did not result in improved outcomes, for both isolated-CABG and valve populations. Conclusions: Our finding of an association between increased valve-specific surgeon volumes with improved valve-surgery outcomes, and absence of an association between these outcomes and annual total-cardiac surgical experience supports the case for sub-specialisation specifically within the field of valve surgery.
Article
Background Although the relation between hospital volume and surgical mortality is well established, for most procedures, the relative importance of the experience of the operating surgeon is uncertain. Methods Using information from the national Medicare claims data base for 1998 through 1999, we examined mortality among all 474,108 patients who underwent one of eight cardiovascular procedures or cancer resections. Using nested regression models, we examined the relations between operative mortality and surgeon volume and hospital volume (each in terms of total procedures performed per year), with adjustment for characteristics of the patients and other characteristics of the providers. Results Surgeon volume was inversely related to operative mortality for all eight procedures (P=0.003 for lung resection, P<0.001 for all other procedures). The adjusted odds ratio for operative death (for patients with a low-volume surgeon vs. those with a high-volume surgeon) varied widely according to the procedure — from 1.24 for lung resection to 3.61 for pancreatic resection. Surgeon volume accounted for a large proportion of the apparent effect of the hospital volume, to an extent that varied according to the procedure: it accounted for 100 percent of the effect for aortic-valve replacement, 57 percent for elective repair of an abdominal aortic aneurysm, 55 percent for pancreatic resection, 49 percent for coronary-artery bypass grafting, 46 percent for esophagectomy, 39 percent for cystectomy, and 24 percent for lung resection. For most procedures, the mortality rate was higher among patients of low-volume surgeons than among those of high-volume surgeons, regardless of the surgical volume of the hospital in which they practiced. Conclusions For many procedures, the observed associations between hospital volume and operative mortality are largely mediated by surgeon volume. Patients can often improve their chances of survival substantially, even at high-volume hospitals, by selecting surgeons who perform the operations frequently.
Article
Left ventricular systolic dysfunction is associated with increased morbidity and mortality in patients undergoing cardiac surgery. The authors performed a meta-analysis investigating the effects of levosimendan in cardiac surgery patients with and without preoperative systolic dysfunction. Meta-analysis of randomized controlled trials. Hospital. The 1,155 patients who participated in 14 randomized controlled trials of perioperative levosimendan were included. None. PubMed, EMBASE, the Cochrane database of clinical trials, and conference proceedings were searched for clinical trials of perioperative levosimendan in patients undergoing cardiac surgery through May 1, 2012. Studies were grouped by mean ejection fraction (EF). Those with a mean EF <40% were designated as low-EF. Pooled results demonstrated a reduction in mortality with levosimendan (risk difference [RD]-4.2%; 95% CI -7.2%, -1.1%; p = 0.008). Subgroup analysis showed that this benefit was confined to the low-EF studies (RD -7.0%; 95% CI -11.0%, -3.1%; p < 0.001). No benefit was observed in the preserved-EF subgroup (RD +1.1%; 95% CI -3.8%, +5.9%; p = 0.66). Significant reductions also were seen in the need for dialysis (RD -4.9%; 95% CI -8.2%, -1.6%; p = 0.003), myocardial injury (RD -5.0%; 95% CI -8.3%, -1.7%; p = 0.003), and postoperative atrial fibrillation (RD -8.1%; 95% CI -13.3%, -3.0%; p = 0.002). Levosimendan was associated with reduced mortality and other adverse outcomes in patients undergoing cardiac surgery, and these benefits were greatest in patients with reduced EF. These data support the need for adequately powered randomized clinical trials to confirm the benefits of levosimendan in patients with reduced EF undergoing cardiac surgery.
Article
To investigate the effects of postoperative intensive glycemic control on patient outcomes. Ineffective perioperative glycemic control has been associated with high mortality and morbidity rates among cardiac surgery patients. 212 cardiac surgery patients were allocated by a quasi-experimental design to: a) a control group (n = 107) with targeted blood glucose levels 161-200 mg/dl or b) a therapy group (n = 105) with blood glucose target 120-160 mg/dl. We compared the two groups on their mortality, length of stay, duration of intubation, incidence of severe hypoglycemia and frequency of postoperative infections. The mean postoperative blood glucose levels were significantly lower for the therapy group compared with the control group (153.9 mg/dl vs. 173.9 md/dl, p < 0.001). The intensive glycemic control was strongly associated with decreased in-hospital mortality (7 deaths/105 patients for the control group vs. 1 death/105 patients for the therapy group; p = 0.033). We did not identify any statistically significant associations regarding the other patient outcomes. This randomized quasi-experimental trial found lower in-hospital mortality with more intense blood glucose control. Effective postoperative glycemic control did not affect the other studied patient outcomes.
Article
Don't know responses in environmental assessment surveys pose difficulties in data interpretation. In this study, the issue of don't know responses on knowledge items in environmental surveys was addressed by ascertaining if the frequency of these responses was related to the sociodemographics of the respondents and to the types of environmental issues. The data showed fewer don't know responses when the environmental issue in question was highly observable. Gender and residence status in the community affected the propensity of respondents to give a don't know response. The findings suggest that even at the local level there is a need for a program of environmental education to help the citizenry become more informed and more involved in the decisionmaking process.
Article
Objective: The aim of this meta-analysis was to investigate the cardioprotective properties of isoflurane versus any comparator in terms of the rate of myocardial infarction and all-cause mortality. Design: Pertinent studies were searched independently in Biomed, Central, PubMed, Embase, and the Cochrane Central Register of clinical trials. The primary endpoint was mortality at the longest follow-up available. Setting: A hospital. Participants: Randomized controlled trials. Intervention: A meta-analysis of 37 trials. Measurements and main results: The 37 included trials randomized 3,539 patients in cardiac (16 studies) and in noncardiac surgery (21 studies) with noninhalation comparators in 55% of trials. The overall analysis showed no difference in mortality between the isoflurane and control groups (16/1,602 [1.0%] v 23/1,937 [1.2%], odds ratios (OR) = 0.76 [0.39-1.47], p = 0.4 with 37 studies included) and no difference in the rate of myocardial infarction (3/1,312 [0.2%] v 1/1,532 [0.07%], OR = 2.03 [0.27-15.49], p = 0.5 with 30 studies included). Mortality was reduced in the isoflurane group when only studies with a low risk of bias were included in the analyses (0/540 [0%] v 5/703 [0.7%] in the control arm, OR = 0.13 [0.02-0.76], p = 0.02) with 4 cardiac and 6 noncardiac trials included and 5 noninhalation and 5 inhalation agents as the comparator. A trend was noted when a subanalysis was performed with propofol as a comparator (1/544 [0.2%] v 6/546 [1.1%], p = 0.05, with 16 studies included). Conclusions: Isoflurane reduced mortality in high-quality studies and showed a trend toward a reduction in mortality when it was compared with propofol. No differences in the rates of overall mortality and myocardial infarction were noted.
Article
The effects of preoperative aspirin use on outcomes of cardiac surgery patients remain uncertain. This study was aimed to evaluate the effect of preoperative aspirin use on major outcomes in cardiac surgery patients. An observational cohort study was performed on consecutive patients (n = 4256) undergoing cardiac surgery in 2 tertiary hospitals. Of all patients, 2868 patients met the inclusion criteria and were divided into 2 groups: those taking (n = 1923) or not taking (n = 945) aspirin within 5 days preceding surgery. Patients in the aspirin group presented significantly more with comorbidities including hypertension, diabetes, peripheral arterial disease, previous myocardial infarction, angina, cerebrovascular disease, older age, and male gender. With propensity scores adjusted and multivariate logistic regression, however, the results of this study showed that preoperative aspirin therapy (vs nonaspirin) significantly reduced the risk of 30-day mortality (3.5% vs 6.5%, OR: 0.611, 95% CI: 0.391-0.956, P = 0.031), postoperative renal failure (3.7% vs 7.1%, OR: 0.384, 95% CI: 0.254-0.579, P < 0.001), dialysis required (1.9% vs 3.6%, OR: 0.441, 95% CI: 0.254-0.579, P < 0.001), intensive care unit stay (mean 107.2 vs 136.1 h, P < 0.001) and a composite outcome-major adverse cardiocerebral events (8.7% vs 10.8%, OR: 0.662, 95% CI:: 0.482-0.909, P = 0.011) in the patients undergoing cardiac surgery. However, readmissions did not show a significant difference between the 2 groups (14.5% vs 12.8%, P = 0.944). Preoperative aspirin therapy is associated with a significant decrease in the risk of major cardiocerebral complications, renal failure, intensive care unit stay and 30-day mortality but does not increase the risk of readmissions in patients undergoing cardiac surgery.
Article
Catecholaminergic inotropes have a place in the management of low output syndrome and decompensated heart failure but their effect on mortality is debated. Levosimendan is a calcium sensitizer that enhances myocardial contractility without increasing myocardial oxygen use. A meta-analysis was conducted to determine the impact of levosimendan on mortality and hospital stay. BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials were searched for pertinent studies. International experts and the manufacturer were contacted. Articles were assessed by four trained investigators, with divergences resolved by consensus. Inclusion criteria were random allocation to treatment and comparison of levosimendan vs. control. There were no restrictions on dose or time of levosimendan administration or on language. Exclusion criteria were: duplicate publications, nonadult studies, oral administration of levosimendan, and no data on main outcomes. Study end points, main outcomes, study design, population, clinical setting, levosimendan dosage, and treatment duration were extracted. Data from 5,480 patients in 45 randomized clinical trials were analyzed. The overall mortality rate was 17.4% (507 of 2,915) among levosimendan-treated patients and 23.3% (598 of 2,565) in the control group (risk ratio 0.80 [0.72; 0.89], p for effect <.001, number needed to treat = 17 with 45 studies included). Reduction in mortality was confirmed in studies with placebo (risk ratio 0.82 [0.69; 0.97], p = .02) or dobutamine (risk ratio 0.68 [0.52-0.88]; p = .003) as comparator and in studies performed in cardiac surgery (risk ratio 0.52 [0.35; 0.76] p = .001) or cardiology (risk ratio 0.75 [0.63; 0.91], p = .003) settings. Length of hospital stay was reduced in the levosimendan group (weighted mean difference = -1.31 [-1.95; -0.31], p for effect = .007, with 17 studies included). A trend toward a higher percentage of patients experiencing hypotension was noted in levosimendan vs. control (risk ratio 1.39 [0.97-1.94], p = .053). Levosimendan might reduce mortality in cardiac surgery and cardiology settings of adult patients.
Article
To describe the factors related to outcome in patients admitted to the intensive care unit (ICU) after major surgery at a national level (in Austria). Analysis of a prospectively collected database of ICU admissions over an 11-year period. Factors associated with mortality and how this changed with time were explored using logistic multilevel modelling. A total of 88,504 surgical patients had a mean ICU length of stay of 6.5 days and total hospital stay of 31.3 days. They had an ICU mortality of 7.6% and a hospital mortality of 11.8%. Factors associated with hospital mortality included age (odds ratio (OR) 1.42 per 10 years of age), urgency of operation (2.02 for emergency when compared to elective), SAPS II score (OR 1.09), reason for admission being a medical cause and the specific nature of the surgery itself: thoracic (OR 1.81), cardiovascular (OR 1.25), trauma (OR 1.22) or gastrointestinal surgery (OR 1.71). In addition patients who had pre-existing chronic renal (OR 1.40), respiratory (OR 1.20) or cardiac failure (OR 1.29), cirrhosis (OR 2.50), alcoholism (OR 1.42), acute kidney injury (OR 1.88) and/or non-metastatic cancer (OR 1.20) were associated with higher hospital mortality than patients without this co-morbidity. There was a reduction in the OR for death over the whole 11-year period. This improved outcome remained valid even after adjusting for the identified risk factors for mortality (OR per year 0.96). This study has shown the high level of demand for critical care for this patient group and an improving rate of survival.