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Chiu and colleagues report a retrospective analysis describing the 5-yr trend in both intraoperative fluid and vasopressor administration in 32 250 patients undergoing elective abdominal surgery within the Multicenter Perioperative Outcomes Group (MPOG) database from 2015 to 2019, and exploring the association between these two factors and acute kidney injury. Modelling predicted the lowest risk for acute kidney injury when the administered crystalloid volume was 15-20 ml kg

Previous studies report a creatinine-based signal of injury within hours after cardiac surgery, which is sooner than expected based on creatinine kinetic modelling. A plausible mechanism for such an early signal has not been established, but might be explained by an acute perioperative increase in creatinine production rate (CrProspective cohort study.Academic medical center.Fifty adult male patients undergoing cardiac surgery.None.Based on the principle of conservation of mass, precisely timed serial measurements of patient weight, plasma and urine creatinine concentration, and urine volume were used to calculate CrPerioperative Cr

Cardiac surgery-associated acute kidney injury (CS-AKI) is common and is associated with increased risk for postoperative morbidity and mortality. Our recent survey of the Society of Cardiovascular Anesthesiologists (SCA) membership showed 6 potentially renoprotective strategies for which clinicians would most value an evidence-based review (ie, intraoperative target blood pressure, choice of specific vasopressor agent, erythrocyte transfusion threshold, use of alpha-2 agonists, goal-directed oxygen delivery on cardiopulmonary bypass [CPB], and the "Kidney Disease Improving Global Outcomes [KDIGO] bundle of care"). Thus, the SCA's Continuing Practice Improvement Acute Kidney Injury Working Group aimed to provide a practice update for each of these strategies in cardiac surgical patients based on the evidence from randomized controlled trials (RCTs). PubMed, EMBASE, and Cochrane library databases were comprehensively searched for eligible studies from inception through February 2021, with search results updated in August 2021. A total of 15 RCTs investigating the effects of the above-mentioned strategies on CS-AKI were included for meta-analysis. For each strategy, the level of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Across the 6 potentially renoprotective strategies evaluated, current evidence for their use was rated as "moderate," "low," or "very low." Based on eligible RCTs, our analysis suggested using goal-directed oxygen delivery on CPB and the "KDIGO bundle of care" in high-risk patients to prevent CS-AKI (moderate level of GRADE evidence). Our results suggested considering the use of vasopressin in vasoplegic shock patients to reduce CS-AKI (low level of GRADE evidence). The decision to use a restrictive versus liberal strategy for perioperative red cell transfusion should not be based on concerns for renal protection (a moderate level of GRADE evidence). In addition, targeting a higher mean arterial pressure during CPB, perioperative use of dopamine, and use of dexmedetomidine did not reduce CS-AKI (a low or very low level of GRADE evidence). This review will help clinicians provide evidence-based care, targeting improved renal outcomes in adult patients undergoing cardiac surgery.

Objective To examine whether supraphysiological oxygen administration during surgery is associated with lower or higher postoperative kidney, heart, and lung injury. Design Observational cohort study. Setting 42 medical centers across the United States participating in the Multicenter Perioperative Outcomes Group data registry. Participants Adult patients undergoing surgical procedures ≥120 minutes’ duration with general anesthesia and endotracheal intubation who were admitted to hospital after surgery between January 2016 and November 2018. Intervention Supraphysiological oxygen administration, defined as the area under the curve of the fraction of inspired oxygen above air (21%) during minutes when the hemoglobin oxygen saturation was greater than 92%. Main outcomes Primary endpoints were acute kidney injury defined using Kidney Disease Improving Global Outcomes criteria, myocardial injury defined as serum troponin >0.04 ng/mL within 72 hours of surgery, and lung injury defined using international classification of diseases hospital discharge diagnosis codes. Results The cohort comprised 350 647 patients with median age 59 years (interquartile range 46-69 years), 180 546 women (51.5%), and median duration of surgery 205 minutes (interquartile range 158-279 minutes). Acute kidney injury was diagnosed in 19 207 of 297 554 patients (6.5%), myocardial injury in 8972 of 320 527 (2.8%), and lung injury in 13 789 of 312 161 (4.4%). The median fraction of inspired oxygen was 54.0% (interquartile range 47.5%-60.0%), and the area under the curve of supraphysiological inspired oxygen was 7951% min (5870-11 107% min), equivalent to an 80% fraction of inspired oxygen throughout a 135 minute procedure, for example. After accounting for baseline covariates and other potential confounding variables, increased oxygen exposure was associated with a higher risk of acute kidney injury, myocardial injury, and lung injury. Patients at the 75th centile for the area under the curve of the fraction of inspired oxygen had 26% greater odds of acute kidney injury (95% confidence interval 22% to 30%), 12% greater odds of myocardial injury (7% to 17%), and 14% greater odds of lung injury (12% to 16%) compared with patients at the 25th centile. Sensitivity analyses evaluating alternative definitions of the exposure, restricting the cohort, and conducting an instrumental variable analysis confirmed these observations. Conclusions Increased supraphysiological oxygen administration during surgery was associated with a higher incidence of kidney, myocardial, and lung injury. Residual confounding of these associations cannot be excluded. Trial registration Open Science Framework osf.io/cfd2m

Objectives The authors sought to (1) characterize the rationale underpinning anesthesiologists’ use of various perioperative strategies hypothesized to affect renal function in adult patients undergoing cardiac surgery, (2) characterize existing belief about the quality of evidence addressing the renal impact of these strategies, and (3) identify potentially renoprotective strategies for which anesthesiologists would most value a detailed, evidence-based review. Design Survey of perioperative practice in adult patients undergoing cardiac surgery. Setting Online survey. Participants Members of the Society of Cardiovascular Anesthesiologists (SCA). Interventions None. Measurements & Main Results The survey was distributed to more than 2,000 SCA members and completed in whole or in part by 202 respondents. Selection of target intraoperative blood pressure (and relative hypotension avoidance) was the strategy most frequently reported to reflect belief about its potential renal effect (79%; 95% CI: 72-85). Most respondents believed the evidence supporting an effect on renal injury of intraoperative target blood pressure during cardiac surgery was of high or moderate quality. Other factors, including a specific nonrenal rationale, surgeon preference, department- or institution-level decisions, tradition, or habit, also frequently were reported to affect decision making across queried strategies. Potential renoprotective strategies most frequently requested for inclusion in a subsequent detailed, evidence-based review were intraoperative target blood pressure and choice of vasopressor agent to achieve target pressure. Conclusions A large number of perioperative strategies are believed to variably affect renal injury in adult patients undergoing cardiac surgery, with wide variation in perceived quality of evidence for a renal effect of these strategies.

Cardiac surgery-associated acute kidney injury (CS-AKI) is common and is associated with increased risk for postoperative morbidity and mortality. Our recent survey of the Society of Cardiovascular Anesthesiologists (SCA) membership showed 6 potentially renoprotective strategies for which clinicians would most value an evidence-based review (ie, intraoperative target blood pressure, choice of specific vasopressor agent, erythrocyte transfusion threshold, use of alpha-2 agonists, goal-directed oxygen delivery on cardiopulmonary bypass [CPB], and the "Kidney Disease Improving Global Outcomes [KDIGO] bundle of care"). Thus, the SCA's Continuing Practice Improvement Acute Kidney Injury Working Group aimed to provide a practice update for each of these strategies in cardiac surgical patients based on the evidence from randomized controlled trials (RCTs). PubMed, EMBASE, and Cochrane library databases were comprehensively searched for eligible studies from inception through February 2021, with search results updated in August 2021. A total of 15 RCTs investigating the effects of the above-mentioned strategies on CS-AKI were included for meta-analysis. For each strategy, the level of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Across the 6 potentially renoprotective strategies evaluated, current evidence for their use was rated as "moderate," "low," or "very low." Based on eligible RCTs, our analysis suggested using goal-directed oxygen delivery on CPB and the "KDIGO bundle of care" in high-risk patients to prevent CS-AKI (moderate level of GRADE evidence). Our results suggested considering the use of vasopressin in vasoplegic shock patients to reduce CS-AKI (low level of GRADE evidence). The decision to use a restrictive versus liberal strategy for perioperative red cell transfusion should not be based on concerns for renal protection (a moderate level of GRADE evidence). In addition, targeting a higher mean arterial pressure during CPB, perioperative use of dopamine, and use of dexmedetomidine did not reduce CS-AKI (a low or very low level of GRADE evidence). This review will help clinicians provide evidence-based care, targeting improved renal outcomes in adult patients undergoing cardiac surgery.

Summary Accurate preoperative risk prediction for perioperative complications such as acute kidney injury (AKI) may serve to better inform patients and families of risk before surgery, assist with resource requirement planning, and aid with cohort enrichment for enrolment into clinical trials. Where a specific risk factor is modifiable, it may offer a potential therapeutic target for risk reduction. The report by Wang and colleagues describes the modest incremental benefit of N-terminal pro brain natriuretic peptide levels when added to almost 20 other variables for the preoperative prediction of AKI after cardiac surgery. This is consistent with previous smaller studies, but there are important additional questions still to be answered before this biomarker might be used for this purpose in clinical practice.

OBJECTIVES: To determine whether randomization of patients undergoing extracorporeal membrane oxygenation to either therapeutic or a low-dose anticoagulation protocol results in a difference in activated partial thromboplastin time and anti-Xa. DESIGN: Randomized, controlled, unblinded study. SETTING: Two ICUs of two university hospitals. PATIENTS: Patients admitted to the ICU, who required extracorporeal membrane oxygenation (venovenous or venoarterial) and who did not have a preexisting indication for therapeutic anticoagulation. INTERVENTIONS: Therapeutic anticoagulation with heparin (target activated partial thromboplastin time between 50 and 70 s) or lower dose heparin (up to 12,000 U/24 hr aiming for activated partial thromboplastin time < 45 s). MEASUREMENTS AND MAIN RESULTS: Thirty-two patients were randomized into two study groups that were not significantly different in demographics and extracorporeal membrane oxygenation characteristics. There was a significant difference in the daily geometric mean heparin dose (11,742 U [95% CI, 8,601-16,031 U] vs 20,710 U [95% CI, 15,343-27,954 U]; p = 0.004), daily geometric mean activated partial thromboplastin time (48.1 s [95% CI, 43.5-53.2 s] vs 55.5 s [95% CI, 50.4-61.2 s]; p = 0.04), and daily geometric mean anti-Xa (0.11 international units/mL [95% CI, 0.07-0.18] vs 0.27 [95% CI, 0.17-0.42]; p = 0.01). We found similar results when considering only venovenous extracorporeal membrane oxygenation episodes; however, no difference in daily geometric mean activated partial thromboplastin time between groups when considering only venoarterial extracorporeal membrane oxygenation episodes. CONCLUSIONS: Allocating patients on extracorporeal membrane oxygenation to two different anticoagulation protocols led to a significant difference in mean daily activated partial thromboplastin time and anti-Xa levels between groups. When considering subgroups analyses, these results were consistent in patients on venovenous extracorporeal membrane oxygenation. Our results support the feasibility of a larger trial in patients undergoing venovenous extracorporeal membrane oxygenation to compare different anticoagulation protocols; however, this study does not provide evidence on the optimal anticoagulation protocol for patients undergoing extracorporeal membrane oxygenation.

Major bleeding in noncardiac surgery is common and associated with serious complications. The antifibrinolytic agent tranexamic acid (TXA) reduces bleeding and may reduce the risk of these complications. TXA also may have immunomodulatory effects that could reduce surgical site infection. Clinical trials of TXA in noncardiac surgery have been insufficiently powered to evaluate its efficacy and safety. Therefore, large randomised controlled trials of its use in noncardiac surgery are required. To ensure that future clinical trials are feasible and acceptable, we undertook a survey of Fellows of the Australian and New Zealand College of Anaesthetists (ANZCA). Our aims were to ascertain current patterns of TXA administration and to assess the acceptability of randomising patients to intravenous TXA or placebo. A 12-item survey was electronically mailed to 1001 ANZCA Fellows. Two hundred and eighty nine responses were received and analysed (response rate 29%). Ninety-eight percent of respondents had used intravenous TXA in noncardiac surgery; 67% give TXA routinely for lower limb arthroplasty, with smaller proportions giving TXA for spinal surgery (40%) and other major orthopaedic surgery (28%). Almost half (49%) give TXA routinely for major trauma surgery. Thirty-six percent indicated that they did not give TXA for major vascular, abdominal, pelvic or thoracic surgery. The majority administered TXA as a single, fixed dose. Fifty-seven percent agreed that there is uncertainty about the relative risks and benefits of perioperative TXA in noncardiac surgery and 87% agreed that large definitive trials determining the safety and efficacy of perioperative TXA in noncardiac surgery are required. These results indicate that for ANZCA Fellows the use of TXA in noncardiac surgery is highly variable, that there is uncertainty about the safety and efficacy of TXA, and that a large trial would be acceptable.

Background Outcome selection underpins clinical trial interpretation. Inconsistency in outcome selection and reporting hinders comparison of different trials' results, reducing the utility of research findings. Methods We conducted an iterative consensus process to develop a set of Core Outcome Measures for Perioperative and Anaesthetic Care (COMPAC), following the established Core Outcome Measures for Effectiveness Trials (COMET) methodology. First, we undertook a systematic review of RCTs in high-impact journals to describe current outcome reporting trends. We then surveyed patients, carers, researchers, and perioperative clinicians about important outcomes after surgery. Finally, a purposive stakeholder sample participated in a modified Delphi process to develop a core outcome set for perioperative and anaesthesia trials. Results Our systematic review revealed widespread inconsistency in outcome reporting, with variable or absent definitions, levels of detail, and temporal criteria. In the survey, almost all patients, carers, and clinicians rated clinical outcome measures critically important, but clinicians rated patient-centred outcomes less highly than patients and carers. The final core outcome set was: (i) mortality/survival (postoperative mortality, long-term survival); (ii) perioperative complications (major postoperative complications/adverse events; complications/adverse events causing permanent harm); (iii) resource use (length of hospital stay, unplanned readmission within 30 days); (iv) short-term recovery (discharge destination, level of dependence, or both); and (v) longer-term recovery (overall health-related quality of life). Conclusions This core set, incorporating important outcomes for both clinicians and patients, should guide outcome selection in future perioperative medicine or anaesthesia trials. Mapping these alongside standardised endpoint definitions will yield a comprehensive perioperative outcome framework.

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research., The development of acute kidney injury (AKI) after major non-cardiac surgery is associated with substantial long-term morbidity and mortality. This joint Consensus Statement from the Acute Disease Quality Initiative and the PeriOperative Quality Initiative provides recommendations for the definition, prevention and management of postoperative AKI.

Objectives With the exception of 0.9% saline, little is known about factors that may contribute to increased serum chloride concentration (SCl−) in patients undergoing cardiac surgery. For the present study, the authors sought to characterize the association between administered chloride load from intravenous fluid and other perioperative variables, with peak perioperative SCl−. Design Secondary analysis of data from a previously published controlled clinical trial in which patients were assigned to a chloride-rich or chloride-limited perioperative fluid strategy (NCT02020538). Setting Academic medical center. Participants The study comprised 1,056 adult patients with normal preoperative SCl− undergoing cardiac surgery. Interventions None Measurements and Main Results Peak perioperative SCl− and hyperchloremia, defined as peak SCl− >110 mmol/L, were selected as co-primary endpoints. Regression modeling identified factors independently associated with these endpoints. Mean (standard deviation) peak perioperative SCl− was 114 (5) mmol/L, and hyperchloremia occurred in 824 (78.0%) of the cohort. In addition to administered volume of 0.9% saline, multivariate linear and logistic regression modeling consistently associated preoperative SCl− (regression coefficient 0.5; 95% confidence interval [CI] 0.4-0.6 mmol/L; odds ratio 1.60; 95% CI 1.41-1.82 per 1 mmol/L increase) and cardiopulmonary bypass duration (regression coefficient 0.1; 95% CI 0.1-0.2 mmol/L; odds ratio 1.12; 95% CI 1.06-1.19 per 10 minutes) with both co-primary outcomes. Multivariate modeling only explained approximately 50% of variability in peak SCl−. Conclusions The present study's data identified an association for both 0.9% saline administration and other nonfluid variables with peak perioperative SCl− and hyperchloremia. Stand-alone strategies to limit administration of chloride-rich intravenous fluid may have limited ability to prevent hyperchloremia in this setting.

To characterize current evidence and current foci of perioperative clinical trials, we systematically reviewed Medline and identified perioperative trials involving 100 or more adult patients undergoing surgery and reporting renal end points that were published in high-impact journals since 2004. We categorized the 101 trials identified based on the nature of the intervention and summarized major trial findings from the five categories most applicable to perioperative management of patients. Trials that targeted ischemia suggested that increasing perioperative renal oxygen delivery with inotropes or blood transfusion does not reliably mitigate acute kidney injury (AKI), although goal-directed therapy with hemodynamic monitors appeared beneficial in some trials. Trials that have targeted inflammation or oxidative stress, including studies of nonsteroidal anti-inflammatory drugs, steroids, N-acetylcysteine, and sodium bicarbonate, have not shown renal benefits, and high-dose perioperative statin treatment increased AKI in some patient groups in two large trials. Balanced crystalloid intravenous fluids appear safer than saline, and crystalloids appear safer than colloids. Liberal compared with restrictive fluid administration reduced AKI in a recent large trial in open abdominal surgery. Remote ischemic preconditioning, although effective in several smaller trials, failed to reduce AKI in two larger trials. The translation of promising preclinical therapies to patients undergoing surgery remains poor, and most interventions that reduced perioperative AKI compared novel surgical management techniques or existing processes of care rather than novel pharmacologic interventions.

The administration of chloride-rich intravenous (IV) fluid and hyperchloraemia have been associated with perioperative renal injury. The aim of this study was to determine whether a comprehensive perioperative protocol for the administration of chloride-limited IV fluid would reduce perioperative renal injury in adults undergoing cardiac surgery. From February 2014 through to December 2015, all adult patients undergoing cardiac surgery within a single academic medical center received IV fluid according to the study protocol. The perioperative protocol governed all fluid administration from commencement of anesthesia through to discharge from the intensive care unit and varied over four sequential periods, each lasting 5 months. In periods 1 and 4 a chloride-rich strategy, consisting of 0.9% saline and 4% albumin, was adopted; in periods 2 and 3, a chloride-limited strategy, consisting of a buffered salt solution and 20% albumin, was used. Co-primary outcomes were peak delta serum creatinine (∆SCr) within 5 days after the operation and KDIGO-defined stage 2 or stage 3 acute kidney injury (AKI) within 5 days after the operation. We enrolled and analysed data from 1136 patients, with 569 patients assigned to a chloride-rich fluid strategy and 567 to a chloride-limited one. Compared with a chloride-limited strategy and adjusted for prespecified covariates, there was no association between a chloride-rich perioperative fluid strategy and either peak ∆S Cr, transformed to satisfy the assumptions of multivariable linear regression [regression coefficient 0.03, 95% confidence interval (CI) −0.03 to 0.08); p = 0.39], or stage 2 or 3 AKI (adjusted odds ratio 0.97, 95% CI 0.65–1.47; p = 0.90]. A perioperative fluid strategy to restrict IV chloride administration was not associated with an altered incidence of AKI or other metrics of renal injury in adult patients undergoing cardiac surgery. Trial Registration: Clinicaltrials.gov Identifier: NCT02020538.

Perioperative acute kidney injury is a common problem. While clinical trials seek to evaluate the impact of interventions on a variety of primary and secondary endpoints with the aim of implementing this knowledge to improve perioperative outcomes, the use of valid and relevant endpoints within clinical trials is of critical importance to achieving this goal. Suitable endpoints must be validated for the study population and in light of the clinical context under investigation while also considering regulatory requirements that govern the licensing of new therapeutic agents as well as the values of patients whose outcomes we seek to improve. Heterogeneity in perioperative clinical trial endpoints and their definitions limits the ability to compare and interpret differences in outcomes across studies or to pool outcomes from different studies in meta-analysis. The Standardized Endpoints in Perioperative Medicine (StEP) initiative is an international collaboration whose goal is to identify and recommend a suite of clearly and precisely defined endpoints across multiple domains, specifically suited for use in perioperative clinical trials. The current review describes the rationale, goals and the planned pathway of the StEP renal subgroup. Development of a set of standardized and core renal endpoints, valid and relevant for use in the perioperative context, precisely defined and yet with sufficient flexibility to encourage broad uptake and application should facilitate high-quality and practice-changing perioperative research into the future.

Background The association between intraoperative oliguria during major abdominal surgery and the subsequent development of postoperative acute kidney injury (AKI) remains poorly defined. We hypothesised that, in such patients, intraoperative oliguria would be an independent predictor of subsequent AKI. Methods We performed a post hoc analysis of data from the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial of conservative vs liberal fluid therapy during and after major abdominal surgery. We used χ2, logistic regression, and fractional polynomials to study the association between intraoperative oliguria defined as a urinary output Results We included 2444 of 2983 patients from the RELIEF trial in this study. A total of 889 patients (36%) met oliguric criteria intraoperatively. Oliguria occurred in 35% of those without AKI, and 44%, 48%, and 45% of those who developed postoperative AKI Stages 1–3, respectively (P Conclusions Intraoperative oliguria, defined as urine output Clinical trial registration NCT01424150.

Background: The Standardising Endpoints for Perioperative Medicine group was established to derive an appropriate set of endpoints for use in clinical trials related to anaesthesia and perioperative medicine. Anaesthetic or analgesic technique during cancer surgery with curative intent may influence the risk of recurrence or metastasis. However, given the current equipoise in the existing literature, prospective, randomised, controlled trials are necessary to test this hypothesis. As such, a cancer subgroup was formed to derive endpoints related to research in onco-anaesthesia based on a current evidence base, international consensus and expert guidance.Methods: We undertook a systematic review to identify measures of oncological outcome used in the oncological, surgical, and wider literature. A multiround Delphi consensus process that included up to 89 clinician–researchers was then used to refine a recommended list of endpoints.Results: We identified 90 studies in a literature search, which were the basis for a preliminary list of nine outcome measures and their definitions. A further two were added during the Delphi process. Response rates for Delphi rounds one, two, and three were 88% (n=9), 82% (n=73), and 100% (n=10), respectively. A final list of 10 defined endpoints was refined and developed, of which six secured approval by ≥70% of the group: cancer health related quality of life, days alive and out of hospital at 90 days, time to tumour progression, disease-free survival, cancer-specific survival, and overall survival (and 5-yr overall survival).Conclusion: Standardised endpoints in clinical outcomes studies will support benchmarking and pooling (meta-analysis) of trials. It is therefore recommended that one or more of these consensus-derived endpoints should be considered for inclusion in clinical trials evaluating a causal effect of anaesthesia–analgesia technique on oncological outcomes.

Statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) are one of the most frequently prescribed medications throughout the world with beneficial effects that extend beyond their lipid-lowering activity. It has been suggested that statins may offer a simple and cost-effective strategy to reduce some of the complications that occur in association with coronary artery bypass graft (CABG) surgery. Limited existing randomized trial evidence in the setting of cardiac surgery suggests that statins may reduce the incidence of postoperative atrial fibrillation. However, any effect of statins on other outcomes is less clear. The clinical significance of specific statin agent and dose, acute statin withdrawal and the potential benefits associated with statin reloading remain important yet currently unresolved issues. Despite limited high-quality evidence, class I recommendations have been made that all patients undergoing coronary artery bypass graft surgery should receive statin therapy unless contraindicated.

Objectives To determine whether preoperative endothelial dysfunction provides risk stratification for perioperative renal injury in patients undergoing noncardiac surgery. The relationship between perioperative renal injury and myocardial injury after noncardiac surgery (MINS) was explored secondarily. Design An observational study. Setting Two academic medical centers. Participants A total of 218 patients scheduled to undergo intermediate or high-risk noncardiac surgery. Interventions None. Measurements and Main Results Endothelial dysfunction was identified preoperatively by a Reactive Hyperemia-Peripheral Arterial Tonometry (RH-PAT) index. Renal injury was defined by peak delta serum creatinine (ΔS Cr ) or creatinine-based kidney disease: Improving global outcomes acute kidney injury (AKI) criteria within 7 days postoperatively. MINS was defined by peak troponin≥0.04 µg/L within 3 days postoperatively. AKI occurred in 22 patients (10.1%). Median RH-PAT index within the study cohort was 1.64 (range 1.03-4.96) and did not differ between patients with or without AKI. When adjusted for covariates, there was no association between RH-PAT index and either AKI or peak ΔS Cr . MINS occurred in 32 patients (14.7%) and was associated independently with the outcome of AKI (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.2-10.8; p = 0.02) and peak ΔS Cr (β-regression coefficient 23; 95% CI, 9-37; p = 0.002). Co-occurrence of AKI and MINS portended a marked increase in 30-day mortality (OR, 43; 95% CI, 6-305; p = 0.001) and delayed time to discharge (hazard ratio, 0.27; 95% CI, 0.13-0.54; p = 0.001). Conclusions For patients undergoing noncardiac surgery, preoperative endothelial function assessed by noninvasive peripheral arterial tonometry was not associated with perioperative AKI. Perioperative renal injury was associated strongly with MINS, and this may represent a mechanism by which AKI increases adverse outcomes.

From the *Department of Anaesthesia & Perioperative Medicine, Alfred Hospital and Monash University, Melbourne, Victoria, Australia; and †Department of Anesthesiology, Columbia University College of Physicians & Surgeons, New York, NY. Address reprint requests to David R. McIlroy, MD, MClinEpi., FANZCA, Alfred Hospital and Monash University, 55 Commercial Road, Melbourne, Victoria, 3004, Australia. E-mail: D.mcilroy@alfred. org.au © 2015 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2015.01.009

Objective To evaluate the prognostic utility of multiple novel urinary biomarkers of renal injury when used alone, in pair-wise combination with an early delta serum creatinine (ΔSCr) term, and combined as a broad biomarker panel for the prediction of serious adverse outcomes that may reflect AKI in patients undergoing cardiac surgery. Design Post-hoc analysis of prospective observational study. Setting Academic medical center. Participants 603 adults undergoing cardiac surgery. Interventions None. Measurements and Main Results Urinary cystatin-c, kidney injury molecule-1, chemokine (C-C motif) ligand 2 and interleukin-18 were measured at baseline and Conclusions Combining novel urinary biomarkers of renal injury with a creatinine-based metric soon after cardiac surgery provided excellent prognostic utility for serious adverse outcomes. Future studies are required to confirm these findings and determine optimal biomarker combinations for cost-effective risk stratification.

Objectives Bleeding is an established complication following cardiac catheterization and lower preoperative hemoglobin concentration is a potentially modifiable risk factor for adverse outcomes after cardiac surgery. However, typical changes in serum hemoglobin concentration after cardiac catheterization are poorly defined. The authors sought to identify the pattern of change in serum hemoglobin concentration within 7 days after cardiovascular catheterization, factors associated with this change and any association with adverse outcomes. Design Retrospective observational study over a 1-year period. Setting U.S. academic medical institution. Participants Participants were 284 adult patients with baseline hemoglobin concentration≥12 g/dL undergoing nonemergent cardiac surgery after cardiovascular catheterization via the femoral arterial route. Interventions None. Measurements and Main Results Lowest daily hemoglobin concentration was recorded where available for up to 7 days after catheterization and before surgery. Generalized estimating equations identified the pattern of change in serum hemoglobin while regression models identified factors associated with hemoglobin decline. Following cardiovascular catheterization average serum hemoglobin declined over time, reaching a nadir 1.4 g/dL (95% CI 1.0-1.8) below baseline 6 days after catheterization. A higher baseline hemoglobin concentration and lower body mass index were associated with greater maximal decline in hemoglobin concentration after catheterization. Acute preoperative hemoglobin decline was not associated with acute kidney injury (AKI) or a composite adverse outcome that may reflect organ ischemia. Conclusions In a cohort of patients before cardiac surgery serum hemoglobin declines during the week after cardiac catheterization, with maximal average decline observed 5 to 7 days after catheterization.

assessmentofendothelial dysfunction could provide additional information for risk stratification. † The association of reduced reactive hyperaemia-peripheral arterial tonometry (RH-PAT) index with myocardial injury was studied prospectively in subjects undergoing intermediate-high risk non-cardiac surgery. † Risk stratification for myocardial injury was improved with the addition of RH-PAT, although there were unexplained differences in prognostic utility between study sites thatcouldlimitapplication. Background. Myocardial injury after non-cardiac surgery (MINS) is a common complication with associated serious morbidity and mortality. Endothelial dysfunction might play an important role in MINS, and its rapid assessment could provide a novel method of risk stratification before surgery. Methods.Westudied238subjectsscheduledtoundergointermediateorhigh-risksurgeryina two-centre prospective study to determine whether preoperative endothelial dysfunction identified by a reactive hyperaemia—peripheral arterial tonometry (RH-PAT) index could provide effective risk stratification for MINS, defined as serum troponin ≥0.04 mg litre 21 , within 3 postoperative days. Results. The primary outcome occurred in 35 subjects (14.7%). Endothelial dysfunction was defined as an RH-PAT index of ≤1.22. Adjusted for age, Lee index and a composite measure of the extent of surgery, endothelial dysfunction was associated with MINS [odds ratio 10.1, 95% confidence interval (CI) 3.3‐30.9, P¼0.001] and increased time to discharge from hospital after surgery (hazard ratio 0.39, 95% CI 0.23‐0.65, P¼0.001). Endothelial dysfunction identified MINS with a sensitivity of 31%, a specificity of 96%, and a positive diagnostic likelihood ratio of 8.0. Risk classification for MINS was improved by the addition of RH-PAT-defined endothelial dysfunction to the Lee index (c-statistic increased from 0.69 to 0.77; integrated discrimination improvement 0.11, P¼0.003). However, prognostic utility varied widely between sites. Conclusions. For patients undergoing non-cardiac surgery, non-invasive assessment of endothelial function might enhance preoperative risk stratification for perioperative myocardial injury. However, unexplained large inter-site variation in prognostic utility could limit widespread application and needs to be further understood.

Objective We sought to characterize the relationship between postoperative blood pressure on the day of surgery and metrics of bleeding. Methods In a preplanned secondary analysis of prospectively collected data from the Limiting IV Chloride to Reduce AKI trial (NCT02020538), univariate and multivariable regression analyses explored the association between peak systolic blood pressure, peak mean arterial pressure, and peak central venous pressure recorded postoperatively on the day of surgery and multiple metrics of bleeding. Patients at increased bleeding risk due to specific criteria were excluded from analysis. The primary outcome was chest tube drainage (milliliters per hour) on the day of surgery. Secondary outcomes included red blood cell transfusion, surgical re-exploration for bleeding, and hospital mortality. Results The study cohort comprised 793 patients. Mean ± standard deviation peak systolic blood pressure, mean arterial pressure, and central venous pressure were 125 ± 15 mm Hg, 83 ± 9 mm Hg, and 12 ± 4 mm Hg, respectively. Median (interquartile range) chest tube drainage on the day of surgery was 33 mL/hour (interquartile range, 23 mL/hour-51 mL/hour). Adjusted for prespecified variables, there was no positive association between peak systolic blood pressure and bleeding outcomes, including chest tube drainage (−2.2 mL/10 mm Hg; 95% confidence interval, −3.9 to −0.5 mL/h/10 mm Hg; P = .01) or volume of transfusion (−15 mL/10 mm Hg; 95% confidence interval, −29 to −1 mL/h/10 mm Hg; P = .04). Results remained broadly consistent across multiple secondary outcomes and regardless of whether systolic blood pressure or mean arterial pressure was the explanatory variable. Conclusions The lack of positive association between peak systolic blood pressure or peak mean arterial pressure with metrics of bleeding after cardiac surgery promotes equipoise for testing the influence of higher blood pressure targets during the early postoperative period.

Objectives Consensus definitions represent an important step toward defining the epidemiology of acute kidney injury (AKI). However, the oliguric component of these definitions remains of uncertain impact and utility after cardiac surgery. The authors sought to define the specific impact of oliguric criteria, both alone and in combination with serum creatinine criteria, on the observed incidence of AKI and associated adverse outcomes following adult cardiac surgery. Design Retrospective observational study over a 1-year period. Setting Academic medical institution. Participants A total of 311 adult patients undergoing elective valve and/or coronary artery bypass graft surgery with cardiopulmonary bypass. Interventions No interventions were performed as part of the study. Measurements and Main Results Hourly urine output and daily serum creatinine were recorded in the 2 days following surgery. AKI was defined by Acute Kidney Injury Network oliguric and serum creatinine criteria. Defined by serum creatinine criteria alone, the incidence of AKI was 17.7% and was associated strongly with in-hospital mortality (odds ratio 6.6, 95% confidence interval 1.4-30.5, p = 0.02) and renal replacement therapy (odds ratio 12.7, 95% confidence interval 2.4-67.3, p = 0.003) as well as time to discharge from the intensive care unit and hospital. Defined by oliguric criteria alone through 48 hours following surgery, the incidence of AKI dramatically increased to 55.6% but was not associated with mortality, renal replacement therapy, or time to discharge. Conclusions Acute Kidney Injury Network oliguric criteria applied over 48 hours after surgery dramatically increased the measured incidence of AKI after cardiac surgery, but was not associated with adverse outcomes.

Objective The authors sought to evaluate the association between the time interval from contrast administration to cardiac surgery and postoperative acute kidney injury (AKI). Design A retrospective observational study over a 1-year period. Setting A US academic medical institution. Participants Six hundred forty-four adult patients undergoing nonemergent cardiac surgery. Interventions No interventions were performed as part of the study. Measurements and Main Results AKI was defined as an increase in serum creatinine by ≥0.3 mg/dL or ≥50% above baseline within the first 2 postoperative days or the commencement of renal replacement therapy within the same period. Using a contrast-to-surgery time interval >7 days as the baseline, multivariable logistic regression analysis determined the association between a contrast-to-surgery time interval ≤1 day or 2 to 7 days and postoperative AKI adjusting for potential confounding variables. The incidence of AKI within the study cohort was 21.9%. After adjusting for other covariates, there was no association between the contrast-to-surgery time and AKI (odds ratio [OR] ≤1 day = 0.93; 95% confidence interval [CI], 0.52-1.66; p = 0.81; OR = 2-7 days = 1.28; 95% CI, 0.78-2.11; p = 0.34). Conclusions In an appropriately selected population, cardiac surgery can be performed within 1 day of cardiovascular catheterization and contrast administration without an increase in the incidence of postoperative AKI. Recommendations to delay cardiac surgery for a specified period after contrast administration to reduce the risk of postoperative AKI are premature. Additional evidence is required before making recommendations on optimal surgical timing after contrast exposure.

Objectives To evaluate brain natriuretic peptide (BNP) as a biomarker of ischemia-reperfusion injury in cardiac transplantation Design A prospective cohort study. Setting A single academic medical center. Participants Adult patients undergoing orthotopic cardiac transplantation (n = 25). Interventions None. Measurements and Main Results The authors performed serial measurements of BNP and troponin-I in cardiac allograft donors and recipients, determining the relationship between these biomarkers and established risk factors for and measures of early graft dysfunction. Postoperative BNP correlated moderately with allograft ischemic time (ρ = 0.52, p = 0.01), donor BNP (ρ = 0.45, p = 0.03), and donor troponin-I (ρ = 0.49, p = 0.01). Postoperative BNP was higher in patients with persistently elevated inotrope requirements and enabled the early identification of such patients. In contrast, there was no association between postoperative troponin-I and these same parameters. Conclusions Postoperative BNP is associated with preimplantation and clinical performance parameters related to allograft ischemia-reperfusion injury at the time of cardiac transplantation, providing preliminary evidence to support its potential use as an ischemia-reperfusion injury biomarker in this context.

Background Perioperative hypothermia has been reported to increase the occurrence of cardiovascular complications. By increasing the activity of sympathetic nervous system, perioperative hypothermia also has the potential to increase cardiac injury and dysfunction associated with subarachnoid hemorrhage. Methods The Intraoperative Hypothermia for Aneurysm Surgery Trial randomized patients undergoing cerebral aneurysm surgery to intraoperative hypothermia (n = 499, 33.3 degrees +/- 0.8 degrees C) or normothermia (n = 501, 36.7 degrees +/- 0.5 degrees C). Cardiovascular events (hypotension, arrhythmias, vasopressor use, myocardial infarction, and others) were prospectively followed until 3-month follow-up and were compared in hypothermic and normothermic patients. A subset of 62 patients (hypothermia, n = 33; normothermia, n = 29) also had preoperative and postoperative (within 24 h) measurement of cardiac troponin-I and echocardiography to explore the association between perioperative hypothermia and subarachnoid hemorrhage-associated myocardial injury and left ventricular function. Results There was no difference between hypothermic and normothermic patients in the occurrence of any single cardiovascular event or in composite cardiovascular events. There was no difference in mortality (6%) between groups, and there was only a single primary cardiovascular death (normothermia). There was no difference between hypothermic and normothermic patients in postoperative versus preoperative left ventricular regional wall motion or ejection fraction. Compared with preoperative values, hypothermic patients had no postoperative increase in cardiac troponin-I (median change 0.00 microg/l), whereas normothermic patients had a small postoperative increase (median change + 0.01 microg/l, P = 0.038). Conclusion In patients undergoing cerebral aneurysm surgery, perioperative hypothermia was not associated with an increased occurrence of cardiovascular events.

Background: There is a need for robust, clearly defined, patient-relevant outcome measures for use in randomised trials in perioperative medicine. Our objective was to establish standard outcome measures for postoperative pulmonary complications research.Methods: A systematic literature search was conducted using MEDLINE, Web of Science, SciELO, and the Korean Journal Database. Definitions were extracted from included manuscripts. We then conducted a three-stage Delphi consensus process to select the optimal outcome measures in terms of methodological quality and overall suitability for perioperative trials.Results: From 2358 records, the full texts of 81 manuscripts were retrieved, of which 45 met the inclusion criteria. We identified three main categories of outcome measure specific to perioperative pulmonary outcomes: (i) composite outcome measures of multiple pulmonary outcomes (27 definitions); (ii) pneumonia (12 definitions); and (iii) respiratory failure (six definitions). These were rated by the group according to suitability for routine use. The majority of definitions were given a low score, and many were imprecise, difficult to apply consistently, or both, in large patient populations. A small number of highly rated definitions were identified as appropriate for widespread use. The group then recommended four outcome measures for future use, including one new definition.Conclusions: A large number of postoperative pulmonary outcome measures have been used, but most are poorly defined. Our four recommended outcome measures include a new definition of postoperative pulmonary complications, incorporating an assessment of severity. These definitions will meet the needs of most clinical effectiveness trials of treatments to improve postoperative pulmonary outcomes.

ESPITE more than half a century of investigation,acute kidney injury (AKI) remains a major healthcareissue in medicine today. Reported to occur in 1–32% of allhospital admissions and 10–90% of intensive care unit ad-missions, the wide variation reflects different criteria used todefineAKI.However,independentofdefinition,adiagnosisof AKI is consistently associated with an increase in bothshort- and long-term morbidity and mortality. Even themildest forms of AKI are independently associated with in-creased early as well as long-term mortality, the risk increas-ing as severity of renal injury increases.

Background Although hypothermia and barbiturates improve neurologic outcomes in animal temporary focal ischemia models, the clinical efficacy of these interventions during temporary occlusion of the cerebral vasculature during intracranial aneurysm surgery (temporary clipping) is not established. Methods A post hoc analysis of patients from the Intraoperative Hypothermia for Aneurysm Surgery Trial who underwent temporary clipping was performed. Univariate and multivariate logistic regression methods were used to test for associations between hypothermia, supplemental protective drug, and short- (24-h) and long-term (3-month) neurologic outcomes. An odds ratio more than 1 denotes better outcome. Results Patients undergoing temporary clipping (n = 441) were assigned to intraoperative hypothermia (33.3 degrees +/- 0.8 degrees C, n = 208) or normothermia (36.7 degrees +/- 0.5 degrees C, n = 233), with 178 patients also receiving supplemental protective drug (thiopental or etomidate) during temporary clipping. Three months after surgery, 278 patients (63%) had good outcome (Glasgow Outcome Score = 1). Neither hypothermia (P = 0.847; odds ratio = 1.043, 95% CI = 0.678-1.606) nor supplemental protective drug (P = 0.835; odds ratio = 1.048, 95% CI = 0.674-1.631) were associated with 3-month Glasgow Outcome Score. The effect of supplemental protective drug did not significantly vary with temperature. The effects of hypothermia and protective drug did not significantly vary with temporary clip duration. Similar findings were made for 24-h neurologic status and 3-month Neuropsychological Composite Score. Conclusion In the Intraoperative Hypothermia for Aneurysm Surgery Trial, neither systemic hypothermia nor supplemental protective drug affected short- or long-term neurologic outcomes of patients undergoing temporary clipping.

While conventional practice is to discontinue aspirin prior to elective cardiac surgery there is evidence that its continuation may be associated with improved perioperative outcomes. However, uncertainty exists regarding the efficacy of antifibrinolytic agents in the presence of aspirin. We performed a systematic review and meta-analysis of the literature to address the question of the effects of antifibrinolytic agents in cardiac surgery patients maintained on aspirin in terms of both efficacy and adverse events. We conducted an extensive search for randomized controlled trials of antifibrinolytic use in adult patients undergoing coronary artery bypass grafting +/- valve surgery, where aspirin therapy was maintained or initiated through the preoperative period. Data from 17 trials (n=1620) confirmed the efficacy of antifibrinolytic therapy to reduce both chest-tube drainage (weighted mean difference 374 ml, 95% CI 275-473 ml; P0.00001) and blood transfusion requirements (odds ratio 0.37, 95% CI 0.27-0.49; P0.00001) in cardiac surgical patients receiving aspirin. We found no difference in the rates of adverse events between groups but observed a trend towards a reduced risk for the composite outcome of thrombotic complications (odds ratio 0.49, 95% CI 0.21-1.13; P=0.09). Antifibrinolytic agents are effective for reducing both chest-tube drainage and transfusion requirements in cardiac surgical patients receiving aspirin. We found no difference between antifibrinolytic and placebo in terms of adverse events but the population was predominantly low-risk. Further studies are required to determine the optimal balance between antiplatelet and antifibrinolytic effects in cardiac surgery.

Objectives To characterize existing practice patterns for intraoperative evaluation and grading of diastolic dysfunction in patients undergoing cardiac surgery. Design A 14-question, multiple-choice survey of current practice for patients with diastolic dysfunction and the use of intraoperative transesophageal echocardiography (TEE) to evaluate, grade, and monitor changes in diastolic function. Setting Online survey. Participants Members of the Society of Cardiovascular Anesthesiologists. Interventions None. Measurements and Main Results Of 515 respondents, there was a near-even spread between those based in an academic setting (53%) and those based in private practice (43%). Most respondents (81%) had completed training with certification in TEE. Most respondents (86%) currently modified their intraoperative management, at least some of the time, if they believed a patient was experiencing diastolic dysfunction, with 72% varying the nature of any modification according to the identified grade of diastolic dysfunction. Although 62% of respondents usually evaluated diastolic dysfunction in the pre-bypass period, only 59% of those evaluating diastolic dysfunction typically graded the dysfunction, with a variety of algorithms used for this purpose. The majority of respondents (62%) typically did not re-evaluate diastolic function using TEE in the post-bypass period. In 2 sample patients with Doppler data provided, there was marked variation in grading of diastolic dysfunction by respondents; this variation remained marked even within subgroups of respondents who typically used the same grading algorithm. Conclusions Marked variation currently exists in how intraoperative TEE is used to evaluate, grade, and monitor diastolic function during cardiac surgery. This suggests clinically important knowledge gaps that should be addressed.

Background We assessed associations between intraoperative neuraxial block and postoperative epidural analgesia, and a composite primary outcome of death or non-fatal myocardial infarction, at 30 days post-randomization in POISE-2 Trial subjects. Methods 10 010 high-risk noncardiac surgical patients were randomized aspirin or placebo and clonidine or placebo. Neuraxial block was defined as intraoperative spinal anaesthesia, or thoracic or lumbar epidural anaesthesia. Postoperative epidural analgesia was defined as postoperative epidural local anaesthetic and/or opioid administration. We used logistic regression with weighting using estimated propensity scores. Results Neuraxial block was not associated with the primary outcome [7.5% vs 6.5%; odds ratio (OR), 0.89; 95% CI (confidence interval), 0.73–1.08; P +0.24], death (1.0% vs 1.4%; OR, 0.84; 95% CI, 0.53–1.35; P +0.48), myocardial infarction (6.9% vs 5.5%; OR, 0.91; 95% CI, 0.74–1.12; P +0.36) or stroke (0.3% vs 0.4%; OR, 1.05; 95% CI, 0.44–2.49; P +0.91). Neuraxial block was associated with less clinically important hypotension (39% vs 46%; OR, 0.90; 95% CI, 0.81–1.00; P +0.04). Postoperative epidural analgesia was not associated with the primary outcome (11.8% vs 6.2%; OR, 1.48; 95% CI, 0.89–2.48; P +0.13), death (1.3% vs 0.8%; OR, 0.84; 95% CI, 0.35–1.99; P +0.68], myocardial infarction (11.0% vs 5.7%; OR, 1.53; 95% CI, 0.90–2.61; P +0.11], stroke (0.4% vs 0.4%; OR, 0.65; 95% CI, 0.18–2.32; P +0.50] or clinically important hypotension (63% vs 36%; OR, 1.40; 95% CI, 0.95–2.09; P +0.09). Conclusions Neuraxial block and postoperative epidural analgesia were not associated with adverse cardiovascular outcomes among POISE-2 subjects.

Background Aspirin administration before cardiac surgery represents a balance between preventing perioperative thrombotic events and promoting surgical bleeding. Clear evidence to guide the preoperative use of aspirin in patients undergoing cardiac surgery is lacking. This systematic review and meta-analysis was performed to evaluate the efficacy and safety of preoperative aspirin, in patients undergoing coronary artery surgery. Methods We conducted a systematic review and meta-analysis of randomized trials involving patients undergoing coronary artery surgery assigned to preoperative aspirin therapy or no aspirin/placebo. The MEDLINE and EMBASE databases and Cochrane Central Register of Controlled Trials were searched up to March 2014 without language restrictions. Two reviewers performed independent quality review and data extraction. Efficacy outcomes of myocardial infarction (MI) and mortality, and safety outcomes of blood loss, red cell transfusion, and surgical re-exploration were compared. Results In 13 trials (n=2399), preoperative aspirin therapy reduced the risk of MI (OR, 0.56; 95% CI, 0.33–0.96; P=0.03), without a reduction in mortality (OR, 1.16; 95% CI, 0.42–3.22; P=0.77). Preoperative aspirin increased postoperative chest tube drainage (mean difference 168 ml; 95% CI, 39–297 ml; P=0.01), red cell transfusion (mean difference 141 ml; 95% CI, 55–226; P=0.001) and need for surgical re-exploration (OR, 1.85, 95% CI, 1.15–2.96; P=0.01). Studies were of low methodological quality, with significant heterogeneity identified. Conclusions In patients undergoing coronary artery surgery, preoperative aspirin reduces perioperative MI, but at a cost of increased bleeding, blood transfusion, and surgical re-exploration.

Background Bispectral index (BIS) monitoring is commonly used to decrease the risk of awareness during anaesthesia. We aimed to determine the relationship between blood alcohol concentration and brain function (as measured by BIS) in healthy adults. Methods In this prospective observational study, 21 anaesthetic registrars self-regulated alcohol consumption over a 3-h period. Expired alcohol concentration (breathalyser) and BIS measurements were performed hourly for 4 h. A venous blood alcohol sample was taken at the conclusion of the study period. Results The main outcome measures were the correlation between blood alcohol and brain function as measured by BIS and the change in BIS from baseline (∆BIS) at 4 h. The median number of standard drinks consumed was 9.1 (IQR 7.7–12.3), range 5.4–17. At 4 h, there was a moderate inverse correlation between BIS and blood alcohol (r = −0.49, P = 0.029) and between ∆BIS and blood alcohol (r = −0.46, P =0.043). Conclusion In healthy young adults, we found a moderate correlation between venous blood alcohol concentration and BIS. This suggests that acute alcohol consumption can decrease BIS. This information may be relevant when providing anaesthesia to intoxicated patients who require urgent or time-critical surgery, although certain limitations of this study should be kept in mind.

maintained with a propofol infusion. A TEE probe was inserted as part of the routine monitoring in lung transplantation. Because of surgical concerns about bleeding, aprotinin, 2 million units (KIU), were given intravenously, followed by an infusion of 500,000 KIU/h. Seven thousand five hundred units of heparin were administered before clamping the right pulmonary vessels. Coagulation was not monitored further at this stage. The transplanted right lung was reperfused without incident. No further heparin was administered for clamping of the left hilar vessels because the surgeons were concerned by the amount of bleeding. It was 5 hours after the initial dose of heparin when the left lung was reperfused. The patient was hemodynamically stable, with normal pulmonary artery pressures (26/15 mmHg), and adequate compliance of the new lungs. However, with clinical concerns regarding ongoing bleeding and an abnormal coagulation profile (international normalized ratio 1.7, activated partial thromboplastin time 117 seconds, platelet count 170 10 9 /mm 3 , fibrinogen 1.8 mg/dL), 50 mg of protamine was administered along with a unit of fresh frozen plasma. At this time, TEE showed a long, narrow, and highly mobile echogenic mass, consistent with thrombus, arising out of the left upper pulmonary vein (LUPV), extending into the left atrium (LA), and crossing the mitral valve in diastole (Fig 1, Video 1 [supplementary videos accompanying this article are available online]). It measured 50 to 55 mm in length and was up to 7 mm wide but occupied less than 50% of the pulmonary vein diameter (Fig 2, Video 2). The residual pulmonary vein diameter was 1.1 cm, and color-flow Doppler did not show turbulent flow at the anastomosis. The other 3 pulmonary veins appeared normal. After the administration of 25,000 U of heparin, cardiopulmonary bypass (CPB) was initiated, the ascending aorta cross-clamped, and a single dose of antegrade cardioplegia given. The large thrombus originating in the LUPV was removed through a left atriotomy. Both left atrial anastomoses and all 4 pulmonary veins were inspected and appeared patent and normal. The aortic cross-clamp was removed, spontaneous cardiac rhythm resumed, and the patient was successfully weaned from CPB with the help of norepinephrine, 0.02 g/kg/min. Hemodynamics remained stable, with a pulmonary artery pressure of 31/17 mmHg, a cardiac index of 3.4 L/min/m 2 , arterial pO2 of 110 mmHg with an inspired oxygen concentration of 60% (FIO2 0.6), and good lung compliance. The patient was transferred to the intensive care unit, intubated, and ventilated, where he had an uncom

Fast-track cardiac anesthesia (FTCA) incorporates early tracheal extubation, decreased length of intensive care unit (ICU) and hospital stay, and (ideally) should avoid or reduce complications to safely achieve cost-savings. A growing body of evidence from randomized trials has identified many anesthetic interventions that can improve outcome after cardiac surgery. These include new short-acting hypnotic, opioid, and neuromuscular blocking drugs. An effective FTCA program requires the appropriate selection of suitable patients, a lowdose opioid anesthetic technique, early tracheal extubation, a short stay in the ICU, and coordinated perioperative care. It is also dependent on the avoidance of postoperative complications such as excessive bleeding, myocardial ischemia, low cardiac output state, arrhythmias, sepsis, and renal failure. These complications will have a much greater adverse effect on hospital length of stay and healthcare costs. A number of clinical trials have identified interventions that can reduce some of these complications. The adoption of effective treatments into clinical practice should improve the effectiveness of FTCA.

Background: Smoking is considered to be a risk factor for patients undergoing surgery and anesthesia, but it is unclear whether this is applicable to patients undergoing ambulatory surgery. The aim of this study was to determine the risk of respiratory complications and wound infection among smokers. Methods: The authors studied a random selection of 489 adult patients undergoing ambulatory surgery. Smoking status was determined by self-report and confirmed with end-expired carbon monoxide analysis. The risk of respiratory complications (i.e., desaturation, cough, laryngospasm, bronchospasm, breath-holding, or apnea) and wound infection (i.e., wound redness or discharge positive microbial culture, requiring antibiotic therapy) in smokers versus nonsmokers was ascertained. Odds ratios were estimated from multivariable logistic regression and adjusted for age, gender, body mass index, partner’s smoking status, domiciliary smoking exposure, and extent and duration of surgery. Results: Most smokers continued to smoke up until the day of surgery. Smokers had a higher rate of respiratory complications (32.8% vs. 25.9%; adjusted odds ratio, 1.71; 95% confidence interval, 1.03‐2.84; P 0.038) and wound infection (3.6% vs. 0.6%; odds ratio, 16.3; 95% confidence interval, 1.58‐175; P 0.019). Odds ratios comparing current plus ex-smokers with nonsmokers were of similar magnitude for most of these complications. Conclusions: Smoking was associated with an increased risk of respiratory complications and postoperative wound infection in ambulatory surgery patients. These findings warrant increased efforts at promoting smoking avoidance and cessation. SMOKING is a major health risk, with just under 20% of all deaths in developed countries attributed to tobacco. 1 It is also generally accepted that smoking increases the risk of complications in patients undergoing anesthesia and surgery. 2–11 Despite this, it is our experience, and that of others, 12 that recommendations to stop smoking before elective surgery are rarely heeded. Most previous studies of perioperative risk associated with smoking were based on self-reporting and did not control for additional risk factors. Also, they may not represent current surgical and anesthetic practice. For example, there has been a marked increase in the proportion of surgery performed on an ambulatory (daystay) basis, and this important group has not been previously studied. We therefore studied a broad range of patients undergoing ambulatory surgery and confirmed their smoking status with end-expired carbon monoxide (COexp) analysis.

ObjectiveTo evaluate ‘days at home up to 30 days after surgery’ (DAH30) as a patient-centred outcome measure.DesignProspective cohort study.Data sourceUsing clinical trial data (seven trials, 2109 patients) we calculated DAH30from length of stay, readmission, discharge destination and death up to 30 days after surgery.Main outcomeThe association between DAH30and serious complications after surgery.ResultsOne or more complications occurred in 263 of 1846 (14.2%) patients, including 19 (1.0%) deaths within 30 days of surgery; 245 (11.6%) patients were discharged to a rehabilitation facility and 150 (7.1%) were readmitted to hospital within 30 days of surgery. The median DAH30was significantly less in older patients (pConclusionsDAH30has construct validity and is a readily obtainable generic patient-centred outcome measure. It is a pragmatic outcome measure for perioperative clinical trials.

Extra corporeal membrane oxygenation (ECMO) is a rescue therapy for reversible cardiac and/or respiratory failure. Despite improvement in management of patients undergoing ECMO, mortality remains high. Due to thrombosis risk, which includes arterial and venous thrombosis as well as in the extracorporeal circuit and components, variable intensity systemic anticoagulation with unfractionated heparin is routinely used. However, bleeding is one of the most frequent complications, can be severe and is independently associated with worse outcomes. Optimal anticoagulation to prevent thrombosis whilst minimising bleeding in adults on ECMO remains unknown. Before conducting a large randomised controlled trial to determine whether lower anticoagulation intensity is safe and effective compared with therapeutic anticoagulation, we aimed to determine the feasibility of randomising ECMO patients to these anticoagulation protocols. Methods: The HELP-ECMO pilot study (ACTRN12613001324707) is a randomised, controlled, unblinded trial at two Australian intensive care units (ICUs). Inclusion criteria were ICU patients who required ECMO (venous-venous [VV] or venous-arterial [VA]). Patients who did not meet any exclusion criteria were randomised to receive either therapeutic anticoagulation with heparin (target activated partial thromboplastin time [aPTT] between 50 and 70 seconds) or low dose heparin (12000 units/24 hours aiming for aPTT Results: Between May 2014 and March 2016, 31 patients who underwent ECMO (9 (29%) VA and 22 (71%) VV) were enrolled; 16 were randomised to low dose and 15 to therapeutic dose heparin. The groups were similar in age (mean 41 years [SD 16.8] vs 43 [SD 17.6] p=0.75), gender (68% vs 80% male, p=0.47), type of ECMO (31% vs 27% VA, p=0.78) and Acute Physiology and Chronic Health Evaluation III illness severity score (mean 65.4 [SD 23.5] vs 61.8 [SD 30.1], p=0.72) and sepsis-related organ failure assessment score (mean 10 [SD 3.6] vs 10 [SD 3.3], p=1.0). The mean duration of ECMO support was 9.33 days (SD 5.97) in the low dose and 9.79 days (SD 4.77) in the therapeutic dose group (p=0.82). For the primary outcomes, there was a significant difference in the daily mean aPTT (48.1 [95% CI 43.5-53.3] vs 56.2 [95% CI 50.7-62.3], p=0.03), daily mean anti-Xa (0.11 [95% CI 0.07-0.18] vs 0.30 [IQR 0.19-0.46], p=0.003) and daily mean heparin dose (11784 units [95% CI 8693-15972] vs 22050 [IQR 16262-29899], p=0.004) in the low dose compared to therapeutic group. There was no difference in thrombotic complications with regard to DVT (2 [12.5%] vs 3 [20%], p=0.57), PE (1 [6.3%] vs 0 [0%], p=0.33), stroke (no events), intracardiac thrombus (1 [6.3%] vs 2 [13.3%], p=0.51), acute pump (1 [6.3%] vs 1[6.7%], p=0.96) and distal perfusion cannula thrombosis (2 [12.5%] vs 0 [0%], p=0.16) in low dose compared with therapeutic group, respectively. With regard to bleeding, there was no difference in intracranial haemorrhage (ICH) (0 [0%] vs 1 [6.7%], p=0.29), retroperitoneal bleeding (1 [6.3%] vs 1 [6.7%], p=0.96), gastrointestinal bleeding (0 [0%] vs 2 [13.3%] , p=0.13), or haemoptysis (1 [6.5%] vs 1 [6.7%], p=0.96) in low dose compared with therapeutic group, respectively. Conclusion: In this pilot trial, administration of a low dose heparin protocol was feasible, and resulted in a significant difference in mean heparin dose administered and daily aPTT and anti-Xa levels between groups. Low dose heparin was not associated with an increase in thrombotic events nor a decrease in bleeding events; however the study was not powered for these outcomes. Our findings support the feasibility of a larger phase III study to evaluate the safety and efficacy of low-dose anticoagulation compared with therapeutic heparin with regard to thrombotic and bleeding events in patients receiving ECMO. Disclosures No relevant conflicts of interest to declare.

Background Aspirin administration before cardiac surgery represents a balance between preventing perioperative thrombotic events and promoting surgical bleeding. Clear evidence to guide the preoperative use of aspirin in patients undergoing cardiac surgery is lacking. This systematic review and meta-analysis was performed to evaluate the efficacy and safety of preoperative aspirin, in patients undergoing coronary artery surgery. Methods We conducted a systematic review and meta-analysis of randomized trials involving patients undergoing coronary artery surgery assigned to preoperative aspirin therapy or no aspirin/placebo. The MEDLINE and EMBASE databases and Cochrane Central Register of Controlled Trials were searched up to March 2014 without language restrictions. Two reviewers performed independent quality review and data extraction. Efficacy outcomes of myocardial infarction (MI) and mortality, and safety outcomes of blood loss, red cell transfusion, and surgical re-exploration were compared. Results In 13 trials (n=2399), preoperative aspirin therapy reduced the risk of MI (OR, 0.56; 95% CI, 0.33–0.96; P=0.03), without a reduction in mortality (OR, 1.16; 95% CI, 0.42–3.22; P=0.77). Preoperative aspirin increased postoperative chest tube drainage (mean difference 168 ml; 95% CI, 39–297 ml; P=0.01), red cell transfusion (mean difference 141 ml; 95% CI, 55–226; P=0.001) and need for surgical re-exploration (OR, 1.85, 95% CI, 1.15–2.96; P=0.01). Studies were of low methodological quality, with significant heterogeneity identified. Conclusions In patients undergoing coronary artery surgery, preoperative aspirin reduces perioperative MI, but at a cost of increased bleeding, blood transfusion, and surgical re-exploration.

Positive end-expiratory pressure (PEEP) is a mechanical technique that is often used when ventilating an unconscious patient. The technique involves adding a quantity of pressure into the lungs at the end of each breath. The process of ventilating a patient causes a degree of deflation in the lungs; between breaths the lungs contain less air than usual. By adding positive pressure at that time, we aim to re-inflate the airways. We know that PEEP can improve respiratory function during a general anaesthetic. We do not know whether patients who receive PEEP have a lower risk of postoperative mortality or respiratory complications, such as pneumonia. In this review, we aimed to assess the postoperative benefits and harms of using PEEP during general anaesthesia. After a search of the literature, we found eight randomized clinical trials (RCTs) involving 330 patients. Four trials reported mortality as an outcome. We pooled these data and found no difference between the group of patients who received PEEP and those who did not, but because of the small number of patients, and the fact that this outcome may be rare, these results did not allow us to make a conclusion about the effect of PEEP on mortality. There were two findings that suggested some benefit of PEEP. First, oxygenation was better on the day after surgery in the PEEP group. Second, radiological imaging showed less atelectasis (areas of collapsed lung) after surgery in the PEEP group. We did calculations to predict how many more patients would be needed in order to be able to make reliable conclusions about the application of PEEP on mortality. This number was 21,200. From the studies that we found, there was no suggestion that intraoperative PEEP causes harm. This finding is reassuring but, due to the small numbers, it is inconclusive. There is currently insufficient evidence to make conclusions about how intraoperative PEEP affects postoperative mortality and respiratory complications.