Keyvan Karkouti

Acute Kidney Injury After Cardiac Surgery Focus on Modifiable Risk Factors

Background— Acute kidney injury (AKI) after cardiac surgery is a major health issue. Lacking effective therapies, risk factor modification may offer a means of preventing this complication. The objective of the present study was to identify and determine the prognostic importance of such risk factors. Methods and Results— Data from a multicenter cohort of 3500 adult patients who underwent cardiac surgery at 7 hospitals during 2004 were analyzed (using multivariable logistic regression modeling) to determine the independent relationships between 3 thresholds of AKI (>25%, >50%, and >75% decrease in estimated glomerular filtration rate within 1 week of surgery or need for postoperative dialysis) with death rates, as well as to identify modifiable risk factors for AKI. The 3 thresholds of AKI occurred in 24% (n=829), 7% (n=228), and 3% (n=119) of the cohort, respectively. All 3 thresholds were independently associated with a >4-fold increase in the odds of death and could be predicted with several perioperative variables, including preoperative intra-aortic balloon pump use, urgent surgery, and prolonged cardiopulmonary bypass. In particular, 3 potentially modifiable variables were also independently and strongly associated with AKI. These were preoperative anemia, perioperative red blood cell transfusions, and surgical reexploration. Conclusions— AKI after cardiac surgery is highly prevalent and prognostically important. Therapies aimed at mitigating preoperative anemia, perioperative red blood cell transfusions, and surgical reexploration may offer protection against this complication.

Universal definition of perioperative bleeding in adult cardiac surgery

OBJECTIVES Perioperative bleeding is common among patients undergoing cardiac surgery; however, the definition of perioperative bleeding is variable and lacks standardization. We propose a universal definition for perioperative bleeding (UDPB) in adult cardiac surgery in an attempt to precisely describe and quantify bleeding and to facilitate future investigation into this difficult clinical problem. METHODS The multidisciplinary International Initiative on Haemostasis Management in Cardiac Surgery identified a common definition of perioperative bleeding as an unmet need. The functionality and usefulness of the UDPB for clinical research was then tested using a large single-center, nonselected, cardiac surgical database. RESULTS A multistaged definition for perioperative bleeding was created based on easily measured clinical end points, including total blood loss from chest tubes within 12 hours, allogeneic blood products transfused, surgical reexploration including cardiac tamponade, delayed sternal closure, and the need for salvage treatment. Depending on these components, bleeding is graded as insignificant, mild, moderate, severe, or massive. When applied to an established cardiac surgery dataset, the UDPB provided insight into the incidence and outcome of bleeding after cardiac surgery. CONCLUSIONS The proposed UDPB in adult cardiac surgery provides a precise classification of bleeding that is useful in everyday practice as well as in clinical research. Once fully validated, the UDPB may be useful as an institutional quality measure and serve as an important end point in future cardiac surgical research.

Advance Targeted Transfusion in Anemic Cardiac Surgical Patients for Kidney Protection An Unblinded Randomized Pilot Clinical Trial

Introduction: Acute kidney injury (AKI) is a serious complication of cardiac surgery, and preoperative anemia and perioperative erythrocyte transfusion are important risk factors. Prophylactic erythrocyte transfusion in anemic patients may, therefore, protect against AKI. Methods: In this unblinded, parallel-group, randomized pilot trial, 60 anemic patients (hemoglobin 10–12 g/dL) undergoing cardiac surgery with cardiopulmonary bypass were randomized (1:1) to prophylactic transfusion (2 units of erythrocytes transfused 1 to 2 days before surgery (n = 29) or standard of care (transfusions as indicated; n = 31). Between-group differences in severity of perioperative anemia, transfusion, and AKI (more than 25% drop in estimated glomerular filtration rate) were measured. The relationships between transfusion, iron levels, and AKI were also measured. Results: Perioperative anemia and erythrocyte transfusions were lower in the prophylactic transfusion group – median (25th, 75th percentiles) for nadir hemoglobin was 8.3 (7.9, 9.1) versus 7.6 (6.9, 8.2) g/dL (P = 0.0008) and for transfusion was 0 (0, 2) versus 2 (1, 4) units (P = 0.0002) – but between-group AKI rates were comparable (11 patients per group). In 35 patients with iron studies, perioperative transfusions were directly related to postoperative transferrin saturation (correlation coefficient 0.6; P = 0.0002), and high (more than 80%) transferrin saturation was associated with AKI (5/5 vs. 8/30; P = 0.005), implicating transfusion-related iron overload as a cause of AKI. Conclusions: In anemic patients, prophylactic erythrocyte transfusion reduces perioperative anemia and erythrocyte transfusions, and may reduce plasma iron levels. Adequately powered studies assessing the effect of this intervention on AKI are warranted.

Association of echocardiography before major elective non-cardiac surgery with postoperative survival and length of hospital stay: population based cohort study

Objective To determine the association of resting echocardiography before elective intermediate to high risk non-cardiac surgery with survival and length of hospital stay. Design Population based retrospective cohort study. Setting Acute care hospitals in Ontario, Canada, between 1 April 1999 and 31 March 2008. Participants Patients aged over 40 years who had elective intermediate to high risk non-cardiac surgery. Intervention Resting echocardiography within 6 months before surgery. Main outcome measures Postoperative survival (30 days and 1 year) and length of hospital stay; postoperative surgical site infection as an outcome for which no association with echocardiography would be expected. Results Of the 264 823 patients in the entire cohort, 15.1% (n=40 084) had echocardiography. After use of propensity score methods to assemble a matched cohort (n=70 996) that reduced differences between patients who had or had not had echocardiography, echocardiography was associated with increases in 30 day mortality (relative risk 1.14, 95% confidence interval 1.02 to 1.27), 1 year mortality (1.07, 1.01 to 1.12), and length of hospital stay but no difference in surgical site infections (1.03, 0.98 to 1.06). The association with mortality was influenced (P=0.02) by whether patients had had stress testing or had risk factors for cardiac complications. No association existed between echocardiography and mortality among patients who had stress testing (relative risk 1.01, 0.92 to 1.11) or among patients at high risk who had not had stress testing (1.00, 0.87 to 1.13). However, echocardiography was associated with mortality in patients at low risk (relative risk 1.44, 1.14 to 1.82) and intermediate risk (1.10, 1.02 to 1.18) who had not had stress testing. Conclusions Preoperative echocardiography was not associated with improved survival or shorter hospital stay after major non-cardiac surgery. These findings highlight the need for further research to guide better use of this common preoperative test.

The role of point-of-care platelet function testing in predicting postoperative bleeding following cardiac surgery: a systematic review and meta-analysis†

This systematic review and meta‐analysis appraises the utility of point‐of‐care platelet function tests for predicting blood loss and transfusion requirements in cardiac surgical patients, and analyses whether their use within a transfusion management algorithm is associated with improved patient outcomes. We included 30 observational studies incorporating 3044 patients in the qualitative assessment, and nine randomised controlled trials including 1057 patients in the meta‐analysis. Platelet function tests demonstrated significant variability in their ability to predict blood loss and transfusion requirements. Their use within a blood transfusion algorithm demonstrated a reduction in blood loss at longest follow‐up (mean difference −102.9 ml (95% CI −149.9 to −56.1 ml), p < 0.001), and transfusion of packed red cells (RR 0.86 (95% CI 0.78−0.94), p = 0.001) and fresh frozen plasma (RR 0.42 (95% CI 0.30−0.59), p < 0.001). Viscoelastic methods used in combination with other platelet function tests achieved greater reduction in blood loss (mean difference −111.8 ml (95% CI −174.9 to −49.1 ml), p = 0.0005) compared with their use alone (mean difference −90.6 ml (95% CI 166.1−15.0 ml), p = 0.02). We conclude that incorporation of point‐of‐care platelet function tests into transfusion management algorithms is associated with a reduction in blood loss and transfusion requirements in cardiac surgery patients.

The pathophysiology and consequences of red blood cell storage

Red cell transfusion therapy is a common treatment modality in contemporary medical practice. Although blood collection and administration is safer and more efficient than ever before, red cells undergo multiple metabolic and structural changes during storage that may compromise their functionality and viability following transfusion. The clinical relevance of these changes is a hotly debated topic that continues to be a matter of intense investigation. In the current review, we begin with an in‐depth overview of the pathophysiological mechanisms underlying red cell storage, with a focus on altered metabolism, oxidative stress and red cell membrane damage. We proceed to review the current state of evidence on the clinical relevance and consequences of the red cell storage lesion, while discussing the strengths and limitations of clinical studies.

Evaluation of a novel transfusion algorithm employing point-of-care coagulation assays in cardiac surgery: a retrospective cohort study with interrupted time-series analysis.

Background:Cardiac surgery requiring the use of cardiopulmonary bypass is frequently complicated by coagulopathic bleeding that, largely due to the shortcomings of conventional coagulation tests, is difficult to manage. This study evaluated a novel transfusion algorithm that uses point-of-care coagulation testing. Methods:Consecutive patients who underwent cardiac surgery with bypass at one hospital before (January 1, 2012 to January 6, 2013) and after (January 7, 2013 to December 13, 2013) institution of an algorithm that used the results of point-of-care testing (ROTEM®; Tem International GmBH, Munich, Germany; Plateletworks®; Helena Laboratories, Beaumont, TX) during bypass to guide management of coagulopathy were included. Pre- and postalgorithm outcomes were compared using interrupted time-series analysis to control for secular time trends and other confounders. Results:Pre- and postalgorithm groups included 1,311 and 1,170 patients, respectively. Transfusion rates for all blood products (except for cryoprecipitate, which did not change) were decreased after algorithm institution. After controlling for secular pre- and postalgorithm time trends and potential confounders, the posttransfusion odds ratios (95% CIs) for erythrocytes, platelets, and plasma were 0.50 (0.32 to 0.77), 0.22 (0.13 to 0.37), and 0.20 (0.12 to 0.34), respectively. There were no indications that the algorithm worsened any of the measured processes of care or outcomes. Conclusions:Institution of a transfusion algorithm based on point-of-care testing was associated with reduced transfusions. This suggests that the algorithm could improve the management of the many patients who develop coagulopathic bleeding after cardiac surgery. The generalizability of the findings needs to be confirmed.

Validity of Thromboelastometry for Rapid Assessment of Fibrinogen Levels in Heparinized Samples During Cardiac Surgery: A Retrospective, Single-center, Observational Study

OBJECTIVE To assess the validity of fibrinogen assay of rotational thromboelastometry (FIBTEM)-derived estimates of fibrinogen in samples collected during cardiopulmonary bypass in cardiac surgical patients by comparison to Clauss method fibrinogen concentration. DESIGN Retrospective observational study. SETTING Single university hospital center. PARTICIPANTS Human participants. INTERVENTIONS Retrospectively obtained laboratory assays including rotational thromboelastometry (ROTEM) and Clauss fibrinogen assay. MEASUREMENTS AND MAIN RESULTS A retrospective review was performed of anesthesia records at a single university teaching hospital during a 1-year period. From paired samples taken near the end of cardiopulmonary bypass, fibrinogen concentrations (Clauss method) were compared with FIBTEM-derived measures of maximal clot firmness (MCF) and clot amplitude at 10 minutes (A10) using Spearmans rank correlation, linear regression, and receiver operating characteristic curve analysis. The study included 1,077 patients. Clauss fibrinogen was correlated strongly with FIBTEM amplitudes (r = 0.78 for MCF and A10; p<0.01). The correlation was related inversely to hemoglobin concentration (p<0.01). The area under the receiver operating characteristic curve was 0.95; the optimal FIBTEM A10 cutoff for diagnosis of a fibrinogen concentration of<1.5 g/L was ≤8 mm. CONCLUSIONS The FIBTEM was a valid point-of-care method for estimating the fibrinogen concentration during cardiopulmonary bypass and may be used for prediction of hypofibrinogenemia before separation from the extracorporeal circuit.

A systematic review and consensus definitions for standardised end-points in perioperative medicine: pulmonary complications

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.

Systematic review and consensus definitions for standardised endpoints in perioperative medicine: postoperative cancer outcomes

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.