Can We Better Differentiate Type A Dissections: Evaluating the Role of Aortic Ratios.

OBJECTIVES: Type A aortic dissection (ATAAD) is hypothesised as a progression of aneurysmal dilation, but 60% of patients in the International Registry of Acute Aortic Dissection (iRAD) registry had a maximum aortic diameter (MAD)<55 mm. We aim to demonstrate that size ratios and aortic wall stress, assessed using a simplified markers, are unique to aortic patients who have had adverse events (ATAAD) compared to those who have not (thoracic aortic aneurysm [TAA]). METHODS: A retrospective cohort analysis of patients who underwent aortic intervention at Waikato Hospital, New Zealand between 2015-2020, comparing dissection (ATAAD) to TAA patients. MAD; ratio of MAD to standardised-points within the aorta; and MAD-to-height collected from computed tomography (CT)-scans of all patients was undertaken. Receiver operating characteristic (ROC)-analysis to determine cut-off point for each marker was undertaken together with multivariable logistic regression comparing both cohorts, cross-validated by propensity-score matched analysis. RESULTS: Cohort of 215 patients, 78 (36.3%) ATAAD and 137 (63.7%) TAA; median age at intervention 63.3 years, 52 (24.2%) females, both cohorts matched for size. Using the entire cohort, the MAD: sinus of Valsalva (SoV) ratio>1.06 (cut-off value) had 4.5-times greater association with ATAAD (95%CI 1.46-13.8) and a 0.1-unit increased conferred 1.45-times greater association with ATAAD (95%CI 1.00-2.08). MAD>55 mm only seen in 33.3% of ATAAD (n=26/78), and not associated with ATAAD (OR 1.88, 95%CI 0.64-5.51). Compared to MAD, MAD:SoV ratio had greater sensitivity (33% vs 73%), lower number-needed-to-treat (17.9 vs 2.7) and superior discrimination (area under the curve [AUC] 0.54 vs 0.71). Findings were consistent with propensity score matched analysis. CONCLUSIONS: MAD:SoV ratio significantly correlates with ATAAD (4.5 times), with superior sensitivity, discrimination, and attributable-risk-percentage compared to MAD alone.

Vascular endothelial cell changes in postcardiac surgery acute kidney injury.

Acute kidney injury (AKI) is common complication of cardiac surgery; however, the phenotype of this condition is poorly defined. The aim of this study was to characterize changes in endothelial structure and function that underlie postcardiopulmonary bypass (post-CPB) AKI. Adult pigs ( n = 16) were randomized to undergo the following procedures ( n = 8 per group): group 1: sham operation, neck dissection with 2.5 h of general anesthesia; and group 2: CPB, 2.5 h of cardiopulmonary bypass. CPB resulted in the depletion of specific epitopes of glycosaminoglycans side chains of the endothelial glycocalyx: Dolichos biflorus agglutinin: mean difference (MD) [95% confidence interval (CI)], P value: -0.26 (-0.42, -0.09), P = 0.0024, Triticum vulgaris (wheat germ) agglutinin: -0.83 (-1.2, -0.38), P = 0.0005, and Ulex europaeus agglutinin 1: -0.25 (-0.49, -0.009), P = 0.041; endothelial membrane protein: thrombomodulin: -3.13 (-5.6, -0.65), P = 0.02; and adherens junction: VE-cadherin: -1.06 (-1.98, -0.145), P = 0.02. CPB also resulted in reductions in microvascular cortical perfusion: -0.62 (-1.02, -0.22), P = 0.006, and increased renal cortex adenosine levels: 2.32 (0.83, 3.8), P = 0.0059. These changes were accompanied by significant reduction in creatinine clearance at 1.5 h postintervention, MD 95% CI; -51.7 (-99.7, -3.7), P = 0.037, and at 24 h, MD (95% CI): -47.3 (-87.7, -7.6), P = 0.023, and proteinuria immediately postintervention MD (95% CI): 18.79 (2.17, 35.4), P = 0.03 vs. sham. In our experimental CPB model, endothelial injury was associated with loss of autoregulation, increase in microvascular permeability, and reduced glomerular filtration. Interventions that promote endothelial homeostasis may have clinical utility in the prevention of postcardiac surgery AKI.

A Comparison of Red Cell Rejuvenation versus Mechanical Washing for the Prevention of Transfusion-associated Organ Injury in Swine.

BACKGROUND: We evaluated the effects of two interventions that modify the red cell storage lesion on kidney and lung injury in experimental models of transfusion. METHODS: White-landrace pigs (n = 32) were allocated to receive sham transfusion (crystalloid), 14-day stored allogeneic red cells, 14-day red cells washed using the red cells washing/salvage system (CATS; Fresenius, Germany), or 14-day red cells rejuvenated using the inosine solution (Rejuvesol solution; Zimmer Biomet, USA) and washed using the CATS device. Functional, biochemical, and histologic markers of organ injury were assessed for up to 24 h posttransfusion. RESULTS: Transfusion of 14 day red cells resulted in lung injury (lung injury score vs. sham, mean difference -0.3 (95% CI, -0.6 to -0.1; P = 0.02), pulmonary endothelial dysfunction, and tissue leukocyte sequestration. Mechanical washing reduced red cell-derived microvesicles but increased cell-free hemoglobin in 14-day red cell units. Transfusion of washed red cells reduced leukocyte sequestration but did not reduce the lung injury score (mean difference -0.2; 95% CI, -0.5 to 0.1; P = 0.19) relative to 14-day cells. Transfusion of washed red cells also increased endothelial activation and kidney injury. Rejuvenation restored adenosine triphosphate to that of fresh red cells and reduced microvesicle concentrations without increasing cell-free hemoglobin release. Transfusion of rejuvenated red cells reduced plasma cell-free hemoglobin, leukocyte sequestration, and endothelial dysfunction in recipients and reduced lung and kidney injury relative to 14-day or washed 14-day cells. CONCLUSIONS: Reversal of the red cell storage lesion by rejuvenation reduces transfusion-associated organ injury in swine.

Changes in renal medulla gene expression in a pre-clinical model of post cardiopulmonary bypass acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication of cardiac surgery using cardiopulmonary bypass (CPB). The pathogenesis is poorly understood and the study of AKI in rodent models has not led to improvements in clinical outcomes. We sought to determine the changes in renal medullary gene expression in a novel and clinically relevant porcine model of CPB-induced AKI. RESULTS: Adult pigs (n = 12 per group) were randomised to undergo sham procedure, or 2.5 hours CPB. AKI was determined using biochemical (Cr51 EDTA clearance, CrCl, urinary IL-18 release) and histological measures. Transcriptomic analyses were performed on renal medulla biopsies obtained 24 hours post intervention or from sham group. Microarray results were validated with real-time polymerase chain reaction and Western Blotting.Of the transcripts examined, 66 were identified as differentially expressed in CPB versus Sham pig's kidney samples, with 19 (29%) upregulated and 47 (71%) down-regulated. Out of the upregulated and downregulated transcripts 4 and 16 respectively were expression sequence tags (EST). The regulated genes clustered into three classes; Immune response, Cell adhesion/extracellular matrix and metabolic process. Upregulated genes included Factor V, SLC16A3 and CKMT2 whereas downregulated genes included GST, CPE, MMP7 and SELL. CONCLUSION: Post CPB AKI, as defined by clinical criteria, is characterised by molecular changes in renal medulla that are associated with both injury and survival programmes. Our observations highlight the value of large animal models in AKI research and provide insights into the failure of findings in rodent models to translate into clinical progress.

Interactions of cardiopulmonary bypass and erythrocyte transfusion in the pathogenesis of pulmonary dysfunction in Swine.

BACKGROUND: Allogeneic erythrocyte transfusion in cardiac surgical patients is associated with a fourfold increase in pulmonary complications. Our understanding of the processes underlying these observations is poor and there is no experimental model of transfusion-related acute lung injury that shows homology to cardiac surgical patients. Our objective was to develop a novel swine recovery model to determine how two clinical risk factors, allogenic erythrocyte transfusion and cardiopulmonary bypass, interact in the genesis of postcardiac surgery acute lung injury. METHODS: Thirty-six pigs were infused with allogeneic 14- or 42-day-old erythrocytes or they underwent cardiopulmonary bypass with or without transfusion of 42-day erythrocyte. Controls received saline. All pigs were recovered and assessed for pulmonary dysfunction, inflammation, and endothelial activation at 24 h. RESULTS: Transfusion of stored allogeneic erythrocytes in pigs compared with sham caused pulmonary dysfunction characterized by reduced lung compliance (mean difference -3.36 [95% CI, -5.31 to -1.42] ml/cm H2O), an increase in protein levels in bronchoalveolar lavage fluid, histological lung injury inflammation, and endothelial activation. Transfusion of blood stored for up to 42 days resulted in greater protein levels in bronchoalveolar lavage fluid, macrophage infiltration, platelet activation, and depletion of T-lymphocytes in recipient lungs versus 14-day-old blood. Transfusion interacted with cardiopulmonary bypass to increase lung injury in the absence of platelet activation. CONCLUSIONS: In this novel large animal model of allogeneic erythrocyte transfusion, pulmonary dysfunction occurs in the absence of any priming event, is increased when combined with other inflammatory stimuli, and is mediated by monocyte activation and T-lymphocyte depletion.

High fat feeding promotes obesity and renal inflammation and protects against post cardiopulmonary bypass acute kidney injury in swine.

INTRODUCTION: Obesity confers a survival advantage in the critically ill and in patients undergoing cardiac surgery. We explored whether an obesogenic high fat diet could confer protection against post cardiopulmonary bypass (CPB) acute kidney injury (AKI) in a swine model. METHODS: In this study, 28 anaesthetised adult female Landrace White swine (55 to 70 kg) were allocated into a 4 group design to either 2.5 hours of CPB or Sham operation with or without pre-procedural high fat (HF) feeding containing 15% lard, 1.5% cholesterol and 1% cholic acid for 12-weeks (Groups: Sham, CPB, CPB + HF and Sham + HF). Our primary endpoint was creatinine clearance measured at 1.5 and 24 hours post intervention. This is a validated index of the glomerular filtration rate (GFR) in swine and an endpoint used in our clinical studies. Secondary endpoints included measures of systemic and renal inflammation, endothelial homeostasis, tubular injury and dysfunction, and inflammatory cell signalling. Differences between groups were calculated using analysis of variance with adjustment for baseline differences for repeated measures. RESULTS: CPB in pigs fed a normal chow diet resulted in AKI. This was characterised by reductions in GFR sustained for up to 24 hours post injury relative to Sham operated pigs fed a normal diet; mean difference 50.2 ml/min (95% CI 5.9 to 94.4). Post CPB AKI was also characterised by renal inflammation, parallel activation of both pro-inflammatory (NF-kB, iNOS) and pro-survival pathways (pAkt, p70s6k, HIF-1α) and apoptosis. Pigs fed a 12-week high fat diet developed obesity and hyperlipidaemia. This was associated with increased redox sensitive pro-inflammatory and anti-apoptotic signalling, and tubular epithelial cell proliferation. High fat feeding also protected swine against post CPB AKI; mean difference in creatinine clearance CPB - CPB + HF -65.3 ml/min (95% CI -106.9 to -23.7), by preserving endothelial homeostasis and function, and preventing the reductions in GFR, loss of ATP and tubular apoptosis that characterise the extension phase of AKI in swine at 24 hours post injury. Reno-protection was not attributed to pAkt signaling. CONCLUSIONS: A high fat diet promoted obesity and renal inflammation and prevented post CPB AKI in swine. This study provides insights into the obesity paradox and the failure of anti-inflammatory interventions to improve clinical outcomes in patients at risk of post cardiac surgery AKI.

Reversal of anemia with allogenic RBC transfusion prevents post-cardiopulmonary bypass acute kidney injury in swine.

Anemia during cardiopulmonary bypass (CPB) is strongly associated with acute kidney injury in clinical studies; however, reversal of anemia with red blood cell (RBC) transfusions is associated with further renal injury. To understand this paradox, we evaluated the effects of reversal of anemia during CPB with allogenic RBC transfusion in a novel large-animal model of post-cardiac surgery acute kidney injury with significant homology to that observed in cardiac surgery patients. Adult pigs undergoing general anesthesia were allocated to a Sham procedure, CPB alone, Sham+RBC transfusion, or CPB+RBC transfusion, with recovery and reassessment at 24 h. CPB was associated with dilutional anemia and caused acute kidney injury in swine characterized by renal endothelial dysfunction, loss of nitric oxide (NO) bioavailability, vasoconstriction, medullary hypoxia, cortical ATP depletion, glomerular sequestration of activated platelets and inflammatory cells, and proximal tubule epithelial cell stress. RBC transfusion in the absence of CPB also resulted in renal injury. This was characterized by endothelial injury, microvascular endothelial dysfunction, platelet activation, and equivalent cortical tubular epithelial phenotypic changes to those observed in CPB pigs, but occurred in the absence of severe intrarenal vasoconstriction, ATP depletion, or reductions in creatinine clearance. In contrast, reversal of anemia during CPB with RBC transfusion prevented the reductions in creatinine clearance, loss of NO bioavailability, platelet activation, inflammation, and epithelial cell injury attributable to CPB although it did not prevent the development of significant intrarenal vasoconstriction and endothelial dysfunction. In conclusion, contrary to the findings of observational studies in cardiac surgery, RBC transfusion during CPB protects pigs against acute kidney injury. Our study underlines the need for translational research into indications for transfusion and prevention strategies for acute kidney injury.

Prevention of post-cardiopulmonary bypass acute kidney injury by endothelin A receptor blockade.

OBJECTIVE: The aim of this study was to determine whether administration of a specific endothelin A receptor antagonist, sitaxsentan sodium, would prevent the development of post-cardiopulmonary bypass acute kidney injury in swine. DESIGN: Experimental study. SETTING: Cardiovascular Research Institute. INTERVENTIONS: Adult pigs (n = 8 per group) were randomized to undergo a sham procedure, cardiopulmonary bypass, or cardiopulmonary bypass plus administration of endothelin A receptor antagonist (RA), with recovery and reassessment at 24 hrs. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary bypass resulted in a significant reduction in creatinine clearance relative to sham pigs (mean difference for cardiopulmonary bypass vs. sham, -50.3 mL/min [95% confidence interval -89.2 to -11.4 mL/min], p = .008). This was reversed by the administration of endothelin A RA during cardiopulmonary bypass (mean difference for cardiopulmonary bypass + endothelin A RA vs. cardiopulmonary bypass, +43.3 mL/min [95% confidence interval +3.3 to +83.4 mL/min], p = .030). Cardiopulmonary bypass also resulted in a significant rise in the specific urinary biomarker of acute kidney injury interleukin-18 compared to sham procedures (mean difference +209 pg/mL [95% confidence interval +119 to +299 pg/mL], p < .001) that was reversed by endothelin A receptor antagonist administration. Post-cardiopulmonary bypass kidney injury was associated with vascular endothelial injury and dysfunction, reduced nitric oxide bioavailability, inflammation, and a significant increase in the expression of the paracrine vasoconstrictors adenosine and endothelin-1. In post-cardiopulmonary bypass kidneys at 24 hrs there was persistent hypoxia at the level of the outer medulla, cortical adenosine triphosphate depletion, and evidence of proximal tubule epithelial cell stress manifest as phenotypic change. There was no evidence of acute tubular necrosis. Administration of endothelin A RA to cardiopulmonary bypass pigs reversed endothelial dysfunction, regional hypoxia, inflammation, and tubular changes. CONCLUSION: In this model, post-cardiopulmonary bypass acute kidney injury is associated with endothelial dysfunction, regional tissue hypoxia, and proximal tubular epithelial cell stress but not acute tubular necrosis. Antagonism of the endothelin-1 A receptor reversed these changes and may represent a therapeutic target for the prevention of post-cardiac surgery acute kidney injury.

Pharmacological therapies for the prevention of acute kidney injury following cardiac surgery: a systematic review.

Post-cardiac surgery acute kidney injury (AKI) is common and is associated with a significant increase in morbidity and mortality. We aimed to systematically review randomised trials that assessed the renoprotective utility of pharmacological agents in patients undergoing cardiac surgery. We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials comparing renoprotective pharmacological interventions with control in adult patients undergoing cardiac surgery with cardiopulmonary bypass. We extracted data for mortality, need for renal replacement therapy (RRT), incidence of AKI, and creatinine clearance at 24-48 h. About 49 randomised controlled trials involving 4605 patients were included. Pharmacological interventions included dopamine, fenoldopam, calcium channel antagonists, natriuretic peptides, diuretics, and N-acetylcysteine. Most trials were of poor quality, with small sample sizes, under-reporting of randomisation procedure, allocation concealment and method of blinding. No pharmacological intervention significantly reduced mortality. Fenoldopam and Atrial Natriuretic Peptide (ANP) reduced the need for renal replacement therapy by 5% (NNT 20, 95% CI 11.3, 83.0) and 3.5% (NNT 29, 95% CI 17.1, 84.4), respectively. Brain Natriuretic Peptide resulted in a 10% reduction in the incidence of AKI (NNT 11, 95% CI 6.2, 32.0). Dopamine caused a significant reduction in creatinine clearance (-4.26 ml/min, 95% CI -7.14, -1.39). The quality of studies that have assessed pharmacological renoprotective agents in cardiac surgery is generally poor. Fenoldopam, ANP and BNP show evidence of renoprotection. Randomised studies evaluating the effect of novel renoprotective agents that are powered to detect clinically relevant differences in outcomes are required.

Evidence-Based Red Blood Cell Transfusion Practices in Cardiac Surgery.

Cardiac surgical patients are among the highest consumers of allogeneic red blood cells (RBCs) due to the prevalence of anemia and bleeding. Up until recently, there was a paucity of high-quality evidence informing transfusion decisions in this patient group which led to wide variability in transfusion decision making. The article reviews and critically analyzes the available evidence for RBC transfusion in cardiac surgery, focusing on trials of transfusion triggers and age of blood, and provides suggestions for future research. Observational studies analyzing outcomes in patients transfused vs those not transfused have consistently shown RBC transfusion to be associated with adverse outcomes. However, multiple sources of bias in these studies invalidate their conclusions. The best available evidence comes from randomized controlled trials which compare liberal vs restrictive transfusion thresholds. To date, 6 randomized controlled trials have been reported in cardiac surgical patients, and pooled analyses have shown no differences in clinical outcomes between the 2 strategies. Similarly, research into age of RBCs and adverse outcomes has failed to demonstrate a pathological effect attributable to the storage lesion; the recent multicenter Red Cell Storage Duration Study (RECESS) trial has demonstrated no difference in outcomes between patients receiving fresh or old RBCs. Future research needs to identify what a safe transfusion threshold may be, and how this differs for different patient groups and different stages of the perioperative journey. There is also a need to evaluate other physiological parameters which, coupled with hemoglobin concentration, can better inform those patients who need an RBC transfusion.

Long-term survival after off-pump versus on-pump coronary artery bypass graft surgery. Does completeness of revascularization play a role?

BACKGROUND: We sought to compare the incidence of incomplete revascularization (IR) and long-term survival (up to 20years) after off-pump (OPCAB) versus on-pump (ONCAB) coronary artery bypass in a high OPCAB volume centre where OPCAB was introduced in 1996 and has become the preferred strategy over the years. METHODS AND RESULTS: From 1996 to 2015 a total of 7,427 OPCAB and 7128 ONCAB procedures were performed at Bristol Heart Institute, United Kingdom. We obtained 5423 propensity matched pairs for final comparison. Mixed effect Cox model accounting for clustering due to different surgeon was used to investigate the treatment effect on mortality. RESULTS: OPCAB was associated with higher rate of incomplete revascularization 13.3% versus 6.7%; P<0.0001). Mean follow-up time was 7.8±4.6year [max 17.3]. At 12years OPCAB was associated with a marginal but significant +3% increase in overall mortality (67.4%[95%CI 65.8-69.1] vs 64.4%[95%CI 62.7-66.2]; stratified log-rank P=0.03). When compared to ONCAB with complete revascularization, OPCAB with IR (HR 1.74;95%CI 1.53-1.99; P<0.001) and ONCAB with IR (HR 1.29; 95%CI 1.06-1.57; P=0.01) but not OPCAB with complete revascularization (HR 1.02;95%CI 0.94-1.11; P=0.63) were associated with increased risk of late mortality. CONCLUSION: Despite completeness of revascularization was achieved in the majority of OPCAB cases, OPCAB remained associated with a significantly higher rate of incomplete revascularization. This translated into a marginal but significant reduction in late survival rates after OPCAB when compared to ONCAB.

Long-term survival after surgical aortic valve replacement among patients over 65†years of age.

OBJECTIVE: Surgical aortic valve replacement (AVR) remains the gold standard therapy for severe aortic stenosis. Long-term survival data following AVR is required. Our objective was to provide a detailed contemporary benchmark of long-term survival following AVR among elderly patients (≥65 years) in the UK. METHODS: We conducted a retrospective cohort study of 1815 adult patients undergoing surgical AVR± coronary artery bypass graft (CABG) surgery at a single UK centre between 1996 and 2011. Our main outcome was patient survival, which was assessed by linkage to census records at the Office for National Statistics. RESULTS: The mean age of the cohort was 75 (±5.6) years. Patients in the AVR alone group had a slightly higher median survival of 10.9 (95% CI 10.5 to 11.8) years than the AVR+CABG group which had a median survival of 9.6 (95% CI 8.7 to 10.1) years (p=0.001 of log-rank test (LRT) for equality of survivor functions). The presence of chronic kidney disease, severely impaired left ventricular function or being a current smoker were each associated with a ≥50% increased risk of long-term mortality. Comparison of our study cohort patients and the reference (operation year, age and gender matched) UK population suggested no difference in survival probability up to 8 years (p=0.55). However, for longer periods of follow-up, the difference became increasingly significant (p<0.0001). CONCLUSIONS: Long-term survival following surgical AVR in patients over 65 years of age is excellent and up to 8 years is comparable to the matched general population.

Indications for red blood cell transfusion in cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Good blood management is an important determinant of outcome in cardiac surgery. Guidelines recommend restrictive red blood cell transfusion. Our objective was to systematically review the evidence from randomised controlled trials and observational studies that are used to inform transfusion decisions in adult cardiac surgery. METHODS: We did a systematic review by searching PubMed, Embase, Cochrane Library, and DARE, from inception to May 1, 2015, databases from specialist societies, and bibliographies of included studies and recent relevant review articles. We included randomised controlled trials that assessed the effect of liberal versus restrictive red blood cell transfusion in patients undergoing cardiac and non-cardiac surgery, and observational studies that assessed the effect of red blood cell transfusion compared with no transfusion on outcomes in adult cardiac patients after surgery. We pooled adjusted odds ratios using fixed-effects and random-effects meta-analyses. The primary outcome was 30-day mortality. FINDINGS: We included data from six cardiac surgical randomised controlled trials (3352 patients), 19 non-cardiac surgical trials (8361 patients), and 39 observational studies (232,806 patients). The pooled fixed effects mortality odds ratios comparing liberal versus restrictive transfusion thresholds was 0.70 (95% CI 0.49-1.02; p=0.060) for cardiac surgical trials and 1.10 (95% CI 0.96-1.27; p=0.16) for trials in settings other than cardiac surgery. By contrast, observational cohort studies in cardiac surgery showed that red blood cell transfusion compared with no transfusion was associated with substantially higher mortality (random effects odds ratio 2.72, 95% CI 2.11-3.49; p<0.0001) and other morbidity, although with substantial heterogeneity and small study effects. INTERPRETATION: Evidence from randomised controlled trials in cardiac surgery refutes findings from observational studies that liberal thresholds for red blood cell transfusion are associated with a substantially increased risk of mortality and morbidity. Observational studies and trials in non-cardiac surgery should not be used to inform treatment decisions or guidelines for patients having cardiac surgery. FUNDING: None.

Pharmacological strategies for the prevention of acute kidney injury following cardiac surgery: an overview of systematic reviews.

CONTEXT: Post cardiac surgery acute kidney injury (AKI) is common, poorly understood and associated with a significant increase in morbidity and mortality. OBJECTIVES: An overview of systematic reviews that have evaluated pharmacological agents for the prevention of AKI post cardiac surgery. DATA SOURCES: We searched electronic databases (PubMed and the Cochrane Database of Systematic Reviews) from inception to January 2014. STUDY SELECTION: Systematic reviews of randomized controlled trials that have evaluated pharmacological agents for the prevention of AKI in adult patients undergoing cardiac surgery. DATA ANALYSIS: Numbers needed to treat (NNT) or harm (NNH) were calculated from pooled events given in each meta-analysis. Primary outcome measures were defined as (i) mortality, (ii) need for renal replacement therapy (RRT), and (iii) acute kidney injury. RESULTS: Data from 7 systematic reviews evaluating 6 different pharmacological renoprotective agents were included. Dopamine, fenoldopam and N-acetylcysteine did not demonstrate any benefit in terms of mortality, need for RRT or incidence of AKI. Atrial natriuretic peptide reduced the need for RRT (NNT = 22 (95% CI: 13 to 73) and brain natriuretic peptide reduced the incidence of AKI (NNT = 11 (95% CI: 6 to 32), although both agents did not demonstrate any effect on mortality. Loop diuretics demonstrated increased incidence of AKI (NNH = 8 (95% CI: 5 to 15). CONCLUSION: There is a paucity of effective renoprotective agents that can be used in adult cardiac surgical patients. There is an urgent need to develop novel renoprotective strategies.

Patient preference for coronary artery bypass graft surgery performed on the arrested or beating heart: a questionnaire study.

OBJECTIVE: Patient choice is now a major facet of health-care policy within the National Health Service. Our objective was to determine whether the patient would like to choose if the 'beating heart' technique or the 'arrested heart' technique is employed for their coronary artery bypass graft (CABG) surgery. METHODS: We undertook a cross-sectional, self-reported questionnaire survey of patients referred to a regional cardiac surgical unit for elective coronary artery surgery between October 2008 and July 2009. The questionnaire was split into five sections as follows: (1) the patients' awareness of 'beating heart' and 'arrested heart' techniques for CABG surgery, (2) an information sheet detailing both techniques, (3) patients' preference of technique to be used for CABG surgery, (4) whether the patient would like to choose their surgeon according to the surgeons' preferred technique and (5) demographics, including age, sex, and educational qualifications. Data are expressed as counts (percentages). RESULTS: The questionnaire was sent to 120 people; 88 returned a completed questionnaire, representing a response rate of 73%. Awareness of 'beating heart' and 'arrested heart' techniques for CABG surgery was reported by 35 respondents (40%). Of these, 74% respondents had no preference of technique used for CABG surgery. After reading the information sheet, 78 (89%) respondents reported no preference of technique used for CABG surgery. As many as 71 (81%) respondents reported that they did not want to be given an opportunity to choose the technique used for CABG surgery, and all respondents preferred to let the surgeon decide the appropriate technique. A binary logistic regression analysis showed that gender, age and level of education were not significant predictors of whether patients wanted to choose the technique to be used for their CABG surgery. CONCLUSION: Cardiac surgical patients prefer to allow the surgeon to determine the technique to be used for their coronary artery operation and do not want to be offered the chance to choose their surgeon according to the surgeons' preferred technique. Involvement of the patient in determining the operative technique is not always desired.

Phosphodiesterase-5 inhibition prevents postcardiopulmonary bypass acute kidney injury in swine.

BACKGROUND: Acute kidney injury after cardiac surgery is common, has no effective treatments, and is associated with adverse outcomes. The aim of this study was to determine whether administration of the phosphodiesterase-5 inhibitor sildenafil citrate (SDF) would prevent the development of post-cardiopulmonary bypass (CPB) acute kidney injury in swine. METHODS: Adult pigs (n = 8 per group) were randomized to undergo sham procedure, CPB, or CPB plus administration of SDF, with recovery and reassessment at 24 hours. RESULTS: Cardiopulmonary bypass resulted in a significant reduction in creatinine clearance relative to sham pigs (mean difference CPB versus sham, -47.9 mL/min; 95% confidence interval [CI]: -93.7 to -2.2; p = 0.039). This was prevented by the administration of SDF during CPB (mean difference CPB+SDF versus CPB, +55.6 mL/min; 95% CI: +6.5 to +104.7; p = 0.024). Cardiopulmonary bypass also resulted in a significant rise in the urinary biomarker interleukin-18 compared with sham procedures (mean difference 209.3 pg/mL; 95% CI: 120.6 to 298.1; p < 0.001) that was prevented by SDF administration. Post-CPB kidney injury was associated with vascular endothelial injury and dysfunction, reduced nitric oxide bioavailability, medullary hypoxia, cortical adenosine triphosphate depletion, inflammation, and evidence of proximal tubule epithelial cell stress manifest as phenotypic change. Administration of SDF to CPB pigs preserved nitric oxide bioavailability and prevented endothelial dysfunction, regional hypoxia, inflammation, and tubular changes. CONCLUSIONS: In this model, phosphodiesterase-5 inhibition using SDF prevented post-CPB acute kidney injury by the preservation of nitric oxide bioavailability, and warrants evaluation as a renoprotective agent in clinical trials.