George Matalanis

Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery--a prospective cohort study.

Objective:To compare the value of novel with conventional serum biomarkers in the prediction of acute kidney injury (AKI) in adult cardiac surgical patients according to preoperative renal function. Design:Single-center, prospective observational study. Setting:Tertiary hospital. Patients:One hundred adult cardiac surgical patients. Measurements and Main Results:We measured concentrations of plasma neutrophil gelatinase-associated lipocalin (NGAL), and serum cystatin C, and creatinine and urea at baseline, on arrival in the intensive care unit (ICU) and at 24 hours postoperatively. We assessed such biomarkers in relation to the development of AKI (>50% increase in creatinine from baseline) and to a composite end point (need for renal replacement therapy and in-hospital mortality). We defined an area under the receiver operating characteristic curve of 0.60–0.69 as poor, 0.70–0.79 as fair, 0.80–0.89 as good, and 0.90–1.00 as excellent in terms of predictive value. On arrival in ICU, plasma NGAL and serum cystatin C were of good predictive value, but creatinine and urea were of poor predictive value. After exclusion of patients with preoperative renal impairment (estimated glomerular filtration rate <60 mL/min), the predictive performance for AKI of all renal biomarkers on arrival in ICU remained unchanged except for cystatin C, which was of fair value in such patients. At 24 hours postoperatively, all renal biomarkers were of good predictive value. On arrival in ICU, novel biomarkers were superior to conventional biomarkers (p < 0.05). Plasma NGAL (p = 0.015) and serum cystatin C (p = 0.007) were independent predictors of AKI and of excellent value in the prediction of the composite end point. Conclusions:Early postoperative measurement of plasma NGAL was of good value in identifying patients who developed AKI after adult cardiac surgery. Plasma NGAL and serum cystatin C were superior to conventional biomarkers in the prediction of AKI and were also of prognostic value in this setting.

Sodium bicarbonate to prevent increases in serum creatinine after cardiac surgery: a pilot double-blind, randomized controlled trial

Objective:To test whether perioperative sodium bicarbonate infusion can attenuate postoperative increases in serum creatinine in cardiac surgical patients. Design:Double-blind, randomized controlled trial. Setting:Operating rooms and intensive care unit at a tertiary hospital. Patients:Cohort of 100 cardiac surgical patients at increased risk of postoperative acute renal dysfunction. Intervention:Patients were randomized to either 24 hrs of intravenous infusion of sodium bicarbonate (4 mmol/kg) or sodium chloride (4 mmol/kg). Measurements and Main Results:The primary outcome measure was the proportion of patients developing acute renal dysfunction defined as a postoperative increase in plasma creatinine concentration >25% of baseline within the first five postoperative days. Secondary outcomes included changes in plasma creatinine, plasma urea, urinary neutrophil gelatinase-associated lipocalin, and urinary neutrophil gelatinase-associated lipocalin/urinary creatinine ratio. Patients were well balanced for baseline characteristics. Sodium bicarbonate infusion increased plasma bicarbonate concentration (p < 0.001), base excess (p < 0.001), plasma pH (p < 0.001), and urine pH (p < 0.001). Fewer patients in the sodium bicarbonate group (16 of 50) developed a postoperative increase in serum creatinine compared with control (26 of 50) (odds ratio 0.43 [95% confidence interval 0.19–0.98]), (p = 0.043). The increase in plasma creatinine, plasma urea, urinary neutrophil gelatinase-associated lipocalin, and urinary neutrophil gelatinase-associated lipocalin/urinary creatinine ratio was less in patients receiving sodium bicarbonate, (p = 0.014; p = 0.047; p = 0.009; p = 0.004). There were no significant side effects. Conclusions:Sodium bicarbonate loading and continuous infusion was associated with a lower incidence of acute renal dysfunction in cardiac surgical patients undergoing cardiopulmonary bypass. The findings of this pilot study justify further investigation. (ClinicalTrials.gov, NCT00334191).

Novel biomarkers early predict the severity of acute kidney injury after cardiac surgery in adults.

BACKGROUND The purpose of this study was to investigate the ability of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, and their combination in predicting the duration and severity of acute kidney injury (AKI) after cardiac surgery in adults. METHODS Using data from a prospective observational study of 100 adult cardiac surgical patients, we correlated early postoperative concentrations of plasma NGAL and serum cystatin C with the duration (time during which AKI persisted according to the Acute Kidney Injury Network criteria) and severity of AKI (change in serum creatinine) and with length of stay in intensive care. RESULTS We found a mean AKI duration of 67.2 +/- 41.0 hours which was associated with prolonged hospitalization (p < 0.001). NGAL, cystatin C, and their combination on arrival in intensive care correlated with subsequent AKI duration (all p < 0.01) and severity (all p < 0.001). The area under the receiver operating characteristic curve for AKI prediction was 0.77 (95% confidence interval: 0.63 to 0.91) for NGAL and 0.76 (95% confidence interval: 0.61 to 0.91) for cystatin C on arrival in intensive care. Both markers also correlated with length of stay in intensive care (p = 0.037; p = 0.001). Neutrophil gelatinase-associated lipocalin and cystatin C were independent predictors of AKI duration and severity and of length of stay in intensive care (all p < 0.05). The value of cystatin C on arrival in intensive care appeared to be due to a carry-over effect from preoperative values. CONCLUSIONS Immediately postoperatively, NGAL and cystatin C correlated with and were independent predictors of duration and severity of AKI and duration of intensive care stay after adult cardiac surgery. The combination of both renal biomarkers did not add predictive value.

A comparison of the RIFLE and Acute Kidney Injury Network classifications for cardiac surgery-associated acute kidney injury: a prospective cohort study.

OBJECTIVES There is an intense debate on whether the RIFLE (R-renal risk, I-injury, F-failure, L-loss of kidney function, E-end-stage renal disease) classification or its recent modification, the Acute Kidney Injury Network definition and classification system should be used to standardize research on acute kidney injury. In this study we compared these classifications with regard to (1) the detection of acute kidney injury, (2) their agreement according to the grading of acute kidney injury across classes, and (3) their prognostic value. METHODS We prospectively enrolled 282 cardiac surgery patients undergoing cardiopulmonary bypass and assigned a RIFLE and Acute Kidney Injury Network class to each patient. The incidence of acute kidney injury and in-hospital mortality across classes was compared by using the chi(2) test, and their prognostic value was compared by using the area under the curve receiver-operating characteristic for in-hospital mortality. RESULTS According to the RIFLE (45.8%) or Acute Kidney Injury Network (44.7%) classification, a similar proportion of patients had acute kidney injury. There was large agreement between classifications according to patients graded as having nonacute kidney injury; however, there was some disagreement across classes for staging the severity of acute kidney injury. The area under the curve for in-hospital mortality was similar for all classifications: 0.91 for the RIFLE classification (95% confidence interval, 0.82-0.99) and 0.94 for the Acute Kidney Injury Network classification (95% confidence interval, 0.81-0.97; P = .6 for area under the curve comparison). CONCLUSIONS In patients undergoing cardiac surgery, modifications of the RIFLE classification for acute kidney injury do not materially improve the clinical usefulness of the definition. Other factors, such as the applicability of the acute kidney injury definition and classification system to be applied, need to be considered.

Pattern and significance of cerebral microemboli during coronary artery bypass grafting

BACKGROUND Strokes that occur during coronary artery bypass grafting are often caused by embolism. Intraoperative transcranial Doppler monitoring can detect cerebral microemboli. The aims of this study were to identify the pattern of microembolic phenomena during various stages of coronary artery bypass grafting, to verify whether numbers of high-intensity transient signals correlated with early neuropsychologic deficits, and to identify, using magnetic resonance imaging scans, whether radiologic evidence of cerebral infarction correlated with microembolic numbers during the bypass period. METHODS Forty-one consecutive patients undergoing coronary bypass grafting with transcranial Doppler monitoring were enrolled in this study. All had preoperative and postoperative magnetic resonance imaging brain scans. A subgroup of 32 patients were studied by comparing microembolic load and early neuropsychological outcomes. RESULTS Transcranial Doppler monitoring confirmed that most microemboli occurred during cardiopulmonary bypass. A significant early neuropsychological deficit after coronary artery bypass grafting did correspond to the total microembolic load during bypass (p = 0.008). However, patients with cerebral infarction on magnetic resonance imaging had significantly more microembolic signal during the preincision phases and not during the bypass period. CONCLUSIONS Microembolic load during bypass is associated with early neuropsychologic deficits. In contrast, patients who show evidence of strokes during coronary artery bypass grafting have a higher microembolic load during the preincision phase than those without cerebral infarction. Differing mechanisms may be responsible for these different outcomes.

Phase II, randomized, controlled trial of high-dose N-acetylcysteine in high-risk cardiac surgery patients

Objective:To assess the effect of high-dose N-acetylcysteine on renal function in cardiac surgery patients at higher risk of postoperative renal failure. Design:Multiblind, placebo-controlled, randomized, phase II clinical trial. Setting:Operating rooms and intensive care units of two tertiary referral hospitals. Patients:A total of 60 cardiac surgery patients at higher risk of postoperative renal failure. Interventions:Patients were allocated to either 24 hrs of high-dose N-acetylcysteine infusion (300 mg/kg body weight in 5% glucose, 1.7 L) or placebo (5% glucose, 1.7 L). Measurements and Main Results:The primary outcome measure was the absolute change in serum creatinine from baseline to peak value within the first five postoperative days. Secondary outcomes included the relative change in serum creatinine, peak serum creatinine level, serum cystatin C, and in urinary output. Further outcomes were needed for renal replacement therapy, length of ventilation, and length of stay in the intensive care unit and hospital. Randomization was successful and patients were well balanced for preoperative and intraoperative characteristics. There was no significant attenuation in the increase in serum creatinine from baseline to peak when comparing N-acetylcysteine with placebo (64.5 ± 91.2 and 38.0 ± 42.4 &mgr;mol/L, respectively; p = .15). Also, there was no attenuation in the increase in serum cystatin C from baseline to peak for N-acetylcysteine compared with placebo (0.45 ± 0.43 and 0.30 ± 0.33 mg/L, respectively; p = .40). Likewise, there was no evidence for differences in any other clinical outcome. Conclusions:In this phase II, randomized, controlled trial, high-dose N-acetylcysteine was no more effective than placebo in attenuating cardiopulmonary bypass–related acute renal failure in high-risk cardiac surgery patients.

The predictive performance of plasma neutrophil gelatinase-associated lipocalin (NGAL) increases with grade of acute kidney injury

BACKGROUND In adult cardiac surgery, the predictive value for AKI of neutrophil gelatinase-associated lipocalin (NGAL) appears to have wide variability. The choice of definition of acute kidney injury (AKI) might, at least in part, account for such variability. METHODS In a prospective study of 100 adult cardiac surgery patients, we assessed the value of postoperative plasma NGAL in predicting AKI according to the degree of severity used for its definition. RESULTS The predictive value of plasma NGAL varied according to the AKI definition used and was higher for more severe AKI (increase in creatinine >50%: mean AUC-ROC 0.79 +/- 0.01) compared to less severe AKI (>25%: mean AUC-ROC 0.65 +/- 0.02); P = 0.001. The discriminatory ability of NGAL for AKI also increased with increasing RIFLE classes (AUC-ROC R: 0.72, I: 0.79, F: 0.80) or AKIN stages (AUC-ROC 1: 0.75, 2: 0.78, 3: 0.81); P = 0.015. It was highest for the prediction of renal replacement therapy (AUC-ROC: 0.83). CONCLUSIONS In adult cardiac surgery patients, the predictive value of NGAL increases with grade of AKI. This observation needs to be taken into account when interpreting any future studies of this biomarker.

Comparable patencies of the radial artery and right internal thoracic artery or saphenous vein beyond 5 years: results from the Radial Artery Patency and Clinical Outcomes trial.

OBJECTIVE To investigate the optimum conduit for coronary targets other than the left anterior descending artery, we evaluated long-term patencies and clinical outcomes of the radial artery, right internal thoracic artery, and saphenous vein through the Radial Artery Patency and Clinical Outcomes trial. METHODS As part of a 10-year prospective, randomized, single-center trial, patients undergoing primary coronary surgery were allocated to the radial artery (n = 198) or free right internal thoracic artery (n = 196) if aged less than 70 years (group 1), or radial artery (n = 113) or saphenous vein (n = 112) if aged at least 70 years (group 2). All patients received a left internal thoracic artery to the left anterior descending, and the randomized conduit was used to graft the second largest target. Protocol-directed angiography has been performed at randomly assigned intervals, weighted toward the end of the study period. Grafts are defined as failed if there was occlusion, string sign, or greater than 80% stenosis, independently reported by 3 assessors. Analysis is by intention to treat. RESULTS At mean follow up of 5.5 years, protocol angiography has been performed in groups 1 and 2 in 237 and 113 patients, respectively. There are no significant differences within each group in preoperative comorbidity, age, or urgency. Patencies were similar for either of the 2 conduits in each group (log rank analysis, P = .06 and P = .54, respectively). The differences in estimated 5-year patencies were 6.6% (radial minus right internal thoracic artery) in group 1 and 2.9% (radial minus saphenous vein graft) in group 2. CONCLUSION At mean 5-year angiography in largely asymptomatic patients, the selection of arterial or venous conduit for the second graft has not significantly affected patency. This finding offers surgeons, for now, enhanced flexibility in planning revascularization.

Early and intensive continuous hemofiltration for severe renal failure after cardiac surgery

BACKGROUND The aim of this study was to test whether early and intensive use of continuous venovenous hemofiltration (CVVH) achieved a better than predicted outcome in patients with severe acute renal failure undergoing cardiac operations, and whether a simple and yet accurate model could be developed to predict their outcome before starting CVVH. METHODS Medical record analysis with collection of demographic, clinical, and outcome information was used. RESULTS Sixty-five consecutive patients were treated with early and intensive CVVH (mean operation to CVVH time, 2.38 days; pump-controlled ultrafiltration rate, 2 L/h) after coronary artery bypass grafting (56.9%), single valve procedure (16.9%), or combined operations (26.2%). In 32.3% of patients, intraaortic balloon counterpulsation was required and 20% of patients were emergencies. Sustained hypotension despite inotropic and vasopressor support occurred in 40% of patients and prolonged mechanical ventilation in 58.5%. Using an outcome prediction score specific for acute renal failure, the predicted risk of death was 66%. Actual mortality was 40% (p = 0.003). Using multivariate logistic regression analysis and neural network analysis, patient outcome could be predicted with good levels of accuracy (receiver operating characteristic 0.89 and 0.9, respectively). CONCLUSIONS Early and aggressive CVVH is associated with better than predicted survival in severe acute renal failure after cardiac operations. Using readily available clinical data, the outcome of such patients can be predicted before the implementation of CVVH.

The intraoperative assessment of ascending aortic atheroma : Epiaortic imaging is superior to both transesophageal echocardiography and direct palpation

OBJECTIVES To determine the optimal method for detecting ascending aortic atheroma intraoperatively by comparing manual palpation by the operating surgeon, intraoperative transesophageal echocardiography, and epiaortic ultrasound (linear and phased-array imaging); and to assess risk factors for severe aortic atheroma. DESIGN A longitudinal prospective study. Assessment of the atheroma by manual palpation was blinded to the results of the ultrasound images. SETTING The study was performed in a single university tertiary referral hospital. PARTICIPANTS One hundred consecutive patients undergoing coronary bypass or valve surgery were studied after their written, informed consent. INTERVENTIONS Potential risk factors were evaluated by both a patient questionnaire and examination of prior hospital records. The ascending aorta was assessed by the following methods: manual palpation by the operating surgeon, intraoperative transesophageal echocardiography, and epiaortic ultrasound (linear and phased-array imaging) performed by an echocardiologist. For analysis, the ascending aorta was divided into three equal segments: proximal, mid, and distal, corresponding to regions of different operative manipulations. MEASUREMENTS AND MAIN RESULTS Age older than 70 years and hypertension were significant risk factors for severe ascending aortic atheroma with adjusted odds ratios of 3.3 (95% CI, 1.2 to 9.3) and 3.9 (95% CI, 1.3 to 12.0), respectively. There was no significant difference in atheroma detection between the two ultrasonic epiaortic probes in any segment; however, epiaortic probes were superior to manual palpation in all segments and also superior to transesophageal echocardiography in the mid and distal segments of the ascending aorta. CONCLUSIONS Age older than 70 years and hypertension are significant risk factors for severe ascending aortic atheroma. Intraoperative detection of ascending aortic atheroma is best achieved by epiaortic ultrasound with either a linear or phased array transducer. Transesophageal echocardiography is an insensitive technique for evaluation of mid and distal ascending aortic atheroma and, therefore, of little value in guiding surgical manipulations such as cross-clamping.