Hours Of Cardiopulmonary Bypass Research Articles

Effects of cardiopulmonary bypass perfusion temperature on perioperative renal function in adult patients undergoing cardiac surgery.

Aims and objectiveThe primary objective of this investigation was to study the effects of cardiopulmonary bypass (CPB) perfusion temperature on renal function parameters [serum creatinine, creatinine clearance, urine albumin, urine protein, and urine albumin/creatinine ratio (ACR)]. The secondary objective was to detect renal complications of CPB.Materials and methodsThis is a prospective longitudinal study of 30 adult patients (17 men, 13 women; mean age, 53.37 ± 16.02 years) who underwent valvular heart surgery [with or without coronary artery bypass grafting (CABG)]. Serum creatinine, creatinine clearance, urine protein, urine albumin, and urine ACR were collected during CPB (at 28 °C, 32 °C, and 37 °C) and postoperatively (at 12 hours, 24 hours, and 48 hours). Data were analyzed using one-way repeated-measures analysis of variance (ANOVA). A significant ANOVA was followed by a Bonferroni–Holm post hoc test.ResultsAlthough serum creatinine (p < 0.001) and creatinine clearance (p = 0.0016) underwent a significant ANOVA change (p < 0.001 and p = 0.0016, respectively) after CPB, there was no statistically significant change compared with their baseline values. Urine ACR showed a significant change at 28 °C (p < 0.01), 32 °C (p < 0.01), and 37 °C (p < 0.05) as compared with baseline values. No significant change in urine albumin was observed during CPB or up to 24 hours. A significant change occurred after 48 hours of CPB (p < 0.05). A significant increase in urine protein was noted after CPB at 12 hours (p < 0.01), 24 hours (p < 0.01), and 48 hours (p < 0.01). Overall, 12 (40%) patients had acute kidney injury (AKI). Ten (33.33%) patients had stage I AKI, one patient progressed to AKI stage II, and another to AKI stage III. Of the 10 patients who had stage I AKI, eight had complete recovery within 48 hours.ConclusionsCPB with moderate hypothermia for valvular heart surgeries can be performed safely in patients with adequate renal functional reserve. The glomerular permeability across the Bowman’s capsule increases after CPB as evidenced by significant proteinuria at 12 hours and increased albuminuria at 48 hours after surgery. There is an increased risk of transient stage I AKI after CPB, from which patients recover within 48 hours.

Cell-Cycle Arrest Biomarkers: Usefulness for Cardiac Surgery-Related Acute Kidney Injury in Neonates and Infants.

Cell cycle arrest urine biomarkers have recently been shown to be early indicators of acute kidney injury in various clinical settings in critically ill adults and children. The product of tissue inhibitor metalloproteinase -1 and insulin-like growth factor binding protein-7 concentrations/1,000 (TIMP-1) × (IGFBP-7) provides stratification of acute kidney injury-risk in adults with critical illness. The present study explores the predictive accuracy of (TIMP-1) × (IGFBP-7) measured early after cardiopulmonary bypass for cardiac surgery-related acute kidney injury in neonates and infants, a population in whom such data are not yet available. Prospective, observational. A tertiary referral pediatric cardiac ICU. Fifty-seven neonates and 110 infants undergoing surgery with cardiopulmonary bypass. None. (TIMP-1) × (IGFBP-7) was measured on the NephroCheck (Astute Medical, San Diego, CA) platform preoperatively, less than 1 hour of cardiopulmonary bypass and 1-3 hours of cardiopulmonary bypass. The incidence of postoperative acute kidney injury, dialysis, and/or death were compared among quintiles of postoperative (TIMP-1) × (IGFBP-7). Multivariable regression was used to assess the added predictive value for renal events of (TIMP-1) × (IGFBP-7) over clinical models. Basal (TIMP-1) × (IGFBP-7) increased with age at surgery (regression coefficient = 0.004 ± 0.001; p = 0.005). (TIMP-1) × (IGFBP-7) increased after cardiopulmonary bypass. Neonates had lower postoperative (TIMP-1) × (IGFBP-7) compared with older infants, despite undergoing longer surgeries and experiencing a higher incidence of postoperative renal events. (TIMP-1) × (IGFBP-7) was not associated with acute kidney injury, dialysis, and/or death and was not a predictor of the aforementioned events when added to a clinical acute kidney injury model including age, duration of cardiopulmonary bypass, and mechanical ventilation prior to surgery. These findings question the usefulness of (TIMP-1) × (IGFBP-7) for the prediction of cardiac surgery-related acute kidney injury in neonates and infants when measured within 3 hours of cardiopulmonary bypass.

Effects of cardiopulmonary bypass on vascular endothelial inflammation and oxidative stress in rats

Objective To investigate the effects of cardiopulmonary bypass (CPB) on vascular endothelial inflammation and oxidative stress in rats and its mechanism. Methods 64 SD male rats were randomly divided into sham group and CPB group, and the CPB rat model was prepared. The vascular endothelial function was compared after 4 hours of CPB. tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 was detected by enzyme linked immunosorbent assay (ELISA). The serum levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) was analyzed using MDA, SOD and GSH test kit. The protein activity of nuclear factor-κB (NF-κB) in aorta was detected by Western blotting. Results Compared with the sham group [(90.17±7.45)%], the diastolicity of aortic vascular in CPB group was significantly decreased [(72.57±5.86)%, t=2.869, P<0.05]. Compared with the sham group [(118.53±9.70), (87.69±10.46), (91.88±10.04) ng/L], the serum levels of TNF-α, IL-6 and IL-1β in the CPB group increased significantly [(203.55±13.29), (170.20±11.81), (176.49±16.11) ng/L] (t=3.347, 4.253, 3.850, P<0.05). Compared with the sham group [(67.38±7.17) U/ml; (21.04±3.7) μmol/L; (20.33±1.79) mg/L] the serum levels of SOD and GSH in the CPB group were significantly decreased, while the serum level of MDA was significantly increased [(40.38±5.21) U/ml; (34.04±5.0) μmol/L; (13.86±1.51) mg/L, t=2.772, 2.397, 3.216, P<0.05]. Western blotting showed that compared with the sham group (0.62±0.04), the relative expression of phospho-NF-κB p65 in the aorta tissue of the CPB group was significantly increased (1.44±0.12, t= 3.750, P<0.05). Conclusion CPB can inhibit vascular endothelial function in rats by enhancing vascular endothelial inflammation and oxidative stress levels. Key words: Cardiopulmonary bypass; Vascular endothelial; Inflammation; Oxidative stress; Nuclear factor-κB

Effects of cardiopulmonary bypass perfusion temperature on perioperative renal function in adult patients undergoing cardiac surgery

Aims and objectiveThe primary objective of this investigation was to study the effects of cardiopulmonary bypass (CPB) perfusion temperature on renal function parameters [serum creatinine, creatinine clearance, urine albumin, urine protein, and urine albumin/creatinine ratio (ACR)]. The secondary objective was to detect renal complications of CPB. Materials and methodsThis is a prospective longitudinal study of 30 adult patients (17 men, 13 women; mean age, 53.37 ± 16.02 years) who underwent valvular heart surgery [with or without coronary artery bypass grafting (CABG)]. Serum creatinine, creatinine clearance, urine protein, urine albumin, and urine ACR were collected during CPB (at 28 °C, 32 °C, and 37 °C) and postoperatively (at 12 hours, 24 hours, and 48 hours). Data were analyzed using one-way repeated-measures analysis of variance (ANOVA). A significant ANOVA was followed by a Bonferroni–Holm post hoc test. ResultsAlthough serum creatinine (p < 0.001) and creatinine clearance (p = 0.0016) underwent a significant ANOVA change (p < 0.001 and p = 0.0016, respectively) after CPB, there was no statistically significant change compared with their baseline values. Urine ACR showed a significant change at 28 °C (p < 0.01), 32 °C (p < 0.01), and 37 °C (p < 0.05) as compared with baseline values. No significant change in urine albumin was observed during CPB or up to 24 hours. A significant change occurred after 48 hours of CPB (p < 0.05). A significant increase in urine protein was noted after CPB at 12 hours (p < 0.01), 24 hours (p < 0.01), and 48 hours (p < 0.01). Overall, 12 (40%) patients had acute kidney injury (AKI). Ten (33.33%) patients had stage I AKI, one patient progressed to AKI stage II, and another to AKI stage III. Of the 10 patients who had stage I AKI, eight had complete recovery within 48 hours. ConclusionsCPB with moderate hypothermia for valvular heart surgeries can be performed safely in patients with adequate renal functional reserve. The glomerular permeability across the Bowman’s capsule increases after CPB as evidenced by significant proteinuria at 12 hours and increased albuminuria at 48 hours after surgery. There is an increased risk of transient stage I AKI after CPB, from which patients recover within 48 hours.

Protocol for a phase III, non-inferiority, randomised comparison of a new fibrinogen concentrate versus cryoprecipitate for treating acquired hypofibrinogenaemia in bleeding cardiac surgical patients: the FIBRES trial

IntroductionCoagulopathic bleeding is a serious complication of cardiac surgery to which an important contributor is acquired hypofibrinogenaemia (plasma fibrinogen <1.5–2.0 g/L). The standard intervention for acquired hypofibrinogenaemia is cryoprecipitate, but...

Furosemide Response Predicts Acute Kidney Injury After Cardiac Surgery in Infants and Neonates.

Cardiac surgery-induced acute kidney injury occurs frequently in neonates and infants and is associated with postoperative morbidity/mortality; early identification of cardiac surgery-induced acute kidney injury may be crucial to mitigate postoperative morbidity. We sought to determine if hourly or 6-hour cumulative urine output after furosemide in the first 24 hours after cardiopulmonary bypass could predict development of cardiac surgery-induced acute kidney injury and other deleterious outcomes. Retrospective chart review. Pediatric cardiac ICU. All infants younger than 90 days old admitted to the cardiac ICU from October 2012 to December 2015 who received at least one dose of furosemide in the first 24 hours after cardiopulmonary bypass surgery. None. Ninety-nine patients met inclusion and exclusion criteria. In total, 45.5% developed cardiac surgery-induced acute kidney injury. Median time between cardiopulmonary bypass and furosemide was 7.7 hours (interquartile range, 4.4-9.5). Six-hour cumulative urine output was 33% lower (p = 0.031) in patients with cardiac surgery-induced acute kidney injury. Area under the curve for prediction of cardiac surgery-induced acute kidney injury was 0.69 (p = 0.002). Other models demonstrated urine output response to furosemide had significant area under the curves for prediction of peak fluid over load greater than 15% (0.68; p = 0.047), prolonged peritoneal dialysis (area under the curve, 0.79; p = 0.007), prolonged mechanical ventilation (area under the curve, 0.79; p < 0.001), prolonged hospitalization (area under the curve, 0.62; p = 0.069) and mortality (area under the curve, 0.72; p = 0.05). Urine output response to furosemide within 24 hours of cardiopulmonary bypass predicts cardiac surgery-induced acute kidney injury development and other important morbidity in children younger than 90 days old; prospective validation is warranted.

Subclinical Kidney Injury in Children Receiving Nonsteroidal Anti-Inflammatory Drugs After Cardiac Surgery

To investigate the association of nonsteroidal anti-inflammatory drug (NSAID) administration with urinary neutrophil gelatinase-associated lipocalin (NGAL) levels in children following cardiopulmonary bypass (CPB) who did not develop acute kidney injury (AKI). In this prospective observational study, urinary NGAL levels were investigated in 210 children who underwent cardiothoracic surgery requiring CPB. Children with clinical AKI (defined as an increase in serum creatinine ≥50% from baseline within 72 hours of CPB) were excluded from the analysis. NSAIDs were administered no sooner than 24 hours after CPB. NGAL levels were compared between children who received NSAIDs (n = 146) and those who did not receive NSAIDs (n = 64). The median age was 3.2 years in the children who received NSAIDs and 2.5 years in those who did not receive NSAIDs (P = .05). Before NSAID administration at 24 hours following CPB, the median NGAL level was 15 ng/mL in both groups (P = .92). Following NSAID administration, the median urinary NGAL level increased to 83 ng/mL (IQR, 45-95 ng/mL) at 72 hours after CPB in those receiving NSAIDs (P < .001). In contrast, the median NGAL level decreased to 10 ng/mL (IQR, 5.4-15.9 ng/mL) at 72 hours after CPB in those who did not receive NSAIDs (P = .01). In multivariable analysis, children receiving NSAIDs demonstrated a 5-fold elevation of urinary NGAL levels at 60-72 hours following CPB compared with those who did not receive NSAIDs (P < .001). NSAID administration was associated with a significant increase in urinary NGAL in children who did not develop clinical AKI following CPB. This indicates that NGAL can detect NSAID-induced subclinical kidney injury in this population.

Methylene Blue for Vasoplegic Syndrome After Cardiac Operation: Early Administration Improves Survival

Vasoplegic syndrome, defined by hypotension despite normal or increased cardiac output, is associated with high mortality rate after cardiopulmonary bypass. Methylene blue (MB) is reported to ameliorate vasoplegic syndrome through the nitric oxide pathway. We hypothesized that early administration of MB would improve outcomes in patients with vasoplegic syndrome after cardiopulmonary bypass. All patients that underwent cardiopulmonary bypass at our institution (Jan 1, 2011 to Jun 30, 2016) were identified through our Society of Thoracic Surgery database. Pharmacy records identified patients receiving MB within 72 hours of cardiopulmonary bypass. Multivariate logistic regression identified predictors of major adverse events among patients receiving MB. A total of 118 cardiopulmonary bypass patients (3.3%) received MB for vasoplegic syndrome. These patients had a higher incidence of comorbidities, and these cases were more commonly reoperative (76.1% versus 41.2%, p < 0.0001) and complex (70.3% versus 31.8%, p < 0.0001). The only difference in preoperative medications was that MB patients had a higher rate of amiodarone use (15.3% versus 2.2%, p < 0.0001). MB patients had significantly higher rates of postoperative complications, except atrial fibrillation. Early (operating room, 40.7%) versus late (intensive care unit, 59.3%) administration of MB was associated with significantly reduced operative mortality rate (10.4% versus 28.6%, p=0.018) and risk-adjusted major adverse events (odd ratio 0.35, p= 0.037). Operative mortality rate is high in patients receiving MB for the treatment of vasoplegia after cardiopulmonary bypass. Early administration of MB improves survival and reduces the risk-adjusted rate of major adverse events in these patients.

Subclavian artery perforation and hemothorax after right internal jugular vein catheterization

Subclavian artery perforation and hemothorax after right internal jugular vein catheterization

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

IntroductionObesity 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.MethodsIn 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.ResultsCPB 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.ConclusionsA 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.

Endothelin and vasopressin influence splanchnic blood flow distribution during and after cardiopulmonary bypass

Gastrointestinal blood flow can be compromised during and after cardiopulmonary bypass. Endothelin has been shown to be involved in the intestinal microcirculatory disturbance of sepsis. The aim of the present study was to analyze the involvement of the endothelin system on intestinal blood flow regulation during cardiopulmonary bypass and the effect of vasopressin given during cardiopulmonary bypass. A total of 24 pigs were studied in 4 groups (n = 6): group I, sham; group II, ischemia/reperfusion with 1 hour of superior mesenteric artery occlusion; group III, cardiopulmonary bypass for 1 hour; and group IV, 1 hour of cardiopulmonary bypass plus vasopressin administration, maintaining the baseline arterial pressure. All the pigs were reperfused for 90 minutes. During the experiment, the hemodynamics and jejunal microcirculation were measured continuously. The jejunal mucosal expression of endothelin-1 and its receptor subtypes A and B were determined using polymerase chain reaction. During cardiopulmonary bypass, superior mesenteric artery flow was preserved but marked jejunal microvascular impairment occurred compared with baseline (mucosal capillary density, 192.2 ± 5.4 vs 150.8 ± 5.1 cm/cm(2); P = .005; tissue blood flow, 501.7 ± 39.3 vs 332.3 ± 27.9 AU; P = .025). The expression of endothelin-1 after cardiopulmonary bypass (3.2 ± 0.4 vs 12.2 ± 0.8 RQ, P = .006) and endothelin subtype A (0.7 ± 0.2 vs 2.4 ± 0.6 RQ; P = .01) was significantly increased compared to the sham group. Vasopressin administration during cardiopulmonary bypass led to normal capillary density (189.9 ± 3.9 vs 178.0 ± 6.3; P = .1) and tissue blood flow (501.7 ± 39.3 vs 494.7 ± 44.4 AU; P = .4) compared with baseline. The expression of endothelin-1 (3.2 ± 0.4 vs 1.8 ± 0.3 RQ; P = .3) and endothelin subtype A (0.7 ± 0.2 vs 0.9 ± 0.2 RQ; P = .5) was not different from the sham group. Cardiopulmonary bypass leads to microvascular impairment of jejunal microcirculation, which is associated with the upregulation of endothelin-1 and endothelin subtype A. The administration of vasopressin minimizes these cardiopulmonary bypass-associated alterations.

High-Dose Tranexamic Acid Is an Independent Predictor of Early Seizure After Cardiopulmonary Bypass

Risk factors associated with early seizure after cardiopulmonary bypass (CPB) were examined. The role of tranexamic acid in seizure development was evaluated. Early seizure was defined as a seizure occurring within 24 hours of CPB, without neurologic deficit or new lesion on brain imaging. Independent determinants of early seizure were examined by multivariate logistic regression modelling. Between 2004 and 2009, early seizure occurred in 119 of 8,929 patients (1.3%). A significant increase in the yearly rate of early seizure was observed in 2004 (0.73%) vs 2009 (1.97%; p<0.0001). Multivariate analysis showed the following variables were independent predictors of early seizure: age older than 75 years (adjusted odds ratio [OR], 2.1; p=0.0001), open heart procedure (OR, 12.0; p<0.0001), preoperative renal failure (OR, 3.2; p<0.0001), peripheral vascular disease (OR, 1.8; p=0.02), and total tranexamic acid dose of 100 mg/kg or more (OR, 2.6; p<0.0001). Risk of seizure was related to tranexamic acid in a dose-dependent fashion, with higher doses associated with increased risk of seizure. The use of CO2 in a subset of patients undergoing open heart procedures did not decrease the incidence of early seizure (4.8% vs 2.5% for no CO2; p=0.27). Postoperative chest tube drainage and blood product use were similar between patients receiving low-dose and high-dose tranexamic acid. High-dose tranexamic acid (≥100 mg/kg) is independently associated with an increased risk of early seizure. Future tranexamic acid trials should assess the blood-conserving effect of tranexamic acid at a lower dosage and specifically monitor for seizure occurrence.

Bivalirudin for Anticoagulation During Hypothermic Cardiopulmonary Bypass and Recombinant Factor VIIa for Iatrogenic Coagulopathy

To describe management of anticoagulation with a decreased dose requirement of bivalirudin during cardiopulmonary bypass using deep hypothermic circulatory arrest (DHCA) and the reversal of the ensuing coagulopathy with recombinant factor VIIa (rFVIIa). A 48-year-old male developed chest pain, hypertension, and an aortic aneurysm requiring urgent surgical repair. At the time of surgery, the patient reported an allergy to heparin, so bivalirudin was used for anticoagulation (1 mg/kg loading dose, followed by intermittent infusions of 1.25-2.5 mg/kg/h over the 5 hours of cardiopulmonary bypass). When the cooling process was initiated, bivalirudin was stopped in anticipation of loss of the clotting cascade function and potential slowing of drug elimination. Bivalirudin was restarted for 45 minutes during the rewarming period because of concern for potential clot formation in the bypass circuit with recovery of hemostasis; it was again stopped due to the patient's activated clotting time (ACT) of 504 seconds. Despite this measure, diffuse and severe coagulopathy was observed upon rewarming, with ACTs longer than 999 seconds. Although multiple blood products were administered, visualization of a clot in the surgical field was not notable. A total dose of rFVIIa 20 μg/kg was administered, resulting in visual clot formation within 4 minutes. On postsurgical day 6, bilateral asymptomatic distal deep vein thromboses were noted on imaging; on postsurgical day 8, fondaparinux 2.5 mg subcutaneously was administered daily to prevent clot extension. The patient was discharged on postoperative day 23 with no acute issues and no further anticoagulants. Alternative anticoagulation agents such as bivalirudin are used in patients who have an allergy or contraindication to heparin. We propose that prolonged coagulopathy after the induction of hypothermia is due to decreased clotting cascade function as well as slowing of protease activity resulting in decreased bivalirudin elimination. We observed a positive response to low-dose rFVIIa, which could be due to activation of the extrinsic pathway and/or a thrombin burst, resulting in hemostasis. Currently, there is limited evidence supporting reversal of direct thrombin inhibitors with rFVIIa. In the setting of DHCA, bivalirudin should be used cautiously, with frequent monitoring of the ACTs and potential cessation of the infusion in anticipation of prolonged drug effect with subsequent potential coagulopathy. If coagulopathy ensues, use of low-dose rFVIIa may be an option to initiate hemostasis. When using rFVIIa, it is important to consider the risk of thrombosis and monitor patients accordingly.

Pattern of activin A and follistatin release in a sheep model of cardiopulmonary bypass

ObjectiveActivin A, a member of transforming growth factor-β superfamily, has been established as a critical cytokine released early in endotoxemia and other inflammatory syndromes. The release of activin A and its binding protein, follistatin during cardiopulmonary bypass (CPB) has not been previously reported. Our study aimed to define the pattern of activin A and follistatin release in a sheep CPB model. MethodsControl group consisted of left thoractomy alone (n=6). CPB was performed using either unfractionated heparin (n=6) or lepirudin (n=6) as anticoagulant. Unlike heparin, lepirudin does not cause activin A and follistatin release on its own. Serum samples were assayed for activin A, follistatin, tumour necrosis factor-α and interleukin-6. ResultsCompared with the control group, CPB using lepirudin was associated with a biphasic release of activin A. The first peak occurred within the first hour of CPB and a second peak occurred within the early post-operative period, coincident with a large release of follistatin. Close correlation was found between follistatin and IL-6 in the control and lepirudin groups, indicative of a role for follistatin in the acute phase response. In contrast to the control and lepirudin groups, CPB using heparin resulted in a concurrent release of activin A and follistatin. ConclusionsCPB is a trigger for the release of biologically-active free activin A into the circulation, at levels considerably greater than that induced by surgery alone. Triggering release of this critical inflammatory cytokine suggests that activin A may contribute to the adverse outcomes associated with systemic inflammation in cardiac surgery.

Neutrophil Gelatinase-Associated Lipocalin Concentrations Predict Development of Acute Kidney Injury in Neonates and Children after Cardiopulmonary Bypass

To investigate neutrophil gelatinase-associated lipocalin (NGAL) as an early acute kidney injury (AKI) biomarker after neonatal and pediatric cardiopulmonary bypass (CPB). Serum and urine samples were obtained before and at intervals after CPB from 374 patients. AKI was defined as a serum creatinine (S(Cr)) concentration increase from baseline ≥0.3 mg/dL in neonates and ≥50% in children within 48 hours of CPB. Logistic regression was used to assess predictors and clinical outcomes associated with AKI. AKI developed in 30% of patients. Plasma and urine NGAL thresholds significantly increased in patients with AKI at 2 hours after CPB and remained elevated at all points, with 2-hour NGAL the earliest, strongest predictor of AKI. In non-neonates, 2-hour plasma and urine NGAL thresholds strongly correlated with length of hospital stay and severity and duration of AKI. Plasma and urine NGAL thresholds are early predictive biomarkers for AKI and its clinical outcomes after CPB. In neonates, we recommend a 2-hour plasma NGAL threshold of 100 ng/mL and 2-hour urine NGAL threshold of 185 ng/mL for diagnosis of AKI. In non-neonates, recommended AKI thresholds are 50 ng/mL for both 2-hour plasma and urine NGAL.

Is the “sterile cockpit” concept applicable to cardiovascular surgery critical intervals or critical events? The impact of protocol-driven communication during cardiopulmonary bypass

There is general enthusiasm for applying strategies from aviation directly to medical care; the application of the "sterile cockpit" rule to surgery has accordingly been suggested. An implicit prerequisite to the evidence-based transfer of such a concept to the clinical domain, however, is definition of periods of high mental workload analogous to takeoff and landing. We measured cognitive demands among operating room staff, mapped critical events, and evaluated protocol-driven communication. With the National Aeronautics and Space Administration Task Load Index and semistructured focus groups, we identified common critical stages of cardiac surgical cases. Intraoperative communication was assessed before (n = 18) and after (n = 16) introduction of a structured communication protocol. Cognitive workload measures demonstrated high temporal diversity among caregivers in various roles. Eight critical events during cardiopulmonary bypass were then defined. A structured, unambiguous verbal communication protocol for these events was then implemented. Observations of 18 cases before implementation including 29.6 hours of cardiopulmonary bypass with 632 total communication exchanges (average 35.1 exchanges/case) were compared with observations of 16 cases after implementation including 23.9 hours of cardiopulmonary bypass with 748 exchanges (average 46.8 exchanges/case, P = .06). Frequency of communication breakdowns per case decreased significantly after implementation (11.5 vs 7.3 breakdowns/case, P = .008). Because of wide variations is cognitive workload among caregivers, effective communication can be structured around critical events rather than defined intervals analogous to the sterile cockpit, with reduction in communication breakdowns.

Myocardial membrane injury in pediatric cardiac surgery: An animal model

Reduced myocardial performance invariably follows pediatric cardiac surgery and is manifested by a low cardiac output state in its severest form. The role of myocardial membrane proteins in this setting is unknown. Dystrophin and dysferlin are involved in membrane integrity, whereas aquaporins selectively transport water. These proteins were examined in a model of pediatric cardiac surgery, together with a trial of poloxamer 188, which may reduce membrane injury. Eight lambs were randomized to saline with or without poloxamer 188. Lambs underwent 2 hours of cardiopulmonary bypass and aortic crossclamping. After a further 9 hours of monitoring, the hearts were assessed for water content, capillary leak, and protein expression. Dystrophin expression was unaffected by ischemia/reperfusion, but dysferlin expression was reduced. Aquaporin 1 protein increased after ischemia/reperfusion. Poloxamer 188 administration was associated with supranormal levels of dystrophin, preservation of dysferlin expression, and normalization of aquaporin 1 expression. Poloxamer 188 was associated with less capillary leak, maintained colloid osmotic pressure, and less hemodilution. Poloxamer 188 was associated with an improved hemodynamic profile (higher blood pressure, higher venous saturation, and lower lactate), although the heart rate tended to be higher. Changes in protein expression within the myocardial membrane were found in a clinically relevant model of pediatric cardiac surgery. Indicators of reduced performance, such as lower blood pressure and lower oxygen delivery, were lessened in association with the administration of the membrane protecting poloxamer 188. Poloxamer 188 was also associated with potentially beneficial changes in membrane protein expression, reduced capillary leakage, and less hemodilution.

Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study

IntroductionAcute kidney injury (AKI) is a frequent complication of cardiopulmonary bypass (CPB). The lack of early biomarkers has impaired our ability to intervene in a timely manner. We previously showed in a small cohort of patients that plasma neutrophil gelatinase-associated lipocalin (NGAL), measured using a research enzyme-linked immunosorbent assay, is an early predictive biomarker of AKI after CPB. In this study we tested whether a point-of-care NGAL device can predict AKI after CPB in a larger cohort.MethodsFirst, in a cross-sectional pilot study including 40 plasma samples (NGAL range 60 to 730 ng/ml) and 12 calibration standards (NGAL range 0 to 1,925 ng/ml), NGAL measurements by enzyme-linked immunosorbent assay and by Triage® NGAL Device (Biosite Inc., San Diego, CA, USA) were highly correlated (r = 0.94). Second, in a subsequent prospective uncontrolled cohort study, 120 children undergoing CPB were enrolled. Plasma was collected at baseline and at frequent intervals for 24 hours after CPB, and analyzed for NGAL using the Triage® NGAL device. The primary outcome was AKI, which was defined as a 50% or greater increase in serum creatinine.ResultsAKI developed in 45 patients (37%), but the diagnosis using serum creatinine was delayed by 2 to 3 days after CPB. In contrast, mean plasma NGAL levels increased threefold within 2 hours of CPB and remained significantly elevated for the duration of the study. By multivariate analysis, plasma NGAL at 2 hours after CPB was the most powerful independent predictor of AKI (β = 0.004, P < 0.0001). For the 2-hour plasma NGAL measurement, the area under the curve was 0.96, sensitivity was 0.84, and specificity was 0.94 for prediction of AKI using a cut-off value of 150 ng/ml. The 2 hour postoperative plasma NGAL levels strongly correlated with change in creatinine (r = 0.46, P < 0.001), duration of AKI (r = 0.57, P < 0.001), and length of hospital stay (r = 0.44, P < 0.001). The 12-hour plasma NGAL strongly correlated with mortality (r = 0.48, P = 0.004) and all measures of morbidity mentioned above.ConclusionAccurate measurements of plasma NGAL are obtained using the point-of-care Triage® NGAL device. Plasma NGAL is an early predictive biomarker of AKI, morbidity, and mortality after pediatric CPB.

Effects of blood washing and autotransfusion during cardiopulmonary bypass on erythrocyte immune and kidney function

To study changes of erythrocyte immune and kidney function after autotransfusion washed red blood cells during cardiopulmonary bypass (CPB). Thirty-two patients undergoing valve replacement with CPB were randomly divided into study group and control group (16 in each group). In study group, the blood in operative field and the residual blood in the extracorporal machine were collected, centrifuged, washed and retransfused to patients. Patients in control group were transfused with the residual blood in the extracorporal machine without any disposal or banked blood. All patients were used with membrane oxygenator. Before CPB, 12 h, 24 h, 72 h and 7 d after CPB, whole blood were taken, then the erythrocyte immune function (C3bRR, RICR) and level of plasma free hemoglobin (FHB) were assayed, and post-operation renal function was compared between the two groups. Moreover, total volume of banked blood transfused to patients after CPB was recorded. (1) After 12 hours, 24 hours, 72 hours, 7 days of CPB, the RBC-C3bRR (14.3% +/- 4.7%, 15.9% +/- 3.6%, 16.6% +/- 2.8%, 19.9% +/- 4.1%) and RBC-ICR (8.7% +/- 1.9%, 9.2% +/- 2.0%, 9.5% +/- 2.6%, 12.0% +/- 2.0%) in study group were significantly elevated than that in control group (RBC-C3bRR 10.7% +/- 2.4%, 11.3% +/- 3.0%, 12.3% +/- 3.5%, 14.5% +/- 2.0%, RBC-ICR 5.9% +/- 1.4%, 6.0% +/- 1.8%, 7.0% +/- 1.7%, 8.7% +/- 2.7%). The erythrocyte immune function after CPB was better and restored faster in study group than that in control group (P < 0.05 in all). (2) After 12 hours, 24 hours of CPB, the levels of FHB (0.41 g/L +/- 0.13 g/L, 0.03 g/L +/- 0.02 g/L) in study group were significantly lower than that in control group (1.02 g/L +/- 0.23 g/L, 0.54 g/L +/- 0.09 g/L) (P < 0.01). After 24 hours of CPB, the level of urinary protein excretion (0.19 g/d +/- 0.08 g/d) in study group was significantly lower than that in control group (0.32 g/d +/- 0.07 g/d) (P < 0.05). (3) After 24 hours of CPB, the level of 24 h creatinine clearance was significantly elevated in study group (68 ml x min(-1) x 1.73 m(-2) +/- 10 ml x min(-1) x 1.73 m(-2)) than that in control group (45 ml x min(-1) x 1.73 m(-2) +/- 4 ml x min(-1) x 1.73 m(-2)) (P < 0.01). (4) The total volume of banked RBCs transfused after CPB were fewer in study group (2.0 U +/- 1.1 U) than that in control group (7.4 U +/- 2.3 U) (P < 0.01). Autotransfusion of washed red blood cells during CPB may improve significantly the erythrocyte immune function and protect kidney function better than transfusion of residual blood in the extracorporal machine or banked blood.

NMDA Receptor Antibodies Predict Adverse Neurological Outcome After Cardiac Surgery in High-Risk Patients

The goal of this study was to compare the predictive ability of S100B, N-methyl-D-aspartate (NMDA) receptor antibodies (NR2Ab) and C-reactive protein (CRP) for neurological deficits after cardiac surgery with cardiopulmonary bypass (CPB). We investigated 557 high-risk adult patients who underwent coronary artery or valve replacement surgery using CPB as a substudy of a prospective, blinded, multicenter clinical trial. Serum concentrations of S100B (n=513 patients), NR2Ab (n=398) and CRP (n=510) were measured preoperatively, 24 and 48 hours after CPB. Neurological adverse events were assessed at baseline and postoperative days 1 and 2; neurocognitive function (mini-mental status examination) was assessed at baseline and on postoperative days 1, 7 and 28. Fifty-five (9.9%) patients had moderate or severe neurological adverse events (confusion/delirium, transient ischemic attack, or stroke) within 48 hours of CPB. Women had significantly more neurological complications than men (15.5% versus 7.8%; P=0.007). Ninety-six percent (24/25) of patients with NR2Ab concentrations > or =2.0 ng/mL preoperatively had neurological complications within 48 hours post-CPB, versus only 5.4% (20/373) of patients with NR2Ab concentrations <2.0 ng/mL, resulting in a 17.9-fold increase (95% CI, 11.6 to 27.6) in postoperative neurological complications for patients with high levels of NR2A antibodies. Preoperative serum S100B and CRP did not predict neurological complications from CPB. Decreased mini-mental status examination scores for orientation, attention and recall were associated with neurological adverse events early after CPB. Preoperative serum concentrations of NR2Ab, but not S100B or CRP, are predictive of severe neurological adverse events after CPB. Patients with a positive NR2Ab test (> or =2.0 ng/mL) preoperatively were nearly 18 times more likely to experience a postoperative neurological event than patients with a negative test (<2.0 ng/mL).