Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci.

Acute kidney injury (AKI) is a common, serious complication of cardiac surgery. Since prior studies have supported a genetic basis for postoperative AKI, we conducted a genome-wide association study (GWAS) for AKI following coronary bypass graft (CABG) surgery. The discovery data set consisted of 873 nonemergent CABG surgery patients with cardiopulmonary bypass (PEGASUS), while a replication data set had 380 cardiac surgical patients (CATHGEN). Single-nucleotide polymorphism (SNP) data were based on Illumina Human610-Quad (PEGASUS) and OMNI1-Quad (CATHGEN) BeadChips. We used linear regression with adjustment for a clinical AKI risk score to test SNP associations with the postoperative peak rise relative to preoperative serum creatinine concentration as a quantitative AKI trait. Nine SNPs meeting significance in the discovery set were detected. The rs13317787 in GRM7|LMCD1-AS1 intergenic region (3p21.6) and rs10262995 in BBS9 (7p14.3) were replicated with significance in the CATHGEN data set and exhibited significantly strong overall association following meta-analysis. Additional fine mapping using imputed SNPs across these two regions and meta-analysis found genome-wide significance at the GRM7|LMCD1-AS1 locus and a significantly strong association at BBS9. Thus, through an unbiased GWAS approach, we found two new loci associated with post-CABG AKI providing new insights into the pathogenesis of perioperative AKI.

High incidence of antibodies to protamine and protamine/heparin complexes in patients undergoing cardiopulmonary bypass.

Protamine is routinely used to reverse heparin anticoagulation during cardiopulmonary bypass (CPB). Heparin interacts with protamine to form ultralarge complexes that are immunogenic in mice. We hypothesized that patients exposed to protamine and heparin during CPB will develop antibodies (Abs) to protamine/heparin (PRT/H) complexes that are capable of platelet activation. Specimens from a recently completed prospective clinical trial (HIT [for heparin-induced thrombocytopenia] 5801 study; n = 500) of CPB patients were examined for PRT/H Abs at baseline, at time of hospital discharge (between days 3 through 7), and 30 days after CPB. PRT/H antibody features were characterized and correlated with adverse cardiovascular outcomes. We found a high incidence of PRT/H antibody formation (29%) in patients undergoing cardiac surgery. PRT/H Abs were of high titer (mean titer 1:14,744), showed heparin-dependent binding, and activated platelets in the presence of protamine. PRT/H Abs showed no cross-reactivity to platelet factor 4/heparin complexes, but were cross-reactive with protamine-containing insulin preparations. In the absence of circulating antigen at day 30, there were no complications of thrombocytopenia, thrombotic events, or long-term cardiovascular events. These studies show that Abs to PRT/H occur commonly after cardiac bypass surgery, share a number of serologic features with HIT Abs, including platelet activation, and may pose health risks to patients requiring drug reexposure.

ABO blood group influences transfusion and survival after cardiac surgery.

ABO dependent variation in von Willebrand factor (vWf) and procoagulant factor VIII (FVIII) is a plausible mechanism for modulating perioperative hemostasis and bleeding. Group AB has the highest and group O the lowest vWf and FVIII levels. Therefore, we tested the hypothesis that ABO blood group is associated with perioperative transfusion and subsequent survival after coronary revascularization. This retrospective study combined demographic, operative, and transfusion data, including follow-up for a median of 2,096 days, for consecutive aortocoronary bypass (CABG) and CABG/valve procedures from 1996-2009 at a tertiary referral University Heart Center. Between group differences were compared by a Kruskall Wallis test, and hazard ratios [95% confidence intervals] are reported for mortality risk-adjusted Cox proportional hazards regression analysis. From 15,454 patients, follow-up records were available for 13,627 patients: 6,413 group O, 5,248 group A, 1,454 group B, and 435 group AB. Packed red blood cells were the most commonly transfused blood product (3 [0-5] units), while group AB received 2 [0-5] units (Kruskall Wallis Chi squared value for between group differences = 8.2; p = 0.04). Group AB favored improved long-term, postoperative survival (Hazard ratio = 0.82 [95%CI 0.68-0.98]; p = 0.03), which became evident approximately a year after surgery. In conclusion, the procoagulant phenotype of blood group AB is associated with fewer transfusions and improved late survival after cardiac surgery. Whether this finding is related to fewer perioperative transfusions, a reduction in later bleeding or other mechanisms remains speculative.

Diastolic dysfunction in patients undergoing cardiac surgery: the role of gender and age-gender interaction.

OBJECTIVES: To test the hypothesis that females presenting for coronary artery bypass graft (CABG) surgery are at a higher risk of left ventricular diastolic dysfunction (LVDD) and that age and gender interact to influence this risk. DESIGN: Retrospective observational study. SETTING: Tertiary university hospital. PARTICIPANTS: Eight hundred-ninety-five adult patients undergoing CABG surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline diastolic function was graded according to a predefined Doppler-based algorithm, which defined LVDD as a binary variable (grades 2 and 3 only) and as a continuous variable (E/e' ratio). The authors found that women were more likely to present with LVDD in 2 multivariate regression models using both LVDD definitions (odds ratio = 2.7; p<0.0001 for logistic model, and parameter estimate (PE) = 2.8; p<0.0001 for the linear model). In addition, there was a significant age and gender interaction on the risk of LVDD in the linear model (PE = 0.08; p = 0.01). A restricted cubic splines analysis revealed a progressively higher risk of LVDD (predicted E/e' ratio) among older women. CONCLUSIONS: The authors confirmed that women undergoing CABG surgery are at higher risk of LVDD compared to men with a significant age-gender interaction suggesting a possible age-related differential effect on LVDD between the genders, a phenomenon previously demonstrated in preclinical studies. Therapies aimed at amelioration of diastolic dysfunction additionally should consider the higher risk in females, especially within the older subset of the patient population.

Dynamic indices of mitral valve function using perioperative three-dimensional transesophageal echocardiography.

OBJECTIVE: Perioperative transesophageal echocardiography is essential for decision-making for mitral valve surgery. While two-dimensional transesophageal echocardiography represents the standard of care, tracking of dynamic changes using three-dimensional imaging permits assessment of morphologic and functional characteristics of the mitral valve. The authors hypothesized that quantitative three-dimensional analysis would reveal distinct differences among diseased, repaired, and normal mitral valves. DESIGN: Case-control observational clinical study. SETTING: Tertiary care hospital. PARTICIPANTS: Using novel mitral valve quantification software, the authors retrospectively analyzed 80 datasets of cardiac surgery patients who underwent intraoperative transesophageal echocardiographic imaging. Twenty patients with degenerative mitral regurgitation were evaluated before and after mitral valve repair. Twenty patients had functional mitral regurgitation, and 20 patients had no mitral valve disease. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures of dynamic mitral valve function were: 1) three-dimensional annulus area, 2) annular displacement distance, 3) annular displacement velocity, and 4) annular area fraction. Other mitral annular tracking indices, in addition to intraobserver reliability and interobserver agreement, also were reported. Annulus area was enlarged in degenerative and functional mitral regurgitation. Annular displacement distance was decreased in functional mitral regurgitation and repaired valves. Annular displacement velocity was decreased in functional mitral regurgitation. Annular area fraction was decreased in functional mitral regurgitation and repaired valves. Intraobserver reliability and interobserver agreement were high for all 4 analyzed indices. CONCLUSIONS: Normal, functional regurgitant, degenerative, and repaired mitral valves have distinctly different dynamic signatures of anatomy and function as reliably determined by perioperative echocardiographic tracking.

Arterial hyperoxia during cardiopulmonary bypass and postoperative cognitive dysfunction.

OBJECTIVE: To determine the effect of arterial normobaric hyperoxia during cardiopulmonary bypass (CPB) on postoperative neurocognitive function. The authors hypothesized that arterial hyperoxia during CPB is associated with neurocognitive decline at 6 weeks after cardiac surgery. DESIGN: Retrospective study of patients undergoing cardiac surgery with CPB. SETTING: A university hospital. PARTICIPANTS: One thousand eighteen patients undergoing coronary artery bypass graft (CABG) or CABG + valve surgery with CPB who previously had been enrolled in prospective cognitive trials. INTERVENTIONS: A battery of neurocognitive measures was administered at baseline and 6 weeks after surgery. Anesthetic and surgical care was managed as clinically indicated. MEASUREMENTS AND MAIN RESULTS: Arterial hyperoxia was assessed primarily as the area under the curve (AUC) for the duration that PaO2 exceeded 200 mmHg during CPB and secondarily as the mean PaO2 during bypass, as a PaO2 = 300 mmHg at any point and as AUC>150 mmHg. Cognitive change was assessed both as a continuous change score and a dichotomous deficit rate. Multivariate regression accounting for age, years of education, baseline cognition, date of surgery, baseline postintubation PaO2, duration of CPB, and percent change in hematocrit level from baseline to lowest level during CPB revealed no significant association between hyperoxia during CPB and postoperative neurocognitive function. CONCLUSIONS: Arterial hyperoxia during CPB was not associated with neurocognitive decline after 6 weeks in cardiac surgical patients.

Predictors of cognitive recovery after cardiac surgery.

BACKGROUND: Postoperative neurocognitive decline occurs frequently. Although predictors of cognitive injury have been well examined, factors that modulate recovery have not. We sought to determine the predictors of cognitive recovery after initial injury following cardiac surgery. METHODS: Two hundred eighty-one patients previously enrolled in cognitive studies who experienced cognitive decline 6 weeks after cardiac surgery were retrospectively evaluated. Eligible patients completed a battery of neurocognitive measures and quality-of-life assessments at baseline, 6 weeks, and 1 year after surgery. Factor analysis was conducted to calculate the cognitive index (CI), a unified, continuous measure of cognitive function. Cognitive recovery was defined as 1-year CI greater than baseline CI. Potential predictors of cognitive recovery including patient characteristics, quality-of-life factors, comorbidities, medications, and intraoperative variables were assessed with multivariable regression modeling; P<0.05 was considered significant. RESULTS: Of the 229 patients in our final data set, 103 (45%) demonstrated cognitive recovery after initial decline in CI at 6 weeks. Multivariable analyses revealed that more education (odds ratio [OR] 1.332 [1.131-1.569], P<0.001), baseline CI (OR 0.987 [0.976-0.998], P=0.02), less decline in CI at 6 weeks (OR 1.044 [1.014-1.075], P=0.004), and greater activities of daily living at 6 weeks (OR 0.891 [0.810-0.981], P=0.02) were significant predictors of cognitive recovery. CONCLUSION: Cognitive recovery occurred in approximately one half of the cardiac surgical patients experiencing early decline. The association between cognitive recovery and Instrumental Activities of Daily Living scores at 6 weeks merits further investigation as it is the only potentially modifiable predictor of recovery.

The effect of aprotinin on outcome after coronary-artery bypass grafting.

BACKGROUND: Aprotinin has recently been associated with adverse outcomes in patients undergoing cardiac surgery. We reviewed our experience with this agent in patients undergoing cardiac surgery at Duke University Medical Center. METHODS: We retrieved data on 10,275 consecutive patients undergoing surgical coronary revascularization at Duke between January 1, 1996, and December 31, 2005. We fit data to a logistic-regression model predicting each patient's likelihood of receiving aprotinin on the basis of preoperative characteristics and to models predicting long-term survival (up to 10 years) and decline in renal function, as measured by increases in serum creatinine levels. RESULTS: A total of 1343 patients (13.2%) received aprotinin, 6776 patients (66.8%) received aminocaproic acid, and 2029 patients (20.0%) received no antifibrinolytic therapy. All patients underwent coronary-artery bypass grafting, and 1181 patients (11.5%) underwent combined coronary-artery bypass grafting and valve surgery. In the risk-adjusted model, survival was worse among patients treated with aprotinin, with a main-effects hazard ratio for death of 1.32 (95% confidence interval [CI], 1.12 to 1.55) for the comparison with patients receiving no antifibrinolytic therapy (P=0.003) and 1.27 (95% CI, 1.10 to 1.46) for the comparison with patients receiving aminocaproic acid (P=0.004). As compared with the use of aminocaproic acid or no antifibrinolytic agent, aprotinin use was also associated with a larger risk-adjusted increase in the serum creatinine level (P<0.001) but not with a greater risk-adjusted incidence of dialysis (P=0.56). CONCLUSIONS: Patients who received aprotinin had a higher mortality rate and larger increases in serum creatinine levels than those who received aminocaproic acid or no antifibrinolytic agent.

A clinical prediction tool to estimate the number of units of red blood cells needed in primary elective coronary artery bypass surgery.

BACKGROUND: Red blood cell (RBC) transfusion is common during cardiac surgical procedures. Empiric crossmatching, without attempting to estimate individual transfusion requirements is typical. We hypothesized that a clinical prediction tool could be developed to estimate the number of units of RBCs needed for coronary artery bypass grafting (CABG) surgery. STUDY DESIGN AND METHODS: With institutional review board approval, detailed demographic, risk factor, and transfusion data of primary elective CABG procedures (n=5887) from September 1, 1993, to June 20, 2002, were studied and the data set was divided into development and validation subgroups. Multivariable ordinal logistic regression was used to develop and validate transfusion risk factors, assign them a relative weight, and create a model to stratify patients into groups depending on predicted need for 0, 2, 4, or more than 4 RBC units. The model was compared with current standard practice of crossmatching 4 RBC units in terms of observed blood product usage over the study period. RESULTS: Demographic and transfusion risk factor variables in the development (n=3876) and validation (n=2011) data sets were similar. The predictive value of the model was good for the development and validation groups, with a c-index of 0.79 and 0.78, respectively. Applying the predictive model reduced the number of crossmatches by 30% without underproviding RBC units and increased the percentage of patients crossmatched exactly for the required number of units from 11% to 21%. CONCLUSIONS: Predictive factors for RBC transfusion were identified and used to construct a clinical tool to conserve blood bank resources without increasing patient risk.

Storage age of transfused platelets and outcomes after cardiac surgery.

BACKGROUND: The relationship between duration of platelet (PLT) storage, currently limited to 5days, and surgical outcomes has not been established. We tested the hypothesis that PLT storage age was associated with adverse outcomes. STUDY DESIGN AND METHODS: A retrospective cohort of aortocoronary bypass (CABG) surgery patients from January 1996 to January 2005 receiving one or more PLT transfusions was selected for study. The composite primary ("short-term") outcome was 30-day mortality or prolonged hospital stay. Secondary outcomes included complications and survival to annual follow-up. Multivariable logistic regression models and Cox proportional hazards regression analysis evaluated the association between PLT storage age and outcomes, expressed as an odds ratio (OR) or hazard ratio with 95% confidence intervals (CIs), respectively. RESULTS: PLT transfusion was administered to 3272 of 10,275 CABG patients and 2578 received units of known storage age, which ranged between 2 and 5days (median, 4days; 25th percentile, 3days; 75th percentile, 5 days). The mortality rate for the 1637 patients receiving a single plateletpheresis transfusion was 3.8%, while 21.6% experienced a prolonged hospital stay or death. After adjusting for the number of PLT and red blood cell (RBC) units transfused, RBC storage age, and preoperative mortality risk, there was no association between PLT storage age and short-term outcome (OR, 1.01; 95% CI, 0.90-1.14), survival (hazard ratio [HR], 1.04; 95% CI, 0.96-1.13), or postoperative infections. CONCLUSIONS: PLT storage age was not associated with adverse short-term outcomes, decreased long-term survival, or infections after cardiac surgery.

Intraoperative systolic blood pressure variability predicts 30-day mortality in aortocoronary bypass surgery patients.

BACKGROUND: Few data support an association between blood pressure variability and clinical outcomes during cardiac surgery. We tested the hypothesis that intraoperative systolic blood pressure variability outside a targeted blood pressure range predicts 30-day mortality in patients undergoing cardiac surgery. METHODS: Electronically captured blood pressure data from 7,504 consecutive coronary bypass surgery procedures between September 1, 1996, and December 31, 2005, were divided into development and validation cohorts. Systolic blood pressure variability episodes outside a blood pressure range (e.g., higher than 135 or lower than 95 mmHg) were characterized by number of episodes, magnitude of episode, duration of episode, and magnitude x duration of excursion (i.e., area under the curve). Multiple logistic regression analysis was used to assess 30-day mortality association. The most predictive mortality risk characteristic and blood pressure range was tested in the validation cohort. RESULTS: A total of 3.1 million intraoperative blood pressure evaluations were analyzed. Systolic blood pressure variability was derived in 5,038 patients and validated in 2,466 patients (8% without cardiopulmonary bypass and 6% with valve procedure). Among all tested indices of blood pressure variability, mean duration of systolic excursion (outside a range of 105-130 mmHg) was most predictive of 30-day mortality (odds ratio = 1.03 per minute, 95% CI 1.02-1.39, P < 0.0001). CONCLUSIONS: Intraoperative blood pressure variability is associated with 30-day postoperative mortality in patients undergoing aortocoronary bypass surgery.

Cognitive function after major noncardiac surgery, apolipoprotein E4 genotype, and biomarkers of brain injury.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a significant cause of morbidity after noncardiac surgery. Identified risk factors are largely limited to demographic characteristics. We hypothesized that POCD was associated with apolipoprotein E4 (APOE4) genotype and plasma biomarkers of brain injury and inflammation. METHODS: Three hundred ninety-four patients older than 55 yr undergoing major elective noncardiac surgery were enrolled in this prospective observational study. Apolipoprotein E genotyping was performed at baseline. Plasma was collected at baseline and end of surgery and at 4.5, 24, and 48-h postoperatively. Six protein biomarkers were assayed (B-type natriuretic peptide, C-reactive protein, D-dimer, matrix metalloproteinase-9, neuron-specific enolase, and S-100B). Neurocognitive testing was conducted at baseline and at 6 weeks and 1 yr after surgery; scores were subjected to factor analysis. The association of APOE4 and biomarkers with POCD was tested using multivariable regression modeling. RESULTS: Three hundred fifty patients (89%) completed 6-week neurocognitive testing. POCD occurred in 54.3% of participants at 6 weeks and 46.1% at 1 yr. There was no difference in POCD between patients with or without the APOE4 allele (56.6 vs. 52.6%; P = 0.58). The continuous cognitive change score (mean +/- SD) was similar between groups (APOE4: 0.05 +/- 0.27 vs. non-APOE4: 0.07 +/- 0.28; P = 0.53). Two hundred ninety-one subjects (74%) completed testing at 1 yr. POCD occurred in 45.9% of APOE4 subjects versus 46.3% of non-APOE4 subjects (P = 0.95). The cognitive score was again similar (APOE4: 0.08 +/- 0.27 vs. non-APOE4: 0.05 +/- 0.25; P = 0.39). Biomarker levels were not associated with APOE4 genotype or cognition at 6 weeks or 1 yr. CONCLUSION: Cognitive decline after major noncardiac surgery is not associated with APOE4 genotype or plasma biomarker levels.

Glycosylated hemoglobin levels and outcome in non-diabetic cardiac surgery patients.

PURPOSE: In diabetics, elevated preoperative hemoglobin A1c (HbA1c) levels are associated with increased complication rates after cardiac surgery. While many non-diabetics also have elevated HbA1c, the relationship with outcome in these patients is not well understood. Therefore, in a cohort of non-diabetic patients, we tested the hypothesis that preoperative HbA1c is associated with early mortality risk after cardiac surgery. METHODS: In this retrospective observational study, we accessed data from a prospectively collected quality assurance database for a cohort of 1,474 non-diabetic elective cardiac surgery patients with documented preoperative HbA1c levels. The relationship of HbA1c with death within 30 days of surgery was examined using logistic regression modeling. Acute kidney injury and infection were similarly assessed using multivariable linear and logistic regression. RESULTS: Thirty-one percent of patients (n = 456) had elevated HbA1c values (>6.0%). Patients with elevated HbA1c had higher fasting and peak intraoperative blood glucose values. Also, an elevated HbA1c level was independently associated with increased 30-day mortality (odds ratio 1.53 per percent increase [1.24-1.91]; P = 0.0005). This relationship persisted even after "borderline" diabetics were excluded. Furthermore, acute kidney injury was associated with elevated baseline HbA1c (P = 0.01). No association was found between HbA1c and postoperative infection risk (P = 0.48). CONCLUSION: In non-diabetics, an elevated preoperative HbA1c level (>6.0%) is independently associated with significantly greater early mortality risk after elective cardiac surgery. Our findings suggest that HbA1c may have value as a screening tool to identify high-risk non-diabetic cardiac surgery patients.

Association of the 98T ELAM-1 polymorphism with increased bleeding after cardiac surgery.

OBJECTIVE: Hemorrhage continues to be a major problem after cardiac surgery despite the routine use of antifibrinolytic drugs, with striking inter-patient variability poorly explained by already known risk factors. The authors tested the hypothesis that genetic polymorphisms of inflammatory mediators and cellular adhesion molecules are associated with bleeding after cardiac surgery. DESIGN: Prospective, observational study. SETTING: Single, tertiary referral university heart center. PARTICIPANTS: Adult patients undergoing aortocoronary surgery with cardiopulmonary bypass. INTERVENTIONS: Patients (n = 759) had 10 mL of blood drawn preoperatively and genomic DNA isolated then genotyped for 17 polymorphisms in 7 candidate genes: tumor necrosis factor, interleukins 1beta and 6, interleukin 1 receptor antagonist, intercellular adhesion molecule-1 (ICAM-1), P-selectin and endothelial leucocyte adhesion molecule-1 (E-selectin). Multivariate analyses were used to relate clinical and genetic factors to bleeding and transfusion. MEASUREMENTS AND MAIN RESULTS: The 98G/T polymorphism of the E-selectin gene was independently associated with bleeding after cardiac surgery (p = 0.002), after adjusting for significant clinical predictors (patient size and baseline hemoglobin concentration). There was a gene dose effect according to the number of minor alleles in the genotype; carriers of the minor allele bled 17% (GT) and 54% (TT) more than wild type (GG) genotypes, respectively (p = 0.01). Carriers of the minor allele also had longer activated partial thromboplastin times (p = 0.0023) and increased fresh frozen plasma transfusion (p = 0.03) compared with wild type. CONCLUSIONS: The authors found a dose-related association between the 98T E-selectin polymorphism and bleeding after cardiac surgery, independent of and additive to standard clinical risk factors.

Randomized, double-blinded, placebo controlled study of neuroprotection with lidocaine in cardiac surgery.

BACKGROUND AND PURPOSE: Cognitive decline after cardiac surgery remains common and diminishes patients' quality of life. Based on experimental and clinical evidence, this study assessed the potential of intravenously administered lidocaine to reduce postoperative cognitive dysfunction after cardiac surgery using cardiopulmonary bypass. METHODS: After IRB approval, 277 patients undergoing cardiac surgery were enrolled into this prospective, randomized, double-blinded placebo controlled clinical trial. Subjects were randomized to receive: (1) Lidocaine as a 1 mg/kg bolus followed by a continuous infusion through 48 hours postoperatively, or (2) Placebo bolus and infusion. Cognitive function was assessed preoperatively and again at 6 weeks and 1 year postoperatively. The effect of lidocaine on postoperative cognition was tested using multivariable regression modeling; P<0.05 was considered significant. RESULTS: Among the 241 allocated subjects (Lidocaine: n=114; Placebo: n=127), the incidence of cognitive deficit in the lidocaine group was 45.5% versus 45.7% in the placebo group (P=0.97). Multivariable analysis revealed a significant interaction between treatment group and diabetes, such that diabetic subjects receiving lidocaine were more likely to suffer cognitive decline (P=0.004). Secondary analysis identified total lidocaine dose (mg/kg) as a significant predictor of cognitive decline and also revealed a protective effect of lower dose lidocaine in nondiabetic subjects. CONCLUSIONS: Lidocaine administered during and after cardiac surgery does not reduce the high rate of postoperative cognitive dysfunction. Higher doses of lidocaine and diabetic status were independent predictors of cognitive decline. Protective effects of lower dose lidocaine in nondiabetic subjects need to be further evaluated.

A prospective, double-blind, randomized clinical feasibility trial of controlling the storage age of red blood cells for transfusion in cardiac surgical patients.

BACKGROUND: Recent evidence demonstrates an association between duration of storage of red blood cells (RBC) and morbidity and mortality after cardiac surgery. We studied the feasibility of two different schemes for categorizing and randomizing age of RBC units transfused in cardiac surgical patients. STUDY DESIGN AND METHODS: In Phase 1, 20 subjects were randomly assigned to standard of care (SOC) versus no RBCs with more than 21 days' storage duration. In Phase 2, 23 subjects were randomized to RBCs of 7 +/- 4 versus 21 +/- 4 days' storage duration. The age of study RBC units was masked. RESULTS: In Phase 1, no patients received RBCs 31 days or older in SOC, and there was overlap in storage age shared in both arms so the predefined feasibility criteria were not met. In Phase 2, it was feasible to deliver specified age RBCs to the 7-day arm (achieved in 100% of subjects), but feasibility was not demonstrated for the 21-day arm (only 50% of subjects transfused with target age RBCs). Significant differences, however, were observed between the 7 +/- 4- and 21 +/- 4-day arms with respect to age of all RBC units (6 +/- 2 vs. 18 +/- 7, p = 0.0002) and maximum age (7 +/- 2 vs. 20 +/- 7, p < 0.0001). CONCLUSION: Given the current storage age distribution of available RBC inventory, use of a SOC arm in future studies is unlikely to result in a large exposure to "old" blood. It is feasible to randomize patients to "younger" RBCs (3-11 days) but design strategies are needed to provide "intermediate-aged" or "old" blood as a comparator.

S100B and brain natriuretic peptide predict functional neurological outcome after intracerebral haemorrhage.

OBJECTIVE: To determine the predictive value of S100b and brain natriuretic peptide (BNP) in order to determine accurately and quickly a discharge prognosis after primary supratentorial intracerebral haemorrhage (ICH). METHODS: After IRB approval and informed consent, blood samples were obtained and analysed from 28 adult patients consecutively admitted to the neuroscience intensive care unit with computed tomography-proven supratentorial ICH from June 2003 and December 2004 within the first 24 h after symptom onset for S100b and BNP. Functional outcomes on discharge were dichotomized to favourable (mRS < 3) or unfavourable. RESULTS: BNP (a neurohormone) and S100b (a marker of glial activation) were found to be independently highly predictive of functional neurological outcome at the time of discharge as measured by the modified Rankin Score (BNP: p < 0.01, r = 0.46; S100b: p < 0.01, r = 0.42) and the Barthel Index (BNP: p < 0.01, r = 0.54; s100b: p < 0.01, r = 0.50). Although inclusion of either biomarker produced additive value when included with traditional clinical prognostic variables, such as the ICH score (Barthel index: p < 0.01, r = 0.66; mRS: p < 0.01, r = 0.96), little predictive power is added with inclusion of both biomarkers in a regression model for neurological outcome. CONCLUSIONS: Serum S100b and BNP levels in the first 24 h after injury accurately predict neurological function at discharge after supratentorial ICH.

Mortality trends associated with acute renal failure requiring dialysis after CABG surgery in the United States.

BACKGROUND/AIMS: Acute renal failure is associated with a high risk of mortality when it complicates coronary artery bypass graft (CABG) surgery. We examined a large nationwide database from 1988 to 2003 and hypothesized that mortality in CABG-associated acute renal failure needing dialysis (ARF-D) had declined during this period. METHODS: The Nationwide Inpatient Sample containing data on inpatient stays across 20% of US hospitals was used for our study. Multivariate logistic regression was used to determine an association between year and ARF-D mortality with standardized risk adjustment. RESULTS: Incidence of ARF-D increased from 0.2 to 0.6% while mortality simultaneously decreased from 47.4% in 1988 to 29.7% in 2003. In the multivariable model, year was significantly associated with declining ARF-D mortality. CONCLUSIONS: The incidence of post-CABG ARF-D more than doubled from 1988 to 2003, while mortality simultaneously decreased by over one-third. Improved survival after ARF-D following CABG may be counterbalanced by increased morbidity and resource utilization.

Assessing teamwork in medical education and practice: relating behavioural teamwork ratings and clinical performance.

BACKGROUND: Problems with communication and team coordination are frequently linked to adverse events in medicine. However, there is little experimental evidence to support a relationship between observer ratings of teamwork skills and objective measures of clinical performance. AIM: Our main objective was to test the hypothesis that observer ratings of team skill will correlate with objective measures of clinical performance. METHODS: Nine teams of medical students were videotaped performing two types of teamwork tasks: (1) low fidelity classroom-based patient assessment and (2) high fidelity simulated emergent care. Observers used a behaviourally anchored rating scale to rate each individual on skills representative of assertiveness, decision-making, situation assessment, leadership, and communication. A checklist-based measure was used to assess clinical team performance. RESULTS: Moderate to high inter-observer correlations and moderate correlations between cases established the validity of a behaviourally anchored team skill rating tool for simulated emergent care. There was moderate to high correlation between observer ratings of team skill and checklist-based measures of team performance for the simulated emergent care cases (r = 0.65, p = 0.06 and r = 0.97, p < 0.0001). CONCLUSIONS: These results provide prospective evidence of a positive relationship between observer ratings of team skills and clinical team performance in a simulated dynamic health care task.

Trends in cardiac surgery-associated acute renal failure in the United States: a disproportionate increase after heart transplantation.

Acute renal failure (ARF) is common after cardiac surgery and more frequent after complex cardiac surgery. While the incidence of ARF is increasing after coronary artery bypass graft (CABG) surgery, trends in other forms of cardiac surgery remain unclear. We investigated the trend of ARF in various cardiac procedures and compared patterns using CABG surgery as a reference group. The study population consisted of discharges from the Nationwide Inpatient Sample from 1988 to 2003, grouped according to surgery as: CABG, CABG with mitral valve, CABG with other valve, valve alone, and heart transplant. Standard diagnostic codes were used to identify ARF among discharges. Multivariable regression was used to determine trends in ARF among various procedures with CABG as a reference group. The incidence of ARF increased in all five groups (p < 0.001) over the 16-year period. The ARF incidence was highest in the heart transplant group (17%). Compared to the CABG population, patients following heart transplantation developed ARF at higher rates during the study period. In contrast, while ARF increased over time in other groups, the rates of rise were slower than in CABG patients. Among heart surgery procedures, ARF incidence is highest in heart transplantation. The incidence of ARF is also increasing at a faster rate in this group of patients in contrast to other procedure groups when compared to CABG surgery. The disproportionate increase in ARF burden after heart transplantation is a concern due to its strong association with chronic kidney disease and mortality.