Stress Biomarkers Do Not Correlate With Risk Factors for Kidney Injury After Cardiac Surgery.

BACKGROUND: The urinary cell cycle arrest biomarkers (UBs) insulin-like growth factor-binding protein-7 and tissue inhibitor of metalloproteinases-2 provide early detection of kidney stress, and elevations may predict cardiac surgery-associated acute kidney injury (CS-AKI). We sought to determine whether known clinical risk factors for CS-AKI correlated with increased UB values. METHODS: UBs were measured over a 12-month period the morning after on-pump cardiac surgery. Patients with a preoperative serum creatinine level greater than 2.0 mg/dL or patients undergoing dialysis were excluded. Known clinical AKI risk factors in patients with elevated UB (>0.3 (ng/mL)2/1000), that is known to correlate with kidney stress, were compared with patients with low scores (≤0.3 (ng/mL)2/1000) by using logistic regression; the analysis was repeated with UB as a continuous variable. RESULTS: A total of 412 patients met inclusion criteria. Unadjusted results demonstrated a clinically similar CS-AKI risk profile in patients with either elevated or low UB values. The Pearson correlation between preoperative estimated glomerular filtration rate and UB was low (r = 0.16). Clinical risk factors for CS-AKI were not associated with elevated UB values in the logistic regression model, thus producing an area under the receiver operating characteristic curve of 0.63. Linear regression analysis also found few associations between CS-AKI clinical risk factors and UB when measured as a continuous variable, (R2) = 0.15. CONCLUSIONS: Traditional CS-AKI clinical risk factors do not differ between patients with normal or elevated UB values. This UB test may identify patients at increased risk for AKI who otherwise would appear to be at low risk by traditional metrics.

Using urinary biomarkers to reduce acute kidney injury following cardiac surgery.

BACKGROUND: Prediction of acute kidney injury (AKI) following cardiac surgery is unreliable through the use of serum creatinine or urinary output alone. Cell cycle arrest urinary biomarkers insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP2) provide early detection of kidney stress and possibly AKI. We sought to determine whether therapeutic interventions driven by elevated urinary biomarkers (UB) reduces post-cardiac surgery stage 2/3 AKI. METHODS: A quality improvement initiative based on UB was undertaken in all adult on-pump cardiac surgical patients with a preoperative serum creatinine level ≤2.0 mg/dL. A UB score the morning after cardiac surgery that was considered positive for kidney stress (≥0.3 [ng/mL]2/1000) triggered activation of a multidisciplinary acute kidney response team (AKRT) with implementation of a predefined staged protocol, including targeted goal-directed fluid management, liberalized transfusion thresholds, continued invasive hemodynamic monitoring and its optimization in the intensive care unit, and avoidance of nephrotoxins. We compared the incidence of stage 2/3 AKI before (pre-UB) versus after (post-UB) implementation of the Kidney Disease: Improving Global Outcomes quality improvement initiative. Standardized, protocolized, evidence-based care pathways were used pre-UB. RESULTS: The incidence of stage 2/3 AKI was compared in 435 pre-UB patients and 412 post-UB patients. Fifty-five percent of the post-UB patients had a moderate or high UB score (≥0.3 [ng/mL]2/1000). Ten patients (2.30%) had stage 2/3 AKI pre-UB, compared with 1 patient (0.24%) post-UB, a relative reduction of 89% (P = .01). The total and postoperative lengths of stay, cost, mortality, and readmissions were similar in the 2 groups. The negative predictive value for AKI of UB <0.3 [ng/mL]2/1000 was 100%. CONCLUSIONS: The routine measurement of UB and subsequent activation of an AKRT are useful post-cardiac surgery therapeutic adjuncts. They are associated with early detection of kidney stress, allowing for targeted proactive intervention, and a significant decrease in postoperative stage 2/3 AKI without increases in cost or length of stay.

Guidelines for Perioperative Care in Cardiac Surgery: Enhanced Recovery After Surgery Society Recommendations.

Enhanced Recovery After Surgery (ERAS) evidence-based protocols for perioperative care can lead to improvements in clinical outcomes and cost savings. This article aims to present consensus recommendations for the optimal perioperative management of patients undergoing cardiac surgery. A review of meta-analyses, randomized clinical trials, large nonrandomized studies, and reviews was conducted for each protocol element. The quality of the evidence was graded and used to form consensus recommendations for each topic. Development of these recommendations was endorsed by the Enhanced Recovery After Surgery Society.

Hemoadsorption to Reduce Plasma-Free Hemoglobin During Cardiac Surgery: Results of REFRESH I Pilot Study.

Generation of plasma-free hemoglobin (pfHb) and activated complement during complex cardiac surgery contributes to end-organ dysfunction. This prospective, multicenter REFRESH I (REduction in FREe Hemoglobin) randomized controlled trial evaluated the safety and feasibility of CytoSorb hemoadsorption therapy to reduce these factors during prolonged cardiopulmonary bypass (CPB). Eligible patients underwent elective, nonemergent complex cardiac surgery with expected CPB duration ≥3 hours. Exclusions included single procedures including primary coronary artery bypass graft, single valves, transplant, and left ventricular assist device extraction. TREATMENT used 2 parallel 300 mL CytoSorb hemoadsorption cartridges in a side circuit during CPB. CONTROL was standard of care. Of 52 enrolled patients, 46 underwent surgery (Safety group, n = 23 vs Control, n = 23), and 38 were evaluated for pfHb reduction (EFFICACY group, n = 18 vs CONTROL, n = 20). Type and number of serious adverse events (44 vs 43 CONTROL) were similar, as was 30-day mortality. Transient reduction in platelets during CPB was observed in both groups, especially TREATMENT, but returned to pretreatment levels after CPB without bleeding. Peak pfHb was positively correlated with CPB length (P = 0.01) but the high variability of pfHb, due to the broad surgical procedure mix, prevented detection of changes in pfHb in the overall EFFICACY population. However, the valve replacement surgery subgroup (8 vs 10 CONTROL) had the highest peak pfHb levels, and TREATMENT demonstrated significant pfHb reductions vs CONTROL (P ≤ 0.05) in CPB ≥3 hours. In the EFFICACY group, C3a and C5a were significantly reduced by treatment throughout surgery. Intraoperative hemoadsorption with CytoSorb was safe and feasible in this randomized, controlled pilot study during complex cardiac surgery. Treatment with CytoSorb resulted in significant reductions in pfHb during valve replacement surgery and reductions in C3a and C5a in the overall EFFICACY group. Future studies will target complex cardiac surgery patients with prolonged CPB to assess hemoadsorption effect on end-organ dysfunction and outcomes.

Effects of an Ambulation Orderly Program Among Cardiac Surgery Patients.

BACKGROUND: Despite the known benefits of ambulation, most hospitalized patients remain physically inactive. One possible approach to this problem is to employ "ambulation orderlies" (AOs) - employees whose main responsibility is to ambulate patients throughout the day. For this study, we examined an AO program implemented among postcardiac surgery patients and its effect on patient outcomes. METHODS: We evaluated postoperative length of stay, hospital complications, discharge disposition, and 30-day readmission for all patients who underwent coronary artery bypass or cardiac valve surgery in the 9 months prior to and after the introduction of the AO program. In addition to pre-post comparisons, we performed an interrupted time series analysis to adjust for temporal trends and differences in baseline characteristics. RESULTS: We included 447 and 478 patients in the pre- and post-AO intervention groups, respectively. Postoperative length of stay was lower in the post-AO group, with median (interquartile range) of 10 (7, 14) days vs 9 (7, 13) days (P <.001), and also had significantly less variability in mean monthly length of stay (Levene's test P = .03). Using adjusted interrupted time series analysis, the program was associated with a decreased mean monthly postoperative length of stay (-1.57 days, P = .04), as well as a significant decrease in the trend of mean monthly postoperative length of stay (P = .01). Other outcomes were unaffected. CONCLUSION: The implementation of an AO program was associated with a significant reduction in postoperative length and variability of hospital stay. These results suggest that an AO program is a reasonable and practical approach towards improving hospital outcomes.

Ambulation Orderlies and Recovery After Cardiac Surgery: A Pilot Randomized Controlled Trial.

BACKGROUND: One potential strategy to increasing physical activity after surgery is to utilize an ambulation orderly (AO), a dedicated employee whose assures frequent patient walking. However, the impact of an AO on physical and functional recovery from surgery is unknown. METHODS: We randomized post-operative cardiac surgical patients to receive either the AO or usual care. We measured average daily step count, changes in 6-minute walk test (6MWT) distance, and changes in functional independence (Barthel Index.) Our primary goal was to test protocols, measure variability in activity, and establish effect sizes. RESULTS: Thirty-six patients were randomized (18 per group, 45% bypass surgery). Overall, patients exhibited significant recovery of physical function from baseline to discharge in the 6MWT (from 83 to 172 meters, p < 0.001) and showed improvement in independent function (Barthel Index, 67 to 87, p <0.001). Moreover, each additional barrier to ambulation (supplemental oxygen, intravenous poles/fluid, walkers, urinary catheters, and chest tubes) reduced average daily step count by 330 steps/barrier, p = 0.04. However, the AO intervention resulted in only a small difference in average daily step counts (2718 vs. 2541 steps/day, Cohen's d = 0.16, 608 patients needed for larger trial), which we attributed to several trial factors that likely weakened the AO intervention. CONCLUSIONS: In this pilot study, we observed significant in-hospital physical and functional recovery from surgery, but the addition of an AO made only marginal differences in daily step counts. Future studies should consider stepped-wedge or cluster trial designs to increase intervention effectiveness. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov unique identifier: NCT02375282.

Development and Validation of a Predictive Model for Short- and Medium-Term Hospital Readmission Following Heart Valve Surgery.

BACKGROUND: Although models exist for predicting hospital readmission after coronary artery bypass surgery, no such models exist for predicting readmission after heart valve surgery (HVS). METHODS AND RESULTS: Using a geographically and structurally diverse sample of US hospitals (Premier Inpatient Database, January 2007-June 2011), we examined patient, hospital, and clinical factors predictive of short- and medium-term hospital readmission post-HVS. We set aside 20% of hospitals for model validation. A generalized estimating equation model accounted for clustering within hospitals. At 219 hospitals, we identified 38 532 patients (67 years, 56% male, 62% aortic valve surgery) who underwent HVS. A total of 3125 (7.8%) and 4943 (12.8%) patients were readmitted to the index hospital within 1 and 3 months, respectively. Our 3-month model predicted readmission rates between 3% and 61% with fair discrimination (C-statistic, 0.67) and good calibration (predicted vs observed differences in validation cohort averaged 1.9% across all deciles of predicted readmission risk). Results were similar for our 1-month model and our simplified 3-month model (suitable for clinical use), which used the 5 strongest predictors of readmission: transfused units of packed Red blood cells, presence of End-stage renal disease, type of Valve surgery, Emergency hospital admission, and hospital Length of stay (REVEaL). CONCLUSIONS: We described and validated key factors that predict short- and medium-term hospital readmission post-HVS. These models should enable clinicians to identify individuals with HVS who are at increased risk for hospital readmission and are most likely to benefit from improved postdischarge care and follow-up.

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines for Cardiopulmonary Bypass--Temperature Management during Cardiopulmonary Bypass.

To improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendation.

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines for Cardiopulmonary Bypass--Temperature Management During Cardiopulmonary Bypass.

UNLABELLED: In order to improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including: 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendations: CLASS I RECOMMENDATIONS: a)The oxygenator arterial outlet blood temperature is recommended to be utilized as a surrogate for cerebral temperature measurement during CPB. (Class I, Level C) b)To monitor cerebral perfusate temperature during warming, it should be assumed that the oxygenator arterial outlet blood temperature under-estimates cerebral perfusate temperature. (Class I, Level C) c)Surgical teams should limit arterial outlet blood temperature to<37°C to avoid cerebral hyperthermia. (Class 1, Level C) d)Temperature gradients between the arterial outlet and venous inflow on the oxygenator during CPB cooling should not exceed 10°C to avoid generation of gaseous emboli. (Class 1, Level C) e)Temperature gradients between the arterial outlet and venous inflow on the oxygenator during CPB rewarming should not exceed 10°C to avoid out-gassing when blood is returned to the patient. (Class 1, Level C) CLASS IIa RECOMMENDATIONS: a)Pulmonary artery or nasopharyngeal temperature recording is reasonable for weaning and immediate post-bypass temperature measurement. (Class IIa, Level C)b)Rewarming when arterial blood outlet temperature ≥30° C: i.To achieve the desired temperature for separation from bypass, it is reasonable to maintain a temperature gradient between arterial outlet temperature and the venous inflow of≤4°C. (Class IIa, Level B) ii.To achieve the desired temperature for separation from bypass, it is reasonable to maintain a rewarming rate≤0.5°C/min. (Class IIa, Level B) NO RECOMMENDATION: No recommendation for a guideline is provided concerning optimal temperature for weaning from CPB due to insufficient published evidence.

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines for Cardiopulmonary Bypass--Temperature Management During Cardiopulmonary Bypass.

In order to improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including: 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendations: No Recommendation No recommendation for a guideline is provided concerning optimal temperature for weaning from CPB due to insufficient published evidence.

Strategies and Devices to Minimize Stroke in Adult Cardiac Surgery.

Stroke after cardiac surgery is a devastating complication with a frequency of 1%-3% and a potential mortality risk of >20%. The approaches that one should consider to minimize the risk of stroke associated with cardiac surgery involve preoperative, intraoperative, and postoperative interventions, which are described in detail.

Effects of red-cell storage duration on patients undergoing cardiac surgery.

BACKGROUND: Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion. METHODS: We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. RESULTS: The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. CONCLUSIONS: The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).

Sildenafil-mediated neovascularization and protection against myocardial ischaemia reperfusion injury in rats: role of VEGF/angiopoietin-1.

Sildenafil citrate (SC), a drug for erectile dysfunction, is now emerging as a cardiopulmonary drug. Our study aimed to determine a novel role of sildenafil on cardioprotection through stimulating angiogenesis during ischaemia (I) reperfusion (R) at both capillary and arteriolar levels and to examine the role of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) in this mechanistic effect. Rats were divided into: control sham (CS), sildenafil sham (SS), control+IR (CIR) and sildenafil+IR (SIR). Rats were given 0.7 mg/kg, (i.v) of SC or saline 30 min. before occlusion of left anterior descending artery followed by reperfusion (R). Sildenafil treatment increased capillary and arteriolar density followed by increased blood flow (2-fold) compared to control. Treatment with sildenafil demonstrated increased VEGF and Ang-1 mRNA after early reperfusion. PCR data were validated by Western blot analysis. Significant reduction in infarct size, cardiomyocyte and endothelial apoptosis were observed in SC-treated rats. Increased phosphorylation of Akt, eNOS and expression of anti-apoptotic protein Bcl-2, and thioredoxin, hemeoxygenase-1 were observed in SC-treated rats. Echocardiography demonstrated increased fractional shortening and ejection fraction following 45 days of reperfusion in the treatment group. Stress testing with dobutamine infusion and echocardiogram revealed increased contractile reserve in the treatment group. Our study demonstrated for the first time a strong additional therapeutic potential of sildenafil by up-regulating VEGF and Ang-1 system, probably by stimulating a cascade of events leading to neovascularization and conferring myocardial protection in in vivo I/R rat model.