Increase In Acute Kidney Injury Research Articles

#530 Cardiorenal effects of dual blockade with ACE inhibitors and ARBs among people with CKD: emulation of a reference trial (ONTARGET) using CPRD

Abstract Background and Aims Cardiovascular disease (CVD) is a leading cause of death globally, and individuals with chronic kidney disease (CKD) are at increased risk. Results from the ONTARGET trial, in conjunction with the ALTITUDE and VA-Nephron-D studies, led to an end of recommendations for dual ACE inhibitor and ARB therapy due to an increase in acute kidney injury. However, these studies had low power to address long-term kidney outcomes and there remains uncertainty about whether dual therapy could be effective at reducing adverse cardiovascular and renal outcomes in patients with CKD. Observational data provides an opportunity to explore such hypotheses in subgroups underrepresented in trials and with power and follow-up enabling estimation of risk of rare outcomes. We aimed to use ONTARGET to perform a reference trial emulation analysis, before extending analysis to explore treatment effectiveness of dual ARB and ACEi use vs ACEi alone in preventing cardiovascular and renal outcomes among those with CKD. Method Using routinely-collected data from the UK Clinical Practice Research Datalink (CPRD) Aurum linked with Hospital Episode Statistics secondary care data, we applied the ONTARGET trial eligibility criteria to patients prescribed an ARB/ACE inhibitor between 1/1/2001-31/7/2019. As the number of patients receiving prescriptions for both medications on the same day was likely to be small in routine care, we used an operational definition to capture dual users. Outcomes included ONTARGET primary cardiovascular composite outcome of cardiovascular-related death, myocardial infarction, stroke, or hospitalisation for heart failure and a composite renal outcome of ≥50% reduction in GFR or end-stage kidney disease (ESKD). Within the trial-eligible cohort, outcomes of interest were compared between groups prescribed dual therapy vs ACE inhibitors alone using a propensity-score—weighted time-to-event analysis using a Cox proportional hazards model. Conditional on successfully benchmarking results against the ONTARGET trial, we explored treatment effect heterogeneity by chronic kidney disease (CKD) at baseline, with CKD defined as estimated glomerular rate (eGFR) < 60 ml/min/1.73 m2. Results 412,406 trial-eligible patients in CPRD were included in analysis. Among those with non-missing eGFR at baseline, 37% had CKD (Table 1). We found similar effectiveness of dual therapy and ACE inhibitors in reducing the risk of the primary composite cardiovascular outcome (HR 0.98 (95% CI: 0.93, 1.03), consistent with the ONTARGET trial results (HR 0.99 (95% CI: 0.92, 1.07), with no evidence of heterogeneity by CKD (P-value for interaction = 0.14). However, dual therapy use was associated with a greater risk for the composite renal outcome compared to ACE inhibitor, HR 1.24 (95% CI: 1.14, 1.35), with no evidence of heterogeneity by CKD (P = 0.93) (Fig. 1). Analysing components of the composite renal outcome separately gave consistent results (≥50% reduction in GFR: HR 1.22 (95% CI: 1.12, 1.33); ESKD: HR 1.34 (95% CI: 1.24, 1.57)), as did a post-hoc sensitivity analysis by proteinuria status (no proteinuria: HR 1.28 (95% CI: 1.03, 1.59); proteinuria: 1.27 (95% CI: 1.08, 1.49)). Conclusion We found evidence that dual therapy use was associated with increased risk of renal outcomes in both those with and without CKD at baseline. Applying a reference trial emulation approach and successfully benchmarking findings against ONTARGET, where confounding was not present due to randomisation, provides confidence in the validity of these results.

The Role of Tryptophan Metabolism in the Occurrence and Progression of Acute and Chronic Kidney Diseases.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common kidney diseases in clinics with high morbidity and mortality, but their pathogenesis is intricate. Tryptophan (Trp) is a fundamental amino acid for humans, and its metabolism produces various bioactive substances involved in the pathophysiology of AKI and CKD. Metabolomic studies manifestthat Trp metabolites like kynurenine (KYN), 5-hydroxyindoleacetic acid (5-HIAA), and indoxyl sulfate (IS) increasein AKI or CKD and act as biomarkers that facilitate the early identification of diseases. Meanwhile, KYN and IS act as ligands to exacerbate kidney damage by activating aryl hydrocarbon receptor (AhR) signal transduction. The reduction of renal function can cause the accumulation of Trp metabolites which in turn accelerate the progression of AKI or CKD. Besides, gut dysbiosis induces the expansion of Enterobacteriaceae family to produce excessive IS, which cannot be excreted due to the deterioration of renal function. The application of Trp metabolism as a target in AKI and CKD will also be elaborated. Thus, this studyaims to elucidate Trp metabolism in the development of AKI and CKD, and explores the relative treatment strategies by targeting Trp from the perspective of metabolomics to provide a reference for their diagnosis and prevention.

57 Effect of High-Dose Ascorbic Acid in Major Burn Patients: A Systematic Review and Meta-Analysis

Abstract Introduction High-dose ascorbic acid (HDAA) plays an important role in oxygen radical elimination which is a major cause of pathophysiological derangement in burn patients. However, there was limited explicit data on the clinical effect of HDAA in major burn patients. The purpose of this study was to identify the benefit and risks of HDAA in major burn patients. Methods MEDLINE, EMBASE, and Cochrane database searches were conducted. An additional search of relevant primary literature and review articles was performed. All the studies related to HDAA and burn were included in the analysis. HDAA group was defined by receiving ascorbic acid 66 mg/kg/day in the first 24 hours. The primary outcome was the 24-hour fluid requirement. The secondary outcomes were in-hospital mortality, 24-hour urine output, ventilator day, hospital length of stay, and in-hospital complications. Pooled incidences and 95% confidence interval (CI) were calculated and summarized using a random effect model on Stata/MP 16.1. Results Of 875 studies, 7 articles (293 patients) were included in this meta-analysis. HDAA significantly reduced 24-hour fluid requirement compared with usual care (no HDAA) (SMD -0.75 ml/kg per TBSA, 95% CI [-1.38 to -0.12]). HDAA group showed a decrease in 24-hour urine output (SMD, 0.65; 95% CI, 0.41 to 0.89). However, it did not demonstrate significant increase in acute kidney injury (RR 1.37, 95% CI [0.60 to 3.13]) and the need for renal replacement therapy (RR 1.31, 95% CI [0.50 to 3.44]). In terms of in-hospital complications, there was no significant difference in abdominal compartment syndrome (RR 0.22, 95% CI [0.08 to 0.89]) and pneumonia or acute respiratory distress syndrome (RR 1.03, 95% CI [0.70 to 1.51]). Though there was a trend to decrease mortality in the HDAA group, there was no statistical difference in mortality (RR 1.27, 95% CI [0.85 to 1.91]). HDAA group had a comparable hospital length of stay (SMD 0.1, 95% CI [-0.44 to 0.63]) and ventilator day (SMD 0.03, 95% CI [-0.64 to 0.70]). Conclusions High-dose ascorbic acid had a clinical benefit in the significant reduction of 24-hour fluid requirement without increasing the risk for acute kidney injury or the need for renal replacement therapy. Though it did not demonstrate a significant improvement in mortality or length of stay, there were no significant reported complications from high-dose ascorbic acid. A multicenter randomized controlled trial is warranted. Applicability of Research to Practice The potential benefit of HDAA in major burn

Parathyroidectomy and Cinacalcet Use in Medicare-Insured Kidney Transplant Recipients

Posttransplant hyperparathyroidism is common, and treatment practices are poorly characterized. The goal of this study was to examine the incidence, associations, and outcomes of posttransplant parathyroidectomy and calcimimetic use in a cohort of Medicare-insured US kidney transplant recipients. Retrospective observational cohort study. We used the US Renal Data System to extract demographic, clinical, and prescription data from Medicare Parts A, B, and D-insured patients who received their first kidney transplant in 2007-2013. We excluded patients with pretransplant parathyroidectomy. Calendar year of transplantation and pretransplant patient characteristics. (1) Incidence of and secular trends in parathyroidectomy and cinacalcet use in the 3 years after transplant; (2) 90-day outcomes after posttransplant parathyroidectomy and cinacalcet initiation. Temporal trends and pretransplant correlates of parathyroidectomy and cinacalcet use were assessed using proportional hazards models and multivariable Poisson regression, respectively. The inclusion criteria were met by 30,127 patients, of whom 10,707 used cinacalcet before transplant, 551 underwent posttransplant parathyroidectomy, and 5,413 filled≥1 prescription for cinacalcet. The rate of posttransplant parathyroidectomy was stable over time. By contrast, cinacalcet use increased during the period studied. Long dialysis vintage and pretransplant cinacalcet use were strongly associated with posttransplant parathyroidectomy and cinacalcet use. Roughly 1 in 4 patients were hospitalized within 90 days of posttransplant parathyroidectomy, with hypocalcemia-related diagnoses being the most common complication. Parathyroidectomy (vs cinacalcet initiation) was not associated with an increase in acute kidney injury. We lacked access to laboratory data to help assess the severity of secondary/tertiary hyperparathyroidism. The cohort was limited to Medicare beneficiaries. Almost one-fifth of our study cohort was treated with parathyroidectomy and/or cinacalcet. Further studies are needed to establish the optimal treatment for posttransplant hyperparathyroidism.

Hormone therapy use and the risk of acute kidney injury in patients with prostate cancer: a population-based cohort study

BackgroundHormone therapy is widely used in prostate cancer. However, studies have raised concerns that hormone therapy, particularly the use of gonadotropin-releasing hormone agonists, could increase the risk of acute kidney injury.MethodsMen newly diagnosed with non-metastatic prostate cancer, from 2012 to 2017, were identified from the Scottish Cancer Registry. A matched comparison cohort of prostate cancer-free men was also identified. Hormone therapy use was determined from the Prescribing Information System in Scotland. The primary outcome was hospitalisations with acute kidney injury taken from Scottish hospital records (SMR01) up to June 2019. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for acute kidney injury by hormone therapy use.ResultsThe prostate cancer cohort contained 10,751 patients followed for 41,997 person years, during which there were 618 hospitalisations with acute kidney injury. Prostate cancer patients had higher rates of acute kidney injury compared with cancer-free controls (adjusted HR = 1.47 95% CI 1.29, 1.69). However, prostate cancer patients currently using hormone therapy (adjusted HR = 1.14 95% CI 0.92, 1.41), including gonadotropin-releasing hormone (GnRH) agonists (adjusted HR = 1.13 95% CI 0.90, 1.40), did not appear to have a marked increase in acute kidney injury compared with prostate cancer patients not using hormone therapy after adjusting for potential confounders.ConclusionsIn our cohort, there was little evidence that gonadotropin-releasing hormone agonists were associated with marked increases in acute kidney injury.

Decreased antibiotic exposure using a procalcitonin protocol for respiratory infections and sepsis in US community hospitals (ProCommunity)

Objective Antibiotic overuse leading to antimicrobial resistance is a global public health concern. Clinical trials have demonstrated that procalcitonin-based decision-making for antibiotic therapy can safely decrease inappropriate antibiotic use in patients with respiratory infections and sepsis, but real-world data are scarce. This study sought to assess the impact of a procalcitonin-based antibiotic stewardship program (protocol plus education) on antibiotic use in community hospitals. Methods An observational, retrospective, matched cohort study was conducted. Eligible patients treated in hospitals with a procalcitonin-based protocol plus education (Procalcitonin cohort hospitals) were matched to patients admitted to facilities without procalcitonin testing (Control cohort hospitals) using a 1:2 ratio. The Control hospitals were facilities where procalcitonin testing was not available on site. Patient matching was based on: (1) age, (2) gender, (3) admission diagnosis code using groupings of the International Classification of Diseases, 10th Revision, (4) whether patients were admitted to the intensive care unit, and (5) whether a blood culture test was performed. Procalcitonin cohort hospitals implemented a quality improvement initiative, where procalcitonin was available, used regularly, and clinicians (physicians and pharmacists) were educated on its use. Results After adjustment, patients in the Procalcitonin cohort had 1.47 fewer antibiotic days (9.1 vs. 8.5 days, 95%CI: −2.72; −0.22, p = .021). There was no difference in length of stay or adverse clinical outcomes except for increase in acute kidney injury (odds ratio = 1.26, 95%CI: 1.01; 1.58, p = .038). Conclusions Patients with respiratory infections and sepsis in hospitals utilizing a procalcitonin-based protocol coupled with education received fewer days of antibiotic therapy.

A Post Hoc Analysis of Osmotherapy Use in the Erythropoietin in Traumatic Brain Injury Study-Associations With Acute Kidney Injury and Mortality.

Mannitol and hypertonic saline are used to treat raised intracerebral pressure in patients with traumatic brain injury, but their possible effects on kidney function and mortality are unknown. A post hoc analysis of the erythropoietin trial in traumatic brain injury (ClinicalTrials.gov NCT00987454) including daily data on mannitol and hypertonic saline use. Twenty-nine university-affiliated teaching hospitals in seven countries. A total of 568 patients treated in the ICU for 48 hours without acute kidney injury of whom 43 (7%) received mannitol and 170 (29%) hypertonic saline. None. We categorized acute kidney injury stage according to the Kidney Disease Improving Global Outcome classification and defined acute kidney injury as any Kidney Disease Improving Global Outcome stage-based changes from the admission creatinine. We tested associations between early (first 2 d) mannitol and hypertonic saline and time to acute kidney injury up to ICU discharge and death up to 180 days with Cox regression analysis. Subsequently, acute kidney injury developed more often in patients receiving mannitol (35% vs 10%; p < 0.001) and hypertonic saline (23% vs 10%; p < 0.001). On competing risk analysis including factors associated with acute kidney injury, mannitol (hazard ratio, 2.3; 95% CI, 1.2-4.3; p = 0.01), but not hypertonic saline (hazard ratio, 1.6; 95% CI, 0.9-2.8; p = 0.08), was independently associated with time to acute kidney injury. In a Cox model for predicting time to death, both the use of mannitol (hazard ratio, 2.1; 95% CI, 1.1-4.1; p = 0.03) and hypertonic saline (hazard ratio, 1.8; 95% CI, 1.02-3.2; p = 0.04) were associated with time to death. In this post hoc analysis of a randomized controlled trial, the early use of mannitol, but not hypertonic saline, was independently associated with an increase in acute kidney injury. Our findings suggest the need to further evaluate the use and choice of osmotherapy in traumatic brain injury.

Short Versus Extended Duration Vancomycin and Piperacillin/Tazobactam and the Incidence of Acute Kidney Injury in Noncritically Ill Patients

Background: Vancomycin plus piperacillin-tazobactam (VPT) is a commonly used empiric combination of antimicrobials. Recently, studies have demonstrated an increase in acute kidney injury (AKI) associated with combination therapy of VPT. However, the majority of studies required patients to be on VPT for a minimum of 48 to 72 hours to be considered for inclusion and had extended treatment durations longer than most empiric, short course regimens. Objective: To assess the incidence of AKI in noncritically ill patients being treated with VPT for short-courses (24 to 60 hours) compared to patients receiving extended-courses (72 hours to 7 days). Methods: This was a retrospective cohort study comparing the incidence of AKI in noncritically ill patients receiving VPT for short and extended durations between January 2016 and August 2018. Fishers exact tests were used for differences in nominal data between groups and Mann-Whitney U tests were used for continuous data. Results: Of the 2567 screened, 154 patients were included in the short-course group and 106 were included in the extended-course group. The incidence of AKI for patients in the short-course group was 12% (19/154) versus 26% (28/106) in the extended-course group (odds ratio: 2.55, 95% CI: 1.33-4.87; P = .004). Conclusion: In noncritically ill patients, a short-course of VPT experienced less AKI compared to an extended-course. Clinicians should continue to practice strict antimicrobial stewardship for VPT therapies expected to continue beyond 72 hours.

281Impact of complications on VA-ECMO support for cardiopulmonary support: analysis of 8,351 adult patients in Germany from 2007 to 2015

Abstract Background Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used for treatment of patients with critical cardiopulmonary failure. However, utilization of VA-ECMO support must be carefully weighed against possible complications. Therefore, we investigated the incidence and impact of complications on VA-ECMO support in one of the largest datasets of VA-ECMO therapy. Material and methods We analyzed complications and outcomes of all VA-ECMO procedures performed in Germany from 2007 to 2015 by using administrative data from the German Federal Health Monitoring System. For the present analyses all cases treated with VA-ECMO between 2007 and 2015 were identified and selected by the primary procedural code (OPS) for VA-ECMO (OPS code 8852.3). Results Among 8,351 patients undergoing VA-ECMO between 2007 and 2015, there were significant changes in complication rates over time such as increase in acute kidney injury (from 35.9% in 2007–2012 to 44.6% in 2013–2015), major bleeding (from 11.3% in 2007–2012 to 19.5% in 2013–2015 and abdominal ischemia (from 4.5% in 2007–2009 to 7.2% in 2013–2015). The incidence of stroke and limb ischemia did not differ over time. Procedure-related and ischemic complications were more frequently observed in non-survivors as compared to survivors (12.2% versus 15.3%, p&lt;0.001) except for major bleeding (20.9% in survivors versus 15.0% in non-survivors, p&lt;0.001). Multivariate analyses retained stroke and acute kidney injury as being significantly associated with 30-day in-hospital mortality, with respective OR [95% CI] of 1.7 [1.0–2.9] and 1.2 [1.1–1.3]. Conclusion In one of the largest registries, major bleeding and ischemic events are the most common complications on VA-ECMO support. Ischemic complications seem to influence outcome more than bleeding complications. However, only stroke and acute kidney injury were independently associated with higher mortality rates. These findings should be incorporated in risk-benefit stratification when initiation of VA-ECMO and in prevention of complications to avoid additional morbidity and mortality in these critically ill patients.

Acute Kidney Injury in the Age of Enhanced Recovery Protocols.

Acute kidney injury is a prevalent complication after abdominal surgery. With increasing adoption of enhanced recovery protocols, concern exists for concomitant increase in acute kidney injury. This study evaluated effects of enhanced recovery on acute kidney injury through identification of risk factors. This was a retrospective cohort study comparing acute kidney injury rates before and after implementation of enhanced recovery protocol. The study was conducted at a large academic medical center. All of the patients undergoing elective colorectal surgery between 2010 and 2016, excluding patients with stage 5 chronic kidney disease, were included. Patients before and after enhanced recovery implementation were compared, with rate of acute kidney injury as the primary outcome. Acute kidney injury was defined as a rise in serum creatinine ≥1.5 times baseline within 30 days of surgery. Multivariable logistic regression identified risk factors for acute kidney injury. A total of 900 cases were identified, including 461 before and 439 after enhanced recovery; 114 cases were complicated by acute kidney injury, including 11.93% of patients before and 13.44% after implementation of enhanced recovery (p = 0.50). Five patients required hemodialysis, with 2 cases after protocol implementation. Multivariable logistic regression identified hypertension, functional status, ureteral stents, nonsteroidal anti-inflammatory drugs, operative time >200 minutes, and increased intravenous fluid administration on postoperative day 1 as predictors of acute kidney injury. Laparoscopic surgery decreased the risk of acute kidney injury. The enhanced recovery protocol was not independently associated with acute kidney injury. The study was limited by its retrospective and nonrandomized before-and-after design. No difference in rates of acute kidney injury was detected before and after implementation of a colorectal enhanced recovery protocol. Independent predictors of acute kidney injury were identified and could be used to alter the protocol in high-risk patients. Future study is needed to determine whether protocol modifications will further decrease rates of acute kidney injury in this population. See Video Abstract at http://links.lww.com/DCR/A568.

Intraoperative Administration of 4-Factor Prothrombin Complex Concentrate Reduces Blood Requirements in Cardiac Transplantation

Assessing the efficacy of intraoperative 4-factor prothrombin complex concentrate (4F-PCC) use in blood product utilization, time to chest closure, intensive care unit (ICU) and hospital length of stay (LOS), thromboembolic complications, renal injury and mortality in left ventricular assist device (LVAD) patients on home anticoagulation therapy with warfarin, undergoing orthotopic heart transplantation (OHT). Retrospective analysis of OHT patients at Tufts Medical Center from May 2013 to October 2016. Single-institution, university hospital setting. Patients with preexisting LVADs who received orthotopic heart transplants (n = 74; 32 patients 4F-PCC, 42 patients no 4F-PCC). Warfarin reversal using 4F-PCC in patients with LVADs undergoing orthotopic heart transplantation with the 4F-PCC dosing partitioned such that one-third was given pre-CPB and two-thirds were given post-CPB. The 4F-PCC group required less plasma (6 [IQR 4] v 1.31 [IQR 2] U, p < 0.001), cryoprecipitate (10 [IQR 10] v 7.50 [IQR 5] U, p < 0.001), and packed red blood cells (5 [IQR 4] v 2 [IQR 1.5] U, p < 0.001) and had a shorter time to chest closure (618.8 ± 111.4 v 547.9 ± 110.1 minutes, p = 0.008). There was no difference in platelet transfusion (2 [IQR 1] v 2 [IQR 1] U, p = 0.16), ICU or hospital LOS, acute kidney injury, or mortality. No thrombotic complications occurred. Replacing plasma with 4F-PCC to reverse preoperative warfarin anticoagulation during OHT was associated with a shorter time to chest closure and less blood product utilization, without an increase in acute kidney injury, thromboembolic complications, or death.

Early Antimicrobial De-escalation Is Associated with Decreased Acute Kidney Injury in Patients Receiving Empiric Combination Therapy

BackgroundCombination antimicrobial therapy is often initiated for empiric treatment of infections. Recently, vancomycin (VAN) and piperacillin-tazobactam (TZP) therapy has been linked to increases in acute kidney injury (AKI). The objective of this study was to determine whether antimicrobial de-escalation had significant impact on AKI rates.MethodsPatient information from 7/1/2007 through 10/1/15 was collected from the University of Kentucky Center for Clinical and Translational Sciences Enterprise Data Trust. Patients were included if they received VAN and TZP in combination for ≥48 hours. Patients with history of CKD, who presented with AKI outside the treatment window or at baseline, or who were pregnant were excluded from this analysis. AKI was assessed with the Risk, Injury, Failure, Loss, End stage (RIFLE) criteria. De-escalation was defined as discontinuation of one or both agents. Patients were categorized based on time to de-escalation from treatment initiation with ≤3 days being early, 4 to 7 days being mid, and >7 days being late de-escalation. Basic descriptive statistics were performed in addition to multivariable logistic regression.ResultsA total of 7644 patients met all inclusion criteria, with 3664 having early, 2394 with mid, and 1586 with late de-escalation. Patients in the late de-escalation group were slightly older, had higher baseline comorbidity, and were more likely to be exposed to concomitant nephrotoxins than patients in the early and mid de-escalation groups. AKI was more common in the late group (42.7% vs. 23.0% and 13.9% for mid and early groups, respectively; P <0.00001). After controlling confounders, late de-escalation had significantly higher odds of AKI occurring (adjusted odds ratio [aOR]=3.3 [95% CI 2.84–3.83]) compared with patients who had early antimicrobial de-escalation. Additionally, patients in the mid de-escalation group were more likely to experience AKI compared with those in the early group (aOR 1.71 [95% CI 1.49–1.96]).ConclusionEarly antimicrobial de-escalation was associated with significant decreases in AKI incidence in patients receiving empiric VAN and TZP therapy. Controlled studies of early antimicrobial de-escalation and AKI are warranted.Disclosures All authors: No reported disclosures.

Perioperative statin therapy in cardiac surgery: a meta-analysis of randomized controlled trials.

BackgroundSeveral studies suggest beneficial effects of perioperative statin therapy on postoperative outcome after cardiac surgery. However, recent randomized controlled trials (RCTs) show potential detrimental effects. The objective of this systematic review is to examine the association between perioperative statin therapy and clinical outcomes in cardiac surgery patients.MethodsElectronic databases were searched up to 1 November 2016 for RCTs of preoperative statin therapy versus placebo or no treatment in adult cardiac surgery. Postoperative outcomes were acute kidney injury, atrial fibrillation, myocardial infarction, stroke, infections, and mortality. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using fixed-effects meta-analyses. Primary analysis was restricted to trials with low risk of bias according to Cochrane methodology, and sensitivity analyses examined whether the risk of bias of included studies was associated with different results. We performed trial sequential analysis (TSA) to test the strength of the results.ResultsWe included data from 23 RCTs involving 5102 patients. Meta-analysis of trials with low risk of bias showed that statin therapy was associated with an increase in acute kidney injury (314 of 1318 (23.82%) with statins versus 262 of 1319 (19.86%) with placebo; OR 1.26 (95%CI 1.05 to 1.52); p = 0.01); these results were supported by TSA. No difference in postoperative atrial fibrillation, myocardial infarction, stroke, infections, or mortality was present. On sensitivity analysis, statin therapy was associated with a slight increase in hospital mortality. Meta-analysis including also trials with high or unclear risk of bias showed no beneficial effects of statin therapy on any postoperative outcomes.ConclusionsThere is no evidence that statin therapy in the days prior to cardiac surgery is beneficial for patients’ outcomes. Particularly, statins are not protective against postoperative atrial fibrillation, myocardial infarction, stroke, or infections. Statins are associated with a possible increased risk of acute kidney injury and a detrimental effect on hospital survival could not be excluded. Future RCTs should further evaluate the safety profile of this therapy in relation to patients’ outcomes and assess the more appropriate time point for discontinuation of statins before cardiac surgery.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1560-6) contains supplementary material, which is available to authorized users.

Single high dose gentamicin for perioperative prophylaxis in orthopedic surgery: Evaluation of nephrotoxicity

Background:Recent studies described an increase in acute kidney injury when high dose gentamicin was included in perioperative prophylaxis for orthopedic surgeries. To this effect, we compared the rate of nephrotoxicity for selected orthopedic surgeries where gentamicin was included (Gentamicin Group) to those where it was not included (Control Group) for perioperative prophylaxis and evaluated risk factors for nephrotoxicity.Methods:Spine, hip and knee surgeries performed between April 2011 and December 2013 were reviewed retrospectively. Gentamicin was given to eligible patients based on age, weight and Creatinine Clearance. Nephrotoxicity was assessed using Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) criteria.Results:Among selected surgeries (N = 1590 in Gentamicin Group: hip = 926, spine = 600, knee = 64; N = 2587 in Control Group: hip = 980, spine = 902, knee = 705), patients’ body weight, serum creatinine, comorbidities and surgery duration were similar in Gentamicin Group and Control Group. Gentamicin median dose was 4.5 mg/kg of dosing weight. Nephrotoxicity rate was 2.5% in Gentamicin Group and 1.8% in Control Group, p = 0.17. Most cases of nephrotoxicity were Risk category by RIFLE criteria (67% in Gentamicin Group and 72% in Control Group, p = 0.49). In logistic regression, risk factors for nephrotoxicity were hospital stay >1 day prior to surgery (odds ratio = 8.1; 95% confidence interval = 2.25–28.97, p = 0.001), knee or hip surgery (odds ratio = 4.7; 95% confidence interval = 2.9–9.48, p = 0.0005) and diabetes (odds ratio = 1.95; 95% confidence interval = 1.13–3.35, p = 0.016). Receipt of gentamicin was not an independent predictor of nephrotoxicity (odds ratio = 1.5; 95% confidence interval = 0.97–2.35, p = 0.07).Conclusion:In this cohort, rate of nephrotoxicity was similar between Gentamicin Group and Control Group. Single high dose gentamicin is a safe and acceptable option for perioperative prophylaxis in eligible patients undergoing orthopedic surgeries.

CO 8 Does acute kidney injury increase respiratory morbidity in post-operative course in tetralogy of Fallot?

CO 8 Does acute kidney injury increase respiratory morbidity in post-operative course in tetralogy of Fallot?

Addressing the Quality Gap: An Order Set and Checklist to Improve Red Blood Cell Transfusion Ordering Practices on the Internal Medicine Ward

▪Background: Recent guidelines, including ASH Choosing Wisely®, recommend the use of restrictive red blood cell (RBC) transfusion strategies. Our aim was to identify gaps in transfusion ordering practices among trainees and staff physicians on the internal medicine inpatient service, by performing an audit to determine compliance with hospital guidelines. This baseline study was then used to develop and implement preprinted orders and a transfusion checklist as an intervention to improve the quality of transfusion practice.Methods: We performed a single-center retrospective audit of all RBC transfusions ordered by trainees and staff physicians for patients admitted to general internal medicine over a 3-month period (June to August 2013). Compliance with institutional guidelines for transfusion indication and dose were ascertained. Secondary measures included documentation of informed consent, ordering of diuretics, and incidence of transfusion-related adverse events. These results guided the development of a checklist, which was implemented alongside evidence-based preprinted order sets in November 2013. The checklist specifically highlighted discussion of life-threatening transfusion risks, documentation of the informed consent process, and indications for pre-transfusion diuretics to prevent transfusion associated circulatory overload. The audit was repeated over a 3-month post-intervention period (November 2013 to January 2014) to assess for improvement. Comparison between the pre- and post-intervention groups was made using the chi-square test and Fisher’s exact test for categorical variables.Results: 90 transfusion orders in 63 patients were audited in the pre-intervention group, compared with 50 transfusion orders in 31 patients post-intervention; total inpatient days declined by 11.5% over the same period. 98.6% of transfusions were ordered by trainees and 1.4% by attending physicians. Baseline compliance for both indication and dose did not change (84.4% pre-intervention vs. 82.0% post-intervention, p = NS), and pre-transfusion hemoglobin was unchanged (69.0 g/L vs. 69.5 g/L). The frequency at which transfusion rate was specified increased after order sets were implemented (83.3% vs. 98.0%, p = 0.01). While the completion of consent forms was unchanged (98.4% vs. 100.0%, p = NS), explicit documentation of a risks and benefits discussion increased significantly (33.3% vs. 61.3%, p = 0.02). The frequency of appropriate diuretic administration increased (36.7% vs. 70.0%, p = 0.01) without increase in acute kidney injury or significant hypokalemia, and the proportion of diuretics ordered pre-transfusion increased (36.4% vs. 90.5%, p < 0.01). No adverse transfusion-related events occurred in either group.Conclusions: In this single-center study, there was good baseline compliance with transfusion guidelines within general internal medicine at our academic center. The development and implementation of preprinted orders and a checklist, based on gaps identified in the documentation of consent and the ordering of diuretics, significantly improved practices in these domains. These data suggest that preprinted orders and targeted checklists may be simple interventions that can be implemented to improve the quality of transfusion practice. DisclosuresNo relevant conflicts of interest to declare.

Cardiopulmonary Bypass Is Associated With Hemolysis and Acute Kidney Injury in Neonates, Infants, and Children*

This pilot study assesses the degree of hemolysis induced by cardiopulmonary bypass and determines its association with acute kidney injury in pediatric patients. Further, it evaluates the degree to which the use of urinary biomarkers neutrophil gelatinase-associated lipocalin and cystatin C correlate with the presence of acute kidney injury and hemolysis following cardiopulmonary bypass. Prospective observational study. A 13-bed pediatric cardiac ICU in a university hospital. Children undergoing cardiac surgery with the use of cardiopulmonary bypass. None. Blood and urine samples were obtained at multiple time points before and after cardiopulmonary bypass. Hemolysis was assessed by measuring levels of plasma hemoglobin and haptoglobin. Acute kidney injury was defined as a doubling in serum creatinine from preoperative baseline and by using the pediatric-modified RIFLE criteria. Urinary neutrophil gelatinase-associated lipocalin and cystatin C levels were measured. A total of 40 patients (range, 3 d to 4.8 yr) were enrolled. Plasma hemoglobin levels increased markedly on separation from cardiopulmonary bypass with a concurrent decrease in haptoglobin. This was associated with an increase in protein oxidation in the plasma. Hemolysis was more evident in younger patients with a longer duration of bypass and in those requiring a blood-primed circuit. Forty percent of patients had a doubling in serum creatinine and acute kidney injury was developed in 88% of patients when defined by the pediatric-modified RIFLE criteria. Controlling for cardiopulmonary bypass time, persistently elevated levels of plasma hemoglobin were associated with a five-fold increase in acute kidney injury. Further, urinary neutrophil gelatinase-associated lipocalin measured 2 hours after separation from cardiopulmonary bypass was associated with acute kidney injury and with elevations in plasma hemoglobin. Cardiopulmonary bypass in pediatric patients results in significant hemolysis, which is associated with the development of acute kidney injury. The biomarker neutrophil gelatinase-associated lipocalin correlates with both acute kidney injury and hemolysis in this population.

Metabolic syndrome is associated with type II endoleak after endovascular abdominal aortic aneurysm repair

Type II endoleak is usually a benign finding after endovascular abdominal aortic aneurysm repair (EVAR). In some patients, however, type II endoleak leads to aneurysm sac expansion and the need for further intervention. We examined which factors, in particular the components of metabolic syndrome (MetS), would lead to an increase risk of endoleak after EVAR. The medical records of all patients who underwent EVAR between 2002 and 2011 at the Veterans Affairs Connecticut Healthcare System were reviewed. MetS was defined as the presence of three or more of the following: hypertension (blood pressure ≥130 mm Hg/≥90 mm Hg), serum triglycerides ≥150 mg/dL, serum high-density lipoproteins ≤50 mg/dL for women and ≤40 mg/dL for men, body mass index ≥30 kg/m(2), and fasting blood glucose ≥110 mg/dL. Development of endoleak, including specific endoleak type, was determined by review of standard radiologic surveillance. During a 9-year period, 79 male patients (mean age, 73.5 years), underwent EVAR for infrarenal abdominal aortic aneurysm (mean 6.2 cm maximal transverse diameter). MetS was present in 52 patients (66%). The distribution of MetS factors among all patients was hypertension in 86%, hypertriglyceridemia in 72%, decreased high-density lipoprotein in 68%, diabetes in 37%, and a body mass index of ≥30 kg/m(2) in 30%. No survival difference was found between the MetS and non-MetS groups (P = .66). There was no difference in perioperative myocardial infarction or visceral ischemia immediately postoperatively between the two groups. Patients with MetS had a significant increase in acute kidney injury (n = 7, P = .0128). Endoleaks of all types were detected in 26% (n = 20) of all patients; patients with MetS had more endoleaks than patients without MetS (35% vs 7.4%, P = .0039). Of the 19 type II endoleaks, 79% were present at the time of EVAR and only 21% developed during surveillance; 95% had MetS (P = .0007). Type II endoleak after EVAR for abdominal aortic aneurysm is associated with MetS. Whether these patients are subject to more subsequent intervention due to sac expansion is unclear. MetS may be a factor to consider in the treatment of type II endoleak.

Risk of acute kidney injury associated with the use of fluoroquinolones

Case reports indicate that the use of fluoroquinolones may lead to acute kidney injury. We studied the association between the use of oral fluoroquinolones and acute kidney injury, and we examined interaction with renin-angiotensin-system blockers. We formed a nested cohort of men aged 40-85 enrolled in the United States IMS LifeLink Health Plan Claims Database between 2001 and 2011. We defined cases as men admitted to hospital for acute kidney injury, and controls were admitted to hospital with a different presenting diagnosis. Using risk-set sampling, we matched 10 controls to each case based on hospital admission, calendar time (within 6 wk), cohort entrance (within 6 wk) and age (within 5 yr). We used conditional logistic regression to assess the rate ratio (RR) for acute kidney injury with current, recent and past use of fluoroquinolones, adjusted by potential confounding variables. We repeated this analysis with amoxicillin and azithromycin as controls. We used a case-time-control design for our secondary analysis. We identified 1292 cases and 12 651 matched controls. Current fluoroquinolone use had a 2.18-fold (95% confidence interval [CI] 1.74-2.73) higher adjusted RR of acute kidney injury compared with no use. There was no association between acute kidney injury and recent (adjusted RR 0.87, 95% CI 0.66-1.16) or past (RR 0.86, 95% CI 0.66-1.12) use. The absolute increase in acute kidney injury was 6.5 events per 10 000 person-years. We observed 1 additional case per 1529 patients given fluoroquinolones or per 3287 prescriptions dispensed. The dual use of fluoroquinolones and renin-angiotensin-system blockers had an RR of 4.46 (95% CI 2.84-6.99) for acute kidney injury. Our case-time-control analysis confirmed an increased risk of acute kidney injury with fluoroquinolone use (RR 2.16, 95% CI 1.52-3.18). The use of amoxicillin or azithromycin was not associated with acute kidney injury. We found a small, but significant, increased risk of acute kidney injury among men with the use of oral fluoroquinolones, as well as a significant interaction between the concomitant use of fluoroquinolones and renin-angiotensin-system blockers.

Acute kidney injury—global health alert

World Kidney Day will be celebrated on March 14 2013, and this year, aims to increase awareness of the global increase in acute kidney injury (AKI). An urgent need exists for a global health strategy to reduce the burden of AKI; efforts focused on preventing AKI should be coupled with early detection, treatment, and follow-up strategies.