Epidemiology of surgery associated acute kidney injury (EPIS-AKI): a prospective international observational multi-center clinical study.

PURPOSE: The incidence, patient features, risk factors and outcomes of surgery-associated postoperative acute kidney injury (PO-AKI) across different countries and health care systems is unclear. METHODS: We conducted an international prospective, observational, multi-center study in 30 countries in patients undergoing major surgery (> 2-h duration and postoperative intensive care unit (ICU) or high dependency unit admission). The primary endpoint was the occurrence of PO-AKI within 72 h of surgery defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary endpoints included PO-AKI severity and duration, use of renal replacement therapy (RRT), mortality, and ICU and hospital length of stay. RESULTS: We studied 10,568 patients and 1945 (18.4%) developed PO-AKI (1236 (63.5%) KDIGO stage 1500 (25.7%) KDIGO stage 2209 (10.7%) KDIGO stage 3). In 33.8% PO-AKI was persistent, and 170/1945 (8.7%) of patients with PO-AKI received RRT in the ICU. Patients with PO-AKI had greater ICU (6.3% vs. 0.7%) and hospital (8.6% vs. 1.4%) mortality, and longer ICU (median 2 (Q1-Q3, 1-3) days vs. 3 (Q1-Q3, 1-6) days) and hospital length of stay (median 14 (Q1-Q3, 9-24) days vs. 10 (Q1-Q3, 7-17) days). Risk factors for PO-AKI included older age, comorbidities (hypertension, diabetes, chronic kidney disease), type, duration and urgency of surgery as well as intraoperative vasopressors, and aminoglycosides administration. CONCLUSION: In a comprehensive multinational study, approximately one in five patients develop PO-AKI after major surgery. Increasing severity of PO-AKI is associated with a progressive increase in adverse outcomes. Our findings indicate that PO-AKI represents a significant burden for health care worldwide.

Protocolization of Analgesia and Sedation Through Smart Technology in Intensive Care: Improving Patient Safety.

BACKGROUND: The risk of medication errors in intensive care units is high, primarily in the drug administration phase. LOCAL PROBLEM: Management of high-alert medications within intensive care units in the study institution varied widely. The aim of this quality improvement project was to protocolize and centralize the management of high-alert medications in acute care settings and to implement smart intravenous infusion pump technology in intensive care units. METHODS: The project was conducted in 4 phases: (1) protocolization and standardization of intravenous mixtures, (2) centralization of intravenous mixture preparation in the Pharmacy Department, (3) programming of the smart pumps, and (4) dissemination and staged implementation of intravenous mixture protocols. Smart pumps (Alaris, CareFusion) were used to deliver the medicines, and the manufacturer's software (Alaris Guardrails, CareFusion) was used to analyze data regarding adherence to the drug library and the number of programming errors detected. RESULTS: Morphine, remifentanil, fentanyl, midazolam, dexmedetomidine, and propofol were included. After implementation of the smart pumps, 3283 infusions were started; of these, 2198 were programmed through the drug library, indicating 67% compliance with the safety software. The pumps intercepted 398 infusion-related programming errors that led to cancellation or reprogramming of drug infusions. CONCLUSIONS: Protocolization and centralization of the preparation of high-alert sedative and analgesic medications for critically ill patients and the administration of these drugs using smart pump technology decrease variability of clinical practice and intercept potentially serious medication errors.

Biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2 trial): study protocol for an international, prospective, randomised controlled multicentre trial.

INTRODUCTION: Previous studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader population of patients undergoing surgery require confirmation. METHODS AND ANALYSIS: The BigpAK-2 trial is an international, randomised, controlled, multicentre trial. The trial aims to enrol 1302 patients undergoing major surgery who are subsequently admitted to the intensive care or high dependency unit and are at high-risk for postoperative AKI as identified by urinary biomarkers (tissue inhibitor of metalloproteinases 2*insulin like growth factor binding protein 7 (TIMP-2)*IGFBP7)). Eligible patients will be randomised to receive either standard of care (control) or a KDIGO-based AKI care bundle (intervention). The primary endpoint is the incidence of moderate or severe AKI (stage 2 or 3) within 72 hours after surgery, according to the KDIGO 2012 criteria. Secondary endpoints include adherence to the KDIGO care bundle, occurrence and severity of any stage of AKI, change in biomarker values during 12 hours after initial measurement of (TIMP-2)*(IGFBP7), number of free days of mechanical ventilation and vasopressors, need for renal replacement therapy (RRT), duration of RRT, renal recovery, 30-day and 60-day mortality, intensive care unit length-of-stay and hospital length-of-stay and major adverse kidney events. An add-on study will investigate blood and urine samples from recruited patients for immunological functions and kidney damage. ETHICS AND DISSEMINATION: The BigpAK-2 trial was approved by the Ethics Committee of the Medical Faculty of the University of Münster and subsequently by the corresponding Ethics Committee of the participating sites. A study amendment was approved subsequently. In the UK, the trial was adopted as an NIHR portfolio study. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research. TRIAL REGISTRATION NUMBER: NCT04647396.

Impact of COVID-19 on Short- and Medium-Term Prescription of Enteral Nutrition in the General Population vs. Older People in the Community of Madrid, Spain.

We aimed to analyse the impact of COVID-19 during 2020 and 2021 on the prescription of enteral nutritional support and its expenditure in the Community of Madrid, Spain, compared to pre-pandemic data from 2016 in the general population vs. elderly. We analysed official electronic prescriptions of all public hospitals of the Community of Madrid. The population over 75 years of age have the higher prescription of nutritional supplements (p < 0.001 vs. other age groups), with no differences between the 45−64 age group compared to the 65−74 age group (χ2 = 3.259, p = 0.196). The first wave of COVID-19 or the first time there was a real awareness of the virus in Spain is similar in a way to the first peak of prescription of enteral nutrition in March 2020. The second peak of prescription was observed in the over 75 age group in July 2020, being more pronounced in December 2020 and March−April of the following year (F = 7.863, p = 0.041). The last peaks correspond to summer 2021 and autumn of the same year (p = 0.031­year 2021 vs. 2020, p = 0.011­year 2021 vs. 2019), where a relationship between increased prescription of enteral nutrition and COVID-19 cases is observed. High-protein and high-calorie dietary therapies were the most prescribed in patients with or without diabetes. All of this entailed higher cost for the Community of Madrid. In conclusion, COVID-19 significantly affected the prescription of nutritional support, especially in the population over 75 years of age.

Study protocol for an observational cohort evaluating incidence and clinical relevance of perioperative elevation of high-sensitivity troponin I and N-terminal pro-brain natriuretic peptide in patients undergoing lung resection.

INTRODUCTION: Myocardial injury after non-cardiac surgery has been defined as myocardial injury due to ischaemia, with or without additional symptoms or ECG changes occurring during or within 30 days after non-cardiac surgery and mainly diagnosed based on elevated postoperative cardiac troponin (cTn) values. In patients undergoing thoracic surgery for lung resection, only postoperative cTn elevations are seemingly not enough as an independent predictor of cardiovascular complications. After lung resection, troponin elevations may be regulated by mechanisms other than myocardial ischaemia. The combination of perioperative natriuretic peptide measurement together with high-sensitivity cTns may help to identify changes in ventricular function during thoracic surgery. Integrating both cardiac biomarkers may improve the predictive value for cardiovascular complications after lung resection. We designed our cohort study to evaluate perioperative elevation of both high-sensitivity troponin I (hs-TnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients undergoing lung resection and to establish a risk score for major cardiovascular postoperative complications. METHODS AND ANALYSIS: We will conduct a prospective, multicentre, observational cohort study, including 345 patients undergoing elective thoracic surgery for lung resection. Cardiac biomarkers such as hs-TnI and NT-proBNP will be measured preoperatively and at postoperatively on days 1 and 2. We will calculate a risk score for major cardiovascular postoperative complications based on both biomarkers' perioperative changes. All patients will be followed up for 30 days after surgery. ETHICS AND DISSEMINATION: All participating centres were approved by the Ethics Research Committee. Written informed consent is required for all patients before inclusion. Results will be disseminated through publication in peer-reviewed journals and presentations at national or international conference meetings. TRIAL REGISTRATION NUMBER: NCT04749212.

Individualized prediction for the occurrence of acute kidney injury during the first postoperative week following cardiac surgery.

STUDY OBJECTIVE: To develop individualized dynamic predictions for the occurrence of acute kidney injury (AKI) during the first postoperative week after cardiac surgery. DESIGN: Observational retrospective cohort study. SETTING: Single university teaching hospital in Madrid, Spain. PATIENTS: 3960 cases of major cardiac surgery performed from January 2002 to December 2013. MEASUREMENTS: Baseline demographic and clinical characteristics, intraoperative risk factors, and repeated postoperative estimated glomerular filtration rates (eGFR). The primary outcome was AKI during the first postoperative week (stage 1 or higher of the Acute Kidney Injury Network). The dataset was split in two random samples (exploratory and validation). By combining time-to-event outcomes (AKI), and longitudinal data (repeated postoperative eGFR), we developed two different joint models for patients with normal and high baseline levels of serum creatinine (sCr). MAIN RESULTS: AKI occurred in 1105 patients (31%, 95% confidence interval [CI] 29.5-32.5) in the exploratory sample and 128 (32.2%, 95% CI 27.6-36.8) in the validation sample. For high baseline sCr patients, the risk of an AKI event was associated with the eGFR trajectory (hazard ratio [HR] 0.91, 95% CI 0.90-0.92), as well as with age, and cardiopulmonary bypass time. The normal baseline sCr model incorporated the same covariates and intraoperative transfusion. In this second model, the risk of an AKI event was associated with both the eGFR trajectory (HR 0.91, 95% CI 0.91-0.92, for the current value of eGFR), and with its slope at that point (HR 0.96, 95% CI 0.94-0.99). So AKI risk decreased when the eGFR values increased, in accordance with the speed of this rise. Internal validation showed good discrimination and calibration of both joint models. The AUCs were always higher than 0.7. CONCLUSIONS: The joint models obtained combining both patient risk factors and postoperative eGFR values, are useful to predict individualized risk of cardiac surgery-associated AKI. Predictions can be updated as new information is gathered.

Preoperative clinical model to predict myocardial injury after non-cardiac surgery: a retrospective analysis from the MANAGE cohort in a Spanish hospital.

OBJECTIVES: To determine preoperative factors associated to myocardial injury after non-cardiac surgery (MINS) and to develop a prediction model of MINS. DESIGN: Retrospective analysis. SETTING: Tertiary hospital in Spain. PARTICIPANTS: Patients aged ≥45 years undergoing major non-cardiac surgery and with at least two measures of troponin levels within the first 3 days of the postoperative period. All patients were screened for the MANAGE trial. PRIMARY AND SECONDARY OUTCOME MEASURES: We used multivariable logistic regression analysis to study risk factors associated with MINS and created a score predicting the preoperative risk for MINS and a nomogram to facilitate bed-side use. We used Least Absolute Shrinkage and Selection Operator method to choose the factors included in the predictive model with MINS as dependent variable. The predictive ability of the model was evaluated. Discrimination was assessed with the area under the receiver operating characteristic curve (AUC) and calibration was visually assessed using calibration plots representing deciles of predicted probability of MINS against the observed rate in each risk group and the calibration-in-the-large (CITL) and the calibration slope. We created a nomogram to facilitate obtaining risk estimates for patients at pre-anaesthesia evaluation. RESULTS: Our cohort included 3633 patients recruited from 9 September 2014 to 17 July 2017. The incidence of MINS was 9%. Preoperative risk factors that increased the risk of MINS were age, American Status Anaesthesiology classification and vascular surgery. The predictive model showed good performance in terms of discrimination (AUC=0.720; 95% CI: 0.69 to 0.75) and calibration slope=1.043 (95% CI: 0.90 to 1.18) and CITL=0.00 (95% CI: -0.12 to 0.12). CONCLUSIONS: Our predictive model based on routinely preoperative information is highly affordable and might be a useful tool to identify moderate-high risk patients before surgery. However, external validation is needed before implementation.

Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study.

BACKGROUND: Critically ill patients with coronavirus disease 19 (COVID-19) have a high fatality rate likely due to a dysregulated immune response. Corticosteroids could attenuate this inappropriate response, although there are still some concerns regarding its use, timing, and dose. METHODS: This is a nationwide, prospective, multicenter, observational, cohort study in critically ill adult patients with COVID-19 admitted into Intensive Care Units (ICU) in Spain from 12th March to 29th June 2020. Using a multivariable Cox model with inverse probability weighting, we compared relevant outcomes between patients treated with early corticosteroids (before or within the first 48 h of ICU admission) with those who did not receive early corticosteroids (delayed group) or any corticosteroids at all (never group). Primary endpoint was ICU mortality. Secondary endpoints included 7-day mortality, ventilator-free days, and complications. RESULTS: A total of 691 patients out of 882 (78.3%) received corticosteroid during their hospital stay. Patients treated with early-corticosteroids (n = 485) had lower ICU mortality (30.3% vs. never 36.6% and delayed 44.2%) and lower 7-day mortality (7.2% vs. never 15.2%) compared to non-early treated patients. They also had higher number of ventilator-free days, less length of ICU stay, and less secondary infections than delayed treated patients. There were no differences in medical complications between groups. Of note, early use of moderate-to-high doses was associated with better outcomes than low dose regimens. CONCLUSION: Early use of corticosteroids in critically ill patients with COVID-19 is associated with lower mortality than no or delayed use, and fewer complications than delayed use.

Estimated glomerular filtration rate is an early biomarker of cardiac surgery-associated acute kidney injury. / La tasa de filtrado glomerular estimada es un biomarcador precoz de la insuficiencia renal aguda asociada a la cirugía cardíaca.

BACKGROUND: and objective Acute kidney injury (AKI) diagnosis is still based on serum creatinine and diuresis. However, increases in creatinine are typically delayed 48h or longer after injury. Our aim was to determine the utility of routine postoperative renal function blood tests, to predict AKI one or 2days in advance in a cohort of cardiac surgery patients. PATIENTS AND METHODS: Using a prospective database, we selected a sample of patients who had undergone major cardiac surgery between January 2002 and December 2013. The ability of the parameters to predict AKI was based on Acute Kidney Injury Network serum creatinine criteria. A cohort of 3,962 cases was divided into 2groups of similar size, one being exploratory and the other a validation sample. The exploratory group was used to show primary objectives and the validation group to confirm results. The ability to predict AKI of several kidney function parameters measured in routine postoperative blood tests, was measured with time-dependent ROC curves. The primary endpoint was time from measurement to AKI diagnosis. RESULTS: AKI developed in 610 (30.8%) and 623 (31.4%) patients in the exploratory and validation samples, respectively. Estimated glomerular filtration rate using the MDRD-4 equation showed the best AKI prediction capacity, with values for the AUC ROC curves between 0.700 and 0.946. We obtained different cut-off values for estimated glomerular filtration rate depending on the degree of AKI severity and on the time elapsed between surgery and parameter measurement. Results were confirmed in the validation sample. CONCLUSIONS: Postoperative estimated glomerular filtration rate using the MDRD-4 equation showed good ability to predict AKI following cardiac surgery one or 2days in advance.

Impact of the implementation of vasoactive drug protocols on costs in the treatment of critically ill patients.

OBJECTIVE: To evaluate the efficiency of the protocolization and centralization of  the preparation of intravenous vasoactive drug mixtures in the treatment of  critically ill patients. METHOD: A prospective interventional study (July 2012-December 2014) was  conducted to measure the impact of different vasoactive drug protocols on costs  in the treatment of critically ill patients. The economic impact was measured by  comparing the direct costs (fixed and variable) of the preparation of intravenous  vasoactive drug mixtures in the Pharmacy Department with their traditional  preparation in hospital care units. The variables time and cost of preparation of  an intravenous mixture were measured. Costs included pharmaceutical product,  diluent, medical supplies, cost of manpower, and use of laminar flow cabinets in  the Pharmacy Department. Costs were measured in Euros. RESULTS: A statistically significant difference was found between processing times in the Pharmacy Department and those in the hospital care unit (2.10 vs 2.86 minutes). Centralized preparation in the Pharmacy Department  was more efficient. The average cost of preparation was €5.24±1.45 in the  Pharmacy Department and €5.62±1.55 in the hospital care unit, although this  difference did not reach statistical significance. If the analysis had included the  cost of intravenous mixtures that had expired prior to their use, the centralized  preparation of the mixtures in the Pharmacy Department would have entailed a  higher cost (€2 174/y). CONCLUSIONS: The centralized preparation of intravenous mixtures in the Pharmacy Department entails significant time savings compared with their preparation in the hospital care unit.

Objetivo: Evaluar la eficiencia de la protocolización y centralización de la  elaboración de mezclas intravenosas de fármacos vasoactivos en el tratamiento  del paciente crítico.Método: Se realizó un estudio prospectivo, de intervención (julio 2012- diciembre 2014) para medir el impacto de la protocolización de mezclas  intravenosas en el coste del tratamiento del paciente crítico. Para realizar el  análisis económico se compararon los costes directos (fijos y variables) de la  preparación de mezclas intravenosas de fármacos vasoactivos en el Servicio de  Farmacia versus preparación en planta. Se midieron las variables tiempo y coste de elaboración de una mezcla intravenosa. Para la determinación del coste final  de elaboración se incluyeron medicamento, diluyente, material fungible,  personal y utilización de las cabinas de flujo laminar. Los costes se midieron en  euros.Resultados: La diferencia encontrada en los tiempos de elaboración entre el  Servicio de Farmacia y la Unidad de Enfermería (2,10 versus 2,86 minutos) fue  estadísticamente significativa y favorable a la elaboración centralizada en el  Servicio de Farmacia. El coste medio de elaboración por mezcla fue 5,24 ± 1,45  euros en el Servicio de Farmacia y 5,62 ± 1,55 euros en planta, aunque la  diferencia encontrada no alcanzó la significación estadística. Al incluir en el  análisis el coste de las mezclas intravenosas caducadas antes de su utilización,  la preparación centralizada en el Servicio de Farmacia supuso un coste superior  (2.174 euros/año).Conclusiones: La elaboración en el Servicio de Farmacia supone un ahorro  significativo de tiempo en comparación con la preparación en planta. La  diferencia de coste de esta alternativa, debida principalmente al impacto de las  mezclas intravenosas caducadas, se eliminaría al optimizar la producción en la  Unidad de Mezclas Intravenosas y al minimizar las pérdidas por caducidad.

Preoperative hydration with 0.9% normal saline to prevent acute kidney injury after major elective open abdominal surgery: A randomised controlled trial.

BACKGROUND: Postoperative acute kidney injury (AKI) is the second leading cause of hospital-acquired AKI. Although many preventive strategies have been tested, none of them has been totally effective. OBJECTIVE: We investigated whether preoperative intravenous hydration with 0.9% normal saline could prevent postoperative AKI. DESIGN: Randomised controlled trial. SETTING: University Ramón y Cajal Hospital, Spain, from June 2006 to February 2011. PATIENTS: Total 328 inpatients scheduled for major elective open abdominal surgery. INTERVENTION: 0.9% normal saline at a dose of 1.5 ml kg h for 12 h before surgery. MAIN OUTCOME MEASURES: The primary outcome was the overall postoperative AKI incidence during the first week after surgery defined by risk, injury, failure, loss, end-stage kidney disease (RIFLE) and AKI network (AKIN) creatinine criteria. Secondary endpoints were the need for ICU admission, renal replacement therapy during the study period and adverse events and hospital mortality during hospital admission. RESULTS: There was no difference in the incidence of AKI between groups: 4.7% in the normal saline group versus 5.0% in the control group and 11.4% in the 0.9% normal saline group versus 7.9% in the control group as assessed by the RIFLE and AKIN creatinine criteria, respectively. Absolute risk reductions (95% confidence interval) were -0.3% (-5.3 to 4.7%) for RIFLE and 3.5% (-10.2 to 3.6%) for AKIN. ICU admission after surgery was required in 44.5% of all participants. Only 2 (0.7%) patients required renal replacement therapy during the first week after surgery. The analysis of adverse events did not show statistically significant differences between the groups except for pain. In our population, 8 (2.4%) patients died during their hospital admission. CONCLUSION: Intravenous hydration with 0.9% normal saline before major open abdominal surgery was not effective in preventing postoperative AKI. No safety concerns were identified during the trial. TRIAL REGISTRATIONS: Clinical trials.gov: NCT00953940 and EUDRA CT: 2005-004755-35.

Impact of a new definition of acute kidney injury based on creatinine kinetics in cardiac surgery patients: a comparison with the RIFLE classification.

OBJECTIVES: Acute kidney injury (AKI) after cardiac surgery is associated with adverse patient outcome. A new definition and staging system for AKI based on creatinine kinetics (CKs) has been proposed recently. Their proponents hypothesize that early absolute increases in serum creatinine (sCr) after kidney injury are superior to percentage increases, especially in patients with chronic kidney disease (CKD). The aims of our study were to measure agreement between CK definition and the current consensus definition [risk, injury, failure, loss and end-stage renal disease (RIFLE) system], and to compare time to diagnosis and prognostic value between both systems. METHODS: Retrospective cohort study. Agreement on AKI diagnosis by both classifications, time to diagnosis and prognostic value of both systems were compared in cardiac surgeries performed during a 6-year period (2002-2007) in a single centre. RESULTS: We found substantial agreement between both classifications (0.67). More patients were diagnosed with AKI by the CK definition than by RIFLE criteria both globally (28.2 vs 13.9%) and in every category (16.5 vs 8.4% for CK-1 vs RIFLE-R; 8.4 vs 3.6% for CK-2 vs RIFLE-I and 3.2 vs 2.0% for CK-3 vs RIFLE-F). Time to diagnosis was shorter for the CK definition (1.8 vs 2.5 days). Prognostic value in terms of information about in-hospital death and need for renal replacement was comparable between classifications. CONCLUSIONS: In cardiac surgery, the CK definition and classification system showed substantial agreement with the current standard, was more sensitive than RIFLE and detected AKI earlier without loss of prognostic information.

Predicting acute renal failure after cardiac surgery: external validation of two new clinical scores.

BACKGROUND AND OBJECTIVES: Different scores to predict acute kidney injury after cardiac surgery have been developed recently. The purpose of this study was to validate externally two clinical scores developed at Cleveland and Toronto. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective analysis was conducted of a prospectively maintained database of all cardiac surgeries performed during a 5-yr period (2002 to 2006) at a University Hospital in Madrid, Spain. Acute kidney injury was defined as the need for renal replacement therapy. For evaluation of the performance of both models, discrimination and calibration were measured. RESULTS: Frequency of acute kidney injury after cardiac surgery was 3.7% in the cohort used to validate the Cleveland score and 3.8% in the cohort used to validate the Toronto score. Discrimination of both models was excellent, with values for the areas under the receiving operator characteristics curves of 0.86 (95% confidence interval 0.81 to 0.9) and 0.82 (95% confidence interval 0.76 to 0.87), respectively. Calibration was poor, with underestimation of the risk for acute kidney injury except for patients within the very-low-risk category. The performance of both models clearly improved after recalibration. CONCLUSIONS: Both models were found to be very useful to discriminate between patients who will and will not develop acute kidney injury after cardiac surgery; however, before using the scores to estimate risk probabilities at a specific center, recalibration may be needed.