EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Br J Anaesth

BACKGROUND: We investigated whether cardiac output measured with pulse wave transit time (esCCO, Nihon Kohden, Tokyo, Japan) is able to track changes in cardiac output induced by an increase in preload (volume expansion/passive leg-raising) or by changes in vasomotor tone (variation in norepinephrine dosage) in critically ill patients. METHODS: Eighty patients for whom the decision to give fluid (500 mL of saline over 15 min) (n=20), to perform passive leg-raising (n=20), and to increase (n=20) or to decrease (n=20) norepinephrine were included by the physician. Cardiac output was measured with pulse wave transit time (CO-esCCO) and transthoracic echocardiography (CO-TTE) before and after therapeutic intervention. RESULTS: Comparison between CO-TTE and CO-esCCO showed a bias of -0.7 l min(-1) and limits of agreement of -4.4 to 2.9 l min(-1), before therapeutic intervention and a bias of -0.5 l min(-1) and limits of agreement of -4.2 to 3.2 l min(-1) after therapeutic intervention. Bias was correlated with systemic vascular resistance (r(2)=0.60, P\textless0.0001). Percentage error was 61% before and 59% after therapeutic intervention. Considering the overall data (n=80), the concordance rate was 84%, polar plot analysis revealed an angular bias (sd) of -11°(35°) and radial limits of agreement of (sd 50°). With regard to passive leg-raising and volume expansion groups (n=40), the concordance rate was 83%, the angular bias (sd) was -20°(36°) and radial limits of agreement ( 50°). Considering variations in norepinephrine dosage groups (n=40), the concordance rate was 86%, the angular bias (sd) was -1.8°(33°) and radial limits of agreement (40°). CONCLUSIONS: esCCO was not able to track changes in cardiac output, induced by an increase in preload or by variations in vasomotor tone. Therefore, esCCO cannot guide haemodynamic interventions in critically ill patients

Prevention of early ventilation-acquired pneumonia (VAP) in comatose brain-injured patients by a single dose of ceftriaxone: PROPHY-VAP study protocol, a multicentre, randomised, double-blind, placebo-controlled trial

International audienceIntroduction: Ventilator-associated pneumonia (VAP) is the first cause of healthcare-associated infections in intensive care units (ICUs) and brain injury is one of the main risk factors for early-onset VAP. Antibiotic prophylaxis has been reported to decrease their occurrence in brain-injured patients, but a lack of controlled randomised trials and the risk of induction of bacterial resistance explain the low level of recommendations. The goal of this study is to determine whether a single dose of ceftriaxone within the 12 hours postintubation after severe brain injury can decrease the risk of early-onset VAP.Methods and analysis: The PROPHY-VAP is a French multicentre, randomised, double-blind, placebo-controlled, clinical trial. Adult brain-injured patients (n=320) with a Glasgow Coma Scale ≤12, requiring mechanical ventilation for more than 48 hours, are randomised to receive either a single dose of ceftriaxone 2 g or a placebo within the 12 hours after tracheal intubation. The primary endpoint is the proportion of patients developing VAP from the 2nd to the 7th day after mechanical ventilation. Secondary endpoints include the proportion of patients developing late VAP (>7 days after tracheal intubation), the number of ventilator-free days, VAP-free days and antibiotic-free days, length of stay in the ICU, proportion of patients with ventilator-associated events and mortality during their ICU stay.Ethics and dissemination: The initial research project was approved by the Institutional Review Board of OUEST III (France) on 20 October 2014 (registration No 2014-001668-36) and carried out according to the principles of the Declaration of Helsinki and the Clinical Trials Directive 2001/20/EC of the European Parliament relating to the Good Clinical Practice guidelines. The results of this study will be presented in national and international meetings and published in an international peer-reviewed journal

Effect of a hypertonic balanced ketone solution on plasma, CSF and brain beta-hydroxybutyrate levels and acid-base status

Purpose: Although glucose is the main source of energy for the human brain, ketones play an important role during starvation or injury. The purpose of our study was to investigate the metabolic effects of a novel hypertonic sodium ketone solution in normal animals. Methods: Adult Sprague-Dawley rats (420-570 g) were divided into three groups of five, one control and two study arms. The control group received an intravenous infusion of 3 % NaCl at 5 ml/kg/h. The animals in the two study arms were assigned to receive one of the two formulations of ketone solutions, containing hypertonic saline with 40 and 120 mmol/l beta-hydroxybutyrate, respectively. This was infused for 6 h and then the animal was euthanized and brains removed and frozen. Results: Both blood and cerebrospinal fluid (CSF) levels of beta-hydroxybutyrate (BHB) demonstrated strong evidence of a change over time (p < 0.0001). There was also strong evidence of a difference between groups (p < 0.0001). Multiple comparisons showed all these means were statistically different (p < 0.05). Measurement of BHB levels in brain tissue found strong evidence of a difference between groups (p < 0.0001) with control: 0.15 mmol/l (0.01), BHB 40: 0.19 mmol/l (0.01), and BHB 120: 0.28 mmol/l (0.01). Multiple comparisons showed all these means were statistically different (p < 0.05). There were no differences over time (p = 0.31) or between groups (p = 0.33) or an interaction between groups and time (p = 0.47) for base excess. Conclusion: The IV infusions of hypertonic saline/BHB are feasible and lead to increased plasma, CSF and brain levels of BHB without significant acid/base effects