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IntroductionContinuous renal replacement therapy (CRRT) is a critical therapeutic intervention for patients with severe acute kidney injury in intensive care. However, premature filter clotting remains a significant challenge during CRRT, impacting treatment efficacy, costs and patient outcomes. Anticoagulation is essential to maintain circuit patency, with regional citrate anticoagulation (RCA) emerging as a preferred strategy due to its favourable bleeding profile. The standard target for post-filter ionised calcium (iCa) concentration during RCA-CRRT is set between 0.25 and 0.35 mmol/L, although evidence supporting this range is limited. We hypothesise that a higher post-filter iCa target (0.35–0.45 mmol/L) can provide comparable circuit patency while potentially reducing adverse effects associated with citrate administration.Methods and analysisThis multicentre randomised controlled non-inferiority trial will compare a low post-filter iCa target (0.25–0.35 mmol/L) with a higher post-filter iCa target (0.35–0.45 mmol/L) in patients undergoing RCA-CRRT in the intensive care unit. A total of 412 CRRT sessions will be randomised with a 1:1 ratio into these two groups. The primary outcome is the incidence of filter clotting. Secondary outcomes include filter lifespan, post-filter iCa levels, citrate infusion rates, the occurrence of metabolic adverse effects, financial costs and blood loss.Ethics and disseminationThe study has obtained approval from the ethics committee (Ethics Committee Est III, Nancy, France) and patients will be included after providing informed consent. The results will be disseminated at academic conferences and in peer-reviewed publications. All procedures were developed in order to assure data protection and confidentiality.Trial registration numberNCT05814341.

IntroductionPostoperative pain management after orthotopic liver transplantation is complex due to impaired liver function and frequent acute kidney dysfunction. Subcostal transversus abdominis plane (TAP) block may be of interest in this population. The aim of this study was to evaluate the impact of subcostal TAP block on opioid consumption after liver transplantation.MethodsWe conducted a before-and-after single center study. During the first period, we included patients whom did not receive an analgesic TAP block. During the second period, we included those with bilateral ultrasound-guided subcostal TAP block (20 mL ropivacaïne 0.2% each side). Patients requiring sedation within 48 hours of surgery as well as patients with combined liver and kidney transplants or skin-only closures were excluded. The primary outcome was cumulative oral morphine consumption within 48 hours after surgery. Secondary outcomes included pain scores and TAP block-related complications.ResultsA total of 132 patients were included in the non-TAP block group and 78 patients in the TAP block group. The median oral morphine equivalent consumption (IQR) within 48 hours following surgery was 74 mg (39; 112) for the non-TAP block group and 50 mg (20; 80) for the TAP block group (p<0.001). There was no difference in pain scores between the two groups. No complications related to the TAP block were reported.ConclusionSubcostal TAP block appears to have a small opioid reducing effect after orthotopic liver transplantation surgery.

Regional citrate anticoagulation (RCA) is the recommended method for anticoagulation in continuous renal replacement therapy (CRRT). However, the optimal post-filter ionized calcium (iCa) target level remains unclear. This study aims to assess the effect of increasing the post-filter iCa target level from 0.25–0.35 mmol/L to 0.30–0.40 mmol/L on filter lifespan until clotting during RCA-CRRT. This before-and-after single-center study included patients who underwent RCA-CRRT sessions without systemic anticoagulation during two periods. The first period included patients with a post-filter iCa target between 0.25 and 0.35 mmol/L, while the second period included those with a target between 0.30 and 0.40 mmol/L. The primary outcome was filter lifespan until clotting. A total of 1037 CRRT sessions were analyzed, with 610 sessions in the first period and 427 sessions in the second period. After adjusting for confounding factors, there was no significant difference in filter lifespan until clotting between the two groups (hazard ratio, 1.020 [0.703; 1.481]; p = 0.92). Increasing the post-filter iCa target level from 0.25–0.35 mmol/L to 0.30–0.40 mmol/L during RCA-CRRT does not reduce filter lifespan until clotting and may decrease unnecessary citrate exposure. However, the optimal post-filter iCa target should be individualized according to the patient's clinical and biological status. •Acute renal failure is common in intensive care.•Continuous renal replacement therapy may be required.•Regional citrate anticoagulation is the recommended method of anticoagulation.•Increasing post-filter calcium target can reduce citrate doses.•Increasing post-filter calcium target does not reduce filter lifespan until clotting.

Background Postextubation respiratory failure (PRF) frequently complicates weaning from mechanical ventilation and may increase morbidity/mortality. Noninvasive ventilation (NIV) alternating with high-flow nasal oxygen (HFNO) may prevent PRF. Methods Ventilated patients without chronic obstructive pulmonary disease (COPD) and at high-risk of PRF defined as a lung ultrasound score (LUS) ≥ 14 assessed during the spontaneous breathing trial, were included in a French-Chinese randomised controlled trial. PRF was defined by 2 among the following signs: SpO 2  < 90%; Respiratory rate > 30 /min; hypercapnia; haemodynamic and/or neurological disturbances of respiratory origin. In the intervention group, prophylactic NIV alternating with HFNO was administered for 48 h following extubation. In the control group, conventional oxygen was used. Clinicians were informed on the LUS in the intervention group, those in the control group remained blind. The primary outcome was the incidence of PRF 48 h after extubation. Secondary outcomes were incidence of PRF and reintubation at day 7, number of ventilator-free days at day 28, length of ICU stay and mortality at day 28 and 90. Results Two hundred and forty patients were randomised and 227 analysed (intervention group = 128 and control group = 99). PRF at H48 was reduced in the intervention group compared to the control group: relative risk 0.52 (0.31 to 0.88), p  = 0.01. The benefit persisted at day 7: relative risk 0.62 (0.44 to 0.96), p  = 0.02. Weaning failure imposing reconnection to mechanical ventilation was not reduced. In patients who developed PRF and were treated by rescue NIV, reintubation was avoided in 44% of control patients and in 12% of intervention patients ( p  = 0.008). Other secondary outcomes were not different between groups. From a resource utilisation standpoint, prophylactic NIV alternating with HFNO was more demanding and costly than conventional oxygen with rescue NIV to achieve same clinical outcome. Conclusions Compared to conventional oxygenation, prophylactic NIV alternating with HFNO significantly reduced postextubation respiratory failure but failed to reduce reintubation rate and mortality in patients without COPD at high risk of extubation failure. Prophylactic NIV alternating with HFNO was as efficient as recue NIV to treat postextubation respiratory failure.

Background Nebulisation of antibiotics is a promising treatment for ventilator-associated pneumonia (VAP) caused by multidrug-resistant organisms. Ensuring effective antibiotic concentrations at the site of infection in the interstitial space fluid is crucial for clinical outcomes. Current assessment methods, such as epithelial lining fluid and tissue homogenates, have limitations in providing longitudinal pharmacokinetic data. Main body Lung microdialysis, an invasive research technique predominantly used in animals, involves inserting probes into lung parenchyma to measure antibiotic concentrations in interstitial space fluid. Lung microdialysis offers unique advantages, such as continuous sampling, regional assessment of antibiotic lung concentrations and avoidance of bronchial contamination. However, it also has inherent limitations including the cost of probes and assay development, the need for probe calibration and limited applicability to certain antibiotics. As a research tool in VAP, lung microdialysis necessitates specialist techniques and resource-intensive experimental designs involving large animals undergoing prolonged mechanical ventilation. However, its potential impact on advancing our understanding of nebulised antibiotics for VAP is substantial. The technique may enable the investigation of various factors influencing antibiotic lung pharmacokinetics, including drug types, delivery devices, ventilator settings, interfaces and disease conditions. Combining in vivo pharmacokinetics with in vitro pharmacodynamic simulations can become feasible, providing insights to inform nebulised antibiotic dose optimisation regimens. Specifically, it may aid in understanding and optimising the nebulisation of polymyxins, effective against multidrug-resistant Gram-negative bacteria. Furthermore, lung microdialysis holds promise in exploring novel nebulisation therapies, including repurposed antibiotic formulations, bacteriophages and immunomodulators. The technique's potential to monitor dynamic biochemical changes in pneumonia, such as cytokines, metabolites and inflammation/infection markers, opens avenues for developing theranostic tools tailored to critically ill patients with VAP. Conclusion In summary, lung microdialysis can be a potential transformative tool, offering real-time insights into nebulised antibiotic pharmacokinetics. Its potential to inform optimal dosing regimen development based on precise target site concentrations and contribute to development of theranostic tools positions it as key player in advancing treatment strategies for VAP caused by multidrug-resistant organisms. The establishment of international research networks, exemplified by LUMINA (lung microdialysis applied to nebulised antibiotics), signifies a proactive step towards addressing complexities and promoting multicentre experimental studies in the future.