Intraoperative protective mechanical ventilation in patients requiring emergency abdominal surgery: the multicentre prospective randomised IMPROVE-2 study protocol

International audienceIntroduction Emergency abdominal surgery is associated with a high risk of postoperative complications. One of the most serious is postoperative respiratory failure (PRF), with reported rates up to 20%–30% and attributable 30-day mortality that can exceed 20%. Lung-protective ventilation, especially the use of low tidal volume, may help reducing the risk of lung injury. The role of positive end-expiratory pressure (PEEP) and recruitment manoeuvre (RM) remains however debated. We aim to evaluate whether a strategy aimed at increasing alveolar recruitment by using higher PEEP levels and RM could be more effective at reducing PRF and mortality after emergency abdominal surgery than a strategy aimed at minimising alveolar distension by using lower PEEP levels without RM.Methods and analysis The IMPROVE-2 study is a multicentre randomised, parallel-group clinical trial of 680 patients requiring emergency abdominal surgery under general anaesthesia. Patients will be randomly allocated in a 1:1 ratio to receive either low PEEP levels (≤5 cm H 2 O) without RM or high PEEP levels individually adjusted according to driving pressure in addition to RM, stratified by centre and according to the presence of shock and hypoxaemia at randomisation. The primary endpoint is a composite of PRF and all-cause mortality by day 30 or hospital discharge. Data will be analysed on the intention-to-treat principle and a per-protocol basis.Ethics and dissemination IMPROVE-2 trial has been approved by an independent ethics committee for all study centres. Participant recruitment began in February 2021. Results will be submitted for publication in international peer-reviewed journals.Trial registration number NCT03987789

Fluid loading in abdominal surgery - saline versus hydroxyethyl starch (FLASH Trial): study protocol for a randomized controlled trial

International audienceBackground : Inappropriate fluid therapy during surgery is associated with significant morbidity and mortality. Fewstudies have examined the effects of particular types of fluids (crystalloid or colloid solutions) in surgical patients,especially with the goal of hemodynamic optimization. Isotonic saline is the most commonly used fluid worldwidebut may be associated with potential nephrotoxicity. Hydroxyethyl starch (HES) solutions are widely used in surgicalpatients as a component of goal-directed fluid optimization strategies, but several large multicenter studies havesuggested increased rates of acute kidney injury and adverse events with the use of HES in ICU patients. Despitewhat may be inferred from physiological studies, the benefit and harm of 0.9 % saline and HES during hemodynamictherapy have not been clearly established in surgical patients.Methods/Design : The FLASH trial is an investigator-initiated, prospective, multicenter, randomized, double-blinded,two-arm trial, randomizing 826 patients with moderate-to-high risk of postoperative complications to receive 6 % HES130/0.4 or 0.9 % saline during individualized goal-directed fluid optimization. The primary outcome measure is acomposite of death or major postoperative complications within 14 days following surgery.Thesamplesizewillallowthedetectionofa10%absolutebetween-groupdifferenceintheprimaryoutcomemeasurewith a type 1 error rate of 5 % and power of 95 %, assuming a 5% mortality rate and 20 % morbidity (thus 25 % for thecomposite endpoint).Discussion : The FLASH trial may provide important data on the efficacy and safety of commonly used fluid solutions andcould have a significant impact on future treatment of surgical patients.Trial registration : ClinicalTrials.gov Identifier: NCT02502773. Registered 16 June 2015

Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) for the prevention of surgical site infection in elective colorectal surgery: study protocol for a multicentre, double-blind, randomised controlled clinical trial.

International audienc

Role of T CD4+ cells, macrophages, C‐LTMRs and spinal‐located Ca v 3.2 calcium channels in inflammation and related pain‐like symptoms in murine inflammatory models

International audienceBackground and purpose: T-type calcium channels, mainly the Cav 3.2 subtype, are important contributors to the nociceptive signaling pathway. We investigated their involvement in inflammation and related pain-like symptoms.Experimental approach: The involvement of Cav 3.2 and T-type channels was investigated using genetic and pharmacological inhibition to assess mechanical allodynia/hyperalgesia and edema development in two murine inflammatory pain models. The location of Cav 3.2 involved in pain-like symptoms was studied in mice with Cav 3.2 knocked out in C-low threshold mechanoreceptors (C-LTMR) and the use of ABT-639, a peripherally restricted T-type channel inhibitor. The anti-edematous effect of Cav 3.2 inhibition was investigated in chimeric mice with immune cells deleted for Cav 3.2. Lymphocytes and macrophages from either green fluorescent protein-targeted Cav 3.2 or KO mice were used to determine the expression of Cav 3.2 protein and the functional status of the cells.Key results: We showed the role of Cav 3.2 channels in the development of pain-like symptoms and edema in the two murine inflammatory pain models. For the first time, we provide evidence of the involvement of Cav 3.2 channels located on C-LTMRs and spinal cord in inflammatory pain. We showed that Cav 3.2 channels located in T cells and macrophages contribute to the inflammatory process.Conclusion and implications: This work highlights the crucial role of Cav 3.2 channels in inflammation and related pain and suggests that targeting Cav 3.2 channels with pharmacological agents could be an attractive and readily evaluable strategy in a clinical trial to relieve chronic inflammatory pain in affected patients

Additional file 1: of Fluid loading in abdominal surgery - saline versus hydroxyethyl starch (FLASH Trial): study protocol for a randomized controlled trial

Acute kidney injury (AKI) risk index. (PDF 50 kb

Impaired muscular fat metabolism in juvenile idiopathic arthritis in inactive disease

Objectives: The objective of this study was to evaluate muscular metabolic function in children with inactive juvenile idiopathic arthritis (JIA).Methods: Fifteen children with inactive JIA and fifteen healthy controls were matched by sex, biological age, and Tanner stage. Participants completed a submaximal incremental exercise test to determine their fat and carbohydrate oxidation rates.Results: Between the two groups, heart rate values and carbohydrate oxidation rates were the same, regardless of the relative intensity of exercise. Lipid oxidation rates were lower in JIA patients, regardless of the percentage of VO2 peak (p < 0.05). Respiratory exchange ratios beyond 50% of VO2 peak were higher in patients with JIA (p < 0.05). Respective maximal fat oxidation rates (MFO) for controls and children with JIA were 218.7 +/- 92.2 vs. 157.5 +/- 65.9 mg . min(-1) (p = 0.03) and 4.9 +/- 1.9 vs. 3.4 +/- 1.2 mg . min(-1) . kg(-1) (p = 0.04). There was no difference between the two groups in heart rate, percentage of VO2 peak, or power of exercise to achieve MFO. Controls reached their MFO at an exercise power significantly higher than did JIA subjects (42.8 +/- 16.8 and 31.9 +/- 9.8 W, p = 0.004).Conclusion: Children with JIA show metabolic disturbance during exercise, even when the disease is considered inactive. This disturbance is seen in a lower lipid oxidation rate during submaximal exercise