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1. Risk factors for therapeutic failure in the management of post-operative peritonitis: a post hoc analysis of the DURAPOP trial

Author

Karim Asehnoune, Sebastien Pease, Philippine Eloy, Alexandre Mignon, Marina Esposito-Farèse, Pascal Raclot, Sami Jaber, Joel Cousson, Soizic Gergaud, Hervé Dupont, Marc Beaussier, Josette Gally, Claude Girard, Melanie Levrard, Claude Meistelman, Gilles Blasco, Jean-Francois Payen, Philippe Gouin, Nathalie Grall, Olivier Collanges, Paer Abback, Thomas Lescot, Sigismond Lasocki, Thomas Gaillard, Sebastien Pily-Floury, Antoine Tesniere, Gaëtan Plantefève, Jean-François Georger, Benoit Veber, Philippe Montravers, Christian Auboyer, Marie-Christine Herault, Florent Wallet, Jean-François Perrier, Regis Bronchard, Yazine Mahjoub, Alain Lepape, Vincent Piriou, Thierry Floch, Emmanuel Samain, Emmanuel Weiss, Thomas Clavier, Mathieu Desmard, Philippe Seguin, Candice Tassin, Yoann Launey, Nouria Belhadj-Tahar, Raphaël Cinotti, Olivier Pajot, Guillaume Besch, Catherine Paugam, Boris Jung, Jean-Marc Delay, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, CHU Rouen, Normandie Université (NU), CHU Pontchaillou [Rennes], Hôpital Beaujon [AP-HP], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), CHU Amiens-Picardie, Université de Picardie Jules Verne (UPJV), DURAPOP trial group: Philippe Montravers, Regis Bronchard, Mathieu Desmard, Herve Dupont, Melanie Levrard, Yazine Mahjoub, Sigismond Lasocki, Soizic Gergaud, Thomas Gaillard, Gaetan Plantefeve, Olivier Pajot, Gilles Blasco, Emmanuel Samain, Guillaume Besch, Sebastien Pily-Floury, Catherine Paugam, Sebastien Pease, Paer Abback, Claude Girard, Jean-Francois Payen, Marie-Christine Herault, Sami Jaber, Boris Jung, Jean-Marc Delay, Josette Gally, Claude Meistelman, Jean-François Perrier, Karim Asehnoune, Raphael Cinotti, Antoine Tesniere, Alexandre Mignon, Thomas Lescot, Nouria Belhadj-Tahar, Marc Beaussier, Alain Lepape, Vincent Piriou, Florent Wallet, Candice Tassin, Joel Cousson, Pascal Raclot, Thierry Floch, Philippe Seguin, Yoann Launey, Benoit Veber, Philippe Gouin, Thomas Clavier, Christian Auboyer, Olivier Collanges, Jean-François Georger, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and MORNET, Dominique

Subjects
medicine.medical_treatment, [SDV]Life Sciences [q-bio], Penicillanic Acid, Logistic regression, 0302 clinical medicine, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Pharmacology (medical), 030212 general & internal medicine, MESH: Penicillanic Acid, Prospective Studies, Original Research, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, AcademicSubjects/MED00290, Piperacillin, Tazobactam Drug Combination, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Piperacillin/tazobactam, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine.drug, Microbiology (medical), MESH: Piperacillin, medicine.medical_specialty, MESH: Peritonitis, Peritonitis, Tazobactam, 03 medical and health sciences, Internal medicine, MESH: Anti-Bacterial Agents, Post-hoc analysis, medicine, AcademicSubjects/MED00740, Humans, Renal replacement therapy, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Pharmacology, Piperacillin, MESH: Humans, business.industry, 030208 emergency & critical care medicine, medicine.disease, Comorbidity, MESH: Prospective Studies, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, AcademicSubjects/MED00230
Abstract

Background Therapeutic failure is a frequent issue in the management of post-operative peritonitis. Objectives A post hoc analysis of the prospective, multicentre DURAPOP trial analysed the risk factors for failures in post-operative peritonitis following adequate source control and empirical antibiotic therapy in critically ill patients. Patients and methods Overall failures assessed post-operatively between Day 8 and Day 45 were defined as a composite of death and/or surgical and/or microbiological failures. Risk factors for failures were assessed using logistic regression analyses. Results Among the 236 analysed patients, overall failures were reported in 141 (59.7%) patients, including 30 (12.7%) deaths, 81 (34.3%) surgical and 95 (40.2%) microbiological failures. In the multivariate analysis, the risk factors associated with overall failures were documented piperacillin/tazobactam therapy [adjusted OR (aOR) 2.10; 95% CI 1.17–3.75] and renal replacement therapy on the day of reoperation (aOR 2.96; 95% CI 1.05–8.34). The risk factors for death were age (aOR 1.08 per year; 95% CI 1.03–1.12), renal replacement therapy on reoperation (aOR 3.95; 95% CI 1.36–11.49) and diabetes (OR 6.95; 95% CI 1.34–36.03). The risk factors associated with surgical failure were documented piperacillin/tazobactam therapy (aOR 1.99; 95% CI 1.13–3.51), peritoneal cultures containing Klebsiella spp. (aOR 2.45; 95% CI 1.02–5.88) and pancreatic source of infection (aOR 2.91; 95% CI 1.21–7.01). No specific risk factors were identified for microbiological failure. Conclusions Our data suggest a predominant role of comorbidities, the severity of post-operative peritonitis and possibly of documented piperacillin/tazobactam treatment on the occurrence of therapeutic failures, regardless of their type.

Published
2021

2. Thoracic Epidural Analgesia and Mortality in Acute Pancreatitis A Multicenter Propensity Analysis

Author

Jean-Yves Lefrant, Laurent Jacob, Stéphanie Bulyez, Raphaël Cinotti, Olivier Joannes-Boyau, Yannick Mallédant, Thomas Kerforne, Marc Leone, Bruno Pereira, Paër-Sélim Abback, Jean-Michel Constantin, Matthieu Jabaudon, Thomas Rimmelé, Nouria Belhadj-Tahar, Philippe Guerci, Brice Lortat-Jacob, Fabienne Tamion, Thierry Dugernier, Hervé Dupont, Philippe Verdier, CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Bordeaux [Bordeaux], Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes physiologiques et conséquences des calcifications cardiovasculaires: rôle des remodelages cardiovasculaires et osseux, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Male, [SDV]Life Sciences [q-bio], MEDLINE, Critical Care and Intensive Care Medicine, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Thoracic epidural, 030202 anesthesiology, Severity of illness, Medicine, Humans, Propensity Score, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, business.industry, 030208 emergency & critical care medicine, Retrospective cohort study, Middle Aged, medicine.disease, 3. Good health, Analgesia, Epidural, Intensive Care Units, Pancreatitis, Anesthesia, Propensity score matching, Acute Disease, Acute pancreatitis, Observational study, Female, business, Splanchnic
Abstract

Recent preclinical and clinical data suggest that thoracic epidural analgesia, a technique primarily aimed at decreasing pain, might exert anti-inflammatory effects, enhance splanchnic and pancreatic blood flow during acute pancreatitis; however, the influence of epidural analgesia on mortality remains under investigated in this setting. This study was therefore designed to assess the impact of epidural analgesia on mortality in ICU patients with acute pancreatitis.Multicenter retrospective, observational, cohort study.Seventeen French and Belgian ICUs.All patients admitted to with acute pancreatitis between June 2009 and March 2014.The primary exposure was thoracic epidural analgesia versus standard care without epidural analgesia. The primary outcome was 30-day mortality. Propensity analyses were used to control for bias in treatment assignment and prognostic imbalances.One thousand three ICU patients with acute pancreatitis were enrolled, of whom 212 died within 30 days. Epidural analgesia was used in 46 patients and was associated with reduced mortality in unadjusted analyses (4% vs. 22%; p = 0.003). After adjustment for baseline variables associated with mortality, epidural analgesia was still an independent predictor of 30-day mortality (adjusted odds ratio, 0.10; [95% CI, 0.02-0.49]; p = 0.004). Using propensity score analysis, the risk of all-cause 30-day mortality in patients with acute pancreatitis receiving epidural analgesia was significantly lower than that in matched patients who did not receive epidural analgesia (2% vs. 17%; p = 0.01).Among critically ill patients with acute pancreatitis, mortality at 30 days was lower in patients who received epidural analgesia than in comparable patients who did not. These findings support ongoing research on the use of epidural analgesia as a therapeutic intervention in acute pancreatitis.

Published
2018

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