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BACKGROUND: Visceral and parietal peritoneum layers have different sensory innervations. Most visceral peritoneum sensory information is conveyed via the vagus nerve to the nucleus of the solitary tract (NTS). We already showed in animal models that intramuscular (i.m.) injection of local anesthetics decreases acute somatic and visceral pain and general inflammation induced by aseptic peritonitis. The goal of the study was to compare the effects of parietal block, i.m. bupivacaine, and vagotomy on spinal cord and NTS stimulation induced by a chemical peritonitis. METHODS: We induced peritonitis in rats using carrageenan and measured cellular activation in spinal cord and NTS under the following conditions, that is, a parietal nerve block with bupivacaine, a chemical right vagotomy, and i.m. microspheres loaded with bupivacaine. Proto-oncogene c-Fos (c-Fos), cluster of differentiation protein 11b (CD11b), and tumor necrosis factor alpha (TNF-α) expression in cord and NTS were studied. RESULTS: c-Fos activation in the cord was inhibited by nerve block 2 hours after peritoneal insult. Vagotomy and i.m. bupivacaine similarly inhibited c-Fos activation in NTS. Forty-eight hours after peritoneal insult, the number of cells expressing CD11b significantly increased in the cord (P = .010). The median difference in the effect of peritonitis compared to control was 30 cells (CI95, 13.5-55). TNF-α colocalized with CD11b. Vagotomy inhibited this microglial activation in the NTS, but not in the cord. This activation was inhibited by i.m. bupivacaine both in cord and in NTS. The median difference in the effect of i.m. bupivacaine added to peritonitis was 29 cells (80% increase) in the cord and 18 cells (75% increase) in the NTS. Our study underlines the role of the vagus nerve in the transmission of an acute visceral pain message and confirmed that systemic bupivacaine prevents noxious stimuli by inhibiting c-Fos and microglia activation. CONCLUSIONS: In rats receiving intraperitoneal carrageenan, i.m. bupivacaine similarly inhibited c-Fos and microglial activation both in cord and in the NTS. Vagal block inhibited activation only in the NTS. Our study underlines the role of the vagus nerve in the transmission of an acute visceral pain message and confirmed that systemic bupivacaine prevents noxious stimuli. This emphasizes the effects of systemic local anesthetics on inflammation and visceral pain.
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Dolor Agudo/prevención & control , Anestésicos Locales/administración & dosificación , Bupivacaína/administración & dosificación , Manejo del Dolor , Núcleo Solitario/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Vagotomía , Nervio Vago/cirugía , Dolor Visceral/prevención & control , Dolor Agudo/inducido químicamente , Dolor Agudo/metabolismo , Dolor Agudo/fisiopatología , Animales , Antígeno CD11b/metabolismo , Carragenina , Modelos Animales de Enfermedad , Inyecciones Intramusculares , Masculino , Microglía/efectos de los fármacos , Microglía/metabolismo , Peritonitis/inducido químicamente , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas Sprague-Dawley , Núcleo Solitario/metabolismo , Núcleo Solitario/fisiopatología , Médula Espinal/metabolismo , Médula Espinal/patología , Factor de Necrosis Tumoral alfa/metabolismo , Nervio Vago/fisiopatología , Dolor Visceral/inducido químicamente , Dolor Visceral/metabolismo , Dolor Visceral/fisiopatologíaRESUMEN
OBJECTIVE: Patient- and organization-related factors are the most common influences affecting the ICU decision-making process. Few studies have investigated ICU physician-related factors and life-sustaining treatment use during nights and weekends, when staffing ratios are low. Here, we described patients admitted during nights/weekends and looked for physician-related determinants of life-sustaining treatment use in these patients after adjustment for patient- and center-related factors. DESIGN: Multicenter observational cohort study of admission procedures during nights/weekends shifts. SUBJECTS: ICU physicians working nights/weekends in 6 French ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics and intensity of care were extracted from the prospective Outcomerea database. Physician characteristics were age, gender, religion and religiosity, ICU experience, specialty, being a permanent ICU staff member, degree in ethics, and degree in intensive care. We used hierarchical mixed models to adjust on center, physician random effects, and admission patient characteristics. Of 156 physicians contacted, 119 (77%) participated. Patients admitted during nights/weekends were younger and had fewer comorbidities and lower treatment intensity during the shift. ICU physicians who are younger than 35 years used more renal replacement therapy (odds ratio, 1.04; 95% CI, 1-1.07; p = 0.04), invasive mechanical ventilation (odds ratio, 1.09; 95% CI, 1.1-1.19; p = 0.04), and vasopressors (odds ratio, 1.16; 95% CI, 1.09-1.23; p < 0.0001). Internal or emergency medicine as the primary specialty was associated with invasive mechanical ventilation (odds ratio, 1.14; 95% CI, 1.04-1.24; p = 0.004) and vasopressor use (odds ratio, 1.09; 95% CI, 1.02-1.17; p = 0.01). Noninvasive ventilation was used less often by physicians with more than 10 years of night/weekend shifts and more often by those with religious beliefs (odds ratio, 1.05; 95% CI, 1.01-1.08; p = 0.008). CONCLUSIONS: Patients admitted during nights/weekends were younger and had fewer comorbidities. Age, specialty, ICU experience, and religious beliefs of the physicians were significantly associated life-sustaining treatments used.
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Atención Posterior/métodos , Citas y Horarios , Unidades de Cuidados Intensivos , Cuidados para Prolongación de la Vida/normas , Evaluación de Resultado en la Atención de Salud , Adulto , Anciano , Actitud del Personal de Salud , Estudios de Cohortes , Cuidados Críticos/métodos , Bases de Datos Factuales , Toma de Decisiones , Femenino , Francia , Humanos , Cuidados para Prolongación de la Vida/tendencias , Masculino , Persona de Mediana Edad , Admisión del Paciente/estadística & datos numéricos , Pautas de la Práctica en Medicina/normas , Pautas de la Práctica en Medicina/tendencias , Estudios ProspectivosRESUMEN
Background: The p38 protein is a ubiquitous mitogen-activated protein kinase involved in the proinflammatory signalling pathway and in the pain response after various noxious stimuli. Many p38 inhibitors have been developed and shown to provide effective analgesia in animal models. They are, however, mainly administered intrathecally or intravenously. Our study aimed to evaluate losmapimod, a novel oral p38 inhibitor, in two murine acute pain models. Methods: Losmapimod (12 mg kg-1) was compared with paracetamol, ketamine, and morphine using thermal and mechanical stimulation after carrageenan injection. A dose-effect study was also performed with this model. Behavioural testing was also performed in a plantar incision model to confirm the analgesic effect of losmapimod. Expression of activated p38 in neurones, microglia, and astrocytes was also investigated at 2, 15, and 24 h after carrageenan injection. Results: Losmapimod was both antiallodynic and antihyperalgesic in the carrageenan pain model and provided an antinociceptive effect similar to that of morphine. The dose of 12 mg kg-1 was shown to be the ED78 and ED64 after thermal and mechanical stimulation, respectively. After plantar incision, losmapimod provided a significant antinociceptive effect. No life-threatening side-effect was observed in the behavioural study. Losmapimod prevented neurone and microglial activation at 2 and 15 h after carrageenan injection, respectively, but no effect was found on astrocytic activation. Conclusion: Losmapimod appears to be a promising drug in severe acute pain conditions. Losmapimod could also be helpful for postoperative pain control, as suggested by its effect after plantar incision.
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BACKGROUND: A 15-month outbreak of carbapenemase-producing Enterobacterales (CPE) occurred in the surgical intensive care unit (SICU) of our institution. We aimed to estimate the financial impact of this outbreak from the perspective of the French public health insurance system. METHODS: The characteristics of the colonised/infected CPE patients and outbreak management according to French national guidelines were prospectively collected. Loss of productivity was assessed in terms of the reduction in total number of admissions (TNA) and discharges and in ICU length of stay (LoS). The additional financial burden associated with this outbreak was estimated by the accounting department of the hospital, including the impact of the extended LoS and restricted admissions. RESULTS: Sixteen CPE patients (19 stays) were hospitalised in the SICU (10/2016-01/2018). The median ICU LoS for the CPE cases was 17 [8-36] days versus 6.5 and 6.1 days in 2016 and 2017, respectively, for the whole SICU population. The total number of lost bed days during the outbreak was 452. The TNA dropped dramatically in 2017 (decrease of 20.6%). The estimated costs were 768,386 EUR for bed days lost; 297,176 EUR and 63,675 EUR for the extended LoS for the CPE cases and the patients on contact precautions, respectively; 34,045 EUR for staff reinforcements; 85,764 EUR for bacteriological screening tests; and 42,857 EUR for antimicrobial treatment. The total financial burden of the outbreak was 1,291,903 EUR. CONCLUSION: Management of a CPE outbreak in the SICU is associated with a huge financial burden for the unit and for the institution.
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Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Enterobacteriaceae , Proteínas Bacterianas , Cuidados Críticos , Brotes de Enfermedades , Enterobacteriaceae , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/prevención & control , Humanos , Unidades de Cuidados Intensivos , beta-LactamasasRESUMEN
PURPOSE: In postoperative peritonitis, Gram stain examination (GSE) of peritoneal fluid has been proposed as a guide for the prescription of glycopeptides and antifungal therapy in empirical antibiotherapy. No data support this approach for Gram-positive cocci. We aimed to evaluate the performance of GSE in predicting the results of the culture of peritoneal fluid. METHODS: In this retrospective single-center study, concordance between GSE and culture of peritoneal fluid was assessed for different types of microorganisms. Factors associated with concordance of the two tests were evaluated in the subpopulation of Gram-positive cocci peritonitis. RESULTS: Among the 152 episodes, the GSE was negative in 57 cases. The negative predictive value and the positive predictive value were 41% and 87% for Gram-positive cocci (GPC), 31% and 86% for Gram-negative bacilli, and 78% and 94% for fungi. GSE is not a reliable guide for the choice of empirical antibiotherapy and cannot reliably rule out the presence of GPC at culture. If we aim to achieve a high rate of adequacy, the systematic use of glycopeptide in the empirical antibiotherapy may be considered. CONCLUSION: GSE shows poor performance to predict the results of culture of peritoneal fluid in postoperative peritonitis. Avoiding covering resistant GPC cannot be based on the result of GSE.
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Antibacterianos/uso terapéutico , Violeta de Genciana , Peritonitis/tratamiento farmacológico , Peritonitis/microbiología , Fenazinas , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/microbiología , Profilaxis Antibiótica , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Paris , Reoperación , Estudios RetrospectivosRESUMEN
Introduction: Recent studies described the threat of emerging multidrug-resistant (MDR) bacteria in intensive care unit (ICU) patients, but few data are available for necrotizing skin and soft tissue infections (NSTI). In a cohort of ICU patients admitted for NSTI, we describe the dynamic changes of microbial population during repeated surgeries. Materials and Methods: This retrospective study compiled consecutive cases admitted for the management of severe NSTI. Clinical characteristics, NSTI features, morbidity and mortality data were collected. The microbiological characteristics of surgical samples obtained during initial surgery were compared with those obtained during the first reoperation, including persistence of initial pathogens and/or emergence of microorganisms. Risk factors for emergence of microorganisms and MDR bacteria were assessed by univariable and multivariable analyses. Results: Among 100 patients {63% male, 58 years old [interquartile ratio (IQR) 50-68]} admitted for NSTI, 54 underwent reoperation with a median [IQR] delay of 3 (1-7) days. Decreased proportions of susceptible strains and emergence of Gram-negative bacteria, including Pseudomonas aeruginosa, staphylococci and enterococci strains, were reported based on the cultures of surgical specimen collected on reoperation. On reoperation, 22 (27%) of the isolated strains were MDR (p < 0.0001 vs. MDR bacteria cultured from the first samples). Broad-spectrum antibiotic therapy as first-line therapy was significantly associated with a decreased emergence of microorganisms. Adequate antibiotic therapy from the initial surgery did not modify the frequency of emergence of microorganisms (p = 0.79) and MDR bacteria (p = 1.0) or the 1-year survival rate. Conclusion: The emergence of microorganisms, including MDR bacteria, is frequently noted in NSTI without affecting mortality.
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PURPOSE: Animal models of regional anaesthesia are useful for studying the effects of blocks and improve their efficacy. The aim of our experiments was to validate a multi-site paravertebral block in the rat. MATERIAL AND METHODS: Dissection and indigo carmine dye injection were performed in five rats (3 rats were dissected and 2 were dye injected). In other groups (n=7rats/group), after inflammation inductive carrageenan injection in the abdominal wall, bupivacaine or saline was injected laterally to the spinal column at the T5, T10, L1, L4 and S1 level. The efficacy of the block on mechanical nociception was measured using von Frey hairs. In addition, we measured c-Fos immunoreactive nuclei in the cord. RESULTS: The multi-site injection showed a perinervous distribution of the injected solution without intra-thoracic, intra-abdominal or epidural diffusion. Bilateral block with a relatively small volume of bupivacaine (0.5 mL) significantly increased the threshold to mechanical pain as compared to control (p=0.007) and significantly decreased the number of c-Fos immunoreactive nuclei in the posterior horn of the spinal cord (p<0.0001). CONCLUSION: This study shows that a parietal abdominal wall block is easy to perform in the rat. This block allows investigators to explore the mechanisms of action of abdominal parietal wall blocks.
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Day-case surgery (DCS) in digestive surgery is a hot topic, and new indications for DCS in the field of gastrointestinal surgery have recently been described. Laparoscopic sleeve gastrectomy (LSG) has become a popular bariatric procedure in recent years. LSG is a reproducible, standardized procedure with a short operating time and possibly simple perioperative management. It therefore meets the criteria to be performed as a DCS procedure. Recently published series of LSG as DCS have demonstrated its feasibility. In this review on LSG performed as DCS, we focused on the management of risks associated with DCS and the results of such type of management. A literature search was conducted in the PubMed and Embase databases. Six studies were selected, comprising a total of 6227 patients. Most published series were retrospective single-center studies. Inclusion criteria were similar between most studies (primary sleeve gastrectomy for most series, patients with a body mass index ≥40 kg/m2 or a body mass index ≥35 kg/m2 in the presence of co-morbidities), while exclusion criteria were based on literature data for some studies (using series on risk factors for morbidity and mortality after Roux-en-Y gastric bypass) and personal experience for other series. The mortality rate of LSG as DCS ranges 0%-.08%, while the overall complication rate ranges 0%-10%. The unplanned overnight admission rate after LSG ranges .8%-8%. The unscheduled hospitalization rates range 2.1%-8.5%. LSG performed as DCS is feasible with good results, but cannot be proposed for all patients. Good selection is necessary in others to avoid increased risk of morbidity and mortality.