Intravenous glutamine decreases lung and distal organ injury in an experimental model of abdominal sepsis

Introduction The protective effect of glutamine, as a pharmacological agent against lung injury, has been reported in experimental sepsis; however, its efficacy at improving oxygenation and lung mechanics, attenuating diaphragm and distal organ injury has to be better elucidated. In the present study, we tested the hypothesis that a single early intravenous dose of glutamine was associated not only with the improvement of lung morpho-function, but also the reduction of the inflammatory process and epithelial cell apoptosis in kidney, liver, and intestine villi. Methods Seventy-two Wistar rats were randomly assigned into four groups. Sepsis was induced by cecal ligation and puncture surgery (CLP), while a sham operated group was used as control (C). One hour after surgery, C and CLP groups were further randomized into subgroups receiving intravenous saline (1 ml, SAL) or glutamine (0.75 g/kg, Gln). At 48 hours, animals were anesthetized, and the following parameters were measured: arterial oxygenation, pulmonary mechanics, and diaphragm, lung, kidney, liver, and small intestine villi histology. At 18 and 48 hours, Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, interleukin (IL)-6 and 10 were quantified in bronchoalveolar and peritoneal lavage fluids (BALF and PLF, respectively). Results CLP induced: a) deterioration of lung mechanics and gas exchange; b) ultrastructural changes of lung parenchyma and diaphragm; and c) lung and distal organ epithelial cell apoptosis. Glutamine improved survival rate, oxygenation and lung mechanics, minimized pulmonary and diaphragmatic changes, attenuating lung and distal organ epithelial cell apoptosis. Glutamine increased IL-10 in peritoneal lavage fluid at 18 hours and bronchoalveolar lavage fluid at 48 hours, but decreased CINC-1 and IL-6 in BALF and PLF only at 18 hours. Conclusions In an experimental model of abdominal sepsis, a single intravenous dose of glutamine administered after sepsis induction may modulate the inflammatory process reducing not only the risk of lung injury, but also distal organ impairment. These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.Centres of Excellence Program (PRONEX-FAPERJ)Brazilian Council for Scientific and Technological Development (CNPq)Carlos Chagas FilhoRio de Janeiro State Research Supporting Foundation (FAPERJ)Sao Paulo State Research Supporting Foundation (FAPESP

Adverse reactions to oxacillin in hospitalized children: a prospective study Reações adversas à oxacilina em crianças hospitalizadas: um estudo prospectivo

OBJECTIVES: follow-up of children exposed to oxacillin during hospitalization focusing on adverse reactions. METHODS: patients were selected from the pediatric wards of two hospitals in Fortaleza (Hospital Universitário Walter Cantídio-HUWC and Hospital Infantil Albert Sabin-HIAS) from the first oxacillin prescription with a prospective cohort study between October, 2000 and July, 2001 (HUWC) and July/2001 and March, 2002 (HIAS). Patients' follow-up was performed by daily visits to the wards and medical charts and prescription analysis. Suspected oxacillininduced adverse reactions (OxAR cases) were notified and classified according to causality and severity. Related statistic tests were completed. RESULTS: of the 130 patients exposed to oxacillin, 27 had OxAR (20.8%). Fever was the most frequent reaction (50%) followed by rash (35.7%). The majority of reactions were considered Probable, for oxacillin was the only medication involved and 92.6% of the cases had Moderate severity with the need of therapeutic interventions caused by OxAR. A significant relation between oxacillin exposure time and OxAR was determined as well as hospitalization time and the appearance of adverse reactions. Exposure time over 14 days to oxacillin was established as a risk factor for OxAR (relative risk = 5.49). CONCLUSIONS: careful administration of oxacillin in children is recommended with established treatment duration. Empiric and prolonged use must be avoided.<br>OBJETIVOS: acompanhar crianças expostas à oxacilina durante hospitalização, com foco na incidência de reações adversas. MÉTODOS: os pacientes foram selecionados em enfermarias pediátricas de dois hospitais de Fortaleza (Hospital Universitário Walter Cantídio-HUWC e Hospital Infantil Albert Sabin-HIAS), desde a primeira prescrição de oxacilina, sendo feita coorte prospectiva entre outubro, 2000 e julho, 2001 (HUWC), e entre julho,2001 e março,2002 (HIAS). O seguimento de pacientes deu-se através de visitas diárias às enfermarias e análise de prontuários e prescrições. Os casos de RAOx foram notificados e classificados quanto à causalidade e gravidade, sendo realizados testes estatísticos pertinentes. RESULTADOS: dos 130 pacientes expostos à oxacilina, 27 apresentaram RAOx (20,8%), sendo febre a reação mais freqüente (50%), seguida do rash cutâneo (35,7%). A maioria das reações foi considerada Provável, pois a oxacilina foi o único medicamento envolvido e 92,6% dos casos tiveram gravidade Moderada, sendo necessárias intervenções terapêuticas devido à RAOx. Uma associação significante entre tempo de exposição à oxacilina e aparecimento de RAOx, assim como entre tempo de internamento e ocorrência de reação foi observada. Um tempo de exposição maior que 14 dias apresentou-se como fator de risco para ocorrência de RAOx (risco relativo = 5,49). CONCLUSÕES: recomenda-se administração cautelosa de oxacilina em crianças, com duração do tratamento estabelecida, evitando-se tratamento empírico e uso prolongado