Impact of withholding early antibiotic therapy in nonseptic surgical patients with suspected nosocomial infection: a retrospective cohort analysis

Abstract Background: Systemic inflammatory responses mimicking infectious complications are often present in surgical patients. Methods: The objective was to assess the association between withholding early antimicrobial therapy while investigating alternative diagnoses and worse outcomes in nonseptic patients with suspected nosocomial infection in a retrospective cohort of critically ill surgical patients. The initiation of antibiotic therapy within 24 h of the suspicion of infection was defined as the Early Empirical Antibiotic strategy (EEA) group and the initiation after 24 h of suspicion or not prescribed was defined as the Conservative Antibiotic strategy (CA) group. Primary outcome was composite: death, sepsis, or septic shock within 14 days. Main exclusion criteria were sepsis or an evident source of infection at inclusion. Results: Three hundred and forty patients were eligible for inclusion (74% trauma patients). Age, sex, reason for hospital admission, SAPS3 score, SOFA score, and use of vasopressors or mechanical ventilation were not different between the groups. Within 14 days of inclusion, 100% (130/130) of EEA patients received antibiotics compared to 57% (120/210) of CA patients. After adjusting for confounding variables, there was no association between primary outcome and the groups. In a post hoc subgroup analysis including only patients with a posteriori confirmed infection (by microbiological cultures), delay in initiation of adequate antimicrobial therapy was independently associated with the primary outcome (Odds Ratio = 1.19 per day of delay; 95% CI 1.05-1.37). Conclusions: Withholding early empiric antibiotic therapy was not associated with progression of organ dysfunction within 14 days in nonseptic surgical patients with suspected nosocomial infection without an obvious source.

Restrictive versus liberal fluid therapy for post-cesarean acute kidney injury in severe preeclampsia: a pilot randomized clinical trial

OBJECTIVES: The aim of this study was to determine whether a restrictive compared to a liberal fluid therapy will increase postoperative acute kidney injury (AKI) in patients with severe preeclampsia. METHODS: A total of 46 patients (mean age, 32 years; standard deviation, 6.8 years) with severe preeclampsia were randomized to liberal (1500 ml of lactated Ringer's, n=23) or restrictive (250 ml of lactated Ringer's, n=23) intravenous fluid regimen during cesarean section. The primary outcome was the development of a postoperative renal dysfunction defined by AKI Network stage ≥1. Serum cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated at postoperative days 1 and 2. ClinicalTrials.gov: NCT02214186. RESULTS: The rate of postoperative AKI was 43.5% in the liberal fluid group and 43.5% in the restrictive fluid group (p=1.0). Intraoperative urine output was higher in the liberal (116 ml/h, IQR 69-191) than in the restrictive fluid group (80 ml/h, IQR 37-110, p<0.05). In both groups, serum cystatin C did not change from postoperative day 1 compared to the preoperative period and significantly decreased on postoperative day 2 compared to postoperative day 1 (p<0.05). In the restrictive fluid group, NGAL levels increased on postoperative day 1 compared to the preoperative period (p<0.05) and decreased on postoperative day 2 compared to postoperative day 1 (p<0.05). CONCLUSION: Among patients with severe preeclampsia, a restrictive fluid regimen during cesarean section was not associated with increased postoperative AKI.

Atividade antibacteriana de tubos endotraqueais revestidos com dióxido de titânio padrão e dopados com nitrogênio: um estudo in vitro / Antibacterial activity of standard and N-doped titanium dioxide-coated endotracheal tubes: an in vitro study

RESUMO Objetivo: Avaliar a atividade antibacteriana contra Staphylococcus aureus e Pseudomonas aeruginosa de dois revestimentos endotraqueais com nanopartículas e fotocatálise sob luz visível. Métodos: Testaram-se dois tipos de nanopartículas de titânio: anatase padrão (TiO2) e TiO2 nano-dopada (N-TiO2). As nanopartículas foram colocadas em superfície interna de segmentos de tubos endotraqueais comerciais, aplicadas sobre um filtro de acetato de celulose; os tubos endotraqueais controle foram deixados sem revestimento de nanopartículas. Em cada tubo endotraqueal foi inoculado um total de 150 unidades formadoras de colônia e, a seguir, estes foram expostos a uma fonte de luz fluorescente (3700 lux, comprimento de onda de 300 - 700nm) por 5, 10, 20, 40, 60 e 80 minutos. Contaram-se as Unidades Formadoras de Colônia após 24 horas de incubação a 37ºC. A inativação bacteriana foi calculada como a redução porcentual do crescimento bacteriano em comparação a tubos não expostos à luz. Resultados: Na ausência de luz, não se observou qualquer atividade antibacteriana relevante contra qualquer das cepas estudadas. Para P. aeruginosa, ambos os revestimentos tiveram inativação bacteriana mais elevada do que o controle em qualquer dos momentos de avaliação (p < 0,001), sendo que não se observaram diferenças entre o revestimento padrão e nano-dopado. Para S. aureus, a inativação foi maior que os controles, começando a partir de 5 minutos para nano-dopado (p = 0,018) e 10 minutos para o revestimento padrão (p = 0,014); a inativação com a forma nano-dopada foi maior do que com a forma padrão aos 20 minutos (p < 0,001), 40 minutos (p < 0,001) e 60 minutos (p < 0,001). Conclusões: O revestimento com nanopartículas de titânio comercial padrão e nano-dopado inibiu o crescimento bacteriano sob a luz fluorescente visível. o revestimento nano-dopado teve maior atividade antibacteriana contra S. aureus em comparação à atividade observada com o revestimento com anatase padrão.

ABSTRACT Objective: The aim of this study was to assess the antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa of two nanoparticle endotracheal tube coatings with visible light-induced photocatalysis. Methods: Two types of titanium dioxide nanoparticles were tested: standard anatase (TiO2) and N-doped TiO2 (N-TiO2). Nanoparticles were placed on the internal surface of a segment of commercial endotracheal tubes, which were loaded on a cellulose acetate filter; control endotracheal tubes were left without a nanoparticle coating. A bacterial inoculum of 150 colony forming units was placed in the endotracheal tubes and then exposed to a fluorescent light source (3700 lux, 300-700 nm wavelength) for 5, 10, 20, 40, 60 and 80 minutes. Colony forming units were counted after 24 hours of incubation at 37°C. Bacterial inactivation was calculated as the percentage reduction of bacterial growth compared to endotracheal tubes not exposed to light. Results: In the absence of light, no relevant antibacterial activity was shown against neither strain. For P. aeruginosa, both coatings had a higher bacterial inactivation than controls at any time point (p < 0.001), and no difference was observed between TiO2 and N-TiO2. For S. aureus, inactivation was higher than for controls starting at 5 minutes for N-TiO2 (p = 0.018) and 10 minutes for TiO2 (p = 0.014); inactivation with N-TiO2 was higher than that with TiO2 at 20 minutes (p < 0.001), 40 minutes (p < 0.001) and 60 minutes (p < 0.001). Conclusions: Nanosized commercial and N-doped TiO2 inhibit bacterial growth under visible fluorescent light. N-TiO2 has higher antibacterial activity against S. aureus compared to TiO2.

Diferenças entre as formas pulmonares e extrapulmonares da síndrome do desconforto respiratório agudo / Comparison between pulmonary and extrapulmonary forms of acute respiratory distress syndrome

A síndrome do desconforto respiratório agudo (SDRA) pode ser causada por uma lesão direta (pulmonar) e/ou indireta (extrapulmonar) ao parênquima pulmonar. O presente estudo teve como objetivo apresentar uma revisão das principais diferenças entre a SDRA pulmonar e a SDRA extrapulmonar, discutindo os aspectos morfofuncionais e a resposta às diferentes estratégias terapêuticas. Esta revisão teve como base uma pesquisa bibliográfica sistemática de artigos clínicos e experimentais sobre a SDRA incluídos nas bases de dados Medline e SciELO. Com base em estudos experimentais, pode-se afirmar que a SDRA pulmonar e a SDRA extrapulmonar não são idênticas no que diz respeito a fisiopatologia, morfologia, mecânica respiratória e resposta às estratégias terapêuticas ventilatórias (pressão expiratória final positiva, manobras de recrutamento e posicionamento) e farmacológicas. Entretanto, os resultados dos estudos clínicos são contraditórios. Isso pode ser atribuído à dificuldade de se classificar a SDRA em pulmonar ou extrapulmonar, à coexistência de mais de um tipo de insulto, assim como a diferenças em relação à fase e à gravidade da SDRA nos pacientes. Concluindo, os pacientes com SDRA pulmonar e SDRA extrapulmonar, embora sejam portadores de síndromes diferentes, continuam sendo tratados da mesma forma. Considera-se fundamental uma melhor compreensão acerca da SDRA para melhor direcionar as estratégias terapêuticas.

The definition of acute respiratory distress syndrome (ARDS) was simplified at the 1998 American-European Consensus Conference of 1998 and now includes the following: bilateral pulmonary infiltrates; arterial oxygen tension/fraction of inspired oxygen < 200 mmHg; and pulmonary capillary wedge pressure < 18 mmHg or no signs of left heart failure.Recently, tomography and other imaging methods have allowed the chest to be analyzed in greater detail, thereby leading to a more complex understanding of ARDS. The use of genetic markers and biomarkers in plasma and bronchoalveolar lavage could lead to earlier ARDS diagnosis, thereby improving prognosis. The introduction of automatic diagnostic screening, together with the analysis of risk factors and prognostic factors associated with the syndrome, will deepen the understanding of ARDS, improving treatment and potentially reducing the associated mortality rates.

Understanding the mechanisms of glutamine action in critically ill patients

Glutamine (Gln) is an important energy source and has been used as a supplementary energy substrate. Furthermore, Gln is an essential component for numerous metabolic functions, including acid-base homeostasis, gluconeogenesis, nitrogen transport and synthesis of proteins and nucleic acids. Therefore, glutamine plays a significant role in cell homeostasis and organ metabolism. This article aims to review the mechanisms of glutamine action during severe illnesses. In critically ill patients, the increase in mortality was associated with a decreased plasma Gln concentration. During catabolic stress, Gln consumption rate exceeds the supply, and both plasma and skeletal muscle pools of free Gln are severely reduced. The dose and route of Gln administration clearly influence its effectiveness: high-dose parenteral appears to be more beneficial than low-dose enteral administration. Experimental studies reported that Gln may protect cells, tissues, and whole organisms from stress and injury through the following mechanisms: attenuation of NF (nuclear factor)-kB activation, a balance between pro- and anti-inflammatory cytokines, reduction in neutrophil accumulation, improvement in intestinal integrity and immune cell function, and enhanced of heat shock protein expression. In conclusion, high-doses of parenteral Gln (>0.50 g/kg/day) demonstrate a greater potential to benefit in critically ill patients, although Gln pathophysiological mechanisms requires elucidation.

A glutamina (Gln) é uma importante fonte de energia e tem sido usada como substrato energético suplementar. Além disso, a Gln é um componente essencial para numerosas funções metabólicas tais como: homeostase ácido-base, gliconeogênese, transporte de nitrogênio e síntese de proteínas e ácidos nucléicos. Portanto, a glutamina desempenha um papel importante na homeostase celular e no metabolismo dos órgãos. Esse artigo objetiva rever os mecanismos de ação da glutamina na doença grave. Em pacientes criticamente enfermos, o aumento da mortalidade foi associado com uma diminuição de Gln plasmática. Durante o estresse catabólico, o consumo de Gln excede a oferta, e a quantidade de glutamina livre no plasma e músculo esquelético encontra-se reduzida. A dose e via de administração da Gln claramente influencia sua eficácia: alta dose por via parenteral parece ser mais benéfica do que uma dose baixa administrada por via enteral. Estudos experimentais relataram que Gln protege as células, tecidos, e todo o organismo do estresse através dos seguintes mecanismos: atenuação na ativação do fator nuclear (NF)-kB, balanço entre citocinas pró- e anti-inflamatórias, redução no acúmulo de neutrófilos, melhora na integridade intestinal e função mune celular, e aumento da expressão da proteína de choque térmico. Em conclusão, o uso de glutamina em altas doses e por via parenteral (>0,50 g/kg/dia) demonstrou ser benéfica em pacientes criticamente enfermos, embora os mecanismos fisiopatoló-gicos necessitam ser melhor elucidados.

Síndrome do desconforto respiratório agudo pulmonar e extrapulmonar: existem diferenças? / Pulmonary and extrapulmonary acute respiratory distress syndrome: are they different?

JUSTIFICATIVA E OBJETIVOS: A patogênese da síndrome do desconforto respiratório agudo (SDRA) tem sido explicada pela presença de uma agressão direta (SDRA pulmonar) e/ou indireta (SDRA extrapulmonar) ao parênquima pulmonar. Evidências indicam que a fisiopatologia da doença pode diferir com o tipo de lesão. O objetivo deste estudo foi apresentar breve revisão das diferenças entre a SDRA pulmonar e a SDRA extrapulmonar e discutir as interações entre os aspectos morfofuncionais e a resposta aos diferentes tratamentos. CONTEÚDO: Esta revisão bibliográfica baseou-se em uma pesquisa sistemática de artigos experimentais e clínicos sobre SDRA incluídos nas bases de dados MedLine e SciElo nos últimos 20 anos. Muitos pesquisadores concordam, com base em estudos experimentais, que a SDRA pulmonar e a SDRA extrapulmonar não são idênticas no que diz respeito aos aspectos morfofuncionais, a resposta à pressão positiva ao final da expiração (PEEP), manobra de recrutamento alveolar, posição prona e outras terapias farmacológicas. Entretanto, os estudos clínicos têm descrito resultados contraditórios, os quais podem ser atribuídos à dificuldade de se classificar a SDRA em uma ou outra etiologia, e de se precisar o início, a fase e a gravidade da SDRA nos pacientes. CONCLUSÕES: Pacientes com SDRA de etiologias distintas perduram sendo considerados como pertencendo a uma mesma síndrome e, assim, são tratados da mesma forma. Logo, é fundamental entender as diferenças fisiopatológicas entre a SDRA pulmonar e extrapulmonar para que a terapia seja mais bem direcionada.

BACKGROUND AND OBJECTIVES: The pathogenesis of acute respiratory distress syndrome (ARDS) has been described by the presence of direct (pulmonary) and/or indirect (extrapulmonary) insult to the lung parenchyma. Evidence indicates that the pathophysiology of ARDS may differ according to the type of primary insult. This article presents a brief overview of differences between pulmonary and extrapulmonary ARDS, and discusses the interactions between morpho-functional aspects and response to differents therapies, both in experimental and clinical studies. CONTENTS: This systematic review included clinical and experimental ARDS studies found in MedLine and SciElo databases in the last 20 years. Many researchers acknowledge that experimental pulmonary and extrapulmonary ARDS are not identical with regard to morpho-functional aspects, the response to positive end-expiratory pressure (PEEP), recruitment manoeuvre, prone position and other adjunctive therapies. However, contradictory results have been reported in different clinical studies, which could be attributed to the difficulty of classifying ARDS in one or the other category, and to the assurance regarding the onset, phase and severity of ARDS in all patients. CONCLUSIONS: Heterogeneous ARDS patients are still considered as belonging to one syndrome, and are therefore treated in a similar manner. Thus, it is important to understand the pathophysiology of pulmonary and extrapulmonary ARDS in an attempt to better treat these patients.

The extracellular matrix of the lung and its role in edema formation

The extracellular matrix is composed of a three-dimensional fiber mesh filled with different macromolecules such as: collagen (mainly type I and III), elastin, glycosaminoglycans, and proteoglycans. In the lung, the extracellular matrix has several functions which provide: 1) mechanical tensile and compressive strength and elasticity, 2) low mechanical tissue compliance contributing to the maintenance of normal interstitial fluid dynamics, 3) low resistive pathway for an effective gas exchange, d) control of cell behavior by the binding of growth factors, chemokines, cytokines and the interaction with cell-surface receptors, and e) tissue repair and remodeling. Fragmentation and disorganization of extracellular matrix components comprises the protective role of the extracellular matrix, leading to interstitial and eventually severe lung edema. Thus, once conditions of increased microvascular filtration are established, matrix remodeling proceeds fairly rapidly due to the activation of proteases. Conversely, a massive matrix deposition of collagen fiber decreases interstitial compliance and therefore makes the tissue safety factor stronger. As a result, changes in lung extracellular matrix significantly affect edema formation and distribution in the lung.

A matriz extracelular é um aglomerado tridimensional demacromoléculas composta por: fibras colágenas (principalmente, tipos I e III), elastina, glicosaminoglicanos e proteoglicanos. No pulmão, a matriz extracelular tem várias funções, tais como: 1) promover estresse tensil e elasticidade tecidual, 2) contribuir para a manutenção da dinâmica de fluidos no interstício, 3) propiciar efetiva troca gasosa, 4) controlar a função celular através de sua ligação com fatores de crescimento, quimiocinas, citocinas e interação com receptores de superfície, e 5) remodelamento e reparo tecidual. A fragmentação e a desorganização da matriz extracelular pode acarretar edema intersticial e, eventualmente, edema alveolar grave. Logo, quando há aumento da filtração microvascular ocorre rápido remodelamento da matriz por ativação de proteases. Destarte, a deposição de fibras colágenas reduz a complacência intersticial limitando o edema. Em conclusão, modificações na matriz extracelular podem afetar a formação e distribuição do edema no pulmão.