Nebulized antibiotics for ventilator-associated pneumonia: a systematic review and meta-analysis

INTRODUCTION: Nebulized antibiotics are a promising new treatment option for ventilator-associated pneumonia. However, more evidence of the benefit of this therapy is required. METHODS: The Medline, Scopus, EMBASE, Biological Abstracts, CAB Abstracts, Food Science and Technology Abstracts, CENTRAL, Scielo and Lilacs databases were searched to identify randomized controlled trials or matched observational studies that compared nebulized antibiotics with or without intravenous antibiotics to intravenous antibiotics alone for ventilator-associated pneumonia treatment. Two reviewers independently collected data and assessed outcomes and risk of bias. The primary outcome was clinical cure. Secondary outcomes were microbiological cure, ICU and hospital mortality, duration of mechanical ventilation, ICU length of stay and adverse events. A mixed-effect model meta-analysis was performed. Trial sequential analysis was used for the main outcome of interest. RESULTS: Twelve studies were analyzed, including six randomized controlled trials. For the main outcome analysis, 812 patients were included. Nebulized antibiotics were associated with higher rates of clinical cure (risk ratio (RR) = 1.23; 95% confidence interval (CI), 1.05 to 1.43; I(2) = 34%; D(2) = 45%). Nebulized antibiotics were not associated with microbiological cure (RR = 1.24; 95% CI, 0.95 to 1.62; I(2) = 62.5), mortality (RR = 0.90; CI 95%, 0.76 to 1.08; I(2) = 0%), duration of mechanical ventilation (standardized mean difference = -0.10 days; 95% CI, -1.22 to 1.00; I(2) = 96.5%), ICU length of stay (standardized mean difference = 0.14 days; 95% CI, -0.46 to 0.73; I(2) = 89.2%) or renal toxicity (RR = 1.05; 95% CI, 0.70 to 1.57; I(2) = 15.6%). Regarding the primary outcome, the number of patients included was below the information size required for a definitive conclusion by trial sequential analysis; therefore, our results regarding this parameter are inconclusive. CONCLUSIONS: Nebulized antibiotics seem to be associated with higher rates of clinical cure in the treatment of ventilator-associated pneumonia. However, the apparent benefit in the clinical cure rate observed by traditional meta-analysis does not persist after trial sequential analysis. Additional high-quality studies on this subject are highly warranted

The validity and reliability of the Portuguese versions of three tools used to diagnose delirium in critically ill patients

OBJECTIVES: The objectives of this study are to compare the sensitivity and specificity of three diagnostic tools for delirium (the Intensive Care Delirium Screening Checklist, the Confusion Assessment Method for Intensive Care Units and the Confusion Assessment Method for Intensive Care Units Flowsheet) in a mixed population of critically ill patients, and to validate the Brazilian Portuguese Confusion Assessment Method for Intensive Care Units. METHODS: The study was conducted in four intensive care units in Brazil. Patients were screened for delirium by a psychiatrist or neurologist using the Diagnostic and Statistical Manual of Mental Disorders. Patients were subsequently screened by an intensivist using Portuguese translations of the three tools. RESULTS: One hundred and nineteen patients were evaluated and 38.6% were diagnosed with delirium by the reference rater. The Confusion Assessment Method for Intensive Care Units had a sensitivity of 72.5% and a specificity of 96.2%; the Confusion Assessment Method for Intensive Care Units Flowsheet had a sensitivity of 72.5% and a specificity of 96.2%; the Intensive Care Delirium Screening Checklist had a sensitivity of 96.0% and a specificity of 72.4%. There was strong agreement between the Confusion Assessment Method for Intensive Care Units and the Confusion Assessment Method for Intensive Care Units Flowsheet (kappa coefficient = 0.96) CONCLUSION: All three instruments are effective diagnostic tools in critically ill intensive care unit patients. In addition, the Brazilian Portuguese version of the Confusion Assessment Method for Intensive Care Units is a valid and reliable instrument for the assessment of delirium among critically ill patients

an international survey before and during the COVID-19 pandemic

Funding Information: The Société Française d’Anesthésie et de Réanimation (SFAR), Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC), Sociedad Argentina de Terapia Intensiva (SATI), Sociedad Chilena de Medicina Intensiva (SOCHIMI), Associação de Medicina Intensiva Brasileira (AMIB-Net) and the Brazilian Research in Intensive Care Network (BricNet) supported this survey. We would also like to thank our friend Tiago Rocha for making the amazing logo for this study. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES)—Finance Code 001. Publisher Copyright: © 2022, The Author(s).Background: Since the publication of the 2018 Clinical Guidelines about sedation, analgesia, delirium, mobilization, and sleep deprivation in critically ill patients, no evaluation and adequacy assessment of these recommendations were studied in an international context. This survey aimed to investigate these current practices and if the COVID-19 pandemic has changed them. Methods: This study was an open multinational electronic survey directed to physicians working in adult intensive care units (ICUs), which was performed in two steps: before and during the COVID-19 pandemic. Results: We analyzed 1768 questionnaires and 1539 (87%) were complete. Before the COVID-19 pandemic, we received 1476 questionnaires and 292 were submitted later. The following practices were observed before the pandemic: the Visual Analog Scale (VAS) (61.5%), the Behavioral Pain Scale (BPS) (48.2%), the Richmond Agitation Sedation Scale (RASS) (76.6%), and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) (66.6%) were the most frequently tools used to assess pain, sedation level, and delirium, respectively; midazolam and fentanyl were the most frequently used drugs for inducing sedation and analgesia (84.8% and 78.3%, respectively), whereas haloperidol (68.8%) and atypical antipsychotics (69.4%) were the most prescribed drugs for delirium treatment; some physicians regularly prescribed drugs to induce sleep (19.1%) or ordered mechanical restraints as part of their routine (6.2%) for patients on mechanical ventilation; non-pharmacological strategies were frequently applied for pain, delirium, and sleep deprivation management. During the COVID-19 pandemic, the intensive care specialty was independently associated with best practices. Moreover, the mechanical ventilation rate was higher, patients received sedation more often (94% versus 86.1%, p < 0.001) and sedation goals were discussed more frequently in daily rounds. Morphine was the main drug used for analgesia (77.2%), and some sedative drugs, such as midazolam, propofol, ketamine and quetiapine, were used more frequently. Conclusions: Most sedation, analgesia and delirium practices were comparable before and during the COVID-19 pandemic. During the pandemic, the intensive care specialty was a variable that was independently associated with the best practices. Although many findings are in accordance with evidence-based recommendations, some practices still need improvement.publishersversionpublishe

Sigh in patients with acute hypoxemic respiratory failure and acute respiratory distress syndrome: the PROTECTION pilot randomized clinical trial

Background: Sigh is a cyclic brief recruitment manoeuvre: previous physiological studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity and increase release of surfactant. Research question: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? Study design and methods: We conducted a multi-center non-inferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or acute respiratory distress syndrome undergoing PSV. Patients were randomized to the No Sigh group and treated by PSV alone, or to the Sigh group, treated by PSV plus sigh (increase of airway pressure to 30 cmH2Ofor 3 seconds once per minute) until day 28 or death or successful spontaneous breathing trial. The primary endpoint of the study was feasibility, assessed as non-inferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiological parameters in the first week from randomization, 28-day mortality and ventilator-free days. Results: Two-hundred fifty-eight patients (31% women; median age 65 [54-75] years) were enrolled. In the Sigh group, 23% of patients failed to remain on assisted ventilation vs. 30% in the No Sigh group (absolute difference -7%, 95%CI -18% to 4%; p=0.015 for non-inferiority). Adverse events occurred in 12% vs. 13% in Sigh vs. No Sigh (p=0.852). Oxygenation was improved while tidal volume, respiratory rate and corrected minute ventilation were lower over the first 7 days from randomization in Sigh vs. No Sigh. There was no significant difference in terms of mortality (16% vs. 21%, p=0.342) and ventilator-free days (22 [7-26] vs. 22 [3-25] days, p=0.300) for Sigh vs. No Sigh. Interpretation: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk

Biomarcadores na encefalopatia séptica: revisão sistemática dos estudos clínicos

OBJETIVO: O objetivo deste estudo foi revisar sistematicamente a importância da enolase específica neuronal e S100B para diagnóstico e monitorização da encefalopatia séptica. MÉTODOS: Foi realizada uma busca no banco de dados PubMed selecionando estudos que avaliaram níveis séricos de S 100 B e enolase específica neuronal em pacientes com sepse, publicados entre Janeiro de 2000 e Abril de 2012. Apenas estudos em humanos e que utilizaram um método adicional de avaliação neurológica foram selecionados. RESULTADOS: Foram identificados nove estudos, dos quais sete associaram concentrações elevadas de S100 beta e enolase específica neuronal ao desenvolvimento de encefalopatia séptica; quatro também as associaram ao aumento de mortalidade. Entretanto, dois trabalhos não encontraram essa associação quando avaliaram S100 beta e um deles não observou correlação entre a enolase específica neuronal e encefalopatia séptica. CONCLUSÃO: A S100 beta e enolase específica neuronal são biomarcadores promissores para diagnóstico e monitorização de pacientes com encefalopatia séptica, mas é necessária uma maior investigação

Delirium rating scales in critically ill patients: a systematic literature review

OBJETIVO: Identificar escalas capazes de estabelecer uma avaliação quantitativa dos sintomas do delirium em pacientes graves por meio de uma revisão sistemática. MÉTODOS: Foram selecionados estudos que avaliaram escalas de estratificação de delirium em pacientes internados em unidades de terapia intensiva a partir de busca na base de dados MedLine. Os estudos de validação dessas escalas foram analisados, e foram identificados os pacientes alvos para aplicação, o avaliador, os sinais e sintomas avaliados, a duração da aplicação, além da sensibilidade e da especificidade de cada escala. RESULTADOS: Seis escalas foram identificadas: o Delirium Detection Score, o Cognitive Test of Delirium, a Memorial Delirium Assessment Scale, o Intensive Care Delirium Screening Checklist, a The Neelon and Champagne Confusion Scale e a Delirium Rating Scale-Revised-98. CONCLUSÃO: As escalas identificadas permitem estratificação e acompanhamento do paciente grave com delirium. Dentre as seis escalas, a mais estudada e que melhor se adequa ao uso em unidade de terapia intensiva foi o Intensive Care Delirium Screening Checklist

Critical Care

p. 1-10Introduction Delirium is a frequent form of acute brain dysfunction in critically ill patients, and several detection tools for it have been developed for use in the Intensive Care Unit (ICU). The objective of this study is to evaluate the current evidence on the accuracy of the Confusion Assessment Method for Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) for the diagnosis of delirium in critically ill patients. Methods A systematic review was conducted to identify articles on the evaluation of the CAM-ICU and the ICDSC in ICU patients. A MEDLINE, SciELO, CINAHL and EMBASE databases search was performed for articles published in the English language, involving adult populations and comparing these diagnostic tools with the gold standard, the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Results were summarized by meta-analysis. The QUADAS scale was used to assess the quality of the studies. Results Nine studies evaluating the CAM-ICU (including 969 patients) and four evaluating the ICDSC (n = 361 patients) were included in the final analysis. The pooled sensitivity of the CAM-ICU was 80.0% (95% confidence interval (CI): 77.1 to 82.6%), and the pooled specificity was 95.9% (95% CI: 94.8 to 96.8%). The diagnostic odds ratio was 103.2 (95% CI: 39.6 to 268.8). The pooled area under the summary receiver operating characteristic curve (AUC) was 0.97. The pooled sensitivity of the ICDSC was 74% (95% CI: 65.3 to 81.5%), and the pooled specificity was 81.9% (95% CI: 76.7 to 86.4%). The diagnostic odds ratio was 21.5 (95% CI: 8.51 to 54.4). The AUC was 0.89. Conclusions The CAM-ICU is an excellent diagnostic tool in critically ill ICU patients, whereas the ICDSC has moderate sensitivity and good specificity. The available data suggest that both CAM-ICU and the ICDSC can be used as a screening tool for the diagnosis of delirium in critically ill patients

Nebulized antibiotics for ventilator-associated pneumonia: a systematic review and meta-analysis

INTRODUCTION: Nebulized antibiotics are a promising new treatment option for ventilator-associated pneumonia. However, more evidence of the benefit of this therapy is required. METHODS: The Medline, Scopus, EMBASE, Biological Abstracts, CAB Abstracts, Food Science and Technology Abstracts, CENTRAL, Scielo and Lilacs databases were searched to identify randomized controlled trials or matched observational studies that compared nebulized antibiotics with or without intravenous antibiotics to intravenous antibiotics alone for ventilator-associated pneumonia treatment. Two reviewers independently collected data and assessed outcomes and risk of bias. The primary outcome was clinical cure. Secondary outcomes were microbiological cure, ICU and hospital mortality, duration of mechanical ventilation, ICU length of stay and adverse events. A mixed-effect model meta-analysis was performed. Trial sequential analysis was used for the main outcome of interest. RESULTS: Twelve studies were analyzed, including six randomized controlled trials. For the main outcome analysis, 812 patients were included. Nebulized antibiotics were associated with higher rates of clinical cure (risk ratio (RR) = 1.23; 95% confidence interval (CI), 1.05 to 1.43; I(2) = 34%; D(2) = 45%). Nebulized antibiotics were not associated with microbiological cure (RR = 1.24; 95% CI, 0.95 to 1.62; I(2) = 62.5), mortality (RR = 0.90; CI 95%, 0.76 to 1.08; I(2) = 0%), duration of mechanical ventilation (standardized mean difference = -0.10 days; 95% CI, -1.22 to 1.00; I(2) = 96.5%), ICU length of stay (standardized mean difference = 0.14 days; 95% CI, -0.46 to 0.73; I(2) = 89.2%) or renal toxicity (RR = 1.05; 95% CI, 0.70 to 1.57; I(2) = 15.6%). Regarding the primary outcome, the number of patients included was below the information size required for a definitive conclusion by trial sequential analysis; therefore, our results regarding this parameter are inconclusive. CONCLUSIONS: Nebulized antibiotics seem to be associated with higher rates of clinical cure in the treatment of ventilator-associated pneumonia. However, the apparent benefit in the clinical cure rate observed by traditional meta-analysis does not persist after trial sequential analysis. Additional high-quality studies on this subject are highly warranted