VATICAN (Ventilator-Associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation): protocol for a multicenter randomized open-label trial of watchful waiting versus antimicrobial therapy for ventilator-associated tracheobronchitis.

BACKGROUND: Ventilator-associated tracheobronchitis is a common condition among invasively ventilated patients in intensive care units, for which the best treatment strategy is currently unknown. We designed the VATICAN (Ventilator-Associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation) trial to assess whether a watchful waiting antibiotic treatment strategy is noninferior to routine antibiotic treatment for ventilator-associated tracheobronchitis regarding days free of mechanical ventilation. METHODS: VATICAN is a randomized, controlled, open-label, multicenter noninferiority trial. Patients with suspected ventilator-associated tracheobronchitis without evidence of ventilator-associated pneumonia or hemodynamic instability due to probable infection will be assigned to either a watchful waiting strategy, without antimicrobial administration for ventilator-associated tracheobronchitis and prescription of antimicrobials only in cases of ventilator-associated pneumonia, sepsis or septic shock, or another infectious diagnosis, or to a routine antimicrobial treatment strategy for seven days. The primary outcome will be mechanical ventilation-free days at 28 days, and a key secondary outcome will be ventilator-associated pneumonia-free survival. Through an intention-to-treat framework with a per-protocol sensitivity analysis, the primary outcome analysis will address noninferiority with a 20% margin, which translates to a 1.5 difference in ventilator-free days. Other analyses will follow a superiority analysis framework. CONCLUSION: The VATICAN trial will follow all national and international ethical standards. We aim to publish the trial in a high-visibility general journal and present it at critical care and infectious disease conferences for dissemination. These results will likely be immediately applicable to the bedside upon trial completion and will provide information with a low risk of bias for guideline development.

Factors associated with carbon dioxide transfer in an experimental model of severe acute kidney injury and hypoventilation during high bicarbonate continuous renal replacement therapy and oxygenation membrane support.

OBJECTIVE: To investigate the factors influencing carbon dioxide transfer in a system that integrates an oxygenation membrane in series with high-bicarbonate continuous veno-venous hemodialysis in hypercapnic animals. METHODS: In an experimental setting, we induced severe acute kidney injury and hypercapnia in five female Landrace pigs. Subsequently, we initiated high (40mEq/L) bicarbonate continuous veno-venous hemodialysis with an oxygenation membrane in series to maintain a pH above 7.25. At intervals of 1 hour, 6 hours, and 12 hours following the initiation of continuous veno-venous hemodialysis, we performed standardized sweep gas flow titration to quantify carbon dioxide transfer. We evaluated factors associated with carbon dioxide transfer through the membrane lung with a mixed linear model. RESULTS: A total of 20 sweep gas flow titration procedures were conducted, yielding 84 measurements of carbon dioxide transfer. Multivariate analysis revealed associations among the following (coefficients ± standard errors): core temperature (+7.8 ± 1.6 °C, p < 0.001), premembrane partial pressure of carbon dioxide (+0.2 ± 0.1/mmHg, p < 0.001), hemoglobin level (+3.5 ± 0.6/g/dL, p < 0.001), sweep gas flow (+6.2 ± 0.2/L/minute, p < 0.001), and arterial oxygen saturation (-0.5 ± 0.2%, p = 0.019). Among these variables, and within the physiological ranges evaluated, sweep gas flow was the primary modifiable factor influencing the efficacy of low-blood-flow carbon dioxide removal. CONCLUSION: Sweep gas flow is the main carbon dioxide removal-related variable during continuous veno-venous hemodialysis with a high bicarbonate level coupled with an oxygenator. Other carbon dioxide transfer modulating variables included the hemoglobin level, arterial oxygen saturation, partial pressure of carbon dioxide and core temperature. These results should be interpreted as exploratory to inform other well-designed experimental or clinical studies.

Changing trends in clinical characteristics and in-hospital mortality of patients with infective endocarditis over four decades.

BACKGROUND: Infective endocarditis continues to be a significant concern and may be undergoing an epidemiological transition. METHODS: Were studied 1804 consecutive episodes of infective endocarditis between 1978 and 2022. The mean age was 48 ( ± 19), and 1162 (64%) patients were male. Temporal trends in demographic data, comorbidities, predisposing conditions, microorganisms, complications and in-hospital death have been studied over the decades (1978-1988, 1989-1999, 2000-2010 and 2011-2022). The outcomes and clinical characteristics were modeled using nonlinear cubic spline functions. FINDINGS: Valve surgery was performed in 50% of the patients and overall in-hospital mortality was 30%. From the first to the fourth decade studied, the average age of patients increased from 29 to 57 years (p < 0.001), with significant declines in the occurrence of rheumatic valvular heart disease (15% to 6%; p < 0.001) and streptococcal infections (46% to 33%; p < 0.001). Healthcare-associated infections have increased (9% to 21%; p < 0.001), as have prosthetic valve endocarditis (26% to 53%; p < 0.001), coagulase-negative staphylococcal infections (4% to 11%; p < 0.001), and related-complications (heart failure, embolic events, and perivalvular abscess; p < 0.001). These changes were associated with a decline in adjusted in-hospital mortality from 34% to 25% (p = 0.019). INTERPRETATION: In the 44 years studied, there was an increase in the mean age of patients, healthcare-related, prosthetic valve, coagulase-negative staphylococci/MRSA infections, and related complications. Notably, these epidemiological changes were associated with a decline in the adjusted in-hospital mortality.

Validation of a low-cost continuous renal replacement therapy dialysate fluid controller for experimental purposes.

BACKGROUND: Continuous renal replacement therapy (CRRT) support is crucial for critically ill patients and it is underexplored in specific situations. Experimental CRRT offers a means to gain insights into these scenarios, but the prohibitive cost of CRRT machines limits their accessibility. This study aimed to develop and validate a low-cost and precise dialysate controller for experimental CRRT. RESULTS: Our results demonstrate a commendable level of precision in affluent flow control, with a robust correlation (R2 = 0.99) for continuous flow and a strong correlation (R2 = 0.95) for intermittent flow. Additionally, we observed acceptable agreement with a bias = 3.4 mL (upper limit 95% = 43.9 mL and lower limit 95% = - 37 mL) for continuous flow and bias = - 20.9 mL (upper limit 95% = 54 mL and lower limit 95% = - 95.7 mL) for intermittent flow, in this way, offering a precise CRRT dose for the subjects. Furthermore, we achieved excellent precision in the cumulative ultrafiltration net (UFnet), with a bias = - 2.8 mL (upper limit 95% = 6.5 mL and lower limit 95% = - 12 mL). These results remained consistent even at low affluent flow rates of 8, 12, and 20 mL/min, which are compatible with CRRT doses of 25-30 mL/kg for medium-sized animals. Moreover, the acceptable precision of our findings persisted when the dialysate controller was subjected to high filter dialysate chamber pressure for an extended duration, up to 797 min. CONCLUSIONS: The low-cost dialysate controller developed and tested in this study offers a precise means of regulating CRRT in experimental settings. Its affordability and accuracy render it a valuable instrument for studying CRRT support in unconventional clinical scenarios, particularly in middle-income countries' experimental ICU laboratories.

Association between piperacillin/tazobactam use and acute kidney injury in critically ill patients: a retrospective multicentre cohort study.

BACKGROUND: Piperacillin/tazobactam is one of the most common antibiotics prescribed in the ICU and the combination of piperacillin/tazobactam with vancomycin has been associated with acute kidney injury (AKI) in critically ill patients. However, data on the risk of AKI with piperacillin/tazobactam, despite vancomycin co-exposure, are lacking. OBJECTIVES: To investigate the association of piperacillin/tazobactam with AKI and renal replacement therapy (RRT) among adult ICU patients. METHODS: We analysed data from patients included in two open access databases (MIMIC-IV and eICU). Critically ill patients who received piperacillin/tazobactam or cefepime (a cephalosporin with similar broad-spectrum activity to piperacillin/tazobactam) during their first ICU stay were eligible for the study. Marginal structural Cox models, accounting for time-fixed covariates and time-dependent covariates were performed. The primary outcomes were AKI and need of RRT. RESULTS: A total of 20 107 patients were included, with 11 213 in the piperacillin/tazobactam group and 8894 in the cefepime group. Exposure to piperacillin/tazobactam was associated with AKI (HR 1.77; 95% CI 1.51-2.07; P < 0.001) and with need of RRT (HR 1.31; 95% CI 1.08-1.57; P = 0.005). Tests for interaction were not statistically significant for occurrence of AKI and RRT in the subgroup of patients exposed to vancomycin or not (P = 0.26 and P = 0.6, respectively). CONCLUSIONS: In critically ill patients, exposure to piperacillin/tazobactam was associated with increased risk of AKI and with increased risk of RRT, regardless of combination therapy with vancomycin.

Adverse events leading to intensive care unit admission in a low-and-middle-income-country: A prospective cohort study and a systematic review.

INTRODUCTION: Adverse events (AE) are frequent in critical care and could be even more prevalent in LMIC due to a shortage of ICU beds and Human resources. There is limited data on how relevant AE are among the reasons for ICU admission, being all of which published by High-Income-Countries services. Our main goal is to describe the rate of adverse events-related ICU admissions and their preventability in a LMIC scenario, comparing our results with previous data. METHODS: This was a prospective cohort study, during a one-year period, in two general ICUs from a tertiary public academic hospital. Our exposure of interest was ICU admission related to an AE in adult patients, we further characterized their preventability and clinical outcomes. We also performed a systematic review to identify and compare previous published data on ICU admissions due to AE. RESULTS: Among all ICU admissions, 12.1% were related to an AE (9.8% caused by an AE, 2.3% related but not directly caused by an AE). These ICU admissions were not associated with a higher risk of death, but most of them were potentially preventable (70.9% of preventability rate, representing 8.6% of all ICU admissions). The meta-analysis resulted in a proportion of ICU admissions due to AE of 11% (95% CI 6%-16%), with a preventability rate of 54% (95% CI 42%-66%). CONCLUSIONS: In this prospective cohort, adverse events were a relevant reason for ICU admission. This result is consistent with data retrieved from non-LMIC as shown in our meta-analysis. The high preventability rate described reinforces that quality and safety programs could work as a tool to optimize scarce resources.

Characteristics of critically ill patients with cancer associated with intensivist's perception of inappropriateness of ICU admission: A retrospective cohort study.

PURPOSE: Although admitting cancer patients to the ICU is no longer an issue, it may be valuable to identify patients perceived least likely to benefit from admission. Our objective was to investigate factors associated with potentially inappropriate ICU admission. METHODS: Retrospective cohort study of patients with cancer with unplanned ICU admission. We classified admissions as appropriate or potentially inappropriate according to Society of Critical Care Medicine guidelines. We used logistic regression model to assess factors associated with inappropriateness for ICU admission. RESULTS: From 3384 patients, 663 (19.6%) were classified as potentially inappropriate. They received more invasive mechanical ventilation (25.3% vs 12.5%, P < 0.001) and vasopressors (34.4% vs 30.1%, P = 0.034), had higher ICU [3 (2,6) vs 2 (1,4), P < 0.001] length-of-stay, higher ICU (32.7% vs 8.4%, P < 0.001), hospital (71.9% vs 21.3%, P < 0.001), and one-year mortality (97.6% vs 54.7%, P < 0.001) compared with those considered appropriate. Performance status impairment, more severe organ dysfunctions at admission, metastatic disease, and source of ICU admission were the characteristics associated with intensivist's perception of inappropriateness of ICU admission. CONCLUSIONS: These findings may help guide ICU admission policies and triage criteria for end-of-life discussions among hospitalized patients with cancer.

Factors associated with carbon dioxide transfer in an experimental model of severe acute kidney injury and hypoventilation during high bicarbonate continuous renal replacement therapy and oxygenation membrane support / Fatores associados à transferência de dióxido de carbono em um modelo experimental de lesão renal aguda grave e hipoventilação durante terapia de substituição renal contínua com alto teor de bicarbonato e suporte com membrana de oxigenação

ABSTRACT Objective To investigate the factors influencing carbon dioxide transfer in a system that integrates an oxygenation membrane in series with high-bicarbonate continuous veno-venous hemodialysis in hypercapnic animals. Methods In an experimental setting, we induced severe acute kidney injury and hypercapnia in five female Landrace pigs. Subsequently, we initiated high (40mEq/L) bicarbonate continuous veno-venous hemodialysis with an oxygenation membrane in series to maintain a pH above 7.25. At intervals of 1 hour, 6 hours, and 12 hours following the initiation of continuous veno-venous hemodialysis, we performed standardized sweep gas flow titration to quantify carbon dioxide transfer. We evaluated factors associated with carbon dioxide transfer through the membrane lung with a mixed linear model. Results A total of 20 sweep gas flow titration procedures were conducted, yielding 84 measurements of carbon dioxide transfer. Multivariate analysis revealed associations among the following (coefficients ± standard errors): core temperature (+7.8 ± 1.6 °C, p < 0.001), premembrane partial pressure of carbon dioxide (+0.2 ± 0.1/mmHg, p < 0.001), hemoglobin level (+3.5 ± 0.6/g/dL, p < 0.001), sweep gas flow (+6.2 ± 0.2/L/minute, p < 0.001), and arterial oxygen saturation (-0.5 ± 0.2%, p = 0.019). Among these variables, and within the physiological ranges evaluated, sweep gas flow was the primary modifiable factor influencing the efficacy of low-blood-flow carbon dioxide removal. Conclusion Sweep gas flow is the main carbon dioxide removal-related variable during continuous veno-venous hemodialysis with a high bicarbonate level coupled with an oxygenator. Other carbon dioxide transfer modulating variables included the hemoglobin level, arterial oxygen saturation, partial pressure of carbon dioxide and core temperature. These results should be interpreted as exploratory to inform other well-designed experimental or clinical studies.

RESUMO Objetivo Investigar os fatores que influenciam a transferência de dióxido de carbono em um sistema que integra uma membrana de oxigenação em série com terapia de substituição renal contínua com alto teor de bicarbonato em animais hipercápnicos. Métodos Em um ambiente experimental, induzimos lesão renal aguda grave e hipercapnia em cinco porcos Landrace fêmeas. Em seguida, iniciamos terapia de substituição renal contínua com alto teor de bicarbonato (40mEq/L) com uma membrana de oxigenação em série para manter o pH acima de 7,25. Em intervalos de 1 hora, 6 horas e 12 horas após o início da terapia de substituição renal contínua, realizamos uma titulação padronizada do fluxo de gás de varredura para quantificar a transferência de dióxido de carbono. Avaliamos os fatores associados à transferência de dióxido de carbono através da membrana pulmonar com um modelo linear misto. Resultados Realizamos 20 procedimentos de titulação do fluxo de gás de varredura, produzindo 84 medições de transferência de dióxido de carbono. A análise multivariada revelou associações entre os seguintes itens (coeficientes ± erros padrão): temperatura central (+7,8 ± 1,6 °C, p < 0,001), pressão parcial pré-membrana de dióxido de carbono (+0,2 ± 0,1mmHg, p < 0,001), nível de hemoglobina (+3,5 ± 0,6g/dL, p < 0,001), fluxo de gás de varredura (+6,2 ± 0,2L/minuto, p < 0,001) e saturação de oxigênio (-0,5% ± 0,2%, p = 0,019). Entre essas variáveis, e dentro das faixas fisiológicas avaliadas, o fluxo do gás de varredura foi o principal fator modificável que influenciou a eficácia da remoção de dióxido de carbono de baixo fluxo sanguíneo. Conclusão O fluxo do gás de varredura é a principal variável relacionada à remoção de dióxido de carbono durante a terapia de substituição renal contínua com um alto nível de bicarbonato acoplado a um oxigenador. Outras variáveis moduladoras da transferência de dióxido de carbono incluíram o nível de hemoglobina, a saturação de oxigênio, a pressão parcial de dióxido de carbono e a temperatura central. Esses resultados devem ser interpretados como exploratórios para informar outros estudos experimentais ou clínicos bem planejados.

Intensivist-led ultrasound-guided percutaneous tracheostomy: a phase IV cohort study / Traqueostomia percutânea guiada por ultrassom conduzida por intensivistas: um estudo de coorte de fase IV

ABSTRACT Objective: To describe, with a larger number of patients in a real-world scenario following routine implementation, intensivist-led ultrasound-guided percutaneous dilational tracheostomy and the possible risks and complications of the procedure not identified in clinical trials. Methods: This was a phase IV cohort study of patients admitted to three intensive care units of a quaternary academic hospital who underwent intensivist-led ultrasound-guided percutaneous tracheostomy in Brazil from September 2017 to December 2021. Results: There were 4,810 intensive care unit admissions during the study period; 2,084 patients received mechanical ventilation, and 287 underwent tracheostomy, 227 of which were performed at bedside by the intensive care team. The main reason for intensive care unit admission was trauma, and for perform a tracheostomy it was a neurological impairment or an inability to protect the airways. The median time from intubation to tracheostomy was 14 days. Intensive care residents performed 76% of the procedures. At least one complication occurred in 29.5% of the procedures, the most common being hemodynamic instability and extubation during the procedure, with only 3 serious complications. The intensive care unit mortality was 29.1%, and the hospital mortality was 43.6%. Conclusion: Intensivist-led ultrasound-guided percutaneous tracheostomy is feasible out of a clinical trial context with outcomes and complications comparable to those in the literature. Intensivists can acquire this competence during their training but should be aware of potential complications to enhance procedural safety.

RESUMO Objetivo: Descrever, com um número maior de pacientes em um cenário do mundo real após a implementação rotineira, a traqueostomia percutânea guiada por ultrassom conduzida por intensivistas e os possíveis riscos e complicações do procedimento não identificados em estudos clínicos. Métodos: Trata-se de estudo de coorte de fase IV de pacientes internados em três unidades de terapia intensiva de um hospital acadêmico quaternário que foram submetidos a traqueostomia percutânea guiada por ultrassom conduzida por intensivistas no Brasil de setembro de 2017 a dezembro de 2021. Resultados: Entre as 4.810 admissões na unidade de terapia intensiva durante o período do estudo, 2.084 pacientes receberam ventilação mecânica, e 287 foram submetidos a traqueostomia, 227 das quais foram realizadas à beira do leito pela equipe de terapia intensiva. O principal motivo para a admissão na unidade de terapia intensiva foi trauma, e para a realização de uma traqueostomia foi comprometimento neurológico ou incapacidade de proteger as vias aéreas. O tempo médio entre a intubação e a traqueostomia foi de 14 dias. Residentes de terapia intensiva realizaram 76% dos procedimentos. Ao menos uma complicação ocorreu em 29,5% dos procedimentos, sendo instabilidade hemodinâmica e extubação durante o procedimento as complicações mais comuns, com apenas três complicações graves. A mortalidade na unidade de terapia intensiva foi de 29,1%, e a mortalidade hospitalar foi de 43,6%. Conclusão: A traqueostomia percutânea guiada por ultrassom conduzida por intensivistas é viável fora do contexto de um estudo clínico com resultados e complicações comparáveis aos da literatura. Os intensivistas podem adquirir essa competência durante seu treinamento, mas devem estar cientes das possíveis complicações para aumentar a segurança do procedimento.

Immunothrombosis and COVID-19 ‒ a nested post-hoc analysis from a 3186 patient cohort in a Latin American public reference hospital.

OBJECTIVE: COVID-19 is associated with an elevated risk of thromboembolism and excess mortality. Difficulties with best anticoagulation practices and their implementation motivated the current analysis of COVID-19 patients who developed Venous Thromboembolism (VTE). METHOD: This is a post-hoc analysis of a COVID-19 cohort, described in an economic study already published. The authors analyzed a subset of patients with confirmed VTE. We described the characteristics of the cohort, such as demographics, clinical status, and laboratory results. We tested differences amid two subgroups of patients, those with VTE or not, with the competitive risk Fine and Gray model. RESULTS: Out of 3186 adult patients with COVID-19, 245 (7.7%) were diagnosed with VTE, 174 (5.4%) of them during admission to the hospital. Four (2.3% of these 174) did not receive prophylactic anticoagulation and 19 (11%) discontinued anticoagulation for at least 3 days, resulting in 170 analyzed. During the first week of hospitalization, the laboratory most altered results were C-reactive protein and D-dimer. Patients with VTE were more critical, had a higher mortality rate, worse SOFA score, and, on average, 50% longer hospital stay. CONCLUSION: Proven VTE incidence in this severe COVID-19 cohort was 7.7%, despite 87% of them complying completely with VTE prophylaxis. The clinician must be aware of the diagnosis of VTE in COVID-19, even in patients receiving proper prophylaxis.

Association of fasting in the first 72 h of intensive care unit stay with outcomes of critically ill patients.

BACKGROUND: Whether fasting early in critical illness course is acceptable is not clear and high-quality data on this topic are lacking. To generate equipoise for future clinical trials and bring additional data to current literature, we compared outcomes of patients fasted during the first 72 h of intensive care unit (ICU) stay to patients receiving any nutrition support during this period. METHODS: Retrospective cohort study of a medical ICU from a tertiary academic center in Brazil. Adult patients treated between November 2017 and February 2022 with an ICU length of stay of ≥5 days were included. Baseline and daily data were retrieved from the prospectively collected administrative database. We did 1:1 propensity score matching to compare patients fasting for at least 72 h with controls. Primary outcome was hospital mortality and secondary outcomes were other resources' use. RESULTS: During the study period, 1591 patients were cared for in this ICU, of which 998 stayed ≥5 days. After excluding readmissions and propensity score matching, 93 patients in the fasting group were matched to 93 controls. Hospital mortality was similar between fasting and matched control groups (odds ratio = 1.04; 95% CI = 0.56-1.94; P > 0.99). Secondary outcomes were not different between groups, including length of stay, days on mechanical ventilation, and incidence of new infections. CONCLUSION: Withholding nutrition support in the first 72 h of ICU stay was not associated with worse outcomes in this cohort of severe critically ill patients.

Intensivist-led ultrasound-guided percutaneous tracheostomy: a phase IV cohort study.

OBJECTIVE: To describe, with a larger number of patients in a real-world scenario following routine implementation, intensivist-led ultrasound-guided percutaneous dilational tracheostomy and the possible risks and complications of the procedure not identified in clinical trials. METHODS: This was a phase IV cohort study of patients admitted to three intensive care units of a quaternary academic hospital who underwent intensivist-led ultrasound-guided percutaneous tracheostomy in Brazil from September 2017 to December 2021. RESULTS: There were 4,810 intensive care unit admissions during the study period; 2,084 patients received mechanical ventilation, and 287 underwent tracheostomy, 227 of which were performed at bedside by the intensive care team. The main reason for intensive care unit admission was trauma, and for perform a tracheostomy it was a neurological impairment or an inability to protect the airways. The median time from intubation to tracheostomy was 14 days. Intensive care residents performed 76% of the procedures. At least one complication occurred in 29.5% of the procedures, the most common being hemodynamic instability and extubation during the procedure, with only 3 serious complications. The intensive care unit mortality was 29.1%, and the hospital mortality was 43.6%. CONCLUSION: Intensivist-led ultrasound-guided percutaneous tracheostomy is feasible out of a clinical trial context with outcomes and complications comparable to those in the literature. Intensivists can acquire this competence during their training but should be aware of potential complications to enhance procedural safety.

Immunothrombosis and COVID-19 ‒ a nested post-hoc analysis from a 3186 patient cohort in a Latin American public reference hospital

Abstract Objective COVID-19 is associated with an elevated risk of thromboembolism and excess mortality. Difficulties with best anticoagulation practices and their implementation motivated the current analysis of COVID-19 patients who developed Venous Thromboembolism (VTE). Method This is a post-hoc analysis of a COVID-19 cohort, described in an economic study already published. The authors analyzed a subset of patients with confirmed VTE. We described the characteristics of the cohort, such as demographics, clinical status, and laboratory results. We tested differences amid two subgroups of patients, those with VTE or not, with the competitive risk Fine and Gray model. Results Out of 3186 adult patients with COVID-19, 245 (7.7%) were diagnosed with VTE, 174 (5.4%) of them during admission to the hospital. Four (2.3% of these 174) did not receive prophylactic anticoagulation and 19 (11%) discontinued anticoagulation for at least 3 days, resulting in 170 analyzed. During the first week of hospitalization, the laboratory most altered results were C-reactive protein and D-dimer. Patients with VTE were more critical, had a higher mortality rate, worse SOFA score, and, on average, 50% longer hospital stay. Conclusion Proven VTE incidence in this severe COVID-19 cohort was 7.7%, despite 87% of them complying completely with VTE prophylaxis. The clinician must be aware of the diagnosis of VTE in COVID-19, even in patients receiving proper prophylaxis.