Early Versus Late Initiation of Renal Replacement Therapy in Critically Ill Patients: Systematic Review and Meta-Analysis.

OBJECTIVE: Early initiation of renal replacement therapy (RRT) effect on survival and renal recovery of critically ill patients is still uncertain. We aimed to systematically review current evidence comparing outcomes of early versus late initiation of RRT in critically ill patients. METHODS: We searched the Medline (via Pubmed), LILACS, Science Direct, and CENTRAL databases from inception until November 2016 for randomized clinical trials (RCTs) or observational studies comparing early versus late initiation of RRT in critically ill patients. The primary outcome was mortality. Duration of mechanical ventilation, intensive care unit (ICU) length of stay (LOS), hospital LOS, and renal function recovery were secondary outcomes. Meta-analysis and trial sequential analysis (TSA) were used for the primary outcome. RESULTS: Sixty-two studies were retrieved and analyzed, including 11 RCTs. There was no difference in mortality between early and late initiation of RRT among RCTs (odds ratio [OR] = 0.78; 95% confidence interval [CI]: 0.52-1.19; I2 = 63.1%). Trial sequential analysis of mortality across all RCTs achieved futility boundaries at both 1% and 5% type I error rates, although a subgroup analysis of studies including only acute kidney injury patients was not conclusive. There was also no difference in time on mechanical ventilation, ICU and hospital LOS, or renal recovery among studies. Early initiation of RRT was associated with reduced mortality among prospective (OR = 0.69; 95% CI: 0.49-0.96; I2 = 85.9%) and retrospective (OR = 0.61; 95% CI: 0.41-0.92; I2 = 90.9%) observational studies, both with substantial heterogeneity. However, subgroup analysis excluding low-quality observational studies did not achieve statistical significance. CONCLUSION: Pooled analysis of randomized trials indicates early initiation of RRT is not associated with lower mortality rates. The potential benefit of reduced mortality associated with early initiation of RRT was limited to low-quality observational studies.

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.

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.

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.

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.

Updates on aneurysmal subarachnoid hemorrhage: is there anything really new?

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a severe disease, with systemic involvement and complex diagnosis and treatment. Since the current guidelines were published by the AHA/ASA, Neurocritical Care Society and the European Stroke Organization in 2012-2013,there has been an evolution in the comprehension of SAH-associated brain injury and its multiple underlying mechanisms. As a result, several clinical and translational trials were developed or are underway. Objective: The aim of this article is to review some updates in the diagnosis and treatment of neurological complications of SAH. Methods: A review of PubMed (May, 2010 to February, 2022) was performed. Data was summarized. Results: Content of five meta-analyses, nine review articles and 23 new clinical trials, including pilots, were summarized. Conclusions:Advances in the comprehension of pathophysiology and improvements in critical care have been reflected in the reduction of mortality in SAH. However, despite the number of publications, the only treatments shown to be effective in adequate, well-controlled clinical trials are nimodipine and repair of the ruptured aneurysm. Thus, doubts about the optimal management of SAH still persist.

Comparison of the accuracy of residents, senior physicians and surrogate decision-makers for predicting hospital mortality of critically ill patients. / Comparação da acurácia de residentes, médicos seniores e decisores substitutos na previsão da mortalidade hospitalar de pacientes críticos.

OBJECTIVE: To compare the predictive performance of residents, senior intensive care unit physicians and surrogates early during intensive care unit stays and to evaluate whether different presentations of prognostic data (probability of survival versus probability of death) influenced their performance. METHODS: We questioned surrogates and physicians in charge of critically ill patients during the first 48 hours of intensive care unit admission on the patient's probability of hospital outcome. The question framing (i.e., probability of survival versus probability of death during hospitalization) was randomized. To evaluate the predictive performance, we compared the areas under the ROC curves (AUCs) for hospital outcome between surrogates and physicians' categories. We also stratified the results according to randomized question framing. RESULTS: We interviewed surrogates and physicians on the hospital outcomes of 118 patients. The predictive performance of surrogate decisionmakers was significantly lower than that of physicians (AUC of 0.63 for surrogates, 0.82 for residents, 0.80 for intensive care unit fellows and 0.81 for intensive care unit senior physicians). There was no increase in predictive performance related to physicians' experience (i.e., senior physicians did not predict outcomes better than junior physicians). Surrogate decisionmakers worsened their prediction performance when they were asked about probability of death instead of probability of survival, but there was no difference for physicians. CONCLUSION: Different predictive performance was observed when comparing surrogate decision-makers and physicians, with no effect of experience on health care professionals' prediction. Question framing affected the predictive performance of surrogates but not of physicians.

OBJETIVO: Comparar o desempenho preditivo de residentes, médicos seniores de unidades de terapia intensiva e decisores substitutos dos pacientes logo no início da internação na unidade de terapia intensiva e avaliar se diferentes apresentações de prognóstico (probabilidade de sobrevida versus probabilidade de óbito) influenciaram seus desempenhos. MÉTODOS: Os decisores substitutos e os médicos responsáveis pelos pacientes críticos foram questionados durante as primeiras 48 horas de internação na unidade de terapia intensiva sobre a probabilidade do desfecho hospitalar do paciente. O enquadramento da pergunta (isto é, a probabilidade de sobrevida versus a probabilidade de óbito durante a internação) foi randomizado. Para avaliar o desempenho preditivo, comparou-se a área sob a curva ROC para desfecho hospitalar entre as categorias decisores substitutos e médicos. Também estratificaram-se os resultados de acordo com o enquadramento da pergunta randomizado. RESULTADOS: Entrevistaram-se decisores substitutos e médicos sobre os desfechos hospitalares de 118 pacientes. O desempenho preditivo dos decisores substitutos foi significativamente inferior ao dos médicos (área sob a curva de 0,63 para decisores substitutos, 0,82 para residentes, 0,80 para residentes de medicina intensiva e 0,81 para médicos seniores de unidade de terapia intensiva). Não houve aumento no desempenho preditivo quanto à experiência dos médicos (ou seja, médicos seniores não previram desfechos melhor que médicos juniores). Os decisores substitutos pioraram seu desempenho de previsão quando perguntados sobre a probabilidade de óbito ao invés da probabilidade de sobrevida, mas não houve diferença entre os médicos. CONCLUSÃO: Observou-se desempenho preditivo diferente ao comparar decisores substitutos e médicos, sem qualquer efeito da experiência no prognóstico dos profissionais de saúde. O enquadramento da pergunta afetou o desempenho preditivo dos substitutos, mas não o dos médicos.

Lung perfusion during veno-venous extracorporeal membrane oxygenation in a model of hypoxemic respiratory failure.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (ECMO) provides blood oxygenation and carbon dioxide removal in acute respiratory distress syndrome. However, during ECMO support, the native lungs still play an important role in gas exchange, functioning as a second oxygenator in series with ECMO. The hypoxic vasoconstriction mechanism diverts regional blood flow within the lungs away from regions with low oxygen levels, optimizing ventilation/perfusion matching. ECMO support has the potential to reduce this adaptive pulmonary response and worsen the ventilation/perfusion mismatch by raising venous oxygen partial pressure. Thus, the objective of this study was to evaluate the effect of ECMO on regional pulmonary perfusion and pulmonary hemodynamics during unilateral ventilation and posterior lung collapse. METHODS: Five Agroceres pigs were instrumented, monitored and submitted to ECMO. We used the Electrical Impedance Tomography (EIT) to evaluate lung ventilation and perfusion in all protocol steps. Effects of ECMO support on pulmonary hemodynamics and perfusion involving two different scenarios of ventilation/perfusion mismatch: (1) right-lung selective intubation inducing collapse of the normal left lung and (2) dorsal lung collapse after repeated lung lavage. Data including hemodynamics, respiratory, lung perfusion/ventilation, and laboratory data over time were analyzed with a mixed generalized model using the subjects as a random factor. RESULTS: The initiation of ECMO support provided a significant reduction in Mean Pulmonary Artery Pressure (PAPm) in both situations of ventilation/perfusion mismatch. However, distribution of lung perfusion did not change with the use of ECMO support. CONCLUSIONS: We found that the use of ECMO support with consequent increase in venous oxygen pressure induced a significant drop in PAPm with no detectable effect on regional lung perfusion in different scenarios of ventilation/perfusion mismatch.

Exploring the association of two oxygenators in parallel or in series during respiratory support using extracorporeal membrane oxygenation. / Investigação da associação de dois oxigenadores em paralelo ou em série durante o suporte respiratório com oxigenação por membrana extracorpórea.

OBJECTIVE: To characterize the pressures, resistances, oxygenation, and decarboxylation efficacy of two oxygenators associated in series or in parallel during venous-venous extracorporeal membrane oxygenation support. METHODS: Using the results of a swine severe respiratory failure associated with multiple organ dysfunction venous-venous extracorporeal membrane oxygenation support model and mathematical modeling, we explored the effects on oxygenation, decarboxylation and circuit pressures of in-parallel and in-series associations of oxygenators. RESULTS: Five animals with a median weight of 80kg were tested. Both configurations increased the oxygen partial pressure after the oxygenators. The return cannula oxygen content was also slightly higher, but the impact on systemic oxygenation was minimal using oxygenators with a high rated flow (~ 7L/minute). Both configurations significantly reduced the systemic carbon dioxide partial pressure. As the extracorporeal membrane oxygenation blood flow increased, the oxygenator resistance decreased initially with a further increase with higher blood flows but with a small clinical impact. CONCLUSION: Association of oxygenators in parallel or in series during venous-venous extracorporeal membrane oxygenation support provides a modest increase in carbon dioxide partial pressure removal with a slight improvement in oxygenation. The effect of oxygenator associations on extracorporeal circuit pressures is minimal.

OBJETIVO: Caracterizar as pressões, as resistências, a oxigenação e a eficácia da descarboxilação de dois oxigenadores associados em série ou em paralelo durante o suporte com oxigenação veno-venosa por membrana extracorpórea. MÉTODOS: Usando os resultados de insuficiência respiratória grave em suínos associada à disfunção de múltiplos órgãos, ao modelo de suporte com oxigenação por membrana extracorpórea veno-venosa e à modelagem matemática, exploramos os efeitos na oxigenação, descarboxilação e pressões do circuito de associações de oxigenadores em paralelo e em série. RESULTADOS: Testaram-se cinco animais com peso mediano de 80kg. Ambas as configurações aumentaram a pressão parcial de oxigênio após os oxigenadores. O teor de oxigênio da cânula de retorno também foi ligeiramente maior, mas o efeito na oxigenação sistêmica foi mínimo, usando oxigenadores com alto fluxo nominal (~ 7L/minuto). Ambas as configurações reduziram significativamente a pressão parcial de dióxido de carbono sistêmico. Como o fluxo sanguíneo na oxigenação por membrana extracorpórea aumentou, a resistência do oxigenador diminuiu inicialmente, com aumento posterior, com fluxos sanguíneos mais altos, mas pouco efeito clínico. CONCLUSÃO: A associação de oxigenadores em paralelo ou em série durante o suporte com oxigenação veno-venosa por membrana extracorpórea proporciona um modesto aumento na depuração da pressão parcial de dióxido de carbono, com leve melhora na oxigenação. O efeito das associações de oxigenadores nas pressões de circuitos extracorpóreos é mínimo.

Evaluation of eleven immunochromatographic assays for SARS-CoV-2 detection: investigating the dengue cross-reaction.

COVID-19 disease is spread worldwide and diagnostic techniques have been studied in order to contain the pandemic. Immunochromatographic (IC) assays are feasible and a low-cost alternative especially in low and middle-income countries, which lack structure to perform certain diagnostic techniques. Here we evaluate the sensitivity and specificity of eleven different IC tests in 145 serum samples from confirmed cases of COVID-19 using RT-PCR and 100 negative serum samples from blood donors collected in February 2019. We also evaluated the cross-reactivity with dengue using 20 serum samples from patients with confirmed diagnosis for dengue collected in early 2019 through four different tests. We found high sensitivity (92%), specificity (100%) and an almost perfect agreement (Kappa 0.92) of IC assay, especially when we evaluated IgG and IgM combined after 10 days from the onset of symptoms with RT-PCR. However, we detected cross-reactivity between dengue and COVID-19 mainly with IgM antibodies (5 to 20% of cross-reaction) and demonstrated the need for better studies about diagnostic techniques for these diseases.

Bedside clinical data subphenotypes of critically ill COVID-19 patients: a cohort study. / Subfenótipos baseados em dados clínicos de beira-leito de pacientes críticos com COVID-19: um estudo de coorte.

OBJECTIVE: To identify more severe COVID-19 presentations. METHODS: Consecutive intensive care unit-admitted patients were subjected to a stepwise clustering method. RESULTS: Data from 147 patients who were on average 56 ± 16 years old with a Simplified Acute Physiological Score 3 of 72 ± 18, of which 103 (70%) needed mechanical ventilation and 46 (31%) died in the intensive care unit, were analyzed. From the clustering algorithm, two well-defined groups were found based on maximal heart rate [Cluster A: 104 (95%CI 99 - 109) beats per minute versus Cluster B: 159 (95%CI 155 - 163) beats per minute], maximal respiratory rate [Cluster A: 33 (95%CI 31 - 35) breaths per minute versus Cluster B: 50 (95%CI 47 - 53) breaths per minute], and maximal body temperature [Cluster A: 37.4 (95%CI 37.1 - 37.7)°C versus Cluster B: 39.3 (95%CI 39.1 - 39.5)°C] during the intensive care unit stay, as well as the oxygen partial pressure in the blood over the oxygen inspiratory fraction at intensive care unit admission [Cluster A: 116 (95%CI 99 - 133) mmHg versus Cluster B: 78 (95%CI 63 - 93) mmHg]. Subphenotypes were distinct in inflammation profiles, organ dysfunction, organ support, intensive care unit length of stay, and intensive care unit mortality (with a ratio of 4.2 between the groups). CONCLUSION: Our findings, based on common clinical data, revealed two distinct subphenotypes with different disease courses. These results could help health professionals allocate resources and select patients for testing novel therapies.

OBJETIVO: Identificar apresentações mais graves de COVID-19. MÉTODOS: Pacientes consecutivamente admitidos à unidade de terapia intensiva foram submetidos à análise de clusters por meio de método de explorações sequenciais. RESULTADOS: Analisamos os dados de 147 pacientes, com média de idade de 56 ± 16 anos e Simplified Acute Physiological Score 3 de 72 ± 18, dos quais 103 (70%) demandaram ventilação mecânica e 46 (31%) morreram na unidade de terapia intensiva. A partir do algoritmo de análise de clusters, identificaram-se dois grupos bem definidos, com base na frequência cardíaca máxima [Grupo A: 104 (IC95% 99 - 109) batimentos por minuto versus Grupo B: 159 (IC95% 155 - 163) batimentos por minuto], frequência respiratória máxima [Grupo A: 33 (IC95% 31 - 35) respirações por minuto versus Grupo B: 50 (IC95% 47 - 53) respirações por minuto] e na temperatura corpórea máxima [Grupo A: 37,4 (IC95% 37,1 - 37,7)ºC versus Grupo B: 39,3 (IC95% 39,1 - 39,5)ºC] durante o tempo de permanência na unidade de terapia intensiva, assim como a proporção entre a pressão parcial de oxigênio no sangue e a fração inspirada de oxigênio quando da admissão à unidade de terapia intensiva [Grupo A: 116 (IC95% 99 - 133) mmHg versus Grupo B: 78 (IC95% 63 - 93) mmHg]. Os subfenótipos foram distintos em termos de perfis inflamatórios, disfunções orgânicas, terapias de suporte, tempo de permanência na unidade de terapia intensiva e mortalidade na unidade de terapia intensiva (com proporção de 4,2 entre os grupos). CONCLUSÃO: Nossos achados, baseados em dados clínicos universalmente disponíveis, revelaram dois subfenótipos distintos, com diferentes evoluções de doença. Estes resultados podem ajudar os profissionais de saúde na alocação de recursos e seleção de pacientes para teste de novas terapias.

Protective ventilation and outcomes of critically ill patients with COVID-19: a cohort study.

BACKGROUND: Approximately 5% of COVID-19 patients develop respiratory failure and need ventilatory support, yet little is known about the impact of mechanical ventilation strategy in COVID-19. Our objective was to describe baseline characteristics, ventilatory parameters, and outcomes of critically ill patients in the largest referral center for COVID-19 in Sao Paulo, Brazil, during the first surge of the pandemic. METHODS: This cohort included COVID-19 patients admitted to the intensive care units (ICUs) of an academic hospital with 94 ICU beds, a number expanded to 300 during the pandemic as part of a state preparedness plan. Data included demographics, advanced life support therapies, and ventilator parameters. The main outcome was 28-day survival. We used a multivariate Cox model to test the association between protective ventilation and survival, adjusting for PF ratio, pH, compliance, and PEEP. RESULTS: We included 1503 patients from March 30 to June 30, 2020. The mean age was 60 ± 15 years, and 59% were male. During 28-day follow-up, 1180 (79%) patients needed invasive ventilation and 666 (44%) died. For the 984 patients who were receiving mechanical ventilation in the first 24 h of ICU stay, mean tidal volume was 6.5 ± 1.3 mL/kg of ideal body weight, plateau pressure was 24 ± 5 cmH2O, respiratory system compliance was 31.9 (24.4-40.9) mL/cmH2O, and 82% of patients were ventilated with protective ventilation. Noninvasive ventilation was used in 21% of patients, and prone, in 36%. Compliance was associated with survival and did not show a bimodal pattern that would support the presence of two phenotypes. In the multivariable model, protective ventilation (aHR 0.73 [95%CI 0.57-0.94]), adjusted for PF ratio, compliance, PEEP, and arterial pH, was independently associated with survival. CONCLUSIONS: During the peak of the epidemic in Sao Paulo, critically ill patients with COVID-19 often required mechanical ventilation and mortality was high. Our findings revealed an association between mechanical ventilation strategy and mortality, highlighting the importance of protective ventilation for patients with COVID-19.

Neuromuscular blockade and airway management during endotracheal intubation in Brazilian intensive care units: a national survey. / Bloqueio neuromuscular e manuseio das vias aéreas na intubação endotraqueal em unidades de terapia intensiva brasileiras: um levantamento nacional.

OBJECTIVE: To describe the use of neuromuscular blockade as well as other practices among Brazilian physicians in adult intensive care units. METHODS: An online national survey was designed and administered to Brazilian intensivists. Questions were selected using the Delphi method and assessed physicians' demographic data, intensive care unit characteristics, practices regarding airway management, use of neuromuscular blockade and sedation during endotracheal intubation in the intensive care unit. As a secondary outcome, we applied a multivariate analysis to evaluate factors associated with the use of neuromuscular blockade. RESULTS: Five hundred sixty-five intensivists from all Brazilian regions responded to the questionnaire. The majority of respondents were male (65%), with a mean age of 38 ( 8.4 years, and 58.5% had a board certification in critical care. Only 40.7% of the intensivists reported the use of neuromuscular blockade during all or in more than 75% of endotracheal intubations. In the multivariate analysis, the number of intubations performed monthly and physician specialization in anesthesiology were directly associated with frequent use of neuromuscular blockade. Etomidate and ketamine were more commonly used in the clinical situation of hypotension and shock, while propofol and midazolam were more commonly prescribed in the situation of clinical stability. CONCLUSION: The reported use of neuromuscular blockade was low among intensivists, and sedative drugs were chosen in accordance with patient hemodynamic stability. These results may help the design of future studies regarding airway management in Brazil.

OBJETIVO: Descrever o uso do bloqueio neuromuscular e de outras práticas entre os médicos brasileiros atuantes em unidades de terapia intensiva para pacientes adultos. MÉTODOS: Um levantamento nacional on-line foi aplicado a intensivistas brasileiros. As questões foram selecionadas utilizando o método Delphi e avaliavam os dados demográficos dos médicos, as características da unidade de terapia intensiva, as práticas relativas ao manuseio das vias aéreas e o uso de bloqueio neuromuscular e sedação durante a intubação endotraqueal na unidade de terapia intensiva. Como desfecho secundário, aplicamos uma análise multivariada para avaliar fatores associados com o uso do bloqueio neuromuscular. RESULTADOS: Responderam ao questionário 565 intensivistas de todas as regiões do país. A maioria dos que responderam era homens (65%), com média de idade de 38 ± 8,4 anos, e 58,5% dos participantes tinham título de especialista em terapia intensiva. Apenas 40,7% dos intensivistas relataram o uso de bloqueio neuromuscular durante todas ou em mais de 75% das intubações endotraqueais. Na análise multivariada, o número de intubações realizadas por mês e a especialização do médico em anestesiologia se associaram diretamente com o uso frequente de bloqueio neuromuscular. Etomidato e cetamina foram utilizados mais comumente na situação clínica de hipotensão e choque, enquanto propofol e midazolam foram mais comumente prescritos em situações de estabilidade hemodinâmica. CONCLUSÃO: O relato de uso de bloqueio neuromuscular foi baixo entre intensivistas, e os fármacos sedativos foram escolhidos segundo a estabilidade hemodinâmica do paciente. Estes resultados podem ajudar no delineamento de futuros estudos relativos ao manuseio das vias aéreas no Brasil.

Adherence to a stress ulcer prophylaxis protocol by critically ill patients: a prospective cohort study. / Adesão a um protocolo de profilaxia de úlcera de estresse em pacientes críticos: estudo de coorte prospectiva.

OBJECTIVE: To evaluate adherence to the stress ulcer prophylaxis protocol in critically ill patients at a tertiary university hospital. METHODS: In this prospective cohort study, we included all adult patients admitted to the medical and surgical intensive care units of an academic tertiary hospital. Our sole exclusion criterion was upper gastrointestinal bleeding at intensive care unit admission. We collected baseline variables and stress ulcer prophylaxis indications according to the institutional protocol and use of prophylaxis. Our primary outcome was adherence to the stress ulcer prophylaxis protocol. Secondary outcomes were appropriate use of stress ulcer prophylaxis, upper gastrointestinal bleeding incidence and factors associated with appropriate use of stress ulcer prophylaxis. RESULTS: Two hundred thirty-four patients were enrolled from July 2nd through July 31st, 2018. Patients were 52 ± 20 years old, 125 (53%) were surgical patients, and the mean SAPS 3 was 52 ± 20. In the longitudinal follow-up, 1499 patient-days were studied; 1069 patient-days had stress ulcer prophylaxis indications, and 777 patient-days contained prophylaxis use (73% stress ulcer prophylaxis protocol adherence). Of the 430 patient-days without stress ulcer prophylaxis indications, 242 involved prophylaxis (56% inappropriate stress ulcer prophylaxis use). The overall appropriate use of stress ulcer prophylaxis was 64%. Factors associated with proper stress ulcer prophylaxis prescription were mechanical ventilation OR 2.13 (95%CI 1.64 - 2.75) and coagulopathy OR 2.77 (95%CI 1.66 - 4.60). The upper gastrointestinal bleeding incidence was 12.8%. CONCLUSION: Adherence to the stress ulcer prophylaxis protocol was low and inappropriate use of stress ulcer prophylaxis was frequent in this cohort of critically ill patients.

Oxygen delivery, carbon dioxide removal, energy transfer to lungs and pulmonary hypertension behavior during venous-venous extracorporeal membrane oxygenation support: a mathematical modeling approach. / Oferta de oxigênio, remoção de dióxido de carbono, transferência de energia aos pulmões e comportamento da hipertensão pulmonar durante o suporte com oxigenação por membrana extracorpórea: um modelo matemático.

OBJECTIVE: To describe (1) the energy transfer from the ventilator to the lungs, (2) the match between venous-venous extracorporeal membrane oxygenation (ECMO) oxygen transfer and patient oxygen consumption (VO2), (3) carbon dioxide removal with ECMO, and (4) the potential effect of systemic venous oxygenation on pulmonary artery pressure. METHODS: Mathematical modeling approach with hypothetical scenarios using computer simulation. RESULTS: The transition from protective ventilation to ultraprotective ventilation in a patient with severe acute respiratory distress syndrome and a static respiratory compliance of 20mL/cm H2O reduced the energy transfer from the ventilator to the lungs from 35.3 to 2.6 joules/minute. A hypothetical patient, hyperdynamic and slightly anemic with VO2 = 200mL/minute, can reach an arterial oxygen saturation of 80%, while maintaining the match between the oxygen transfer by ECMO and the VO2 of the patient. Carbon dioxide is easily removed, and normal PaCO2 is easily reached. Venous blood oxygenation through the ECMO circuit may drive the PO2 stimulus of pulmonary hypoxic vasoconstriction to normal values. CONCLUSION: Ultraprotective ventilation largely reduces the energy transfer from the ventilator to the lungs. Severe hypoxemia on venous-venous-ECMO support may occur despite the matching between the oxygen transfer by ECMO and the VO2 of the patient. The normal range of PaCO2 is easy to reach. Venous-venous-ECMO support potentially relieves hypoxic pulmonary vasoconstriction.

OBJETIVO: Descrever a transferência de energia do ventilador mecânico para os pulmões; o acoplamento entre a transferência de oxigênio por oxigenação por membrana extracorpórea venovenosa (ECMO-VV) e o consumo de oxigênio do paciente; a remoção de dióxido de carbono com ECMO; e o efeito potencial da oxigenação venosa sistêmica na pressão arterial pulmonar. MÉTODOS: Modelo matemático com cenários hipotéticos e utilização de simulações matemáticas por computador. RESULTADOS: A transição de ventilação protetora para ventilação ultraprotetora em um paciente com síndrome da angústia respiratória aguda grave e complacência respiratória estática de 20mL/cmH2O reduziu a transferência de energia do ventilador para os pulmões de 35,3 para 2,6 joules por minuto. Em um paciente hipotético, hiperdinâmico e ligeiramente anêmico com consumo de oxigênio de 200mL/minuto, é possível atingir saturação arterial de oxigênio de 80%, ao mesmo tempo em que se mantém o equilíbrio entre a transferência de oxigênio pela ECMO e o consumo de oxigênio do paciente. O dióxido de carbono é facilmente removido e a pressão parcial de dióxido de carbono normal é facilmente obtida. A oxigenação do sangue venoso, por meio do circuito da ECMO, pode direcionar o estímulo da pressão parcial de oxigênio na vasoconstrição pulmonar por hipóxia para valores normais. CONCLUSÃO: A ventilação ultraprotetora reduz amplamente a transferência de energia do ventilador para os pulmões. A hipoxemia grave no suporte com ECMO-VV pode ocorrer, a despeito do acoplamento entre a transferência de oxigênio, por meio da ECMO, e o consumo de oxigênio do paciente. A faixa normal de pressão parcial de dióxido de carbono é fácil de atingir. O suporte com ECMO-VV potencialmente alivia a vasoconstrição pulmonar hipóxica.

Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in adult patients: a systematic review and meta-analysis. / Oxigenação por membrana extracorpórea para síndrome do desconforto respiratório agudo grave em pacientes adultos: revisão sistemática e metanálise.

OBJECTIVE: The evidence of improved survival with the use of extracorporeal membrane oxygenation (ECMO) in acute respiratory distress syndrome is still uncertain. METHODS: This systematic review and meta-analysis was registered in the PROSPERO database with the number CRD-42018098618. We performed a structured search of Medline, Lilacs, and ScienceDirect for randomized controlled trials evaluating the use of ECMO associated with (ultra)protective mechanical ventilation for severe acute respiratory failure in adult patients. We used the Cochrane risk of bias tool to evaluate the quality of the evidence. Our primary objective was to evaluate the effect of ECMO on the last reported mortality. Secondary outcomes were treatment failure, hospital length of stay and the need for renal replacement therapy in both groups. RESULTS: Two randomized controlled studies were included in the meta-analysis, comprising 429 patients, of whom 214 were supported with ECMO. The most common reason for acute respiratory failure was pneumonia (60% - 65%). Respiratory ECMO support was associated with a reduction in last reported mortality and treatment failure with risk ratios (RR: 0.76; 95%CI 0.61 - 0.95 and RR: 0.68; 95%CI 0.55 - 0.85, respectively). Extracorporeal membrane oxygenation reduced the need for renal replacement therapy, with a RR of 0.88 (95%CI 0.77 - 0.99). Intensive care unit and hospital lengths of stay were longer in ECMO-supported patients, with an additional P50th 14.84 (P25th - P75th: 12.49 - 17.18) and P50th 29.80 (P25th - P75th: 26.04 - 33.56] days, respectively. CONCLUSION: Respiratory ECMO support in severe acute respiratory distress syndrome patients is associated with a reduced mortality rate and a reduced need for renal replacement therapy but a substantial increase in the lengths of stay in the intensive care unit and hospital. Our results may help bedside decision-making regarding ECMO initiation in patients with severe respiratory distress syndrome.

OBJETIVO: A evidência de melhora da sobrevivência com uso de oxigenação por membrana extracorpórea na síndrome do desconforto respiratório agudo ainda permanece incerta. MÉTODOS: Esta revisão sistemática e metanálise foi registrada na base de dados PROSPERO com o número CRD-42018098618. Conduzimos uma busca estruturada nas bases Medline, LILACS e ScienceDirect visando a ensaios randomizados e controlados que tivessem avaliado o uso de oxigenação por membrana extracorpórea associada com ventilação mecânica (ultra)protetora em pacientes adultos com síndrome do desconforto respiratório agudo grave. Utilizamos a ferramenta de riscos de viés da Cochrane para avaliar a qualidade da evidência. O desfecho primário consistiu em avaliar o efeito do uso oxigenação por membrana extracorpórea no último relato de mortalidade. Os desfechos secundários foram: falha terapêutica, tempo de permanência no hospital e necessidade de terapia de substituição renal em ambos os grupos. RESULTADOS: Incluíram-se na metanálise dois ensaios randomizados e controlados, compreendendo 429 pacientes, dos quais 214 receberam suporte respiratório extracorpóreo. A razão mais comum para a insuficiência respiratória foi pneumonia (60% - 65%). O suporte respiratório com oxigenação por membrana extracorpórea foi associado a uma redução na mortalidade e redução em falha terapêutica com taxas de risco (RR: 0,76; IC95% 0,61 - 0,95; RR: 0,68; IC95% 0,55 - 0,85, respectivamente). O uso de oxigenação por membrana extracorpórea reduziu a necessidade de terapia de substituição renal com uma RR de 0,88 (IC95% 0,77 - 0,99). O tempo de permanência na unidade de terapia intensiva e no hospital foram maiores no grupo de pacientes que recebeu suporte com oxigenação por membrana extracorpórea, com acréscimo de 14,84 (P25°-P75°: 12,49 - 17,18) e 29,80 (P25°- P75°: 26,04 - 33,56) dias, respectivamente. CONCLUSÃO: O suporte com oxigenação por membrana extracorpórea na síndrome do desconforto respiratório agudo grave está associado a uma redução da taxa de mortalidade e da necessidade de terapia de substituição renal, porém apresenta aumento substancial no tempo de permanência na unidade de terapia intensiva e no hospital. Nossos resultados podem ajudar no processo decisório junto ao leito quanto ao início do suporte com oxigenação por membrana extracorpórea na síndrome do desconforto respiratório agudo grave.

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.