Association between Type of Fluid Received Prior to Enrollment, Type of Admission, and Effect of Balanced Crystalloid in Critically Ill Adults: A Secondary Exploratory Analysis of the BaSICS Clinical Trial.

Rationale: The effects of balanced crystalloid versus saline on clinical outcomes for ICU patients may be modified by the type of fluid that patients received for initial resuscitation and by the type of admission. Objectives: To assess whether the results of a randomized controlled trial could be affected by fluid use before enrollment and admission type. Methods: Secondary post hoc analysis of the BaSICS (Balanced Solution in Intensive Care Study) trial, which compared a balanced solution (Plasma-Lyte 148) with 0.9% saline in the ICU. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups (balanced solutions only, 0.9% saline only, a mix of both, and no fluid before enrollment) and according to admission type (planned, unplanned with sepsis, and unplanned without sepsis). The association between 90-day mortality and the randomization group was assessed using a hierarchical logistic Bayesian model. Measurements and Main Results: A total of 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio [OR], 0.95; 89% credible interval [CrI], 0.66-10.51; probability of benefit, 0.58); however, probability of benefit was high for patients who received only balanced solutions before enrollment (regardless of admission type, OR, 0.78; 89% CrI, 0.56-1.03; probability of benefit, 0.92), mostly because of a benefit in unplanned admissions due to sepsis (OR, 0.70; 89% CrI, 0.50-0.97; probability of benefit, 0.96) and planned admissions (OR, 0.79; 89% CrI, 0.65-0.97; probability of benefit, 0.97). Conclusions: There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients who exclusively received balanced fluids before trial enrollment. Clinical trial registered with www.clinicaltrials.gov (NCT02875873).

Effect of Slower vs Faster Intravenous Fluid Bolus Rates on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial.

Importance: Slower intravenous fluid infusion rates could reduce the formation of tissue edema and organ dysfunction in critically ill patients; however, there are no data to support different infusion rates during fluid challenges for important outcomes such as mortality. Objective: To determine the effect of a slower infusion rate vs control infusion rate on 90-day survival in patients in the intensive care unit (ICU). Design, Setting, and Participants: Unblinded randomized factorial clinical trial in 75 ICUs in Brazil, involving 11 052 patients requiring at least 1 fluid challenge and with 1 risk factor for worse outcomes were randomized from May 29, 2017, to March 2, 2020. Follow-up was concluded on October 29, 2020. Patients were randomized to 2 different infusion rates (reported in this article) and 2 different fluid types (balanced fluids or saline, reported separately). Interventions: Patients were randomized to receive fluid challenges at 2 different infusion rates; 5538 to the slower rate (333 mL/h) and 5514 to the control group (999 mL/h). Patients were also randomized to receive balanced solution or 0.9% saline using a factorial design. Main Outcomes and Measures: The primary end point was 90-day survival. Results: Of all randomized patients, 10 520 (95.2%) were analyzed (mean age, 61.1 years [SD, 17.0 years]; 44.2% were women) after excluding duplicates and consent withdrawals. Patients assigned to the slower rate received a mean of 1162 mL on the first day vs 1252 mL for the control group. By day 90, 1406 of 5276 patients (26.6%) in the slower rate group had died vs 1414 of 5244 (27.0%) in the control group (adjusted hazard ratio, 1.03; 95% CI, 0.96-1.11; P = .46). There was no significant interaction between fluid type and infusion rate (P = .98). Conclusions and Relevance: Among patients in the intensive care unit requiring fluid challenges, infusing at a slower rate compared with a faster rate did not reduce 90-day mortality. These findings do not support the use of a slower infusion rate. Trial Registration: ClinicalTrials.gov Identifier: NCT02875873.

Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial.

IMPORTANCE: Intravenous fluids are used for almost all intensive care unit (ICU) patients. Clinical and laboratory studies have questioned whether specific fluid types result in improved outcomes, including mortality and acute kidney injury. OBJECTIVE: To determine the effect of a balanced solution vs saline solution (0.9% sodium chloride) on 90-day survival in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, factorial, randomized clinical trial conducted at 75 ICUs in Brazil. Patients who were admitted to the ICU with at least 1 risk factor for worse outcomes, who required at least 1 fluid expansion, and who were expected to remain in the ICU for more than 24 hours were randomized between May 29, 2017, and March 2, 2020; follow-up concluded on October 29, 2020. Patients were randomized to 2 different fluid types (a balanced solution vs saline solution reported in this article) and 2 different infusion rates (reported separately). INTERVENTIONS: Patients were randomly assigned 1:1 to receive either a balanced solution (n = 5522) or 0.9% saline solution (n = 5530) for all intravenous fluids. MAIN OUTCOMES AND MEASURES: The primary outcome was 90-day survival. RESULTS: Among 11 052 patients who were randomized, 10 520 (95.2%) were available for the analysis (mean age, 61.1 [SD, 17] years; 44.2% were women). There was no significant interaction between the 2 interventions (fluid type and infusion speed; P = .98). Planned surgical admissions represented 48.4% of all patients. Of all the patients, 60.6% had hypotension or vasopressor use and 44.3% required mechanical ventilation at enrollment. Patients in both groups received a median of 1.5 L of fluid during the first day after enrollment. By day 90, 1381 of 5230 patients (26.4%) assigned to a balanced solution died vs 1439 of 5290 patients (27.2%) assigned to saline solution (adjusted hazard ratio, 0.97 [95% CI, 0.90-1.05]; P = .47). There were no unexpected treatment-related severe adverse events in either group. CONCLUSION AND RELEVANCE: Among critically ill patients requiring fluid challenges, use of a balanced solution compared with 0.9% saline solution did not significantly reduce 90-day mortality. The findings do not support the use of this balanced solution. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02875873.

Mobilization practices in the ICU: A nationwide 1-day point- prevalence study in Brazil.

BACKGROUND: Mobilization of critically ill patients is safe and may improve functional outcomes. However, the prevalence of mobilization activities of ICU patients in Brazil is unknown. METHODS: A one-day point prevalence prospective study with a 24-hour follow-up period was conducted in Brazil. Demographic data, ICU characteristics, prevalence of mobilization activities, level of patients' mobilization, and main reasons for not mobilizing patients were collected for all adult patients with more than 24hs of ICU stay in the 26 participating ICUs. Mobilization activity was defined as any exercise performed during ICU stay. RESULTS: In total, 358 patients were included in this study. Mobilization activities were performed in 87.4% of patients. Patients received mobilization activities while under invasive mechanical ventilation (44.1%), noninvasive ventilation (11.7%), or without any ventilatory support (44.2%). Passive exercises were more frequently performed [46.5% in all patients; 82.3% in mechanically ventilated patients]. Mobilization activities included in-bed exercise regimen (72.2%). Out-of-bed mobility was reported in 39.9% of mobilized patients, and in 16.3% of patients under invasive mechanical ventilation. The presence of an institutional early mobility protocol was associated with early mobilization (OR, 3.19; 95% CI, 1.23 to 8.22; p = 0.016), and with out-of-bed exercise (OR, 5.80; 95% CI, 1.33 to 25.30; p = 0.02). CONCLUSION: Mobilization activities in critically ill patients in Brazil was highly prevalent, although there was almost no active mobilization in the mechanically ventilated patients. Moreover, the presence of an institutional early mobility protocol was associated with a threefold higher chance of ICU mobilization during that day.

Comparison of three transfusion protocols prior to central venous catheterization in patients with cirrhosis: A randomized controlled trial.

BACKGROUND: Transfusion of blood components prior to invasive procedures in cirrhosis patients is high and associated with adverse events. OBJECTIVES: We compared three transfusion strategies prior to central venous catheterization in cirrhosis patients. PATIENTS/METHODS: Single center randomized trial that included critically ill cirrhosis patients with indication for central venous line in a tertiary private hospital in Brazil. INTERVENTIONS: Restrictive protocol, thromboelastometry-guided protocol, or usual care (based on coagulogram). The primary endpoint was the proportion of patients transfused with any blood component (ie, fresh frozen plasma, platelets, or cryoprecipitate). The secondary endpoints included incidence of bleeding and transfusion-related adverse events. RESULTS: A total of 57 patients (19 per group; 64.9% male; mean age, 53.4 ± 11.3 years) were enrolled. Prior to catheterization, 3/19 (15.8%) in the restrictive arm, 13/19 (68.4%) in the thromboelastometry-guided arm, and 14/19 (73.7%) in the coagulogram-guided arm received blood transfusion (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.01-0.45; P = .002 for restrictive versus coagulogram-guided arm; OR, 0.09; 95% CI, 0.01-0.56; P = .006 for restrictive versus thromboelastometry-guided arm; and OR, 0.77; 95% CI, 0.14-4.15; P = .931 for thromboelastometry-guided versus coagulogram-guided arm). The restrictive protocol was cost saving. No difference in bleeding, length of stay, mortality, and transfusion-related adverse events was found. CONCLUSIONS: The use of a restrictive strategy is associated with a reduction in transfusion prior to central venous catheterization and costs in critically ill cirrhosis patients. No effect on bleeding was found among the groups.

Quality Improvement Initiatives in Sepsis in an Emerging Country: Does the Institution's Main Source of Income Influence the Results? An Analysis of 21,103 Patients.

OBJECTIVE: We aimed to assess the results of a quality improvement initiative in sepsis in an emerging setting and to analyze it according to the institutions' main source of income (public or private). DESIGN: Retrospective analysis of the Latin American Sepsis Institute database from 2005 to 2014. SETTINGS: Brazilian public and private institutions. PATIENTS: Patients with sepsis admitted in the participant institutions. INTERVENTIONS: The quality improvement initiative was based on a multifaceted intervention. The institutions were instructed to collect data on 6-hour bundle compliance and outcomes in patients with sepsis in all hospital settings. Outcomes and compliance was measured for eight periods of 6 months each, starting at the time of the enrollment in the intervention. The primary outcomes were hospital mortality and compliance with 6-hour bundle. MEASUREMENTS AND MAIN RESULTS: We included 21,103 patients; 9,032 from public institutions and 12,071 from private institutions. Comparing the first period with the eigth period, compliance with the 6-hour bundle increased from 13.5% to 58.2% in the private institutions (p < 0.0001) and from 7.4% to 15.7% in the public institutions (p < 0.0001). Mortality rates significantly decreased throughout the program in private institutions, from 47.6% to 27.2% in the eighth period (adjusted odds ratio, 0.45; 95% CI, 0.32-0.64). However, in the public hospitals, mortality diminished significantly only in the first two periods. CONCLUSION: This quality improvement initiative in sepsis in an emerging country was associated with a reduction in mortality and with improved compliance with quality indicators. However, this reduction was sustained only in private institutions.

Study protocol for the Balanced Solution versus Saline in Intensive Care Study (BaSICS): a factorial randomised trial.

BACKGROUND: The effectiveness and safety of balanced crystalloid fluids compared with saline (0.9% sodium chloride) as a fluid of choice in critically ill patients remain unclear. The effects of different fluid infusion rates on outcomes are also unknown. OBJECTIVES: To test the hypothesis that a balanced crystalloid solution, compared with saline, decreases 90-day all-cause mortality among critically ill patients; and to test the hypothesis that slow, compared with rapid, infusion rate decreases 90-day mortality in this population of patients. METHODS: The Balanced Solution versus Saline in Intensive Care Study (BaSICS) is a pragmatic, 2 ??2 factorial, randomised controlled trial. A total of 11 000 patients will be recruited from at least 100 Brazilian intensive care units. Patients will be randomised to receive Plasma-Lyte 148 or saline, and to rapid infusion (999 mL/h) or slow infusion (333 mL/h). Study fluids will be used for resuscitation episodes (at rapid or slow infusion rates), dilution of compatible medications and maintenance solutions. Patients, health care providers and investigators will be blinded to the solutions being tested. The rate of bolus infusion will not be blinded. OUTCOMES: The primary outcome is 90-day all-cause mortality. Secondary outcomes are: incidence of renal failure requiring renal replacement therapy within 90 days, incidence of acute kidney injury (Kidney Disease: Improving Global Outcomes stages 2 and 3), incidence of non-renal organ dysfunction assessed by Sepsis-related Organ Failure Assessment score at Days 3 and 7, and number of mechanical ventilationfree days within the first 28 days after randomisation. RESULTS AND CONCLUSIONS: The BaSICS trial will provide robust evidence on whether a balanced crystalloid, compared with saline, improves important patient outcomes in critically ill patients. BaSICS will also provide relevant information on whether bolus infusion rate affects outcomes in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02875873.

Readmission to the Intensive Care Unit: Incidence, Risk Factors, Resource Use, and Outcomes. A Retrospective Cohort Study.

RATIONALE: Readmission to the intensive care unit (ICU) is associated with poor clinical outcomes, increased length of ICU and hospital stay, and higher costs. Nevertheless, knowledge of epidemiology of ICU readmissions, risk factors, and attributable outcomes is restricted to developed countries. OBJECTIVES: To determine the effect of ICU readmissions on in-hospital mortality, determine incidence of ICU readmissions, identify predictors of ICU readmissions and hospital mortality, and compare resource use and outcomes between readmitted and nonreadmitted patients in a developing country. METHODS: This retrospective single-center cohort study was conducted in a 40-bed, open medical-surgical ICU of a private, tertiary care hospital in São Paulo, Brazil. The Local Ethics Committee at Hospital Israelita Albert Einstein approved the study protocol, and the need for informed consent was waived. All consecutive adult (≥18 yr) patients admitted to the ICU between June 1, 2013 and July 1, 2015 were enrolled in this study. RESULTS: Comparisons were made between patients readmitted and not readmitted to the ICU. Logistic regression analyses were performed to identify predictors of ICU readmissions and hospital mortality. Out of 5,779 patients admitted to the ICU, 576 (10%) were readmitted to the ICU during the same hospitalization. Compared with nonreadmitted patients, patients readmitted to the ICU were more often men (349 of 576 patients [60.6%] vs. 2,919 of 5,203 patients [56.1%]; P = 0.042), showed a higher (median [interquartile range]) severity of illness (Simplified Acute Physiology III score) at index ICU admission (50 [41-61] vs. 42 [32-54], respectively, for readmitted and nonreadmitted patients; P < 0.001), and were more frequently admitted due to medical reasons (425 of 576 [73.8%] vs. 2,998 of 5,203 [57.6%], respectively, for readmitted and nonreadmitted patients; P < 0.001). Simplified Acute Physiology III score (P < 0.001), ICU admission from the ward (odds ratio [OR], 1.907; 95% confidence interval [CI], 1.463-2.487; P < 0.001), vasopressors need during index ICU stay (OR, 1.391; 95% CI, 1.130-1.713; P = 0.002), and length of ICU stay (P = 0.001) were independent predictors of ICU readmission. After adjusting for severity of illness, ICU readmission (OR, 4.103; 95% CI, 3.226-5.518; P < 0.001), admission source, presence of cancer, use of vasopressors, mechanical ventilation or renal replacement therapy, length of ICU stay, and nighttime ICU discharge were associated with increased risk of in-hospital death. CONCLUSIONS: Readmissions to the ICU were frequent and strongly related to poor outcomes. The degree to which ICU readmissions are preventable as well as the main causes of preventable ICU readmissions need to be further determined.

Avaliação de teste de tubo T como estratégia inicial de suspensão da ventilação mecânica / Evaluation of T tube trial as a strategy of weaning from mechanical ventilation

JUSTIFICATIVA E OBJETIVOS: A retirada precoce da ventilação mecânica (VM) é importante para reduzir a morbimortalidade de pacientes internados em Unidades de Terapia Intensiva. O objetivo deste estudo foi avaliar a utilização do teste de Tubo T (TT) como método de retirada de VM. MÉTODO: Foram incluídos neste estudo os pacientes admitidos na UTI que apresentavam os seguintes critérios: VM > 24 horas, ausência de doença neuromuscular, relação PaO2/FiO2 > 200, estabilidade hemodinâmica, reversão da causa da intubação traqueal e drive respiratório adequado. Todos foram submetidos ao teste de tubo T. Considerou-se falha a ocorrência de FR > 30 irpm, hipoxemia, taquicardia, disritmias cardíacas, hipertensão ou hipotensão arterial. Após 2 horas de teste TT sem critérios de falha, os pacientes foram extubados. Considerou-se como sucesso na retirada da VM a manutenção por 48 horas de autonomia ventilatória. RESULTADOS: Foram incluídos 49 pacientes com idade média de 51,8 ± 21,7 anos. As incidências de SDRA e choque séptico foram 26,5 por cento e 32,7 por cento e o tempo médio de VM foi 11,9 ± 13 dias. A retirada da VM ocorreu em 79,2 por cento, re-intubação em 31,6 por cento, com tempo médio 13 ± 8,7 horas, sendo 75 por cento devido à falência respiratória. Não houve correlação entre extubação e níveis de hemoglobina, PaO2/FiO2, idade, sexo, SDRA ou choque séptico prévios. O sucesso da retirada da VM (48 horas de autonomia) não se correlacionou com nenhuma das variáveis descritas. Os resultados foram considerados significativos se p < 0,05. CONCLUSÕES: O tubo T mostrou ser método adequado para a retirada da VM na maioria dos pacientes. Entretanto, a taxa de re-intubação foi elevada, podendo ser conseqüência do longo tempo do TT, da ventilação mecânica prévia ou da falha dos critérios de indicação de extubação traqueal.

BACKGROUND AND OBJECTIVES: Weaning from mechanical ventilation (MV) is an important strategy to reduce morbidity and mortality in critical care patients. In this setting, this study aimed at evaluation of T-tube trial (TT) in weaning from MV. METHODS: Patient admitted in the ICU were included if they present the following inclusion criteria: MV > 24 hours, no neuromuscular disorders, PaO2/FiO2 ratio >200, hemodynamic stability, reversion of the cause of respiratory failure, adequate respiratory drive. All were submitted to TT. Failure was defined by the presence of one of these symptoms: RR > 30 ipm, hypoxemia, tachycardia, arrhythmia, hypertension or hypotension. After two hours of TT, patients without failure criteria were extubated. After 48 hours of adequate spontaneous respiration the patient was considered successful weaned. Results were considered significant if p < 0.05. RESULTS: Forty-nine patients were included with a mean age 51.8 ± 21.7 years. The incidence of ARDS and septic shock were 26.5 percent and 32.7 percent and mean duration of MV was 11.9 ± 13 days. Discontinuation of MV occurred in 79.2 percent, reintubation in 31.6 percent, in a mean time of 13 ± 8.7 hours and in 75 percent of the cases it was due to respiratory failure. There was no correlation between success in TT and hemoglobin levels, PaO2/FiO2 ratio, age, gender, prior ARDS or septic shock. Weaning success was not correlated with none of the above variables. CONCLUSIONS: TT was adequated for weaning from mechanical ventilation in the majority of the cases. However, reintubation rate was high. Possible causes are the long period of TT, prior mechanical ventilation or the failure in the criteria used to indicate extubation.

[Evaluation of T tube trial as a strategy of weaning from mechanical ventilation]. / Avaliação de teste de tubo T como estratégia inicial de suspensão da ventilação mecânica.

BACKGROUND AND OBJECTIVES: Weaning from mechanical ventilation (MV) is an important strategy to reduce morbidity and mortality in critical care patients. In this setting, this study aimed at evaluation of T-tube trial (TT) in weaning from MV. METHODS: Patient admitted in the ICU were included if they present the following inclusion criteria: MV > 24 hours, no neuromuscular disorders, PaO2/FiO2 ratio >200, hemodynamic stability, reversion of the cause of respiratory failure, adequate respiratory drive. All were submitted to TT. Failure was defined by the presence of one of these symptoms: RR > 30 ipm, hypoxemia, tachycardia, arrhythmia, hypertension or hypotension. After two hours of TT, patients without failure criteria were extubated. After 48 hours of adequate spontaneous respiration the patient was considered successful weaned. Results were considered significant if p < 0.05. RESULTS: Forty-nine patients were included with a mean age 51.8 ± 21.7 years. The incidence of ARDS and septic shock were 26.5% and 32.7% and mean duration of MV was 11.9 ± 13 days. Discontinuation of MV occurred in 79.2%, reintubation in 31.6%, in a mean time of 13 ± 8.7 hours and in 75% of the cases it was due to respiratory failure. There was no correlation between success in TT and hemoglobin levels, PaO2/FiO2 ratio, age, gender, prior ARDS or septic shock. Weaning success was not correlated with none of the above variables. CONCLUSIONS: TT was adequated for weaning from mechanical ventilation in the majority of the cases. However, reintubation rate was high. Possible causes are the long period of TT, prior mechanical ventilation or the failure in the criteria used to indicate extubation.

Avaliaçäo da perfusäo tecidual no choque / Tissue perfusion assessment in shock

Apesar das diversas inovaçöes tecnológicas e do melhor entendimento fisiopatológico dos estados de choque, esta condiçäo permanece com elevada taxa de morbimortalidade. Uma das explicaçöes mais aceitas para a taxa elevada é o desenvolvimento da síndrome de disfunçäo de múltiplos órgäos (SDMO), secundária à hipoperfusäo tecidual persistente. Assim, é evidente a importância da avaliaçäo da perfusäo tecidual em tais quadros, bem como possíveis interferências terapêuticas a partir da avaliaçäo. Nesta revisäo, säo abordadas noçöes básicas sobre a monitorizaçäo clínica e laboratorial da perfusäo tecidual no choque, incluindo transporte de O2, consumo e taxa de extraçäo de O2, saturaçäo venosa mista de O2, lactato e gradiente gastroarterial de CO2. Tais dados säo fundamentais para a correta interpretaçäo e melhor intervençäo terapêutica, visando adequar o desequilíbrio presente entre oferta/consumo de 02 e, desta forma, interromper a série de eventos fisiopatológicos que resulta em SDMO e, em muitas condiçöes, em morte. Nesse contexto, algumas metas devem ser alcançadas durante a ressuscitaçäo de pacientes com síndrome do choque, a saber: pressäo arterial média > 65 mmHg; diurese ü 1 ml/kg/hora; débito cardíaco suficiente para manter uma SvO2 > 65 por cento; lactato sérico < 2 mmol/L, destacando que, mesmo quando normalizadas as variáveis sistêmicas de oxigenaçäo, graves distúrbios perfusionais regionais ainda podem existir, sendo necessário recorrer à monitorizaçäo regional através da avaliaçäo do pC02-gap.