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OBJECTIVE: : Early treatment in sepsis may improve outcome. The aim of this study was to evaluate how the delay in starting resuscitation influences the severity of sepsis and the treatment needed to achieve hemodynamic stability. DESIGN: : Prospective, randomized, controlled experimental study. SETTING: : Experimental laboratory in a university hospital. SUBJECTS: : Thirty-two anesthetized and mechanically ventilated pigs. INTERVENTIONS: : Pigs were randomly assigned (n = 8 per group) to a nonseptic control group or one of three groups in which fecal peritonitis (peritoneal instillation of 2 g/kg autologous feces) was induced, and a 48-hr period of protocolized resuscitation started 6 ([Delta]T-6 hrs), 12 ([Delta]T-12 hrs), or 24 ([Delta]T-24 hrs) hrs later. The aim of this study was to evaluate the impact of delays in resuscitation on disease severity, need for resuscitation, and the development of sepsis-associated organ and mitochondrial dysfunction. MEASUREMENTS AND MAIN RESULTS: : Any delay in starting resuscitation was associated with progressive signs of hypovolemia and increased plasma levels of interleukin-6 and tumor necrosis factor-[alpha] prior to resuscitation. Delaying resuscitation increased cumulative net fluid balances (2.1 ± 0.5 mL/kg/hr, 2.8 ± 0.7 mL/kg/hr, and 3.2 ± 1.5 mL/kg/hr, respectively, for groups [Delta]T-6 hrs, [Delta]T-12 hrs, and [Delta]T-24 hrs; p < .01) and norepinephrine requirements during the 48-hr resuscitation protocol (0.02 ± 0.04 [mu]g/kg/min, 0.06 ± 0.09 [mu]g/kg/min, and 0.13 ± 0.15 ug/kg/min; p = .059), decreased maximal brain mitochondrial complex II respiration (p = .048), and tended to increase mortality (p = .08). Muscle tissue adenosine triphosphate decreased in all groups (p < .01), with lowest values at the end in groups [Delta]T-12 hrs and [Delta]T-24 hrs. CONCLUSIONS: : Increasing the delay between sepsis initiation and resuscitation increases disease severity, need for resuscitation, and sepsis-associated brain mitochondrial dysfunction. Our results support the concept of a critical window of opportunity in sepsis resuscitation. [ABSTRACT FROM AUTHOR]

Importance: Maneuvers assessing fluid responsiveness before an intravascular volume expansion may limit useless fluid administration, which in turn may improve outcomes., Objective: To describe maneuvers for assessing fluid responsiveness in mechanically ventilated patients., Registration: The protocol was registered at PROSPERO: CRD42019146781., Information Sources and Search: PubMed, EMBASE, CINAHL, SCOPUS, and Web of Science were search from inception to 08/08/2023., Study Selection and Data Collection: Prospective and intervention studies were selected., Statistical Analysis: Data for each maneuver were reported individually and data from the five most employed maneuvers were aggregated. A traditional and a Bayesian meta-analysis approach were performed., Results: A total of 69 studies, encompassing 3185 fluid challenges and 2711 patients were analyzed. The prevalence of fluid responsiveness was 49.9%. Pulse pressure variation (PPV) was studied in 40 studies, mean threshold with 95% confidence intervals (95% CI) = 11.5 (10.5-12.4)%, and area under the receiver operating characteristics curve (AUC) with 95% CI was 0.87 (0.84-0.90). Stroke volume variation (SVV) was studied in 24 studies, mean threshold with 95% CI = 12.1 (10.9-13.3)%, and AUC with 95% CI was 0.87 (0.84-0.91). The plethysmographic variability index (PVI) was studied in 17 studies, mean threshold = 13.8 (12.3-15.3)%, and AUC was 0.88 (0.82-0.94). Central venous pressure (CVP) was studied in 12 studies, mean threshold with 95% CI = 9.0 (7.7-10.1) mmHg, and AUC with 95% CI was 0.77 (0.69-0.87). Inferior vena cava variation (∆IVC) was studied in 8 studies, mean threshold = 15.4 (13.3-17.6)%, and AUC with 95% CI was 0.83 (0.78-0.89)., Conclusions: Fluid responsiveness can be reliably assessed in adult patients under mechanical ventilation. Among the five maneuvers compared in predicting fluid responsiveness, PPV, SVV, and PVI were superior to CVP and ∆IVC. However, there is no data supporting any of the above mentioned as being the best maneuver. Additionally, other well-established tests, such as the passive leg raising test, end-expiratory occlusion test, and tidal volume challenge, are also reliable., (© 2024. The Author(s).)

Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown., Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction., Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023., Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first., Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models., Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group., Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin., Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.

Background: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated., Methods: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study., Conclusion: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients., Clinicaltrials.gov Registry: NCT05558098.

Objective: The incidence of thrombotic events and acute kidney injury is high in critically ill patients with COVID-19. We aimed to evaluate and compare the coagulation profiles of patients with COVID-19 developing acute kidney injury versus those who did not, during their intensive care unit stay., Methods: Conventional coagulation and platelet function tests, fibrinolysis, endogenous inhibitors of coagulation tests, and rotational thromboelastometry were conducted on days 0, 1, 3, 7, and 14 following intensive care unit admission., Results: Out of 30 patients included, 13 (43.4%) met the criteria for acute kidney injury. Comparing both groups, patients with acute kidney injury were older: 73 (60-84) versus 54 (47-64) years, p=0.027, and had a lower baseline glomerular filtration rate: 70 (51-81) versus 93 (83-106) mL/min/1.73m2, p=0.004. On day 1, D-dimer and fibrinogen levels were elevated but similar between groups: 1780 (1319-5517) versus 1794 (726-2324) ng/mL, p=0.145 and 608 (550-700) versus 642 (469-722) g/dL, p=0.95, respectively. Rotational thromboelastometry data were also similar between groups. However, antithrombin activity and protein C levels were lower in patients who developed acute kidney injury: 82 (75-92) versus 98 (90-116), p=0.028 and 70 (52-82) versus 88 (78-101) µ/mL, p=0.038, respectively. Mean protein C levels were lower in the group with acute kidney injury across multiple time points during their stay in the intensive care unit., Conclusion: Critically ill patients experiencing acute kidney injury exhibited lower endogenous anticoagulant levels. Further studies are needed to understand the role of natural anticoagulants in the pathophysiology of acute kidney injury within this population.

Objective: To describe and compare the clinical characteristics and outcomes of patients admitted to intensive care units during the first and second waves of the COVID-19 pandemic., Methods: In this retrospective single-center cohort study, data were retrieved from the Epimed Monitor System; all adult patients admitted to the intensive care unit between March 4, 2020, and October 1, 2021, were included in the study. We compared the clinical characteristics and outcomes of patients admitted to the intensive care unit of a quaternary private hospital in São Paulo, Brazil, during the first (May 1, 2020, to August 31, 2020) and second (March 1, 2021, to June 30, 2021) waves of the COVID-19 pandemic., Results: In total, 1,427 patients with COVID-19 were admitted to the intensive care unit during the first (421 patients) and second (1,006 patients) waves. Compared with the first wave group [median (IQR)], the second wave group was younger [57 (46-70) versus 67 (52-80) years; p<0.001], had a lower SAPS 3 Score [45 (42-52) versus 49 (43-57); p<0.001], lower SOFA Score on intensive care unit admission [3 (1-6) versus 4 (2-6); p=0.018], lower Charlson Comorbidity Index [0 (0-1) versus 1 (0-2); p<0.001], and were less frequently frail (10.4% versus 18.1%; p<0.001). The second wave group used more noninvasive ventilation (81.3% versus 53.4%; p<0.001) and high-flow nasal cannula (63.2% versus 23.0%; p<0.001) during their intensive care unit stay. The intensive care unit (11.3% versus 10.5%; p=0.696) and in-hospital mortality (12.3% versus 12.1%; p=0.998) rates did not differ between both waves., Conclusion: In the first and second waves, patients with severe COVID-19 exhibited similar mortality rates and need for invasive organ support, despite the second wave group being younger and less severely ill at the time of intensive care unit admission.

Objective: The main objective was to assess the clinical characteristics, associated factors, and outcomes of patients admitted to the ICU for candidemia. The secondary objective was to examine the relationship of candidemia with the length of stay and mortality., Methods: The analysis was a retrospective single-center cohort study addressing the effect of invasive candidemia on outcomes. This study was performed in a medical-surgical ICU located in a tertiary private hospital in São Paulo, Brazil. Data was collected through the review of the hospital database., Results: In total, 18,442 patients were included in our study, including 22 patients with candidemia. The median age was similar in patients with and without candidemia [67 (56-84) vs. 67 (51-80)]. Most patients were male, and the proportion of men was higher among patients with candidemia (77% vs. 55.3%). The rates of renal replacement therapy (40.9% vs. 3.3%), mechanical ventilation (63.6% vs. 29.6%), and parenteral nutrition (40.9% vs. 4.8%) were higher in patients with candidemia than in those without candidemia. The mortality rate (77.3% vs. 11.9%) and length of hospital stay [42 days (23.0-78.8) vs. 8 days (5.0-17.0)] were significantly higher in patients with candidemia., Conclusions: Patients with candidemia are prone to longer hospital stay and mortality. In addition, we found associations of candidemia with the use of invasive mechanical ventilation, renal replacement therapy, and parenteral nutrition.

Purpose: To reanalyze the results of the Balanced Solutions in Intensive Care Study (BaSICS) through hierarchical endpoint analysis with win ratio., Methods: All patients with full data in BaSICS trial were elected for the analysis. BaSICS compared balanced solutions (Plasma Lye 148) versus 0.9% saline in critically ill patients requiring fluid challenge. The win ratio was defined as a hierarchical endpoint of 90-day mortality, recepit of kidney replacement therapy, hospital length-of-stay (LOS), and intensive care unit (ICU) LOS. Both unstratified and stratified (by admission type: planned admission, unplanned admission with sepsis, and unplanned admission without sepsis) approaches were used. A subgroup analysis was performed in patients with traumatic brain injury., Results: A total of 10,490 patients were included in the analysis, resulting in 27,587,566 unique combinations for unstratified WR. Unstratified Win ratio was 1.02 (95% confidence interval 0.97; 1.07), which was similar to stratified WR. No stratum in the stratified analysis resulted in significant results. Subgroup analysis confirmed the possible harm of balanced solutions in traumatic brain injury patients (WR 0.80; 95% confidence interval 0.64; 0.99)., Conclusion: In this reanalysis of BaSICS, a win ratio analysis largely replicated the results of the main trial, yielding neutral results except for the subgroup of patients with traumatic brain injury where a signal of harm was found., Competing Interests: Declaration of Competing Interest FGZ has received grants for investigator-initiated trials from Bactiguard (Sweden), and Ionis Pharmaceuticals (USA), unrelated to the topic of this study. LCPA has received lecturing fees from Baxter®., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To describe the effects of balanced solution use on the short-term outcomes of patients with traumatic brain injury enrolled in BaSICS trial., Methods: Patients were randomized to receive either 0.9% saline or balanced solution during their intensive care unit stay. The primary endpoint was 90-day mortality, and the secondary outcomes were days alive and free of intensive care unit stay at 28 days. The primary endpoint was assessed using Bayesian logistic regression. The secondary endpoint was assessed using a Bayesian zero-inflated beta binomial regression., Results: We included 483 patients (236 in the 0.9% saline arm and 247 in the balanced solution arm). A total of 338 patients (70%) with a Glasgow coma scale score ≤ 12 were enrolled. The overall probability that balanced solutions were associated with higher 90-day mortality was 0.98 (OR 1.48; 95%CrI 1.04 - 2.09); this mortality increment was particularly noticeable in patients with a Glasgow coma scale score below 6 at enrollment (probability of harm of 0.99). Balanced solutions were associated with -1.64 days alive and free of intensive care unit at 28 days (95%CrI -3.32 - 0.00) with a probability of harm of 0.97., Conclusion: There was a high probability that balanced solutions were associated with high 90-day mortality and fewer days alive and free of intensive care units at 28 days.ClinicalTrials.gov: NCT02875873.

Background: Severe coronavirus disease 2019 (COVID-19) patients frequently require mechanical ventilation (MV) and undergo prolonged periods of bed rest with restriction of activities during the intensive care unit (ICU) stay. Our aim was to address the degree of mobilization in critically ill patients with COVID-19 undergoing to MV support., Methods: Retrospective single-center cohort study. We analyzed patients' mobility level, through the Perme ICU Mobility Score (Perme Score) of COVID-19 patients admitted to the ICU. The Perme Mobility Index (PMI) was calculated [PMI = ΔPerme Score (ICU discharge-ICU admission)/ICU length of stay], and patients were categorized as "improved" (PMI > 0) or "not improved" (PMI ≤ 0). Comparisons were performed with stratification according to the use of MV support., Results: From February 2020, to February 2021, 1,297 patients with COVID-19 were admitted to the ICU and assessed for eligibility. Out of those, 949 patients were included in the study [524 (55.2%) were classified as "improved" and 425 (44.8%) as "not improved"], and 396 (41.7%) received MV during ICU stay. The overall rate of patients out of bed and able to walk ≥ 30 meters at ICU discharge were, respectively, 526 (63.3%) and 170 (20.5%). After adjusting for confounders, independent predictors of improvement of mobility level were frailty (OR: 0.52; 95% CI: 0.29-0.94; p = 0.03); SAPS III Score (OR: 0.75; 95% CI: 0.57-0.99; p = 0.04); SOFA Score (OR: 0.58; 95% CI: 0.43-0.78; p < 0.001); use of MV after the first hour of ICU admission (OR: 0.41; 95% CI: 0.17-0.99; p = 0.04); tracheostomy (OR: 0.54; 95% CI: 0.30-0.95; p = 0.03); use of extracorporeal membrane oxygenation (OR: 0.21; 95% CI: 0.05-0.8; p = 0.03); neuromuscular blockade (OR: 0.53; 95% CI: 0.3-0.95; p = 0.03); a higher Perme Score at admission (OR: 0.35; 95% CI: 0.28-0.43; p < 0.001); palliative care (OR: 0.05; 95% CI: 0.01-0.16; p < 0.001); and a longer ICU stay (OR: 0.79; 95% CI: 0.61-0.97; p = 0.04) were associated with a lower chance of mobility improvement, while non-invasive ventilation within the first hour of ICU admission and after the first hour of ICU admission (OR: 2.45; 95% CI: 1.59-3.81; p < 0.001) and (OR: 2.25; 95% CI: 1.56-3.26; p < 0.001), respectively; and vasopressor use (OR: 2.39; 95% CI: 1.07-5.5; p = 0.03) were associated with a higher chance of mobility improvement., Conclusion: The use of MV reduced mobility status in less than half of critically ill COVID-19 patients., Competing Interests: The authors have declared that no competing interests exist.

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).

Objective:  Determine the predictive criteria for success in inducing labor for live fetuses using misoprostol in pregnant women. Secondarily, the objective is to determine the rates of vaginal or cesarean delivery, duration of induction, interval of administration of misoprostol, the main causes of induction of labor and indication for operative delivery., Methods:  Medical records of 873 pregnant women admitted for cervical maturation from January 2017 to December 2018 were reviewed in a descriptive observational study of retrospective analysis, considering the following response variables: age, parity, Bishop Index, doses of misoprostol, labor induction time. Logistic regression models were used to predict success with misoprostol in non-operative deliveries., Results:  Of the 873 patients evaluated, 72% evolved with vaginal delivery, 23% of the cases were cesarean, 5% forceps or vacuum-extractor. For non-operative delivery the predictive variables at admission were age, parity, gestational age and dilation. During hospitalization, fewer vaginal touches, amniotomy or amniorrhexis with clear fluid lead to a shorter induction time and a greater chance of non-operative delivery. False positives and false negatives of the model were always below 50% and correct answers above 65%., Conclusion:  At admission, age less than 24 years, previous normal births, lower the gestational age and greater the dilation, were predictive of greater probability of non-operative delivery. During hospitalization, the less vaginal touches and occurrence of amniotomy/amniorrhexis with clear liquid indicate shorter induction time. Future studies with a prospective design and analysis of other factors are necessary to assess the replicability, generalization of these findings., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Ketamine is unique among anesthetics and analgesics. The drug is a rapid-acting general anesthetic that produces an anesthetic state characterized by profound analgesia, preserved pharyngeal-laryngeal reflexes, normal or slightly enhanced skeletal muscle tone, cardiovascular and respiratory stimulation, and occasionally a transient and minimal respiratory depression. Research has demonstrated the efficacy of its use on anesthesia, pain, palliative care, and intensive care. Recently, it has been used for postoperative and chronic pain, as an adjunct in psychotherapy, as a treatment for depression and posttraumatic stress disorder, as a procedural sedative, and as a treatment for respiratory and/or neurologic clinical conditions. Despite being a safe and widely used drug, many physicians, such as intensivists and those practicing in emergency care, are not aware of the current clinical applications of ketamine. The objective of this narrative literature review is to present the theoretical and practical aspects of clinical applications of ketamine in intensive care unit and emergency department settings.

Objective: The TELE-critical Care verSus usual Care On ICU PErformance (TELESCOPE) trial aims to assess whether a complex telemedicine intervention in intensive care units, which focuses on daily multidisciplinary rounds performed by remote intensivists, will reduce intensive care unit length of stay compared to usual care., Methods: The TELESCOPE trial is a national, multicenter, controlled, open label, cluster randomized trial. The study tests the effectiveness of daily multidisciplinary rounds conducted by an intensivist through telemedicine in Brazilian intensive care units. The protocol was approved by the local Research Ethics Committee of the coordinating study center and by the local Research Ethics Committee from each of the 30 intensive care units, following Brazilian legislation. The trial is registered with ClinicalTrials. gov (NCT03920501). The primary outcome is intensive care unit length of stay, which will be analyzed accounting for the baseline period and cluster structure of the data and adjusted by prespecified covariates. Secondary exploratory outcomes included intensive care unit performance classification, in-hospital mortality, incidence of nosocomial infections, ventilator-free days at 28 days, rate of patients receiving oral or enteral feeding, rate of patients under light sedation or alert and calm, and rate of patients under normoxemia., Conclusion: According to the trial's best practice, we report our statistical analysis prior to locking the database and beginning analyses. We anticipate that this reporting practice will prevent analysis bias and improve the interpretation of the reported results.ClinicalTrials.gov registration: NCT03920501.

Objective: To evaluate clinical practices and hospital resource organization during the early COVID-19 pandemic in Brazil., Methods: This was a multicenter, cross-sectional survey. An electronic questionnaire was provided to emergency department and intensive care unit physicians attending COVID-19 patients. The survey comprised four domains: characteristics of the participants, clinical practices, COVID-19 treatment protocols and hospital resource organization., Results: Between May and June 2020, 284 participants [median (interquartile ranges) age 39 (33 - 47) years, 56.3% men] responded to the survey; 33% were intensivists, and 9% were emergency medicine specialists. Half of the respondents worked in public hospitals. Noninvasive ventilation (89% versus 73%; p = 0.001) and highflow nasal cannula (49% versus 32%; p = 0.005) were reported to be more commonly available in private hospitals than in public hospitals. Mechanical ventilation was more commonly used in public hospitals than private hospitals (70% versus 50%; p = 0,024). In the Emergency Departments, positive endexpiratory pressure was most commonly adjusted according to SpO2, while in the intensive care units, positive end-expiratory pressure was adjusted according to the best lung compliance. In the Emergency Departments, 25% of the respondents did not know how to set positive end-expiratory pressure. Compared to private hospitals, public hospitals had a lower availability of protocols for personal protection equipment during tracheal intubation (82% versus 94%; p = 0.005), managing mechanical ventilation [64% versus 75%; p = 0.006] and weaning patients from mechanical ventilation [34% versus 54%; p = 0.002]. Finally, patients spent less time in the emergency department before being transferred to the intensive care unit in private hospitals than in public hospitals [2 (1 - 3) versus 5 (2 - 24) hours; p < 0.001]., Conclusion: This survey revealed significant heterogeneity in the organization of hospital resources, clinical practices and treatments among physicians during the early COVID-19 pandemic in Brazil.

Objective: To describe clinical characteristics, resource use, outcomes, and to identify predictors of in-hospital mortality of patients with COVID-19 admitted to the intensive care unit., Methods: Retrospective single-center cohort study conducted at a private hospital in São Paulo (SP), Brazil. All consecutive adult (≥18 years) patients admitted to the intensive care unit, between March 4, 2020 and February 28, 2021 were included in this study. Patients were categorized between survivors and non-survivors according to hospital discharge., Results: During the study period, 1,296 patients [median (interquartile range) age: 66 (53-77) years] with COVID-19 were admitted to the intensive care unit. Out of those, 170 (13.6%) died at hospital (non-survivors) and 1,078 (86.4%) were discharged (survivors). Compared to survivors, non-survivors were older [80 (70-88) versus 63 (50-74) years; p<0.001], had a higher Simplified Acute Physiology Score 3 [59 (54-66) versus 47 (42-53) points; p<0.001], and presented comorbidities more frequently. During the intensive care unit stay, 56.6% of patients received noninvasive ventilation, 32.9% received mechanical ventilation, 31.3% used high flow nasal cannula, 11.7% received renal replacement therapy, and 1.5% used extracorporeal membrane oxygenation. Independent predictors of in-hospital mortality included age, Sequential Organ Failure Assessment score, Charlson Comorbidity Index, need for mechanical ventilation, high flow nasal cannula, renal replacement therapy, and extracorporeal membrane oxygenation support., Conclusion: Patients with severe COVID-19 admitted to the intensive care unit exhibited a considerable morbidity and mortality, demanding substantial organ support, and prolonged intensive care unit and hospital stay.

Background and Objectives: Patients who develop post-operative acute kidney injury (AKI) have a poor prognosis, especially when undergoing high-risk surgery. Therefore, the objective of this study was to evaluate the outcome of patients with AKI acquired after non-cardiac surgery and the possible risk factors for this complication., Methods: A multicenter, prospective cohort study with patients admitted to intensive care units (ICUs) after non-cardiac surgery was conducted to assess whether they developed AKI. The patients who developed AKI were then compared to non-AKI patients., Results: A total of 29 ICUs participated, of which 904 high-risk surgical patients were involved in the study. The occurrence of AKI in the post-operative period was 15.8%, and the mortality rate of post-operative AKI patients at 28 days was 27.6%. AKI was strongly associated with 28-day mortality (OR = 2.91; 95% CI 1.51-5.62; p  = 0.001), and a higher length of ICU and hospital stay ( p  < 0.001). Independent factors for the risk of developing AKI were pre-operative anemia (OR = 7.01; 95% CI 1.69-29.07), elective surgery (OR = 0.45; 95% CI 0.21-0.97), SAPS 3 (OR = 1.04; 95% CI 1.02-1.06), post-operative vasopressor use (OR = 2.47; 95% CI 1.34-4.55), post-operative infection (OR = 8.82; 95% CI 2.43-32.05) and the need for reoperation (OR= 7.15; 95% CI 2.58-19.79)., Conclusion: AKI was associated with the risk of death in surgical patients and those with anemia before surgery, who had a higher SAPS 3, needed a post-operative vasopressor, or had a post-operative infection or needed reoperation were more likely to develop AKI post-operatively.

Background and Objectives: Hypothermia occurs commonly during surgery and can cause postoperative complications. We aimed to describe the characteristics and outcomes of hypothermia in patients undergoing major surgeries., Methods: This prospective, observational, multicenter study of a nationally representative sample included all patients over 18 years of age admitted to an intensive care unit (ICU). Thirty ICUs were selected randomly at national level. The main outcome measure was the proportion of patients who developed postoperative hypothermia in the first 24 hours of ICU admission. Patients were divided into three groups based on temperature: <35°C, <36°C, and ≥36°C (no hypothermia). Patients' characteristics, postoperative complications, and risk factors were evaluated in all groups. To verify whether hypothermia was a strong risk factor for postoperative complications, a Kaplan-Meier curve was generated and adjusted using a Cox regression model., Results: In total, 738 patients had their temperatures measured. The percentage of patients with temperature <35°C (median [Q1-Q3], 34.7°C [34.3-34.9°C]) was 19.1% (95% confidence interval [CI] = 16.1-22.5) and that of patients with temperature <36°C (median [Q1-Q3], 35.4°C [35.0-35.8°C]) was 64% (95% CI = 58.3-70.0). The percentage of surgical complications was 38.9%. Patients with hypothermia were older, had undergone abdominal surgeries, had undergone procedures of longer duration, and had more comorbidities. A postoperative temperature ≤35°C was an independent risk for composite postoperative complications (hazard ratio = 1.523, 95% CI = 1.15-2.0), especially coagulation and infection., Conclusions: Inadvertent hypothermia was frequent among patients admitted to the ICU and occurred more likely after abdominal surgery, after a long procedure, in elderly patients, and in patients with a higher number of comorbidities. Low postoperative temperature was associated with postoperative complications., Competing Interests: The authors have declared that no competing interests exist.

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.

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.

Objective: To investigate the impact of intensive care unit admission during medical handover on mortality., Methods: Post-hoc analysis of data extracted from a prior study aimed at addressing the impacts of intensive care unit readmission on clinical outcomes. This retrospective, single-center, propensity-matched cohort study was conducted in a 41-bed general open-model intensive care unit. Patients were assigned to one of two cohorts according to time of intensive care unit admission: Handover Group (intensive care unit admission between 6:30 am and 7:30 am or 6:30 pm and 7:30 pm) or Control Group (intensive care unit admission between 7:31 am and 6:29 pm or 7:31 pm and 6:29 am). Patients in the Handover Group were propensity-matched to patients in the Control Group at a 1:2 ratio., Results: A total of 6,650 adult patients were admitted to the intensive care unit between June 1st 2013 and May 31st 2015. Following exclusion of non-eligible participants, 5,779 patients (389; 6.7% and 5,390; 93.3%, Handover and Control Group) were deemed eligible for propensity score matching. Of these, 1,166 were successfully matched (389; 33.4% and 777; 66.6%, Handover and Control Group). Following propensity-score matching, intensive care unit admission during handover was not associated with increased risk of intensive care unit (OR: 1.40; 95%CI: 0.92-2.11; p=0.113) or in-hospital (OR: 1.23; 95%CI: 0.85-1.75; p=0.265) mortality., Conclusion: Intensive care unit admission during medical handover did not affect in-hospital mortality in this propensity-matched, single-center cohort study.

Introduction: The Coronavirus Disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. Data on the mobility level of patients with COVID-19 in the intensive care unit (ICU) are needed., Objective: To describe the mobility level of patients with COVID-19 admitted to the ICU and to address factors associated with mobility level at the time of ICU discharge., Methods: Single center, retrospective cohort study. Consecutive patients admitted to the ICU with confirmed COVID-19 infection were analyzed. The mobility status was assessed by the Perme Score at admission and discharge from ICU with higher scores indicating higher mobility level. The Perme Mobility Index (PMI) was calculated [PMI = ΔPerme Score (ICU discharge-ICU admission)/ICU length of stay]. Based on the PMI, patients were divided into two groups: "Improved" (PMI > 0) and "Not improved" (PMI ≤ 0)., Results: A total of 136 patients were included in this analysis. The hospital mortality rate was 16.2%. The Perme Score improved significantly when comparing ICU discharge with ICU admission [20.0 (7-28) points versus 7.0 (0-16) points; P < 0.001]. A total of 88 patients (64.7%) improved their mobility level during ICU stay, and the median PMI of these patients was 1.5 (0.6-3.4). Patients in the improved group had a lower duration of mechanical ventilation [10 (5-14) days versus 15 (8-24) days; P = 0.021], lower hospital length of stay [25 (12-37) days versus 30 (11-48) days; P < 0.001], and lower ICU and hospital mortality rate. Independent predictors for mobility level were lower age, lower Charlson Comorbidity Index, and not having received renal replacement therapy., Conclusion: Patients' mobility level was low at ICU admission; however, most patients improved their mobility level during ICU stay. Risk factors associated with the mobility level were age, comorbidities, and use of renal replacement therapy., Competing Interests: The authors have declared that no competing interests exist.

Background: Critically ill patients with COVID-19 may develop multiple organ dysfunction syndrome, including acute kidney injury (AKI). We report the incidence, risk factors, associations, and outcomes of AKI and renal replacement therapy (RRT) in critically ill COVID-19 patients., Methods: We performed a retrospective cohort study of adult patients with COVID-19 diagnosis admitted to the intensive care unit (ICU) between March 2020 and May 2020. Multivariable logistic regression analysis was applied to identify risk factors for the development of AKI and use of RRT. The primary outcome was 60-day mortality after ICU admission., Results: 101 (50.2%) patients developed AKI (72% on the first day of invasive mechanical ventilation [IMV]), and thirty-four (17%) required RRT. Risk factors for AKI included higher baseline Cr (OR 2.50 [1.33-4.69], p = 0.005), diuretic use (OR 4.14 [1.27-13.49], p = 0.019), and IMV (OR 7.60 [1.37-42.05], p = 0.020). A higher C-reactive protein level was an additional risk factor for RRT (OR 2.12 [1.16-4.33], p = 0.023). Overall 60-day mortality was 14.4% {23.8% (n = 24) in the AKI group versus 5% (n = 5) in the non-AKI group (HR 2.79 [1.04-7.49], p = 0.040); and 35.3% (n = 12) in the RRT group versus 10.2% (n = 17) in the non-RRT group, respectively (HR 2.21 [1.01-4.85], p = 0.047)}., Conclusions: AKI was common among critically ill COVID-19 patients and occurred early in association with IMV. One in 6 AKI patients received RRT and 1 in 3 patients treated with RRT died in hospital. These findings provide important prognostic information for clinicians caring for these patients., (© 2020 S. Karger AG, Basel.)

Background: Coagulation abnormalities in COVID-19 patients have not been addressed in depth., Objective: To perform a longitudinal evaluation of coagulation profile of patients admitted to the ICU with COVID-19., Methods: Conventional coagulation tests, rotational thromboelastometry (ROTEM), platelet function, fibrinolysis, antithrombin, protein C and S were measured at days 0, 1, 3, 7 and 14. Based on median total maximum SOFA score, patients were divided in two groups: SOFA ≤ 10 and SOFA > 10., Results: Thirty patients were studied. Some conventional coagulation tests, as aPTT, PT and INR remained unchanged during the study period, while alterations on others coagulation laboratory tests were detected. Fibrinogen levels were increased in both groups. ROTEM maximum clot firmness increased in both groups from Day 0 to Day 14. Moreover, ROTEM-FIBTEM maximum clot firmness was high in both groups, with a slight decrease from day 0 to day 14 in group SOFA ≤ 10 and a slight increase during the same period in group SOFA > 10. Fibrinolysis was low and decreased over time in all groups, with the most pronounced decrease observed in INTEM maximum lysis in group SOFA > 10. Also, D-dimer plasma levels were higher than normal reference range in both groups and free protein S plasma levels were low in both groups at baseline and increased over time, Finally, patients in group SOFA > 10 had lower plasminogen levels and Protein C ​​than patients with SOFA <10, which may represent less fibrinolysis activity during a state of hypercoagulability., Conclusion: COVID-19 patients have a pronounced hypercoagulability state, characterized by impaired endogenous anticoagulation and decreased fibrinolysis. The magnitude of coagulation abnormalities seems to correlate with the severity of organ dysfunction. The hypercoagulability state of COVID-19 patients was not only detected by ROTEM but it much more complex, where changes were observed on the fibrinolytic and endogenous anticoagulation system., Competing Interests: The authors have declared that no competing interests exist.

Microvascular dysfunction has been associated with adverse outcomes in critically ill patients, and the current concept of hemodynamic incoherence has gained attention. Our objective was to perform a comprehensive analysis of microcirculatory perfusion parameters and to investigate the best variables that could discriminate patients with and without circulatory shock during early intensive care unit (ICU) admission. This prospective observational study comprised a sample of 40 adult patients with and without circulatory shock (n = 20, each) admitted to the ICU within 24 h. Peripheral clinical [capillary refill time (CRT), peripheral perfusion index (PPI), skin-temperature gradient (Tskin-diff)] and laboratory [arterial lactate and base excess (BE)] perfusion parameters, in addition to near-infrared spectroscopy (NIRS)-derived variables were simultaneously assessed. While lactate, BE, CRT, PPI and Tskin-diff did not differ significantly between the groups, shock patients had lower baseline tissue oxygen saturation (StO 2 ) [81 (76-83) % vs. 86 (76-90) %, p = 0.044], lower StO 2 min [50 (47-57) % vs. 55 (53-65)  %, p = 0.038] and lower StO 2 max [87 (80-92) % vs. 93 (90-95) %, p = 0.017] than patients without shock. Additionally, dynamic NIRS variables [recovery time (r = 0.56, p = 0.010), descending slope (r = - 0.44, p = 0.05) and ascending slope (r = - 0.54, p = 0.014)] and not static variable [baseline StO 2 (r = - 0.24, p = 0.28)] exhibited a significant correlation with the administered dose of norepinephrine. In our study with critically ill patients assessed within the first twenty-four hours of ICU admission, among the perfusion parameters, only NIRS-derived parameters could discriminate patients with and without shock.

Background: Venous-arterial carbon dioxide (CO 2 ) to arterial-venous oxygen (O 2 ) content difference ratio (Cv-aCO 2 /Ca-vO 2 ) > 1 is supposed to be both sensitive and specific for anaerobic metabolism. What regional hemodynamic and metabolic parameters determine the ratio has not been clarified., Objectives: To address determinants of systemic and renal, spleen, gut and liver Cv-aCO 2 /Ca-vO 2 ., Methods: Post hoc analysis of original data from published experimental studies aimed to address effects of different fluid resuscitation strategies on oxygen transport, lactate metabolism and organ dysfunction in fecal peritonitis and endotoxin infusion, and from animals in cardiac tamponade or hypoxic hypoxia. Systemic and regional hemodynamics, blood flow, lactate uptake, carbon dioxide and oxygen-derived variables were determined. Generalized estimating equations (GEE) were fit to assess contributors to systemic and regional Cv-aCO 2 /Ca-vO 2 ., Results: Median (range) of pooled systemic Cv-aCO 2 /Ca-vO 2 in 64 pigs was 1.02 (0.02 to 3.84). While parameters reflecting regional lactate exchange were variably associated with the respective regional Cv-aCO 2 /Ca-vO 2 ratios, only regional ratios were independently correlated with systemic ratio: renal Cv-aCO 2 /Ca-vO 2 (β = 0.148, 95% CI 0.062 to 0.234; p = 0.001), spleen Cv-aCO 2 /Ca-vO 2 (β = 0.065, 95% CI 0.002 to 0.127; p = 0.042), gut Cv-aCO 2 /Ca-vO 2 (β = 0.117, 95% CI 0.025 to 0.209; p = 0.013), liver Cv-aCO 2 /Ca-vO 2 (β = - 0.159, 95% CI - 0.297 to - 0.022; p = 0.023), hepatosplanchnic Cv-aCO 2 /Ca-vO 2 (β = 0.495, 95% CI 0.205 to 0.786; p = 0.001)., Conclusion: In a mixed set of animals in different shock forms or during hypoxic injury, hepatosplanchnic Cv-aCO 2 /Ca-vO 2 ratio had the strongest independent association with systemic Cv-aCO 2 /Ca-vO 2 , while no independent association was demonstrated for lactate or hemodynamic variables.

Background: The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19., Methods: We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278., Findings: 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94-1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups., Interpretation: In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19., Funding: COALITION COVID-19 Brazil and EMS., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective:  Gonadotropin-releasing hormone analogues (GnRH-a) have been used preoperatively before hysteroscopic myomectomy to decrease the size and vascularization of the myomas, but evidence to support this practice is weak. Our objective was to analyze the use of GnRH-a in the reduction of submucous fibroid as a facilitator for surgical hysteroscopy from published clinical trials., Data Sources:  Studies from electronic databases (Pubmed, Scielo, EMBASE, Scopus, PROSPERO), published between 1980 and December 2018. The keywords used were fibroid , GnRH analogue , submucous , histeroscopy , histeroscopic resection and their correspondents in Portuguese., Study Selection:  The inclusion criteria were controlled trials that evaluated the GnRH-a treatment before hysteroscopic resection of submucous myomas. Four clinical trials were included in the meta-analysis., Data Collection:  Two review authors extracted the data without modification of the original data, using the agreed form. We resolved discrepancies through discussion or, if required, we consulted a third person., Data Synthesis:  The present meta-analysis included a total of 213 women and showed no statistically significant differences in the use of GnRH-a compared with the control group for complete resection of submucous myoma (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.80-1.11); operative time (mean difference [MD]: - 3.81; 95%CI : - 3.81-2.13); fluid absorption (MD: - 65.90; 95%CI: - 9.75-2.13); or complications (RR 0.92; 95%CI: 0.18-4.82)., Conclusion:  The present review did not support the routine preoperative use of GnRH-a prior to hysteroscopic myomectomy. However, it is not possible to determine its inferiority when compared with the other methods due to the heterogeneity of existing studies and the small sample size., Competing Interests: The authors have no conflict of interests to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

High central venous pressure (CVP) acutely decreases venous return. How this affects hepatic oxygen transport in sepsis remains unclear. The aim of this study was to evaluate the effects of repeated increases in CVP via standard nursing procedures (NPs) on hepato-splanchnic and renal oxygen transport in a prolonged porcine sepsis model. Twenty anesthetized and mechanically ventilated pigs with regional hemodynamics monitored were randomized to fecal peritonitis or controls ( n = 10 pigs/group). Resuscitation was started after 8 h of observation and continued for 3 days. NPs were performed at baseline and 8 h, 32 h, 56 h, and 72 h after resuscitation started. NPs increased CVP by 4-7 mmHg in both groups. In controls, this was associated with less decrease in hepatic arterial (Q ha ; 62 ± 70 mL/min) than portal venous flow (Q pv ; 364 ± 151 mL/min). Portal venous oxygen content and hepatic O 2 delivery (Do 2 ) and consumption (V̇o 2 ) decreased by 11 ± 6 mL/dL and 0.9 ± 0.3 and 0.4 ± 0.3 mL·min -1 ·kg -1 , respectively. In septic animals, hepatic Do 2 decreased more in response to increasing CVP (1.5 ± 0.9 mL·min -1 ·kg -1 ), which was attributable to a larger fall in both Q ha (88 ± 66 ml/min) and portal O 2 content (14 ± 10 mL/dL, all P < 0.05). This resulted in numerically lower hepatic V̇o 2 since O 2 extraction did not increase significantly. In control conditions, a smaller decrease in Q ha compared with Q pv helped to limit the reduction in hepatic V̇o 2 in response to acute CVP increase. In sepsis, the contribution of Q ha to maintain hepatic Do 2 was reduced, which jeopardized hepatic V̇o 2 further. Renal arterial flow was similarly affected by CVP increase as Q ha . NEW & NOTEWORTHY Sepsis impairs intrinsic mechanisms to attenuate effects of increasing back pressure on hepatic oxygen transport.

Background: In most emergency situations or severe illness, patients are unable to consent for clinical trial enrollment. In such circumstances, the decision about whether to participate in a scientific study or not is made by a legally designated representative., Objective: To address the willingness of patients admitted to the intensive care unit (ICU) to be enrolled in a scientific study as volunteers, and to assess the agreement between patients' and their legal representatives' opinion concerning enrollment in a scientific study., Methods: This survey was conducted in two hospitals in São Paulo, Brazil. Patients (≥18 years) with preserved cognitive functions accompanied by a surrogate admitted to the ICU were eligible for this study. A survey containing 28 questions for patients and 8 questions for surrogates was applied within the first 48h from ICU admission. The survey for patients comprised three sections: demographic characteristics, opinion about participation in clinical research and knowledge about the importance of research. The survey for legal representatives contained two sections: demographic characteristics and assessment of legal representatives' opinion in authorizing patients to be enrolled in research., Results: Between January 2017 and May 2018, 208 pairs of ICU patients and their respective legal representatives answered the survey. Out of 208 ICU patients answering the survey, 73.6% (153/208) were willing to be enrolled in the study as volunteers. Of those patients, 65.1% (97/149) would continue participating in a research even if their legal representative did not support their enrollment. Agreement between patients' and surrogates' opinion concerning participation was poor [Kappa = 0.11 (IC95% -0.02 to 0.25)]. If a consent for study participation had been obtained, 69.1% (103/149) of patients would continue participating in the study until its conclusion, and 23.5% (35/149) would allow researchers to use data collected to date, but would withdraw from the study on that occasion., Conclusion: The majority of patients admitted to the ICU were willing to be enrolled in a scientific study as volunteers, also after a deferred informed consent procedure has been used. Nevertheless, contradictory opinions between patients and their and their legal representatives' concerning enrollment in a scientific study were often observed., Competing Interests: he authors have declared that no competing interests exist.

Objective: To evaluate the frequency of severe burnout syndrome among critical care providers and to correlate it with work engagement., Methods: A self-administered survey including the Maslach Burnout Inventory, Depression Anxiety and Stress Scales, and Gallup questionnaire was distributed. All analyses were stratified by setting (intensive care unit or step-down unit) and by professional group (nurses versus physicians versus physiotherapists)., Results: Between February 2017 and June 2017, 206 out of 325 invited professionals (63.4%) answered the questionnaires. Of these, 55 were physicians (26.7%), 88 were physiotherapists (42.7%) and 63 were nurses (30.6%). The frequency of severe burnout was 34.3% (27.9 - 41.4%), and no difference was found between professional groups or settings. The frequency of severe or very severe cases of depression, anxiety or stress was 12.9%, 11.4% and 10.5%, respectively. The median (interquartile range) score observed on the Gallup questionnaire was 41 (34 - 48), and no differences were found between professional groups or settings. There was a negative correlation between burnout and work engagement (r = -0.148; p = 0.035)., Conclusion: There is a high frequency of severe burnout among critical care providers working in the intensive care unit and step-down unit. There was a negative correlation between burnout and work engagement.

The care for patients suffering from cardiopulmonary arrest in a context of a COVID-19 pandemic has particularities that should be highlighted. The following recommendations from the Brazilian Association of Emergency Medicine (ABRAMEDE), the Brazilian Society of Cardiology (SBC) and the Brazilian Association of Intensive Medicine (AMIB) and the Brazilian Society of Anesthesiology (SBA), associations and societies official representatives of specialties affiliated to the Brazilian Medical Association (AMB), aim to guide the various assistant teams, in a context of little solid evidence, maximizing the protection of teams and patients. It is essential to wear full Personal Protective Equipment (PPE) for aerosols during the care of Cardiopulmonary Resuscitation (CPR) and it is imperative to consider and treat the potential causes in these patients, especially hypoxia and arrhythmias caused by changes in the QT interval or myocarditis. The installation of an advanced invasive airway must be obtained early and the use of High Efficiency Particulate Arrestance (HEPA) filters at the interface with the valve bag is mandatory; situations of occurrence of CPR during mechanical ventilation and in a prone position demand peculiarities that are different from the conventional CPR pattern. Faced with the care of a patient diagnosed or suspected of COVID-19, the care follows the national and international protocols and guidelines 2015 ILCOR (International Alliance of Resuscitation Committees), AHA 2019 Guidelines (American Heart Association) and the Update of the Cardiopulmonary Resuscitation and Emergency Care Directive of the Brazilian Society of Cardiology 2019., (.)

In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation).

Care for patients with cardiac arrest in the context of the coronavirus disease 2019 (COVID-19) pandemic has several unique aspects that warrant particular attention. This joint position statement by the Brazilian Association of Emergency Medicine (ABRAMEDE), Brazilian Society of Cardiology (SBC), Brazilian Association of Intensive Care Medicine (AMIB), and Brazilian Society of Anesthesiology (SBA), all official societies representing the corresponding medical specialties affiliated with the Brazilian Medical Association (AMB), provides recommendations to guide health care workers in the current context of limited robust evidence, aiming to maximize the protection of staff and patients alike. It is essential that full aerosol precautions, which include wearing appropriate personal protective equipment, be followed during resuscitation. It is also imperative that potential causes of cardiac arrest of particular interest in this patient population, especially hypoxia, cardiac arrhythmias associated with QT prolongation, and myocarditis, be considered and addressed. An advanced invasive airway device should be placed early. Use of HEPA filters at the bag-valve interface is mandatory. Management of cardiac arrest occurring during mechanical ventilation or during prone positioning demands particular ventilator settings and rescuer positioning for chest compressions which deviate from standard cardiopulmonary resuscitation techniques. Apart from these logistical issues, care should otherwise follow national and international protocols and guidelines, namely the 2015 International Liaison Committee on Resuscitation (ILCOR) and 2019 American Heart Association (AHA) guidelines and the 2019 Update to the Brazilian Society of Cardiology Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Guideline.

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., Competing Interests: The authors have declared that no competing interests exist.

Objective: To define the epidemiological profile and the main determinants of morbidity and mortality in noncardiac high surgical risk patients in Brazil., Methods: This was a prospective, observational and multicenter study. All noncardiac surgical patients admitted to intensive care units, i.e., those considered high risk, within a 1-month period were evaluated and monitored daily for a maximum of 7 days in the intensive care unit to determine complications. The 28-day postoperative, intensive care unit and hospital mortality rates were evaluated., Results: Twenty-nine intensive care units participated in the study. Surgeries were performed in 25,500 patients, of whom 904 (3.5%) were high-risk (95% confidence interval - 95%CI 3.3% - 3.8%) and were included in the study. Of the participating patients, 48.3% were from private intensive care units, and 51.7% were from public intensive care units. The length of stay in the intensive care unit was 2.0 (1.0 - 4.0) days, and the length of hospital stay was 9.5 (5.4 - 18.6) days. The complication rate was 29.9% (95%CI 26.4 - 33.7), and the 28-day postoperative mortality rate was 9.6% (95%CI 7.4 - 12.1). The independent risk factors for complications were the Simplified Acute Physiology Score 3 (SAPS 3; odds ratio - OR = 1.02; 95%CI 1.01 - 1.03) and Sequential Organ Failure Assessment Score (SOFA) on admission to the intensive care unit (OR = 1.17; 95%CI 1.09 - 1.25), surgical time (OR = 1.001, 95%CI 1.000 - 1.002) and emergency surgeries (OR = 1.93, 95%CI, 1.10 - 3.38). In addition, there were associations with 28-day mortality (OR = 1.032; 95%CI 1.011 - 1.052), SAPS 3 (OR = 1.041; 95%CI 1.107 - 1.279), SOFA (OR = 1.175, 95%CI 1.069 - 1.292) and emergency surgeries (OR = 2.509; 95%CI 1.040 - 6.051)., Conclusion: Higher prognostic scores, elderly patients, longer surgical times and emergency surgeries were strongly associated with higher 28-day mortality and more complications during the intensive care unit stay.

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., (© 2019 International Society on Thrombosis and Haemostasis.)

Purpose: To study whether ICU staffing features are associated with improved hospital mortality, ICU length of stay (LOS) and duration of mechanical ventilation (MV) using cluster analysis directed by machine learning., Methods: The following variables were included in the analysis: average bed to nurse, physiotherapist and physician ratios, presence of 24/7 board-certified intensivists and dedicated pharmacists in the ICU, and nurse and physiotherapist autonomy scores. Clusters were defined using the partition around medoids method. We assessed the association between clusters and hospital mortality using logistic regression and with ICU LOS and MV duration using competing risk regression., Results: Analysis included data from 129,680 patients admitted to 93 ICUs (2014-2015). Three clusters were identified. The features distinguishing between the clusters were: the presence of board-certified intensivists in the ICU 24/7 (present in Cluster 3), dedicated pharmacists (present in Clusters 2 and 3) and the extent of nurse autonomy (which increased from Clusters 1 to 3). The patients in Cluster 3 exhibited the best outcomes, with lower adjusted hospital mortality [odds ratio 0.92 (95% confidence interval (CI), 0.87-0.98)], shorter ICU LOS [subhazard ratio (SHR) for patients surviving to ICU discharge 1.24 (95% CI 1.22-1.26)] and shorter durations of MV [SHR for undergoing extubation 1.61(95% CI 1.54-1.69)]. Cluster 1 had the worst outcomes., Conclusion: Patients treated in ICUs combining 24/7 expert intensivist coverage, a dedicated pharmacist and nurses with greater autonomy had the best outcomes. All of these features represent achievable targets that should be considered by policy makers with an interest in promoting equal and optimal ICU care.

Extracorporeal membrane oxygenation is a modality of extracorporeal life support that allows for temporary support in pulmonary and/or cardiac failure refractory to conventional therapy. Since the first descriptions of extracorporeal membrane oxygenation, significant improvements have occurred in the device and the management of patients and, consequently, in the outcomes of critically ill patients during extracorporeal membrane oxygenation. Many important studies about the use of extracorporeal membrane oxygenation in patients with acute respiratory distress syndrome refractory to conventional clinical support, under in-hospital cardiac arrest and with cardiogenic refractory shock have been published in recent years. The objective of this literature review is to present the theoretical and practical aspects of extracorporeal membrane oxygenation support for respiratory and/or cardiac functions in critically ill patients.

Background: Discussions about invasiveness of care (advanced directives) and end-of-life issues have become frequent among intensivists and patients. Nevertheless, there are considerable divergences in the attitudes between intensivists and patients toward end-of-life care in the intensive care units (ICU)., Methods: The goal was to compare the preferences between intensivists and general public regarding ICU admission of a hypothetical patient with six different clinical outcomes. For that, intensivists and the general public (university graduate professionals outside the area of health) were invited to participate in this study. A survey was conducted with a hypothetical patient with six different clinical outcomes ranging from ICU discharge without any neurological sequelae, nor dependence for daily activities, to death. The WHOQOL-BREF was applied. Comparisons were made between the answers provided by intensivists regarding what they would choose for themselves and their patients, and the preferences of general public., Results: Between July 2013 and July 2016, 300 participants in 5 hospitals in São Paulo, Brazil were invited to participate in this study, of whom 257 (85.7%) responded the survey. Eighty-two intensivists responded what they would choose for themselves, 81 intensivists responded what they would choose for their patients, and 94 people from general public responded what they would choose for themselves. Quality of life did not differ among the groups. In all scenarios, except when the outcome was severe disability or death, intensivists were more likely to choose ICU admission for their patients than for themselves (p < .05 for all). Compared with general public, intensivists were more likely to choose ICU admission for themselves only when the best clinical scenario outcome is considered (p < .001). General public was significantly less prone to choosing ICU admission than intensivists when choosing for their patients, in three out of six scenarios (p < .001 for all)., Conclusions: Considerable divergences exist between intensivists' and patients' preferences toward end-of-life care. Advanced care planning and effective ongoing communication among intensivists, patients and relatives are essential to improve end-of-life decisions and the quality of care., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To investigate the impacts of continuous venovenous hemodiafiltration on the microcirculation in patients with acute kidney injury., Methods: A prospective observational pilot study conducted in a 40-bed, open clinical-surgical intensive care unit of a private tertiary care hospital located in the city of São Paulo (SP), Brazil. Microcirculation was assessed using near-infrared spectroscopy by means of a 15mm probe placed over the thenar eminence. Vascular occlusion test was performed on the forearm to be submitted to near-infrared spectroscopy by inflation of a sphygmomanometer cuff to 30mmHg higher than the systolic arterial pressure. The primary endpoint was the assessment of near-infrared spectroscopy-derived parameters immediately before, 1, 4 and 24 hours after the initiation of continuous venovenous hemodiafiltration., Results: Nine patients were included in this pilot study over a period of 2 months. Minimum tissue oxygen saturation measured during the vascular occlusion test was the only near-infrared spectroscopy-derived parameter to differed over the time (decrease compared to baseline values up to 24 hours after initiation of continuous venovenous hemodiafiltration)., Conclusion: The impacts of microcirculatory dysfunction on clinical outcomes of patients undergoing to continuous venovenous hemodiafiltration need to be further investigated.

Objective:  The gestational complication most associated with perinatal mortality and morbidity is spontaneous preterm birth with gestational age < 37 weeks. Therefore, it is necessary to identify its risk factors and attempt its prevention. The benefits of the pessary in prematurity are under investigation. Our objective was to analyze the use of the pessary in the prevention of preterm births in published studies, and to compare its efficacy with other methods., Methods:  Randomized clinical trials published between 2010 and 2018 were selected from electronic databases. Studies on multiple gestations were excluded., Results:  Two studies were in favor of the pessary as a preventive method, one study was contrary to the method and another two showed no statistically significant difference. The meta-analysis showed no statistical difference with the use of a cervical pessary in the reduction of births < 37 (odds ratio [OR]: 0.63; confidence interval [95% CI]: 0.38-1.06) and < 34 weeks (OR: 0.74; 95% CI: 0.35-1.57) CONCLUSION:  The pooled data available to date seems to show a lack of efficacy of the cervical pessary in the prevention of preterm birth, although the heterogeneity of the studies made comparisons more difficult., Competing Interests: The authors have no conflicts of interest to declare., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Background: Nighttime ICU discharge, i.e., discharge from the ICU during the night hours, has been associated with increased readmission rates, hospital length of stay (LOS) and in-hospital mortality. We sought to determine the frequency of nighttime ICU discharge and identify whether nighttime ICU discharge is associated with worse outcomes in a private adult ICU located in Brazil., Methods: Post hoc analysis of a cohort study addressing the effect of ICU readmissions on outcomes. This retrospective, single center, propensity matched cohort study was conducted in a medical-surgical ICU located in a private tertiary care hospital in São Paulo, Brazil. Based on time of transfer, patients were categorized into nighttime (7:00 pm to 6:59 am) and daytime (7:00 am to 6:59 pm) ICU discharge and were propensity-score matched at a 1:2 ratio. The primary outcome of interest was in-hospital mortality., Results: Among 4,313 eligible patients admitted to the ICU between June 2013 and May 2015, 1,934 patients were matched at 1:2 ratio [649 (33.6%) nighttime and 1,285 (66.4%) daytime discharged patients]. The median (IQR) cohort age was 66 (51-79) years and SAPS III score was 43 (33-55). In-hospital mortality was 6.5% (42/649) in nighttime compared to 5.6% (72/1,285) in daytime discharged patients (OR, 1.17; 95% CI, 0.79 to 1.73; p = 0.444). While frequency of ICU readmission (OR, 0.95; 95% CI, 0.78 to 1.29; p = 0.741) and length of hospital stay did not differ between the groups, length of ICU stay was lower in nighttime compared to daytime ICU discharged patients [1 (1-3) days vs. 2 (1-3) days, respectively, p = 0.047]., Conclusion: In this propensity-matched retrospective cohort study, time of ICU discharge did not affect in-hospital mortality., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Frail patients are known to experience poor outcomes. Nevertheless, we know less about how frailty manifests itself in patients' physiology during critical illness and how it affects resource use in intensive care units (ICU). We aimed to assess the association of frailty with short-term outcomes and organ support used by critically ill patients., Methods: Retrospective analysis of prospective collected data from 93 ICUs in Brazil from 2014 to 2015. We assessed frailty using the modified frailty index (MFI). The primary outcome was in-hospital mortality. Secondary outcomes were discharge home without need for nursing care, ICU and hospital length of stay (LOS), and utilization of ICU organ support and transfusion. We used mixed logistic regression and competing risk models accounting for relevant confounders in outcome analyses., Results: The analysis consisted of 129,680 eligible patients. There were 40,779 (31.4%) non-frail (MFI = 0), 64,407 (49.7%) pre-frail (MFI = 1-2) and 24,494 (18.9%) frail (MFI ≥ 3) patients. After adjusted analysis, frailty was associated with higher in-hospital mortality (OR 2.42, 95% CI 1.89-3.08), particularly in patients admitted with lower SOFA scores. Frail patients were less likely to be discharged home (OR 0.36, 95% CI 0.54-0.79) and had higher hospital and ICU LOS than non-frail patients. Use of all forms of organ support (mechanical ventilation, non-invasive ventilation, vasopressors, dialysis and transfusions) were more common in frail patients and increased as MFI increased., Conclusions: Frailty, as assessed by MFI, was associated with several patient-centered endpoints including not only survival, but also ICU LOS and organ support.