Acute Kidney Injury and Renal Replacement Therapy in Critically Ill COVID-19 Patients: Risk Factors and Outcomes: A Single-Center Experience in Brazil.

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.

The effects of acute kidney injury in a multicenter cohort of high-risk surgical patients.

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.

Assessment of the peripheral microcirculation in patients with and without shock: a pilot study on different methods.

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 (StO2) [81 (76-83) % vs. 86 (76-90) %, p = 0.044], lower StO2min [50 (47-57) % vs. 55 (53-65)  %, p = 0.038] and lower StO2max [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 StO2 (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.

Thromboelastometry analysis of thrombocytopenic dengue patients: a cross-sectional study.

BACKGROUND: Dengue virus infection (DVI) is a prevalent and potentially fatal viral disease associated with coagulopathy. So far, the coagulation profile of DVI patients with thrombocytopenia has not been assessed through a viscoelastic test such as rotational thromboelastometry. We aimed to describe the prevalence and characteristics of coagulation abnormalities in dengue fever outpatients with thrombocytopenia, addressed by both rotational thromboelastometry and conventional coagulation tests. METHODS: This was a cross-sectional study conducted between April 6th and May 5th 2015 in São Paulo, Brazil during a dengue outbreak. Thromboelastometry (ROTEM®) and the conventional coagulation tests prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time (TT), platelet count and fibrinogen levels were performed in 53 patients with DVI and thrombocytopenia. RESULTS: Despite a median interquartile range (IQR) platelet count of 77 (63-88) x 109/L in DVI patients, conventional coagulation tests and plasma fibrinogen levels were within the normal range. Subjects demonstrated hypocoagulability in 71.7% (38/53) in INTEM and 54.7% (29/53) in EXTEM DVI patients. FIBTEM analyses detected only 5.7% (3/53) with hypocoagulability among this population. The median (IQR) clotting time (CT), clot formation time (CFT) and maximum clot firmness (MCF) on INTEM were, respectively, 177 (160-207) sec, 144 (108-178) sec and 48 (42-52) mm. On EXTEM, median (IQR) CT, CFT and MCF were, respectively, 69 (65-78) sec, 148 (126-198) sec and 49 (44-55) mm. Median (IQR) MCF on FIBTEM was 15 (13-18) mm. CONCLUSION: Thromboelastometry impairment is highly prevalent in DVI patients with thrombocytopenia, particularly in INTEM and EXTEM analyses, while standard coagulation tests are normal in this setting. Clinical implications remain to be established.

Time course of blood lactate levels, inflammation, and mitochondrial function in experimental sepsis.

BACKGROUND: A decrease in blood lactate levels (Lac) >10% during the first hours of resuscitation in sepsis is associated with better outcomes, but the mechanisms are unclear. Our objective was to investigate the relationship between the time course of Lac, inflammatory response, and mitochondrial respiration during experimental sepsis. METHODS: Original data from two previously published studies were reanalyzed. In cohort 1, pigs were randomized to be resuscitated for 48 h starting at 6, 12, and 24 h, respectively, after fecal peritonitis induction (n = 8 each). Animals were categorized according to the decrease in Lac during the first 6 h of resuscitation (early if ≥10% [Lac ≥10%] or late if <10% or increased [Lac <10%]), and systemic hemodynamics, inflammatory parameters, and mitochondrial function were compared between groups. In a second group of animals with fecal peritonitis and 24 h of resuscitation (n = 16, cohort 2), abdominal regional Lac exchange was measured, and animals were categorized according to the decrease in Lac as in cohort 1. RESULTS: Overall mortality was 20% (4 of 20) in the Lac ≥10% group and 60% (12 of 20) in the Lac <10% group (p = 0.022). In cohort 1, systemic hemodynamics were similar in the Lac ≥10% (n = 13) and Lac <10% (n = 11) groups. Plasma interleukin-6 levels increased during unresuscitated sepsis and decreased during resusciation in both groups, but they were lower at study end in the Lac ≥10% group (p = 0.047). Complexes I and II maximal (state 3) and resting (state 4) isolated brain mitochondrial respiration at study end was higher in the Lac ≥10% group than in the Lac <10% group, whereas hepatic, myocardial, and skeletal muscle mitochondrial respiration was similar in both groups. In cohort 2, mesenteric, total hepatic, and renal blood flow at study end was higher in the Lac ≥10% group (n = 7) than in the Lac <10% group (n = 9), despite similar cardiac output. Hepatic lactate influx and uptake in the Lac ≥10% group were approximately 1.5 and 3 times higher, respectively, than in the Lac <10% group (p = 0.066 for both). CONCLUSIONS: A decrease in Lac >10% during early resuscitation (6 h) after abdominal sepsis is associated with lower levels of plasma interleukin-6 and improved brain but not hepatic or muscle mitochondrial respiration. Blood flow redistribution to abdominal organs in animals with early decrease in Lac concentrations increases the potential to both deliver and extract Lac.

Arterial blood pressure targets in septic shock: is it time to move to an individualized approach?

Xu and colleagues evaluated the impact of increasing mean arterial blood pressure levels through norepinephrine administration on systemic hemodynamics, tissue perfusion, and sublingual microcirculation of septic shock patients with chronic hypertension. The authors concluded that, although increasing arterial blood pressure improved sublingual microcirculation parameters, no concomitant improvement in systemic tissue perfusion indicators was found. Here, we discuss why resuscitation targets may need to be individualized, taking into account the patient's baseline condition, and present directions for future research in this field.

Performance of noninvasive ventilation in acute respiratory failure in critically ill patients: a prospective, observational, cohort study.

BACKGROUND: Noninvasive ventilation (NIV) is used in critically ill patients with acute respiratory failure (ARF) to avoid endotracheal intubation. However, the impact of NIV use on ARF patient's outcomes is still unclear. Our objectives were to evaluate the rate of NIV failure in hypoxemic patients with an arterial carbon dioxide partial pressure (PaCO2) < 45 mmHg or ≥ 45 mmHg at ICU admission, the predictors of NIV failure, ICU and hospital length of stay and 28-day mortality. METHODS: Prospective single center cohort study. All consecutive patients admitted to a mixed ICU during a three-month period who received NIV, except for palliative care purposes, were included in this study. Demographic data, APACHE II score, cause of ARF, number of patients that received NIV, incidence of NIV failure, length of ICU, hospital stay and mortality rate were compared between NIV failure and success groups. RESULTS: Eighty-five from 462 patients (18.4 %) received NIV and 26/85 (30.6 %) required invasive mechanical ventilation. NIV failure patients were comparatively younger (67 ± 21 vs. 77 ± 14 years; p = 0.031), had lower arterial bicarbonate (p = 0.005), lower PaCO2 levels (p = 0.032), higher arterial lactate levels (p = 0.046) and APACHE II score (p = 0.034) compared to NIV success patients. NIV failure occurred in 25.0 % of patients with PaCO2 ≥ 45 mmHg and in 33.3 % of patients with PaCO2 < 45 mmHg (p = 0.435). NIV failure was associated with an increased risk of in-hospital death (OR 4.64, 95 % CI 1.52 to 14.18; p = 0.007) and length [median (IQR)] of ICU [12 days (8-31) vs. 2 days (1-4); p < 0.001] and hospital [30 (19-42) vs. 15 (9-33) days; p = 0.010] stay. Predictors of NIV failure included age (OR 0.96, 95 % CI 0.93 to 0.99; p = 0.007) and APACHE II score (OR 1.13, 95 % CI 1.02 to 1.25; p = 0.018). CONCLUSION: NIV failure was associated with an increased risk of in-hospital death, ICU and hospital stay and was not affected by baseline PaCO2 levels. Patients that failed were comparatively younger and had higher APACHE II score, suggesting the need for a careful selection of patients that might benefit from NIV. A well-designed study on the impact of a short monitored NIV trial on outcomes is needed.

Increasing mean arterial blood pressure in sepsis: effects on fluid balance, vasopressor load and renal function.

INTRODUCTION: The objective of this study was to evaluate the effects of two different mean arterial blood pressure (MAP) targets on needs for resuscitation, organ dysfunction, mitochondrial respiration and inflammatory response in a long-term model of fecal peritonitis. METHODS: Twenty-four anesthetized and mechanically ventilated pigs were randomly assigned (n = 8/group) to a septic control group (septic-CG) without resuscitation until death or one of two groups with resuscitation performed after 12 hours of untreated sepsis for 48 hours, targeting MAP 50-60 mmHg (low-MAP) or 75-85 mmHg (high-MAP). RESULTS: MAP at the end of resuscitation was 56 ± 13 mmHg (mean ± SD) and 76 ± 17 mmHg respectively, for low-MAP and high-MAP groups. One animal each in high- and low-MAP groups, and all animals in septic-CG died (median survival time: 21.8 hours, inter-quartile range: 16.3-27.5 hours). Norepinephrine was administered to all animals of the high-MAP group (0.38 (0.21-0.56) mcg/kg/min), and to three animals of the low-MAP group (0.00 (0.00-0.25) mcg/kg/min; P = 0.009). The high-MAP group had a more positive fluid balance (3.3 ± 1.0 mL/kg/h vs. 2.3 ± 0.7 mL/kg/h; P = 0.001). Inflammatory markers, skeletal muscle ATP content and hemodynamics other than MAP did not differ between low- and high-MAP groups. The incidence of acute kidney injury (AKI) after 12 hours of untreated sepsis was, respectively for low- and high-MAP groups, 50% (4/8) and 38% (3/8), and in the end of the study 57% (4/7) and 0% (P = 0.026). In septic-CG, maximal isolated skeletal muscle mitochondrial Complex I, State 3 respiration increased from 1357 ± 149 pmol/s/mg to 1822 ± 385 pmol/s/mg, (P = 0.020). In high- and low-MAP groups, permeabilized skeletal muscle fibers Complex IV-state 3 respiration increased during resuscitation (P = 0.003). CONCLUSIONS: The MAP targets during resuscitation did not alter the inflammatory response, nor affected skeletal muscle ATP content and mitochondrial respiration. While targeting a lower MAP was associated with increased incidence of AKI, targeting a higher MAP resulted in increased net positive fluid balance and vasopressor load during resuscitation. The long-term effects of different MAP targets need to be evaluated in further studies.

Characteristics, risk factors, and outcomes of bloodstream Candida infections in the intensive care unit: a retrospective cohort study.

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.

COVID-19-associated coagulopathy and acute kidney injury in critically ill patients.

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.

Clinical characteristics and outcomes of patients with COVID-19 admitted to the intensive care unit during the first and second waves of the pandemic in Brazil: a single-center retrospective cohort study.

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.

Dapagliflozin in patients with critical illness: rationale and design of the DEFENDER study.

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.

A nationwide survey on health resources and clinical practices during the early COVID-19 pandemic in Brazil. / Estudo nacional sobre recursos da saúde e práticas clínicas durante o início da pandemia da COVID-19 no Brasil.

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.

OBJETIVO: Avaliar as práticas clínicas e a organização dos recursos hospitalares durante o início da pandemia da COVID-19 no Brasil. METÓDOS: Foi realizado um estudo transversal multicêntrico. Um questionário on-line foi disponibilizado a médicos dos serviços de emergência e das unidades de terapia intensiva que atendiam pacientes com COVID-19. O questionário contemplava quatro aspectos: perfil dos participantes, práticas clínicas, protocolos de tratamento da COVID-19 e organização dos recursos hospitalares. RESULTADOS: Entre maio e junho de 2020, 284 participantes (56,3% homens), com idade mediana de 39 (intervalo interquartil de 33 - 47), responderam ao questionário; 33% eram intensivistas e 9% eram especialistas em medicina de emergência. Metade dos respondentes trabalhava em hospitais públicos. Verificou-se que a ventilação não invasiva (89% versus 73%; p = 0,001) e a cânula nasal de alto fluxo (49% versus 32%; p = 0,005) encontravam-se mais frequentemente disponíveis em hospitais privados do que nos públicos. A ventilação mecânica foi mais frequentemente utilizada em hospitais públicos do que em privados (70% versus 50%; p = 0,024). Nos serviços de emergência, a pressão positiva expiratória final foi mais frequentemente ajustada de acordo com a saturação de oxigênio, enquanto nas unidades de terapia intensiva, a pressão positiva expiratória final foi ajustada de acordo com a melhor complacência pulmonar. Nos serviços de emergência, 25% dos respondentes não sabiam como ajustar a pressão positiva expiratória final. Comparativamente aos hospitais privados, os hospitais públicos tiveram menor disponibilidade de protocolos para Equipamentos de Proteção Individual durante a intubação traqueal (82% versus 94%; p = 0,005), o manejo da ventilação mecânica (64% versus 75%; p = 0,006) e o desmame dos pacientes da ventilação mecânica (34% versus 54%; p = 0,002). Finalmente, os pacientes passaram menos tempo no serviço de emergência antes de serem transferidos à unidade de terapia intensiva em hospitais privados do que em hospitais públicos (idade mediana de 2 (1 - 3) versus idade mediana de 5 (2 - 24) horas; p < 0,001). CONCLUSÃO: Este estudo revelou heterogeneidade considerável entre os médicos em termos de organização dos recursos hospitalares, práticas clínicas e tratamentos durante o início da pandemia da COVID-19 no Brasil.

Antimicrobial Stewardship Programs: A Review of Strategies to Avoid Polymyxins and Carbapenems Misuse in Low Middle-Income Countries.

Antibiotics misuse and overuse are concerning issues worldwide, especially in low middle-income countries. These practices contribute to the increasing rates of antimicrobial resistance. One efficient strategy to avoid them is antimicrobial stewardship programs. In this review, we focus on the possible approaches to spare the prescription of polymyxins and carbapenems for the treatment of Acinetobacter baumannii, carbapenem-resistant Enterobacterales, and Pseudomonas aeruginosas infections. Additionally, we highlight how to implement cumulative antibiograms and biomarkers to a sooner de-escalation of antibiotics.

Analysis of mobility level of COVID-19 patients undergoing mechanical ventilation support: A single center, retrospective cohort study.

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.

Ketamine use in critically ill patients: a narrative review. / Uso de cetamina em pacientes críticos: uma revisão narrativa.

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.

A cetamina é única entre os anestésicos e analgésicos. A droga é um anestésico geral de ação rápida que produz um estado anestésico caracterizado por analgesia profunda, reflexos faríngeolaríngeos preservados, tônus músculo esquelético normal ou ligeiramente aumentado, estimulação cardiovascular e respiratória e, ocasionalmente, insuficiência respiratória transitória e mínima. Estudos demonstraram a eficácia de seu uso em anestesia, na dor, em cuidados paliativos e em cuidados intensivos. Recentemente, tem sido empregada para dores pós-operatórias e crônicas, como coadjuvante em psicoterapia, como tratamento para depressão e transtorno de estresse pós-traumático, como sedativo para procedimentos cirúrgicos e como tratamento para condições clínicas respiratórias e/ou neurológicas. Apesar de ser um medicamento seguro e amplamente utilizado, muitos médicos, como intensivistas e emergencistas, não estão cientes das aplicações clínicas atuais da cetamina. O objetivo desta revisão bibliográfica narrativa é apresentar aspectos teóricos e práticos das aplicações clínicas da cetamina em ambientes de unidade de terapia intensiva e serviços de emergência.

Statistical analysis of a cluster-randomized clinical trial on adult general intensive care units in Brazil: TELE-critical care verSus usual Care On ICU PErformance (TELESCOPE) trial. / Plano de análise estatística de um ensaio clínico randomizado em cluster em unidades de terapia intensiva geral adulto no Brasil: TELE-critical care verSus usual Care On ICU PErformance (TELESCOPE).

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.

OBJETIVO: O ensaio TELE-critical Care verSus usual Care On ICU PErformance (TELESCOPE) visa avaliar se uma intervenção complexa por telemedicina em unidades de terapia intensiva, que se concentra em rondas multidisciplinares diárias realizadas por intensivistas a distância, reduzirá o tempo de permanência na unidade de terapia intensiva em comparação com os cuidados habituais. MÉTODOS: O TELESCOPE é um ensaio nacional, multicêntrico, controlado, aberto, randomizado em cluster. O estudo testa a eficácia de rondas multidisciplinares diárias realizadas por um intensivista por meio de telemedicina em unidades de terapia intensiva brasileiras. O protocolo foi aprovado pelo Comitê de Ética em Pesquisa local do centro coordenador do estudo e pelo Comitê de Ética em Pesquisa local de cada uma das 30 unidades de terapia intensiva, de acordo com a legislação brasileira. O ensaio está registado no ClinicalTrials.gov (NCT03920501). O desfecho primário é o tempo de internação na unidade de terapia intensiva, que será analisado considerando o período basal e a estrutura dos dados em cluster, sendo ajustado por covariáveis predefinidas. Os desfechos exploratórios secundários incluem a classificação de desempenho da unidade de terapia intensiva, a mortalidade hospitalar, a incidência de infecções nosocomiais, o número de dias sem ventilação mecânica aos 28 dias, a taxa de pacientes que recebem alimentação oral ou enteral, a taxa de pacientes sob sedação leve ou em alerta e calmos e a taxa de pacientes sob normoxemia. CONCLUSÃO: De acordo com as melhores práticas do ensaio, divulgamos nossa análise estatística antes de bloquear a base de dados e iniciar as análises. Esperamos que essa prática de notificação evite o viés das análises e aprimore a interpretação dos resultados apresentados.Registro no ClinicalTrials.gov: NCT03920501.

Effects of balanced solution on short-term outcomes in traumatic brain injury patients: a secondary analysis of the BaSICS randomized trial. / Efeitos da solução balanceada em desfechos de curto prazo em pacientes com traumatismo craniencefálico: uma análise secundária do ensaio clínico randomizado BaSICS.

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.

OBJETIVO: Descrever os efeitos do uso de soluções balanceadas nos desfechos de curto prazo de pacientes com traumatismo craniencefálico incluídos no estudo BaSICS. MÉTODOS: Os pacientes foram randomizados para receber solução salina 0,9% ou solução balanceada durante a internação em unidade de terapia intensiva. O desfecho primário foi mortalidade em 90 dias, já os desfechos secundários foram dias de vida e sem internação em unidade de terapia intensiva aos 28 dias. O desfecho primário foi avaliado por regressão logística bayesiana. O desfecho secundário foi avaliado usando regressão beta-binomial inflada de zeros bayesiana. RESULTADOS: Incluímos 483 pacientes (236 no braço de solução salina 0,9% e 247 no braço de solução balanceada). Foram incluídos 338 pacientes (70%) com pontuação na escala de coma de Glasgow ≤ 12. A probabilidade geral de que soluções balanceadas estivessem associadas a maior mortalidade em 90 dias foi de 0,98 (RC de 1,48; ICr95% 1,04 - 2,09). Esse aumento de mortalidade foi particularmente perceptível em pacientes com pontuação na escala de coma de Glasgow abaixo de 6 no momento da inclusão (probabilidade de dano de 0,99). Soluções balanceadas foram associadas a -1,64 dia de vida e sem internação em unidade de terapia intensiva aos 28 dias (ICr95% -3,32 - 0,00) com probabilidade de dano de 0,97. CONCLUSÃO: Houve alta probabilidade de que soluções balanceadas estivessem associadas a alta mortalidade em 90 dias, menos dias de vida e sem internação em unidade de terapia intensiva aos 28 dias.ClinicalTrials.gov: NCT02875873.

Effect of spontaneous breathing on ventilator-free days in critically ill patients-an analysis of patients in a large observational cohort.

BACKGROUND: Mechanical ventilation can injure lung tissue and respiratory muscles. The aim of the present study is to assess the effect of the amount of spontaneous breathing during mechanical ventilation on patient outcomes. METHODS: This is an analysis of the database of the 'Medical Information Mart for Intensive Care (MIMIC)'-III, considering intensive care units (ICUs) of the Beth Israel Deaconess Medical Center (BIDMC), Boston, MA. Adult patients who received invasive ventilation for at least 48 hours were included. Patients were categorized according to the amount of spontaneous breathing, i.e., ≥50% ('high spontaneous breathing') and <50% ('low spontaneous breathing') of time during first 48 hours of ventilation. The primary outcome was the number of ventilator-free days. RESULTS: In total, the analysis included 3,380 patients; 70.2% were classified as 'high spontaneous breathing', and 29.8% as 'low spontaneous breathing'. Patients in the 'high spontaneous breathing' group were older, had more comorbidities, and lower severity scores. In adjusted analysis, the amount of spontaneous breathing was not associated with the number of ventilator-free days [20.0 (0.0-24.2) vs. 19.0 (0.0-23.7) in high vs. low; absolute difference, 0.54 (95% CI, -0.10 to 1.19); P=0.101]. However, 'high spontaneous breathing' was associated with shorter duration of ventilation in survivors [6.5 (3.6 to 12.2) vs. 7.6 (4.1 to 13.9); absolute difference, -0.91 (95% CI, -1.80 to -0.02); P=0.046]. CONCLUSIONS: In patients surviving and receiving ventilation for at least 48 hours, the amount of spontaneous breathing during this period was not associated with an increased number of ventilator-free days.