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ABSTRACT Objective To investigate the effects of lycopene supplementation on inflammation, lung histopathology and systemic DNA damage in an experimentally induced lung injury model, ventilated by conventional mechanical ventilation and high-frequency oscillatory ventilation, compared with a control group. Methods Fifty-five rabbits sampled by convenience were supplemented with 10mg/kg lycopene for 21 days prior to the experiment. Lung injury was induced by tracheal infusion of warm saline. The rabbits were randomly assigned to the control group and subjected to protective conventional mechanical ventilation (n = 5) without supplementation or the experimental group that was subjected to acute lung injury and provided conventional mechanical ventilation and high-frequency oscillatory ventilation with and without lycopene supplementation (n = 10 rabbits in each group). Lung oxidative stress and the inflammatory response were assessed based on the number of polymorphonuclear leukocytes in bronchoalveolar lavage fluid, DNA damage and pulmonary histological damage. Results A significant worsening of oxygenation and a decrease in static lung compliance was noted in all groups after pulmonary injury induction (partial pressure of oxygen before 451.86 ± 68.54 and after 71 ± 19.27, p < 0.05). After 4 hours, the high-frequency oscillatory ventilation groups with and without lycopene supplementation as well as the group receiving protective conventional mechanical ventilation with lycopene supplementation showed significant oxygenation improvement compared with the protective conventional mechanical ventilation group without supplementation (partial pressure of oxygen of the group with mechanical ventilation without lycopene of 102 ± 42, of the group that received conventional protective mechanical ventilation with lycopene supplementation of 362 ± 38, of the high-frequency group without lycopene supplementation of 420 ± 28 and of the high-frequency group with lycopene supplementation of 422 ± 25; p < 0.05). Compared with rabbits not receiving supplementation, those in the groups that received protective conventional mechanical ventilation with lycopene supplementation and high-frequency oscillatory ventilation with lycopene supplementation had significantly less inflammation as well as less histological injury (p < 0.05). Compared with rabbits subjected to protective conventional mechanical ventilation, significantly lower DNA damage was observed in rabbits supplemented with lycopene (p < 0.05). Conclusion Lycopene supplementation reduces inflammatory and histopathological lung injuries, regardless of the associated ventilatory mode. In addition, lycopene improved oxygenation and reduced DNA damage when protective conventional mechanical ventilation was used.

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ABSTRACT Objective To define the incidence of ventriculostomy-associated infections and their impact on the mortality and functional outcomes of patients with aneurysmal subarachnoid hemorrhage. Methods We prospectively included all consecutive adult aneurysmal subarachnoid hemorrhage patients admitted to the neurological intensive care units of the Instituto Estadual do Cérebro Paulo Niemeyer (Rio de Janeiro, Brazil) and Hospital Cristo Redentor (Rio Grande do Sul, Brazil) who required external ventricular drains from July 2015 to December 2020. Daily clinical and laboratory variables were collected at admission and during the hospital stay. The presence of ventriculostomy-associated infections was evaluated daily, according to the Centers for Disease Control and Prevention and Infectious Diseases Society of America criteria. Hospital and 12-month outcomes were compared between patients with and without ventriculostomy-associated infections via both univariate and multivariate analyses. Results Out of the 676 patients screened, 271 received external ventricular drains (40%) and were included in the study. The mean age was 54 years (IQR 46–63), 198 were female (72%), 47% had poor grade status (World Federation of Neurological Surgeons scale 4 and 5), and 75% had modified Fisher 3 or 4. The mean time from admission to external ventricular drain placement was 8.8 days. Ventriculostomy-associated infections developed in 127 patients (47%), and the mean time from external ventricular drain to ventriculostomy-associated infection diagnosis was 4.4 days. Hospital and 12-month mortality rates did not differ between the ventriculostomy-associated infection group and the nonventriculostomy-associated infection group (36% versus 40% and 43% versus 49%, respectively). Poor functional outcomes, defined as modified Rankin scores of 4 to 6, showed no difference between groups at hospital discharge (ventriculostomy-associated infections 75% versus nonventriculostomy-associated infections 73%; p = NS) or at 12 months (ventriculostomy-associated infections 49% versus nonventriculostomy-associated infections 53%; p = NS). Conclusion Ventriculostomy-associated infections are common complications after aneurysmal subarachnoid hemorrhage. Although it was not associated with hospital mortality or functional outcomes in our cohort, improving diagnostic accuracy and preventive measures is essential for better understanding the long-term impact of one of the most severe infectious complications after aneurysmal subarachnoid hemorrhage.

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ABSTRACT Objective Although the efficacy of high-flow nasal oxygen therapy in delaying or avoiding intubation in patients with hypoxemic respiratory failure has been studied, its potential for facilitating early weaning from invasive mechanical ventilation remains unexplored. Methods In this randomized controlled trial, 80 adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation for > 48 hours were enrolled and divided into two groups: conventional weaning and early weaning via high-flow nasal oxygen. In the conventional weaning group, the spontaneous breathing trial was performed after the PaO2/FiO2 ratio was ≥ 200, whereas in the high-flow nasal oxygen group, the spontaneous breathing trial was conducted earlier when the PaO2/FiO2 ratio was 150 - 200. Following each successful spontaneous breathing trial, patients were extubated and put on oxygen supplementation via a venturi mask or high-flow nasal oxygen on the basis of their group allocation. The primary objective was to compare extubation failure (reintubation within 48 hours). The secondary objectives were to compare total invasive mechanical ventilation, oxygen requirement and sedation requirement days, ventilator-associated pneumonia incidence, invasive mechanical ventilation-free days, intensive care unit length of stay, and intensive care unit all-cause mortality. Results Extubation failure was not significantly different between the high-flow nasal oxygen group and the conventional weaning group [12.5% versus 25%, respectively; odds ratio (95%CI) 0.5 (0.19 - 1.33)] (p = 0.25). Early weaning from invasive mechanical ventilation via high-flow nasal oxygen was associated with significantly increased invasive mechanical ventilation-free days and total oxygen requirement days (p = 0.02 and p = 0.01, respectively). No significant between-group differences were observed in total invasive mechanical ventilation days, ventilator-associated pneumonia incidence, intensive care unit length of stay, sedation duration, or all-cause mortality. Conclusion Among patients with acute hypoxemic respiratory failure, early extubation with high-flow nasal oxygen is a feasible and superior alternative to the conventional method of weaning, as it increases the number of invasive mechanical ventilation-free days.

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ABSTRACT Objective This study aimed to explore the association between high outliers and intensive care unit admissions and to identify the factors contributing to high intensive care unit costs. Methods This retrospective cohort study used data from 17 Belgian hospitals from 2018 and 2019. The study focused on the 10 most frequently admitted diagnosis-related groups in the intensive care unit. The dataset included medical discharge summaries and cost per stay from the hospital perspective. Results A total of 39,279 hospital stays were analyzed, 11,124 of which were intensive care unit admissions; additionally, 2,500 of these stays were high outliers. The proportion of high outliers was significantly greater in the intensive care unit group, and admission to the intensive care unit was significantly associated with high outliers in the multivariate analyses. Factors associated with high intensive care unit outliers included the medical diagnosis-related group category, patients from nursing homes, intensive care unit stay duration exceeding 4 days, and specific technical procedures (measurement of intracranial pressure, continuous hemofiltration, and mechanical ventilation). Conclusion Admission to the intensive care unit increases the likelihood of being classified as an outlier, thus significantly impacting hospital costs. This study identified factors that can be used to predict intensive care unit outliers, which can enable adjustments to diagnosis-related group-based funding for intensive care units.

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ABSTRACT Objective: To verify whether the rectus femoris muscle mass in mechanically ventilated patients assessed by ultrasonography at intensive care unit discharge is associated with functional status at hospital discharge. Methods: This cohort study was conducted at a tertiary hospital in Brazil between August 2019 and November 2020. We included patients over 18 years who were previously independent (Barthel index > 60) and underwent mechanical ventilation for at least 48 hours within 96 hours of admission. Ultrasonographic measurements of the rectus femoris cross-sectional area and right quadriceps thickness were performed upon enrollment, five days after enrollment, and at intensive care unit discharge. The primary outcome was assessing functional capacity via the Barthel index at hospital discharge. Results: Of the 78 patients included, 35 had assessable primary outcomes. Twenty (57.1%) patients were considered functionally dependent (Barthel index < 60). The Barthel index at hospital discharge was correlated with the cross-sectional area (r = 0.53; p = 0.001) and quadriceps thickness (r = 0.43; p = 0.01) at intensive care unit discharge. Multiple linear regression analysis revealed that the cross-sectional area at intensive care unit discharge was independently associated with the Barthel index. Conclusion: We found that muscle mass assessed by cross-sectional area ultrasonography at intensive care unit discharge was significantly correlated with functional capacity at hospital discharge.

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ABSTRACT Objective: The goal of this study was to assess the Portuguese Intensive Care Referral Network, namely the mission and organization of the Portuguese National Health Service Intensive Care Medicine Services and patient flows between them. Methods: The study was based on the responses to a semi-structured questionnaire by the directors of the forty-one Intensive Care Medicine Services, characterizing four domains: a) number, type, and management of beds; b) human resources and their consumption; c) outreach, including activities in the resuscitation room, intra-hospital emergency team and follow-up clinics; and d) referral network. Results: The number of active Intensive Care Medicine Services beds in Portugal markedly increased in the last 12 years, but the beds/habitant ratio is still below the Organization for Economic Cooperation and Development average. The activation of all installed beds would likely allow for the reduction of the hospital care gap perceived by many of the Intensive Care Medicine Services directors. There is significant geographic heterogeneity in the beds/habitant ratio and in the performance of outreach activities. The number of intensivists is rapidly growing, but nursing staff should be augmented, especially rehabilitation nurses. The referral network is globally complied, but the secondary transport of critical patients needs improvement and an electronic information system, which can be constantly updated, is seen as a relevant decision aid. Conclusion: Although intensive care medicine has significantly strengthened in the last 12 years, both in number of beds and in role and mission, there is still relevant heterogeneity in the beds/habitant ratio and in the performance of outreach activities among different Intensive Care Medicine Services.

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ABSTRACT Objective To identify predictive factors for failure in the installation of high-flow nasal cannulas in children diagnosed with acute viral bronchiolitis under 24 months of age admitted to the pediatric intensive care unit. Methods This work was a retrospective single-center cohort study conducted from March 2018 to July 2023 involving infants under 24 months of age who were diagnosed with acute viral bronchiolitis and who received high-flow nasal cannulas upon admission to the pediatric intensive care unit. Patients were categorized into two groups, the Success Group and Failure Group, on the basis of high-flow nasal cannula therapy efficacy. The primary outcome was treatment failure, which was defined as the transition to invasive or noninvasive ventilation. The analyzed variables included age, sex, weight, high-flow nasal cannula parameters, vital signs, risk factors, comorbidities, and imaging. Acute viral bronchiolitis severity was assessed using the Wood-Downes Scale, and functional status was assessed via the Functional Status Scale, both of which were administered by trained physiotherapists. Results In total, 162 infants with acute viral bronchiolitis used high-flow nasal cannulas, with 17.28% experiencing treatment failure. The significant differences between the Failure and Success Groups included age (p = 0.001), weight (p = 0.002), bronchiolitis severity (p = 0.004), initial high-flow nasal cannula flow (p = 0.001), and duration of use (p = 0.000). The cutoff values for initial flow (≤ 12L/min), weight (≤ 5kg), and Wood-Downes score (≥ 9 points) were determined from the ROC curves. Initial flow ≤ 12L/min was the most predictive for failure (AUC = 0.71; 95%CI: 0.61 - 0.84; p = 0.001). Multivariate analysis indicated that weight was a protective factor (RR = 0.87; 95%CI: 0.78 - 0.98), duration of use reduced the risk of failure (RR = 0.49; 95%CI: 0.38 - 0.64; p = 0.000), and Wood-Downes score was not significant (RR = 1.04; 95%CI: 0.95 - 1.14; p = 0.427). Weight explained 84.7% of the variation in initial flow. Conclusion Risk factors for high-flow nasal cannula therapy failure in bronchiolitis patients include younger age, consequently lower weight, and a lower initial flow rate.

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ABSTRACT Objective: To evaluate the ability of Brazilian pediatricians to recognize sepsis and septic shock in children. Methods: A cross-sectional multicenter survey was conducted among Brazilian pediatricians between May and June 2023, before the release of the new Phoenix sepsis criteria in 2024. An online electronic system was used for surveys to characterize the knowledge and skills of physicians in the diagnosis and treatment of sepsis in children. The questions related to the diagnosis and treatment of sepsis and septic shock in children were based on the International Pediatric Sepsis Consensus Conference, the American College of Critical Care Medicine Guidelines, and the Surviving Sepsis Campaign in Pediatrics. Descriptive statistical analyses were performed using R software. Results: Pediatricians were surveyed about the recognition, knowledge, and management of pediatric patients with sepsis and septic shock. The responses of 355 physicians from all regions of Brazil were analyzed, with the majority from the southeastern region of the country (53.3%). In clinical practice, the most utilized criteria for diagnosing sepsis included inappropriate tachycardia (92%), temperature alteration (88.2%), and the presence of a suspected or confirmed infectious focus (87.9%). For septic shock, capillary refill time alteration (87.1%), arterial hypotension (84.8%), and changes in the level of consciousness (82.2%) were the predominant indicators. A total of 55.6% pediatricians reported having the potential to obtain venous or intraosseous access within 5 minutes, and 59.3% could administer antibiotics within the first hour. Approximately one-quarter (27.5%) of the participants responded that it was possible to infuse 40 - 60mL/kg in 1 hour. The most commonly used solution for fluid resuscitation was isotonic saline (70.9%), followed by Ringer's lactate (45.0%). The infusion of a vasopressor was considered in patients who did not improve after receiving an infusion of 40 - 60mL/kg (75.8%). Conclusion: This is the first study to assess the knowledge of sepsis and septic shock among the Brazilian pediatric population. The results reveal a significant deficiency in the recognition of sepsis. This study demonstrated a gap between evidence and clinical practice. Adherence to international guidelines needs to be improved.

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ABSTRACT Objective Agitation is a major problem in the intensive care unit. However, no treatment has clearly emerged as effective and safe. Using target trial emulation, we aimed to test the hypothesis that early intervention with dexmedetomidine would accelerate agitation resolution. Methods We read clinical notes in an electronic medical records system with natural language processing to identify patients with agitation. We obtained their demographics, trajectories, associations, and outcomes. We used g-formulas to study the possible effects of dexmedetomidine on agitation resolution and key outcomes. Results We screened 7525 patients. Overall, 2242 patients (29.8%) developed within-intensive care unit agitation, and 2052 (27.3%) were eligible for inclusion in the target trial emulation, with 314 treated with dexmedetomidine. Dexmedetomidine-treated patients had more severe illness and were more likely to have unplanned emergency admissions with medical diagnoses. However, they achieved higher rates of resolution of within-intensive care unit agitation (94% versus 72%; p < 0.001) and lower 30-day mortality (5% versus 9%; p = 0.033). Early initiation of dexmedetomidine accelerated the resolution of agitation (risk ratio [RR] 1.13 [95%CI 1.03 - 1.21]; risk difference [RD] 9.8% [95%CI 2.6% - 15.4%]); extubation by Day 30 (RR 1.03 [95%CI 1.02 - 1.04]; RD 3.1% [95%CI 2.2% - 4.2%]); and reduced the chance of having a tracheostomy by Day 30 (RR 0.67 [95%CI 0.34 - 0.99]; RD -3.5% [95%CI -7.0% - -0.0%]) Conclusion Through target trial emulation analysis, early dexmedetomidine was associated with an increased rate of resolution of agitation and extubation and decreased tracheostomy risk.

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ABSTRACT Objective To perform a cross-cultural adaptation of the State Behavioral Scale to Brazilian Portuguese, assess its psychometric quality and use the scale to evaluate the level of sedation of patients on mechanical ventilation in the pediatric intensive care unit of a tertiary care hospital. Methods After receiving authorization by the main author, the State Behavioral Scale was adapted according to the following steps: translation of the original version into Portuguese; synthesis of the Portuguese versions; evaluation by a committee of judges; reverse translation by native speakers of the source language; synthesis of retroversions; pretest; and evaluation of psychometric quality. Results The adapted scale was administered to 20 patients by four evaluators, who performed daily evaluations in pairs simultaneously and independently. The intraclass correlation coefficient was 0.939 (p < 0.001) for the State Behavioral Scale and 0.976 (p < 0.001) for the COMFORT-B scale. The two scales were strongly correlated, with Spearman coefficients ranging from 0.884 to 0.908 (p < 0.001). In the study sample, most children (n = 43 observations; 48.9%) had scores of -1 (responsive to light touch or voice) or 0 (awake and able to calm down), which corresponded to light sedation. Conclusion The translated and adapted version of the State Behavioral Scale showed high interrater agreement and high correlation with the COMFORT-B scale. The application of the scale showed an adequate level of sedation in most patients.

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ABSTRACT Objective: To evaluate risk factors, molecular profiles, and hospital mortality of carbapenem-resistant Enterobacterales (CRE) infections in intensive care unit patients. Methods: In this retrospective, multicenter cohort study, intensive care unit admissions from 52 intensive care units between January 2019 and December 2020 were analyzed in a nested case-control design. Patients with carbapenem-resistant Enterobacterales infections were propensity score-matched 1:1 to those with carbapenem-susceptible Enterobacterales infections. Hierarchical conditional logistic regression identified risk factors for carbapenem-resistant Enterobacterales, and multivariable logistic regression assessed the association of carbapenem-resistant Enterobacterales with 60-day in-hospital mortality. Molecular genotyping was also conducted. Results: Matching resulted in 250 carbapenem-resistant Enterobacterales patients and 250 carbapenem-susceptible Enterobacterales patients. Sepsis was more common in the carbapenem-resistant Enterobacterales group (58% versus 35%; p < 0.001). Risk factors for carbapenem-resistant Enterobacterales included major premorbid assistance requirements (OR 1.72, 95%CI 0.99 - 3.01; p = 0.06) and intensive care unit readmission (OR 1.87, 95%CI 1.00 - 3.49; p = 0.05), although with weak associations. Acute COVID-19 (OR 3.55, 95%CI 1.96 - 6.45; p < 0.001) also increased the odds of resistance. Carbapenem-resistant Enterobacterales infection was associated with twice the likelihood of 60-day mortality after adjusting for covariates (OR 1.95, 95%CI 1.26 - 3.02; p < 0.001). The predominant bacteria and carbapenemase resistance genes included Klebsiella pneumoniae (79%), Klebsiella pneumoniae carbapenemase (73%), New Delhi metallo-beta-lactamase (13%), and xacillinase-48 (9%). Conclusion: Carbapenem-resistant Enterobacterales-related infections in intensive care unit patients were associated with major premorbid dependence, intensive care unit readmission, and acute COVID-19. In addition, carbapenem-resistant Enterobacterales infections were independently associated with poorer hospital outcomes. This study also characterized the resistance profile of Enterobacterales in Brazilian intensive care units, which are dominated by K. pneumoniae with high rates of carbapenemase and increased rates of New Delhi metallo-beta-lactamase, in comparison with previous reports.

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ABSTRACT Purpose: To translate, cross-culturally adapt and evaluate the clinimetric properties of the Chelsea Critical Care Physical Assessment for the functional evaluation of patients admitted to intensive care units in Brazil. Methods: The steps involved in the translation and cross-cultural adaptation of the instrument included the following: initial translation, synthesis, back-translation, review by an expert committee and pretesting. Intra- and interrater reliability and agreement were analyzed with data generated from physical therapists’ assessments of the same group of patients with the translated and adapted instrument (n = 30). The evaluations were performed by two physical therapists who independently and blindly obtained scores from the patients. Qualitative analysis was performed by the review committee with the expert-adapted and expert-synthesized translation of the Chelsea Critical Care Physical Assessment scale into Portuguese, and the content validity index was calculated. Results: Agreement was achieved between the translations of the Chelsea Critical Care Physical Assessment scale into Brazilian. Conceptual, idiomatic, semantic and experimental equivalences between the original and translated versions were obtained, resulting in the Brazilian version of the instrument, called the Avaliação Física em Cuidados Intensivos Chelsea, with a content validity index of 0.91. Evaluation of the clinimetric properties revealed evidence of high degrees of agreement and reliability, as all properties had an intraclass correlation coefficient above 0.75. The total intraclass correlation coefficient was 0.99. Conclusion: A version of the Chelsea Critical Care Physical Assessment scale can be reliably used in Brazil for functional assessment following its translation and cross-cultural adaptation to Brazilian Portuguese and shows evidence of excellent interrater reliability.

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ABSTRACT Objective: To describe the clinical profile, procedures applied and outcomes of patients undergoing palliative extubation in the pediatric intensive care unit at a high-complexity teaching hospital in the northeastern region of Brazil. Methods: This is a descriptive analysis of a case series that included patients aged under 14 years who underwent palliative extubation in the pediatric intensive care unit between 2016 and 2023 (seven years). Data on admission diagnoses, palliative extubation indications, applied therapies, and outcomes following palliative extubation were retrieved from medical records. Results: In total, 35 patients were included in the service database. In eight patients, reports could not be found, and these patients were excluded. Twenty-seven patients aged between five days and ten years, mostly females (51.8%) and those with chronic diseases (77.8%), were included in the study. All patients were classified on the basis of World Health Organization pediatric palliative care indication categories. Palliative extubation was considered after the identification of severe neurological impairment, inadequate response or absence of curative therapies, and failure of mechanical ventilation weaning. Palliative care approaches were discussed with the family in 74% of the cases before palliative extubation. Following palliative extubation, 48.1% of patients presented symptoms, and dyspnea (84.6%) and agitation (53.8%) were the most common symptoms. Death occurred in 88.8% of the children from 20 minutes to 38 days after palliative extubation at the hospital. Three children (11.2%) were discharged from the hospital. Conclusion: Palliative extubation was mostly performed in infants diagnosed with complex chronic conditions and severe and irreversible diseases, all of whom were referred to other palliative care. Death in the hospital while controlling for some symptoms was the main outcome.

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ABSTRACT Objective To evaluate the correlation and concordance of pulmonary artery systolic pressure values measured via right heart catheterization and estimated via transthoracic echocardiography based on data from a multicenter cohort of patients with pulmonary hypertension in Colombia. Methods A retrospective study was conducted of patients with pulmonary hypertension classified into Groups 1 or 4 according to the definitions of the ESC/ERS-PH-2022 guidelines. Patients were obtained from the Colombian Pulmonary Hypertension Network (HAPredco) database. Results A total of 633 patients were identified and included in this study. Among these patients, 77.7% (n = 492) had complete data from transthoracic echocardiography at diagnosis, 58,3% (n = 369) had complete data from right heart catheterization at the time of diagnosis, and 264 (41.7%) had complete data from both tests at diagnosis, with a difference in days between them of 1 (84). The values of pulmonary artery systolic pressure estimated by transthoracic echocardiography and those obtained by right heart catheterization were significantly correlated (p < 0.001) in the entire population evaluated, as was the correlation assessed for those patients with a gap of ≤ 7 days (p = 0.0001) or ≤ 48 hours (p = 0.041) between the two examinations; however, these findings presented a low Spearman (0.32 for ≤ 7 days and 0.264 for ≤ 48 hours) and Lin´s correlation coefficient (0.32 for ≤ 7 days and 0.21 for ≤ 48 hours). Conclusion The pulmonary artery systolic pressure values estimated via transthoracic echocardiography and measured via right heart catheterization were significantly but weakly linearly correlated, with low concordance. These findings suggest interindividual variability between the pulmonary artery systolic pressure values obtained by the two methods, which may have clinical significance in follow-up and decision-making.

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ABSTRACT Objective To evaluate the consistency of current evidence supporting the use of extracorporeal cardiopulmonary resuscitation to treat patients with cardiac arrest and assess the plausibility of implementing an extracorporeal cardiopulmonary resuscitation program in a public health care system hospital in a middle-income country. Methods A systematic review, meta-analysis, meta-regression analysis, and trial sequence analysis were performed to assess the consistency of current evidence supporting the use of extracorporeal cardiopulmonary resuscitation to treat patients with cardiac arrest. Additionally, a local cardiac arrest registry was analyzed to identify potential patients eligible for extracorporeal cardiopulmonary resuscitation. Results The systematic review included 31 studies. The main and sensitivity analyses consistently demonstrated that extracorporeal cardiopulmonary resuscitation was associated with favorable neurological outcomes (cerebral performance category 1 or 2, RR 1.45, 95%CI 1.19 - 1.77) and survival (RR 1.29, 95%CI 1.10 - 1.52). Age was inversely related to neurological outcome and survival. Our cardiac arrest registry included 55 patients with a median age of 54 years and a survival rate of 18.2% (10/55). Survivors had an initial shockable rhythm. In the most inclusive scenario, 13 patients would have been eligible for extracorporeal cardiopulmonary resuscitation. Under stricter criteria (age ≤ 65 years, low-flow time ≤ 30 min, and number of defibrillations ≥ 3), 4 patients would have been eligible. Conclusion Extracorporeal cardiopulmonary resuscitation in patients with refractory cardiac arrest is associated with improved neurological outcomes and survival. The use of an extracorporeal cardiopulmonary resuscitation program in our hospital is plausible. Using conservative eligibility criteria, we estimate that at least four patients would be eligible for extracorporeal cardiopulmonary resuscitation within six months of the program initiation.

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ABSTRACT Objective: Frailty is a multidimensional syndrome characterized by diminished physiological reserve, increasing the risk of adverse outcomes, particularly in intensive care unit patients. The Clinical Frailty Scale, ranging from 1 (nonfrail) to 9 (terminally ill), is widely used to quantify frailty. This post hoc analysis of the Palliative Multicenter Study in Intensive Care (PalMuSIC) assesses the impact of frailty and clinical severity on short- and long-term outcomes. Methods: This subanalysis involved 23 Portuguese intensive care units and 335 patients. Patients admitted between March 1 and May 15, 2019, aged ≥ 18 years, and hospitalized for > 24 hours in the intensive care unit were eligible. The severity of illness was assessed using SAPS II, and frailty was assessed using the clinical frailty scale, which was recorded by a nurse and a doctor in charge. Patients were classified as frail (clinical frailty scale score ≥ 5), prefrail (clinical frailty scale score = 4), or nonfrail (clinical frailty scale score < 4). The outcomes measured included intensive care unit and hospital LOS (length of stay), need for organ support, infections, mortality at hospital discharge and mortality at 6 months post discharge. We divided the population in half according to the length of their intensive care unit stay to evaluate a possible interaction between intensive care unit length of stay and frailty. Results: The mean age was 63.2 years, and 66% were male. The mean SAPS II score was 41.8. Frailty was observed in 23.0% of the patients. Frail patients had higher hospital mortality (39.0% frail patients versus 28.2% prefrail patients versus 11.8% nonfrail patients) and 6-month mortality (frail 49.4% frail patients versus 30.6% prefrail patients versus 15.6% nonfrail patients). Patients with longer intensive care unit stays had higher 6-month mortality rates than did those with shorter intensive care unit stays did, which resulted in more frail patients: odds ratio (95% confidence interval) 3.1 (1.2 - 7.8) versus odds ratio 1.8 (0.9 - 4.0) in nonfrail patients. Conclusion: Frailty may significantly impact hospital and 6-month mortality. In our cohort, a longer intensive care unit length of stay was associated with worse long-term outcomes, especially in frail patients.

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ABSTRACT Objective: This study aimed to compare sedation management during and after intubation in the emergency department with that in the intensive care unit. Methods: This was a single-center retrospective cohort study of adults who were intubated in the emergency department or intensive care unit and who received mechanical ventilation between January 2018 and February 2022. We collected data from electronic medical records. The primary outcome was the duration from intubation to the first documentation of light sedation, which was defined as a Sedation Agitation Scale score of 3 - 4. Results: This study included 264 patients, 95 (36%) of whom were intubated in the emergency department and 169 (64%) in the intensive care unit. With respect to the anesthetic agents used for intubation, ketamine was the most frequently used drug in the emergency department and was used more frequently than in the intensive care unit (61% versus 40%; p = 0.001). Propofol was the predominant sedative used in the intensive care unit, with a higher prevalence than in the emergency department (50% versus 33%; p = 0.01). Additionally, benzodiazepines and fentanyl were more frequently used in the intensive care unit (39% versus 6%; p < 0.001 and 68% versus 9.5%; p < 0.001, respectively). Within 24 hours after intubation, 68% (65/95) of the emergency department patients and 82% (138/169) of the patients intubated in the intensive care unit achieved light sedation, with median durations of 13.5 hours and 10.5 hours, respectively. Patients who were intubated in the emergency department were less likely to achieve light sedation at 24 hours (adjusted hazard ratio 0.64; p = 0.04; 95%CI, 0.42 - 0.97). Conclusion: Compared with intensive care unit patients, critically ill patients who were intubated in the emergency department are at risk of deeper sedation and a longer time to achieve light sedation.

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ABSTRACT Objective: To assess the accuracy of Brazilian television depictions of cardiopulmonary arrest, their management, and outcomes and to compare the observed outcomes with prior data from observational studies. Methods: Investigators screened episodes, identified cardiac arrest scenes, collected relevant information, and assessed outcomes. Cardiac arrest scenes were then analyzed using the American Heart Association guidelines. The primary outcome was survival with favorable neurologic outcomes. Secondary outcomes were the return of spontaneous circulation and the number of Advanced Cardiovascular Life Support deviations in each event. Results: Fifty-nine cardiac arrests were included in the study. Death occurred in 55.9% of patients, and return of spontaneous circulation was obtained in 54.2%. Survival rate was 44.1%, and 42.4% of the patients had favorable neurologic outcomes. Adherence to Advanced Cardiovascular Life Support guidelines did not demonstrate a significant impact on survival with favorable neurological outcomes, as evidenced by comparable odds ratios (0.86 [95%CI 0.22 - 2.36] for 3 - 5 deviations and 0.69 [95%CI 0.07 - 5.93] for ≥ 6 deviations using 0 - 2 deviations as reference). Television shows depicted a significantly higher proportion of favorable outcomes than real-world Brazilian cohorts for out-of-hospital and in-hospital scenarios (50% versus 20.5%, p = 0.107; and 43.3% versus 17.4%, p < 0.0001, respectively). Conclusion: In Brazilian television shows, the portrayal of cardiopulmonary resuscitation is inaccurate and tends to overstate the likelihood of favorable outcomes following cardiac arrests.

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ABSTRACT Background: There are notable gaps in the understanding of the underlying pathophysiology of persistent critical illness (PerCI) and its extensive implications for patient outcomes. In this context, whether different PerCI definitions could yield distinct long-term outcomes for intensive care unit survivors is currently unknown. Methods: This prospective cohort study spanned 10 Brazilian hospitals from March 2015 to December 2017. We enrolled emergency medical and surgical patients with intensive care unit stays exceeding 72 hours and tracked them for more than 12 months after intensive care unit discharge. Chronic patients were classified using four widely recognized persistent critical illness definitions from the literature: 1) mechanical ventilation > 21 days or tracheostomy for mechanical ventilation weaning; 2) mechanical ventilation duration > 14 days; 3) intensive care unit stay > 10 days; and 4) intensive care unit stay > 8 days accompanied by specific clinical conditions warranting extended intensive care unit care. Additionally, the data were compared to those of survivors who did not meet any of the four persistent critical illness criteria. Results: The study enrolled 1,616 patients, with 609 (37.7%) fulfilling one or more persistent critical illness definitions. The twelve-month survival rates among persistent critical illness patients varied by definition. At 12 months, patients with PerCI definitions centered on mechanical ventilation duration had markedly lower survival rates than non-persistent critical illness patients did (definition 1: HR: 1.49, 95%CI: 1.10 - 2.02; definition 2: HR: 1.66, 95%CI: 1.20 - 2.30). In contrast, definitions based on intensive care unit length of stay produced survival rates more aligned with non-persistent critical illness patients (definition 3: HR: 1.01, 95%CI: 0.82 - 1.25; definition 4: HR: 1.10, 95%CI: 0.88 - 1.30). Conclusion: Compared with other critically ill patients, patients with persistent critical illness definitions that are based on the duration of mechanical ventilation are associated with reduced 12-month survival, highlighting the impact of prolonged respiratory support on patient outcomes.

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ABSTRACT Purpose: Pain may pose significant challenges in the intensive care unit, especially in mechanically ventilated patients. Methadone has recently emerged as an alternative option for eliciting acute analgesia. In this systematic review, we evaluated the use of methadone in mechanically ventilated patients in the intensive care unit. Source: We searched MEDLINE, EMBASE, Wiley's Cochrane Library, CINAHL, PubMed (non-MEDLINE), Scopus, and LILACS databases from inception to January 24th, 2025. Eligible studies included randomized controlled trials and observational studies that compared the use of methadone to the standard of care or to other analgosedation strategies in mechanically ventilated patients in the intensive care unit. The primary outcome was the duration of mechanical ventilation. The secondary outcomes included opioid-associated adverse effects and scores regarding pain, agitation, and delirium. Principal findings: The search strategy yielded 3,523 studies. A total of 773 patients were included across the 12 studies (including 7 abstracts and 5 manuscripts). Patient populations included patients with trauma, those with burns, those at high risk for fentanyl abstinence syndrome, those with opioid use disorder, those with opioid withdrawal symptoms, and those who had received fentanyl for 72 hours prior to weaning. Overall, compared with the group that did not receive methadone, the methadone group was associated with more ventilator-free days, shorter weaning times, and a greater probability of successful weaning on day 5. Most of the studies exhibited high risks of bias; moreover, the overall quality of the evidence was low. Conclusion: Few studies have evaluated the use of methadone in mechanically ventilated patients. Based on the low-quality evidence, methadone may be associated with improved patient-centered outcomes. Further research is warranted with respect to this topic.

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ABSTRACT Objective To revisit the VENTIlatory Strategies for Patients with Severe Traumatic Brain Injury (VENTILO) survey, focusing on ventilatory management practices among healthcare professionals in low- and middle-income countries. Methodology A cross-sectional on-line survey, VENTIlatory strategies for patients with severe traumatic brain injury in the LOw- and Middle-Income CountrieS (VENTILOMICS), was conducted using the original VENTILO survey questionnaire, developed following a review of literature on respiratory management in traumatic brain injury patients, captured demographics of participants, type of hospital/specialty and available neuromonitoring tools; protocols for mechanical ventilation and weaning, and respiratory management strategies. Descriptive statistics were computed for all study variables. We analyzed data based on the economic status of the low- and middle-income countries. Results There were 204 respondents from 28 low- and middle-income countries. Our results indicate that 55 - 70% of respondents recommend tidal volumes of 6 - 8mL/kg for patients with high or medium partial pressure of arterial oxygen/inspired fraction of oxygen, while tidal volumes of 4 - 6mL/kg is preferred for those with low partial pressure of arterial oxygen/inspired fraction of oxygen ratios. For patients with intracranial hypertension, lower positive end-expiratory pressure levels were utilized. Conclusion The findings suggest a consistent approach to lung-protective ventilation across low-and middle-income countries, with notable variations influenced by local resources and economic status. This study highlights the necessity for tailored research and guidelines to address the specific challenges faced in traumatic brain injury management within low-and middle-income countries.

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ABSTRACT Objective: To develop a score (Palineo score) to identify the palliative care needs of newborn patients admitted to a Brazilian neonatal intensive care unit of a tertiary maternity hospital that serves as a reference center for high-risk pregnancies, ensuring timely follow-up by a specialist. Methods: Patients were assessed by three specialists using a questionnaire that included the same clinical elements as those used for the Palineo score but did not assign scores to the criteria. The score was determined by the consensus reached by the specialists. A score was subsequently assigned to each component of the Palineo score, allowing for comparisons between the specialists’ assessments and the Palineo score. All the information was retrospectively obtained from the electronic medical records. Data were collected and evaluated on the third and seventh days of life and then weekly until discharge from the neonatal intensive care unit, transfer to another service, or death. The Palineo score was applied to each patient to establish discriminatory cutoff points for the classifications initially assigned by the specialists. Results: The score showed agreement across the evaluations (k = 0.85). The discriminant values of the Palineo score between patients classified as palliative intent and associated palliative care revealed exceptional accuracy for both the first application of the score (p < 0.001) and the final application (p < 0.001). The discriminant values between patients categorized as associated palliative care and those categorized as specialized palliative care showed exceptional accuracy for the first application (p = 0.005) and final application (p < 0.001) of the score. Conclusion: Despite exceptional accuracy, discrepant values should be considered with caution. This study should be replicated in a larger sample.

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ABSTRACT Objective: Implementing the Checklist for Early Recognition and Treatment of Acute Illness and Injury (CERTAIN) decision support tool for structured intensive care unit admission and rounding was associated with an increased adherence to best care practices. We determined whether this association was patient sex-dependent. Design: Post hoc analysis of CERTAIN. Setting: prospective multinational quality improvement study. Patients: Adult patients admitted to one of the participating intensive care units. Interventions: Implementation of the CERTAIN decision support tool. Measurements: We compared incidence rates of omission of delivery of ten best care practices, including deep vein thrombosis and peptic ulcer prophylaxis, head of bed elevation, daily oral care, spontaneous breathing trials, family conferences, assessment of need for central lines and urinary catheters, and prescription of antimicrobials and sedation, between sexes, before and after implementation of the decision support tool. In addition, we determined whether sex differences existed amongst high-and middle-income countries. Main results: CERTAIN comprised a total of 4,256 patients, with 588 females and 859 males before the implementation of the decision support tool and 1,169 females and 1,640 males after its implementation. Overall, there was no notable difference in care between sexes, neither before nor after implementation, and both sexes in high-income and middle-income countries experienced equal benefits from checklist implementation. Conclusion: The impact of a clinical decision support tool for structured intensive care unit admission and rounding on adherence to best care practices showed minimal variation between sexes.

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ABSTRACT Objective: To evaluate how secular changes in tidal volume and respiratory rate influence the mechanical power of ventilation during the first 24 hours in critically ill patients over two decades and to compare their effects in patients with high and low respiratory system compliance. Methods: This secondary analysis of the Amsterdam University Medical Center database included two time periods: 2003 to 2009 and 2010 to 2016. The primary endpoint was mechanical power. Analyses also assessed secular changes in mechanical power in patients with respiratory system compliance groups. Results: Among 4,877 patients (2,536 patients in 2003 - 2009, and 2,341 in 2010 - 2016), median tidal volume decreased (mean difference of −0.6 [-0.4 to −0.7] mL/kg predicted body weight; p < 0.01), median respiratory rate increased (mean difference of +1.0 [+0.75 to +1.25] breath/minute; p < 0.01), and median mechanical power fell from 12.1 (8.7 - 16.7) J/minute to 10.4 (7.6 - 14.6) J/minute (mean difference of −1.7 [-1.2 to −2.0] J/minute; p < 0.01). In patients with low respiratory system compliance, median mechanical power decreased more significantly (13.4 J/minute to 11.7 J/minute, mean difference of −1.7 J/minute; p < 0.01) compared to those with high respiratory system compliance (10.5 J/minute to 9.7 J/minute, mean difference of −0.8 J/minute; p < 0.01) despite comparable respiratory rate changes Conclusion: In this single-center cohort, secular changes in tidal volume and respiratory rate were associated with lower mechanical power, particularly in patients with low respiratory system compliance.

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ABSTRACT Objective To investigate the relationship between sonographic and radiological scores of lung edema with metrics of shunt, dead space, and respiratory mechanics in critically ill patients under invasive ventilation for greater than 24 hours. Methods This is a secondary analysis of a prospective observational study involving invasively ventilated critically ill patients. The radiographic assessment of lung edema score and the global lung ultrasound score were utilized to evaluate pulmonary edema. Measurements for assessing shunt and dead space included the ratio of partial pressure of oxygen to fraction of inspired oxygen ratio, ventilatory ratio, and corrected minute volume, respectively. Respiratory mechanics were assessed through dynamic respiratory system compliance, driving pressure, and mechanical power of ventilation. Results A total of 364 invasively ventilated patients were included; one-third of them were classified as having acute respiratory distress syndrome. Median radiographic assessment of lung edema and global lung ultrasound scores were 15 [8 to 20] and 7 [3 to 13], respectively. Both scores explained little of the variance in partial pressure of oxygen to fraction of inspired oxygen ratio, ventilatory ratio, corrected minute volume, respiratory system compliance, driving pressure, and mechanical power (R2 = 0.05-0.12). Patients without acute respiratory distress syndrome exhibited a stronger association between the radiographic assessment of lung edema score and partial pressure of oxygen to fraction of inspired oxygen ratio, as well as between the global lung ultrasound score and respiratory system compliance. In contrast, patients with acute respiratory distress syndrome demonstrated stronger associations between the radiographic assessment of lung edema score and mechanical power and between the global lung ultrasound score and dead space metrics. A positive interaction of positive end-expiratory pressure was found only for the association between partial pressure of oxygen to fraction of inspired oxygen ratio and the radiographic assessment of lung edema and global lung ultrasound scores. Conclusion The radiographic assessment of lung edema score and the global lung ultrasound score poorly correlate with shunt, dead space, and respiratory mechanics metrics in invasively ventilated patients. A counterintuitive moderation effect of acute respiratory distress syndrome status is observed in some of these associations.

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ABSTRACT Objective Traumatic brain injury leads to disruption of the hypothalamic-pituitary axis. The aim of this study was to evaluate anterior pituitary gland function in the acute phase following traumatic brain injury and its relationship with patient outcomes. Methods This was a prospective cohort of traumatic brain injury patients admitted to the intensive care unit. The levels of adrenocorticotropic hormone, growth hormone, and thyroid-stimulating hormone on Days 0, 3 and 7 after the injury were measured. The Glasgow Outcome Scale-Extended (GOSE) was used for 6-month outcomes. Results A total of 88 traumatic brain injury patients (79% male, 41 ± 19 years old) who were admitted to the intensive care unit were studied. The frequencies of hormone levels below the range were as follows: adrenocorticotropic hormone, 81% on Day 0, 75% on Day 3, and 68% on Day 7; growth hormone, 76% on Day 0, 65% on Day 3, and 61% on Day 7; and thyroid-stimulating hormone, 42% on Day 0, 41% on Day 3, and 14% on Day 7. Traumatic brain injury severity was associated with Day 0 adrenocorticotropic hormone (p = 0.03) and Day 7 growth hormone (p = 0.03) levels and inversely associated with Day 3 thyroid-stimulating hormone (p = 0.03) levels. Glial fibrillary astrocytic protein was directly associated with Day 3 adrenocorticotropic hormone (OR 1.02, 95%CI 1.01 - 1.03; p < 0.001) and inversely associated with Day 7 thyroid-stimulating hormone (OR 1.02, 95%CI: 1.02 - 1.03; p = 0.04) levels. There was no significant association between hormone levels and mortality or the 6-month Glasgow Outcome Scale-Extended score. Conclusion Anterior pituitary hormone disturbances are common following a traumatic brain injury, and the degree of dysfunction is related to the injury severity. No associations were found with mortality or disability. Further investigations are warranted to standardize the measurement of pituitary function after traumatic brain injury and clarify its prognostic/therapeutic role.

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ABSTRACT Objective: To describe the epidemiology of patients requiring neurocritical care in intensive care units in Curitiba, Brazil, examine differences based on primary acute neurological diagnoses, and identify predictors of mortality and unfavorable intensive care unit outcomes. Methods: This was a retrospective cohort study involving patients aged 18 years or older who were admitted to the intensive care units of seven hospitals from January 2017 to December 2022. Patients admitted for primary neurological diagnoses were compared with those admitted for other causes. Cox regression models were used to assess factors associated with mortality and unfavorable outcomes (modified Rankin Scale scores of 4–6) in neurocritical care. Results: A total of 62,101 patients were included, with 10,884 admitted for neurological reasons. Compared with non-neurological patients, those with neurological diagnoses were significantly older and had lower levels of consciousness upon admission but lower APACHE II and SOFA scores, shorter intensive care unit stays, and lower mortality rates. Despite this, surviving patients admitted with neurological diagnoses experienced greater functional limitations. The leading causes of neurological admission included postoperative monitoring of intracranial surgery (32.6%), ischemic stroke (19%), traumatic brain injury (17%), seizure (7.1%), hemorrhagic stroke (6.5%), subarachnoid hemorrhage (4.5%), encephalopathy (4.2%), spinal cord conditions (3.8%), central nervous system infection (1.8%), neuromuscular diseases (0.8%), and other conditions (2.5%). Older age, use of vasoactive drugs upon admission, creatinine level ≥ 1.5mg/dL, lower level of consciousness within the first 24 hours, and primary neurological diagnoses of ischemic stroke, hemorrhagic stroke, subarachnoid hemorrhage, encephalopathy, and other conditions emerged as independent predictors of an increased hazard ratio of death and an unfavorable intensive care unit outcome. Conclusion: Patients admitted to intensive care units due to neurological disorders had lower mortality rates but developed higher degrees of functional dependence. Among neurocritically ill patients, those requiring vasoactive drugs upon admission, those with elevated creatinine levels (≥ 1.5mg/dL), and those admitted due to ischemic stroke, hemorrhagic stroke, or subarachnoid hemorrhage had a greater risk of death and unfavorable outcomes.

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ABSTRACT Objective: To perform a systematic literature review to summarise current evidence of the incidence and clinical impact of late-onset hyperlactatemia in intensive care patients about case-fatality and morbidity. Methods: MEDLINE, EMBASE, and ClinicalTrials.gov were searched using medical subject headings from database inception to 27 November 2024. Before the search, the protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO). Two independent reviewers screened the search results, and studies were included if they were original research that assessed late-onset hyperlactatemia in critically ill patients. Risk of bias was assessed using the Newcastle-Ottawa Scale, and the data were analysed using a descriptive approach without meta-analysis. Results: Of the 10,388 screened studies, 6 were included in the final manuscript, 5 retrospective and 1 prospective. All were assessed as good quality studies. Five were cardiac surgical patients, and one was general intensive care patients. All six studies reported the incidence of late-onset hyperlactatemia, which ranged from 8.5 to 70.8%. Two studies reported increased intensive care unit and/or hospital case-fatality with late-onset hyperlactatemia; however, small absolute numbers limited the interpretability. Conclusion: The limited data regarding late-onset hyperlactatemia make it difficult to draw significant conclusions regarding the relationship to clinical outcomes. However, the few available studies suggest that it is a common finding and highlight the need for further research to assess the underlying aetiologies and association with clinical outcomes.

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ABSTRACT Objective: To evaluate the impact of an ascending positive end-expiratory pressure titration strategy on respiratory mechanics and mechanical power in patients without lung injury. Methods: An incremental positive end-expiratory pressure titration was performed in 4cmH2O steps, starting from zero end-expiratory pressure and progressing to 16cmH2O. Differences (Δ) in respiratory system static compliance, plateau pressure, driving pressure, and mechanical power were assessed during lung-protective ventilation. Mechanical power formulas proposed by Gattinoni et al. and Costa et al. were used. Analyses were also performed on the static elastic components, dynamic elastic components, total elastic power, and resistive components. Results: Increasing positive end-expiratory pressure levels were associated with a progressive rise in mechanical power, plateau pressure, total and static elastic power, and a decline in compliance. Mechanical power showed strong positive correlations with: ΔPplat (p < 0.001); Δelastic dynamic power (p < 0.001); Δdriving pressure (p < 0.001); and Δtotal elastic power (p < 0.001). Δmechanical power correlated strongly with Δresistive power (p < 0.001), but not with other mechanical power components or mechanics. Conclusion: Progressive positive end-expiratory pressure increase in patients without lung disease significantly raises total mechanical power and its elastic components, particularly static elastic power. These changes may occur silently and without significant alterations in driving pressure or compliance.

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ABSTRACT Objective: To assess the perceptions of intensive care unit health care professionals in Brazil regarding postintensive care syndrome and the importance attributed to it by individuals and institutions. Methods: A web-based survey was conducted among intensive care unit professionals across all five Brazilian geopolitical regions. The questionnaire was used to collect demographic and professional data and to explore participants’ perceptions of postintensive care syndrome, including a focus on patient/family-centered outcomes and long-term intensive care unit consequences. Results: A total of 1,527 intensive care unit professionals responded, 61.3% of whom were women. The responses represented 12 professional categories, including physicians (51.1%), physiotherapists (16.9%), nurses (12.7%), and psychologists (5.8%). Among the participants, 50.4% had training or certification in critical care, and 59.9% had more than five years of experience. However, 24% had never heard of postintensive care syndrome. Awareness was significantly higher among those with specialized training (85.2% versus 66.6%; p < 0.001). Only 26.4% reported that their institutions had protocols for postintensive care syndrome assessment before hospital discharge. A significant difference emerged between individual and institutional priorities regarding patient/family-centered outcomes and postintensive care unit care (p < 0.001). In 60% of the cases, intensive care unit teams were not involved in patients’ hospital discharge. Conclusion: Despite moderate awareness of postintensive care syndrome among intensive care unit professionals, there is a considerable gap between staff and the institutional prioritization of postintensive care unit care in Brazil. This highlights the need to increase awareness and develop structured postintensive care unit care protocols, ensuring improved long-term outcomes for intensive care unit patients and their families.

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ABSTRACT Background ANDROMEDA-SHOCK 2 is an international, multicenter, randomized controlled trial comparing hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock to standard care resuscitation to test the hypothesis that the former is associated with lower morbidity and mortality in terms of hierarchal analysis of outcomes. Objective To report the statistical plan for the ANDROMEDA--SHOCK 2 randomized clinical trial. Methods We briefly describe the trial design, patients, methods of randomization, interventions, outcomes, and sample size. We portray our planned statistical analysis for the hierarchical primary outcome using the stratified win ratio method, as well as the planned analysis for the secondary and tertiary outcomes. We also describe the subgroup and sensitivity analyses. Finally, we provide details for presenting our results, including mock tables, baseline characteristics, and the effects of treatments on outcomes. Conclusion According to best trial practices, we report our statistical analysis plan and data management plan prior to locking the database and initiating the analyses. We anticipate that this practice will prevent analysis bias and improve the utility of the study’s reported results.

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ABSTRACT Background The perioperative management of patients undergoing cardiac surgery is highly complex and involves numerous factors. There is a strong association between cardiac surgery and perioperative complications. The Brazilian Surgical Identification Study (BraSIS 2) aims to assess the incidence of death and early postoperative complications, identify potential risk factors, and examine both the demographic characteristics of patients and the epidemiology of cardiovascular procedures. Methods and analysis BraSIS 2 is a multicenter observational study of patients who undergo cardiac surgery and who are admitted to the intensive care unit. The primary objective is to describe the risk factors and incidence of mortality or severe postoperative complications occurring within the first 3 postoperative days of cardiac surgery or until intensive care unit discharge (whichever event occurs first). Severe postoperative complications include acute myocardial infarction, acute respiratory distress syndrome, cardiorespiratory arrest with return of spontaneous circulation, Kidney Disease Improving Global Outcomes stage ≥ 2, a new surgical approach being conducted in an unscheduled event of urgency or emergency, renal replacement therapy, septic shock, severe bleeding, severe hemodynamic instability, stroke, unplanned reintubation, and unplanned use of a circulatory assistance device. The secondary outcomes include the evaluation of patient characteristics and descriptions of the performed surgeries and administered anesthesia. This study will also assess intraoperative and postoperative complications, as well as risk factors associated with postoperative complications and mortality. We expect to recruit 500 patients from at least 10 Brazilian intensive care units. Trial registration: NCT06154473; partial results.

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ABSTRACT Introduction: In patients with acute respiratory distress syndrome (ARDS), mortality risk is typically assessed using the arterial partial pressure of oxygen (PaO2) divided by the fraction of inspired oxygen (FiO2), known as the PaO2/FiO2 ratio. Recently, the SpO2/FiO2 ratio, which uses peripheral oxygen saturation (SpO2) instead of PaO2, has been suggested as a reasonable alternative when there is little access to arterial blood gas analyses. Additionally, equations that predict PaO2 from SpO2 values could offer another viable method for assessment. Aim: To evaluate the accuracy of methods for predicting PaO2 from SpO2 values and compare risk stratification based on measured versus predicted PaO2/FiO2 ratios using a large database that harmonizes the individual data of patients included in four observational studies. Methods and analysis: The individual data from four observational studies (‘Epidemiology of Respiratory Insufficiency in Critical Care study’ [ERICC], ‘Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure’ [LUNG SAFE], ‘PRactice of VENTilation in critically ill patients without ARDS’ [PRoVENT], and ‘PRactice of VENTilation in critically ill patients in Middle–income Countries’ [PRoVENT–iMiC]) were harmonized and pooled into a database named ‘PRoPERLy II’. The primary endpoint of this planned analysis will be the accuracy of currently available methods to predict PaO2 from SpO2 values. The secondary endpoint will be the accuracy of classification based on SpO2/FiO2 ratio and the predicted PaO2/FiO2 ratio. Dissemination: Our planned analysis addresses a clinically important research question by comparing different equations for predicting PaO2 from SpO2 values.

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ABSTRACT Introduction: This systematic review outlines a comprehensive approach to identify and analyze prognostic factors associated with mortality in adult cancer patients with sepsis in the intensive care unit. The review will focus on all-cause 28-day mortality, and where not available, we will use 30-day, intensive care unit, or in-hospital mortality. Methods and analysis: We present a protocol for the systematic review of prognostic factors for mortality in adult cancer patients with sepsis managed in the intensive care unit. Our primary outcome is 28-day mortality, and where not available, we will use 30-day, intensive care unit, or in-hospital mortality. The secondary outcome is the global mortality incidence. Studies on the basis of the population (sepsis and neoplasms), prognostic study methods and outcome of interest (mortality) will be included. We will search the following databases: Medline, PubMed, EMBASE, SCOPUS, Web of Science, and Bireme-BVS, until April 5, 2024. The risk of bias will be assessed using the QUIPS tool. A meta-analysis will be conducted where possible to generate pooled estimates for identified prognostic factors. Two authors will independently assess the risk of bias in each study using the Quality in Prognostic Studies tool. The GRADE approach will be employed to evaluate the overall quality of evidence and the strength of the recommendations. Findings will be disseminated through publication in a peer-reviewed journal. This review aims to provide clinicians with valuable insights into factors influencing mortality risk in this high-risk population, ultimately informing clinical decision-making and improving patient outcomes. Ethics and socialization: The results of this review will be published in a peer-reviewed scientific journal. Does not require ethical approval.

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ABSTRACT Objective: This manuscript describes the protocol of an investigator-initiated, international, multicenter, long-term, prospective observational study named PRactice of VENTilation in PEDiatric Patients (PRoVENT-PED), designed to investigate the epidemiology, respiratory support practices and outcomes of critically ill pediatric patients. Design: Data will be collected biannually over 10 years during predefined 4-week intervals, with an additional optional period to accommodate data collection during an epidemic or pandemic. The specific focus of PRoVENT-PED will evolve as the study progresses, initially emphasizing collecting detailed ventilator data from invasively ventilated patients. In later phases, the focus will shift to noninvasive respiratory support and typical aspects of respiratory support, like patient-ventilator asynchronies, weaning practices, and rescue therapies, as extracorporeal support. PRoVENT-PED includes patients under 18 years of age, admitted to a participating intensive care unit, and receiving respiratory support. The endpoints vary with the focus in each phase but will always include a set of key settings and ventilation parameters and related outcomes. If applicable, potentially modifiable factors and associations with outcomes will be studied. The pilot feasibility study demonstrated that the electronic capturing system effectively collects all necessary data within a reasonable time limit, with little missing data. Conclusion: PRoVENT-PED is a 10-year, international, multicenter study focused on collecting data on respiratory support practices in critically ill pediatric patients. Its scope evolves from invasive to noninvasive ventilatory support, ultimately encompassing patient-ventilator asynchronies, weaning practices, and rescue therapies.

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ABSTRACT Objective: To assess whether surface disinfection with organosilane in the intensive care unit reduces the occurrence of healthcare-associated infections. Methods: This multicenter, controlled, cluster-randomized trial includes 14 intensive care units in Brazil from November 2023 to December 2024. The local hygiene team of the included intensive care units will disinfect bed surfaces with organosilane or with usual care for 6 months, followed by a sequential crossover of another 6 months. The primary outcome is the incidence of healthcare-associated infections, specifically ventilator-associated pneumonia, central-line-associated bloodstream infections, and catheter-associated urinary tract infections. The secondary endpoints are the contamination of the environment by multidrug-resistant microorganisms (i.e., oxacillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, carbapenem-resistant Enterobacter, Pseudomonas, and Acinetobacter), the incidence of specific infections (i.e., ventilator-associated pneumonia, central-line associated bloodstream infection, and catheter-associated urinary tract infection) and the cost of the patient's intensive care unit stay. We will enroll all adult patients admitted after the study begins in each participant's intensive care unit. Ethics and dissemination: The institutional review board of the coordinator center and each enrolled center approved the study protocol. We will disseminate the results in peer-reviewed journals and at scientific meetings, regardless of the study's outcome.

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ABSTRACT Objective To identify modifiable intensive care unit factors associated with outcomes among patients receiving invasive mechanical ventilation in a low-income setting. Methods This prospective, multicenter, registry-embedded observational study has two components: a prospective registry-based cohort assessing patient- and care-process-related factors and a cross-sectional intensive care unit survey evaluating organizational structure. Functional intensive care units in Uganda will be included. Patients aged ≥ 15 years old requiring invasive mechanical ventilation will be enrolled. Patients extubated within 48 hours, transferred after > 24 hours, and imminent early death will be excluded. Primary outcomes will include 28-day intensive care unit mortality, intensive care unit length of stay, and mechanical ventilation duration. Tracheostomy-related outcomes will be explored in a pre-planned sub-study. Factors potentially associated with outcomes will be categorized into non-modifiable and potentially modifiable factors. Non-modifiable factors will include patient-related factors like age, comorbidities, and illness severity; potentially modifiable factors include processes of care (e.g., sedation levels) and intensive care unit organizational structure (e.g., staffing patterns). Multilevel multivariable logistic regression models will assess association outcomes. Survival analysis (Kaplan-Meier curves) will explore mortality trends. Confounders will be identified using directed acyclic graphs. Results (anticipated findings) This study will generate high-quality data on modifiable intensive care unit factors associated with ventilated patient outcomes in low-resource settings. Conclusion This is Uganda’s first registry-embedded, multicenter intensive care unit study to systematically potentially modifiable factors associated with ventilated patient outcomes. This study will provide evidence-based insights to optimize critical care management in low- and middle-income countries by leveraging real-time intensive care unit registry data.

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ABSTRACT Background: The optimal and safest hypnotic agent for rapid sequence intubation in critically ill patients remains uncertain. Factors such as hypovolemia, vasoplegia, hypoxemia, and acidosis can influence the efficacy and safety of induction agents. Propofol is commonly used for this purpose; however, it is associated with the risk of exacerbating hypotension. Ketamine, which has a more favorable hemodynamic profile, may offer a safer alternative in these patients. Objective: To assess whether ketamine is a safer alternative to propofol for rapid sequence intubation by reducing the incidence of hypotension during induction in critically ill patients. Methods: This will be a randomized, open-label, pragmatic, bicenter study. A total of 170 critically ill patients requiring endotracheal intubation in the intensive care unit will be randomly assigned to receive either ketamine or propofol as the hypnotic agent. Randomization will be conducted using RedCap with a 1:1 ratio and variable block sizes, stratified by study site and vasopressor use during intubation. Results: The primary outcome will be the occurrence of hypotension, defined as the lowest mean arterial pressure recorded within the first 10 minutes following induction. Secondary outcomes, assessed within 1-hour post-induction, include mortality, incidence of cardiopulmonary arrest, the occurrence of severe hypotension (systolic blood pressure < 80mmHg), the occurrence of severe hypoxemia (oxygen saturation < 85%), and the number of intubation attempts. Conclusion: The PROMINE study will provide valuable evidence to guide the selection of hypnotic agents for rapid sequence intubation in critically ill patients. It will contribute to a better understanding of the hemodynamic effects associated with propofol and ketamine in this context, potentially informing clinical practice.

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ABSTRACT Background: The effect of different levels of positive end-expiratory pressure in invasively ventilated critically ill patients remains a matter of debate. The REstricted versus Liberal Positive End-Expiratory Pressure in Patients Without ARDS (RELAx) is a multicentric, randomized trial comparing a lower positive end-expiratory pressure strategy versus a higher positive end-expiratory pressure strategy in ventilated patients without acute respiratory distress syndrome, which demonstrated non-inferiority of lower positive end-expiratory pressure compared to higher positive end-expiratory pressure on ventilator-free days. The primary analysis was published in 2020, and a frequentist statistical approach was applied. Aim: To present the protocol of the Bayesian analysis plan that will be used to re-analyse the RELAx trial to provide complementary and additional insight into this clinical trial. Methods: This re-analysis will focus on the probability of superiority of the intervention. As an ordinal variable, the primary outcome will be ventilator-free days at day 28, and posterior estimates will be obtained by fitting a hierarchical cumulative logistic regression model. Secondary outcomes will be mortality at day 28, as a binary outcome, and ventilation duration, as a continuous outcome. We will adopt neutral, pessimistic, and optimistic priors informed by current literature, and a fourth prior derived from an expert's survey. Probability thresholds will be defined for superiority, severe harm, and a region of practical equivalence. Discussion: The RELAx trial findings raise the hypothesis that a lower positive end-expiratory pressure strategy may be at least as effective, if not superior, in specific patient-centred outcomes. This analysis is designed to augment and contextualize the original frequentist analysis of the largest randomized trial comparing positive end-expiratory pressure strategies in non-acute respiratory distress syndrome patients. Results will be presented with a continuum of credible intervals and probabilities of effects to facilitate a nuanced interpretation. We offer clinically meaningful insights that complement and extend the trial's original analysis by reporting probabilities of benefit, harm, and equivalence.

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ABSTRACT Objective: To assess the impact of a multicomponent intervention on the health-related quality of life of patients with hypoxemic respiratory failure requiring invasive mechanical ventilation. Methods: A cluster stepped-wedge randomized clinical trial will be conducted in intensive care units across Brazil. Intensive care units with ≥ 8 beds and the capacity to admit patients with acute hypoxemic respiratory failure will be included. Within each intensive care unit, adult patients with acute hypoxemic respiratory failure requiring invasive mechanical ventilation, in whom SARS-CoV-2 infection is part of the differential diagnosis, will be enrolled. The intervention consists of a telemedicine-based quality improvement program focused on disability prevention and rehabilitation strategies, implemented during the patient's intensive care unit stay, continued through ward admission, and extending up to 2 months post-hospital discharge. The primary outcome is health-related quality of life assessed using the EuroQol 5-Dimension 3-Level scale 90 days after discharge from the hospital. Secondary outcomes include rehospitalization within 30 days from hospital discharge, as well as all-cause mortality, anxiety, depression, cognitive impairment, new disabilities for instrumental activities of daily living, and return to work or studies 90 days after discharge from the hospital. Results: The study protocol has been approved by the research ethics committees of all participant institutions. It was registered at ClinicalTrials.gov (NCT06343545) before the first participant was included. We aim to disseminate the findings through conferences and peer-reviewed journals. Conclusion: The "Tele-Rehab MV trial" may provide further information on the role of early multicomponent interventions aimed at disability prevention and rehabilitation for critically ill patients with acute hypoxemic respiratory failure.

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ABSTRACT Objective: To investigate whether continuous positive airway pressure during spontaneous breathing trial is non-inferior to pressure support by comparing both techniques in mechanically ventilated children. Methods: This is a multicenter, open-label, non-inferiority randomized controlled trial. The primary outcome is successful liberation from invasive mechanical ventilation for at least 48 hours post-extubation. Secondary outcomes include the need for post-extubation respiratory support and the length of stay in the pediatric intensive care unit. The sample size is estimated to be 170 participants. Non-inferiority will be assessed using the Farrington-Manning test. The trial registration number is NCT06593288 (clinicaltrials.gov). Infants older than 36 weeks corrected gestational age and < 18 years old admitted to the pediatric intensive care unit requiring invasive mechanical ventilation for at least 24 hours and ready to wean will be included. Patients with chronic pulmonary conditions, congenital heart disease, upper airway abnormalities, morbid obesity, and in palliative care will be excluded. Patients who have passed the extubation readiness test will be randomized to receive either continuous positive airway pressure or pressure support during a spontaneous breathing trial. Results: the results of the study should be ready and published within a year. Conclusion: The transition from mechanical ventilation to spontaneous breathing is a pivotal moment in the care of critically ill children. Yet, limited high-quality evidence informs the optimal approach to spontaneous breathing trials. Our protocol outlines a rigorously designed non-inferiority randomized controlled trial comparing spontaneous breathing trials conducted with and without pressure support.

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ABSTRACT Mechanical ventilation can be a life-saving intervention, but its implementation requires a multidisciplinary approach, with an understanding of its indications and contraindications due to the potential for complications. The management of mechanical ventilation should be part of the curricula during clinical training; however, trainees and practicing professionals frequently report low confidence in managing mechanical ventilation, often seeking additional sources of knowledge. Review articles, consensus statements and clinical practice guidelines have become important sources of guidance in mechanical ventilation, and although clinical practice guidelines offer rigorously developed recommendations, they take a long time to develop and can address only a limited number of clinical questions. The Associação de Medicina Intensiva Brasileira and the Sociedade Brasileira de Pneumologia e Tisiologia sponsored the development of a joint statement addressing all aspects of mechanical ventilation, which was divided into 38 topics. Seventy-five experts from all regions of Brazil worked in pairs to perform scoping reviews, searching for publications on their specific topic of mechanical ventilation in the last 20 years in the highest impact factor journals in the areas of intensive care, pulmonology, and anesthesiology. Each pair produced suggestions and considerations on their topics, which were presented to the entire group in a plenary session for modification when necessary and approval. The result was a comprehensive document encompassing all aspects of mechanical ventilation to provide guidance at the bedside. In this article, we report the methodology used to produce the document and highlight the most important suggestions and considerations of the document, which has been made available to the public in Portuguese.

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ABSTRACT Technological advances and interprofessional teamwork have significantly improved survival rates of critically ill patients. However, this progress has also introduced new challenges, such as intensive care unit-acquired weakness, which can contribute to postintensive care syndrome. Both conditions are associated with increased morbidity and mortality, prolonged length of hospital stay, higher social and health care costs, and reduced quality of life for patients and their families. Timely physical therapy plays a crucial role in mitigating intensive care unit-acquired weakness and postintensive care syndrome. Key recommendations for the effective rehabilitation of patients in the intensive care unit include education and training, communication and collaboration, patient screening, planning of activities, distribution of functions focused on teamwork, patient cooperation, safety assessments, patient positioning, functional mobilization, and documentation of outcomes. This narrative review aims to update the current understanding of the influence of physical therapy and critical care teamwork on intensive care unit patients and to provide evidence-based recommendations for promoting early mobilization in the intensive care unit setting.

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ABSTRACT Chronic dialysis patients account for a high proportion of intensive care unit admissions. The prevalent dialysis population is growing worldwide, accompanied by increasing medical complexity and comorbidities. Critical care physicians must be familiar with the unique clinical characteristics of this patient group. There is relatively little evidence specifically concerning the assessment and treatment of critically unwell individuals on long-term dialysis. This narrative review explores the approach to the management of chronic dialysis patients in the intensive care unit.

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ABSTRACT Respect for autonomy and human vulnerability are bioethical principles that are frequently involved in decision-making dilemmas in the context of critical care. Multiple challenges are involved in the tasks of assessing and respecting the autonomy of critically ill patients with respect to the critical illness in question, patients' cognitive status and the context of intensive care units; furthermore, time constraints and emotional stress complicate decision-making for all stakeholders in this context. In addition, critically ill patients are inherently vulnerable to multiple sources of potential unintended harm. Therefore, clinicians working in intensive care units must develop the skills necessary to acknowledge, assess and mitigate those risks. In this manuscript, we review the literature on this topic. We also propose a practical approach that can help overcome some of those challenges; specifically, we advocate for the adoption of a relational approach to autonomy and shared decision-making, which could help overcome those challenges, thereby promoting more effective and ethical patient care.

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ABSTRACT Significant physical and neuropsychiatric challenges, diminished life quality, and heightened demand for healthcare services often mark the period following discharge from the intensive care unit and hospitalization. Most follow-up care for these patients relies on clinic-based models, necessitating visits to healthcare facilities for rehabilitation and continued monitoring. However, this approach can create barriers for the most severely affected individuals, potentially worsening health inequities. In contrast, home care offers a viable solution by providing essential social support and assistance to patients with varying healthcare needs, allowing them to preserve their independence within the familiar environment of their own homes and communities. This model presents a promising alternative to the conventional clinic-based post-intensive care unit recovery system. It is cost-effective and better aligned with the preferences of an increasing number of individuals who choose to stay at home rather than move to institutional settings for care.

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ABSTRACT Bayesian analysis is being used with increasing frequency in critical care research and brings advantages and disadvantages compared to traditional Frequentist techniques. This study overviews this methodology and explains the terminology encountered when appraising this literature. Setting different priors can impact the interpretation of new results, and we describe an approach to understanding this. Finally, the strengths and challenges of adopting a Bayesian analysis compared to Frequentist techniques are explored.

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ABSTRACT Artificial intelligence technologies are rapidly advancing and significantly impacting healthcare, particularly in critical care environments where rapid, precise decision-making is crucial. They promise reductions in clinical errors, enhanced diagnostic accuracy, optimized treatment plans, and better resource allocation. Artificial intelligence applications are widespread across medical fields, with numerous artificial intelligence/machine learning-enabled medical devices approved by regulatory bodies, like the US Food and Drug Administration, aiding in diagnosis, monitoring, and personalized patient care. However, integrating artificial intelligence into healthcare presents challenges, notably the potential to exacerbate existing biases and disparities, especially when systems are trained on homogeneous datasets lacking diversity. Biased artificial intelligence can negatively affect patient outcomes for underrepresented groups, perpetuating health disparities. Additional concerns include data privacy and security, lack of transparency, algorithmic bias, and regulatory hurdles. Addressing these risks requires ensuring diverse and representative datasets, implementing robust auditing and monitoring practices, enhancing transparency, involving diverse perspectives in artificial intelligence development, and promoting critical thinking among healthcare professionals. Furthermore, the environmental impact of artificial intelligence, huge models reliant on energy-intensive data centers, poses challenges due to increased greenhouse gas emissions and resource consumption, disproportionately affecting low-income countries and exacerbating global inequalities. Systemic changes driven by corporate responsibility, government policy, and adopting sustainable artificial intelligence practices within healthcare are necessary. This narrative review explores the current landscape of artificial intelligence in healthcare, highlighting its potential benefits and delineating associated risks and challenges, underscoring the importance of mitigating biases and environmental impacts to ensure equitable and sustainable integration of artificial intelligence technologies in healthcare settings.

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ABSTRACT The PROtective VEntilation (PROVE) Network is a globally-recognized collaborative research group dedicated to advancing research, education, and collaboration in the field of mechanical ventilation. Established to address critical questions in intraoperative and intensive care ventilation, the network focuses on improving outcomes for patients undergoing mechanical ventilation in diverse settings, including operating rooms, intensive care units, burn units, and resource-limited environments in low- and middle-income countries. The PROVE Network is committed to generating high-quality evidence through a comprehensive portfolio of investigations, including randomized clinical trials, observational research, and meta-analyses. Its work has significantly contributed to understanding optimal ventilation strategies in critically ill patients, such as those with COVID-19, and in exploring innovative approaches like closed-loop ventilation systems. The network has spearheaded pioneering studies that have shaped clinical practice worldwide by integrating expertise from a wide range of disciplines. A defining feature of the PROVE Network is its emphasis on mentorship and collaboration. It fosters a supportive environment where junior researchers are guided by experienced mentors, ensuring the transfer of knowledge and promoting inclusivity. The network prioritizes gender balance and diversity, recognizing the value of varied perspectives in driving meaningful innovation and advancing research excellence. This paper reviews the history, key projects, and leadership of the PROVE Network, highlighting its impactful contributions to the field of mechanical ventilation. By uniting researchers globally, the PROVE Network exemplifies the power of collaboration in addressing complex clinical challenges, including personalized ventilation and the use of Artificial Intelligence, and improving patient care.

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ABSTRACT Objective To map the development and implementation of competency-based education in intensive care multiprofessional training on the basis of national and international literature. Methods A scoping review was conducted with searches in six databases and gray literature. Results The initial search identified 1,636 potentially eligible records, and 31 studies were included in the final sample. The data were grouped into three themes: development of competency-based education, implementation of competency-based education in curricula, continuing education and training programs, and student assessment. The studies were published between 2000 and 2024 and focused primarily on medical education, with a predominance of publications from North America and Europe. Heterogeneity was identified in the conceptual strategies of competency-based education, with an initial focus on skill lists evolving into core competencies, milestones, and entrustable professional activities. Benefits such as transparency in the learning process, individualized tracking, and the promotion of reflective learning were identified. Challenges to implementing effective competency-based education include the need for faculty training, resistance to change, a lack of time and resources, and the development of more robust assessment tools. The lack of studies on competency-based education in Latin America and the reduced number of studies in other health fields, such as nursing and physiotherapy, were highlighted. Conclusion Competency-based education appears promising for training in intensive care; however, further research is needed to assess its impact on quality of care and patient safety, as well as to broaden the discussion to include diverse contexts and health fields.

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ABSTRACT The cardiovascular system primarily delivers oxygen and nutrients to tissues. Oxygen delivery depends on cardiac output and arterial oxygen content. While left ventricular function is often emphasized, broader cardiovascular changes, including peripheral vascular function and right ventricular performance, are crucial, especially during shock or cardiopulmonary interactions with mechanical ventilation or fluid challenges. Indeed, the primary role of the left ventricle is to maintain a high central arterial pressure with a minimal filling pressure and to do so efficiently with every beat. Cardiac output is driven by tissue metabolic demand, as feeding arterioles adjust their vasomotor tone to autoregulate blood flow. These adjustments are reflected in proportional changes in venous return to the right ventricle. Right ventricular dysfunction reduces cardiac output primarily by causing systemic venous hypertension, a condition the cardiovascular system is poorly adapted to. Understanding these principles is vital for managing the optimization phase of shock resuscitation. In this narrative review, we aim to provide a comprehensive discussion of the physiological determinants of hemodynamics of circulatory function in shock. This structured yet flexible approach offers an integrative perspective on right ventricular and venous function, highlighting their complexity in hemodynamic regulation.

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ABSTRACT Background Rapid Response Teams have been widely implemented in high-income countries and play a crucial role in the early identification and management of clinically deteriorating patients. However, their implementation in low and middle-income settings has not been adequately described. Our goal was to map the current evidence in this setting. Methods We conducted a scoping review to map the published literature about Rapid Response Teams in low- and middle-income countries, according to year of publication, study type, team composition, reported outcomes, and potential roles of the team. Results After screening 6,679 studies, 52 fulfilled eligibility criteria: 36 full-text studies and 16 conference abstracts. Most of the studies were from Brazil (51.2%), followed by India (19.2%) and Turkey (7.7%), with the two earliest reports being conference abstracts published in 2009. The predominant design was before-and-after studies (20; 38.4%), followed by cohort studies (16; 30.8%). An intensive care unit physician was always a member of the Rapid Response Teams in 55.9% of the studies and an intensive care unit nurse in 23.5%. The number of Rapid Response Teams calls in the before-and-after studies ranged from 2.39 to 124 per 1,000 admissions. Reported outcomes varied, with most studies focusing on mortality (26, 50%) and code blue incidence (21; 40.4%). Four (7.7%) studies reported an active role of Rapid Response Teams in goals of care discussions. Conclusion We found that evidence on Rapid Response Teams in low- and middle-income countries remains limited, with a time lag in publications compared to high-income countries. Our findings highlight the need for further studies and policy initiatives to evaluate the effectiveness of implementing Rapid Response Teams in resource-constrained settings.

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ABSTRACT Apnea is a major complication of acute respiratory tract infection in young infants and may lead to the need for ventilatory support. Caffeine is methylxanthine, which is considered the mainstay of pharmacologic treatment for apnea of prematurity. On the basis of neonatal guidelines, caffeine has been used as a respiratory stimulant for the treatment of acute respiratory tract infection-related apnea, despite low evidence of its ability to improve clinical outcomes. Hyperlactatemia has been reported in adults with caffeine poisoning. Clarithromycin acts as an inhibitor of human cytochrome P450 and may impair drug metabolism. However, there are no published data concerning lactic acidosis associated with caffeine-clarithromycin coadministration. We report a case of hyperlactatemia in a young infant born prematurely who presented to the emergency department with acute respiratory tract infection-associated apnea and who required noninvasive ventilatory support. Because respiratory viruses were not detected in the nasopharyngeal aspirates and the chest radiography revealed interstitial opacities, clarithromycin (15mg/kg/day) was started via a nasoduodenal tube. In polysomnography, dysmaturity and immaturity of the central nervous system were evident. Hence, caffeine treatment was initiated at a loading dose of 10mg/kg followed by a maintenance dose of 5mg/kg/day. After treatment initiation, the child experienced ventilatory improvement and apnea control. However, a progressive increase in the serum lactate concentration and high anion gap metabolic acidosis were observed, despite hemodynamic stability. Following discontinuation of both drugs, the serum concentrations of lactate gradually returned to normal values. Thus, clarithromycin-caffeine coadministration may cause a sharp increase in lactate concentrations and should be avoided in young infants with acute respiratory tract infection-associated apnea.

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ABSTRACT A 26-year-old female with a history of depression was admitted after ingesting 7.5g of bupropion. Her clinical status rapidly deteriorated into a coma and myoclonic status, which was complicated by lung aspiration. Initial treatment with high-dose midazolam and later propofol failed to control her myoclonus. Sevoflurane inhalation therapy (6.5 mg/hour) was initiated, and complete resolution of myoclonus was achieved within hours. Propofol was discontinued, and the sevoflurane dose was gradually tapered over 24 hours without myoclonus recurrence. The patient awoke agitated but neurologically intact, was extubated, and fully recovered by Day 10. This case highlights the efficacy of sevoflurane in managing refractory myoclonic status due to bupropion toxicity, especially when electroencephalogram monitoring is unavailable. Sevoflurane rapid titration and elimination allow precise sedation control and safe neurological assessment. Inhaled anesthetics may also be beneficial in other ICU scenarios, including status epilepticus, severe asthma, and hemodynamic instability. This successful outcome demonstrates the potential of sevoflurane as an alternative therapy in critical toxicological emergencies.

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ABSTRACT In recent years, venovenous extracorporeal membrane oxygenation has become a critical therapeutic tool for patients with severe respiratory failure. Neurological complications, including brain death, are common in this population, and confirming brain death in venovenous extracorporeal membrane oxygenation-supported patients presents unique challenges. In Brazil, an apnea test is mandatory for confirming brain death. However, its application in patients on venovenous extracorporeal membrane oxygenation, which predominantly addresses venoarterial extracorporeal membrane oxygenation cases, is not well defined in the literature. This report outlines our standardized approach for conducting apnea tests in three patients with suspected brain death during ongoing venovenous extracorporeal membrane oxygenation support. We describe three cases from a cohort of 93 extracorporeal membrane oxygenation patients treated for severe respiratory failure. The apnea test was conducted after 24 hours of observation without sedation. Given the physiological nuances of extracorporeal membrane oxygenation, where carbon dioxide clearance is primarily influenced by sweep flow, we adopted a low-sweep-flow protocol (200mL/minute) to achieve a partial pressure of carbon dioxide greater than 55mmHg, consistent with brain death criteria. In cases of severe hypoxemia during the test, extracorporeal membrane oxygenation blood flow can be temporarily increased to maintain oxygenation. All patients received concurrent renal support, which also facilitated carbon dioxide clearance. Our findings suggest that the apnea test with very low sweep flow is a safe and feasible method for diagnosing brain death in venovenous extracorporeal membrane oxygenation-supported patients. This physiologically grounded approach provides a clinically viable strategy for managing the complex interplay between gas exchange, oxygenation, and carbon dioxide clearance during the apnea test.

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ABSTRACT Restoring immune homeostasis after an acute insult is essential for achieving a full recovery from an acute respiratory distress syndrome episode. Immune monitoring tools that are not exclusive to the blood compartment are in great demand to help guide treatment decisions. In this longitudinal study, we report a case of severe malaria-associated acute respiratory distress syndrome supported by venovenous extracorporeal membrane oxygenation. Although there was persistent lymphopenia, we observed dynamic shifts in T cells and rare innate lymphoid cell populations. The type 2 immune profile was preponderant at the acute phase, and decreased exhausted T-cell populations indicated recovery. There were significantly different blood and bronchoalveolar lavage fluid profiles. Multiple-compartment immune monitoring is possible and valuable for precise immune modulation.