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Background: Critically ill patients are at increased risk of health care-associated infections due to various devices (central line-associated bloodstream infection, catheter-associated urinary tract infection, and ventilator-associated pneumonia), which pose a significant threat to this population. Among several strategies, daily bathing with chlorhexidine digluconate, a water-soluble antiseptic, has been studied as an intervention to decrease the incidence of health care-associated infections in the intensive care unit; however, its ability to reduce all health care-associated infections due to various devices is unclear. We designed the Daily Chlorhexidine Bath for Health Care Associated Infection Prevention (CLEAN-IT) trial to assess whether daily chlorhexidine digluconate bathing reduces the incidence of health care-associated infections in critically ill patients compared with soap and water bathing., Methods: The CLEAN-IT trial is a multicenter, open-label, cluster randomized crossover clinical trial. All adult patients admitted to the participating intensive care units will be included in the trial. Each cluster (intensive care unit) will be randomized to perform either initial chlorhexidine digluconate bathing or soap and water bathing with crossover for a period of 3 to 6 months, depending on the time of each center's entrance to the study, with a 1-month washout period between chlorhexidine digluconate bathing and soap and water bathing transitions. The primary outcome is the incidence of health care-associated infections due to devices. The secondary outcomes are the incidence of each specific health care-associated infection, rates of microbiological cultures positive for multidrug-resistant pathogens, antibiotic use, intensive care unit and hospital length of stay, and intensive care unit and hospital mortality., Conclusion: The CLEAN-IT trial will be used to study feasible and affordable interventions that might reduce the health care-associated infection burden in critically ill patients.

Purpose: To evaluate the frequency of rapid response team (RRT) calls by time of day and their association with in-hospital mortality., Materials and Methods: This was a retrospective cohort study of all RRT calls at a tertiary teaching hospital in Porto Alegre, Brazil. Patients were categorized according to the time of initial RRT activation. Activations were classified as daytime (7:00-18:59) or nighttime (19:00-6:59). The primary outcome was in-hospital mortality rate. The secondary outcome was ICU admission within 48 h of RRT assessment., Results: During the study period, 4522 patients were included in the final analysis. Cardiovascular and respiratory changes were more common causes of nighttime activation, whereas neurological and laboratory changes were more common during the daytime. The in-hospital mortality rate was 23.9% (1081/4522). Nighttime RRT calls were not associated with worse outcomes than daytime calls. However, a decrease in the number of calls was observed during nursing handover periods (7:00, 13:00 and 19:00). Two time periods were associated with increased adjusted odds for mortality: 12:00-13:00 (adjusted OR 2.277; 95% CI 1.392-3.725) and 19:00-20:00 (adjusted OR 1.873; CI 1.873; 95% 1.099-3.190)., Conclusion: We found that nighttime RRT calls were not associated with worse outcomes than daytime RRT calls. However, a decrease in the number of calls and higher mortality was observed during nursing handover periods., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Serotonin is a mediator of pulmonary hypoxic vasoconstriction. Experimental studies have shown that serotonin-mediated pulmonary vasoconstriction can be inhibited by cyproheptadine. The aim of this study is to assess whether treatment with cyproheptadine compared to usual care increases ventilatory support-free days during the first 28 days in patients with coronavirus disease 2019 (COVID-19) requiring ventilatory support., Materials and Methods: This randomized, single-center, open-label clinical trial included patients who were admitted to the intensive care unit (ICU) requiring ventilatory support due to COVID-19. Patients allocated to the intervention group received cyproheptadine for 10 days. The primary outcome was ventilator-free days during the first 28 days., Results: Nineteen patients were randomized to receive cyproheptadine and 21 to the control group. The number of ventilatory support-free days during the first 28 days was not different between the two groups (15.0; 95% CI, 0.0-24.0 days in the control group vs 7.0; 95% CI, 0.0-19.0 days in the intervention group; p = 0.284)., Conclusion: In patients with COVID-19 and in need of ventilatory support, the use of cyproheptadine plus usual care, compared with usual care alone, did not increase the number of ventilatory support-free days in 28 days., How to Cite This Article: Boniatti MM, Nedel WL, Rihl MF, Schwarz P, Parolo E, Moretti MMS, et al . Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients with COVID-19: An Open-label, Randomized Clinical Trial. Indian J Crit Care Med 2023;27(7):517-521., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2023; The Author(s).)

Background: Viral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and co-infections are currently in limit. Thus, the primary purpose of this review is to perform an overarching investigation on the cases of latent virus reactivation and co-infection in COVID-19 patients to build collective evidence contributing to improving patient health. The aim of the study was to conduct a literature review to compare the patient characteristics and outcomes of reactivations and co-infections of different viruses., Methods: Our population of interest included confirmed COVID-19 patients who were diagnosed with a viral infection either concurrently or following their COVID-19 diagnosis. We extracted the relevant literature through a systematic search using the key terms in the online databases including the EMBASE, MEDLINE, Latin American Caribbean Health Sciences Literature (LILACS), from inception onwards up to June 2022. The authors independently extracted data from eligible studies and assessed the risk of bias using the Consensus-based Clinical Case Reporting (CARE) guidelines and the Newcastle-Ottawa Scale (NOS). Main patient characteristics, frequency of each manifestation, and diagnostic criteria used in studies were summarized in tables., Results: In total, 53 articles were included in this review. We identified 40 reactivation studies, 8 coinfection studies, and 5 studies where concomitant infection in COVID-19 patients was not distinguished as either reactivation or coinfection. Data were extracted for 12 viruses including IAV, IBV, EBV, CMV, VZV, HHV-1, HHV-2, HHV-6, HHV-7, HHV-8, HBV, and Parvovirus B19. EBV, HHV-1, and CMV were most frequently observed within the reactivation cohort, whereas IAV and EBV within the coinfection cohort. In both reactivation and coinfection groups, patients reported cardiovascular disease, diabetes, and immunosuppression as comorbidities, acute kidney injury as complication, and lymphopenia and elevated D-dimer and CRP levels from blood tests. Common pharmaceutical interventions in two groups included steroids and antivirals., Conclusion: Overall, these findings expand our knowledge on the characteristics of COVID-19 patients with viral reactivations and co-infections. Our experience with current review indicates a need for further investigations on virus reactivation and coinfection among COVID-19 patients., (© 2023. Pan American Health Organization.)

Background: Nosocomial sepsis is a major healthcare issue, but there are few data on estimates of its attributable mortality. We aimed to estimate attributable mortality fraction (AF) due to nosocomial sepsis., Methods: Matched 1:1 case-control study in 37 hospitals in Brazil. Hospitalized patients in participating hospitals were included. Cases were hospital non-survivors and controls were hospital survivors, which were matched by admission type and date of discharge. Exposure was defined as occurrence of nosocomial sepsis, defined as antibiotic prescription plus presence of organ dysfunction attributed to sepsis without an alternative reason for organ failure; alternative definitions were explored. Main outcome measurement was nosocomial sepsis-attributable fractions, estimated using inversed-weight probabilities methods using generalized mixed model considering time-dependency of sepsis occurrence., Results: 3588 patients from 37 hospitals were included. Mean age was 63 years and 48.8% were female at birth. 470 sepsis episodes occurred in 388 patients (311 in cases and 77 in control group), with pneumonia being the most common source of infection (44.3%). Average AF for sepsis mortality was 0.076 (95% CI 0.068-0.084) for medical admissions; 0.043 (95% CI 0.032-0.055) for elective surgical admissions; and 0.036 (95% CI 0.017-0.055) for emergency surgeries. In a time-dependent analysis, AF for sepsis rose linearly for medical admissions, reaching close to 0.12 on day 28; AF plateaued earlier for other admission types (0.04 for elective surgery and 0.07 for urgent surgery). Alternative sepsis definitions yield different estimates., Conclusion: The impact of nosocomial sepsis on outcome is more pronounced in medical admissions and tends to increase over time. The results, however, are sensitive to sepsis definitions., (© 2023. The Author(s).)

Purpose: To assess the association between acute disease severity and 1-year quality of life in patients discharged after hospitalisation due to coronavirus disease 2019 (COVID-19)., Methods: We conducted a prospective cohort study nested in 5 randomised clinical trials between March 2020 and March 2022 at 84 sites in Brazil. Adult post-hospitalisation COVID-19 patients were followed for 1 year. The primary outcome was the utility score of EuroQol five-dimension three-level (EQ-5D-3L). Secondary outcomes included all-cause mortality, major cardiovascular events, and new disabilities in instrumental activities of daily living. Adjusted generalised estimating equations were used to assess the association between outcomes and acute disease severity according to the highest level on a modified ordinal scale during hospital stay (2: no oxygen therapy; 3: oxygen by mask or nasal prongs; 4: high-flow nasal cannula oxygen therapy or non-invasive ventilation; 5: mechanical ventilation)., Results: 1508 COVID-19 survivors were enrolled. Primary outcome data were available for 1156 participants. At 1 year, compared with severity score 2, severity score 5 was associated with lower EQ-5D-3L utility scores (0.7 vs 0.84; adjusted difference, - 0.1 [95% CI - 0.15 to - 0.06]); and worse results for all-cause mortality (7.9% vs 1.2%; adjusted difference, 7.1% [95% CI 2.5%-11.8%]), major cardiovascular events (5.6% vs 2.3%; adjusted difference, 2.6% [95% CI 0.6%-4.6%]), and new disabilities (40.4% vs 23.5%; adjusted difference, 15.5% [95% CI 8.5%-22.5]). Severity scores 3 and 4 did not differ consistently from score 2., Conclusions: COVID-19 patients who needed mechanical ventilation during hospitalisation have lower 1-year quality of life than COVID-19 patients who did not need mechanical ventilation during hospitalisation., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To describe the IMPACTO-MR, a Brazilian nationwide intensive care unit platform study focused on the impact of health care-associated infections due to multidrug-resistant bacteria., Methods: We described the IMPACTO-MR platform, its development, criteria for intensive care unit selection, characterization of core data collection, objectives, and future research projects to be held within the platform., Results: The core data were collected using the Epimed Monitor System® and consisted of demographic data, comorbidity data, functional status, clinical scores, admission diagnosis and secondary diagnoses, laboratory, clinical, and microbiological data, and organ support during intensive care unit stay, among others. From October 2019 to December 2020, 33,983 patients from 51 intensive care units were included in the core database., Conclusion: The IMPACTO-MR platform is a nationwide Brazilian intensive care unit clinical database focused on researching the impact of health care-associated infections due to multidrug-resistant bacteria. This platform provides data for individual intensive care unit development and research and multicenter observational and prospective trials.

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

Background: The effects of convalescent plasma (CP) therapy in hospitalised patients with coronavirus disease 2019 (COVID-19) remain uncertain. This study investigates the effect of CP on clinical improvement in these patients., Methods: This is an investigator-initiated, randomised, parallel arm, open-label, superiority clinical trial. Patients were randomly (1:1) assigned to two infusions of CP plus standard of care (SOC) or SOC alone. The primary outcome was the proportion of patients with clinical improvement 28 days after enrolment., Results: A total of 160 (80 in each arm) patients (66.3% critically ill, 33.7% severely ill) completed the trial. The median (interquartile range (IQR)) age was 60.5 (48-68) years; 58.1% were male and the median (IQR) time from symptom onset to randomisation was 10 (8-12) days. Neutralising antibody titres >1:80 were present in 133 (83.1%) patients at baseline. The proportion of patients with clinical improvement on day 28 was 61.3% in the CP+SOC group and 65.0% in the SOC group (difference -3.7%, 95% CI -18.8-11.3%). The results were similar in the severe and critically ill subgroups. There was no significant difference between CP+SOC and SOC groups in pre-specified secondary outcomes, including 28-day mortality, days alive and free of respiratory support and duration of invasive ventilatory support. Inflammatory and other laboratory marker values on days 3, 7 and 14 were similar between groups., Conclusions: CP+SOC did not result in a higher proportion of clinical improvement on day 28 in hospitalised patients with COVID-19 compared to SOC alone., Competing Interests: Conflict of interest: L. Sekine has nothing to disclose. Conflict of interest: B. Arns has nothing to disclose. Conflict of interest: B.R. Fabro has nothing to disclose. Conflict of interest: M.M. Cipolatt has nothing to disclose. Conflict of interest: R.R.G. Machado received support from “Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)” (2017/24769-2). Conflict of interest: E.L. Durigon has nothing to disclose. Conflict of interest: E. Parolo has nothing to disclose. Conflict of interest: J.A.S. Pellegrini has nothing to disclose. Conflict of interest: M.V. Viana has nothing to disclose. Conflict of interest: P. Schwarz has nothing to disclose. Conflict of interest: T.C. Lisboa has nothing to disclose. Conflict of interest: J.M.S. Dora has nothing to disclose. Conflict of interest: J.P. Portich has nothing to disclose. A.A. Paz has nothing to disclose. L. Silla has nothing to disclose. A.M. Balsan has nothing to disclose. Conflict of interest: F.d-S. Schirmer has nothing to disclose. Conflict of interest: J.P.M. Franz has nothing to disclose. Conflict of interest: L.M. da-Silveira has nothing to disclose. Conflict of interest: R.C. Breunig has nothing to disclose. Conflict of interest: V. Petersen has nothing to disclose. Conflict of interest: M. Sosnoski has nothing to disclose. Conflict of interest: N.F. Mesquita has nothing to disclose. Conflict of interest: F.C.Z. Volpato has nothing to disclose. Conflict of interest: D. Sganzerla has nothing to disclose. Conflict of interest: M. Falavigna has nothing to disclose. Conflict of interest: R.G. Rosa received research grants from Brazilian Ministry of Health. Conflict of interest: A.P. Zavascki is a research fellow of the National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology, Brazil (304226/2018-1), and receives a research grant not related to this work from Pfizer (WI242215 2018)., (Copyright ©The authors 2022.)

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

Background: Handgrip strength is an alternative measure to assess peripheral muscle strength and is correlated with the Medical Research Council (MRC) scale, with promising values for diagnosing ICU-acquired weakness (ICUAW). Because ICUAW has been associated with delayed weaning from mechanical ventilation, we hypothesized that ICUAW evaluated with both the MRC scale score and handgrip strength are associated with failure of a spontaneous breathing trial (SBT) and duration of mechanical ventilation weaning., Methods: We conducted a prospective observational study in 3 general ICUs with a total of 54 beds at 2 academic hospitals. Adult subjects with > 48 h of mechanical ventilation who were eligible for weaning were included in the study., Results: In the evaluation before the first SBT, the MRC score ( P < .001) and handgrip strength ( P < .001) were significantly different between subjects extubated after a successful first SBT (simple weaning) and those extubated any time after a failed first SBT (difficult weaning). Only the MRC score discriminated between first SBT success or failure ( P < .001); in multivariate analysis, the MRC score was significantly associated with first SBT failure (odds ratio 0.91, 95% CI 0.88-0.97, P < .001) and difficult weaning (odds ratio 0.91, 95% CI 0.87-0.96, P < .001). Handgrip strength exhibited good accuracy in identifying ICUAW., Conclusions: MRC score was independently associated with SBT failure and difficult or prolonged weaning., Competing Interests: This work was supported by grants from the Fundo de Incentivo à Pesquisa do Hospital de Clínicas de Porto Alegre. The authors have disclosed no conflicts of interest., (Copyright © 2021 by Daedalus Enterprises.)

Introduction: The long-term effects caused by COVID-19 are unknown. The present study aims to assess factors associated with health-related quality of life and long-term outcomes among survivors of hospitalization for COVID-19 in Brazil., Methods: This is a multicenter prospective cohort study nested in five randomized clinical trials designed to assess the effects of specific COVID-19 treatments in over 50 centers in Brazil. Adult survivors of hospitalization due to proven or suspected SARS-CoV-2 infection will be followed-up for a period of 1 year by means of structured telephone interviews. The primary outcome is the 1-year utility score of health-related quality of life assessed by the EuroQol-5D3L. Secondary outcomes include all-cause mortality, major cardiovascular events, rehospitalizations, return to work or study, physical functional status assessed by the Lawton-Brody Instrumental Activities of Daily Living, dyspnea assessed by the modified Medical Research Council dyspnea scale, need for long-term ventilatory support, symptoms of anxiety and depression assessed by the Hospital Anxiety and Depression Scale, symptoms of posttraumatic stress disorder assessed by the Impact of Event Scale-Revised, and self-rated health assessed by the EuroQol-5D3L Visual Analog Scale. Generalized estimated equations will be performed to test the association between five sets of variables (1- demographic characteristics, 2- premorbid state of health, 3- characteristics of acute illness, 4- specific COVID-19 treatments received, and 5- time-updated postdischarge variables) and outcomes., Ethics and Dissemination: The study protocol was approved by the Research Ethics Committee of all participant institutions. The results will be disseminated through conferences and peer-reviewed journals.

Objective: To contribute to updating the recommendations for brain-dead potential organ donor management., Methods: A group of 27 experts, including intensivists, transplant coordinators, transplant surgeons, and epidemiologists, answered questions related to the following topics were divided into mechanical ventilation, hemodynamics, endocrine-metabolic management, infection, body temperature, blood transfusion, and checklists use. The outcomes considered were cardiac arrests, number of organs removed or transplanted as well as function / survival of transplanted organs. The quality of evidence of the recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system to classify the recommendations., Results: A total of 19 recommendations were drawn from the expert panel. Of these, 7 were classified as strong, 11 as weak and 1 was considered a good clinical practice., Conclusion: Despite the agreement among panel members on most recommendations, the grade of recommendation was mostly weak.

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

Objective: To report the statistical analysis plan (first version) for the Balanced Solutions versus Saline in Intensive Care Study (BaSICS)., Methods: BaSICS is a multicenter factorial randomized controlled trial that will assess the effects of Plasma-Lyte 148 versus 0.9% saline as the fluid of choice in critically ill patients, as well as the effects of a slow (333mL/h) versus rapid (999mL/h) infusion speed during fluid challenges, on important patient outcomes. The fluid type will be blinded for investigators, patients and the analyses. No blinding will be possible for the infusion speed for the investigators, but all analyses will be kept blinded during the analysis procedure., Results: BaSICS will have 90-day mortality as its primary endpoint, which will be tested using mixed-effects Cox proportional hazard models, considering sites as a random variable (frailty models) adjusted for age, organ dysfunction and admission type. Important secondary endpoints include renal replacement therapy up to 90 days, acute renal failure, organ dysfunction at days 3 and 7, and mechanical ventilation-free days within 28 days., Conclusion: This manuscript provides details on the first version of the statistical analysis plan for the BaSICS trial and will guide the study's analysis when follow-up is finished.

Objective: To evaluate renal responsiveness in oliguric critically ill patients after a fluid challenge., Methods: We conducted a prospective observational study in one university intensive care unit. Patients with urine output < 0.5mL/kg/h for 3 hours with a mean arterial pressure > 60mmHg received a fluid challenge. We examined renal fluid responsiveness (defined as urine output > 0.5mL/kg/h for 3 hours) after fluid challenge., Results: Forty-two patients (age 67 ± 13 years; APACHE II score 16 ± 6) were evaluated. Patient characteristics were similar between renal responders and renal nonresponders. Thirteen patients (31%) were renal responders. Hemodynamic or perfusion parameters were not different between those who did and those who did not increase urine output before the fluid challenge. The areas under the receiver operating characteristic curves were calculated for mean arterial pressure, heart rate, creatinine, urea, creatinine clearance, urea/creatinine ratio and lactate before the fluid challenge. None of these parameters were sensitive or specific enough to predict reversal of oliguria., Conclusion: After achieving hemodynamic stability, oliguric patients did not increase urine output after a fluid challenge. Systemic hemodynamic, perfusion or renal parameters were weak predictors of urine responsiveness. Our results suggest that volume replacement to correct oliguria in patients without obvious hypovolemia should be done with caution.

Background: Highly active antiretroviral therapy (HAART) has reduced HIV-related morbidity and mortality at all stages of infection and reduced transmission of HIV. Currently, the immediate start of HAART is recommended for all HIV patients, regardless of the CD4 count. There are several concerns, however, about starting treatment in critically ill patients. Unpredictable absorption of medication by the gastrointestinal tract, drug toxicity, drug interactions, limited reserve to tolerate the dysfunction of other organs resulting from hypersensitivity to drugs or immune reconstitution syndrome, and the possibility that subtherapeutic levels of drug may lead to viral resistance are the main concerns. The objective of our study was to compare the early onset (up to 5 days) with late onset (after discharge from the ICU) of HAART in HIV-infected patients admitted to the ICU., Methods: This was a randomized, open-label clinical trial enrolling HIV-infected patients admitted to the ICU of a public hospital in southern Brazil. Patients randomized to the intervention group had to start treatment with HAART within 5 days of ICU admission. For patients in the control group, treatment should begin after discharge from the ICU. The patients were followed up to determine mortality in the ICU, in the hospital and at 6 months. The primary outcome was hospital mortality. The secondary outcome was mortality at 6 months., Results: The calculated sample size was 344 patients. Unfortunately, we decided to discontinue the study due to a progressively slower recruitment rate. A total of 115 patients were randomized. The majority of admissions were for AIDS-defining illnesses and low CD4. The main cause of admission was respiratory failure. Regarding the early and late study groups, there was no difference in hospital (66.7% and 63.8%, p = 0.75) or 6-month (68.4% and 79.2%, p = 0.20) mortality. After multivariate analysis, the only independent predictors of in-hospital mortality were shock and dialysis during the ICU stay. For the mortality outcome at 6 months, the independent variables were shock and dialysis during the ICU stay and tuberculosis at ICU admission., Conclusions: Although the early termination of the study precludes definitive conclusions being made, early HAART administration for HIV-infected patients admitted to the ICU compared to late administration did not show benefit in hospital mortality or 6-month mortality. ClinicalTrials.gov, NCT01455688. Registered 20 October 2011, https://clinicaltrials.gov/show/NCT01455688., Competing Interests: The authors have declared that no competing interests exist.

Ventilator-associated lower respiratory tract infection is one of the most frequent complications in mechanically ventilated patients. Ventilator-associated tracheobronchitis has been considered a disease that does not warrant antibiotic treatment by the medical community for many years. In the last decade, several studies have shown that tracheobronchitis could be considered an intermediate process that leads to ventilator-associated pneumonia. Furthermore, ventilator-associated tracheobronchitis has a limited impact on overall mortality but shows a significant association with increased patient costs, length of stay, antibiotic use, and duration of mechanical ventilation. Although we still need clear evidence, especially concerning treatment modalities, the present study on ventilator-associated tracheobronchitis highlights that there are important impacts of including this condition in clinical management and epidemiological and infection surveillance.

We have read the study about the association between high red blood cell distribution width and higher ward mortality after intensive care unit discharge. The study increases the evidence that RDW may be a marker of severity for patients discharged from the ICU. However, in this letter, we comment on issues that need further discussion., Competing Interests: Not applicableNot applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objectives: To assess early mobilization practices of mechanically ventilated patients in southern Brazilian intensive care units (ICUs) and to identify barriers associated with early mobilization and possible complications., Methods: A prospective, observational, multicenter, 1-day point-prevalence study was conducted across 11 ICUs and included all mechanically ventilated adult patients. Hospital and ICU characteristics and patients' demographic data, the highest level of mobilization achieved in the 24 hours prior to the survey and related barriers, and complications that occurred during mobilization were collected in the hospital and the ICU., Results: A total of 140 patients were included with a mean age of 57±17 years. The median and interquartile range was 7 (3-17) days for the length of ICU stay to the day of the survey and 7 (3-16) days for the duration of mechanical ventilation (MV). The 8-level mobilization scale was classified into two categories: 126 patients (90%) remained in bed (level 1-3) and 14 (10%) were mobilized out of bed (level 4-8). Among patients with an endotracheal tube, tracheostomy, and noninvasive ventilation, 2%, 23%, and 50% were mobilized out of bed, respectively (p<0.001 for differences among the three groups). Weakness (20%), cardiovascular instability (19%), and sedation (18%) were the most commonly observed barriers to achieving a higher level of mobilization. No complications were reported., Conclusions: In southern Brazilian ICUs, the prevalence of patient mobilization was low, with only 10% of all mechanically ventilated patients and only 2% of patients with an endotracheal tube mobilized out of bed as part of routine care.

Background: Red blood cell distribution width (RDW) is a predictor of mortality in critically ill patients. Our objective was to investigate the association between the RDW at ICU discharge and the risk of ICU readmission or unexpected death in the ward., Methods: A secondary analysis of prospectively collected data study was conducted including patients discharged alive from the ICU to the ward. The target variable was the RDW collected at ICU discharge. Elevated RDW was defined as an RDW > 16%. Outcomes of interest included readmission to the ICU, unexpected death in the ward and in-hospital death. Variables with a p-value <0.1 in the univariate analysis or with biological plausibility for the occurrence of the outcome were included in the Cox proportional hazards model for adjustment., Results: We included 813 patients. A total of 138 readmissions to the ICU and 44 unexpected deaths in the ward occurred. Elevated RDW at ICU discharge was independently associated with readmission to the ICU or unexpected death in the ward after multivariable adjustment (HR: 1.901; 95% CI 1.357-2.662). Other variables associated with this outcome included age, tracheostomy and mean corpuscular volume (MCV) at ICU discharge. Similar results were obtained after the exclusion of unexpected deaths in the ward (HR 1.940; CI 1.312-2.871) and for in-hospital deaths (HR 1.716; 95% CI 1.141-2.580)., Conclusions: Elevated RDW at ICU discharge is independently associated with ICU readmission and in-hospital death., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Introduction: Higher mortality for patients admitted to intensive care units (ICUs) during the weekends has been occasionally reported with conflicting results that could be related to organisational factors. We investigated the effects of ICU organisational and staffing patterns on the potential association between weekend admission and outcomes in critically ill patients., Methods: We included 59 614 patients admitted to 78 ICUs participating during 2013. We defined 'weekend admission' as any ICU admission from Friday 19:00 until Monday 07:00. We assessed the association between weekend admission with hospital mortality using a mixed logistic regression model controlling for both patient-level (illness severity, age, comorbidities, performance status and admission type) and ICU-level (decrease in nurse/bed ratio on weekend, full-time intensivist coverage, use of checklists on weekends and number of institutional protocols) confounders. We performed secondary analyses in the subgroup of scheduled surgical admissions., Results: A total of 41 894 patients (70.3%) were admitted on weekdays and 17 720 patients (29.7%) on weekends. In univariable analysis, weekend admitted patients had higher ICU (10.9% vs 9.0%, P<0.001) and hospital (16.5% vs 13.5%, P<0.001) mortality. After adjusting for confounders, weekend admission was not associated with higher hospital mortality (OR 1.05, 95% CI 0.99 to 1.12, P=0.095). However, a 'weekend effect' was still observed in scheduled surgical admissions, as well as in ICUs not using checklists during the weekends. For unscheduled admissions, no 'weekend effect' was observed regardless of ICU's characteristics. For scheduled surgical admissions, a 'weekend effect' was present only in ICUs with a low number of implemented protocols and those with a reduction in the nurse/bed ratio and not applying checklists during weekends., Conclusions: ICU organisational factors, such as decreased nurse-to-patient ratio, absence of checklists and fewer standardised protocols, may explain, in part, increases in mortality in patients admitted to the ICU mortality on weekends., Competing Interests: Competing interests: MS and JIFS are founders and equity shareholders of Epimed Solutions, which commercialises the Epimed Monitor System, a cloud-based software for ICU management and benchmarking. The other authors declare that they have no conflict of interest., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The performance of severity-of-illness scores varies in different scenarios and must be validated prior of being used in a specific settings and geographic regions. Moreover, models' calibration may deteriorate overtime and performance of such instruments should be reassessed regularly. Therefore, we aimed at to validate the SAPS 3 in a large contemporary cohort of patients admitted to Brazilian ICUs. In addition, we also compared the performance of the SAPS 3 with the MPM 0 -III., Methods: This is a retrospective cohort study in which 48,816 (medical admissions = 67.9%) adult patients are admitted to 72 Brazilian ICUs during 2013. We evaluated models' discrimination using the area under the receiver operating characteristic curve (AUROC). We applied the calibration belt to evaluate the agreement between observed and expected mortality rates (calibration)., Results: Mean SAPS 3 score was 44.3 ± 15.4 points. ICU and hospital mortality rates were 11.0 and 16.5%. We estimated predicted mortality using both standard (SE) and Central and South American (CSA) customized equations. Predicted mortality rates were 16.4 ± 19.3% (SAPS 3-SE), 21.7 ± 23.2% (SAPS 3-CSA) and 14.3 ± 14.0% (MPM 0 -III). Standardized mortality ratios (SMR) obtained for each model were: 1.00 (95% CI, 0.98-0.102) for the SAPS 3-SE, 0.75 (0.74-0.77) for the SAPS 3-CSA and 1.15 (1.13-1.18) for the MPM 0 -III. Discrimination was better for SAPS 3 models (AUROC = 0.85) than for MPM 0 -III (AUROC = 0.80) (p < 0.001). We applied the calibration belt to evaluate the agreement between observed and expected mortality rates (calibration): the SAPS 3-CSA overestimated mortality throughout all risk classes while the MPM 0 -III underestimated it uniformly. The SAPS 3-SE did not show relevant deviations from ideal calibration., Conclusions: In a large contemporary database, the SAPS 3-SE was accurate in predicting outcomes, supporting its use for performance evaluation and benchmarking in Brazilian ICUs.

We compared the discriminatory capacity of the sequential organ failure assessment (SOFA) versus the systemic inflammatory response syndrome (SIRS) score for predicting ICU mortality, need for and length of mechanical ventilation, ICU stay, and hospitalization in patients with suspected infection admitted to a mixed Brazilian ICU. We performed a retrospective analysis of a longitudinal ICU database from a tertiary hospital in Southern Brazil. Patients were categorized according to whether they met the criteria for sepsis according to SOFA (variation ≥2 points over the baseline clinical condition) and SIRS (SIRS score ≥2 points). From January 2008 to December 2014, 1487 patients were admitted to the ICU due to suspected infection. SOFA ≥2 identified more septic patients than SIRS ≥2 (79.0% [n=1175] vs. 68.5% [n=1020], p<0.001). There was no difference between the two scores in predicting ICU mortality (area under the receiver operating characteristic curve (AUROC)=0.64 vs. 0.64, p=0.99). SOFA ≥2 was marginally better than SIRS ≥2 in predicting need for mechanical ventilation (AUROC=0.64 vs. 0.62, p=0.001), ICU stay>7 days (AUROC=0.65 vs. 0.63, p=0.004), and length of hospitalization >10 days (AUROC=0.61 vs. 0.59, p<0.001). There was no difference between the two scores in predicting mechanical ventilation >7 days., (Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012"., Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development., Methods: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable., Results: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions., Conclusions: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.", Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development., Methods: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable., Results: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions., Conclusions: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Objective: Studies suggest an association between vitamin D deficiency and morbidity/mortality in critically ill patients. Several issues remain unexplained, including which vitamin D levels are related to morbidity and mortality and the relevance of vitamin D kinetics to clinical outcomes. We conducted this study to address the association of baseline vitamin D levels and vitamin D kinetics with morbidity and mortality in critically ill patients., Method: In 135 intensive care unit (ICU) patients, vitamin D was prospectively measured on admission and weekly until discharge from the ICU. The following outcomes of interest were analyzed: 28-day mortality, mechanical ventilation, length of stay, infection rate, and culture positivity., Results: Mortality rates were higher among patients with vitamin D levels <12 ng/mL (versus vitamin D levels >12 ng/mL) (32.2% vs. 13.2%), with an adjusted relative risk of 2.2 (95% CI 1.07-4.54; p< 0.05). There were no differences in the length of stay, ventilation requirements, infection rate, or culture positivity., Conclusions: This study suggests that low vitamin D levels on ICU admission are an independent risk factor for mortality in critically ill patients. Low vitamin D levels at ICU admission may have a causal relationship with mortality and may serve as an indicator for vitamin D replacement among critically ill patients.

This article describes a patient presenting with dyspnea and platypnea and whose only clinical finding was presence of patent foramen ovale with a right to left shunt, without pulmonary hypertension, characteristic of the rare Platypnea-Orthodeoxya Syndrome, with very interesting pathophysiological findings and with therapeutic alternatives not yet defined.

Introduction: This study sought to assess the prognostic value of the kinetics of procalcitonin (PCT), C-reactive protein (CRP) and clinical scores (clinical pulmonary infection score (CPIS), Sequential Organ Failure Assessment (SOFA)) in the outcome of ventilator-associated pneumonia (VAP) at an early time point, when adequacy of antimicrobial treatment is evaluated., Methods: This prospective observational cohort study was conducted in a teaching hospital. The subjects were 75 patients consecutively admitted to the intensive care unit from October 2003 to August 2005 who developed VAP. Patients were followed for 28 days after the diagnosis, when they were considered survivors. Patients who died before the 28th day were non-survivors. There were no interventions., Results: PCT, CRP and SOFA score were determined on day 0 and day 4. Variables included in the univariable logistic regression model for survival were age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, decreasing DeltaSOFA, decreasing DeltaPCT and decreasing DeltaCRP. Survival was directly related to decreasing DeltaPCT with odds ratio (OR) = 5.67 (95% confidence interval 1.78 to 18.03), decreasing DeltaCRP with OR = 3.78 (1.24 to 11.50), decreasing DeltaSOFA with OR = 3.08 (1.02 to 9.26) and APACHE II score with OR = 0.92 (0.86 to 0.99). In a multivariable logistic regression model for survival, only decreasing DeltaPCT with OR = 4.43 (1.08 to 18.18) and decreasing DeltaCRP with OR = 7.40 (1.58 to 34.73) remained significant. Decreasing DeltaCPIS was not related to survival (p = 0.59). There was a trend to correlate adequacy to survival. Fifty percent of the 20 patients treated with inadequate antibiotics and 65.5% of the 55 patients on adequate antibiotics survived (p = 0.29)., Conclusion: Measurement of PCT and CRP at onset and on the fourth day of treatment can predict survival of VAP patients. A decrease in either one of these marker values predicts survival.