Search

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

Background: The influence of high positive end-expiratory pressure (PEEP) with recruitment maneuvers on the occurrence of postoperative pulmonary complications after surgery is still not definitively established. Bayesian analysis can help to gain further insights from the available data and provide a probabilistic framework that is easier to interpret. Our objective was to estimate the posterior probability that the use of high PEEP with recruitment maneuvers is associated with reduced postoperative pulmonary complications in patients with intermediate-to-high risk under neutral, pessimistic, and optimistic expectations regarding the treatment effect., Methods: Multilevel Bayesian logistic regression analysis on individual patient data from three randomized clinical trials carried out on surgical patients at Intermediate-to-High Risk for postoperative pulmonary complications. The main outcome was the occurrence of postoperative pulmonary complications in the early postoperative period. We studied the effect of high PEEP with recruitment maneuvers versus Low PEEP Ventilation. Priors were chosen to reflect neutral, pessimistic, and optimistic expectations of the treatment effect., Results: Using a neutral, pessimistic, or optimistic prior, the posterior mean odds ratio (OR) for High PEEP with recruitment maneuvers compared to Low PEEP was 0.85 (95% Credible Interval [CrI] 0.71 to 1.02), 0.87 (0.72 to 1.04), and 0.86 (0.71 to 1.02), respectively. Regardless of prior beliefs, the posterior probability of experiencing a beneficial effect exceeded 90%. Subgroup analysis indicated a more pronounced effect in patients who underwent laparoscopy (OR: 0.67 [0.50 to 0.87]) and those at high risk for PPCs (OR: 0.80 [0.53 to 1.13]). Sensitivity analysis, considering severe postoperative pulmonary complications only or applying a different heterogeneity prior, yielded consistent results., Conclusion: High PEEP with recruitment maneuvers demonstrated a moderate reduction in the probability of PPC occurrence, with a high posterior probability of benefit observed consistently across various prior beliefs, particularly among patients who underwent laparoscopy., Competing Interests: Declaration of interests: GM: No conflict of interests FZ: Received consulting fees from Baxter. LB: No conflicts of interest NSC: No conflicts of interest TB: No conflicts of interest SNTH: No conflicts of interest CF: No conflicts of interest JL: No conflicts of interest MS: no conflicts of interest PP: No conflicts of interest MGdA: Received consulting fees from Zoll and Drager medical and Ambu Inc and honoraria for lectures from MSD. MJS: No conflicts of interest ASN: Received honorary from Drager medical for lectures; Own stocks in Endpoint Health, (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

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

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

Background: Using the frequentist approach, a recent meta-analysis of three randomized clinical trials in patients undergoing intraoperative ventilation during general anesthesia for major surgery failed to show the benefit of ventilation that uses high positive end-expiratory pressure with recruitment maneuvers when compared to ventilation that uses low positive end-expiratory pressure without recruitment maneuvers. Methods: We designed a protocol for a Bayesian analysis using the pooled dataset. The multilevel Bayesian logistic model will use the individual patient data. Prior distributions will be prespecified to represent a varying level of skepticism for the effect estimate. The primary endpoint will be a composite of postoperative pulmonary complications (PPC) within the first seven postoperative days, which reflects the primary endpoint of the original studies. We preset a range of practical equivalence to assess the futility of the intervention with an interval of odds ratio (OR) between 0.9 and 1.1 and assess how much of the 95% of highest density interval (HDI) falls between the region of practical equivalence. Ethics and dissemination: The used data derive from approved studies that were published in recent years. The findings of this current analysis will be reported in a new manuscript, drafted by the writing committee on behalf of the three research groups. All investigators listed in the original trials will serve as collaborative authors., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Mazzinari G et al.)

Background: High intraoperative PEEP with recruitment manoeuvres may improve perioperative outcomes. We re-examined this question by conducting a patient-level meta-analysis of three clinical trials in adult patients at increased risk for postoperative pulmonary complications who underwent non-cardiothoracic and non-neurological surgery., Methods: The three trials enrolled patients at 128 hospitals in 24 countries from February 2011 to February 2018. All patients received volume-controlled ventilation with low tidal volume. Analyses were performed using one-stage, two-level, mixed modelling (site as a random effect; trial as a fixed effect). The primary outcome was a composite of postoperative pulmonary complications within the first week, analysed using mixed-effect logistic regression. Pre-specified subgroup analyses of nine patient characteristics and seven procedure and care-delivery characteristics were also performed., Results: Complete datasets were available for 1913 participants ventilated with high PEEP and recruitment manoeuvres, compared with 1924 participants who received low PEEP. The primary outcome occurred in 562/1913 (29.4%) participants randomised to high PEEP, compared with 620/1924 (32.2%) participants randomised to low PEEP (unadjusted odds ratio [OR]=0.87; 95% confidence interval [95% CI], 0.75-1.01; P=0.06). Higher PEEP resulted in 87/1913 (4.5%) participants requiring interventions for desaturation, compared with 216/1924 (11.2%) participants randomised to low PEEP (OR=0.34; 95% CI, 0.26-0.45). Intraoperative hypotension was associated more frequently (784/1913 [41.0%]) with high PEEP, compared with low PEEP (579/1924 [30.1%]; OR=1.87; 95% CI, 1.60-2.17)., Conclusions: High PEEP combined with recruitment manoeuvres during low tidal volume ventilation in patients undergoing major surgery did not reduce postoperative pulmonary complications., Clinical Trial Registration: NCT03937375 (Clinicaltrials.gov)., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

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

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

Objective: Severity of illness scores used in critical care for benchmarking, quality assurance and risk stratification have been mainly created in high-income countries. In low and middle-income countries (LMICs), they cannot be widely utilized due to the demand for large amounts of data that may not be available (e.g. laboratory results). We attempt to create a new severity prognostication model using fewer variables that are easier to collect in an LMIC., Setting: Two intensive care units, one private and one public, from São Paulo, Brazil PATIENTS: An ICU for the first time., Interventions: None., Measurements and Mains Results: The dataset from the private ICU was used as a training set for model development to predict in-hospital mortality. Three different machine learning models were applied to five different blocks of candidate variables. The resulting 15 models were then validated on a separate dataset from the public ICU, and discrimination and calibration compared to identify the best model. The best performing model used logistic regression on a small set of 10 variables: highest respiratory rate, lowest systolic blood pressure, highest body temperature and Glasgow Coma Scale during the first hour of ICU admission; age; prior functional capacity; type of ICU admission; source of ICU admission; and length of hospital stay prior to ICU admission. On the validation dataset, our new score, named SEVERITAS, had an area under the receiver operating curve of 0.84 (0.82 - 0.86) and standardized mortality ratio of 1.00 (0.91-1.08). Moreover, SEVERITAS had similar discrimination compared to SAPS-3 and better discrimination than the simplified TropICS and R-MPM., Conclusions: Our study proposes a new ICU mortality prediction model using simple logistic regression on a small set of easily collected variables may be better suited than currently available models for use in low and middle-income countries., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Over the last 30 years, a variety of studies reporting the effects of vitamin A on memory have been published., Objective: To perform a rigorous systematic review of the literature on vitamin A and memory in order to organize evidence-based data on the subject., Methods: Four authors carried out the systematic review in accordance with strict guidelines. The terms "vitamin A" OR "retinol" OR "retinoic acid" AND "memory" OR "cognition" OR "Alzheimer" were searched in virtually all medical research databases., Results: From 236 studies containing the key words, 44 were selected for this review, numbering 10 reviews and 34 original articles. Most studies used animal models for studying vitamin A and cognition. Birds, mice and rats were more frequently employed whereas human studies accounted for only two reports on brain tissue from autopsies and one on the role of isotretinoin in cognition among individuals taking this medication to treat acne., Conclusion: Vitamin A may be an important and viable complement in the treatment and prevention of Alzheimer's disease. Clinical trials are imperative and, at present, there is no evidence-based data to recommend vitamin A supplementation for the prevention or treatment of Alzheimer's disease., Competing Interests: Disclosure: The authors report no conflicts of interest.

Unlabelled: Incidental parathyroidectomy is a common event in thyroid surgery. The literature shows a finding of parathyroid glands ranging from 6.4% to 31% in pathological specimens of the thyroid gland., Objective: To collect the amount of parathyroid glands found in surgical specimens of thyroidectomy and correlate with the histopathological and demographic variables., Methods: Retrospective study based on pathological reports of thyroidectomy from January 2007 to December 2008., Results: 442 patients were submitted to total thyroidectomy, and 2.93% had parathyroid glands, which corresponded to 13 of this total. The presence of papillary thyroid carcinoma associated with incidental parathyroidectomy was 10.11%, compared to the benign lesion: 1.4%., Conclusion: Papillary thyroid carcinoma was the variable associated with increased number of incidental parathyroidectomy.