Development and validation of the Ex-Care BR model: a multicentre initiative for identifying Brazilian surgical patients at risk of 30-day in-hospital mortality.

BACKGROUND: Surgical risk stratification is crucial for enhancing perioperative assistance and allocating resources efficiently. However, existing models may not capture the complexity of surgical care in Brazil. Using data from various healthcare settings nationwide, we developed a new risk model for 30-day in-hospital mortality (the Ex-Care BR model). METHODS: A retrospective cohort study was conducted in 10 hospitals from different geographic regions in Brazil. Data were analysed using multilevel logistic regression models. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC), Brier score, and calibration plots. Derivation and validation cohorts were randomly assigned. RESULTS: A total of 107,372 patients were included, and 30-day in-hospital mortality was 2.1% (n=2261). The final risk model comprised four predictors related to the patient and surgery (age, ASA physical status classification, surgical urgency, and surgical size), and the random effect related to hospitals. The model showed excellent discrimination (AUROC=0.93, 95% confidence interval [CI], 0.93-0.94), calibration, and overall performance (Brier score=0.017) in the derivation cohort (n=75,094). Similar results were observed in the validation cohort (n=32,278) (AUROC=0.93, 95% CI, 0.92-0.93). CONCLUSIONS: The Ex-Care BR is the first model to consider regional and organisational peculiarities of the Brazilian surgical scene, in addition to patient and surgical factors. It is particularly useful for identifying high-risk surgical patients in situations demanding efficient allocation of limited resources. However, a thorough exploration of mortality variations among hospitals is essential for a comprehensive understanding of risk. CLINICAL TRIAL REGISTRATION: NCT05796024.

Troponin elevation as a marker of short deterioration and one-year death in a high-risk surgical patient cohort in a low and middle income country setting: a postoperative approach to increase surveillance.

PURPOSE: Myocardial injury after noncardiac surgery is common and mostly asymptomatic. The ideal target population that will benefit from routine troponin measurements in low and middle income countries (LMICs) is unclear. This study aims to evaluate the clinical outcomes of a cohort of high-risk surgical patients according to high-sensitivity troponin T (hsTnT) in an LMIC setting. METHODS: We conducted a prospective cohort study of 442 high-risk patients undergoing noncardiac surgery at a Brazilian hospital between February 2019 and March 2020. High-sensitivity troponin T levels were measured preoperatively, 24 hr, and 48 hr after surgery and stratified into three groups: normal (< 20 ng·L-1); minor elevation (20-65 ng·L-1); and major elevation (> 65 ng·L-1). We performed survival analysis to determine the association between myocardial injury and one-year mortality. We described medical interventions and evaluated unplanned intensive care unit (ICU) admission and complications using multivariable models. RESULTS: Postoperative myocardial injury occurred in 45% of patients. Overall, 30-day mortality was 8%. Thirty-day and one-year mortality were higher in patients with hsTnT ≥ 20 ng·L-1. One-year mortality was 18% in the unaltered troponin group vs 31% and 41% for minor and major elevation groups, respectively. Multivariable analysis of one-year survival showed a hazard ratio (HR) of 1.94 (95% confidence interval [CI], 1.22 to 3.09) for the minor elevation group and a HR of 2.73 (95% CI, 1.67 to 4.45) for the troponin > 65 ng·L-1 group. Patients with altered troponin had more unplanned ICU admissions (13% vs 5%) and more complications (78% vs 48%). CONCLUSION: This study supports evidence that hsTnT is an important prognostic marker and a strong predictor of all-cause mortality after surgery. Troponin measurement in high-risk surgical patients could potentially be used as tool to scale-up care in LMIC settings. STUDY REGISTRATION: ClinicalTrials.gov (NCT04187664); first submitted 5 December 2019.

RéSUMé: OBJECTIF: Les lésions myocardiques après une chirurgie non cardiaque sont courantes et la plupart du temps asymptomatiques. Nous ne connaissons pas la population cible idéale qui bénéficierait de mesures régulières de la troponine dans les pays à revenu faible et intermédiaire (PRFI). Cette étude vise à évaluer les issues cliniques d'une cohorte de patient·es de chirurgie à haut risque grâce à la troponine T à haute sensibilité (hsTnT) dans un contexte de PRFI. MéTHODE: Nous avons mené une étude de cohorte prospective auprès de 442 patient·es à haut risque bénéficiant d'une chirurgie non cardiaque dans un hôpital brésilien entre février 2019 et mars 2020. Les taux de troponine T à haute sensibilité ont été mesurés avant l'opération, 24 heures et 48 heures après la chirurgie, et stratifiés en trois groupes : normaux (< 20 ng·L−1), élévation mineure (20­65 ng·L−1) et élévation majeure (> 65 ng·L−1). Nous avons réalisé une analyse de survie pour déterminer l'association entre les lésions myocardiques et la mortalité à un an. Nous avons décrit les interventions médicales et évalué les admissions non planifiées à l'unité de soins intensifs (USI) ainsi que les complications à l'aide de modèles multivariables. RéSULTATS: Une lésion myocardique postopératoire est survenue chez 45 % des patient·es. La mortalité globale à 30 jours était de 8 %. La mortalité à trente jours et à un an était plus élevée chez les patient·es avec une hsTnT ≥ 20 ng·L−1. La mortalité à un an était de 18 % dans le groupe troponine inchangée vs 31 % et 41 % pour les groupes à élévation mineure et majeure de la troponine, respectivement. L'analyse multivariée de la survie à un an a montré un rapport de risque (RR) de 1,94 (intervalle de confiance [IC] à 95 %, 1,22 à 3,09) pour le groupe d'élévation mineure et un RR de 2,73 (IC 95 %, 1,67 à 4,45) pour le groupe avec une troponine > 65 ng·L−1. Les admissions non planifiées à l'USI étaient plus fréquentes chez les patient·es présentant une troponine altérée (13 % vs 5 %), tout comme les complications (78 % vs 48 %). CONCLUSION: Cette étude soutient les données probantes selon lesquelles la hsTnT est un marqueur pronostique important et un prédicteur fort de la mortalité toutes causes confondues après la chirurgie. La mesure de la troponine chez la patientèle chirurgicale à risque élevé pourrait potentiellement être utilisée comme outil pour intensifier les soins dans les PRFI. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT04187664); soumis pour la première fois le 5 décembre 2019.

Developing and validating a machine learning ensemble model to predict postoperative delirium in a cohort of high-risk surgical patients: A secondary cohort analysis.

BACKGROUND: Postoperative delirium (POD) has a negative impact on prognosis, length of stay and the burden of care. Although its prediction and identification may improve postoperative care, this need is largely unmet in the Brazilian public health system. OBJECTIVE: To develop and validate a machine-learning prediction model and estimate the incidence of delirium. We hypothesised that an ensemble machine-learning prediction model that incorporates predisposing and precipitating features could accurately predict POD. DESIGN: A secondary analysis nested in a cohort of high-risk surgical patients. SETTING: An 800-bed, quaternary university-affiliated teaching hospital in Southern Brazil. We included patients operated on from September 2015 to February 2020. PATIENTS: We recruited 1453 inpatients with an all-cause postoperative 30-day mortality risk greater than 5% assessed preoperatively by the ExCare Model. MAIN OUTCOME MEASURE: The incidence of POD classified by the Confusion Assessment Method, up to 7 days postoperatively. Predictive model performance with different feature scenarios were compared with the area under the receiver operating characteristic curve. RESULTS: The cumulative incidence of delirium was 117, giving an absolute risk of 8.05/100 patients. We developed multiple machine-learning nested cross-validated ensemble models. We selected features through partial dependence plot analysis and theoretical framework. We treated the class imbalance with undersampling. Different feature scenarios included: 52 preoperative, 60 postoperative and only three features (age, preoperative length of stay and the number of postoperative complications). The mean areas (95% confidence interval) under the curve ranged from 0.61 (0.59 to 0.63) to 0.74 (0.73 to 0.75). CONCLUSION: A predictive model composed of three indicative readily available features performed better than those with numerous perioperative features, pointing to its feasibility as a prognostic tool for POD. Further research is required to test the generalisability of this model. TRIAL REGISTRATION: Institutional Review Board Registration number 04448018.8.0000.5327 (Brazilian CEP/CONEP System, available in https://plataformabrasil.saude.gov.br/ ).

The need for data describing the surgical population in Latin America.

Latin American countries have a huge diversity in sociocultural factors, ethnicity, geography, and political systems. Provision of healthcare varies widely in Latin America, and it is unclear how these disparities relate to outcomes for individual patients undergoing surgery. The Latin American Surgical Outcome Study (LASOS), with its pragmatic design, will provide a snapshot of surgical activity throughout Latin America and identify the next steps needed to improve postoperative outcomes.

Measuring emotional preoperative stress by an app approach and its applicability to predict postoperative pain.

BACKGROUND: The Brief Measure of Emotional Preoperative Stress (B-MEPS) was developed to evaluate the preoperative individual vulnerability to emotional stress. To obtain a refined version of B-MEPS suitable for an app approach, this study aimed: (i) to identify items with more discriminant properties; (ii) to classify the level of preoperative emotional stress based on cut-off points; (iii) to assess concurrent validity through correlation with the Central Sensitization Inventory (CSI) score; (iv) to confirm whether the refined version of B-MEPS is an adequate predictive measure for identification of patients prone to intense postoperative pain. METHODS: We include 1016 patients who had undergone surgical procedures in a teaching hospital. The generalized partial credit model of item response theory and latent class model were employed, respectively, to reduce the number of items and to create cut-off points. We applied the CSI and assessed pain by Visual Analog Scale (0-10) and by the amount of postoperative morphine consumption. RESULTS: The refined B-MEPS shows satisfactory reliability (Cronbach's alpha 0.79). Preoperative emotional stress, according to the cut-off points, is classified into categories: low, intermediate or high stress. The refined B-MEPS exhibited a linear association with the CSI scores (r2 = 0.53, p < 0.01). Patients with higher levels of emotional stress displayed a positive association with moderate to severe pain and greater morphine consumption. CONCLUSION: The refined version of B-MEPS, along with an interface of easy applicability, assess emotional vulnerability at the bedside before surgery. This app may support studies focused on intervening with perioperative stress levels.

Latin American surgical outcomes study: study protocol for a multicentre international observational cohort study of patient outcomes after surgery in Latin American countries.

Background: Reported data suggest that 4.2 million deaths will occur within 30 days of surgery worldwide each year, half of which are in low- and middle-income countries. Postoperative complications are a leading cause of long-term morbidity and mortality. Patients who survive and leave the hospital after surgical complications regularly experience reductions in long-term survival and functional independence, resulting in increased costs. With a high volume of surgery performed, there is a growing perception of the substantial impact of even minor enhancements in perioperative care. The Latin American Surgical Outcomes Study (LASOS) is an international, multicentre, prospective cohort study of adults submitted to in-patient surgery in Latin America aiming to provide detailed data describing postoperative complications and surgical mortality. Methods: LASOS is a 7 day cohort study of adults undergoing surgery in Latin America. Details of preoperative risk factors, intraoperative care, and postoperative outcomes will be collected. The primary outcome will be in-hospital postoperative complications of any cause. Secondary outcomes include in-hospital all-cause mortality, duration of hospital stay after surgery, and admission to a critical care unit within 30 days after surgery during the index hospitalisation. Results: The LASOS results will be published in peer-reviewed journals, reported and presented at international meetings, and widely disseminated to patients and public in participating countries via mainstream and social media. Conclusions: The LASOS may augment our understanding of postoperative complications and surgial mortality in Latin America. Clinical trial registration: NCT05169164.

Few and feasible preoperative variables can identify high-risk surgical patients: derivation and validation of the Ex-Care risk model.

BACKGROUND: The development of feasible preoperative risk tools is desirable, especially for low-middle income countries with limited resources and complex surgical settings. This study aimed to derive and validate a preoperative risk model (Ex-Care model) for postoperative mortality and compare its performance with current risk tools. METHODS: A multivariable logistic regression model predicting in-hospital mortality was developed using a large Brazilian surgical cohort. Patient and perioperative predictors were considered. Its performance was compared with the Charlson comorbidity index (CCI), Revised Cardiac Risk Index (RCRI), and the Surgical Outcome Risk Tool (SORT). RESULTS: The derivation cohort included 16 618 patients. In-hospital death occurred in 465 patients (2.8%). Age, with adjusted splines, degree of procedure (major vs non-major), ASA physical status, and urgency were entered in a final model. It showed high discrimination with an area under the receiver operating characteristic curve (AUROC) of 0.926 (95% confidence interval [CI], 0.91-0.93). It had superior accuracy to the RCRI (AUROC, 0.90 vs 0.76; P<0.01) and similar to the CCI (0.90 vs 0.82; P=0.06) and SORT models (0.90 vs 0.92; P=0.2) in the temporal validation cohort of 1173 patients. Calibration was adequate in both development (Hosmer-Lemeshow, 9.26; P=0.41) and temporal validation cohorts (Hosmer-Lemeshow 5.29; P=0.71). CONCLUSIONS: The Ex-Care risk model proved very efficient at identifying high-risk surgical patients. Although multicentre studies are needed, it should have particular value in low resource settings to better inform perioperative health policy and clinical decision-making.

Access to pain management for cancer patients treated under the Brazilian private healthcare system / Acesso ao tratamento da dor de pacientes com câncer atendidos no sistema de saúde privado brasileiro

Objective: To reflect about current pain management in cancer patients treated under the Brazilian Private Healthcare System, considering legal boundaries, access to essential drugs and involved ethical issues. Panelists aimed to reach a consensus about recommendations to increase access to proper analgesia for patients with cancer secondary pain. Methods: Four Brazilian specialists, being a radiation oncologist (and bioethicist), an oncologist, a pain specialist and a CEO of a private healthcare plan, met after the 2019 American Society of Clinical Oncology (ASCO) meeting, held in Chicago, and discussed the aforementioned subjects. A consensus was reached and is described below. Results: Cancer pain is prevailing in our country, probably undertreated, and may be a prevalent cause of medical services overuse, which may increase healthcare costs. Thus, there may be an opportunity to improve patient's quality of life, with a positive budget impact for private healthcare plans, if this treatment becomes mandatorily reimbursed. There are several studies in the literature showing similar results, but this should be prospectively studied, preferable using real word evidence, at the Brazilian scenario. Cancer pain treatment protocols, designed by specialists, should be designed in agreement with all stakeholders. Conclusion: Panelists agreed that pain treatment, which must be considered a human right, is a clear priority in Brazil. All stakeholders should collaborate in designing protocols to improve patient's quality of life, consequently improving health insurance's budgets. If so, this would have clear consequences in access to innovative cancer treatments, as those discussed during the 2019 ASCO meeting.

Objetivo: Refletir sobre o manejo atual da dor em pacientes com câncer atendidos no sistema de saúde privado brasileiro, considerando limites legais, acesso a medicamentos essenciais e questões éticas envolvidas. Os participantes do painel procuraram chegar a um consenso sobre recomendações para aumentar o acesso à analgesia adequada para pacientes com dor secundária ao diagnóstico de câncer. Métodos: Quatro especialistas brasileiros reuniram-se após a reunião da Sociedade Americana de Oncologia Clínica (ASCO) de 2019, realizada em Chicago, e discutiram os mencionados assuntos. Um consenso foi alcançado e é descrito abaixo. Resultados: A dor oncológica prevalece em nosso país, provavelmente subtratada, e pode ser uma causa predominante de uso excessivo de serviços médicos, o que pode aumentar os custos com saúde. Assim, pode haver uma oportunidade de melhorar a qualidade de vida do paciente, com um impacto orçamentário positivo para planos de saúde privados, se esse tratamento for obrigatoriamente reembolsado. Existem vários estudos na literatura que mostram resultados semelhantes, mas isso deve ser estudado prospectivamente, preferencialmente usando evidências provenientes de dados de mundo real, no cenário brasileiro. Os protocolos de tratamento da dor do câncer, preparados por especialistas, devem ser elaborados de acordo com todas as partes interessadas. Conclusão: Os participantes do painel concordaram que o tratamento da dor, que deve ser considerado um direito humano, é uma clara prioridade no Brasil. Todas as partes interessadas devem colaborar na elaboração de protocolos para melhorar a qualidade de vida do paciente, consequentemente melhorando os orçamentos do seguro de saúde. Nesse caso, isso teria consequências claras no acesso a tratamentos inovadores contra o câncer, como os discutidos durante a reunião da ASCO em 2019.

Perioperative mortality related to anesthesia within 48 h and up to 30 days following surgery: A retrospective cohort study of 11,562 anesthetic procedures.

STUDY OBJECTIVE: Studying postoperative in-hospital mortality is crucial to the understanding of the perioperative process failures and to the implementation of strategies to improve patient outcomes. We intend to classify the causes of perioperative deaths up to 30 days after procedures requiring anesthesia and to evaluate the risk factors for early (48 h) or late (30 day) mortality. DESIGN: Retrospective cohort study. SETTING: A quaternary University Hospital from South Brazil. PATIENTS: The information related to the perioperative care was collected from surgeries performed between January 2012 and December 2011. INTERVENTIONS: None (observational study). MEASUREMENTS: Three anesthesiologists classified the causes of deaths according to the ANZCA (Australian and New Zealand College of Anesthetists) classification, used in the report of Anesthesia-Related Mortality in Australia since 1985, which defines eight death categories. The risk factors for early or late death were analyzed in a regression model. MAIN RESULTS: 11.562 surgeries were performed, with a mortality incidence of 2.75% within 30 days (319 deaths). Most deaths were inevitable (50.7%), as they were related to advanced illnesses and would occur regardless of anesthetic or surgical procedures. The second most common cause was related to surgical complications (25%). The death rate having anesthesia as a likely contributor was 1.72:10.000 procedures, and as a potential contributor 7.78:10.000. These deaths occurred significantly earlier (<48 h) when compared to deaths from other causes. Transoperative vasopressor, extremes of age and out-of-hour surgery were independent variables associated to early deaths. CONCLUSIONS: The study confirms that postoperative mortality in which anesthesia was involved occurred earlier in the perioperative period. In addition, it was revealed that this involvement of anesthesia as a morbidity contributor shows higher frequency when considering the anesthesiologist perioperative role, and when assessing the mortality in the long term (30 days).

Effects of Transcranial Direct Current Stimulation Block Remifentanil-Induced Hyperalgesia: A Randomized, Double-Blind Clinical Trial.

Background: Remifentanil-induced hyperalgesia (r-IH) involves an imbalance in the inhibitory and excitatory systems. As the transcranial Direct Current Stimulation (tDCS) modulates the thalamocortical synapses in a top-down manner, we hypothesized that the active (a)-t-DCS would be more effective than sham(s)-tDCS to prevent r-IH. We used an experimental paradigm to induce temporal summation of pain utilizing a repetitive cold test (rCOLDT) assessed by the Numerical Pain Score (NPS 0-10) and we evaluated the function of the descending pain modulatory system (DPMS) by the change on the NPS (0-10) during the conditioned pain modulation (CPM)-task (primary outcomes). We tested whether a-tDCS would be more effective than s-tDCS to improve pain perception assessed by the heat pain threshold (HPT) and the reaction time during the ice-water pain test (IPT) (secondary outcomes). Methods: This double-blinded, factorial randomized trial included 48 healthy males, ages ranging 19-40 years. They were randomized into four equal groups: a-tDCS/saline, s-tDCS/saline, a-tDCS/remifentanil and s-tDCS/remifentanil. tDCS was applied over the primary motor cortex, during 20 min at 2 mA, which was introduced 10 min after starting remifentanil infusion at 0.06 µg⋅kg-1⋅min-1 or saline. Results: An ANCOVA mixed model revealed that during the rCOLDT, there was a significant main effect on the NPS scores (F = 3.81; P = 0.01). The s-tDCS/remifentanil group presented larger pain scores during rCOLDT, [mean (SD) 5.49 (1.04)] and a-tDCS/remifentanil group had relative lower pain scores [4.15 (1.62)]; showing its blocking effect on r-IH. a-tDCS/saline and s-tDCS/saline groups showed lowest pain scores during rCOLDT, [3.11 (1.2)] and [3.15 (1.62)], respectively. The effect of sedation induced by remifentanil during the rCOLDT was not significant (F = 0.76; P = 0.38). Remifentanil groups showed positive scores in the NPS (0-10) during the CPM-task, that is, it produced a disengagement of the DPMS. Also, s-tDCS/Remifentanil compared to a-tDCS showed lower HPT and larger reaction-time during the IPT. Conclusion: These findings suggest that effects of a-tDCS prevent the summation response induced by r-IH during rCOLDT and the a-tDCS blocked the disengagement of DPMS. Thereby, tDCS could be considered as a new approach to contra-regulate paradoxical mechanisms involved in the r-IH. Clinical trials identification: NCT02432677. URL:https://clinicaltrials.gov/.

Clinical efficacy of dexmedetomidine alone is less than propofol for conscious sedation during ERCP.

BACKGROUND: Propofol is an accepted method of sedation for an ERCP and generally achieves deep sedation rather than conscious sedation, and dexmedetomidine has sedative properties of equivalent efficacy. OBJECTIVE: To examine the hypothesis that dexmedetomidine is as effective as propofol combined with fentanyl for providing conscious sedation during an ERCP. DESIGN AND SETTING: Randomized, blind, double-dummy clinical trial. PATIENTS: Twenty-six adults, American Society of Anesthesiologists status I to III, underwent an ERCP. INTERVENTIONS: Patients were randomized to receive either propofol (n = 14) (target plasma concentration range 2-4 microg/mL) combined with fentanyl 1 microg/kg, or dexmedetomidine (n = 12) 1 microg/kg for 10 minutes, followed by 0.2 to 0.5 microg/kg/min. Additional sedatives were used if adequate sedation was not achieved at the maximum dose allowed. MAIN OUTCOMES MEASUREMENTS: The sedation level was assessed by the Richmond alertness-sedation scale and the demand for additional sedatives. Furthermore, heart rate, blood pressure, oxygen saturation, and respiratory rate were continuously assessed. RESULTS: The relative risk (RR) was 2.71 (95% CI, 1.31-5.61) and the number of patients that needed to be treated (NNT) was 1.85 (95% CI, 1.19-4.21) to observe one additional patient with drowsiness 15 minutes after sedation in the dexmedetomidine group. Also, the RR was 9.42 (95% CI, 1.41-62.80), and the NNT was 1.42 (95% CI, 1.0-2.29) to require additional analgesic. However, there was also a greater reduction in blood pressure, a lower heart rate, and greater sedation after the procedure. CONCLUSIONS: Dexmedetomidine alone was not as effective as propofol combined with fentanyl for providing conscious sedation during an ERCP. Furthermore, dexmedetomidine was associated with greater hemodynamic instability and a prolonged recovery.