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Abstract Aims Drug‐refractory electrical storm (ES) is a life‐threatening medical emergency. We describe the use of venoarterial extracorporeal membrane oxygenation (VA‐ECMO) in drug‐refractory ES without a reversible trigger, for which specific guideline recommendations are still lacking. Methods and results Retrospective observational study in four Iberian centres on the indications, treatment, complications, and outcome of drug‐refractory ES not associated with acute coronary syndromes, decompensated heart failure, drug toxicity, electrolyte disturbances, endocrine emergencies, concomitant acute illness with fever, or poor compliance with anti‐arrhythmic drugs, requiring VA‐ECMO for circulatory support. Thirty‐four (6%) out of 552 patients with VA‐ECMO for cardiogenic shock were included [71% men; 57 (44–62) years], 65% underwent cardiopulmonary resuscitation before VA‐ECMO implantation, and 26% during cannulation. Left ventricular unloading during VA‐ECMO was used in 8 (24%) patients: 3 (9%) with intraaortic balloon pump, 3 (9%) with LV vent, and 2 (6%) with Impella. Thirty (88%) had structural heart disease and 8 (24%) had an implantable cardioverter‐defibrillator. The drug‐refractory ES was mostly due to monomorphic ventricular tachycardia (VT) and ventricular fibrillation (VF) (59%), isolated monomorphic VT (26%), polymorphic VT (9%), or VF (6%). Thirty‐one (91%) required deep sedation, 44% overdrive pacing, 36% catheter ablation, and 26% acute autonomic modulation. The main complications were nosocomial infection (47%), bleeding (24%), and limb ischaemia (21%). Eighteen (53%) were weaned from VA‐ECMO, and 29% had heart transplantation. Twenty‐seven (79%) survived to hospital discharge (48 (33–82) days). Non‐survivors were older [62 (58–67) vs. 54 (43–58); P

Background: Carbapenemase-producing Enterobacterales (CPE) is an increasing problem in healthcare settings. This study aimed to identify the source of a CPE outbreak that occurred in 2022, in a tertiary hospital in the North of Portugal, to identify exposed patients, and to assess the risk of becoming CPE-positive following hospital admission. Methods: A multi-disciplinary investigation was conducted including descriptive, analytical, and molecular epidemiology, environmental screening, and assessment of infection control measures. Clinical and environmental isolates were analyzed using whole-genome sequencing and phylogenetic analysis. Additionally, a prospective observational cohort study was conducted to further investigate the risk factors associated with the emergence of new cases in cohorts of CPE-negative admitted patients. Results: We observed the presence of multispecies KPC-, IMP-, and/or NDM-producing isolates. Genetically indistinguishable clinical and environmental isolates were found on the same room/ward. The ST45 KPC-3-producing Klebsiella pneumoniae clone was the responsible for the outbreak. During patients’ treatment, we detected the emergence of resistance to ceftazidime-avibactam, associated with mutations in the blaKPC-3 gene (blaKPC-46, blaKPC-66 and blaKPC-124, the last variant never previously reported), suggesting a vertical evolutionary trajectory. Patients aged ≥ 75 years, hygiene/feeding-care dependent, and/or subjected to secretion aspiration were risk factors for CPE colonization after hospital admission. Additionally, cases with previous admission to the emergency department suggest that CPE dissemination may occur not only during hospitalization but also in the emergency department. Conclusion: Overall, the study highlights that selection pressure with antibiotics, like ceftazidime-avibactam, is a contributing factor to the emergence of new β-lactamase variants and antibiotic resistance. It also shows that the hospital environment can be a significant source of CPE transmission, and that routine use of infection control measures and real-time molecular epidemiology investigations are essential to ensure the long-term termination of CPE outbreaks and prevent future resurgences.

Abstract Background Extubation during extracorporeal oxygenation (ECMO) in severe acute respiratory distress syndrome (ARDS) has not been well studied. Despite the potential benefits of this strategy, weaning from ECMO before liberation from invasive mechanical ventilation remains the most frequent approach. Our aim was to evaluate the safety and feasibility of a standardized approach for extubation during ECMO in patients with severe ARDS. Results We conducted a prospective observational study to assess the safety and feasibility of a standardized approach for extubation during ECMO in severe ARDS among 254 adult patients across 4 intensive care units (ICU) from 2 tertiary ECMO centers over 6 years. This consisted of a daily assessment of clinical and gas exchange criteria based on an Extracorporeal Life Support Organization guideline, with extubation during ECMO after validation by a dedicated intensive care medicine specialist. Fifty-four (21%) patients were extubated during ECMO, 167 (66%) did not reach the clinical criteria, and in 33 (13%) patients, gas exchange precluded extubation during ECMO. At ECMO initiation, there were fewer extrapulmonary organ dysfunctions (lower SOFA score [OR, 0.88; 95% CI, 0.79–0.98; P = .02] with similar PaO2/FiO2) when compared with patients not extubated during ECMO. Extubation during ECMO associated with shorter duration of invasive mechanical ventilation (7 (4–18) vs. 32 (18–54) days; P

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Objective: Identify lung sequelae of COVID-19 through radiological and pulmonary function assessment. Design: Prospective, longitudinal, cohort study from March 2020 to March 2021. Setting: Intensive Care Units (ICU) in a tertiary hospital in Portugal. Patients: 254 patients with COVID-19 admitted to ICU due to respiratory illness. Interventions: A chest computed tomography (CT) scan and pulmonary function tests (PFT) were performed at 3 to 6 months. Main variables of interest: CT-scan; PFT; decreased diffusion capacity of carbon monoxide (DLCO). Results: All CT scans revealed improvement in the follow-up, with 72% of patients still showing abnormalities, 58% with ground glass opacities and 62% with evidence of fibrosis. PFT had abnormalities in 94 patients (46%): thirteen patients (7%) had an obstructive pattern, 35 (18%) had a restrictive pattern, and 58 (30%) had decreased DLCO. There was a statistically significant association between abnormalities in the follow-up CT scan and older age, more extended hospital and ICU stay, higher SAPS II and APACHE scores and invasive ventilation. Mechanical ventilation, especially with no lung protective parameters, was associated with abnormalities in PFT. Multivariate regression showed more abnormalities in lung function with more extended ICU hospitalization, chronic obstructive pulmonary disease (COPD), chronic kidney disease, invasive mechanical ventilation, and ventilation with higher plateau pressure, and more abnormalities in CT-scan with older age, more extended ICU stay, organ solid transplants and ventilation with higher positive end-expiratory pressure (PEEP). Conclusions: Most patients with severe COVID-19 still exhibit abnormalities in CT scans or lung function tests three to six months after discharge. Resumen: Objetivo: Identificar secuelas pulmonares de COVID-19 através de evaluación radiológica y de función pulmonar.Diseño: Estudio prospectivo, longitudinal, de cohortes de marzo de 2020 a marzo de 2021. Ámbito: Unidades de Cuidados Intensivos (UCI) en un hospital terciario en Portugal. Pacientes: Se incluyeron un total de 254 pacientes con COVID-19 confirmada por ensayo de reacción en cadena de la polimerasa con transcriptasa inversa en tiempo real de hisopos nasales/faríngeos. Intervenciones: Se realizaron una tomografía axial computarizada (TAC) de tórax y pruebas de función pulmonar (PFP) a los 3 a 6 meses. Principales variables de interés: TAC; PFP; Disminución de capacidad de difusión de monóxido de carbono (DLCO). Resultados: Todas TAC revelaron una mejora en el seguimiento, con el 72 % de los pacientes que aún mostraban anomalías, el 58 % con opacidades en vidrio esmerilado y el 62 % con evidencia de fibrosis. La PFP presentó anomalías en 94 pacientes (46 %): trece pacientes tenían un patrón obstructivo, 35 un patrón restrictivo y 58 tenían una DLCO disminuida. La regresión logística multivariada mostró más anomalías en la función pulmonar con hospitalización en la UCI más prolongada, enfermedad pulmonar obstructiva crónica (EPOC), enfermedad renal crónica, ventilación mecánica invasiva y ventilación con presión de meseta más alta, y más anomalías en la tomografía computarizada con mayor edad, estancia más prolongada en la UCI, y ventilación con mayor Titulación de Pression Positiva Expiratória (PEEP). Conclusiones: La mayoría de los pacientes con COVID-19 grave aún presentan anomalías en las tomografías computarizadas o en las pruebas de función pulmonar de tres a seis meses después del alta.

Abstract The current COVID‐19 pandemic was an exceptional health situation, including for drug use. As there was no known effective drug for COVID‐19 at the beginning of the pandemic, different drug candidates were proposed. In this article, we present the challenges for an academic Safety Department to manage the global safety of a European trial during the pandemic. The National Institute for Health and Medical Research (Inserm) conducted a European multicenter, open‐label, randomized, controlled trial involving three repurposed and one‐in development drugs (lopinavir/ritonavir, IFN‐β1a, hydroxychloroquine, and remdesivir) in adults hospitalized with COVID‐19. From 25 March 2020 to 29 May 2020, the Inserm Safety Department had to manage 585 Serious Adverse Events (SAEs) initial notification and 396 follow‐up reports. The Inserm Safety Department's staff was mobilized to manage these SAEs and to report Expedited safety reports to the competent authorities within the legal timeframes. More than 500 queries were sent to the investigators due to a lack of or incoherent information on SAE forms. At the same time, the investigators were overwhelmed by the management of patients suffering from COVID‐19 infection. These particular conditions of missing data and lack of accurate description of adverse events made evaluation of the SAEs very difficult, particularly the assessment of the causal role of each investigational medicinal product. In parallel, working difficulties were accentuated by the national lockdown, frequent IT tool dysfunctions, delayed implementation of monitoring and the absence of automatic alerts for SAE form modification. Although COVID‐19 is a confounding factor per se, the delay in and quality of SAE form completion and the real‐time medical analysis by the Inserm Safety Department were major issues in the quick identification of potential safety signals. To conduct a high‐quality clinical trial and ensure patient safety, all stakeholders must take their roles and responsibilities.

RESUMO Objetivo: Avaliar a influência das características dos pacientes na hiperlactatemia em uma população admitida com infecção em unidades de terapia intensiva, bem como a influência da gravidade da hiperlactatemia na mortalidade hospitalar. Metódos: Foi realizada uma análise post hoc da hiperlactatemia no INFAUCI, um estudo nacional prospectivo, observacional e multicêntrico, que incluiu 14 unidades de terapia intensiva portuguesas. Foram selecionados pacientes admitidos com infecção em unidades de terapia intensiva com dosagem de lactato nas primeiras 12 horas de admissão. A sepse foi identificada de acordo com a definição Sepsis-2 aceita no momento da coleta de dados. A gravidade da hiperlactatemia foi classificada como leve (2 - 3,9mmol/L), moderada (4,0 - 9,9mmol/L) ou grave (> 10mmol/L). Resultados: De 1.640 pacientes admitidos com infecção, a hiperlactatemia ocorreu em 934 (57%) e foi classificada como leve, moderada e grave em 57,0%, 34,4% e 8,7% dos pacientes, respectivamente. A presença de hiperlactatemia e um maior grau de hiperlactatemia se associaram a um maior Simplified Acute Physiology Score II, a maior Índice de Comorbidade de Charlson e à presença de choque séptico. Em relação à curva Receiver Operating Characteristic do lactato para mortalidade hospitalar, foi encontrada área sob a curva de 0,64 (IC95% 0,61 - 0,72), que aumentou para 0,71 (IC95% 0,68 - 0,74) quando se combinou o Sequential Organ Failure Assessment. A mortalidade intra-hospitalar com outras covariáveis ajustadas pelo Simplified Acute Physiology Score II se associou à hiperlactatemia moderada e grave, com razão de chances de 1,95 (IC95% 1,4 - 2,7; p < 0,001) e 4,54 (IC95% 2,4 - 8,5; p < 0,001), respectivamente. Conclusão: Os níveis de lactato sanguíneo correlacionam-se independentemente com a mortalidade intra-hospitalar para graus moderados e graves de hiperlactatemia.

RESUMO Introdução: A Sociedade Portuguesa de Cuidados Intensivos e o Grupo de Infeção e Sépsis emitiram previamente recomendações visando à organização dos serviços de saúde e ao manejo dos doentes críticos com COVID-19. Em virtude da evolução do conhecimento, o painel de peritos voltou a se organizar para rever a atual evidência e emitir recomendações atualizadas. Métodos: Foi reunido um painel nacional de peritos que declararam não ter conflitos de interesse para o desenvolvimento das recomendações. Foram desenvolvidas perguntas operacionais conforme a metodologia PICO, e foi conduzida uma revisão sistemática rápida por meio da consulta de diferentes fontes bibliográficas. O painel determinou a direção e a força das recomendações com a utilização de duas rodadas de um método Delphi, conduzido seguindo princípios do sistema GRADE. Uma recomendação forte recebeu a redação “recomenda-se”, e uma recomendação fraca foi redigida como “sugere-se”. Resultados: Foram emitidas 48 recomendações e 30 sugestões abrangendo os seguintes tópicos: diagnóstico de infecção por SARS-CoV-2, coinfecção e superinfecção; critérios de admissão, cura e suspensão de isolamento; organização dos serviços; Equipamentos de Proteção Individual; terapêuticas de suporte respiratório e outras e terapêuticas específicas (antivirais, imunomodeladores e anticoagulação). Conclusão: Essas recomendações, especificamente orientadas para a realidade portuguesa, mas que podem se aplicar também aos Países Africanos de Língua Oficial Portuguesa e ao Timor-Leste, visam apoiar os profissionais de saúde no manejo de doentes críticos com COVID-19. Pretende-se que sejam constantemente revistas, de modo a refletir o avanço de nossa compreensão e o da terapêutica dessa patologia.

PurposeTo analyze the long-term consequences of critical COVID-19, regarding physical, mental, cognitive and functional impairments, and to describe its evolution through time.MethodsProspective cohort study, with consecutive inclusion of patients admitted due to SARS-CoV-2 to intensive care units(ICU) of a tertiary-care center, between May/2020 and September/2021. All included patients were included in Physical and Rehabilitation Medicine(PRM) inpatient programs during ICU stay. Eligible patients were evaluated on PRM appointments 6 and 12 months after ICU discharge. In each visit, physical examination and a predefined set of scales were applied, aiming to comprehensively evaluate the three domains (physical, mental and cognitive) of post-intensive care syndrome and the patients' functionality. Statistical analysis encompassed descriptive and univariate analysis.ResultsA total of 42 patients were included: 66.7% males, mean age of 62 yo. In the physical domain, 6 months after ICU discharge, there was a significant reduction in quality of life (p-value = 0.034), muscle strength (p-value = 0.002), gait ability (p-valueConclusionCritical COVID-19 survivors present significant physical, mental and cognitive impairments 6 and 12 months after ICU discharge, despite their positive evolution through time.

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Abstract Introduction Antimicrobial resistance is a major public health threat. Antimicrobial stewardship (AMS) is one of the key strategies to overcome resistance, but robust evidence on the effect of specific interventions is lacking. We report an interrupted time series (ITS) analysis of a persuasive AMS intervention implemented during a KPC producing Klebsiella pneumoniae outbreak. Methods A controlled ITS for carbapenem consumption, total antibiotic consumption and antibiotic-free days, between January 2012 and May 2018 was performed, using segmented regression analysis. The AMS intervention was implemented in the Vascular Surgery ward starting on April 2016 in the context of a KPC outbreak. The General Surgery ward was taken as a control group. Data were aggregated by month for both wards, including 51 pre-intervention and 26 intervention points. Results The AMS intervention produced a level change in carbapenem consumption of − 11.14 DDDs/100 patient-days accompanied by a decreasing trend of total antibiotic consumption and stable rate of antibiotic-free days in Vascular Surgery ward. These differences were not apparent in the control group. No differences in mortality or readmission rates between pre-intervention and intervention periods were noticed in any of the groups. Conclusion Persuasive AMS interventions on top of previously implemented restrictive interventions can reduce carbapenem consumption without increasing total antibiotic consumption. Starting persuasive AMS interventions in an outbreak setting does not compromise the sustainability of the intervention.

Introduction: Long-term health impairments are often experienced among survivors of critical illness, which may have a negative impact on their quality of life. The aim of this study was to characterize COVID-19 survivors of critical illness and to evaluate health-related quality of life and disability following hospital discharge. Material and Methods: This is a retrospective case-series study that included COVID-19 survivors admitted to the Intensive Care Medicine Department of a University Hospital. Follow-up evaluation was performed between the 30th and the 90th day after discharge. Quality of life was explored using the five-level version of the EQ-5D instrument (EQ-5D-5L) and functionality using the 12-question World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Results: Forty-five survivors were enrolled, 28 (62.2%) men, median age 63.0 years. The EQ-5D-5L questionnaire showed moderate to extreme problems in some dimension in 29 patients (64.4%): mobility in six (13.3%), self-care in seven (13.3%), usual activities in 23 (51.1%), pain/discomfort in 14 (31.1%) and anxiety/depression in 17 (37.8%). When using the 12-question WHODAS 2.0 questionnaire, moderate to extreme disability was reported in some question in 37 patients (82.2%): 19 (42.2%) in standing for long periods, 18 (40.0%) in long-distance walking; 14 (31.1%) on taking care of household responsibilities and 17 (37.8%) in their day-to-day work; 23 (51.1%) felt emotionally affected by their health problems. Discussion: Based on COVID-19 survivors-reported outcomes after critical illness, mobility, pain/discomfort, and anxiety/depression were the main problems that persisted one to three months after hospital discharge. Conclusion: An organized follow-up structure is crucial to improve health-related quality of life in critical COVID-19 survivors.

Abstract Background Early sepsis diagnosis is crucial for the correct management of burn patients, and it clearly influences outcomes. The systemic inflammatory response triggered by burns mimics sepsis presentation and complicates early sepsis diagnosis. Biomarkers were advocated to aid the diagnosis of early sepsis. Serum procalcitonin (PCT) exhibits fair accuracy and good correlation with sepsis severity, being used in diverse clinical settings. However, few studies have evaluated perioperative changes in PCT levels in burn patients. The present study evaluated PCT kinetics during the first days after burn injury and subsequent surgical interventions to assess PCT utility in distinguishing septic from non-septic inflammatory responses. Methods This study was a retrospective observational study of all burn patients admitted to the Coimbra Burns Unit (Portugal) between January 2011 and December 2014 who presented with a total burn surface area ≥ 15% and who underwent subsequent surgery. PCT kinetics were investigated a) during the first five days after burn injury and b) preoperatively during the five days after surgery in three subsets of patients, including those with no preoperative and no postoperative sepsis (NN), no preoperative but postoperative sepsis (NS), and preoperative and postoperative sepsis (SS). A total of 145 patients met the selection criteria and were included in the analysis. Results PCT levels in the first five days after burn injury were significantly higher in patients who developed at least one sepsis episode (n = 85) compared with patients who did not develop sepsis (n = 60). PCT values > 1.00 ng/mL were clearly associated with sepsis. Study participants (n = 145) underwent a total of 283 surgical interventions. Their distribution by preoperative/postoperative sepsis status was 142 (50.2%) in NN; 62 (21.9%) in NS; and 79 (27.9%) in SS. PCT values exhibited a parallel course in the three groups that peaked on the second postoperative day and returned to preoperative levels on the third day or later. The lowest PCT values were found in NN, and the highest values were observed in SS; the NS values were intermediate. Conclusions PCT kinetics coupled with a clinical examination may be helpful for sepsis diagnosis during the first days after burn injury and burn surgery.

Introduction: The ideal biomarker to assess response and prognostic assessment in the infected critically ill patient is still not available. The aims of our study were to analyze the association between early C-reactive protein kinetics and duration and appropriateness of antibiotic therapy and its usefulness in predicting mortality in infected critically ill patients. Material and Methods: We have carried out an observational retrospective study in a cohort of 60 patients with community-acquired pneumonia, aspiration pneumonia and bacteremia at an intensive care unit. We have collected C-reactive protein consecutive serum levels for eight days as well as duration and appropriateness of initial antibiotic therapy. C-reactive protein kinetic groups were defined based on the levels at days 0, 4 and 7. With a follow-up of one year, we have evaluated mortality at different time-points. Results: We have obtained three different C-reactive protein kinetic groups from the sample: fast response, delayed but fast response and delayed and slow response. We did not find statistically significant associations between C-reactive protein kinetics and early (intensive care unit, hospital and 28-days) or late (six months and one year) mortality and antibiotic therapy duration (p > 0.05). Although there were no statistically significant differences between the appropriateness of antibiotic therapy and the defined groups (p = 0.265), no patient with inappropriate antibiotic therapy presented a fast response pattern. Discussion: Several studies suggest the importance of this protein in infection. Conclusion: Early C-reactive protein kinetics is not associated with response and prognostic assessment in infected critically ill patients. Nevertheless, a fast response pattern tends to exclude initial inappropriate antibiotic therapy.

Abstract Background Due to greater infection susceptibility, sepsis is the main cause of death in burn patients. Quick diagnosis and patient stratification, early and appropriated antimicrobial therapy, and focus control are crucial for patients’ survival. On the other hand, superfluous extension of therapy is associated with adverse events and arousal of microbial resistance. The use of biomarkers, necessarily coupled with close clinical examination, may predict outcomes, stratifying patients who need more intensive care, and monitor the efficacy of antimicrobial therapy, allowing faster de-escalation or stop, reducing the development of resistance and possibly the financial burden, without increasing mortality. The aim of this work is to check the suitability of procalcitonin (PCT) to fulfill these goals in a large sample of septic burn patients. Methods One hundred and one patients, with 15% or more of total body surface area (TBSA) burned, admitted from January 2011 to December 2014 at Coimbra Burns Unit (CBU), in Portugal were included in the sample. All patients had a diagnosis of sepsis, according to the American Burn Association (ABA) criteria. The sample was factored by survival (68 survivors and 33 non-survivors). The maximum value of PCT in each day was used for statistical analysis. Data were summarized by location measures (mean, median, minimum, maximum, quartiles) and dispersion measures (standard error and range measures). Statistical analysis was performed with SPSS© 23.0 IBM© for Windows©. Results There were statistically significant differences between PCT levels of patients from the survivor and non-survivor groups during the first and the last weeks of hospitalization as well as during the first week after sepsis suspicion, being slightly higher during this period. During the first 7 days of antimicrobial therapy, PCT was always higher in the non-survivor, still without reaching statistical significance, but when the analysis was extended till the 15th day, PCT increased significantly, rapidly, and steadily, denouncing therapy failure. Conclusion Despite being not an ideal biomarker, PCT proved to have good prognostic power in septic burn patients, paralleling the evolution of the infectious process and reflecting the efficacy of antimicrobial therapy, and the inclusion of its serial dosing may be advised to reinforce antimicrobial stewardship programs at burn units; meanwhile, more accurate approaches are not available.

Introduction: The use of endotracheal suctioning is a common procedure in intensive care units, which implies various risks, namely hypoxemia, atelectasis, arterial hypertension, microbial colonization, etc. Nevertheless, healthcare professionals can adopt certain strategies to prevent these adverse events. Aim: To describe good practice relating to endotracheal suctioning in patients undergoing invasive ventilation. Materials and Methods: Integrative literature review. The research occurred in December 2015, using the databases B-on, PUBMED and RCAAP and 534 documents were found. After inclusion/exclusion and quality criteria evaluation, four studies were accepted for inclusion in this review. Results: Recommendations encountered were: suction only when necessary, pre-oxygenate, use a suction catheter with half the diameter of the endotracheal tube, avoid saline instillation, employ a closed aspiration system when FiO2 or positive end-expiratory pressure is elevated, limit the procedural duration to under 15 seconds and monitor the patient. Conclusion: The review demonstrates that some conclusions are not consensual, which represents a limitation of this study, since more experimental studies are needed, which represents a limitation of this study, since more experimental studies are needed. However, the stimulation of open debate, reflection, as well as the adoption of preventative measures, can lead to safer practice.

The continuous development of resuscitation techniques and intensive care reduced the mortality rate induced by the initial shock in burn patients and, currently, infections (especially sepsis) are the main causes of mortality of these patients. The misuse of antimicrobial agents is strongly related to antimicrobial and adverse patient outcomes, development of microbial resistance and increased healthcare-related costs. To overcome these risks, antimicrobial stewardship is mandatory and biomarkers are useful to avoid unnecessary medical prescription, to monitor antimicrobial therapy and to support the decision of its stop. Among a large array of laboratory tests, procalcitonin (PCT) emerged as the leading biomarker to accurately and time-effectively indicate the presence of systemic infection. In the presence of systemic infection, PCT blood levels undergo a sudden and dramatic increase, following the course of the infection, and quickly subside after the control of the septic process. This work is a meta-analysis on PCT performance as a biomarker for sepsis. This meta-analysis showed that overall pooled area under the curve (AUC) is 0.83 (95% CI = 0.76 to 0.90); the estimated cut-off is 1.47 ng/mL. The overall sepsis effect in PCT levels is significant and strong (Cohen's d is 2.1 and 95% CI = 1.1 to 3.2). This meta-analysis showed PCT may be considered as a biomarker with a strong diagnostic ability to discriminate between the septic from the non-septic burn patients. Thus, this work encourages the determination of PCT levels in clinical practice for the management of these patients, in order to timely identify the susceptibility to sepsis and to initiate the antimicrobial therapy, improving the patients' outcomes.

RESUMO A atual epidemia de COVID-19 foi declarada em 31 de dezembro de 2019 no mercado de frutos do mar da cidade de Wuhan, com rápida disseminação na China e, posteriormente, envolvendo múltiplos países (como maior expressão na Coreia do Sul, Japão, Itália e Irã) incluindo, desde 1º de março, Portugal. A maioria dos doentes infetados apresenta doença ligeira sem necessidade de hospitalização. Dentre os internados, de 6% a 10% necessitam de cuidados intensivos. As presentes recomendações visam facilitar a organização dos serviços de medicina intensiva para a resposta ao COVID-19, proporcionado os melhores cuidados aos doentes e protegendo os profissionais de saúde.

Abstract Background Hospital-acquired bloodstream infections are common in the intensive care unit (ICU) and have a high mortality rate. Patients with cirrhosis are especially susceptible to infections, yet there is a knowledge gap in the epidemiological distinctions in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients in the ICU. It has been suggested that cirrhotic patients, present a trend towards more gram-positive infections, and especially enterococcal infections. This study aims to describe epidemiological differences in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients hospitalized in the ICU regarding infection sources, microorganisms and mortality. Methods Using prospective Eurobact-2 international cohort study data, we compared hospital-acquired bloodstream infections sources and microorganisms in cirrhotic and non-cirrhotic patients. The association between Enterococcus faecium and cirrhosis was studied using a multivariable mixed logistic regression. The association between cirrhosis and mortality was assessed by a multivariable frailty Cox model. Results Among the 1059 hospital-acquired bloodstream infections patients included from 101 centers, 160 had cirrhosis. Hospital-acquired bloodstream infection source in cirrhotic patients was primarily abdominal (35.6%), while it was pulmonary (18.9%) for non-cirrhotic (p

Abstract Background Mental health symptoms among healthcare professionals (HCP) in intensive care units (ICUs) are a significant concern affecting both HCP well-being and patient care outcomes. Cross-sectional studies among members of the European Society of Intensive Care Medicine (ESICM) report up to 50% burnout rates. Determinants of burnout include communication, team cohesion, psychological support, and well-being promotion. We designed the 'Hello Bundle' intervention to mitigate burnout among ICU-HCPs by fostering positive social interactions and a supportive work environment. This justification synthesizes evidence from social psychology, positive psychology, and healthcare communication research to support the intervention. The 'Hello Bundle' aims to enhance interpersonal relationships, improve team cohesion, and reduce burnout rates. The six components include: Hello campaign posters, email reminders, integrating greetings in morning huddles, hello jars, lead-by-example initiatives, and a daily updated hello board in each ICU. This protocol describes a cluster randomized controlled trial to evaluate the effectiveness of the intervention. Methods This protocol describes a cluster randomized controlled trial (RCT) conducted among ESICM-affiliated ICUs, consisting of at least 73 clusters with in average of 50 respondents per cluster, totaling approximately 7300 participants. Intervention clusters will implement the 6-component Hello Bundle between October 14 and November 10, 2024, while control clusters will be wait-listed to receive the intervention in January 2025 after the RCT concludes. Clusters will be matched based on ICU size (fewer or more than 20 beds), region, and average 2023 mortality. The primary outcome is the proportion of HCPs with burnout between intervention and control clusters at the end of the intervention. Secondary outcomes include comparing the following between clusters: (1) number of HCPs with high emotional exhaustion; (2) number with high depersonalization; (3) number with loss of accomplishment; (4) perception of ethical climate (5) satisfaction at work (VAS); (6) professional conflicts; (7) intention to leave the ICU (VAS); (8) patient-centered care rating; (9) family-centered care rating. The last secondary outcome is the comparison of burnout rates before and after the intervention in the intervention cluster. Outcomes will be based on HCP reports collected within four weeks before and after the intervention. Discussion This is the first large trial of healthcare communication, social, and positive psychology intervention among ICU-HCPs. It holds the potential to provide valuable insights into effective strategies for addressing burnout in ICU settings, ultimately benefiting both HCPs and patients. Trial registration: This trial was registered on ClinicalTrials.Gov on June 18, 2024. Registration: NCT06453616.

Abstract Background The past years have witnessed dramatic changes in the population admitted to the intensive care unit (ICU). Older and sicker patients are now commonly treated in this setting due to the newly available sophisticated life support. However, the short- and long-term benefit of this strategy is scarcely studied. Methods The Critically Ill patients’ mortality by age: Long-Term follow-up (CIMbA-LT) was a multicentric, nationwide, retrospective, observational study addressing short- and long-term prognosis of patients admitted to Portuguese multipurpose ICUs, during 4 years, according to their age and disease severity. Patients were followed for two years after ICU admission. The standardized hospital mortality ratio (SMR) was calculated according to the Simplified Acute Physiology Score (SAPS) II and the follow-up risk, for patients discharged alive from the hospital, according to official demographic national data for age and gender. Survival curves were plotted according to age group. Results We included 37.118 patients, including 15.8% over 80 years old. The mean SAPS II score was 42.8 ± 19.4. The ICU all-cause mortality was 16.1% and 76% of all patients survive until hospital discharge. The SAPS II score overestimated hospital mortality [SMR at hospital discharge 0.7; 95% confidence interval (CI) 0.63–0.76] but accurately predicted one-year all-cause mortality [1-year SMR 1.01; (95% CI 0.98–1.08)]. Survival curves showed a peak in mortality, during the first 30 days, followed by a much slower survival decline thereafter. Older patients had higher short- and long-term mortality and their hospital SMR was also slightly higher (0.76 vs. 0.69). Patients discharged alive from the hospital had a 1-year relative mortality risk of 6.3; [95% CI 5.8–6.7]. This increased risk was higher for younger patients [21.1; (95% CI 15.1–39.6) vs. 2.4; (95% CI 2.2–2.7) for older patients]. Conclusions Critically ill patients’ mortality peaked in the first 30 days after ICU admission. Older critically ill patients had higher all-cause mortality, including a higher hospital SMR. A long-term increased relative mortality risk was noted in patients discharged alive from the hospital, but this was more noticeable in younger patients.

Abstract Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI − 0.1% [− 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (− 3.2% [− 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 ).

Abstract Background The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. Methods We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients’ characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. Results A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p

Consumption of antimicrobials is an important driver of antimicrobial resistance. There is limited knowledge of the key determinants of antimicrobial prescribing behavior in hospitals. An understanding of these determinants is required for the successful design, adoption, and implementation of quality improvement interventions in Antimicrobial Stewardship Programs (ASP). This study aimed to describe the main factors that influence the doctor’s decision on antimicrobials prescribing and to identify the behaviors that drive physicians’ decision making. A structured web-based questionnaire focused on behavioral components of antimicrobial prescription was applied to the medical staff of three different departments—Internal Medicine, General Surgery, and Intensive Care Medicine—of a university hospital. All doctors agreed that inadequate use of antimicrobials increases AMR. A total of 77% of the surgeons and 100% of the internists and intensivists perceived antimicrobial prescription as a priority in the department. Full autonomy in antimicrobial prescription was preferred by internists (64%) but not by surgeons (18%) and intensivists (24%). Most physicians were keen to have ASP advice, but most did not want advice from colleagues of the same service. Almost all surgeons ask for advice when prescribing, but only 68% of the internists do it. Less than half of all physicians and only 25% of the surgeons felt free to prescribe contrary to guidelines. Most physicians, particularly in Intensive Care Medicine (94%), adopt the “wait and see” strategy when no microbiologic confirmation is available, but 27% of the surgeons start empirical therapy. In conclusion, the context of antimicrobial prescription, autonomy, and confidence in antimicrobial prescription demonstrated heterogeneity between the three departments and this should be considered when planning ASP.

Aims: Inflammation-driven endothelitis seems to be a hallmark of acute heart failure (AHF) and cardiogenic shock (CS). Endocan, a soluble proteoglycan secreted by the activated endothelium, contributes to inflammation and endothelial dysfunction, but has been scarcely explored in human AHF. We aimed to evaluate serum (S-Endocan) and urinary endocan (U-Endocan) profiles in AHF and CS patients and to correlate them with biomarkers/parameters of inflammation, endothelial activation, cardiovascular dysfunction and prognosis.Methods: Blood and spot urine were collected from patients with AHF (n = 23) or CS (n = 25) at days 1–2 (admission), 3-4 and 5-8 and from controls (blood donors, n = 22) at a single time point. S-Endocan, U-Endocan, serum IL-1β, IL-6, tumour necrosis factor-α (S-TNF-α), intercellular adhesion molecule-1 (S-ICAM-1), vascular cell adhesion molecule-1 (S-VCAM-1) and E-selectin were determined by ELISA or multiplex immunoassays. Serum C-reactive protein (S-CRP), plasma B-type natriuretic peptide (P-BNP) and high-sensitivity troponin I (P-hs-trop I), lactate, urea, creatinine and urinary proteins, as well as prognostic scores (APACHE II, SAPS II) and echocardiographic left ventricular ejection fraction (LVEF) were also evaluated.Results: Admission S-Endocan was higher in both patient groups, with CS presenting greater values than AHF (AHF and CS vs. Controls, p < 0.001; CS vs. AHF, p < 0.01). Admission U-Endocan was only higher in CS patients (p < 0.01 vs. Controls). At admission, S-VCAM-1, S-IL-6 and S-TNF-α were also higher in both patient groups but there were no differences in S-E-selectin and S-IL-1β among the groups, nor in P-BNP, S-CRP or renal function between AHF and CS. Neither endocan nor other endothelial and inflammatory markers were reduced during hospitalization (p > 0.05). S-Endocan positively correlated with S-VCAM-1, S-IL-6, S-CRP, APACHE II and SAPS II scores and was positively associated with P-BNP in multivariate analyses. Admission S-Endocan raised in line with LVEF impairment (p = 0.008 for linear trend).Conclusion: Admission endocan significantly increases across AHF spectrum. The lack of reduction in endothelial and inflammatory markers throughout hospitalization suggests a perpetuation of endothelial dysfunction and inflammation. S-Endocan appears to be a biomarker of endothelitis and a putative therapeutic target in AHF and CS, given its association with LVEF impairment and P-BNP and its positive correlation with prognostic scores.

Cysteinyl leukotrienes (CysLT) are potent vascular leakage-promoting agents but have been scarcely explored in human septic shock (SS). We evaluated CysLT at admission and during hospitalization and their correlation with endothelial dysfunction, inflammation, oxidative stress, the renin–angiotensin–aldosterone system, and cardiac, renal, respiratory, and hepatic parameters in SS patients. Blood and spot-urine samples were collected at days 1–2 (admission), 3–4, and 5–8 in SS patients (n = 13) and at a single time point in controls (n = 22). Urinary CysLT (u-CysLT) and isoprostanes, plasma, and urinary angiotensinogen, serum myeloperoxidase, and IL-10 were quantified by ELISA. Serum intercellular-adhesion molecule-1, vascular cell-adhesion molecule-1, E-selectin, tumor necrosis factor-α, IL-1β, and IL-6 were measured by multiplex immunoassays. Routine markers were evaluated using automated analyzers. At admission, SS patients had increased u-CysLT, endothelial activation, inflammation, oxidative stress, and plasma and urinary angiotensinogen, as well as cardiac, respiratory, hepatic, and renal injury/dysfunction. There were no changes in u-CysLT during hospitalization. Both correlation and multivariate analyses showed positive relationships of u-CysLT with endothelial activation, inflammation, oxidative stress, proteinuria, and hepatic injury/dysfunction markers. These results suggest that u-CysLT may be potential non-invasive biomarkers for monitoring the pathophysiological mechanisms underlying SS, as well as putative therapeutic targets.

Abstract Background The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe. Methods A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). Results During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02–1.06, p

Abstract Antimicrobials are among the most important and commonly prescribed drugs in the management of critically ill patients and beta-lactams are the most common antibiotic class used. Critically ill patient’s pathophysiological factors lead to altered pharmacokinetics and pharmacodynamics of beta-lactams. A comprehensive bibliographic search in PubMed database of all English language articles published from January 2000 to December 2017 was performed, allowing the selection of articles addressing the pharmacokinetics or pharmacodynamics of beta-lactam antibiotics in critically ill patients. In critically ill patients, several factors may increase volume of distribution and enhance renal clearance, inducing high intra- and inter-patient variability in beta-lactam concentration and promoting the risk of antibiotic underdosing. The duration of infusion of beta-lactams has been shown to influence the fT > minimal inhibitory concentration and an improved beta-lactam pharmacodynamics profile may be obtained by longer exposure with more frequent dosing, extended infusions, or continuous infusions. The use of extracorporeal support techniques in the critically ill may further contribute to this problem and we recommend not reducing standard antibiotic dosage since no drug accumulation was found in the available literature and to maintain continuous or prolonged infusion, especially for the treatment of infections caused by multidrug-resistant bacteria. Prediction of outcome based on concentrations in plasma results in overestimation of antimicrobial activity at the site of infection, namely in cerebrospinal fluid and the lung. Therefore, although no studies have assessed clinical outcome, we recommend using higher than standard dosing, preferably with continuous or prolonged infusions, especially when treating less susceptible bacterial strains at these sites, as the pharmacodynamics profile may improve with no apparent increase in toxicity. A therapeutic drug monitoring-guided approach could be particularly useful in critically ill patients in whom achieving target concentrations is more difficult, such as obese patients, immunocompromised patients, those infected by highly resistant bacterial strains, patients with augmented renal clearance, and those undergoing extracorporeal support techniques.

Abstract Background Antibiotic resistance (AMR) is a growing public health problem worldwide, in part related to inadequate antibiotic use. A better knowledge of physicians’ motivations, attitudes and practice about AMR and prescribing should enable the design and implementation of effective antibiotic stewardship programs (ASPs). The objective of the study was to assess attitudes and perceptions concerning AMR and use of antibiotics among surgeons who regularly perform emergency or trauma surgery. Methods A cross-sectional web-based survey was conducted contacting 4904 individuals belonging to a mailing list provided by the World Society of Emergency Surgery. Participation was voluntary and anonymous. The survey was open for 5 weeks (from May 3, 2017, to June 6, 2017), within which two reminders were sent. The self-administered questionnaire was developed by a multidisciplinary team; reliability and validity were assessed. Results The overall response rate was 12.5%. Almost all participants considered AMR an important worldwide problem, but 45.6% of them underrated the problem in their own hospitals. Surgeons provided with periodic reports on local AMR demonstrated a lower underrating in their hospital. Only 66.3% of the surgeons stated to receive periodic reports on local AMR data, and among them, 56.2% had consulted them to select an antibiotic in the previous month. Availability of systematic reports about AMR, availability of guidelines for therapy of infections, and advice from an infectious diseases specialist were considered very helpful measures to improve antibiotic prescribing by 68.0, 65.7, and 64.9%, respectively. Persuasive and restrictive ASPs were both considered helpful measures by 64.5%. Moreover, 86.3% considered locally developed guidelines more useful than national ones. Only 21.9% received formal training in antibiotic prescribing in the previous year; among them, 86.6% declared to be interested in receiving more training. Conclusions Availability of periodic reports on local AMR data was considered an important tool to guide surgeons in choosing the correct antibiotic and to increase awareness of the problem of AMR. Local guidelines for therapy of infections should be implemented in every emergency surgery setting, and developed by a multidisciplinary team directly involving surgeons, infectious diseases specialists, and microbiologists, and formally established in an ASP.

Although antimicrobial consumption is considered the main driver of antimicrobial resistance (AMR), other factors probably have a significant but less studied impact. The study’s goal was to assess AMR drivers across different European countries and quantify their possible contributions using the latest data available. Using the ESAC-Net (European Surveillance of Antimicrobial Consumption Network) database, the ESVAC (European Surveillance of Veterinary Antimicrobial Consumption) database and the OECD (Organisation for Economic Cooperation and Development) information, a dataset including 23 European countries was created. Associations between AMR and potential contributing factors were assessed using bivariate correlation and multiple linear regression models for multivariable analyses. Factors associated with the AMR rate among European countries were human ambulatory consumption of antibiotics and per capita expenditure on health, meaning that the higher human ambulatory consumption of antibiotics and the lower the per capita expenditure on health, the higher the AMR. Both variables together explain 74% of AMR variation. Private expenditure on health in terms of % GDP (Gross Domestic Profit) was positively related to a higher AMR rate. In conclusion, considering antibiotic consumption as the most important factor contributing to AMR may be a deviant focus, as resistance transmission may be paramount for AMR levels. Low per capita expenditure on health, probably a surrogate of worse healthcare conditions and a high level of resistance transmission, has a strong correlation with the AMR rate. Increasing public expenditure on healthcare, to strengthen infection control structures and processes interventions, seems relevant to tackle antimicrobial resistance at the European scale.

Background: The COVID-19 pandemic poses novel challenges in antimicrobial consumption metrics and stewardship strategies. COVID-19 patients became the major cause of hospital admission during the first wave of the pandemic, often leading to an antimicrobial prescription upon admission or treatment for superinfections. The aim of this study was to understand how antimicrobial consumption was impacted at the beginning of the pandemic in a tertiary care hospital, a reference center for COVID-19. Materials and Methods: A retrospective before-and-after study was done. Descriptive statistics of discharges, patient-days, and antimicrobial use indicators (defined daily doses (DDD)/100 discharges, DDD/100 patient-days) for various groups were calculated for the first three months of the pandemic (March, April, and May 2020) as a quarterly value, and for each year in 2011–2019, and their annual percentage changes were used to estimate 95% confidence intervals. The indicators were compared to patient type (medical/surgical), type of admission (urgent/elective), and age groups using Spearman’s correlation coefficient. Results: Statistically significant increases occurred in 2020 for total antibacterials, macrolides, cephalosporins, amoxicillin/clavulanic acid, carbapenems, meropenem, and third-generation cephalosporins, while a reduction was seen in cefazolin/cefoxitin. A correlation was found between antibacterial consumption and patient or admission type. In 2020, unlike in pre-pandemic years, there was a different impact in DDD/100 discharges and DDD/100 patient-days due to increased lengths-of-stay and longer antimicrobial therapy. Conclusions: The COVID-19 pandemic led to an increase in antimicrobial consumption with a different impact in DDD/100 discharges and DDD/100 patient-days. This highlights the need to use both indicators simultaneously to better understand the causes of antimicrobial consumption variation and improve the design of effective antimicrobial stewardship interventions.

Abstract Background Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. Methods A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery. Results The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4–6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p