Identification of Distinct Clinical Phenotypes of Critically Ill COVID-19 Patients: Results from a Cohort Observational Study.

Purpose: COVID-19 presents complex pathophysiology, and evidence collected points towards an intricate interaction between viral-dependent and individual immunological mechanisms. Identifying phenotypes through clinical and biological markers may provide a better understanding of the subjacent mechanisms and an early patient-tailored characterization of illness severity. Methods: A multicenter prospective cohort study was performed in 5 hospitals in Portugal and Brazil for one year between 2020-2021. All adult patients with an Intensive Care Unit admission with SARS-CoV-2 pneumonia were eligible. COVID-19 was diagnosed using clinical and radiologic criteria with a SARS-CoV-2 positive RT-PCR test. A two-step hierarchical cluster analysis was made using several class-defining variables. Results: 814 patients were included. The cluster analysis revealed a three-class model, allowing for the definition of three distinct COVID-19 phenotypes: 407 patients in phenotype A, 244 patients in phenotype B, and 163 patients in phenotype C. Patients included in phenotype A were significantly older, with higher baseline inflammatory biomarkers profile, and a significantly higher requirement of organ support and mortality rate. Phenotypes B and C demonstrated some overlapping clinical characteristics but different outcomes. Phenotype C patients presented a lower mortality rate, with consistently lower C-reactive protein, but higher procalcitonin and interleukin-6 serum levels, describing an immunological profile significantly different from phenotype B. Conclusions: Severe COVID-19 patients exhibit three different clinical phenotypes with distinct profiles and outcomes. Their identification could have an impact on patients' care, justifying different therapy responses and inconsistencies identified across different randomized control trial results.

Antibiotic Consumption and Deviation of Prescribed Daily Dose From the Defined Daily Dose in Critical Care Patients: A Point-Prevalence Study.

Background: The consumption of antibiotics is one of the metrics used to evaluate the impact of antimicrobial stewardship programs (ASP). The aim of this study was to determine the prevalence of antibiotic consumption in Brazilian intensive care units (ICUs) and estimate the deviation of the prescribed daily dose (PDD) from the defined daily dose (DDD). Methods: This is a multicenter, observational, point-prevalence study carried out in adult ICUs of 8 Brazilian hospitals from August 2019, to February 2020. We collected data on the patient's demographic and clinical characteristics, antibiotic therapy, classification and site of infections. The DU90 (antibiotic accounting for 90% of the volume utilized) was calculated, and the antibiotics were classified by the Anatomical Therapeutic Chemical (ATC) Index and the World Health Organization (WHO) Access, Watch, Reserve (AWaRe) groups. For the most prevalent antibiotics, the deviation of PDD from DDD was determined. Results: Three hundred thirty-two patients from 35 ICUs were analyzed. The prevalence of antibiotic use was 52.4%. The patients in use of antibiotics were predominantly over 60 years of age (81.6%) with pulmonary infections (45.8%). A predominance of empirical regimens was observed (62.6%) among antibiotic therapies. The highest frequencies of prescriptions observed were for piperacillin + tazobactam (16.1%), meropenem (13.3%), amoxicillin + clavulanate (7.2%), azithromycin (7.2%), and teicoplanin (6.1%). The watch (64.2%) and reserve (9.6%) categories of the AWaRe classification accounted for 73.8% of all antibiotics, and they were prescribed alone or in combinations. High variability of doses was observed for the most prescribed antibiotics, and large deviations of PDD from the DDD were observed for meropenem, teicoplanin, and tigecycline. Conclusions: The high prevalence of antibiotic prescription was related to a predominance of empirical regimens and antibiotics belonging to the WHO Watch classification. High variability of doses and large deviations of PDD from DDD for meropenem, teicoplanin, and tigecycline was observed, suggesting that DDD may be insufficient to monitor the consumption of these antibiotics in the ICU population. The variability of doses found for the most prescribed antibiotics suggests the need for monitoring and intervention targets for antibiotic stewardship teams.

Impact of different frequencies of controlled breath and pressure-support levels during biphasic positive airway pressure ventilation on the lung and diaphragm in experimental mild acute respiratory distress syndrome.

BACKGROUND: We hypothesized that a decrease in frequency of controlled breaths during biphasic positive airway pressure (BIVENT), associated with an increase in spontaneous breaths, whether pressure support (PSV)-assisted or not, would mitigate lung and diaphragm damage in mild experimental acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 hours, animals were randomly assigned to: 1) BIVENT-100+PSV0%: airway pressure (Phigh) adjusted to VT = 6 mL/kg and frequency of controlled breaths (f) = 100 bpm; 2) BIVENT-50+PSV0%: Phigh adjusted to VT = 6 mL/kg and f = 50 bpm; 3) BIVENT-50+PSV50% (PSV set to half the Phigh reference value, i.e., PSV50%); or 4) BIVENT-50+PSV100% (PSV equal to Phigh reference value, i.e., PSV100%). Positive end-expiratory pressure (Plow) was equal to 5 cmH2O. Nonventilated animals were used for lung and diaphragm histology and molecular biology analysis. RESULTS: BIVENT-50+PSV0%, compared to BIVENT-100+PSV0%, reduced the diffuse alveolar damage (DAD) score, the expression of amphiregulin (marker of alveolar stretch) and muscle atrophy F-box (marker of diaphragm atrophy). In BIVENT-50 groups, the increase in PSV (BIVENT-50+PSV50% versus BIVENT-50+PSV100%) yielded better lung mechanics and less alveolar collapse, interstitial edema, cumulative DAD score, as well as gene expressions associated with lung inflammation, epithelial and endothelial cell damage in lung tissue, and muscle ring finger protein 1 (marker of muscle proteolysis) in diaphragm. Transpulmonary peak pressure (Ppeak,L) and pressure-time product per minute (PTPmin) at Phigh were associated with lung damage, while increased spontaneous breathing at Plow did not promote lung injury. CONCLUSION: In the ARDS model used herein, during BIVENT, the level of PSV and the phase of the respiratory cycle in which the inspiratory effort occurs affected lung and diaphragm damage. Partitioning of inspiratory effort and transpulmonary pressure in spontaneous breaths at Plow and Phigh is required to minimize VILI.

Impact of Different Tidal Volume Levels at Low Mechanical Power on Ventilator-Induced Lung Injury in Rats.

Tidal volume (VT) has been considered the main determinant of ventilator-induced lung injury (VILI). Recently, experimental studies have suggested that mechanical power transferred from the ventilator to the lungs is the promoter of VILI. We hypothesized that, as long as mechanical power is kept below a safe threshold, high VT should not be injurious. The present study aimed to investigate the impact of different VT levels and respiratory rates (RR) on lung function, diffuse alveolar damage (DAD), alveolar ultrastructure, and expression of genes related to inflammation [interleukin (IL)-6], alveolar stretch (amphiregulin), epithelial [club cell secretory protein (CC)16] and endothelial [intercellular adhesion molecule (ICAM)-1] cell injury, and extracellular matrix damage [syndecan-1, decorin, and metalloproteinase (MMP)-9] in experimental acute respiratory distress syndrome (ARDS) under low-power mechanical ventilation. Twenty-eight Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, 21 animals were randomly assigned to ventilation (2 h) with low mechanical power at three different VT levels (n = 7/group): (1) VT = 6 mL/kg and RR adjusted to normocapnia; (2) VT = 13 mL/kg; and 3) VT = 22 mL/kg. In the second and third groups, RR was adjusted to yield low mechanical power comparable to that of the first group. Mechanical power was calculated as [(Δ[Formula: see text]/Est,L)/2]× RR (ΔP,L = transpulmonary driving pressure, Est,L = static lung elastance). Seven rats were not mechanically ventilated (NV) and were used for molecular biology analysis. Mechanical power was comparable among groups, while VT gradually increased. ΔP,L and mechanical energy were higher in VT = 22 mL/kg than VT = 6 mL/kg and VT = 13 mL/kg (p < 0.001 for both). Accordingly, DAD score increased in VT = 22 mL/kg compared to VT = 6 mL/kg and VT = 13 mL/kg [23(18.5-24.75) vs. 16(12-17.75) and 16(13.25-18), p < 0.05, respectively]. VT = 22 mL/kg was associated with higher IL-6, amphiregulin, CC16, MMP-9, and syndecan-1 mRNA expression and lower decorin expression than VT = 6 mL/kg. Multiple linear regression analyses indicated that VT was able to predict changes in IL-6 and CC16, whereas ΔP,L predicted pHa, oxygenation, amphiregulin, and syndecan-1 expression. In the model of ARDS used herein, even at low mechanical power, high VT resulted in VILI. VT control seems to be more important than RR control to mitigate VILI.

Ventilação mecânica domiciliar: uma realidade cada vez mais frequente / Mechanical ventilation home: an increasingly frequent reality

Desde que a ventilação mecânica foi difundida após a epidemia de poliomielite até os dias atuais com o avanço das estratégias diagnósticas e terapêuticas, houve significativo aumento na sobrevida dos pacientes criticamente enfermos. Este subgrupo de sobreviventes encontra-se em um estado cronicamente crítico e dentre outras disfunções e terapias de suporte, caracteriza-se pela necessidade de ventilação mecânica prolongada. Paralelo a este fato, o envelhecimento populacional eleva a chance de internações hospitalares com necessidade de assistência ventilatória invasiva. Nos dias de hoje, a ventilação mecânica domiciliar é uma realidade e tornou-se uma opção viável para pacientes com insuficiência respiratória crônica, também estimulada pelo crescimento da utilização de ventilação não invasiva com pressão positiva, o reconhecimento de diferentes tipos de pacientes que podem se beneficiar desta técnica e redução dos custos hospitalares através da desospitalização.Atualmente possuímos diversos tipos e modelos de ventiladores exclusivos para ventilação mecânica domiciliar, assim como interfaces e a escolha do dispositivo ideal para cada paciente pode ser uma tarefa árdua. Porém não pode ser esquecido que o objetivo principal da utilização da ventilação domiciliar deve ser o controle dos sintomas decorrentes da doença do paciente e consequente melhora da qualidade de vida...

Since mechanical ventilation was widespread after the polio epidemic to the present day with the advancement of diagnostic and therapeutic strategies, a significant increase in survival of critically ill patients. This subgroup of survivors is in a critical state and chronically various etiologies and therapies support, characterized by the need for prolonged mechanical ventilation. Parallel to this fact, population aging increases the chance of hospitalizations requiring invasive mechanical ventilation. Today, home mechanical ventilation is a reality and has become a viable option for patients with chronic respiratory insufficiency, also encouraged by the increasing use of noninvasive positive pressure ventilation, recognition of different types of patients who may benefit from this technique and reduced hospital costs through deinstitutionalization.We currently have various types and models of home mechanical ventilatiors, as well as interfaces and choosing the right device for each patient can be a chore. But it can not be forgotten that the main purpose of using home ventilation is to control the symptoms of the patient’s illness and consequent improvement in quality of life...