Procalcitonin (PCT) levels for ruling-out bacterial coinfection in ICU patients with influenza: A CHAID decision-tree analysis

Objectives: To define which variables upon ICU admission could be related to the presence of coinfection using CHAID (Chi-squared Automatic Interaction Detection) analysis. Methods: A secondary analysis from a prospective, multicentre, observational study (2009-2014) in ICU patients with confirmed A(H1N1)pdm09 infection. We assessed the potential of biomarkers and clinical variables upon admission to the ICU for coinfection diagnosis using CHAID analysis. Performance of cut-off points obtained was determined on the basis of the binominal distributions of the true (+) and true (−) results. Results: Of the 972 patients included, 196 (20.3%) had coinfection. Procalcitonin (PCT; ng/mL 2.4 vs. 0.5, p < 0.001), but not C-reactive protein (CRP; mg/dL 25 vs. 38.5; p = 0.62) was higher in patients with coinfection. In CHAID analyses, PCT was the most important variable for coinfection. PCT <0.29 ng/mL showed high sensitivity (Se = 88.2%), low Sp (33.2%) and high negative predictive value (NPV = 91.9%). The absence of shock improved classification capacity. Thus, for PCT <0.29 ng/mL, the Se was 84%, the Sp 43% and an NPV of 94% with a post-test probability of coinfection of only 6%. Conclusion: PCT has a high negative predictive value (94%) and lower PCT levels seems to be a good tool for excluding coinfection, particularly for patients without shock

Mortality comparison between the first and second/third waves among 3,795 critical COVID-19 patients with pneumonia admitted to the ICU : A multicentre retrospective cohort study

It is unclear whether the changes in critical care throughout the pandemic have improved the outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the intensive care units (ICUs). We conducted a retrospective cohort study in adults with COVID-19 pneumonia admitted to 73 ICUs from Spain, Andorra and Ireland between February 2020 and March 2021. The first wave corresponded with the period from February 2020 to June 2020, whereas the second/third waves occurred from July 2020 to March 2021. The primary outcome was ICU mortality between study periods. Mortality predictors and differences in mortality between COVID-19 waves were identified using logistic regression. As of March 2021, the participating ICUs had included 3795 COVID-19 pneumonia patients, 2479 (65·3%) and 1316 (34·7%) belonging to the first and second/third waves, respectively. Illness severity scores predicting mortality were lower in the second/third waves compared with the first wave according with the Acute Physiology and Chronic Health Evaluation system (median APACHE II score 12 [IQR 9-16] vs 14 [IQR 10-19]) and the organ failure assessment score (median SOFA 4 [3-6] vs 5 [3-7], p <0·001). The need of invasive mechanical ventilation was high (76·1%) during the whole study period. However, a significant increase in the use of high flow nasal cannula (48·7% vs 18·2%, p <0·001) was found in the second/third waves compared with the first surge. Significant changes on treatments prescribed were also observed, highlighting the remarkable increase on the use of corticosteroids to up to 95.9% in the second/third waves. A significant reduction on the use of tocilizumab was found during the study (first wave 28·9% vs second/third waves 6·2%, p <0·001), and a negligible administration of lopinavir/ritonavir, hydroxychloroquine, and interferon during the second/third waves compared with the first wave. Overall ICU mortality was 30·7% (n = 1166), without significant differences between study periods (first wave 31·7% vs second/third waves 28·8%, p = 0·06). No significant differences were found in ICU mortality between waves according to age subsets except for the subgroup of 61-75 years of age, in whom a reduced unadjusted ICU mortality was observed in the second/third waves (first 38·7% vs second/third 34·0%, p = 0·048). Non-survivors were older, with higher severity of the disease, had more comorbidities, and developed more complications. After adjusting for confounding factors through a multivariable analysis, no significant association was found between the COVID-19 waves and mortality (OR 0·81, 95% CI 0·64-1·03; p = 0·09). Ventilator-associated pneumonia rate increased significantly during the second/third waves and it was independently associated with ICU mortality (OR 1·48, 95% CI 1·19-1·85, p <0·001). Nevertheless, a significant reduction both in the ICU and hospital length of stay in survivors was observed during the second/third waves. Despite substantial changes on supportive care and management, we did not find significant improvement on case-fatality rates among critical COVID-19 pneumonia patients. Ricardo Barri Casanovas Foundation (RBCF2020) and SEMICYU

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Estrés oxidativo en pacientes con neumonía grave valoración y correlación con factores pronósticos

Nuestra hipótesis fue que el nivel de estrés oxidativo (EO),valorado mediante diversos biomarcadores (BM) en sangre, se asocia con la evolución de pacientes con neumonía grave (NG) ingresados en la unidad de cuidados intensivos (UCI). El objetivo principal fue determinar la relación entre diferentes BM antioxidantes (SOD, CAT, GPx,GR, GSH) y de daño celular (TBARS) con la evolución de pacientes con NG y con infarto agudo de miocardio (IAM) (grupo control). Se registraron características clínicas y extrajeron muestras de sangre(al ingreso, 72 horas y al alta) para la determinación de BM. Se incluyeron 21 pacientes con NG (bacteriana n= 18, viral n= 3) y 12 con IAM. Los TBARS fueron mayores en NG bacteriana que NG viral y control, pero similar entre sobrevivientes y fallecidos. Concluimos que los TBARS no se asociaron con la evolución. El EO fue mayor en neumonía bacteriana respecto de neumonía viral y grupo control.Oxidative Stress (OS) is considered the basic mechanism of injury in pneumonia, which results in a severe injury to the lung parenchyma. The magnitude that reaches the systemic inflammation and oxidation in patients with severe pneumonia (SP)may condition its subsequent evolution. Hypothesis: The level of EO, measured by various biomarkers (BM) in blood is associated with the evolution of patients with NG admitted to ICU

Estrés oxidativo en pacientes con neumonía grave valoración y correlación con factores pronósticos

Nuestra hipótesis fue que el nivel de estrés oxidativo (EO),valorado mediante diversos biomarcadores (BM) en sangre, se asocia con la evolución de pacientes con neumonía grave (NG) ingresados en la unidad de cuidados intensivos (UCI). El objetivo principal fue determinar la relación entre diferentes BM antioxidantes (SOD, CAT, GPx,GR, GSH) y de daño celular (TBARS) con la evolución de pacientes con NG y con infarto agudo de miocardio (IAM) (grupo control). Se registraron características clínicas y extrajeron muestras de sangre(al ingreso, 72 horas y al alta) para la determinación de BM. Se incluyeron 21 pacientes con NG (bacteriana n= 18, viral n= 3) y 12 con IAM. Los TBARS fueron mayores en NG bacteriana que NG viral y control, pero similar entre sobrevivientes y fallecidos. Concluimos que los TBARS no se asociaron con la evolución. El EO fue mayor en neumonía bacteriana respecto de neumonía viral y grupo control.Oxidative Stress (OS) is considered the basic mechanism of injury in pneumonia, which results in a severe injury to the lung parenchyma. The magnitude that reaches the systemic inflammation and oxidation in patients with severe pneumonia (SP)may condition its subsequent evolution. Hypothesis: The level of EO, measured by various biomarkers (BM) in blood is associated with the evolution of patients with NG admitted to ICU

In vitro evaluation of aerosol delivery of aztreonam lysine (AZLI): an adult mechanical ventilation model

International audienc

The prognostic value of muscle regional oxygen saturation index in severe community-acquired pneumonia: a prospective observational study.

BACKGROUND: Community-acquired pneumonia (CAP) mortality exceeds 20 % in critical care patients despite appropriate antibiotic therapy. Regional tissue oxygen saturation index (rSO2) measured with near-infrared spectroscopy (NIRS) might facilitate early detection for patients at risk of serious complications. Our objectives were to determine the relationship between early determination of rSO2 and mortality and to compare discrimination power for mortality of rSO2 and other resuscitation variables in critically ill CAP patients. METHODS: This is a prospective observational study. Patients with CAP were enrolled within 6 h to intensive care admission. Demographics and clinical variables were recorded. rSO2 was determined using NIRS in brachioradialis muscle. All variables were determined at baseline and 24 h after admission. RESULTS: Forty patients were enrolled. Fourteen patients (35 %) had a baseline rSO2 < 60 % and 7 of them died (50 %). Only 1 of 26 (3.8 %) patients with rSO2 ≥ 60 % died (p = 0.007). The area under ROC curve (AUROC) showed consistent mortality discrimination at baseline (0.84, p = 0.03) and at 24 h (0.86, p = 0.006) for rSO2 values. Cox regression analysis showed that "low" rSO2 at ICU admission (hazard ratio (HR) = 8.99; 95 % confidence interval (CI) 1.05-76.8; p = 0.045) and "low" rSO2 at 24 h (HR = 13.18; 95 % CI 1.52-113.6; p = 0.019) were variables independently associated with mortality. In contrast, other variables such as Acute Physiology and Chronic Health Evaluation (APACHE II) score (HR = 1.09; 95 % CI 0.99-1.19; p = 0.052) were not associated with mortality. CONCLUSIONS: Our findings suggest that forearm skeletal muscle rSO2 differs in patients with severe CAP according to outcome and might be an early prognosis tool.This study was partially supported by grants from the Fondo de Investigación Sanitaria (FIS PI10/01538, PI13/02011) and SGR2013/092

Homo- and Heterobinuclear Cu²⁺ and Zn²⁺ Complexes of Ditopic Aza Scorpiand Ligands as Superoxide Dismutase Mimics

Two polytopic aza-scorpiand-like ligands, 6-[7-(diaminoethyl)-3,7-diazaheptyl]-3,6,9-triaza-1-(2,6-pyridina)­cyclodecaphane (<b>L1</b>) and 6-[6′-[3,6,9-triaza-1-(2,6-pyridina)­cyclodecaphan-6-yl]-3-azahexyl]-3,6,9-triaza-1-(2,6-pyridina)­cyclodecaphane (<b>L2</b>), have been synthesized. The acid–base behavior and Cu²⁺, Zn²⁺, and Cu²⁺/Zn²⁺ mixed coordination have been analyzed by potentiometry, cyclic voltammetry, and UV–vis spectroscopy. The resolution of the crystal structures of [Cu₂<b>L2</b>Cl₂]­(ClO₄)₂·1.67H₂O (<b>1</b>), [Cu₂H<b>L2</b>Br₂]­(ClO₄)₃·1.5H₂O (<b>2</b>), and [CuZn<b>L2</b>Cl₂]­(ClO₄)₂·1.64H₂O (<b>3</b>) shows, in agreement with the solution data, the formation of homobinuclear Cu²⁺/Cu²⁺ and heterobinuclear Cu²⁺/Zn²⁺ complexes. The metal ions are coordinated within the two macrocyclic cavities of the ligand with the involvement of a secondary amino group of the bridge in the case of <b>1</b> and <b>3</b>. Energy-dispersive X-ray spectroscopy confirms the 1:1 Cu²⁺/Zn²⁺ stoichiometry of <b>3</b>. The superoxide dismutase (SOD) activities of the Cu²⁺/Cu²⁺ and Cu²⁺/Zn²⁺ complexes of <b>L1</b> and <b>L2</b> have been evaluated using nitro blue tetrazolium assays at pH 7.4. The IC₅₀ and <i>k</i>_cat values obtained for the [Cu₂<b>L1</b>]⁴⁺ complex rank among the best values reported in the literature for Cu-SOD mimics. Interestingly, the binuclear Cu²⁺ complexes of <b>L1</b> and <b>L2</b> have low toxicity in cultures of mammalian cell lines and show significant antioxidant activity in a copper-dependent SOD (SOD1)-defective yeast model. The results are rationalized by taking into account the binding modes of the Cu²⁺ ions in the different complexes

<i>In vitro</i> evaluation of aerosol delivery of aztreonam lysine (AZLI): an adult mechanical ventilation model

<p><b>Background</b>: The delivery profile of Aztreonam lysine (AZLI) during mechanical ventilation (MV) is unknown. We evaluated the amount of AZLI drug delivered using an <i>in vitro</i> model of adult MV.</p> <p><b>Methods</b>: An adult lung model designed to mimic current clinical practice was used. Both nebulizers were placed before a Y-piece and 4 settings were tested: A) Aeroneb solo® [AS] with a t-piece; B) AS with the spacer; C) M-Neb® [MN] with a t-piece and D) MN with the spacer. Performance was evaluated in terms of: 1) Mass median aerodynamic diameter (MMAD); 2) Geometric standard deviation (GSD), 3) Fine particle dose (FPD), 4) Fine particle fraction (FPF), 5) Inhalable mass (IM), and 6) Recovery rate (RR).</p> <p><b>Results</b>: Both devices showed an adequate delivery of AZLI during MV, with MMAD between 2.4–2.5 µm and 87% of FPF. The FPD (38.8 and 31.7), IM (44.8 and 36.1) and RR (30 and 24) were similar for AS and MN respectively. Nebulizer aerosol delivery increased (50 and 70% respectively) for both nebulizers when using the spacer.</p> <p><b>Conclusion</b>: Both AS and MN showed a good aerosol delivery profile for AZLI during <i>in vitro</i> mechanical ventilation. Better aerosol delivery performance was obtained using the spacer.</p

Early oseltamivir treatment improves survival in critically ill patients with influenza pneumonia

Background: The relationship between early oseltamivir treatment (within 48 h of symptom onset) and mortality in patients admitted to intensive care units (ICUs) with severe influenza is disputed. This study aimed to investigate the association between early oseltamivir treatment and ICU mortality in critically ill patients with influenza pneumonia. Methods: This was an observational study of patients with influenza pneumonia admitted to 184 ICUs in Spain during 2009-2018. The primary outcome was to evaluate the association between early oseltamivir treatment and ICU mortality compared with later treatment. Secondary outcomes were to compare the duration of mechanical ventilation and ICU length of stay between the early and later oseltamivir treatment groups. To reduce biases related to observational studies, propensity score matching and a competing risk analysis were performed. Results: During the study period, 2124 patients met the inclusion criteria. All patients had influenza pneumonia and received oseltamivir before ICU admission. Of these, 529 (24.9%) received early oseltamivir treatment. In the multivariate analysis, early treatment was associated with reduced ICU mortality (OR 0.69, 95% CI 0.51-0.95). After propensity score matching, early oseltamivir treatment was associated with improved survival rates in the Cox regression (hazard ratio 0.77, 95% CI 0.61-0.99) and competing risk (subdistribution hazard ratio 0.67, 95% CI 0.53-0.85) analyses. The ICU length of stay and duration of mechanical ventilation were shorter in patients receiving early treatment. Conclusions: Early oseltamivir treatment is associated with improved survival rates in critically ill patients with influenza pneumonia, and may decrease ICU length of stay and mechanical ventilation duration