High-Flow Oxygen with Capping or Suctioning for Tracheostomy Decannulation.

BACKGROUND: When patients with a tracheostomy tube reach a stage in their care at which decannulation appears to be possible, it is common practice to cap the tracheostomy tube for 24 hours to see whether they can breathe on their own. Whether this approach to establishing patient readiness for decannulation leads to better outcomes than one based on the frequency of airway suctioning is unclear. METHODS: In five intensive care units (ICUs), we enrolled conscious, critically ill adults who had a tracheostomy tube; patients were eligible after weaning from mechanical ventilation. In this unblinded trial, patients were randomly assigned either to undergo a 24-hour capping trial plus intermittent high-flow oxygen therapy (control group) or to receive continuous high-flow oxygen therapy with frequency of suctioning being the indicator of readiness for decannulation (intervention group). The primary outcome was the time to decannulation, compared by means of the log-rank test. Secondary outcomes included decannulation failure, weaning failure, respiratory infections, sepsis, multiorgan failure, durations of stay in the ICU and hospital, and deaths in the ICU and hospital. RESULTS: The trial included 330 patients; the mean (±SD) age of the patients was 58.3±15.1 years, and 68.2% of the patients were men. A total of 161 patients were assigned to the control group and 169 to the intervention group. The time to decannulation was shorter in the intervention group than in the control group (median, 6 days [interquartile range, 5 to 7] vs. 13 days [interquartile range, 11 to 14]; absolute difference, 7 days [95% confidence interval, 5 to 9]). The incidence of pneumonia and tracheobronchitis was lower, and the duration of stay in the hospital shorter, in the intervention group than in the control group. Other secondary outcomes were similar in the two groups. CONCLUSIONS: Basing the decision to decannulate on suctioning frequency plus continuous high-flow oxygen therapy rather than on 24-hour capping trials plus intermittent high-flow oxygen therapy reduced the time to decannulation, with no evidence of a between-group difference in the incidence of decannulation failure. (REDECAP ClinicalTrials.gov number, NCT02512744.).

Association between ventilatory ratio and mortality in patients with acute respiratory distress syndrome and COVID 19: A multicenter, retrospective cohort study.

BACKGROUND: Mortality rates in patients with COVID-19 undergoing mechanical ventilation in the intensive care unit are high. The causes of this mortality have been rigorously investigated. The aim of the present study is to establish mortality risk factors related to lung mechanics measured at days 1 and 5 in patients with covid-19 ARDS managed with invasive mechanical ventilation in the intensive care unit. METHODS: A retrospective observational multicenter study including consecutive patients with a confirmed diagnosis of COVID-19-induced ARDS, admitted to three institutions and seven intensive care units in the city of Bogota between May 20, 2020 and May 30, 2022 who required mechanical ventilation for at least five days. Data were collected from the medical records of patients who met the inclusion criteria on day 1 and day 5 of mechanical ventilation. The primary outcome assessed was mortality at day 30. RESULTS: A total of 533 consecutive patients admitted with ARDS with COVID-19 were included. Ventilatory ratio, plateau pressure and driving pressure measured on day 5 were significantly higher in non-survivors (p < 0.05). Overall, 30-day follow-up mortality was 48.8%. The increases between day 1 and day 5 in the ventilatory ratio (OR 1.42, 95%CI 1.03-2.01, p = 0.04), driving pressure (OR 1.56, 95%CI 1.10-2.22, p = 0.01); and finally plateau pressure (OR 1.9, 95%CI 1.34-2.69, p = 0.001) were associated with an increased risk of death. There was no association between deterioration of PaO2/FIO2 index and mortality (OR 1.34, 95%CI 0.96-1.56, p = 0.053). CONCLUSIONS: Ventilatory ratio, plateau pressure, driving pressure, and age were identified as independent risk factors for 30-day mortality in patients with ARDS due to COVID-19 on day 5 of invasive mechanical ventilation.

Timing of intubation and ICU mortality in COVID-19 patients: a retrospective analysis of 4198 critically ill patients during the first and second waves.

BACKGROUND: The optimal time to intubate patients with SARS-CoV-2 pneumonia has not been adequately determined. While the use of non-invasive respiratory support before invasive mechanical ventilation might cause patient-self-induced lung injury and worsen the prognosis, non-invasive ventilation (NIV) is frequently used to avoid intubation of patients with acute respiratory failure (ARF). We hypothesized that delayed intubation is associated with a high risk of mortality in COVID-19 patients. METHODS: This is a secondary analysis of prospectively collected data from adult patients with ARF due to COVID-19 admitted to 73 intensive care units (ICUs) between February 2020 and March 2021. Intubation was classified according to the timing of intubation. To assess the relationship between early versus late intubation and mortality, we excluded patients with ICU length of stay (LOS) < 7 days to avoid the immortal time bias and we did a propensity score and a cox regression analysis. RESULTS: We included 4,198 patients [median age, 63 (54‒71) years; 71% male; median SOFA (Sequential Organ Failure Assessment) score, 4 (3‒7); median APACHE (Acute Physiology and Chronic Health Evaluation) score, 13 (10‒18)], and median PaO2/FiO2 (arterial oxygen pressure/ inspired oxygen fraction), 131 (100‒190)]; intubation was considered very early in 2024 (48%) patients, early in 928 (22%), and late in 441 (10%). ICU mortality was 30% and median ICU stay was 14 (7‒28) days. Mortality was higher in the "late group" than in the "early group" (37 vs. 32%, p < 0.05). The implementation of an early intubation approach was found to be an independent protective risk factor for mortality (HR 0.6; 95%CI 0.5‒0.7). CONCLUSIONS: Early intubation within the first 24 h of ICU admission in patients with COVID-19 pneumonia was found to be an independent protective risk factor of mortality. TRIAL REGISTRATION: The study was registered at Clinical-Trials.gov (NCT04948242) (01/07/2021).

Non-invasive oxygenation support in acutely hypoxemic COVID-19 patients admitted to the ICU: a multicenter observational retrospective study.

BACKGROUND: Non-invasive oxygenation strategies have a prominent role in the treatment of acute hypoxemic respiratory failure during the coronavirus disease 2019 (COVID-19). While the efficacy of these therapies has been studied in hospitalized patients with COVID-19, the clinical outcomes associated with oxygen masks, high-flow oxygen therapy by nasal cannula and non-invasive mechanical ventilation in critically ill intensive care unit (ICU) patients remain unclear. METHODS: In this retrospective study, we used the best of nine covariate balancing algorithms on all baseline covariates in critically ill COVID-19 patients supported with > 10 L of supplemental oxygen at one of the 26 participating ICUs in Catalonia, Spain, between March 14 and April 15, 2020. RESULTS: Of the 1093 non-invasively oxygenated patients at ICU admission treated with one of the three stand-alone non-invasive oxygenation strategies, 897 (82%) required endotracheal intubation and 310 (28%) died during the ICU stay. High-flow oxygen therapy by nasal cannula (n = 439) and non-invasive mechanical ventilation (n = 101) were associated with a lower rate of endotracheal intubation (70% and 88%, respectively) than oxygen masks (n = 553 and 91% intubated), p < 0.001. Compared to oxygen masks, high-flow oxygen therapy by nasal cannula was associated with lower ICU mortality (hazard ratio 0.75 [95% CI 0.58-0.98), and the hazard ratio for ICU mortality was 1.21 [95% CI 0.80-1.83] for non-invasive mechanical ventilation. CONCLUSION: In critically ill COVID-19 ICU patients and, in the absence of conclusive data, high-flow oxygen therapy by nasal cannula may be the approach of choice as the primary non-invasive oxygenation support strategy.

Metabolic Signatures Associated with Severity in Hospitalized COVID-19 Patients.

The clinical evolution of COVID-19 pneumonia is poorly understood. Identifying the metabolic pathways that are altered early with viral infection and their association with disease severity is crucial to understand COVID-19 pathophysiology, and guide clinical decisions. This study aimed at assessing the critical metabolic pathways altered with disease severity in hospitalized COVID-19 patients. Forty-nine hospitalized patients with COVID-19 pneumonia were enrolled in a prospective, observational, single-center study in Barcelona, Spain. Demographic, clinical, and analytical data at admission were registered. Plasma samples were collected within the first 48 h following hospitalization. Patients were stratified based on the severity of their evolution as moderate (N = 13), severe (N = 10), or critical (N = 26). A panel of 221 biomarkers was measured by targeted metabolomics in order to evaluate metabolic changes associated with subsequent disease severity. Our results show that obesity, respiratory rate, blood pressure, and oxygen saturation, as well as some analytical parameters and radiological findings, were all associated with disease severity. Additionally, ceramide metabolism, tryptophan degradation, and reductions in several metabolic reactions involving nicotinamide adenine nucleotide (NAD) at inclusion were significantly associated with respiratory severity and correlated with inflammation. In summary, assessment of the metabolomic profile of COVID-19 patients could assist in disease severity stratification and even in guiding clinical decisions.

Delay in diagnosis of influenza A (H1N1)pdm09 virus infection in critically ill patients and impact on clinical outcome.

BACKGROUND: Patients infected with influenza A (H1N1)pdm09 virus requiring admission to the ICU remain an important source of mortality during the influenza season. The objective of the study was to assess the impact of a delay in diagnosis of community-acquired influenza A (H1N1)pdm09 virus infection on clinical outcome in critically ill patients admitted to the ICU. METHODS: A prospective multicenter observational cohort study was based on data from the GETGAG/SEMICYUC registry (2009-2015) collected by 148 Spanish ICUs. All patients admitted to the ICU in which diagnosis of influenza A (H1N1)pdm09 virus infection had been established within the first week of hospitalization were included. Patients were classified into two groups according to the time at which the diagnosis was made: early (within the first 2 days of hospital admission) and late (between the 3rd and 7th day of hospital admission). Factors associated with a delay in diagnosis were assessed by logistic regression analysis. RESULTS: In 2059 ICU patients diagnosed with influenza A (H1N1)pdm09 virus infection within the first 7 days of hospitalization, the diagnosis was established early in 1314 (63.8 %) patients and late in the remaining 745 (36.2 %). Independent variables related to a late diagnosis were: age (odds ratio (OR) = 1.02, 95 % confidence interval (CI) 1.01-1.03, P < 0.001); first seasonal period (2009-2012) (OR = 2.08, 95 % CI 1.64-2.63, P < 0.001); days of hospital stay before ICU admission (OR = 1.26, 95 % CI 1.17-1.35, P < 0.001); mechanical ventilation (OR = 1.58, 95 % CI 1.17-2.13, P = 0.002); and continuous venovenous hemofiltration (OR = 1.54, 95 % CI 1.08-2.18, P = 0.016). The intra-ICU mortality was significantly higher among patients with late diagnosis as compared with early diagnosis (26.9 % vs 17.1 %, P < 0.001). Diagnostic delay was one independent risk factor for mortality (OR = 1.36, 95 % CI 1.03-1.81, P < 0.001). CONCLUSIONS: Late diagnosis of community-acquired influenza A (H1N1)pdm09 virus infection is associated with a delay in ICU admission, greater possibilities of respiratory and renal failure, and higher mortality rate. Delay in diagnosis of flu is an independent variable related to death.

Risk factors and outcomes of ventilator-associated pneumonia in patients with traumatic brain injury: A systematic review and meta-analysis.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a common complication in traumatic brain injury (TBI) patients, which increases morbidity and negatively affects outcomes. Risk factors and outcomes in these patients remain controversial. The aim of the present study is to explore the risk factors and clinical outcomes of patients with VAP and TBI. METHODS: Two researchers conducted independent systematic literature searches of Pubmed, Cochrane Database, Scopus, Medline Ovid, Science Direct databases, published from inception to January 2024. The Newcastle-Ottawa scale was used to assess study quality. A meta-analysis was performed using a random-effects model when heterogeneity I2 > 50 % and a fixed-effects model when I2 < 50 %; in addition, a subgroup analysis was performed to explore VAP risk factors, and publication bias was assessed with the funnel plot and Begg's and Egger's tests. All results were considered statistically significant when p < 0.05. The certainty of the evidence was evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology. RESULTS: Twelve studies were included in the meta-analysis with a total of 2883 patients. Male gender [OR 1.58 (95 % CI 1.23, 2.02) p < 0.05 I2 0 %] and abbreviated injury scale (head: H-AIS) [≥ 3 OR 2.79 (95 % CI 1.58, 4.93) p < 0.05 I2 0 %] increased the risk of VAP. After subgroup analysis, blood transfusion on admission [OR 1.97 (95 % CI 1.16-3.35) p ≤0.05 I2 5 %] and barbiturate infusion [OR 3.55 (95 % CI 2.01-6.30) p ≤0.05 I2 0 %] became risk factors. Prophylactic antibiotic use [OR 0.67 (95 % CI 0.51-0.88) p ≤0.05 I2 0 %] and younger age MD -3.29 (95 % CI -5.18, -1.40) p ≤0.05 I2 41 %] emerged as significant protective factors. In VAP patients ICU stay [MD 7.02 (95 % CI 6.05-7.99) p ≤0.05 I2 37 %], duration of mechanical ventilation [MD 5.79 (95 % CI 4.40, 7.18) p ≤0.05 I2 79 %] and hospital stay [MD 11.88 (95 % CI 8.71-15.05) p ≤0.05 I2 0 %] were significantly increased. The certainty of the evidence was moderate-high for the outcomes studied. CONCLUSIONS: Male gender, H-AIS ≥ 3, blood transfusion on admission, and barbiturate infusion were risk factors for VAP. In patients with VAP, ICU stay, duration of mechanical ventilation, hospital stay were significantly increased.

Switches in non-invasive respiratory support strategies during acute hypoxemic respiratory failure: Need to monitoring from a retrospective observational study.

OBJECTIVE: To explore combined non-invasive-respiratory-support (NIRS) patterns, reasons for NIRS switching, and their potential impact on clinical outcomes in acute-hypoxemic-respiratory-failure (AHRF) patients. DESIGN: Retrospective, single-center observational study. SETTING: Intensive Care Medicine. PATIENTS: AHRF patients (cardiac origin and respiratory acidosis excluded) underwent combined NIRS therapies such as non-invasive-ventilation (NIV) and High-Flow-Nasal-Cannula (HFNC). INTERVENTIONS: Patients were classified based on the first NIRS switch performed (HFNC-to-NIV or NIV-to-HFNC), and further specific NIRS switching strategies (NIV trial-like vs. Non-NIV trial-like and single vs. multiples switches) were independently evaluated. MAIN VARIABLES OF INTEREST: Reasons for switching, NIRS failure and mortality rates. RESULTS: A total of 63 patients with AHRF were included, receiving combined NIRS, 58.7% classified in the HFNC-to-NIV group and 41.3% in the NIV-to-HFNC group. Reason for switching from HFNC to NIV was AHRF worsening (100%), while from NIV to HFNC was respiratory improvement (76.9%). NIRS failure rates were higher in the HFNC-to-NIV than in NIV-to-HFNC group (81% vs. 35%, p < 0.001). Among HFNC-to-NIV patients, there was no difference in the failure rate between the NIV trial-like and non-NIV trial-like groups (86% vs. 78%, p = 0.575) but the mortality rate was significantly lower in NIV trial-like group (14% vs. 52%, p = 0.02). Among NIV to HFNC patients, NIV failure was lower in the single switch group compared to the multiple switches group (15% vs. 53%, p = 0.039), with a shorter length of stay (5 [2-8] vs. 12 [8-30] days, p = 0.001). CONCLUSIONS: NIRS combination is used in real life and both switches' strategies, HFNC to NIV and NIV to HFNC, are common in AHRF management. Transitioning from HFNC to NIV is suggested as a therapeutic escalation and in this context performance of a NIV-trial could be beneficial. Conversely, switching from NIV to HFNC is suggested as a de-escalation strategy that is deemed safe if there is no NIRS failure.

Effect of aggressive vs conservative screening and confirmatory test on time to extubation among patients at low or intermediate risk: a randomized clinical trial.

PURPOSE: This study aimed to determine the best strategy to achieve fast and safe extubation. METHODS: This multicenter trial randomized patients with primary respiratory failure and low-to-intermediate risk for extubation failure with planned high-flow nasal cannula (HFNC) preventive therapy. It included four groups: (1) conservative screening with ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) ≥ 150 and positive end-expiratory pressure (PEEP) ≤ 8 cmH2O plus conservative spontaneous breathing trial (SBT) with pressure support 5 cmH2O + PEEP 0 cmH2O); (2) screening with ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) ≥ 150 and PEEP ≤ 8 plus aggressive SBT with pressure support 8 + PEEP 5; (3) aggressive screening with PaO2/FiO2 > 180 and PEEP 10 maintained until the SBT with pressure support 8 + PEEP 5; (4) screening with PaO2/FiO2 > 180 and PEEP 10 maintained until the SBT with pressure support 5 + PEEP 0. Primary outcomes were time-to-extubation and simple weaning rate. Secondary outcomes included reintubation within 7 days after extubation. RESULTS: Randomization to the aggressive-aggressive group was discontinued at the interim analysis for safety reasons. Thus, 884 patients who underwent at least 1 SBT were analyzed (conservative-conservative group, n = 256; conservative-aggressive group, n = 267; aggressive-conservative group, n = 261; aggressive-aggressive, n = 100). Median time to extubation was lower in the groups with aggressive screening (p < 0.001). Simple weaning rates were 45.7%, 76.78% (205 patients), 71.65%, and 91% (p < 0.001), respectively. Reintubation rates did not differ significantly (p = 0.431). CONCLUSION: Among patients at low or intermediate risk for extubation failure with planned HFNC, combining aggressive screening with preventive PEEP and a conservative SBT reduced the time to extubation without increasing the reintubation rate.

Comparing lung aeration and respiratory effort using two different spontaneous breathing trial: T-piece vs pressure support ventilation.

OBJECTIVE: To assess the changes in lung aeration and respiratory effort generated by two different spontaneous breathing trial (SBT): T-piece (T-T) vs pressure support ventilation (PSV). DESIGN: Prospective, interventionist and randomized study. SETTING: Intensive Care Unit (ICU) of Hospital del Mar. PARTICIPANTS: Forty-three ventilated patients for at least 24 h and considered eligible for an SBT were included in the study between October 2017 and March 2020. INTERVENTIONS: 30-min SBT with T-piece (T-T group, 20 patients) or 8-cmH2O PSV and 5-cmH2O positive end expiratory pressure (PSV group, 23 patients). MAIN VARIABLES OF INTEREST: Demographics, clinical data, physiological variables, lung aeration evaluated with electrical impedance tomography (EIT) and lung ultrasound (LUS), and respiratory effort using diaphragmatic ultrasonography (DU) were collected at different timepoints: basal (BSL), end of SBT (EoSBT) and one hour after extubation (OTE). RESULTS: There were a loss of aeration measured with EIT and LUS in the different study timepoints, without statistical differences from BSL to OTE, between T-T and PSV [LUS: 3 (1, 5.5) AU vs 2 (1, 3) AU; p = 0.088; EELI: -2516.41 (-5871.88, 1090.46) AU vs -1992.4 (-3458.76, -5.07) AU; p = 0.918]. Percentage of variation between BSL and OTE, was greater when LUS was used compared to EIT (68.1% vs 4.9%, p ≤ 0.001). Diaphragmatic excursion trend to decrease coinciding with a loss of aeration during extubation. CONCLUSION: T-T and PSV as different SBT strategies in ventilated patients do not show differences in aeration loss, nor estimated respiratory effort or tidal volume measured by EIT, LUS and DU.

Prognostic factors in oncological patients with solid tumours requiring intensive care unit admission.

The aim of the present study was to identify factors predicting in-hospital mortality in patients with cancer admitted to a medical Intensive Care Unit (ICU), and to evaluate their functional status and survival during follow-up at the oncology service in the initial 12 months after hospital discharge. A retrospective observational study was performed on 129 consecutive oncological patients with solid tumours admitted to the medical ICU of the Hospital del Mar (Barcelona, Spain) between January 2016 and June 2018. Demographics, and clinical data in-ICU and in-hospital mortality were recorded. Post-hospital discharge follow-up was also carried out. ICU and hospital mortality rates were 24% (n=31) and 40.3% (n=52), respectively. Sequential Organ Failure Assessment (SOFA) score (HR, 1.20; 95% CI, 1.01-1.42; P=0.037), neutropenia on admission (HR, 8.53; 95% CI, 2.15-33.82; P=0.002), metastatic disease (HR, 3.92; 95% CI, 1.82-8.45; P<0.001), need for invasive mechanical ventilation (HR, 5.78; 95% CI, 1.61-20.73; P=0.007), surgery during hospital admission (HR, 0.23; 95% CI, 0.09-0.61; P=0.003) and ICU stay (>48 h) (HR, 0.11; 95% CI, 0.04-0.29; P<0.001) were the independent risk factors for ICU mortality. Overall, 59.5% of the survivors had good functional status at hospital discharge and 28.7% of patients with cancer admitted to the ICU were alive 1 year after hospital discharge, most of them (85.7%) with good functional status (Eastern Cooperative Oncology Group 0-1). In conclusion, hospital mortality may be associated with SOFA score at ICU admission, the need for invasive mechanical ventilation, neutropenia and metastatic disease. Only 40% of patients with oncological disease admitted to the ICU died during their hospital stay, and >50% of the survivors presented good functional status at hospital discharge. Notably, 1 year after hospital discharge, 28.7% of patients were alive, most of them with a good functional status.

European Network for ICU-Related Respiratory Infections (ENIRRIs): a multinational, prospective, cohort study of nosocomial LRTI.

PURPOSE: Lower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes. METHODS: A prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups. RESULTS: 1060 patients with LRTI (72.5% male sex, median age 64 [50-74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates. CONCLUSION: VHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study.

Untargeted detection of the carbonyl metabolome by chemical derivatization and liquid chromatography-tandem mass spectrometry in precursor ion scan mode: Elucidation of COVID-19 severity biomarkers.

Metabolomics (both targeted and untargeted) has become the gold standard in biomarker discovery. Whereas targeted approaches only provide information for the selected markers, thus hampering the determination of out-of-the-box markers, the common bottleneck of untargeted metabolomics is the identification of detected biomarkers. In this study, we developed a strategy based on derivatization and LC-MS/MS detection in a precursor ion scan for the untargeted determination of a specific part of the metabolome (carbonyl-containing metabolites). The usefulness of this guided metabolomics approach has been demonstrated by elucidating carbonyl-containing biomarkers of COVID-19 severity. First, the LC-MS/MS behavior of 63 model compounds after O-benzylhydroxylamine derivatization was studied. A precursor ion scan of m/z 91 was selected as a suitable approach for the untargeted detection of carbonyl-containing metabolites. The method was able to detect ≈300 potential carbonyl-containing molecules in plasma, including mono-/di-/tricarbonylic compounds with satisfactory intra-day and inter-day repeatability and RSDs commonly <15%. Additionally, the semiquantitative nature of the precursor ion scan method was confirmed by comparison with a fully validated targeted method. The application of the guided metabolomics method to COVID-19 plasma samples revealed the presence of four potential COVID-19 severity biomarkers. Based on their LC-MS/MS behavior, these biomarkers were elucidated as 2-hydroxybutyrate, 2,3-dihydroxybutyrate, 2-oxobutyrate and 2-hydroxy-3-methylbutyrate. Their structures were confirmed by comparison with reference materials. The alterations of these biomarkers with COVID-19 severity were confirmed by a target analysis of a larger set of samples. Our results confirm that guided metabolomics is an alternative approach for the untargeted detection of selected families of metabolites; this approach can accelerate their elucidation and provide new perspectives for the establishment of health/disease biomarkers.

Association between histological diaphragm atrophy and ultrasound diaphragm expiratory thickness in ventilated patients.

BACKGROUND: Diaphragm fiber atrophy has been evidenced after short periods of mechanical ventilation (MV) and related to critical illness-associated diaphragm weakness. Atrophy is described as a decrease in diaphragm fiber cross-sectional area (CSA) in human diaphragm biopsy, but human samples are still difficult to obtain in clinics. In recent years, ultrasound has become a useful tool in intensive care to evaluate diaphragm anatomy. The present study aimed to evaluate the ability of diaphragm expiratory thickness (Tdi) measured by ultrasound to predict diaphragm atrophy, defined by a decrease in diaphragm fiber CSA obtained through diaphragm biopsy (the gold standard technique) in ventilated patients. METHODS: Diaphragm biopsies and diaphragm ultrasound were performed in ventilated donors and in control subjects. Demographic variables, comorbidities, severity on admission, treatment, laboratory test results and evolution variables were evaluated. Immunohistochemical analysis to determine CSA and ultrasound measurements of Tdi at end-expiration were performed, and median values of the control group were used as thresholds to determine agreement between them in further analysis. Sensitivity, specificity, and positive and negative predictive values of an ultrasound Tdi cutoff for detecting histologic atrophy were calculated. Agreement between two ultrasound observers was also assessed. RESULTS: Thirty-five ventilated organ donors and 5 ventilated controls were included, without differences in basic characteristics. CSA and Tdi were lower in donors than in controls. All donors presented lower CSA, but only 74% lower Tdi regarding control group thresholds. The cut-off value for lower diaphragm expiratory thickness (Tdi < 1.7 mm) presented a sensitivity of 73%, a specificity of 67%, a positive predictive value of 96% and a negative predictive value of 17% for determining the presence of diaphragm atrophy (CSA < 2851 µm2). CONCLUSIONS: Diaphragm atrophy and thickness reduction is associated to MV. While a lower Tdi in diaphragm ultrasound is a good tool for diagnosing atrophy, normal or increased Tdi cannot rule atrophy out showing that both parameters should not be considered as synonymous.

Early Tracheostomy for Managing ICU Capacity During the COVID-19 Outbreak: A Propensity-Matched Cohort Study.

BACKGROUND: During the first wave of the COVID-19 pandemic, shortages of ventilators and ICU beds overwhelmed health care systems. Whether early tracheostomy reduces the duration of mechanical ventilation and ICU stay is controversial. RESEARCH QUESTION: Can failure-free day outcomes focused on ICU resources help to decide the optimal timing of tracheostomy in overburdened health care systems during viral epidemics? STUDY DESIGN AND METHODS: This retrospective cohort study included consecutive patients with COVID-19 pneumonia who had undergone tracheostomy in 15 Spanish ICUs during the surge, when ICU occupancy modified clinician criteria to perform tracheostomy in Patients with COVID-19. We compared ventilator-free days at 28 and 60 days and ICU- and hospital bed-free days at 28 and 60 days in propensity score-matched cohorts who underwent tracheostomy at different timings (≤ 7 days, 8-10 days, and 11-14 days after intubation). RESULTS: Of 1,939 patients admitted with COVID-19 pneumonia, 682 (35.2%) underwent tracheostomy, 382 (56%) within 14 days. Earlier tracheostomy was associated with more ventilator-free days at 28 days (≤ 7 days vs > 7 days [116 patients included in the analysis]: median, 9 days [interquartile range (IQR), 0-15 days] vs 3 days [IQR, 0-7 days]; difference between groups, 4.5 days; 95% CI, 2.3-6.7 days; 8-10 days vs > 10 days [222 patients analyzed]: 6 days [IQR, 0-10 days] vs 0 days [IQR, 0-6 days]; difference, 3.1 days; 95% CI, 1.7-4.5 days; 11-14 days vs > 14 days [318 patients analyzed]: 4 days [IQR, 0-9 days] vs 0 days [IQR, 0-2 days]; difference, 3 days; 95% CI, 2.1-3.9 days). Except hospital bed-free days at 28 days, all other end points were better with early tracheostomy. INTERPRETATION: Optimal timing of tracheostomy may improve patient outcomes and may alleviate ICU capacity strain during the COVID-19 pandemic without increasing mortality. Tracheostomy within the first work on a ventilator in particular may improve ICU availability.

SARS-CoV-2 could be spread through hospital medication dispensed to patients: A prospective observational study.

ABSTRACT: Our objective was to analyze in vitro the persistence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in the packaging material of the drugs dispensed to hospital wards. Additionally, to evaluate if the protection with a double plastic bag prevents the contamination of the medication dispensed to an intensive care unit (ICU).On the first part, different materials containing different drugs within an ICU were sampled to confirm the lack of contamination by SARS-CoV-2. The confirmation of the virus was performed using real time reverse transcription polymerase chain reaction. As a control group, in the microbiology laboratory we inoculated the virus into the different surfaces containing the same drugs included in the first part. Samples were obtained with a sterile swab at 3, 6, 8, 10, 14, 21, and 30 days after inoculation and analyzed through real time reverse transcription polymerase chain reaction.None of the studied materials containing the drugs within an ICU was contaminated by SARS-CoV-2. In the second part, SARS-CoV-2 was found in all surfaces for up to 30 days.The use of double-bag unit-dose system to deliver medication in a pandemic seems effective to prevent the potential transmission of SARS-CoV-2. A striking SARS-CoV-2 RNA stability of up to 30 days was found in the surfaces containing the drugs.

Evolution of Antimicrobial Consumption During the First Wave of COVID-19 Pandemic.

Background: The first wave of COVID-19 pandemic may have significantly impacted antimicrobial consumption in hospitals. The objective of this study was to assess the evolution of antimicrobial consumption during this period. Methods: A retrospective quasi-experimental before-after study was conducted in a Spanish tertiary care hospital. The study compared two periods: pre-pandemic, from January 2018 to February 2020, and during the COVID-19 pandemic from March to June 2020. Antimicrobial consumption was analyzed monthly as defined daily doses (DDD)/100 bed-days and overall hospital and ICU consumption were evaluated. Results: An increase in the hospital consumption was noticed. Although only ceftaroline achieved statistical significance (p = 0.014), a rise was observed in most of the studied antimicrobials. A clear temporal pattern was detected. While an increase in ceftriaxone and azithromycin was observed during March, an increment in the consumption of daptomycin, carbapenems, linezolid, ceftaroline, novel cephalosporin/ß-lactamase inhibitors or triazoles during April-May was noticed. In the ICU, these findings were more evident, namely ceftriaxone (p = 0.029), carbapenems (p = 0.002), daptomycin (p = 0.002), azithromycin (p = 0.030), and linezolid (p = 0.011) but followed a similar temporal pattern. Conclusion: An increase in the antimicrobial consumption during the first wave of COVID-19 pandemic was noticed, especially in the ICU. Availability of updated protocols and antimicrobial stewardship programs are essential to optimize these outcomes.

Successfully non-surgical management of flail chest as first manifestation of multiple myeloma: A case report.

BACKGROUND: Multiple myeloma is a malignant neoplasm of the bone marrow characterized by neoplastic proliferation of monoclonal plasma cells with a high relationship with destructive bone disease. We present a case of a patient diagnosed with multiple myeloma and sternal fracture in association with multiple bilateral rib fractures and thoracic kyphosis, who developed a severe acute respiratory failure, thus complicating the initial presentation of multiple myeloma. We discuss the therapeutic implications of this uncommon presentation. CASE SUMMARY: A 56-year-old man presented to Hematological Department after he had been experiencing worsening back pain over the last five months, with easy fatigability and progressive weight loss. He had no history of previous trauma. The chemical blood tests were compatible with a diagnosis of multiple myeloma. A radiographic bone survey of all major bones revealed, in addition to multiple bilateral rib fractures, a sternal fracture and compression fracture at T9, T10, T11 and L1 vertebrae. Subcutaneous fat biopsy was positive for amyloid. We started treatment with bortezomib and dexamethasone. After 24 h of treatment, he presented dyspnea secondary to flail chest. He required urgent intubation and ventilatory support being transferred to intensive care unit for further management. The patient remained connected to mechanical ventilation (positive pressure) as treatment which stabilized the thorax. A second cycle of bortezomib plus dexamethasone was started and analgesia was optimized. The condition of the patient improved, as evidenced by callus formation on successive computed tomography scans. The patient was taken off the ventilator one month later, and he was extubated successfully, being able to breathe unaided without paradoxical motion. CONCLUSION: This case highlights the importance of combination between bortezomib and dexamethasone to induce remission of multiple myeloma and the initiation of positive airway pressure with mechanical ventilation to stabilize chest wall to solve the respiratory failure. This combined approach allowed to obtain a quick and complete resolution of the clinical situation.

Aeration changes induced by high flow nasal cannula are more homogeneous than those generated by non-invasive ventilation in healthy subjects.

BACKGROUND: Non-invasive mechanical ventilation (NIV) is a standard respiratory support technique used in intensive care units. High-Flow Nasal Cannula (HFNC) has emerged as an alternative, but further evidence is needed. The lung aeration and diaphragm changes achieved with these two strategies in healthy subjects have not been compared to date. METHODS: Twenty healthy subjects were recruited. Ten were ventilated with NIV and ten underwent HFNC. Lung impedance and diaphragmatic ultrasound measurements were performed before and after 30 min of respiratory support. The Mar-index was defined as the ratio of the diaphragm excursion-time index to the respiratory rate. RESULTS: Both groups showed significant decreases in respiratory rate (NIV: 14.4 (4.1) vs 10.4 (1.6), p = 0.009; HFNC: 13.6 (4.3) vs 7.9 (1.5) bpm, p = 0.002) and significant increases in the end-expiratory lung impedance (EELI) (NIV: 66,348(10,761) vs. 73,697 (6858), p = 0.005; HFNC: 66,252 (9793) vs 69,869 (9135), p = 0.012). NIV subjects showed a significant increase in non-dependent silent spaces (4.13 (2.25) vs 5.81 (1.49)%, p = 0.037) while the increase was more homogeneous with HFNC. The variation in EELI tended to be higher in NIV than in HFNC (8137.08 (6152.04) vs 3616.94 (3623.03), p = 0.077). The Mar-index was higher in HFNC group (13.15 vs 5.27 cm-sec2/bpm, p = 0.02). CONCLUSIONS: NIV and HFNC increased EELI in healthy subjects, suggesting an increase in the functional residual capacity. The EELI increase may be higher in NIV, but HFNC produced a more homogeneous change in lung ventilation. HFNC group has a higher MAR-index that could reflect a different ventilatory system adaptation.

Effects on hemodynamics and gas exchange of omega-3 fatty acid-enriched lipid emulsion in acute respiratory distress syndrome (ARDS): a prospective, randomized, double-blind, parallel group study.

INTRODUCTION: We investigated the effects on hemodynamics and gas exchange of a lipid emulsion enriched with omega-3 fatty acids in patients with ARDS. METHODS: The design was a prospective, randomized, double-blind, parallel group study in our Intensive Medicine Department of Vall d'Hebron University Hospital (Barcelona-Spain). We studied 16 consecutive patients with ARDS and intolerance to enteral nutrition (14 men and 2 women; mean age: 58 +/- 13 years; APACHE II score: 17.8 +/- 2.3; Lung Injury Score: 3.1 +/- 0.5; baseline PaO2/FiO2 ratio: 149 +/- 40). Patients were randomized into 2 groups: Group A (n = 8) received the study emulsion Lipoplus 20%, B.Braun Medical (50% MCT, 40% LCT, 10% omega-3); Group B (n = 8) received the control emulsion Intralipid Fresenius Kabi (100% LCT). Lipid emulsions were administered during 12 h at a dose of 0.12 g/kg/h. Measurements of the main hemodynamic and gas exchange parameters were made at baseline (immediately before administration of the lipid emulsions), every hour during the lipid infusion, at the end of administration, and six hours after the end of administration lipid infusion. RESULTS: No statistically significant changes were observed in the different hemodynamic values analyzed. Likewise, the gas exchange parameters did not show statistically significant differences during the study. No adverse effect attributable to the lipid emulsions was seen in the patients analyzed. CONCLUSION: The lipid emulsion enriched with omega-3 fatty acids was safe and well tolerated in short-term administration to patients with ARDS. It did not cause any significant changes in hemodynamic and gas exchange parameters. TRIAL REGISTRATION: ISRCTN63673813.