Central venous pressure and dynamic indices to assess fluid appropriateness in critically ill patients: A pilot study.

BACKGROUND: The correct identification of the appropriateness of fluid administration is important for the treatment of critically ill patients. Static and dynamic indices used to identify fluid responsiveness have been developed throughout the years, nonetheless fluid responsiveness does not indicate that fluid administration is appropriate, and indexes to evaluate appropriateness of fluid administration are lacking. The aim of this study was to evaluate if central venous pressure (CVP) anddynamic indices could correctly identify fluid appropriateness for critically ill patients. METHODS: Data from 31 ICU patients, for a total of 53 observations, was included in the analysis. Patients were divided into two cohorts based on the appropriateness of fluid administration. Fluid appropriateness was defined in presence of a low cardiac index (< 2.5 l/min/m2) without any sign of fluid overload, as assessed by global end-diastolic volume index, extravascular lung water index or pulmonary artery occlusion pressure. RESULTS: For 10 patients, fluid administration was deemed appropriate, while for 21 patients it was deemed inappropriate. Central venous pressure was not different between the two cohorts (mean CVP 11 (4) mmHg in the fluid inappropriate group, 12 (4) mmHg in the fluid appropriate group, p 0.58). The same is true for pulse pressure variation (median PPV 5 [2, 9] % in the fluid inappropriate group, 4 [3, 13] % in the fluid appropriate group, p 0.57), for inferior vena cava distensibility (mean inferior vena cava distensibility 24 (14) % in the fluid inappropriate group, 22 (16) % in the fluid appropriate group, p 0.75) and for changes in end tidal carbon dioxide during a passive leg raising test (median d.ETCO2 1.5 [0.0, 2.0]% in the fluid inappropriate group, 1.0 [0.0, 2.0] % in the fluid appropriate group, p 0.98). There was no association between static and dynamic indices and fluid appropriateness. CONCLUSIONS: Central venous pressure, pulse pressure variation, changes in end tidal carbon dioxide during a passive leg raising test, inferior vena cava distensibility were not associated with fluid appropriateness in our cohorts.

Respiratory system compliance at the same PEEP level is similar in COVID and non-COVID ARDS.

BACKGROUND: The comparison of respiratory system compliance (Crs) between COVID and non-COVID ARDS patients has been the object of debate, but few studies have evaluated it when considering applied positive end expiratory pressure (PEEP), which is one of the known determinants of Crs itself. The aim of this study was to compare Crs taking into account the applied PEEP. METHODS: Two cohorts of patients were created: those with COVID-ARDS and those with non-COVID ARDS. In the whole sample the association between Crs and type of ARDS at different PEEP levels was adjusted for anthropometric and clinical variables. As secondary analyses, patients were matched for predicted functional residual capacity and the same association was assessed. Moreover, the association between Crs and type of ARDS was reassessed at predefined PEEP level of 0, 5, 10, and 15 cmH2O with a propensity score-weighted linear model. RESULTS: 367 patients were included in the study, 276 patients with COVID-ARDS and 91 with non-COVID ARDS. The association between Crs and type of ARDS was not significant in both the complete cohorts (p = 0.17) and in the matched cohorts (p = 0.92). This was true also for the propensity score weighted association at PEEP 5, 10 and 15 cmH2O, while it was statistically significant at PEEP 0 (with a median difference of 3 ml/cmH2O, which in our opinion is not clinically significant). CONCLUSIONS: The compliance of the respiratory system is similar between COVID ARDS and non-COVID ARDS when calculated at the same PEEP level and while taking into account patients' anthropometric characteristics.

Flow Index accurately identifies breaths with low or high inspiratory effort during pressure support ventilation.

BACKGROUND: Flow Index, a numerical expression of the shape of the inspiratory flow-time waveform recorded during pressure support ventilation, is associated with patient inspiratory effort. The aim of this study was to assess the accuracy of Flow Index in detecting high or low inspiratory effort during pressure support ventilation and to establish cutoff values for the Flow index to identify these conditions. The secondary aim was to compare the performance of Flow index,of breathing pattern parameters and of airway occlusion pressure (P0.1) in detecting high or low inspiratory effort during pressure support ventilation. METHODS: Data from 24 subjects was included in the analysis, accounting for a total of 702 breaths. Breaths with high inspiratory effort were defined by a pressure developed by inspiratory muscles (Pmusc) greater than 10 cmH2O while breaths with low inspiratory effort were defined by a Pmusc lower than 5 cmH2O. The areas under the receiver operating characteristic curves of Flow Index and respiratory rate, tidal volume,respiratory rate over tidal volume and P0.1 were analyzed and compared to identify breaths with low or high inspiratory effort. RESULTS: Pmusc, P0.1, Pressure Time Product and Flow Index differed between breaths with high, low and intermediate inspiratory effort, while RR, RR/VT and VT/kg of IBW did not differ in a statistically significant way. A Flow index higher than 4.5 identified breaths with high inspiratory effort [AUC 0.89 (CI 95% 0.85-0.93)], a Flow Index lower than 2.6 identified breaths with low inspiratory effort [AUC 0.80 (CI 95% 0.76-0.83)]. CONCLUSIONS: Flow Index is accurate in detecting high and low spontaneous inspiratory effort during pressure support ventilation.

Antibody Response after BNT162b2 Vaccination in Healthcare Workers Previously Exposed and Not Exposed to SARS-CoV-2.

The Pfizer/BioNtech Comirnaty vaccine (BNT162b2 mRNA COVID-19) against SARS-CoV-2 is currently in use in Italy. Antibodies to evaluate SARS-CoV-2 infection prior to administration are not routinely tested; therefore, two doses may be administered to asymptomatic previously exposed subjects. The aim of this study is to assess if any difference in antibody concentration between subjects exposed and not exposed to SARS-CoV-2 prior to BNT162b2 was present after the first dose and after the second dose of vaccine. Data were retrospectively collected from the clinical documentation of 337 healthcare workers who underwent SARS-CoV-2 testing before and after BNT162b2. Total anti RBD (receptor-binding domain) antibodies against SARS-CoV-2's spike protein were measured before and 21 days after the first dose, and 12 days after the second dose of BNT162b2. Twenty-one days after the first dose, there was a statistically significant difference in antibody concentration between the two groups, which was also maintained twelve days after the second dose. In conclusion, antibody response after receiving BNT162b2 is greater in subjects who have been previously exposed to SARS-CoV-2 than in subjects who have not been previously exposed to the virus, both after 21 days after the first dose and after 12 days from the second dose. Antibody levels, 21 days after the first dose, reached a titer considered positive by the test manufacturer in the majority of subjects who have been previously infected with SARS-CoV-2. Evaluating previous infection prior to vaccination in order to give the least effective number of doses should be considered.

Flow Index: a novel, non-invasive, continuous, quantitative method to evaluate patient inspiratory effort during pressure support ventilation.

BACKGROUND: The evaluation of patient effort is pivotal during pressure support ventilation, but a non-invasive, continuous, quantitative method to assess patient inspiratory effort is still lacking. We hypothesized that the concavity of the inspiratory flow-time waveform could be useful to estimate patient's inspiratory effort. The purpose of this study was to assess whether the shape of the inspiratory flow, as quantified by a numeric indicator, could be associated with inspiratory effort during pressure support ventilation. METHODS: Twenty-four patients in pressure support ventilation were enrolled. A mathematical relationship describing the decay pattern of the inspiratory flow profile was developed. The parameter hypothesized to estimate effort was named Flow Index. Esophageal pressure, airway pressure, airflow, and volume waveforms were recorded at three support levels (maximum, minimum and baseline). The association between Flow Index and reference measures of patient effort (pressure time product and pressure generated by respiratory muscles) was evaluated using linear mixed effects models adjusted for tidal volume, respiratory rate and respiratory rate/tidal volume. RESULTS: Flow Index was different at the three pressure support levels and all group comparisons were statistically significant. In all tested models, Flow Index was independently associated with patient effort (p < 0.001). Flow Index prediction of inspiratory effort agreed with esophageal pressure-based methods. CONCLUSIONS: Flow Index is associated with patient inspiratory effort during pressure support ventilation, and may provide potentially useful information for setting inspiratory support and monitoring patient-ventilator interactions.

COVID-19 ARDS Is Characterized by Increased Dead Space Ventilation Compared With Non-COVID ARDS.

BACKGROUND: ARDS in patients with coronavirus disease 2019 (COVID-19) is characterized by microcirculatory alterations in the pulmonary vascular bed, which could increase dead-space ventilation more than in non-COVID-19 ARDS. We aimed to establish if dead-space ventilation is different in patients with COVID-19 ARDS when compared with patients with non-COVID-19 ARDS. METHODS: A total of 187 subjects with COVID-19 ARDS and 178 subjects with non-COVID-19 ARDS who were undergoing invasive mechanical ventilation were included in the study. The association between the ARDS types and dead-space ventilation, compliance of the respiratory system, subjects' characteristics, organ failures, and mechanical ventilation was evaluated by using data collected in the first 24 h of mechanical ventilation. RESULTS: Corrected minute ventilation (V˙E), a dead-space ventilation surrogate, was higher in the subjects with COVID-19 ARDS versus in those with non-COVID-19 ARDS (median [interquartile range] 12.6 [10.2-15.8] L/min vs 9.4 [7.5-11.6] L/min; P < .001). Increased corrected V˙E was independently associated with COVID-19 ARDS (odds ratio 1.24, 95% CI 1.07-1.47; P = .007). The best compliance of the respiratory system, obtained after testing different PEEPs, was similar between the subjects with COVID-19 ARDS and the subjects with non-COVID-19 ARDS (mean ± SD 38 ± 11 mL/cm H2O vs 37 ± 11 mL/cm H2O, respectively; P = .61). The subjects with COVID-19 ARDS received higher median (interquartile range) PEEP (12 [10-14] cm H2O vs 8 [5-9] cm H2O; P < .001) and lower median (interquartile range) tidal volume (5.8 [5.5-6.3] mL/kg vs 6.6 [6.1-7.3] mL/kg; P < .001) than the subjects with non-COVID-19 ARDS, being these differences maintained at multivariable analysis. In the multivariable analysis, the subjects with COVID-19 ARDS showed a lower risk of anamnestic arterial hypertension (odds ratio 0.18, 95% CI 0.07-0.45; P < .001) and lower neurologic sequential organ failure assessment score (odds ratio 0.16, 95% CI 0.09-0.27; P < .001) than the subjects with non-COVID-19 ARDS. CONCLUSIONS: Indirect measurements of dead space were higher in subjects with COVID-19 ARDS compared with subjects with non-COVID-19 ARDS. The best compliance of the respiratory system was similar in both ARDS forms provided that different PEEPs were applied. A wide range of compliance is present in every ARDS type; therefore, the setting of mechanical ventilation should be individualized patient by patient and not based on the etiology of ARDS.

Effect of Corticosteroids on Mortality in Hospitalized COVID-19 Patients Not Receiving Invasive Mechanical Ventilation.

The most beneficial effect of corticosteroid therapy in COVID-19 patients has been shown in subjects receiving invasive mechanical ventilation (IMV), corresponding to a score of 6 on the World Health Organization (WHO) COVID-19 Ordinal Scale for Clinical Improvement (OSCI). The aim of this observational, single-center, prospective study was to assess the association between corticosteroids and hospital mortality in coronavirus disease 2019 (COVID-19) patients who did not receive IMV (OSCI 3-5). Included were 1,311 COVID-19 patients admitted to nonintensive care wards, and they were divided in two cohorts: (i) 480 patients who received corticosteroid therapy and (ii) 831 patients who did not. The median daily dose was of 8 mg of dexamethasone or equivalent, with a mean therapy duration of 5 (3-9) days. The indication to administer or withhold corticosteroids was given by the treating physician. In-hospital mortality was similar between the two cohorts after adjusting for possible confounders (adjusted odds ratio (ORadj) 1.04, 95% confidence interval (CI), 0.81-1.34, P = 0.74). There was also no difference in Intensive Care Unit (ICU) admission (ORadj 0.81, 95% CI, 0.56-1.17, P = 0.26). COVID-19 patients with noninvasive mechanical ventilation (NIMV) had a lower risk for ICU admission if they received steroid therapy (ORadj 0.58, 95% CI, 0.35-0.94, P = 0.03). In conclusion, corticosteroids were overall not associated with a difference in hospital mortality for patients with COVID-19 with OSCI 3-5. In the subgroup of patients with NIMV (OSCI 5), corticosteroids reduced ICU admission, whereas the effect on mortality requires further studies.

Corticosteroid treatment has no effect on hospital mortality in COVID-19 patients.

Since the start of the novel coronavirus 2019 (COVID-19) pandemic, corticosteroid use has been the subject of debate. The available evidence is uncertain, and knowledge on the subject is evolving. The aim of our cohort study was to evaluate the association between corticosteroid therapy and hospital mortality, in patients hospitalized with COVID-19 after balancing for possible confounders. One thousand four hundred forty four patients were admitted to our hospital with a positive RT-PCR test for SARS-CoV-2, 559 patients (39%) were exposed to corticosteroids during hospital stay, 844 (61%) were not exposed to corticosteroids. In the cohort of patients exposed to corticosteroids, 171 (30.6%) died. In the cohort of patients not exposed to corticosteroids, 183 (21.7%) died (unadjusted p < 0.001). Nonetheless, exposure to corticosteroids was not associated with in-hospital mortality after balancing with overlap weight propensity score (adjusted p = 0.25). Patients in the corticosteroids cohort had a reduced risk of ICU admission (adjusted p < 0.001). Treatment with corticosteroids did not affect hospital mortality in patients with COVID-19 after balancing for confounders. A possible advantage of corticosteroid therapy was to reduce Intensive Care Unit admission, which could be useful in reducing pressure on Intensive Care Units in times of limited resources, as during the COVID-19 pandemic.

Early Percutaneous Tracheostomy in Coronavirus Disease 2019: Association With Hospital Mortality and Factors Associated With Removal of Tracheostomy Tube at ICU Discharge. A Cohort Study on 121 Patients.

OBJECTIVES: Early tracheotomy, defined as a procedure performed within 10 days from intubation, is associated with more ventilator free days, shorter ICU stay, and lower mortality than late tracheotomy. During the coronavirus disease 2019 pandemic, it was especially important to save operating room resources and to have a shorter ICU stay for patients, when ICUs had insufficient beds. In this context of limited resources, early percutaneous tracheostomy could be an effective way to manage mechanically ventilated patients. Nevertheless, current recommendations suggest delaying or avoiding the tracheotomy in coronavirus disease 2019 patients. Aim of the study was to analyze the hospital mortality of coronavirus disease 2019 patients who had received early percutaneous tracheostomy and factors associated with removal of tracheostomy cannula at ICU discharge. DESIGN: Cohort study. SETTING: Coronavirus disease 2019 ICU. PATIENTS: Adult patients with coronavirus disease 2019 3 days after ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three days after ICU admission, 164 patients were present in ICU and included in the analysis. One-hundred and twenty-one patients (74%) were tracheostomized, whereas the other 43 (26%) were managed with translaryngeal intubation only. In multivariable analysis, early percutaneous tracheostomy was associated with lower hospital mortality. Sixty-six of tracheostomized patients (55%) were discharged alive from the hospital. Age and male sex were the only characteristics that were independently associated with mortality in the tracheostomized patients (45.5% and 62.8% in tracheostomized and nontracheostomized patients, respectively; p = 0.009). Tracheostomy tube was removed in 47 of the tracheostomized patients (71%). The only variable independently associated with weaning from tracheostomy at ICU discharge was a faster start of spontaneous breathing after tracheotomy was performed. CONCLUSIONS: Early percutaneous tracheostomy was safe and effective in coronavirus disease 2019 patients, giving a good chance of survival and of weaning from tracheostomy cannula at ICU discharge.

Corrected Minute Ventilation Is Associated With Mortality in ARDS Caused by COVID-19.

BACKGROUND: The ratio of dead space to tidal volume (VD/VT) is associated with mortality in patients with ARDS. Corrected minute ventilation ([Formula: see text]) is a simple surrogate of dead space, but, despite its increasing use, its association with mortality has not been proven. The aim of our study was to assess the association between [Formula: see text] and hospital mortality. We also compared the strength of this association with that of estimated VD/VT and ventilatory ratio. METHODS: We performed a retrospective study with prospectively collected data. We evaluated 187 consecutive mechanically ventilated subjects with ARDS caused by novel coronavirus disease (COVID-19). The association between [Formula: see text] and hospital mortality was assessed in multivariable logistic models. The same was done for estimated VD/VT and ventilatory ratio. RESULTS: Mean ± SD [Formula: see text] was 11.8 ± 3.3 L/min in survivors and 14.5 ± 3.9 L/min in nonsurvivors (P < .001) and was independently associated with mortality (adjusted odds ratio 1.15, P = .01). The strength of association of [Formula: see text] with mortality was similar to that of VD/VT and ventilatory ratio. CONCLUSIONS: [Formula: see text] was independently associated with hospital mortality in subjects with ARDS caused by COVID-19. [Formula: see text] could be used at the patient's bedside for outcome prediction and severity stratification, due to the simplicity of its calculation. These findings need to be confirmed in subjects with ARDS without viral pneumonia and when lung-protective mechanical ventilation is not rigorously applied.

Pneumomediastinum and subcutaneous emphysema in COVID-19: barotrauma or lung frailty?

BACKGROUND: In mechanically ventilated acute respiratory distress syndrome (ARDS) patients infected with the novel coronavirus disease (COVID-19), we frequently recognised the development of pneumomediastinum and/or subcutaneous emphysema despite employing a protective mechanical ventilation strategy. The purpose of this study was to determine if the incidence of pneumomediastinum/subcutaneous emphysema in COVID-19 patients was higher than in ARDS patients without COVID-19 and if this difference could be attributed to barotrauma or to lung frailty. METHODS: We identified both a cohort of patients with ARDS and COVID-19 (CoV-ARDS), and a cohort of patients with ARDS from other causes (noCoV-ARDS).Patients with CoV-ARDS were admitted to an intensive care unit (ICU) during the COVID-19 pandemic and had microbiologically confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. NoCoV-ARDS was identified by an ARDS diagnosis in the 5 years before the COVID-19 pandemic period. RESULTS: Pneumomediastinum/subcutaneous emphysema occurred in 23 out of 169 (13.6%) patients with CoV-ARDS and in three out of 163 (1.9%) patients with noCoV-ARDS (p<0.001). Mortality was 56.5% in CoV-ARDS patients with pneumomediastinum/subcutaneous emphysema and 50% in patients without pneumomediastinum (p=0.46).CoV-ARDS patients had a high incidence of pneumomediastinum/subcutaneous emphysema despite the use of low tidal volume (5.9±0.8 mL·kg-1 ideal body weight) and low airway pressure (plateau pressure 23±4 cmH2O). CONCLUSIONS: We observed a seven-fold increase in pneumomediastinum/subcutaneous emphysema in CoV-ARDS. An increased lung frailty in CoV-ARDS could explain this finding more than barotrauma, which, according to its etymology, refers to high transpulmonary pressure.

Thromboprophylaxis with enoxaparin is associated with a lower death rate in patients hospitalized with SARS-CoV-2 infection. A cohort study.

BACKGROUND: Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection is associated with hypercoagulability caused by direct invasion of endothelial cells and\or proinflammatory cytokine release. Thromboprophylaxis with enoxaparin is recommended by current guidelines, but evidence is still weak. The aim of this study was to assess the impact of thromboprophylaxis with enoxaparin on hospital mortality in patients admitted for Coronavirus disease 2019 (COVID-19). The effects of enoxaparin on intensive care admission and hospital length-of-stay were evaluated as secondary outcomes. METHODS: Observational cohort study, with data collected from patients admitted to Poliambulanza Foundation with positive real time reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 from 20th February to 10th May 2020. Multivariate logistic regression with overlap weight propensity score was used to model hospital mortality and intensive care admission, hospital length-of-stay was analyzed with a multivariate Poisson regression. Seven hundred and ninety nine (57%) patients who received enoxaparin at least once during the hospitalization were included in the enoxaparin cohort, 604 (43%) patients who did not were included in the control cohort. FINDINGS: At the adjusted analysis enoxaparin was associated with lower in-hospital mortality (Odds Ratio 0·53, 95% C.I. 0·40-0·70) compared with no enoxaparin treatment. Hospital length-of-stay was longer for patients treated with enoxaparin (Incidence Rate Ratios 1·45, 95% C.I. 1·36-1·54). Enoxaparin treatment was associated with reduced risk of intensive care admission at the adjusted analysis (Odds Ratio 0·48, 95% C.I. 0·32-0·69). INTERPRETATION: This study shows that treatment with enoxaparin during hospital stay is associated with a lower death rate and, while results from randomized clinical trials are still pending, this study supports the use of thromboprophylaxis with enoxaparin in all patients admitted for COVID-19. Moreover, when enoxaparin is used on the wards, it reduces the risk of Intensive Care Unit admission.

Impact of Azithromycin and/or Hydroxychloroquine on Hospital Mortality in COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to widespread use of hydroxychloroquine and azithromycin despite the lack of conclusive evidence for their safety and efficacy. We evaluated the association between treatment with hydroxychloroquine and/or azithromycin and hospital mortality as the primary outcome. We compared the hospital mortality of patients treated with hydroxychloroquine alone, azithromycin alone, or their combination to the mortality of patients who received neither drug. A logistic multivariate model with overlap weight propensity score was used for estimation of odds ratios (ORs) with 95% confidence intervals (95% CIs). One thousand four hundred and three patients with SARS-CoV-2 infection were admitted to the hospital. At the time of the analysis, the outcome was available for 1376 (98%) of them. Five hundred and eighty-seven patients (42%) received azithromycin and 377 patients (27%) received hydroxychloroquine, alone or in combination. In-hospital mortality was 26%. After the adjusted analysis, azithromycin alone was associated with lower mortality (OR 0.60, 95% CI 0.42-0.85) compared to no treatment. Hydroxychloroquine alone (OR 0.76, 95% CI 0.53-1.08) and the combination of azithromycin and hydroxychloroquine (OR 1.13, 95% CI 0.77-1.69) were not associated with hospital mortality. In this cohort of patients, azithromycin alone was associated with lower hospital mortality but hydroxychloroquine was not associated with increased or reduced mortality. While we await randomized clinical trials, these data support the use of azithromycin in novel coronavirus disease 2019 (COVID-19) and can contribute to better understanding of its role in further meta-analyses.