Barotrauma during Noninvasive Respiratory Support in COVID-19 Pneumonia Outside ICU: The Ancillary COVIMIX-2 Study.

BACKGROUND: Noninvasive respiratory support (NIRS) has been extensively used during the COVID-19 surge for patients with acute respiratory failure. However, little data are available about barotrauma during NIRS in patients treated outside the intensive care unit (ICU) setting. METHODS: COVIMIX-2 was an ancillary analysis of the previous COVIMIX study, a large multicenter observational work investigating the frequencies of barotrauma (i.e., pneumothorax and pneumomediastinum) in adult patients with COVID-19 interstitial pneumonia. Only patients treated with NIRS outside the ICU were considered. Baseline characteristics, clinical and radiological disease severity, type of ventilatory support used, blood tests and mortality were recorded. RESULTS: In all, 179 patients were included, 60 of them with barotrauma. They were older and had lower BMI than controls (p < 0.001 and p = 0.045, respectively). Cases had higher respiratory rates and lower PaO2/FiO2 (p = 0.009 and p < 0.001). The frequency of barotrauma was 0.3% [0.1-1.3%], with older age being a risk factor for barotrauma (OR 1.06, p = 0.015). Alveolar-arterial gradient (A-a) DO2 was protective against barotrauma (OR 0.92 [0.87-0.99], p = 0.026). Barotrauma required active treatment, with drainage, in only a minority of cases. The type of NIRS was not explicitly related to the development of barotrauma. Still, an escalation of respiratory support from conventional oxygen therapy, high flow nasal cannula to noninvasive respiratory mask was predictive for in-hospital death (OR 15.51, p = 0.001). CONCLUSIONS: COVIMIX-2 showed a low frequency for barotrauma, around 0.3%. The type of NIRS used seems not to increase this risk. Patients with barotrauma were older, with more severe systemic disease, and showed increased mortality.

Corrigendum: Comfort during non-invasive ventilation.

[This corrects the article DOI: 10.3389/fmed.2022.874250.].

Comfort During Non-invasive Ventilation.

Non-invasive ventilation (NIV) has been shown to be effective in avoiding intubation and improving survival in patients with acute hypoxemic respiratory failure (ARF) when compared to conventional oxygen therapy. However, NIV is associated with high failure rates due, in most cases, to patient discomfort. Therefore, increasing attention has been paid to all those interventions aimed at enhancing patient's tolerance to NIV. Several practical aspects have been considered to improve patient adaptation. In particular, the choice of the interface and the ventilatory setting adopted for NIV play a key role in the success of respiratory assistance. Among the different NIV interfaces, tolerance is poorest for the nasal and oronasal masks, while helmet appears to be better tolerated, resulting in longer use and lower NIV failure rates. The choice of fixing system also significantly affects patient comfort due to pain and possible pressure ulcers related to the device. The ventilatory setting adopted for NIV is associated with varying degrees of patient comfort: patients are more comfortable with pressure-support ventilation (PSV) than controlled ventilation. Furthermore, the use of electrical activity of the diaphragm (EADi)-driven ventilation has been demonstrated to improve patient comfort when compared to PSV, while reducing neural drive and effort. If non-pharmacological remedies fail, sedation can be employed to improve patient's tolerance to NIV. Sedation facilitates ventilation, reduces anxiety, promotes sleep, and modulates physiological responses to stress. Judicious use of sedation may be an option to increase the chances of success in some patients at risk for intubation because of NIV intolerance consequent to pain, discomfort, claustrophobia, or agitation. During the Coronavirus Disease-19 (COVID-19) pandemic, NIV has been extensively employed to face off the massive request for ventilatory assistance. Prone positioning in non-intubated awake COVID-19 patients may improve oxygenation, reduce work of breathing, and, possibly, prevent intubation. Despite these advantages, maintaining prone position can be particularly challenging because poor comfort has been described as the main cause of prone position discontinuation. In conclusion, comfort is one of the major determinants of NIV success. All the strategies aimed to increase comfort during NIV should be pursued.

Lung ultrasound monitoring: impact on economics and outcomes.

PURPOSE OF REVIEW: This review aims to summarize the impact of lung ultrasonography (LUS) on economics and possible impact on patients' outcomes, proven its diagnostic accuracy in patients with acute respiratory failure. RECENT FINDINGS: Despite some previous ethical concerns on LUS examination, today this technique has showed several advantages. First, it is now clear that the daily use of LUS can provide a relevant cost reduction in healthcare of patients with acute respiratory failure, while reducing the risk of transport of patients to radiological departments for chest CT scan. In addition, LUS reduces the exposition to x-rays since can replace the bedside chest X-ray examination in many cases. Indeed, LUS is characterized by a diagnostic accuracy that is even superior to portable chest X-ray when performed by well trained personnel. Finally, LUS examination is a useful tool to predict the course of patients with pneumonia, including the need for hospitalization and ICU admission, noninvasive ventilation failure and orotracheal intubation, weaning success, and mortality. SUMMARY: LUS should be implemented not only in Intensive Care Units, but also in other setting like emergency departments. Since most data comes from the recent coronavirus disease 2019 pandemic, further investigations are required in Acute Respiratory Failure of different etiologies.

Treatment of patients with 'do not intubate orders'.

PURPOSE OF REVIEW: Do-not-intubate (DNI) orders are more frequently encountered over time. This widespread diffusion of DNI orders make it essential to develop therapeutic strategies matching patient's and his family willingness. The present review sheds light on the therapeutic approaches employed to support respiratory function of patients with DNI orders. RECENT FINDINGS: In DNI patients, several approaches have been described to relieve dyspnoea and address acute respiratory failure (ARF). Despite its extensive use, supplemental oxygen is not so useful in assuring dyspnoea relief. Noninvasive respiratory support (NIRS) is frequently employed to treat ARF in DNI patients. Also, to enhance DNI patients comfort during NIRS, it is worthy to point out the role of analgo-sedative medications. Lastly, a particular aspect concerns the first waves of coronavirus disease 2019 pandemic, when DNI orders have been pursued on factors unrelated to patient's wishes, in the total absence of family support due to the lockdown policy. In this setting, NIRS has been extensively employed in DNI patients with a survival rate of around 20%. SUMMARY: In dealing with DNI patients, the individualization of treatments is of pivotal importance to respect patient's preferences and improve quality of life at the same time.

Ventilatory associated barotrauma in COVID-19 patients: A multicenter observational case control study (COVI-MIX-study).

BACKGROUND: The risk of barotrauma associated with different types of ventilatory support is unclear in COVID-19 patients. The primary aim of this study was to evaluate the effect of the different respiratory support strategies on barotrauma occurrence; we also sought to determine the frequency of barotrauma and the clinical characteristics of the patients who experienced this complication. METHODS: This multicentre retrospective case-control study from 1 March 2020 to 28 February 2021 included COVID-19 patients who experienced barotrauma during hospital stay. They were matched with controls in a 1:1 ratio for the same admission period in the same ward of treatment. Univariable and multivariable logistic regression (OR) were performed to explore which factors were associated with barotrauma and in-hospital death. RESULTS: We included 200 cases and 200 controls. Invasive mechanical ventilation was used in 39.3% of patients in the barotrauma group, and in 20.1% of controls (p<0.001). Receiving non-invasive ventilation (C-PAP/PSV) instead of conventional oxygen therapy (COT) increased the risk of barotrauma (OR 5.04, 95% CI 2.30 - 11.08, p<0.001), similarly for invasive mechanical ventilation (OR 6.24, 95% CI 2.86-13.60, p<0.001). High Flow Nasal Oxygen (HFNO), compared with COT, did not significantly increase the risk of barotrauma. Barotrauma frequency occurred in 1.00% [95% CI 0.88-1.16] of patients; these were older (p=0.022) and more frequently immunosuppressed (p=0.013). Barotrauma was shown to be an independent risk for death (OR 5.32, 95% CI 2.82-10.03, p<0.001). CONCLUSIONS: C-PAP/PSV compared with COT or HFNO increased the risk of barotrauma; otherwise HFNO did not. Barotrauma was recorded in 1.00% of patients, affecting mainly patients with more severe COVID-19 disease. Barotrauma was independently associated with mortality. TRIAL REGISTRATION: this case-control study was prospectively registered in clinicaltrial.gov as NCT04897152 (on 21 May 2021).

Quality of Life in COVID-Related ARDS Patients One Year after Intensive Care Discharge (Odissea Study): A Multicenter Observational Study.

BACKGROUND: Investigating the health-related quality of life (HRQoL) after intensive care unit (ICU) discharge is necessary to identify possible modifiable risk factors. The primary aim of this study was to investigate the HRQoL in COVID-19 critically ill patients one year after ICU discharge. METHODS: In this multicenter prospective observational study, COVID-19 patients admitted to nine ICUs from 1 March 2020 to 28 February 2021 in Italy were enrolled. One year after ICU discharge, patients were required to fill in short-form health survey 36 (SF-36) and impact of event-revised (IES-R) questionnaire. A multivariate linear or logistic regression analysis to search for factors associated with a lower HRQoL and post-traumatic stress disorded (PTSD) were carried out, respectively. RESULTS: Among 1003 patients screened, 343 (median age 63 years [57-70]) were enrolled. Mechanical ventilation lasted for a median of 10 days [2-20]. Physical functioning (PF 85 [60-95]), physical role (PR 75 [0-100]), emotional role (RE 100 [33-100]), bodily pain (BP 77.5 [45-100]), social functioning (SF 75 [50-100]), general health (GH 55 [35-72]), vitality (VT 55 [40-70]), mental health (MH 68 [52-84]) and health change (HC 50 [25-75]) describe the SF-36 items. A median physical component summary (PCS) and mental component summary (MCS) scores were 45.9 (36.5-53.5) and 51.7 (48.8-54.3), respectively, considering 50 as the normal value of the healthy general population. In all, 109 patients (31.8%) tested positive for post-traumatic stress disorder, also reporting a significantly worse HRQoL in all SF-36 domains. The female gender, history of cardiovascular disease, liver disease and length of hospital stay negatively affected the HRQoL. Weight at follow-up was a risk factor for PTSD (OR 1.02, p = 0.03). CONCLUSIONS: The HRQoL in COVID-19 ARDS (C-ARDS) patients was reduced regarding the PCS, while the median MCS value was slightly above normal. Some risk factors for a lower HRQoL have been identified, the presence of PTSD is one of them. Further research is warranted to better identify the possible factors affecting the HRQoL in C-ARDS.

Lung ultrasound to evaluate aeration changes in response to recruitment maneuver and prone positioning in intubated patients with COVID-19 pneumonia: preliminary study.

BACKGROUND: This single-center preliminary prospective observational study used bedside ultrasound to assess the lung aeration modifications induced by recruitment maneuver and pronation in intubated patients with acute respiratory disease syndrome (ARDS) related to coronavirus 2019 disease (COVID-19). All adult intubated COVID-19 patients suitable for pronation were screened. After enrollment, patients underwent 1 h in a volume-controlled mode in supine position (baseline) followed by a 35-cmH2O-recruitment maneuver of 2 min (recruitment). Final step involved volume-controlled mode in prone position set as at baseline (pronation). At the end of the first two steps and 1 h after pronation, a lung ultrasound was performed, and global and regional lung ultrasound score (LUS) were analyzed. Data sets are presented as a median and 25th-75th percentile. RESULTS: From January to May 2022, 20 patients were included and analyzed. Global LUS reduced from 26.5 (23.5-30.0) at baseline to 21.5 (18.0-23.3) and 23.0 (21.0-26.3) at recruitment (p < 0.001) and pronation (p = 0.004). In the anterior lung regions, the regional LUS were 1.8 (1.1-2.0) following recruitment and 2.0 (1.6-2.2) in the supine (p = 0.008) and 2.0 (1.8-2.3) in prone position (p = 0.023). Regional LUS diminished from 2.3 (2.0-2.5) in supine to 2.0 (1.8-2.0) with recruitment in the lateral lung zones (p = 0.036). Finally, in the posterior lung units, regional LUS improved from 2.5 (2.3-2.8) in supine to 2.3 (1.8-2.5) through recruitment (p = 0.003) and 1.8 (1.3-2.2) with pronation (p < 0.0001). CONCLUSIONS: In our investigation, recruitment maneuver and prone positioning demonstrated an enhancement in lung aeration when compared to supine position, as assessed by bedside lung ultrasound. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , Number NCT05209477, prospectively registered and released on 01/26/2022.

VENTILATORY ASSOCIATED BAROTRAUMA IN COVID-19 PATIENTS: A MULTICENTER OBSERVATIONAL CASE CONTROL STUDY (COVI-MIX-STUDY)

Background The risk of barotrauma associated with different types of ventilatory support is unclear in COVID-19 patients. The primary aim of this study was to evaluate the effect of the different respiratory support strategies on barotrauma occurrence;we also sought to determine the frequency of barotrauma and the clinical characteristics of the patients who experienced this complication. Methods This multicentre retrospective case-control study from 1 March 2020 to 28 February 2021 included COVID-19 patients who experienced barotrauma during hospital stay. They were matched with controls in a 1:1 ratio for the same admission period in the same ward of treatment. Univariable and multivariable logistic regression (OR) were performed to explore which factors were associated with barotrauma and in-hospital death. Results We included 200 cases and 200 controls. Invasive mechanical ventilation was used in 39.3% of patients in the barotrauma group, and in 20.1% of controls (p<0.001). Receiving non-invasive ventilation (C-PAP/PSV) instead of conventional oxygen therapy (COT) increased the risk of barotrauma (OR 5.04, 95% CI 2.30 - 11.08, p<0.001), similarly for invasive mechanical ventilation (OR 6.24, 95% CI 2.86-13.60, p<0.001). High Flow Nasal Oxygen (HFNO), compared with COT, did not significantly increase the risk of barotrauma. Barotrauma frequency occurred in 1.00% [95% CI 0.88-1.16] of patients;these were older (p=0.022) and more frequently immunosuppressed (p=0.013). Barotrauma was shown to be an independent risk for death (OR 5.32, 95% CI 2.82-10.03, p<0.001). Conclusions C-PAP/PSV compared with COT or HFNO increased the risk of barotrauma;otherwise HFNO did not. Barotrauma was recorded in 1.00% of patients, affecting mainly patients with more severe COVID-19 disease. Barotrauma was independently associated with mortality. Trial registration this case-control study was prospectively registered in clinicaltrial.gov as NCT04897152 (on 21 May 2021).

Level of Diffusion and Training of Lung Ultrasound during the COVID-19 Pandemic - A National Online Italian Survey (ITALUS) from the Lung Ultrasound Working Group of the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI).

PURPOSE: The goal of this survey was to describe the use and diffusion of lung ultrasound (LUS), the level of training received before and during the COVID-19 pandemic, and the clinical impact LUS has had on COVID-19 cases in intensive care units (ICU) from February 2020 to May 2020. MATERIALS AND METHODS: The Italian Lung Ultrasound Survey (ITALUS) was a nationwide online survey proposed to Italian anesthesiologists and intensive care physicians carried out after the first wave of the COVID-19 pandemic. It consisted of 27 questions, both quantitative and qualitative. RESULTS: 807 responded to the survey. The median previous LUS experience was 3 years (IQR 1.0-6.0). 473 (60.9 %) reported having attended at least one training course on LUS before the COVID-19 pandemic. 519 (73.9 %) reported knowing how to use the LUS score. 404 (52 %) reported being able to use LUS without any supervision. 479 (68.2 %) said that LUS influenced their clinical decision-making, mostly with respect to patient monitoring. During the pandemic, the median of patients daily evaluated with LUS increased 3-fold (p < 0.001), daily use of general LUS increased from 10.4 % to 28.9 % (p < 0.001), and the daily use of LUS score in particular increased from 1.6 % to 9.0 % (p < 0.001). CONCLUSION: This survey showed that LUS was already extensively used during the first wave of the COVID-19 pandemic by anesthesiologists and intensive care physicians in Italy, and then its adoption increased further. Residency programs are already progressively implementing LUS teaching. However, 76.7 % of the sample did not undertake any LUS certification.

Bivalirudin vs. Enoxaparin in Intubated COVID-19 Patients: A Pilot Multicenter Randomized Controlled Trial.

(1) Background: In COVID-19 patients, the occurrence of thromboembolic complications contributes to disease progression and mortality. In patients at increased risk for thrombotic complications, therapeutic enoxaparin should be considered. However, critically ill COVID-19 patients could develop resistance to enoxaparin. Bivalirudin, a thrombin inhibitor, may be an alternative. This pilot multicenter randomized controlled trial aims to ascertain if bivalirudin may reduce the time spent under invasive mechanical ventilation, as compared to enoxaparin. (2) Methods: Intubated COVID-19 patients at risk for thrombo-embolic complications were randomized to receive therapeutic doses of enoxaparin or bivalirudin. We ascertained the time spent under invasive mechanical ventilation during the first 28 days from Intensive Care Unit (ICU) admission. A standardized weaning protocol was implemented in all centers. In addition, we assessed the occurrence of thromboembolic complications, the number of patients requiring percutaneous tracheostomy, the gas exchange, the reintubation rate, the ICU length of stay, the ICU and 28-days mortalities. (3) Results: We enrolled 58 consecutive patients. Bivalirudin did not reduce the time spent under invasive mechanical ventilation as compared to enoxaparin (12 [8; 13] vs. 13 [10; 15] days, respectively; p = 0.078). Thrombotic (p = 0.056) and embolic (p = 0.423) complications, need for tracheostomy (p = 0.423) or reintubation (p = 0.999), the ICU length of stay (p = 0.076) and mortality (p = 0.777) were also similar between treatments. Patients randomized to bivalirudin showed a higher oxygenation at day 7 and 15 after randomization, when compared to enoxaparin group. (4) Conclusions: In intubated COVID-19 patients at increased risk for thromboembolic complications, bivalirudin did not reduce the time spent under invasive mechanical ventilation, nor improved any other clinical outcomes.

Diaphragm ultrasound evaluation during weaning from mechanical ventilation in COVID-19 patients: a pragmatic, cross-section, multicenter study.

BACKGROUND: Diaphragmatic dysfunction is a major factor responsible for weaning failure in patients that underwent prolonged invasive mechanical ventilation for acute severe respiratory failure from COVID-19. This study hypothesizes that ultrasound measured diaphragmatic thickening fraction (DTF) could provide corroborating information for weaning COVID-19 patients from mechanical ventilation. METHODS: This was an observational, pragmatic, cross-section, multicenter study in 6 Italian intensive care units. DTF was assessed in COVID-19 patients undergoing weaning from mechanical ventilation from 1st March 2020 to 30th June 2021. Primary aim was to evaluate whether DTF is a predictive factor for weaning failure. RESULTS: Fifty-seven patients were enrolled, 25 patients failed spontaneous breathing trial (44%). Median length of invasive ventilation was 14 days (IQR 7-22). Median DTF within 24 h since the start of weaning was 28% (IQR 22-39%), RASS score (- 2 vs - 2; p = 0.031); Kelly-Matthay score (2 vs 1; p = 0.002); inspiratory oxygen fraction (0.45 vs 0.40; p = 0.033). PaO2/FiO2 ratio was lower (176 vs 241; p = 0.032) and length of intensive care stay was longer (27 vs 16.5 days; p = 0.025) in patients who failed weaning. The generalized linear regression model did not select any variables that could predict weaning failure. DTF was correlated with pH (RR 1.56 × 1027; p = 0.002); Kelly-Matthay score (RR 353; p < 0.001); RASS (RR 2.11; p = 0.003); PaO2/FiO2 ratio (RR 1.03; p = 0.05); SAPS2 (RR 0.71; p = 0.005); hospital and ICU length of stay (RR 1.22 and 0.79, respectively; p < 0.001 and p = 0.004). CONCLUSIONS: DTF in COVID-19 patients was not predictive of weaning failure from mechanical ventilation, and larger studies are needed to evaluate it in clinical practice further. Registered: ClinicalTrial.gov (NCT05019313, 24 August 2021).

Noninvasive respiratory support outside the intensive care unit for acute respiratory failure related to coronavirus-19 disease: a systematic review and meta-analysis.

BACKGROUND: Noninvasive respiratory support (NIRS) has been diffusely employed outside the intensive care unit (ICU) to face the high request of ventilatory support due to the massive influx of patients with acute respiratory failure (ARF) caused by coronavirus-19 disease (COVID-19). We sought to summarize the evidence on clinically relevant outcomes in COVID-19 patients supported by NIV outside the ICU. METHODS: We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register, along with medRxiv and bioRxiv repositories for pre-prints, for observational studies and randomized controlled trials, from inception to the end of February 2021. Two authors independently selected the investigations according to the following criteria: (1) observational study or randomized clinical trials enrolling ≥ 50 hospitalized patients undergoing NIRS outside the ICU, (2) laboratory-confirmed COVID-19, and (3) at least the intra-hospital mortality reported. Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed. Data extraction was independently performed by two authors to assess: investigation features, demographics and clinical characteristics, treatments employed, NIRS regulations, and clinical outcomes. Methodological index for nonrandomized studies tool was applied to determine the quality of the enrolled studies. The primary outcome was to assess the overall intra-hospital mortality of patients under NIRS outside the ICU. The secondary outcomes included the proportions intra-hospital mortalities of patients who underwent invasive mechanical ventilation following NIRS failure and of those with 'do-not-intubate' (DNI) orders. RESULTS: Seventeen investigations (14 peer-reviewed and 3 pre-prints) were included with a low risk of bias and a high heterogeneity, for a total of 3377 patients. The overall intra-hospital mortality of patients receiving NIRS outside the ICU was 36% [30-41%]. 26% [21-30%] of the patients failed NIRS and required intubation, with an intra-hospital mortality rising to 45% [36-54%]. 23% [15-32%] of the patients received DNI orders with an intra-hospital mortality of 72% [65-78%]. Oxygenation on admission was the main source of between-study heterogeneity. CONCLUSIONS: During COVID-19 outbreak, delivering NIRS outside the ICU revealed as a feasible strategy to cope with the massive demand of ventilatory assistance. REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/prospero/ , CRD42020224788, December 11, 2020.

Microbiome in Critical Care: An Unconventional and Unknown Ally.

BACKGROUND: The digestive tract represents an interface between the external environment and the body where the interaction of a complex polymicrobial ecology has an important influence on health and disease. The physiological mechanisms that are altered during hospitalization and in the intensive care unit (ICU) contribute to the pathobiota's growth. Intestinal dysbiosis occurs within hours of being admitted to ICU. This may be due to different factors, such as alterations of normal intestinal transit, administration of various medications, or alterations in the intestinal wall, which causes a cascade of events that will lead to the increase of nitrates and decrease of oxygen concentration, and the liberation of free radicals. OBJECTIVE: This work aims to report the latest updates on the microbiota's contribution to developing sepsis in patients in the ICU department. In this short review, the latest scientific findings on the mechanisms of intestinal immune defenses performed both locally and systemically have been reviewed. Additionally, we considered it necessary to review the literature on the basis of the many studies carried out on the microbiota in the critically ill as a prevention to the spread of the infection in these patients. MATERIALS AND METHODS: This review has been written to answer four main questions: 1- What are the main intestinal flora's defense mechanisms that help us to prevent the risk of developing systemic diseases? 2- What are the main Systemic Abnormalities of Dysbiosis? 3- What are the Modern Strategies Used in ICU to Prevent the Infection Spreading? 4- What is the Relationship between COVID-19 and Microbiota? We reviewed 72 articles using the combination of following keywords: "microbiota" and "microbiota" and "intensive care", "intensive care" and "gut", "critical illness", "microbiota" and "critical care", "microbiota" and "sepsis", "microbiota" and "infection", and "gastrointestinal immunity" in: Cochrane Controlled Trials Register, Cochrane Library, Medline and Pubmed, Google Scholar, Ovid/Wiley. Moreover, we also consulted the site ClinicalTrials.com to find out studies that have been recently conducted or are currently ongoing. RESULTS: The critical illness can alter intestinal bacterial flora leading to homeostasis disequilibrium. Despite numerous mechanisms, such as epithelial cells with calciform cells that together build a mechanical barrier for pathogenic bacteria, the presence of mucous associated lymphoid tissue (MALT) which stimulates an immune response through the production of interferon-gamma (IFN-y) and THN-a or or from the production of anti-inflammatory cytokines produced by lymphocytes Thelper 2. But these defenses can be altered following hospitalization in ICU and lead to serious complications, such as acute respiratory distress syndrome (ARDS), health care associated pneumonia (HAP) and ventilator associated pneumonia (VAP), systemic infection and multiple organ failure (MOF), but also to the development of coronary artery disease (CAD). In addition, the microbiota has a significant impact on the development of intestinal complications and the severity of the SARS-COVID-19 patients. CONCLUSION: The microbiota is recognized as one of the important factors that can worsen the clinical conditions of patients who are already very frail in the intensive care unit. At the same time, the microbiota also plays a crucial role in the prevention of ICU-associated complications. By using the resources that are available, such as probiotics, synbiotics or fecal microbiota transplantation (FMT), we can preserve the integrity of the microbiota and the GUT, which will later help maintain homeostasis in ICU patients.

Can Lung Ultrasound Be the Ideal Monitoring Tool to Predict the Clinical Outcome of Mechanically Ventilated COVID-19 Patients? An Observational Study.

BACKGROUND: During the COVID-19 pandemic, lung ultrasound (LUS) has been widely used since it can be performed at the patient's bedside, does not produce ionizing radiation, and is sufficiently accurate. The LUS score allows for quantifying lung involvement; however, its clinical prognostic role is still controversial. METHODS: A retrospective observational study on 103 COVID-19 patients with respiratory failure that were assessed with an LUS score at intensive care unit (ICU) admission and discharge in a tertiary university COVID-19 referral center. RESULTS: The deceased patients had a higher LUS score at admission than the survivors (25.7 vs. 23.5; p-value = 0.02; cut-off value of 25; Odds Ratio (OR) 1.1; Interquartile Range (IQR) 1.0-1.2). The predictive regression model shows that the value of LUSt0 (OR 1.1; IQR 1.0-1.3), age (OR 1.1; IQR 1.0-1.2), sex (OR 0.7; IQR 0.2-3.6), and days in spontaneous breathing (OR 0.2; IQR 0.1-0.5) predict the risk of death for COVID-19 patients (Area under the Curve (AUC) 0.92). Furthermore, the surviving patients showed a significantly lower difference between LUS scores at admission and discharge (mean difference of 1.75, p-value = 0.03). CONCLUSION: Upon entry into the ICU, the LUS score may play a prognostic role in COVID-19 patients with ARDS. Furthermore, employing the LUS score as a monitoring tool allows for evaluating the patients with a higher probability of survival.

What's new on the management of obstetric patients who tested positive for COVID-19?

To date, there is still partial data on the effects of COVID-19 on pregnant women. The constant collection of information results in a continuous updating of the knowledge about the best management of pregnant patients affected by COVID-19. This work aimed to summarize the state of the art on prevention and management of SARS-CoV-2 infection in obstetric patients. This was enabled by a comprehensive literature search for the most recent and relevant publications on the subject, including guidelines and recommendations. Management of these women by a multidisciplinary team is of crucial importance, given the extreme clinical complexity of this condition. Every health worker involved must put in place all possible procedures to protect themselves from contagion. Neuraxial anesthesia should be favored in the management of labor and caesarean section over other modalities, unless there are contraindications based on the patient's status. There is still no standardized drug treatment in pregnant women with COVID-19 due to their exclusion from studies conducted to evaluate pharmacological therapies. Nevertheless, various drugs have been used to treat this disease in pregnancy, although the data at our disposal are still few. As regards mRNA vaccines, it seems that their immunogenicity, safety and tolerability in pregnant women are comparable to those of non-pregnant women of the same age. More studies are certainly needed in infected pregnant women to establish treatment and prevention protocols for this special category of patients.

Lung Ultrasound Signs and Their Correlation With Clinical Symptoms in COVID-19 Pregnant Women: The "PINK-CO" Observational Study.

OBJECTIVE: To analyze the application of lung ultrasound (LUS) diagnostic approach in obstetric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and compare LUS score and symptoms of the patients. DESIGN: A single-center observational retrospective study from October 31, 2020 to March 31, 2021. SETTING: Department of Ob/Gyn at the University-Hospital of Udine, Italy. PARTICIPANTS: Pregnant women with SARS-CoV-2 diagnosed with reverse transcription-PCR (RT-PCR) swab test were subdivided as symptomatic and asymptomatic patients with COVID-19. EXPOSURE: Lung ultrasound evaluation both through initial evaluation upon admission and through serial evaluations. MAIN OUTCOME: Reporting LUS findings and LUS score characteristics. RESULTS: Symptomatic patients with COVID-19 showed a higher LUS (median 3.5 vs. 0, p < 0.001). LUS was significantly correlated with COVID-19 biomarkers as C-reactive protein (CPR; p = 0.011), interleukin-6 (p = 0.013), and pro-adrenomedullin (p = 0.02), and inversely related to arterial oxygen saturation (p = 0.004). The most frequent ultrasound findings were focal B lines (14 vs. 2) and the light beam (9 vs. 0). CONCLUSION: Lung ultrasound can help to manage pregnant women with SARS-CoV-2 infection during a pandemic surge. STUDY REGISTRATION: ClinicalTrials.gov, NCT04823234. Registered on March 29, 2021.

Effect of awake prone position on diaphragmatic thickening fraction in patients assisted by noninvasive ventilation for hypoxemic acute respiratory failure related to novel coronavirus disease.

BACKGROUND: Awake prone position is an emerging rescue therapy applied in patients undergoing noninvasive ventilation (NIV) for acute hypoxemic respiratory failure (ARF) related to novel coronavirus disease (COVID-19). Although applied to stabilize respiratory status, in awake patients, the application of prone position may reduce comfort with a consequent increase in the workload imposed on respiratory muscles. Thus, we primarily ascertained the effect of awake prone position on diaphragmatic thickening fraction, assessed through ultrasound, in COVID-19 patients undergoing NIV. METHODS: We enrolled all COVID-19 adult critically ill patients, admitted to intensive care unit (ICU) for hypoxemic ARF and undergoing NIV, deserving of awake prone positioning as a rescue therapy. Exclusion criteria were pregnancy and any contraindication to awake prone position and NIV. On ICU admission, after NIV onset, in supine position, and at 1 h following awake prone position application, diaphragmatic thickening fraction was obtained on the right side. Across all the study phases, NIV was maintained with the same setting present at study entry. Vital signs were monitored throughout the entire study period. Comfort was assessed through numerical rating scale (0 the worst comfort and 10 the highest comfort level). Data were presented in median and 25th-75th percentile range. RESULTS: From February to May 2021, 20 patients were enrolled and finally analyzed. Despite peripheral oxygen saturation improvement [96 (94-97)% supine vs 98 (96-99)% prone, p = 0.008], turning to prone position induced a worsening in comfort score from 7.0 (6.0-8.0) to 6.0 (5.0-7.0) (p = 0.012) and an increase in diaphragmatic thickening fraction from 33.3 (25.7-40.5)% to 41.5 (29.8-50.0)% (p = 0.025). CONCLUSIONS: In our COVID-19 patients assisted by NIV in ICU, the application of awake prone position improved the oxygenation at the expense of a greater diaphragmatic thickening fraction compared to supine position. Trial registration ClinicalTrials.gov, number NCT04904731. Registered on 05/25/2021, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04904731 .

Predictors of intubation and mortality in COVID-19 patients: a retrospective study.

BACKGROUND: Estimating the risk of intubation and mortality among COVID-19 patients can help clinicians triage these patients and allocate resources more efficiently. Thus, here we sought to identify the risk factors associated with intubation and intra-hospital mortality in a cohort of COVID-19 patients hospitalized due to hypoxemic acute respiratory failure (ARF). RESULTS: We included retrospectively a total of 187 patients admitted to the subintensive and intensive care units of the University Hospital "Maggiore della Carità" of Novara between March 1st and April 30th, 2020. Based on these patients' demographic characteristics, early clinical and laboratory variables, and quantitative chest computerized tomography (CT) findings, we developed two random forest (RF) models able to predict intubation and intra-hospital mortality. Variables independently associated with intubation were C-reactive protein (p < 0.001), lactate dehydrogenase level (p = 0.018) and white blood cell count (p = 0.026), while variables independently associated with mortality were age (p < 0.001), other cardiovascular diseases (p = 0.029), C-reactive protein (p = 0.002), lactate dehydrogenase level (p = 0.018), and invasive mechanical ventilation (p = 0.001). On quantitative chest CT analysis, ground glass opacity, consolidation, and fibrosis resulted significantly associated with patient intubation and mortality. The major predictors for both models were the ratio between partial pressure of arterial oxygen and fraction of inspired oxygen, age, lactate dehydrogenase, C-reactive protein, glycemia, CT quantitative parameters, lymphocyte count, and symptom onset. CONCLUSIONS: Altogether, our findings confirm previously reported demographic, clinical, hemato-chemical, and radiologic predictors of adverse outcome among COVID-19-associated hypoxemic ARF patients. The two newly developed RF models herein described show an overall good level of accuracy in predicting intra-hospital mortality and intubation in our study population. Thus, their future development and implementation may help not only identify patients at higher risk of deterioration more effectively but also rebalance the disproportion between resources and demand.

Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care expert consensus statement on the use of lung ultrasound in critically ill patients with coronavirus disease 2019 (ITACO).

BACKGROUND: To produce statements based on the available evidence and an expert consensus (as members of the Lung Ultrasound Working Group of the Italian Society of Analgesia, Anesthesia, Resuscitation, and Intensive Care, SIAARTI) on the use of lung ultrasound for the management of patients with COVID-19 admitted to the intensive care unit. METHODS: A modified Delphi method was applied by a panel of anesthesiologists and intensive care physicians expert in the use of lung ultrasound in COVID-19 intensive critically ill patients to reach a consensus on ten clinical questions concerning the role of lung ultrasound in the following: COVID-19 diagnosis and monitoring (with and without invasive mechanical ventilation), positive end expiratory pressure titration, the use of prone position, the early diagnosis of pneumothorax- or ventilator-associated pneumonia, the process of weaning from invasive mechanical ventilation, and the need for radiologic chest imaging. RESULTS: A total of 20 statements were produced by the panel. Agreement was reached on 18 out of 20 statements (scoring 7-9; "appropriate") in the first round of voting, while 2 statements required a second round for agreement to be reached. At the end of the two Delphi rounds, the median score for the 20 statements was 8.5 [IQR 8.9], and the agreement percentage was 100%. CONCLUSION: The Lung Ultrasound Working Group of the Italian Society of Analgesia, Anesthesia, Resuscitation, and Intensive Care produced 20 consensus statements on the use of lung ultrasound in COVID-19 patients admitted to the ICU. This expert consensus strongly suggests integrating lung ultrasound findings in the clinical management of critically ill COVID-19 patients.