Publications by authors named "Antonio Pesenti"

295 Publications

Time course of risk factors associated with mortality of 1260 critically ill patients with COVID-19 admitted to 24 Italian intensive care units.

Intensive Care Med 2021 09 9;47(9):995-1008. Epub 2021 Aug 9.

Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Purpose: To evaluate the daily values and trends over time of relevant clinical, ventilatory and laboratory parameters during the intensive care unit (ICU) stay and their association with outcome in critically ill patients with coronavirus disease 19 (COVID-19).

Methods: In this retrospective-prospective multicentric study, we enrolled COVID-19 patients admitted to Italian ICUs from February 22 to May 31, 2020. Clinical data were daily recorded. The time course of 18 clinical parameters was evaluated by a polynomial maximum likelihood multilevel linear regression model, while a full joint modeling was fit to study the association with ICU outcome.

Results: 1260 consecutive critically ill patients with COVID-19 admitted in 24 ICUs were enrolled. 78% were male with a median age of 63 [55-69] years. At ICU admission, the median ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO/FiO) was 122 [89-175] mmHg. 79% of patients underwent invasive mechanical ventilation. The overall mortality was 34%. Both the daily values and trends of respiratory system compliance, PaO/FiO, driving pressure, arterial carbon dioxide partial pressure, creatinine, C-reactive protein, ferritin, neutrophil, neutrophil-lymphocyte ratio, and platelets were associated with survival, while for lactate, pH, bilirubin, lymphocyte, and urea only the daily values were associated with survival. The trends of PaO/FiO, respiratory system compliance, driving pressure, creatinine, ferritin, and C-reactive protein showed a higher association with survival compared to the daily values.

Conclusion: Daily values or trends over time of parameters associated with acute organ dysfunction, acid-base derangement, coagulation impairment, or systemic inflammation were associated with patient survival.
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http://dx.doi.org/10.1007/s00134-021-06495-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351771PMC
September 2021

Sharing Mechanical Ventilator: In Vitro Evaluation of Circuit Cross-Flows and Patient Interactions.

Membranes (Basel) 2021 Jul 20;11(7). Epub 2021 Jul 20.

Department of Anaesthesia and Intensive Care Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.

During the COVID-19 pandemic, a shortage of mechanical ventilators was reported and ventilator sharing between patients was proposed as an ultimate solution. Two lung simulators were ventilated by one anesthesia machine connected through two respiratory circuits and T-pieces. Five different combinations of compliances (30-50 mL × cmHO) and resistances (5-20 cmHO × L × s) were tested. The ventilation setting was: pressure-controlled ventilation, positive end-expiratory pressure 15 cmHO, inspiratory pressure 10 cmHO, respiratory rate 20 bpm. Pressures and flows from all the circuit sections have been recorded and analyzed. Simulated patients with equal compliance and resistance received similar ventilation. Compliance reduction from 50 to 30 mL × cmHO decreased the tidal volume (V) by 32% (418 ± 49 vs. 285 ± 17 mL). The resistance increase from 5 to 20 cmHO × L × s decreased V by 22% (425 ± 69 vs. 331 ± 51 mL). The maximal alveolar pressure was lower at higher compliance and resistance values and decreased linearly with the time constant (r² = 0.80, < 0.001). The minimum alveolar pressure ranged from 15.5 ± 0.04 to 16.57 ± 0.04 cmHO. Cross-flows between the simulated patients have been recorded in all the tested combinations, during both the inspiratory and expiratory phases. The simultaneous ventilation of two patients with one ventilator may be unable to match individual patient's needs and has a high risk of cross-interference.
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http://dx.doi.org/10.3390/membranes11070547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307053PMC
July 2021

Compassionate use of anti-IL6 receptor antibodies in critically ill patients with acute respiratory distress syndrome due to SARS-COV-2.

Minerva Anestesiol 2021 Aug 2. Epub 2021 Aug 2.

Department of Intensive Care Medicine and Anesthesiology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Background: COVID-19 patients developing the acute respiratory distress syndrome (ARDS) show increased production of pro-inflammatory cytokines, including interleukin-6 (IL-6). The use of humanized monoclonal antibody against interleukin-6 receptor (IL-6R) may represent a potential treatment strategy. We analyzed the effects of compassionate use of Tocilizumab and Sarilumab on clinical outcome of patients affected by ARDS due COVID-19.

Methods: This single-center, observational, exploratory study was performed during the acute phase of COVID-19 outbreak, between March 7th and April 21st, 2020 in a University Hospital in Rome, Italy. All consecutive adult patients admitted to the intensive care unit with laboratory-confirmed COVID-19 and fulfilling ARDS criteria were enrolled. Patients who were treated with anti-IL-6R therapy were compared to those who were not, as per clinical decision. Inverse probability weights were applied to weight individual's contribution to survival curves and in the multivariate regression model.

Results: Among 105 ARDS patients, 65 received compassionate treatment with anti-IL-6R therapy [43 (66%) Tocilizumab and 22 (34%) Sarilumab, respectively], with oxygenation improvement. In the multivariable Cox proportional regression hazards model with propensity score inverse probability weighting, patients who received anti-IL-6R treatment had lower risk of death compared to those who did not, with a hazard ration of 0.34 [95% confidence interval 0.17-0.74], p=0.001.

Conclusions: Our data suggest that immune modulator therapy based on anti-human IL-6 receptor monoclonal antibodies might lead to improved outcome in patients with ARDS due to COVID-19. These data support the need for confirmatory randomized trials to assess the effect of immune modulator therapies on mortality.
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http://dx.doi.org/10.23736/S0375-9393.21.15609-3DOI Listing
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.

Crit Care 2021 07 30;25(1):268. Epub 2021 Jul 30.

Department of Medicine and Surgery, University of Perugia, Piazza Università 1, 06123, Perugia, Italy.

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.
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http://dx.doi.org/10.1186/s13054-021-03697-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324455PMC
July 2021

Impact of the COVID-19 outbreak on severe trauma trends and healthcare system reassessment in Lombardia, Italy: an analysis from the regional trauma registry.

World J Emerg Surg 2021 07 19;16(1):39. Epub 2021 Jul 19.

Emergency Department, Department of General Surgery and Trauma Team, ASST Niguarda, Milan, Italy.

Backgrounds: The COVID-19 pandemic drastically strained the health systems worldwide, obligating the reassessment of how healthcare is delivered. In Lombardia, Italy, a Regional Emergency Committee (REC) was established and the regional health system reorganized, with only three hospitals designated as hubs for trauma care. The aim of this study was to evaluate the effects of this reorganization of regional care, comparing the distribution of patients before and during the COVID-19 outbreak and to describe changes in the epidemiology of severe trauma among the two periods.

Methods: A cohort study was conducted using retrospectively collected data from the Regional Trauma Registry of Lombardia (LTR). We compared the data of trauma patients admitted to three hub hospitals before the COVID-19 outbreak (September 1 to November 19, 2019) with those recorded during the pandemic (February 21 to May 10, 2020) in the same hospitals. Demographic data, level of pre-hospital care (Advanced Life Support-ALS, Basic Life Support-BLS), type of transportation, mechanism of injury (MOI), abbreviated injury score (AIS, 1998 version), injury severity score (ISS), revised trauma score (RTS), and ICU admission and survival outcome of all the patients admitted to the three trauma centers designed as hubs, were reviewed. Screening for COVID-19 was performed with nasopharyngeal swabs, chest ultrasound, and/or computed tomography.

Results: During the COVID-19 pandemic, trauma patients admitted to the hubs increased (46.4% vs 28.3%, p < 0.001) with an increase in pre-hospital time (71.8 vs 61.3 min, p < 0.01), while observed in hospital mortality was unaffected. TRISS, ISS, AIS, and ICU admission were similar in both periods. During the COVID-19 outbreak, we observed substantial changes in MOI of severe trauma patients admitted to three hubs, with increases of unintentional (31.9% vs 18.5%, p < 0.05) and intentional falls (8.4% vs 1.2%, p < 0.05), whereas the pandemic restrictions reduced road- related injuries (35.6% vs 60%, p < 0.05). Deaths on scene were significantly increased (17.7% vs 6.8%, p < 0.001).

Conclusions: The COVID-19 outbreak affected the epidemiology of severe trauma patients. An increase in trauma patient admissions to a few designated facilities with high level of care obtained satisfactory results, while COVID-19 patients overwhelmed resources of most other hospitals.
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http://dx.doi.org/10.1186/s13017-021-00383-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287111PMC
July 2021

Addition of 5% CO2 to Inspiratory Gas Prevents Lung Injury in an Experimental Model of Pulmonary Artery Ligation.

Am J Respir Crit Care Med 2021 Jul 12. Epub 2021 Jul 12.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 9339, Department of Anesthesia, Critical Care and Emergency, Milan, Italy.

Rationale: Unilateral ligation of the pulmonary artery may induce lung injury through multiple mechanisms, which might be dampened by inhaled CO2.

Objectives: To characterize bilateral lung injury due to unilateral ligation of pulmonary artery in healthy swine undergoing controlled mechanical ventilation and its prevention by 5% CO2 inhalation. To investigate relevant pathophysiological mechanisms.

Methods: Sixteen healthy pigs were allocated to surgical ligation of the left pulmonary artery (Ligation group), 7 to surgical ligation of the left pulmonary artery and inhalation of 5% CO2 (Ligation + FiCO2 5%), and 6 to no intervention (No Ligation). Then, all animals received mechanical ventilation with tidal volume (Vt) 10 ml/Kg, positive end-expiratory pressure 5 cmH2O, respiratory rate 25 bpm and FiO2 50% (±FiCO2 5%) for 48 hours or until development of severe lung injury.

Measurements And Main Results: Histological, physiological and quantitative CT-scan data were compared between groups to characterize lung injury. Electrical impedance tomography and immunohistochemistry analysis were performed in a subset of animals to explore mechanisms of injury. Animals from the Ligation group developed bilateral lung injury as assessed by significantly higher histological score, larger increase in lung weight, poorer oxygenation, and worse respiratory mechanics in comparison to the Ligation + FiCO2 5% group. In the Ligation group, the right lung received larger fraction of Vt, and inflammation was more represented, while CO2 dampened both processes.

Conclusions: Mechanical ventilation induces bilateral lung injury within 48 hours in healthy pigs undergoing left pulmonary artery ligation. Inhalation of 5% CO2 prevents injury, likely through decreased stress to the right lung and anti-inflammatory effects. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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http://dx.doi.org/10.1164/rccm.202101-0122OCDOI Listing
July 2021

Why and how do we need comprehensive international clinical epidemiology of ARDS?

Intensive Care Med 2021 Sep 3;47(9):1014-1016. Epub 2021 Jul 3.

Department of Anesthesia and Critical Care, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy.

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http://dx.doi.org/10.1007/s00134-021-06469-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254436PMC
September 2021

Alkaline Liquid Ventilation of the Membrane Lung for Extracorporeal Carbon Dioxide Removal (ECCOR): In Vitro Study.

Membranes (Basel) 2021 Jun 22;11(7). Epub 2021 Jun 22.

Anesthesia and Critical Care, Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy.

Extracorporeal carbon dioxide removal (ECCOR) is a promising strategy to manage acute respiratory failure. We hypothesized that ECCOR could be enhanced by ventilating the membrane lung with a sodium hydroxide (NaOH) solution with high CO absorbing capacity. A computed mathematical model was implemented to assess NaOH-CO interactions. Subsequently, we compared NaOH infusion, named "alkaline liquid ventilation", to conventional oxygen sweeping flows. We built an extracorporeal circuit with two polypropylene membrane lungs, one to remove CO and the other to maintain a constant PCO (60 ± 2 mmHg). The circuit was primed with swine blood. Blood flow was 500 mL × min. After testing the safety and feasibility of increasing concentrations of aqueous NaOH (up to 100 mmol × L), the CO removal capacity of sweeping oxygen was compared to that of 100 mmol × L NaOH. We performed six experiments to randomly test four sweep flows (100, 250, 500, 1000 mL × min) for each fluid plus 10 L × min oxygen. Alkaline liquid ventilation proved to be feasible and safe. No damages or hemolysis were detected. NaOH showed higher CO removal capacity compared to oxygen for flows up to 1 L × min. However, the highest CO extraction power exerted by NaOH was comparable to that of 10 L × min oxygen. Further studies with dedicated devices are required to exploit potential clinical applications of alkaline liquid ventilation.
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http://dx.doi.org/10.3390/membranes11070464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306443PMC
June 2021

Low noncarbonic buffer power amplifies acute respiratory acid-base disorders in patients with sepsis: an in vitro study.

J Appl Physiol (1985) 2021 08 17;131(2):464-473. Epub 2021 Jun 17.

Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Patients with sepsis have typically reduced concentrations of hemoglobin and albumin, the major components of noncarbonic buffer power (). This could expose patients to high pH variations during acid-base disorders. The objective of this study is to compare, in vitro, noncarbonic of patients with sepsis with that of healthy volunteers, and evaluate its distinct components. Whole blood and isolated plasma of 18 patients with sepsis and 18 controls were equilibrated with different CO mixtures. Blood gases, pH, and electrolytes were measured. Noncarbonic and noncarbonic due to variations in strong ion difference () were calculated for whole blood. Noncarbonic and noncarbonic normalized for albumin concentrations () were calculated for isolated plasma. Representative values at pH = 7.40 were compared. Albumin proteoforms were evaluated via two-dimensional electrophoresis. Hemoglobin and albumin concentrations were significantly lower in patients with sepsis. Patients with sepsis had lower noncarbonic both of whole blood (22.0 ± 1.9 vs. 31.6 ± 2.1 mmol/L, < 0.01) and plasma (0.5 ± 1.0 vs. 3.7 ± 0.8 mmol/L, < 0.01). Noncarbonic was lower in patients (16.8 ± 1.9 vs. 24.4 ± 1.9 mmol/L, < 0.01) and strongly correlated with hemoglobin concentration ( = 0.94, < 0.01). Noncarbonic was lower in patients [0.01 (-0.01 to 0.04) vs. 0.08 (0.06-0.09) mmol/g, < 0.01]. Patients with sepsis and controls showed different amounts of albumin proteoforms. Patients with sepsis are exposed to higher pH variations for any given change in CO due to lower concentrations of noncarbonic buffers and, possibly, an altered buffering function of albumin. In both patients with sepsis and healthy controls, electrolyte shifts are the major buffering mechanism during respiratory acid-base disorders. Patients with sepsis are poorly protected against acute respiratory acid-base derangements due to a lower noncarbonic buffer power, which is caused both by a reduction in the major noncarbonic buffers, i.e. hemoglobin and albumin, and by a reduced buffering capacity of albumin. Electrolyte shifts from and to the red blood cells determining acute variations in strong ion difference are the major buffering mechanism during acute respiratory acid-base disorders.
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http://dx.doi.org/10.1152/japplphysiol.00787.2020DOI Listing
August 2021

An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients.

Crit Care 2021 06 9;25(1):199. Epub 2021 Jun 9.

Critical Care Research Group, The Prince Charles Hospital, Chermside, Australia.

Background: Heterogeneous respiratory system static compliance (C) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous small-case series or studies conducted at a national level.

Methods: We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe C-calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)]-and its association with ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide.

Results: We studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of C within the first seven days of MV. Median (IQR) age was 62 (52-71), patients were predominantly males (68%) and from Europe/North and South America (88%). C, within 48 h from endotracheal intubation, was available in 649 patients and was neither associated with the duration from onset of symptoms to commencement of MV (p = 0.417) nor with PaO/FiO (p = 0.100). Females presented lower C than males (95% CI of C difference between females-males: - 11.8 to - 7.4 mL/cmHO p < 0.001), and although females presented higher body mass index (BMI), association of BMI with C was marginal (p = 0.139). Ventilatory management varied across C range, resulting in a significant association between C and driving pressure (estimated decrease - 0.31 cmHO/L per mL/cmH0 of C, 95% CI - 0.48 to - 0.14, p < 0.001). Overall, 28-day ICU mortality, accounting for the competing risk of being discharged within the period, was 35.6% (SE 1.7). Cox proportional hazard analysis demonstrated that C (+ 10 mL/cm HO) was only associated with being discharge from the ICU within 28 days (HR 1.14, 95% CI 1.02-1.28, p = 0.018).

Conclusions: This multicentre report provides a comprehensive account of C in COVID-19 patients on MV. C measured within 48 h from commencement of MV has marginal predictive value for 28-day mortality, but was associated with being discharged from ICU within the same period. Trial documentation: Available at https://www.covid-critical.com/study .

Trial Registration: ACTRN12620000421932.
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http://dx.doi.org/10.1186/s13054-021-03518-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188162PMC
June 2021

Unmatched ventilation and perfusion measured by electrical impedance tomography predicts the outcome of ARDS.

Crit Care 2021 06 3;25(1):192. Epub 2021 Jun 3.

Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.

Background: In acute respiratory distress syndrome (ARDS), non-ventilated perfused regions coexist with non-perfused ventilated regions within lungs. The number of unmatched regions might reflect ARDS severity and affect the risk of ventilation-induced lung injury. Despite pathophysiological relevance, unmatched ventilation and perfusion are not routinely assessed at the bedside. The aims of this study were to quantify unmatched ventilation and perfusion at the bedside by electrical impedance tomography (EIT) investigating their association with mortality in patients with ARDS and to explore the effects of positive end-expiratory pressure (PEEP) on unmatched ventilation and perfusion in subgroups of patients with different ARDS severity based on PaO/FiO and compliance.

Methods: Prospective observational study in 50 patients with mild (36%), moderate (46%), and severe (18%) ARDS under clinical ventilation settings. EIT was applied to measure the regional distribution of ventilation and perfusion using central venous bolus of saline 5% during end-inspiratory pause. We defined unmatched units as the percentage of only ventilated units plus the percentage of only perfused units.

Results: Percentage of unmatched units was significantly higher in non-survivors compared to survivors (32[27-47]% vs. 21[17-27]%, p < 0.001). Percentage of unmatched units was an independent predictor of mortality (OR 1.22, 95% CI 1.07-1.39, p = 0.004) with an area under the ROC curve of 0.88 (95% CI 0.79-0.97, p < 0.001). The percentage of ventilation to the ventral region of the lung was higher than the percentage of ventilation to the dorsal region (32 [27-38]% vs. 18 [13-21]%, p < 0.001), while the opposite was true for perfusion (28 [22-38]% vs. 36 [32-44]%, p < 0.001). Higher percentage of only perfused units was correlated with lower dorsal ventilation (r =  - 0.486, p < 0.001) and with lower PaO/FiO ratio (r =  - 0.293, p = 0.039).

Conclusions: EIT allows bedside assessment of unmatched ventilation and perfusion in mechanically ventilated patients with ARDS. Measurement of unmatched units could identify patients at higher risk of death and could guide personalized treatment.
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http://dx.doi.org/10.1186/s13054-021-03615-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173510PMC
June 2021

Development of a Critical Care Response - Experiences from Italy During the Coronavirus Disease 2019 Pandemic.

Anesthesiol Clin 2021 Jun 12;39(2):265-284. Epub 2021 Feb 12.

Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, Milano 20122, Italy; Department of Anesthesia, Intensive Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda, 10, Milano 20122, Italy.

Italy was the first western country facing an outbreak of coronavirus disease 2019 (COVID-19). The first Italian patient diagnosed with COVID-19 was admitted, on Feb. 20, 2020, to the intensive care unit (ICU) in Codogno (Lodi, Lombardy, Italy), and the number of reported positive cases increased to 36 in the next 24 hours, and then exponentially for 18 days. This triggered a response that resulted in a massive surge in ICU bed capacity. The COVID19 Lombardy Network organized a structured logistic response and provided scientific evidence to highlight information on COVID-19 associated respiratory failure.
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http://dx.doi.org/10.1016/j.anclin.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879060PMC
June 2021

Pulmonary volume-feedback and ventilatory pattern after bilateral lung transplantation using neurally adjusted ventilatory assist ventilation.

Br J Anaesth 2021 07 21;127(1):143-152. Epub 2021 Apr 21.

Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Italy.

Background: Bilateral lung transplantation results in pulmonary vagal denervation, which potentially alters respiratory drive, volume-feedback, and ventilatory pattern. We hypothesised that Neurally Adjusted Ventilatory Assist (NAVA) ventilation, which is driven by diaphragm electrical activity (EAdi), would reveal whether vagally mediated pulmonary-volume feedback is preserved in the early phases after bilateral lung transplantation.

Methods: We prospectively studied bilateral lung transplant recipients within 48 h of surgery. Subjects were ventilated with NAVA and randomised to receive 3 ventilatory modes (baseline NAVA, 50%, and 150% of baseline NAVA values) and 2 PEEP levels (6 and 12 cm HO). We recorded airway pressure, flow, and EAdi.

Results: We studied 30 subjects (37% female; age: 37 (27-56) yr), of whom 19 (63%) had stable EAdi. The baseline NAVA level was 0.6 (0.2-1.0) cm HO μV. Tripling NAVA level increased the ventilatory peak pressure over PEEP by 6.3 (1.8), 7.6 (2.4), and 8.7 (3.2) cm HO, at 50%, 100%, and 150% of baseline NAVA level, respectively (P<0.001). EAdi peak decreased by 10.1 (9.0), 9.5 (9.4) and 8.8 μV (8.7) (P<0.001), accompanied by small increases in tidal volume, 8.3 (3.0), 8.7 (3.6), and 8.9 (3.3) ml kg donor's predicted body weight at 50%, 100%, and 150% of baseline NAVA levels, respectively (P<0.001). Doubling PEEP did not affect tidal volume.

Conclusions: NAVA ventilation was feasible in the majority of patients during the early postoperative period after bilateral lung transplantation. Despite surgical vagotomy distal to the bronchial anastomoses, bilateral lung transplant recipients maintained an unmodified respiratory pattern in response to variations in ventilatory assistance and PEEP.

Clinical Trial Registration: NCT03367221.
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http://dx.doi.org/10.1016/j.bja.2021.03.010DOI Listing
July 2021

Hospital-Acquired Infections in Critically Ill Patients With COVID-19.

Chest 2021 08 20;160(2):454-465. Epub 2021 Apr 20.

Department of Anaesthesia and Intensive Care, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.

Background: Few small studies have described hospital-acquired infections (HAIs) occurring in patients with COVID-19.

Research Question: What characteristics in critically ill patients with COVID-19 are associated with HAIs and how are HAIs associated with outcomes in these patients?

Study Design And Methods: Multicenter retrospective analysis of prospectively collected data including adult patients with severe COVID-19 admitted to eight Italian hub hospitals from February 20, 2020, through May 20, 2020. Descriptive statistics and univariate and multivariate Weibull regression models were used to assess incidence, microbial cause, resistance patterns, risk factors (ie, demographics, comorbidities, exposure to medication), and impact on outcomes (ie, ICU discharge, length of ICU and hospital stays, and duration of mechanical ventilation) of microbiologically confirmed HAIs.

Results: Of the 774 included patients, 359 patients (46%) demonstrated 759 HAIs (44.7 infections/1,000 ICU patient-days; 35% multidrug-resistant [MDR] bacteria). Ventilator-associated pneumonia (VAP; n = 389 [50%]), bloodstream infections (BSIs; n = 183 [34%]), and catheter-related BSIs (n = 74 [10%]) were the most frequent HAIs, with 26.0 (95% CI, 23.6-28.8) VAPs per 1,000 intubation-days, 11.7 (95% CI, 10.1-13.5) BSIs per 1,000 ICU patient-days, and 4.7 (95% CI, 3.8-5.9) catheter-related BSIs per 1,000 ICU patient-days. Gram-negative bacteria (especially Enterobacterales) and Staphylococcus aureus caused 64% and 28% of cases of VAP, respectively. Variables independently associated with infection were age, positive end expiratory pressure, and treatment with broad-spectrum antibiotics at admission. Two hundred thirty-four patients (30%) died in the ICU (15.3 deaths/1,000 ICU patient-days). Patients with HAIs complicated by septic shock showed an almost doubled mortality rate (52% vs 29%), whereas noncomplicated infections did not affect mortality. HAIs prolonged mechanical ventilation (median, 24 days [interquartile range (IQR), 14-39 days] vs 9 days [IQR, 5-13 days]; P < .001), ICU stay (24 days [IQR, 16-41 days] vs 9 days [IQR, 6-14 days]; P = .003), and hospital stay (42 days [IQR, 25-59 days] vs 23 days [IQR, 13-34 days]; P < .001).

Interpretation: Critically ill patients with COVID-19 are at high risk for HAIs, especially VAPs and BSIs resulting from MDR organisms. HAIs prolong mechanical ventilation and hospitalization, and HAIs complicated by septic shock almost double mortality.

Trial Registry: ClinicalTrials.gov; No.: NCT04388670; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056844PMC
August 2021

Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients.

Crit Care 2021 04 6;25(1):128. Epub 2021 Apr 6.

Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.

Background: Limited data are available on the use of prone position in intubated, invasively ventilated patients with Coronavirus disease-19 (COVID-19). Aim of this study is to investigate the use and effect of prone position in this population during the first 2020 pandemic wave.

Methods: Retrospective, multicentre, national cohort study conducted between February 24 and June 14, 2020, in 24 Italian Intensive Care Units (ICU) on adult patients needing invasive mechanical ventilation for respiratory failure caused by COVID-19. Clinical data were collected on the day of ICU admission. Information regarding the use of prone position was collected daily. Follow-up for patient outcomes was performed on July 15, 2020. The respiratory effects of the first prone position were studied in a subset of 78 patients. Patients were classified as Oxygen Responders if the PaO/FiO ratio increased ≥ 20 mmHg during prone position and as Carbon Dioxide Responders if the ventilatory ratio was reduced during prone position.

Results: Of 1057 included patients, mild, moderate and severe ARDS was present in 15, 50 and 35% of patients, respectively, and had a resulting mortality of 25, 33 and 41%. Prone position was applied in 61% of the patients. Patients placed prone had a more severe disease and died significantly more (45% vs. 33%, p < 0.001). Overall, prone position induced a significant increase in PaO/FiO ratio, while no change in respiratory system compliance or ventilatory ratio was observed. Seventy-eight % of the subset of 78 patients were Oxygen Responders. Non-Responders had a more severe respiratory failure and died more often in the ICU (65% vs. 38%, p = 0.047). Forty-seven % of patients were defined as Carbon Dioxide Responders. These patients were older and had more comorbidities; however, no difference in terms of ICU mortality was observed (51% vs. 37%, p = 0.189 for Carbon Dioxide Responders and Non-Responders, respectively).

Conclusions: During the COVID-19 pandemic, prone position has been widely adopted to treat mechanically ventilated patients with respiratory failure. The majority of patients improved their oxygenation during prone position, most likely due to a better ventilation perfusion matching.

Trial Registration: clinicaltrials.gov number: NCT04388670.
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http://dx.doi.org/10.1186/s13054-021-03552-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022297PMC
April 2021

A Community-Based Model to the COVID-19 Humanitarian Crisis.

Front Cell Infect Microbiol 2021 15;11:639579. Epub 2021 Mar 15.

Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

A multidisciplinary group, mainly from Bergamo region - the epicenter of the COVID-19 pandemic crisis in Italy on march 2020- has developed concept of creating intermediate care facilities and proposes a three-tier model of community-based care, with the goal of reducing hospital admissions, contagion and mortality related to hospital overloading and optimizing human resources.
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http://dx.doi.org/10.3389/fcimb.2021.639579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009176PMC
April 2021

Quantification of Recirculation During Veno-Venous Extracorporeal Membrane Oxygenation: In Vitro Evaluation of a Thermodilution Technique.

ASAIO J 2021 Mar 29. Epub 2021 Mar 29.

From the School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy Center for Preclinical Research, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy Department of Anesthesia and Critical Care, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy Department of Anesthesia and Critical Care, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.

Veno-venous extracorporeal membrane oxygenation (vv-ECMO) represents one of the most advanced respiratory support for patients suffering from severe acute respiratory distress syndrome. During vv-ECMO a certain amount of extracorporeal oxygenated blood can flow back from the reinfusion into the drainage cannula without delivering oxygen to the patient. Detection and quantification of this dynamic phenomenon, defined recirculation, are critical to optimize the ECMO efficiency. Our study aimed to measure the recirculation fraction (RF) using a thermodilution technique. We built an in vitro circuit to simulate patients undergoing vv-ECMO (ECMO flow: 1.5, 3, and 4.5 L/min) with different cardiac output, using a recirculation bridge to achieve several known RFs (from 0% to 50%). The RF, computed as the ratio of the area under temperature-time curves (AUC) of the drainage and reinfusion, was significantly related to the set RF (AUC ratio (%) = 0.979 × RF (%) + 0.277%, p < 0.0001), but it was not dependent on tested ECMO and cardiac output values. A Bland-Altman analysis showed an AUC ratio bias (precision) of -0.21% for the overall data. Test-retest reliability showed an intraclass correlation coefficient of 0.993. This study proved the technical feasibility and computation validity of the applied thermodilution technique in computing vv-ECMO RF.
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http://dx.doi.org/10.1097/MAT.0000000000001428DOI Listing
March 2021

Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients From 29 Countries.

JAMA 2021 03;325(12):1164-1172

School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events.

Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients.

Design, Setting, And Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents.

Exposures: Tracheal intubation.

Main Outcomes And Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure <65 mm Hg at least once, <90 mm Hg for >30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation <80%) or cardiac arrest. The secondary outcomes included intensive care unit mortality.

Results: Of 3659 patients screened, 2964 (median age, 63 years; interquartile range [IQR], 49-74 years; 62.6% men) from 197 sites across 5 continents were included. The main reason for intubation was respiratory failure in 52.3% of patients, followed by neurological impairment in 30.5%, and cardiovascular instability in 9.4%. Primary outcome data were available for all patients. Among the study patients, 45.2% experienced at least 1 major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 42.6% of all patients undergoing emergency intubation, followed by severe hypoxemia (9.3%) and cardiac arrest (3.1%). Overall ICU mortality was 32.8%.

Conclusions And Relevance: In this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events-in particular cardiovascular instability-were observed frequently.
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http://dx.doi.org/10.1001/jama.2021.1727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988368PMC
March 2021

Mechanical ventilation parameters in critically ill COVID-19 patients: a scoping review.

Crit Care 2021 03 20;25(1):115. Epub 2021 Mar 20.

General Intensive Care Unit, Shaare Zedek Medical Center, Jerusalem, Israel.

Background: The mortality of critically ill patients with COVID-19 is high, particularly among those receiving mechanical ventilation (MV). Despite the high number of patients treated worldwide, data on respiratory mechanics are currently scarce and the optimal setting of MV remains to be defined. This scoping review aims to provide an overview of available data about respiratory mechanics, gas exchange and MV settings in patients admitted to intensive care units (ICUs) for COVID-19-associated acute respiratory failure, and to identify knowledge gaps.

Main Text: PubMed, EMBASE, and MEDLINE databases were searched from inception to October 30, 2020 for studies providing at least one ventilatory parameter collected within 24 h from the ICU admission. The quality of the studies was independently assessed using the Newcastle-Ottawa Quality Assessment Form for Cohort Studies. A total of 26 studies were included for a total of 14,075 patients. At ICU admission, positive end expiratory pressure (PEEP) values ranged from 9 to 16.5 cm of water (cmHO), suggesting that high levels of PEEP were commonly used for setting MV for these patients. Patients with COVID-19 are severely hypoxemic at ICU admission and show a median ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO/FiO) ranging from 102 to 198 mmHg. Static respiratory system compliance (Crs) values at ICU admission were highly heterogenous, ranging between 24 and 49 ml/cmHO. Prone positioning and neuromuscular blocking agents were widely used, ranging from 17 to 81 and 22 to 88%, respectively; both rates were higher than previously reported in patients with "classical" acute respiratory distress syndrome (ARDS).

Conclusions: Available data show that, in mechanically ventilated patients with COVID-19, respiratory mechanics and MV settings within 24 h from ICU admission are heterogeneous but similar to those reported for "classical" ARDS. However, to date, complete data regarding mechanical properties of respiratory system, optimal setting of MV and the role of rescue treatments for refractory hypoxemia are still lacking in the medical literature.
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http://dx.doi.org/10.1186/s13054-021-03536-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980724PMC
March 2021

Endothelial damage in septic shock patients as evidenced by circulating syndecan-1, sphingosine-1-phosphate and soluble VE-cadherin: a substudy of ALBIOS.

Crit Care 2021 03 19;25(1):113. Epub 2021 Mar 19.

Department of Cardiovascular Medicine, Mario Negri Institute for Pharmacological Research IRCCS, Via Mario Negri 2, 20156, Milan, Italy.

Background: Septic shock is characterized by breakdown of the endothelial glycocalyx and endothelial damage, contributing to fluid extravasation, organ failure and death. Albumin has shown benefit in septic shock patients. Our aims were: (1) to identify the relations between circulating levels of syndecan-1 (SYN-1), sphingosine-1-phosphate (S1P) (endothelial glycocalyx), and VE-cadherin (endothelial cell junctions), severity of the disease, and survival; (2) to evaluate the effects of albumin supplementation on endothelial dysfunction in patients with septic shock.

Methods: This was a retrospective analysis of a multicenter randomized clinical trial on albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis Trial, ALBIOS). Concentrations of SYN-1, S1P, soluble VE-cadherin and other biomarkers were measured on days 1, 2 and 7 in 375 patients with septic shock surviving up to 7 days after randomization.

Results: Plasma concentrations of SYN-1 and VE-cadherin rose significantly over 7 days. SYN-1 and VE-cadherin were elevated in patients with organ failure, and S1P levels were lower. SYN-1 and VE-cadherin were independently associated with renal replacement therapy requirement during ICU stay, but only SYN-1 predicted its new occurrence. Both SYN-1 and S1P, but not VE-cadherin, predicted incident coagulation failure. Only SYN-1 independently predicted 90-day mortality. Albumin significantly reduced VE-cadherin, by 9.5% (p = 0.003) at all three time points.

Conclusion: Circulating components of the endothelial glycocalyx and of the endothelial cell junctions provide insights into severity and progression of septic shock, with special focus on incident coagulation and renal failure. Albumin supplementation lowered circulating VE-cadherin consistently over time.

Clinical Trial Registration: ALBIOS ClinicalTrials.gov number NCT00707122.
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http://dx.doi.org/10.1186/s13054-021-03545-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980645PMC
March 2021

Albumin replacement therapy in immunocompromised patients with sepsis - Secondary analysis of the ALBIOS trial.

J Crit Care 2021 Jun 9;63:83-91. Epub 2021 Feb 9.

Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy; Department of Anesthesia and Critical Care, Azienda-Ospedaliero Universitaria S. Luigi Gonzaga, Orbassano, Italy.

Background: The best fluid replacement strategy and the role of albumin in immunocompromised patients with sepsis is unclear.

Methods: We performed a secondary analysis of immunocompromised patients enrolled in the ALBIOS trial which randomized patients with severe sepsis or septic shock to receive either 20% albumin (target 30 g per liter or more) and crystalloid or crystalloid alone during ICU stay.

Results: Of 1818 patients originally enrolled, 304 (16.4%) were immunocompromised. One-hundred-thirty-nine (45.7%) patients were randomized in the albumin while 165 (54.2%) in the crystalloid group. At 90 days, 69 (49.6%) in the albumin group and 89 (53.9%) in the crystalloids group died (hazard ratio - HR - 0.94; 95% CI 0.69-1.29). No differences were observed with regards to 28-day mortality, SOFA score (and sub-scores), length of stay in the ICU and in the hospital, proportion of patients who had developed acute kidney injury or received renal replacement therapy, duration of mechanical ventilation. Albumin was not independently associated with a higher or lower 90-day mortality (HR 0.979, 95% CI 0.709-1.352) as compared to crystalloid.

Conclusion: Albumin replacement during the ICU stay, as compared with crystalloids alone, did not affect clinical outcomes in a cohort of immunocompromised patients with sepsis.
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http://dx.doi.org/10.1016/j.jcrc.2021.01.016DOI Listing
June 2021

Enabling a learning healthcare system with automated computer protocols that produce replicable and personalized clinician actions.

J Am Med Inform Assoc 2021 06;28(6):1330-1344

Department of Pediatrics, Perelman School of Medicine.

Clinical decision-making is based on knowledge, expertise, and authority, with clinicians approving almost every intervention-the starting point for delivery of "All the right care, but only the right care," an unachieved healthcare quality improvement goal. Unaided clinicians suffer from human cognitive limitations and biases when decisions are based only on their training, expertise, and experience. Electronic health records (EHRs) could improve healthcare with robust decision-support tools that reduce unwarranted variation of clinician decisions and actions. Current EHRs, focused on results review, documentation, and accounting, are awkward, time-consuming, and contribute to clinician stress and burnout. Decision-support tools could reduce clinician burden and enable replicable clinician decisions and actions that personalize patient care. Most current clinical decision-support tools or aids lack detail and neither reduce burden nor enable replicable actions. Clinicians must provide subjective interpretation and missing logic, thus introducing personal biases and mindless, unwarranted, variation from evidence-based practice. Replicability occurs when different clinicians, with the same patient information and context, come to the same decision and action. We propose a feasible subset of therapeutic decision-support tools based on credible clinical outcome evidence: computer protocols leading to replicable clinician actions (eActions). eActions enable different clinicians to make consistent decisions and actions when faced with the same patient input data. eActions embrace good everyday decision-making informed by evidence, experience, EHR data, and individual patient status. eActions can reduce unwarranted variation, increase quality of clinical care and research, reduce EHR noise, and could enable a learning healthcare system.
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http://dx.doi.org/10.1093/jamia/ocaa294DOI Listing
June 2021

Heparin-Free Lung Transplantation on Venovenous Extracorporeal Membrane Oxygenation Bridge.

ASAIO J 2021 Jan 28. Epub 2021 Jan 28.

From the Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy Department of Thoracic Surgery and Lung Transplant, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Extracorporeal membrane oxygenation (ECMO) bridge to lung transplantation (LuTX) exposes the patients to a high risk of perioperative bleeding secondary to systemic anticoagulation and coagulation factors deficiency. With this case series, we propose innovative "no-heparin" management of ECMO-bridge support during LuTX, based upon 1) control heparin resistance with antithrombin III in the preoperative period; 2) relying upon a fully functional, brand new heparinized ECMO circuit; 3) completely avoiding perioperative heparin; 4) hampering fibrinolysis with tranexamic acid; and 5) limiting venoarterial (VA) ECMO escalation, and the following need for full anticoagulation. Following the application of this new approach, we carried out three challenging clinical cases of bilateral ECMO-bridged LuTX effectively, with limited intraoperative blood requirement and no major postoperative bleeding or thromboembolic events. Of note, two of them had an extremely high risk for hemorrhage due to complete right lung anatomic derangement in case number 2 and surgical adhesion following first LuTX in case number 3, while for the case number 1, no blood products were administered during surgery. Despite the limited patient population, such an approach relies on a strong rationale and may be beneficial for managing ECMO bridging to LuTX. Prospective studies are necessary to confirm the validity of our strategy.
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http://dx.doi.org/10.1097/MAT.0000000000001371DOI Listing
January 2021

Case Report: Late-Onset Congenital Adrenal Hyperplasia and Acute Covid-19 Infection in a Pregnant Woman: Multidisciplinary Management.

Front Endocrinol (Lausanne) 2020 15;11:602535. Epub 2021 Jan 15.

Endocrinology Unit, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Background: The impact of the Covid-19 infection on patients with chronic endocrine disease is not fully known. We describe here the first case of a pregnant woman with Covid-19 acute infection and non-classical congenital adrenal hyperplasia (NCAH).

Case Description: A woman at 36 weeks of gestation was referred to our Maternity Hospital for premature rupture of membranes (PROM). Her medical history was positive for NCAH on chronic steroid replacement till the age of 17 years (cortisone acetate and dexamethasone, both in the morning). At admission, her naso-oro-pharyngeal swab resulted positive for SARS-CoV-2. Due to hyperpyrexia and late preterm PROM, cesarean section was planned, and she was started on a 100 mg-bolus of hydrocortisone, followed by continuous infusion of 200 mg/24 h. A female neonate in good clinical condition and with a negative nasopharyngeal Covid-19 swab was delivered. On second day, the mother was in good condition and was switched to oral steroid therapy. On third day she worsened, with radiological signs of acute pulmonary embolism. Oro-tracheal intubation and mechanical ventilation were started, and she was switched back to intravenous steroid therapy. On April 30, pulmonary embolism was resolved, and on May 13th she was discharged in good condition.

Conclusions: We report the first case of Covid-19 acute infection that occurred in late-pregnancy in a woman with NCAH on chronic steroid replacement. The management of the patient in a reference center with early involvement of a multidisciplinary team granted prompt care and adequate protection for all the involved sanitary operators.
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http://dx.doi.org/10.3389/fendo.2020.602535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845779PMC
February 2021

Volatile Sedation for Acute Respiratory Distress Syndrome Patients on Venovenous Extracorporeal Membrane Oxygenation and Ultraprotective Ventilation.

Crit Care Explor 2021 Jan 8;3(1):e0310. Epub 2021 Jan 8.

Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca, Monza, Italy.

Patients on extracorporeal support for severe acute respiratory distress syndrome may require a prolonged period of deep sedation. In these patients, volatile sedation may represent a valid alternative to IV drugs. The aim of our study was to describe the feasibility of volatile sedation in a large cohort of acute respiratory distress syndrome patients undergoing venovenous extracorporeal membrane oxygenation and ultraprotective ventilation.

Design: Retrospective monocentric study.

Setting: Adult ICU, ASST Monza, Italy.

Patients: Adult patients who underwent volatile sedation with isoflurane during venovenous extracorporeal membrane oxygenation between 2009 and 2019.

Interventions: Isoflurane was delivered via the AnaConDa system. The sedation level, hemodynamics, and laboratory tests were compared between the volatile sedation phase and the IV sedation phases before and after the isoflurane sedation period.

Measurements And Main Results: About 74 patients (50 yr [43-56 yr]) were included. Median duration of venovenous extracorporeal membrane oxygenation support was 22 days (14-51 d). Volatile sedation started on day 3 (2-6) of extracorporeal membrane oxygenation support, and its median duration was 7 days (4-13 d), ranging from 1 to 38 days. A total of 970 venovenous extracorporeal membrane oxygenation days were analyzed. During the volatile phase, the sedation level was slightly deeper (bispectral index 39 ± 6) compared with the IV phase before and after isoflurane (42 ± 8 and 43 ± 9, respectively, < 0.001). Requirements of fentanyl and remifentanyl were reduced during the volatile phase. Minor differences in hemodynamics were observed during volatile sedation: mean arterial pressure was lower (75 ± 13 vs 79 ± 14 and 80 ± 15; < 0.001), whereas cardiac output was higher (8.5 ± 1.9 vs 7.9 ± 1.8 and 8.0 ± 1.8; = 0.003). Aspartate aminotransferase levels were lower during the volatile sedation phases ( < 0.001), whereas alanine aminotransferase, triglycerides, and creatine phosphokinase were more altered during the IV sedation phase before isoflurane ( < 0.001).

Conclusions: Volatile sedation represents an alternative to IV agents to achieve long-term deep sedation in critically ill patients on extracorporeal membrane oxygenation undergoing ultraprotective ventilation.
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http://dx.doi.org/10.1097/CCE.0000000000000310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803679PMC
January 2021

Noninvasive Ventilatory Support of Patients with COVID-19 outside the Intensive Care Units (WARd-COVID).

Ann Am Thorac Soc 2021 06;18(6):1020-1026

Department of Anesthesia and Intensive Care Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, Italy.

Treatment with noninvasive ventilation (NIV) in coronavirus disease (COVID-19) is frequent. Shortage of intensive care unit (ICU) beds led clinicians to deliver NIV also outside ICUs. Data about the use of NIV in COVID-19 is limited. To describe the prevalence and clinical characteristics of patients with COVID-19 treated with NIV outside the ICUs. To investigate the factors associated with NIV failure (need for intubation or death). In this prospective, single-day observational study, we enrolled adult patients with COVID-19 who were treated with NIV outside the ICU from 31 hospitals in Lombardy, Italy. We collected data on demographic and clinical characteristics, ventilatory management, and patient outcomes. Of 8,753 patients with COVID-19 present in the hospitals on the study day, 909 (10%) were receiving NIV outside the ICU. A majority of patients (778/909; 85%) patients were treated with continuous positive airway pressure (CPAP), which was delivered by helmet in 617 (68%) patients. NIV failed in 300 patients (37.6%), whereas 498 (62.4%) patients were discharged alive without intubation. Overall mortality was 25%. NIV failure occurred in 152/284 (53%) patients with an arterial oxygen pressure (Pa)/fraction of inspired oxygen (Fi) ratio <150 mm Hg. Higher C-reactive protein and lower Pa/Fi and platelet counts were independently associated with increased risk of NIV failure. The use of NIV outside the ICUs was common in COVID-19, with a predominant use of helmet CPAP, with a rate of success >60% and close to 75% in full-treatment patients. C-reactive protein, Pa/Fi, and platelet counts were independently associated with increased risk of NIV failure.Clinical trial registered with ClinicalTrials.gov (NCT04382235).
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http://dx.doi.org/10.1513/AnnalsATS.202008-1080OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456729PMC
June 2021

Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study.

Eur Respir J 2021 06 10;57(6). Epub 2021 Jun 10.

Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Heath Toronto, Toronto, ON, Canada.

Background: Current incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS).

Methods: An international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmHO. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral bilateral opacities were compared.

Findings: 12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved.

Interpretation: More than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.
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http://dx.doi.org/10.1183/13993003.03317-2020DOI Listing
June 2021

Barotrauma in mechanically ventilated patients with Coronavirus disease 2019: a survey of 38 hospitals in Lombardy, Italy.

Minerva Anestesiol 2021 02 16;87(2):193-198. Epub 2020 Dec 16.

Department of Anesthesiology and Intensive Care Units, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

Background: The aim was to describe the incidence and risk factors of barotrauma in patients with the Coronavirus disease 2019 (COVID-19) on invasive mechanical ventilation, during the outbreak in our region (Lombardy, Italy).

Methods: The study was an electronic survey open from March 27 to May 2, 2020. Patients with COVID-19 who developed barotrauma while on invasive mechanical ventilation from 61 hospitals of the COVID-19 Lombardy Intensive Care Unit network were involved.

Results: The response rate was 38/61 (62%). The incidence of barotrauma was 145/2041 (7.1%; 95%-CI: 6.1-8.3%). Only a few cases occurred with ventilatory settings that may be considered non-protective such as a plateau airway pressure >35 cmH2O (2/113 [2%]), a driving airway pressure >15 cmH2O (30/113 [27%]), or a tidal volume >8 mL/kg of ideal body weight and a plateau airway pressure >30 cmH2O (12/134 [9%]).

Conclusions: Within the limits of a survey, patients with COVID-19 might be at high risk for barotrauma during invasive (and allegedly lung-protective) mechanical ventilation.
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http://dx.doi.org/10.23736/S0375-9393.20.15002-8DOI Listing
February 2021

Preparedness of ICU networks for pandemics.

Curr Opin Crit Care 2021 02;27(1):13-19

Department of Pathophysiology and Transplantation, University of Milan.

Purpose Of Review: The recent COVID-19 outbreak has clearly shown how epidemics/pandemics can challenge developed countries' healthcare systems. Proper management of equipment and human resources is critical to provide adequate medical care to all patients admitted to the hospital and the ICU for both pandemic-related and unrelated reasons.

Recent Findings: Appropriate separate paths for infected and noninfected patients and prompt isolation of infected critical patients in dedicated ICUs play a pivotal role in limiting the contagions and optimizing resources during pandemics. The key to handle these challenging events is to learn from past experiences and to be prepared for future occurrences. Hospital space should be redesigned to quickly increase medical and critical care capacity, and healthcare workers (critical and noncritical) should be trained in advance.

Summary: A targeted improvement of hospital and ICU protocols will increase medical care quality for patients admitted to the hospital for any clinical reasons during a pandemic.
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http://dx.doi.org/10.1097/MCC.0000000000000792DOI Listing
February 2021

Right Ventricle Dysfunction in Patients With Adult Cystic Fibrosis Enlisted for Lung Transplant.

Transplant Proc 2021 Jan-Feb;53(1):260-264. Epub 2020 Nov 27.

Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Knowledge of preoperative right heart function of adult patients with cystic fibrosis (CF) awaiting lung transplant (LUTX) is limited. The echocardiography of adult patients with CF enlisted for LUTX was retrospectively analyzed and compared with standards and invasive analyses (right heart catheterization, multigated radionuclide ventriculography). We included 49 patients (reported as mean ± standard deviation; 29 ± 9 years of age; forced expiratory volume in first second of expiration, 31% ± 11% predicted; lung allocation score, 36 ± 5; invasive mean pulmonary artery pressure, 17 ± 5 mm Hg; multigated radionuclide ventriculography right ventricle [RV] ejection fraction, 50% ± 9%). Patients had increased RV end-diastolic area, RV wall thickness, and increased pulmonary artery acceleration time with subnormal tricuspid annular plane systolic excursion, tissue Doppler positive peak systolic velocity, and fraction area change. Subnormal tricuspid annular plane systolic excursion (< 23 mm), tissue Doppler positive peak systolic velocity (< 14 cm/s), and fraction area change (< 49%) had high sensitivity and negative predictive value in predicting impaired RV. EJECTION FRACTION: A good correlation between echocardiographic estimated and invasively measured systolic pulmonary artery pressure was observed (R = 0.554, P < .001). Adults with CF awaiting LUTX have morphologic alterations of the right heart, with subclinical impairment of RV systolic function. Echocardiography may be used as a bedside, repeatable, and reliable noninvasive test to screen further deterioration in RV function while on the waiting list for LUTX. More prospective follow-up echocardiographic studies are necessary to confirm such a hypothesis.
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http://dx.doi.org/10.1016/j.transproceed.2020.09.020DOI Listing
April 2021
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