Portal hypertension-like pattern in coronavirus disease 2019 acute respiratory distress syndrome.

OBJECTIVES: Although respiratory failure is the most common feature in coronavirus disease 2019 (COVID-19), abdominal organ involvement is likewise frequently observed. To investigate visceral and thoracic circulation and abdominal organ damage in COVID-19 patients. MATERIALS AND METHODS: A monocentric observational study was carried on. In COVID-19 patients affected by acute respiratory distress syndrome (ARDS) (n = 31) or mild pneumonia (n = 60) thoracoabdominal circulation was evaluated using Doppler-ultrasound and computed tomography. The study also included non-COVID-19 patients affected by ARDS (n = 10) or portal hypertension (n = 10) for comparison of the main circulatory changes. RESULTS: Patients affected by COVID-19 ARDS showed hyperdynamic visceral flow and increased portal velocity, hepatic artery resistance-index, and spleen diameter relative to those with mild-pneumonia (p = 0.001). Splanchnic circulatory parameters significantly correlated with the main respiratory indexes (p < 0.001) and pulmonary artery diameter (p = 0.02). The chest and abdominal vascular remodeling pattern of COVID-19 ARDS patients resembled the picture observed in the PH group, while differed from that of the non-COVID ARDS group. A more severe COVID-19 presentation was associated with worse liver dysfunction and enhanced inflammatory activation; these parameters both correlated with abdominal (p = 0.04) and chest imaging measures (p = 0.03). CONCLUSION: In COVID-19 ARDS patients there are abdominal and lung vascular modifications that depict a portal hypertension-like pattern. The correlation between visceral vascular remodeling, pulmonary artery enlargement, and organ damage in these critically ill patients is consistent with a portal hyperlfow-like syndrome that could contribute to the peculiar characteristics of respiratory failure in these patients. CLINICAL RELEVANCE STATEMENT: our data suggest that the severity of COVID-19 lung involvement is directly related to the development of a portal hyperflow-like syndrome. These observations should help in defining the need for a closer monitoring, but also to develop dedicated therapeutic strategies.

Impact of Positive End-Expiratory Pressure and FiO2 on Lung Mechanics and Intrapulmonary Shunt in Mechanically Ventilated Patients with ARDS Due to COVID-19 Pneumonia.

Purpose: This study aimed to investigate the effects of inspired oxygen fraction (FiO2) and positive end-expiratory pressure (PEEP) on gas exchange in mechanically ventilated patients with COVID-19. Methods: Two FiO2 (100%, 40%) were tested at 3 decreasing levels of PEEP (15, 10, and 5 cmH2O). At each FiO2 and PEEP, gas exchange, respiratory mechanics, hemodynamics, and the distribution of ventilation and perfusion were assessed with electrical impedance tomography. The impact of FiO2 on the intrapulmonary shunt (delta shunt) was analyzed as the difference between the calculated shunt at FiO2 100% (shunt) and venous admixture at FiO2 40% (venous admixture). Results: Fourteen patients were studied. Decreasing PEEP from 15 to 10 cmH2O did not change shunt (24 [21-28] vs 27 [24-29]%) or venous admixture (18 [15-26] vs 23 [18-34]%) while partial pressure of arterial oxygen (FiO2 100%) was higher at PEEP 15 (262 [198-338] vs 256 [147-315] mmHg; P < .05). Instead when PEEP was decreased from 10 to 5 cmH2O, shunt increased to 36 [30-39]% (P < .05) and venous admixture increased to 33 [30-43]% (P < .05) and partial pressure of arterial oxygen (100%) decreased to 109 [76-177] mmHg (P < .05). At PEEP 15, administration of 100% FiO2 resulted in a shunt greater than venous admixture at 40% FiO2, ((24 [21-28] vs 18 [15-26]%, P = .005), delta shunt 5.5% (2.3-8.8)). Compared to PEEP 10, PEEP of 5 and 15 cmH2O resulted in decreased global and pixel-level compliance. Cardiac output at FiO2 100% resulted higher at PEEP 5 (5.4 [4.4-6.5]) compared to PEEP 10 (4.8 [4.1-5.5], P < .05) and PEEP 15 cmH2O (4.7 [4.5-5.4], P < .05). Conclusion: In this study, PEEP of 15 cmH2O, despite resulting in the highest oxygenation, was associated with overdistension. PEEP of 5 cmH2O was associated with increased shunt and alveolar collapse. Administration of 100% FiO2 was associated with an increase in intrapulmonary shunt in the setting of high PEEP. Trial registration: NCT05132933.

Corticosteroids in sepsis and community-acquired pneumonia.

Sepsis and septic shock, which are often caused by pneumonia, impact millions of people every year. Despite adequate antibiotic therapy, mortality remains high, up to 45% in septic shock, which is characterized by an inappropriate, excessive immune response of the host. Moreover, critical illness-related corticosteroid insufficiency often coexists. Against this background, several trials and meta-analyses evaluated corticosteroid therapy as adjuvant therapy with heterogeneous results. Indeed, before 2000, high-dosage, short courses of corticosteroid treatment resulted in no benefit on mortality and a higher rate of adverse events. After 2000, thanks to a deeper understanding of the pathophysiology, low-dosage with longer courses of treatment were tested. With this regimen, a faster decrease in inflammation and faster resolution of shock, with a low rate of mild adverse events, was demonstrated although no clear effect on mortality was shown. To date, guidelines on sepsis and septic shock and guidelines on severe community-acquired pneumonia suggest corticosteroid use in selected patients. Furthermore, by utilizing latent class analysis, phenotypes of sepsis patients who benefit the most from corticosteroid treatment were recently identified. Future research should be guided by a precision medicine approach to identify adequate dosage and duration of corticosteroid treatment for appropriate patients. This article is freely available.

Incidence of asymptomatic catheter-related thrombosis in intensive care unit patients: a prospective cohort study.

BACKGROUND: Catheter-related thrombosis (CRT) incidence, rate, and risk factors vary in literature due to differences in populations, catheters, diagnostic methods, and statistical approaches. The aim of this single-center, prospective, observational study was to assess incidence, incidence rate (IR), cumulative incidence, and risk factors by means of IR ratio (IRR) of asymptomatic CRT in a non-oncologic Intensive Care Unit (ICU) population. CRT development was assessed daily by means of ultrasound screening. The proportions of patients and catheters developing CRT and CRT incidence rates, expressed as the number of events per catheter-days (cd), were calculated. Kalbfleisch and Prentice's method was used to estimate the cumulative incidence of CRTs. Univariate and multivariable Poisson regression models were fitted to calculate IRR in risk factors analysis. RESULTS: Fifty (25%, 95% CI 19-31) out of 203 included patients, and 52 (14%, 95% CI 11-18) out of 375 catheters inserted developed CRT [IR 17.7 (13.5-23.2) CRTs/1000*cd], after 5 [3-10] days from insertion. Forty-six CRTs (88%) were partial thrombosis. All CRTs remained asymptomatic. Obesity and ECMO support were patient-related protective factors [IRR 0.24 (0.10-0.60), p = 0.002 and 0.05 (0.01-0.50), p = 0.011, respectively]. The internal jugular vein had higher CRT IR than other sites [20.1 vs. 5.9 CRTs/1000*cd, IRR 4.22 (1.22-14.63), p = 0.023]. Pulmonary artery catheter and left-side cannulation were catheter-related risk factors [IRR 4.24 (2.00-9.00), p < 0.001 vs. central venous catheters; IRR 2.69 (1.45-4.98), p = 0.002 vs. right cannulation, respectively]. No statistically significant effect of the number of simultaneously inserted catheters [IRR 1.11 (0.64-1.94), p = 0.708] and of the catheterization length [IRR 1.09 (0.97-1.22), p = 0.155] was detected. The ICU length of stay was longer in CRT patients (20 [15-31] vs. 6 [4-14] days, p < 0.001), while no difference in mortality was observed. CONCLUSIONS: CRTs are frequent but rarely symptomatic. This study suggests that obesity and ECMO are protective factors, while pulmonary artery catheter, internal jugular vein and left-side positioning are risk factors for CRT.

Incidence, microbiological and immunological characteristics of ventilator-associated pneumonia assessed by bronchoalveolar lavage and endotracheal aspirate in a prospective cohort of COVID-19 patients: CoV-AP study.

BACKGROUND: No univocal recommendation exists for microbiological diagnosis of ventilator-associated pneumonia (VAP). Sampling of either proximal or distal respiratory tract likely impacts on the broad range of VAP incidence between cohorts. Immune biomarkers to rule-in/rule-out VAP diagnosis, although promising, have not yet been validated. COVID-19-induced ARDS made VAP recognition even more challenging, often leading to overdiagnosis and overtreatment. We evaluated the impact of different respiratory samples and laboratory techniques on VAP incidence and microbiological findings in COVID-19 patients. METHODS: Prospective single-centre cohort study conducted among COVID-19 mechanically ventilated patients in Policlinico Hospital (Milan, Italy) from January 2021 to May 2022. Microbiological confirmation of suspected VAP (sVAP) was based on concomitant endotracheal aspirates (ETA) and bronchoalveolar lavage (BAL). Conventional and fast microbiology (FILMARRAY® Pneumonia Panel plus, BALFAPPP) as well as immunological markers (immune cells and inflammatory cytokines) was analysed. RESULTS: Seventy-nine patients were included. Exposure to antibiotics and steroid therapy before ICU admission occurred in 51/79 (64.6%) and 60/79 (65.9%) patients, respectively. Median duration of MV at VAP suspicion was 6 (5-9) days. Incidence rate of microbiologically confirmed VAP was 33.1 (95% CI 22.1-44.0) and 20.1 (95% CI 12.5-27.7) according to ETA and BAL, respectively. Concordance between ETA and BAL was observed in 35/49 (71.4%) cases, concordance between BALFAPPP and BAL in 39/49 (79.6%) cases. With BAL as reference standard, ETA showed 88.9% (95% CI 70.8-97.7) sensitivity and 50.0% (95% CI 28.2-71.8) specificity (Cohen's Kappa 0.40, 95% CI 0.16-0.65). BALFAPPP showed 95.0% (95% CI 75.1-99.9) sensitivity and 69% (95% CI 49.2-84.7) specificity (Cohen's Kappa 0.60, 95% CI 0.39-0.81). BAL IL-1ß differed significantly between VAP (135 (IQR 11-450) pg/ml) and no-VAP (10 (IQR 2.9-105) pg/ml) patients (P = 0.03). CONCLUSIONS: In COVID-19 ICU patients, differences in microbial sampling at VAP suspicion could lead to high variability in VAP incidence and microbiological findings. Concordance between ETA and BAL was mainly limited by over 20% of ETA positive and BAL negative samples, while BALFAPPP showed high sensitivity but limited specificity when evaluating in-panel targets only. These factors should be considered when comparing results of cohorts with different sampling. BAL IL-1ß showed potential in discriminating microbiologically confirmed VAP. CLINICAL TRIAL REGISTRATION: NCT04766983, registered on February 23, 2021.

Hemodynamic failure and graft dysfunction after lung transplant: A possible clinical continuum with immediate and long-term consequences.

INTRODUCTION: The postoperative hemodynamic management after lung transplant (LUTX) is guided by limited evidence. We aimed to describe and evaluate risk factors and outcomes of postoperative vasoactive support of LUTX recipients. METHODS: In a single-center retrospective analysis of consecutive adult LUTX, two cohorts were identified: (1) patients needing prolonged vasoactive support (>12 h from ICU admission) (VASO+); (2) or not (VASO-). Postoperative hemodynamic characteristics were thoroughly analyzed. Risk factors and outcomes of VASO+ versus VASO- cohorts were assessed by multivariate logistic regression and propensity score matching. RESULTS: One hundred and thirty-eight patients were included (86 (62%) VASO+ versus 52 (38%) VASO-). Vasopressors (epinephrine, norepinephrine, dopamine) were used in the first postoperative days (vasoactive inotropic score at 12 h: 6 [4-12]), while inodilators (dobutamine, levosimendan) later. Length of vasoactive support was 3 [2-4] days. Independent predictors of vasoactive use were: LUTX indication different from cystic fibrosis (p = .003), higher Oto score (p = .020), longer cold ischemia time (p = .031), but not preoperative cardiac catheterization. VASO+ patients showed concomitant hemodynamic and graft impairment, with longer mechanical ventilation (p = .010), higher primary graft dysfunction (PGD) grade at 72 h (PGD grade > 0 65% vs. 31%, p = .004, OR 4.2 [1.54-11.2]), longer ICU (p < .001) and hospital stay (p = .013). Levosimendan as a second-line inodilator appeared safe. CONCLUSIONS: Vasoactive support is frequently necessary after LUTX, especially in recipients of grafts of lesser quality. Postoperative hemodynamic dysfunction requiring vasopressor support and graft dysfunction may represent a clinical continuum with immediate and long-term consequences. Further studies may elucidate if this represents a possible treatable condition.

Potential benefits of using an energy-dense, high-protein formula enriched with ß-hydroxy-ß-methylbutyrate, fructo-oligosaccharide, and vitamin D for enteral feeding in the ICU: A pilot case-control study in COVID-19 patients.

OBJECTIVES: The aim of this study was to investigate the potential benefits of using an energy-dense, high-protein (HP) formula enriched with ß-hydroxy-ß-methylbutyrate (HMB), fructo-oligosaccharide (FOS), and vitamin D (VitD) for enteral feeding in the intensive care unit (ICU). METHODS: This was a nested case-control multicenter study. Mechanically ventilated patients with COVID-19 in whom enteral nutrition was not contraindicated and receiving an energy-dense, HP-HMB-FOS-VitD formula (1.5 kcal/mL; 21.5% of calories from protein; n = 53) were matched (1:1) by age (±1 y), sex, body mass index (±1 kg/m2) and Sequential Organ Failure Assessment score (±1 point) and compared with patients fed with a standard HP, fiber-free formula (1.25-1.3 kcal/mL; 20% of calories from protein; n = 53). The primary end point was daily protein intake (g/kg) on day 4. Protein-calorie intake on day 7, gastrointestinal intolerance, and clinical outcomes were addressed as secondary end points. RESULTS: The use of a HP-HMB-FOS-VitD formula resulted in higher protein intake on days 4 and 7 (P = 0.006 and P = 0.013, respectively), with similar energy intake but higher provision of calories from enteral nutrition at both times (P <0 .001 and P = 0.017, respectively). Gastrointestinal tolerance was superior, with fewer patients fed with a HP-HMB-FOS-VitD formula reporting at least one symptom of intolerance (55 versus 74%; odds ratio [OR], 0.43; 95% confidence interval [CI], 0.18-0.99; P = 0.046) and constipation (38 versus 66%; OR, 0.27; 95% CI, 0.12-0.61; P = 0.002). A lower rate of ICU-acquired infections was also observed (42 versus 72%; OR, 0.29; 95% CI, 0.13-0.65; P = 0.003), although no difference was found in mortality, ICU length of stay, and ventilation-free survival. CONCLUSIONS: An energy-dense, HP-HMB-FOS-VitD formula provided a more satisfactory protein intake and a higher provision of caloric intake from enteral nutrition than a standard HP formula in mechanically ventilated patients with COVID-19. Lower rates of gastrointestinal intolerance and ICU-acquired infections were also observed.

The role of hypoxia and inflammation in the regulation of iron metabolism and erythropoiesis in COVID-19: The IRONCOVID study.

Coronavirus Disease (COVID-19) can be considered as a human pathological model of inflammation combined with hypoxia. In this setting, both erythropoiesis and iron metabolism appear to be profoundly affected by inflammatory and hypoxic stimuli, which act in the opposite direction on hepcidin regulation. The impact of low blood oxygen levels on erythropoiesis and iron metabolism in the context of human hypoxic disease (e.g., pneumonia) has not been fully elucidated. This multicentric observational study was aimed at investigating the prevalence of anemia, the alterations of iron homeostasis, and the relationship between inflammation, hypoxia, and erythropoietic parameters in a cohort of 481 COVID-19 patients admitted both to medical wards and intensive care units (ICU). Data were collected on admission and after 7 days of hospitalization. On admission, nearly half of the patients were anemic, displaying mild-to-moderate anemia. We found that hepcidin levels were increased during the whole period of observation. The patients with a higher burden of disease (i.e., those who needed intensive care treatment or had a more severe degree of hypoxia) showed lower hepcidin levels, despite having a more marked inflammatory pattern. Erythropoietin (EPO) levels were also lower in the ICU group on admission. After 7 days, EPO levels rose in the ICU group while they remained stable in the non-ICU group, reflecting that the initial hypoxic stimulus was stronger in the first group. These findings strengthen the hypothesis that, at least in the early phases, hypoxia-driven stimuli prevail over inflammation in the regulation of hepcidin and, finally, of erythropoiesis.

Impact of dexamethasone on the incidence of ventilator-associated pneumonia in mechanically ventilated COVID-19 patients: a propensity-matched cohort study.

OBJECTIVE: To assess the impact of treatment with steroids on the incidence and outcome of ventilator-associated pneumonia (VAP) in mechanically ventilated COVID-19 patients. DESIGN: Propensity-matched retrospective cohort study from February 24 to December 31, 2020, in 4 dedicated COVID-19 Intensive Care Units (ICU) in Lombardy (Italy). PATIENTS: Adult consecutive mechanically ventilated COVID-19 patients were subdivided into two groups: (1) treated with low-dose corticosteroids (dexamethasone 6 mg/day intravenous for 10 days) (DEXA+); (2) not treated with corticosteroids (DEXA-). A propensity score matching procedure (1:1 ratio) identified patients' cohorts based on: age, weight, PEEP Level, PaO2/FiO2 ratio, non-respiratory Sequential Organ Failure Assessment (SOFA) score, Charlson Comorbidity Index (CCI), C reactive protein plasma concentration at admission, sex and admission hospital (exact matching). INTERVENTION: Dexamethasone 6 mg/day intravenous for 10 days from hospital admission. MEASUREMENTS AND MAIN RESULTS: Seven hundred and thirty-nine patients were included, and the propensity-score matching identified two groups of 158 subjects each. Eighty-nine (56%) DEXA+ versus 55 (34%) DEXA- patients developed a VAP (RR 1.61 (1.26-2.098), p = 0.0001), after similar time from hospitalization, ICU admission and intubation. DEXA+ patients had higher crude VAP incidence rate (49.58 (49.26-49.91) vs. 31.65 (31.38-31.91)VAP*1000/pd), (IRR 1.57 (1.55-1.58), p < 0.0001) and risk for VAP (HR 1.81 (1.31-2.50), p = 0.0003), with longer ICU LOS and invasive mechanical ventilation but similar mortality (RR 1.17 (0.85-1.63), p = 0.3332). VAPs were similarly due to G+ bacteria (mostly Staphylococcus aureus) and G- bacteria (mostly Enterobacterales). Forty-one (28%) VAPs were due to multi-drug resistant bacteria. VAP was associated with almost doubled ICU and hospital LOS and invasive mechanical ventilation, and increased mortality (RR 1.64 [1.02-2.65], p = 0.040) with no differences among patients' groups. CONCLUSIONS: Critically ill COVID-19 patients are at high risk for VAP, frequently caused by multidrug-resistant bacteria, and the risk is increased by corticosteroid treatment. TRIAL REGISTRATION: NCT04388670, retrospectively registered May 14, 2020.

Use of high flow nasal cannula in patients with acute respiratory failure in general wards under intensivists supervision: a single center observational study.

BACKGROUND: Few data exist on high flow nasal cannula (HFNC) use in patients with acute respiratory failure (ARF) admitted to general wards. RATIONALE AND OBJECTIVES: To retrospectively evaluate feasibility and safety of HFNC in general wards under the intensivist-supervision and after specific training. METHODS: Patients with ARF (dyspnea, respiratory rate-RR > 25/min, 150 < PaO2/FiO2 < 300 mmHg during oxygen therapy) admitted to nine wards of an academic hospital were included. Gas-exchange, RR, and comfort were assessed before HFNC and after 2 and 24 h of application. RESULTS: 150 patients (81 male, age 74 [60-80] years, SOFA 4 [2-4]), 123 with de-novo ARF underwent HFNC with flow 60 L/min [50-60], FiO2 50% [36-50] and temperature 34 °C [31-37]. HFNC was applied a total of 1399 days, with a median duration of 7 [3-11] days. No major adverse events or deaths were reported. HFNC did not affect gas exchange but reduced RR (25-22/min at 2-24 h, p < 0.001), and improved Dyspnea Borg Scale (3-1, p < 0.001) and comfort (3-4, p < 0.001) after 24 h. HFNC failed in 20 patients (19.2%): 3 (2.9%) for intolerance, 14 (13.4%) escalated to NIV/CPAP in the ward, 3 (2.9%) transferred to ICU. Among these, one continued HFNC, while the other 2 were intubated and they both died. Predictors of HFNC failure were higher Charlson's Comorbidity Index (OR 1.29 [1.07-1.55]; p = 0.004), higher APACHE II Score (OR 1.59 [1.09-4.17]; p = 0.003), and cardiac failure as cause of ARF (OR 5.26 [1.36-20.46]; p = 0.02). CONCLUSION: In patients with mild-moderate ARF admitted to general wards, the use of HFNC after an initial training and daily supervision by intensivists was feasible and seemed safe. HFNC was effective in improving comfort, dyspnea, and respiratory rate without effects on gas exchanges. Trial registration This is a single-centre, noninterventional, retrospective analysis of clinical data.

Early caloric deficit is associated with a higher risk of death in invasive ventilated COVID-19 patients.

BACKGROUND & AIMS: The aim of this study was to evaluate the nutritional support management in mechanically ventilated coronavirus disease 2019 (COVID-19) patients and explore the association between early caloric deficit and mortality, taking possible confounders (i.e. obesity) into consideration. METHODS: This was a prospective study carried out during the first pandemic wave in the intensive care units (ICUs) of two referral University Hospitals in Lombardy, Italy. Two hundred twenty-two consecutive mechanically ventilated COVID-19 patients were evaluated during the ICU stay. In addition to major demographic and clinical data, we recorded information on the route and amount of nutritional support provided on a daily basis. RESULTS: Among patients still in the ICUs and alive on day 4 (N = 198), 129 (65.2%) and 72 (36.4%) reached a satisfactory caloric and protein intake, respectively, mainly by enteral route. In multivariable analysis, a satisfactory caloric intake on day 4 was associated with lower mortality (HR = 0.46 [95%CI, 0.42-0.50], P < 0.001). Mild obesity (body mass index [BMI] ≥30 and < 35 kg/m2) was associated with higher mortality (HR = 1.99 [95%CI, 1.07-3.68], P = 0.029), while patients with moderate-severe obesity (BMI≥35 kg/m2) were less likely to be weaned from invasive mechanical ventilation (HR = 0.71 [95%CI, 0.62-0.82], P < 0.001). CONCLUSIONS: This study confirmed the negative prognostic and clinical role of obesity in mechanically ventilated COVID-19 patients and suggested that early caloric deficit may independently contribute to worsen survival in this patients' population. Therefore, any effort should be made to implement an adequate timely nutritional support in all COVID-19 patients during the ICU stay.

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

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 H2O). 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 H2O µV-1. 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 H2O, 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-1 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.

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

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.

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

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 PaO2/FiO2 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 PaO2/FiO2 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.

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

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 (R2 = 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.

Practical Clinical Application of an Extracorporeal Carbon Dioxide Removal System in Acute Respiratory Distress Syndrome and Acute on Chronic Respiratory Failure.

We retrospectively reviewed the medical records of 11 patients supported with a veno-venous low-flow extracorporeal carbon dioxide (CO2) removal (ECCO2R) device featuring a large gas exchange surface membrane lung (ML) (i.e., 1.8 m). Seven patients suffered from exacerbation of a chronic pulmonary disease, while four subjects were affected by acute respiratory distress syndrome (ARDS). Twenty-four hours of ECCO2R treatment reduced arterial PCO2 from 63 ± 12 to 54 ± 11 mm Hg (p < 0.01), increased arterial pH from 7.29 ± 0.07 to 7.39 ± 0.06 (p < 0.01), and decreased respiratory rate from 32 ± 10 to 21 ± 8 bpm (p < 0.05). Extracorporeal blood flow and CO2 removal were 333 ± 37 and 94 ± 18 ml/min, respectively. The median duration of ECCO2R treatment was 7 days (6.5-9.5). All four ARDS patients were invasively ventilated at the time of treatment start, no one was extubated and they all died. Among the seven patients with exacerbation of chronic pulmonary diseases, four were managed with noninvasive ventilation at ECCO2R institution, while three were extubated after starting the extracorporeal treatment. No one of these seven patients was intubated or re-intubated after ECCO2R institution and five (71%) survived to hospital discharge. A low-flow ECCO2R device with a large surface ML removes a relevant amount of CO2 resulting in a decreased arterial PCO2, an increased arterial pH, and in a reduced ventilatory load.