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.

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.

A Minimally Invasive and Highly Effective Extracorporeal CO2 Removal Device Combined With a Continuous Renal Replacement Therapy.

OBJECTIVES: Extracorporeal carbon dioxide removal is used to treat patients suffering from acute respiratory failure. However, the procedure is hampered by the high blood flow required to achieve a significant CO2 clearance. We aimed to develop an ultralow blood flow device to effectively remove CO2 combined with continuous renal replacement therapy (CRRT). DESIGN: Preclinical, proof-of-concept study. SETTING: An extracorporeal circuit where 200 mL/min of blood flowed through a hemofilter connected to a closed-loop dialysate circuit. An ion-exchange resin acidified the dialysate upstream, a membrane lung to increase Pco2 and promote CO2 removal. PATIENTS: Six, 38.7 ± 2.0-kg female pigs. INTERVENTIONS: Different levels of acidification were tested (from 0 to 5 mEq/min). Two l/hr of postdilution CRRT were performed continuously. The respiratory rate was modified at each step to maintain arterial Pco2 at 50 mm Hg. MEASUREMENTS AND MAIN RESULTS: Increasing acidification enhanced CO2 removal efficiency of the membrane lung from 30 ± 5 (0 mEq/min) up to 145 ± 8 mL/min (5 mEq/min), with a 483% increase, representing the 73% ± 7% of the total body CO2 production. Minute ventilation decreased accordingly from 6.5 ± 0.7 to 1.7 ± 0.5 L/min. No major side effects occurred, except for transient tachycardia episodes. As expected from the alveolar gas equation, the natural lung Pao2 dropped at increasing acidification steps, given the high dissociation between the oxygenation and CO2 removal capability of the device, thus Pao2 decreased. CONCLUSIONS: This new extracorporeal ion-exchange resin-based multiple-organ support device proved extremely high efficiency in CO2 removal and continuous renal support in a preclinical setting. Further studies are required before clinical implementation.

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.

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.

Cerebrospinal fluid and arterial acid-base equilibria in spontaneously breathing third-trimester pregnant women.

BACKGROUND: Acid-base status in full-term pregnant women is characterised by hypocapnic alkalosis. Whether this respiratory alkalosis is primary or consequent to changes in CSF electrolytes is not clear. METHODS: We enrolled third-trimester pregnant women (pregnant group) and healthy, non-pregnant women of childbearing age (controls) undergoing spinal anaesthesia for Caesarean delivery and elective surgery, respectively. Electrolytes, strong ion difference (SID), partial pressure of carbon dioxide ( [Formula: see text] ), and pH were measured in simultaneously collected CSF and arterial blood samples. RESULTS: All pregnant women (20) were hypocapnic, whilst only four (30%) of the controls (13) had an arterial [Formula: see text] <4.7 kPa (P<0.001). The incidence of hypocapnic alkalosis was higher in the pregnant group (65% vs 8%; P=0.001). The CSF-to-plasma Pco2 difference was significantly higher in pregnant women (1.5 [0.3] vs 1.0 [0.4] kPa; P<0.001), mainly because of a decrease in arterial Pco2 (3.9 [0.3] vs 4.9 [0.5] kPa; P<0.001). Similarly, the CSF-to-plasma difference in SID was less negative in pregnant women (-7.8 [1.4] vs -11.4 [2.3] mM; P<0.001), mainly because of a decreased arterial SID (31.5 [1.2] vs 36.1 [1.9] mM; P<0.001). The major determinant of the reduced plasma SID of pregnant women was a relative increase in plasma chloride compared with sodium. CONCLUSIONS: Primary hypocapnic alkalosis characterises third-trimester pregnant women leading to chronic acid-base adaptations of CSF and plasma. The compensatory SID reduction, mainly sustained by an increase in chloride concentration, is more pronounced in plasma than in CSF, as the decrease in Pco2 is more marked in this compartment. CLINICAL TRIAL REGISTRATION: NCT03496311.

Limitations of arterial partial pressure of oxygen to fraction of inspired oxygen ratio for the evaluation of donor lung function.

BACKGROUND: Evaluation of donor lung function relies on the arterial oxygen partial pressure to inspired oxygen fraction ratio (PaO2 /FiO2 ) measurement. Hemodynamic, metabolic derangements, and therapeutic intervention occurring during brain dead observation may influence the evaluation of gas exchange. METHODS: We performed a mathematical analysis to explore the influence of the extrapulmonary determinants on the interpretation of PaO2 /FiO2 in the brain-dead donor and during Ex-Vivo Lung Perfusion (EVLP). RESULTS: High FiO2 and increased mixed venous oxygen saturation, caused by increased delivery and reduced consumption of oxygen, raise the PaO2 /FiO2 despite substantial intrapulmonary shunt. Anemia does not modify the PaO2 /FiO2 -intrapulmonary shunt relationship. During EVLP, the reduced artero-venous difference in oxygen content increases the PaO2 /FiO2 without this corresponding to an optimal graft function, while the reduced perfusate oxygen-carrying capacity linearizes the PaO2 /FiO2 -intrapulmonary shunt relationship. CONCLUSIONS: Adopting PaO2 /FiO2 to evaluate graft suitability for transplantation should account for extrapulmonary factors affecting its interpretation.

Regional blood acidification inhibits coagulation during extracorporeal carbon dioxide removal (ECCO2 R).

BACKGROUND: Consumption of platelets and coagulation factors during extracorporeal carbon dioxide removal (ECCO2 R) increases bleeding complications and associated mortality. Regional infusion of lactic acid enhances ECCO2 R by shifting the chemical equilibrium from bicarbonate to carbon dioxide. Our goal was to test if regional blood acidification during ECCO2 R inhibits platelet function and coagulation. METHODS: An ECCO2 R system containing a hemofilter circulated blood at 0.25 L/min in eight healthy ewes (Ovis aries) for 36 h. Three of the sheep received ECCO2 R with no recirculation compared to five sheep that received ECCO2 R plus 12 h of regional blood acidification via the hemofilter, placed upstream from the oxygenator, into which 4.4 M lactic acid was infused. Blood gases, platelet count and function, thromboelastography, coagulation-factor activity, and von Willebrand factor activity (vWF:Ag) were measured at baseline, at start of lactic acid infusion, and after 36 h of extracorporeal circulation. RESULTS: Twelve hours of regional acid infusion significantly inhibited platelet aggregation response to adenosine diphosphate; vWF; and platelet expression of P-selectin compared to control. It also significantly reduced consumption of fibrinogen and of coagulation factors V, VII, IX, compared to control. CONCLUSIONS: Regional acidification reduces platelet activation and vitamin-K-dependent coagulation-factor consumption during ECCO2 R. This is the first report of a simple method that may enhance effective anticoagulation for ECCO2 R.

Interobserver variability in the evaluation of primary graft dysfunction after lung transplantation: impact of radiological training and analysis of discordant cases.

PURPOSE: Radiologic criteria for the diagnosis of primary graft dysfunction (PGD) after lung transplantation are nonspecific and can lead to misinterpretation. The primary aim of our study was to assess the interobserver agreement in the evaluation of chest X-rays (CXRs) for PGD diagnosis and to establish whether a specific training could have an impact on concordance rates. Secondary aim was to analyze causes of interobserver discordances. MATERIAL AND METHODS: We retrospectively enrolled 164 patients who received bilateral lung transplantation at our institution, between February 2013 and December 2019. Three radiologists independently reviewed postoperative CXRs and classified them as suggestive or not for PGD. Two of the Raters performed a specific training before the beginning of the study. A senior thoracic radiologist subsequently analyzed all discordant cases among the Raters with the best agreement. Statistical analysis to calculate interobserver variability was percent agreement, Cohen's kappa and intraclass correlation coefficient. RESULTS: A total of 473 CXRs were evaluated. A very high concordance among the two trained Raters, 1 and 2, was found (K = 0.90, ICC = 0.90), while a poorer agreement was found in the other two pairings (Raters 1 and 3: K = 0.34, ICC = 0.40; Raters 2 and 3: K = 0.35, ICC = 0.40). The main cause of disagreement (52.4% of discordant cases) between Raters 1 and 2 was the overestimation of peribronchial thickening in the absence of unequivocal bilateral lung opacities or the incorrect assessment of unilateral alterations. CONCLUSION: To properly identify PGD, it is recommended for radiologists to receive an adequate specific training.

Ventilation of coronavirus disease 2019 patients.

PURPOSE OF REVIEW: To summarize the current knowledge of pathophysiology and ventilatory management of acute respiratory failure in COVID-19. RECENT FINDINGS: Early reports suggested that COVID-19 is an 'atypical ARDS' with profound hypoxemia with normal respiratory system compliance (Crs). Contrarily, several more populated analyses showed that COVID-19 ARDS has pathophysiological features similar to non-COVID-19 ARDS, with reduced Crs, and high heterogeneity of respiratory mechanics, hypoxemia severity, and lung recruitability. There is no evidence supporting COVID-19-specific ventilatory settings, and the vast amount of available literature suggests that evidence-based, lung-protective ventilation (i.e. tidal volume ≤6 ml/kg, plateau pressure ≤30 cmH2O) should be enforced in all mechanically ventilated patients with COVID-19 ARDS. Mild and moderate COVID-19 can be managed outside of ICUs by noninvasive ventilation in dedicated respiratory units, and no evidence support an early vs. late intubation strategy. Despite widely employed, there is no evidence supporting the efficacy of rescue therapies, such as pronation, inhaled vasodilators, or extracorporeal membrane oxygenation. SUMMARY: Given the lack of evidence-based specific ventilatory strategies and a large amount of literature showing pathophysiological features similar to non-COVID-19 ARDS, evidence-based lung-protective ventilatory strategies should be pursued in all patients with COVID-19 ARDS.

SARS-CoV-2 RNA in plasma samples of COVID-19 affected individuals: a cross-sectional proof-of-concept study.

BACKGROUND: Recent studies showed that plasma SARS-CoV-2 RNA seems to be associated with worse COVID-19 outcome. However, whether specific population can be at higher risk of viremia are to date unexplored. METHODS: This cross-sectional proof-of-concept study included 41 SARS-CoV-2-positive adult individuals (six affected by haematological malignancies) hospitalized at two major hospital in Milan, for those demographic, clinical and laboratory data were available. SARS-CoV-2 load was quantified by ddPCR in paired plasma and respiratory samples. To assess significant differences between patients with and patients without viremia, Fisher exact test and Wilcoxon test were used for categorical and continuous variables, respectively. RESULTS: Plasma SARS-CoV-2 RNA was found in 8 patients (19.5%), with a median (IQR) value of 694 (209-1023) copies/mL. Viremic patients were characterized by an higher mortality rate (50.0% vs 9.1%; p = 0.018) respect to patients without viremia. Viremic patients were more frequently affected by haematological malignancies (62.5% vs. 3.0%; p < 0.001), and had higher viral load in respiratory samples (9,404,000 [586,060-10,000,000] vs 1560 [312-25,160] copies/mL; p = 0.002). CONCLUSIONS: Even if based on a small sample population, this proof-of-concept study poses the basis for an early identification of patients at higher risk of SARS-CoV-2 viremia, and therefore likely to develop severe COVID-19, and supports the need of a quantitative viral load determination in blood and respiratory samples of haematologic patients with COVID-19 in order to predict prognosis and consequently to help their further management.

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.

Extracorporeal Chloride Removal by Electrodialysis. A Novel Approach to Correct Acidemia.

Rationale: Acidemia is a severe condition among critically ill patients. Despite lack of evidence, sodium bicarbonate is frequently used to correct pH; however, its administration is burdened by several side effects. We hypothesized that the reduction of plasma chloride concentration could be an alternative strategy to correct acidemia.Objectives: To evaluate feasibility, safety, and effectiveness of a novel strategy to correct acidemia through extracorporeal chloride removal by electrodialysis.Methods: Ten swine (six treated and four control animals) were sedated, mechanically ventilated and connected to an extracorporeal electrodialysis device capable of selectively removing chloride. In random order, an arterial pH of 7.15 was induced either through reduction of ventilation (respiratory acidosis) or through lactic acid infusion (metabolic acidosis). Acidosis was subsequently sustained for 12-14 hours. In treatment pigs, soon after reaching target acidemia, electrodialysis was started to restore pH.Measurements and Main Results: During respiratory acidosis, electrodialysis reduced plasma chloride concentration by 26 ± 5 mEq/L within 6 hours (final pH = 7.36 ± 0.04). Control animals exhibited incomplete and slower compensatory response to respiratory acidosis (final pH = 7.29 ± 0.03; P < 0.001). During metabolic acidosis, electrodialysis reduced plasma chloride concentration by 15 ± 3 mEq/L within 4 hours (final pH = 7.34 ± 0.07). No effective compensatory response occurred in control animals (final pH = 7.11 ± 0.08; P < 0.001). No complications occurred.Conclusions: We described the first in vivo application of an extracorporeal system targeted to correct severe acidemia by lowering plasma chloride concentration. Extracorporeal chloride removal by electrodialysis proved to be feasible, safe, and effective. Further studies are warranted to assess its performance in the presence of impaired respiratory and renal functions.

Assessment of spontaneous breathing during pressure controlled ventilation with superimposed spontaneous breathing using respiratory flow signal analysis.

Integrating spontaneous breathing into mechanical ventilation (MV) can speed up liberation from it and reduce its invasiveness. On the other hand, inadequate and asynchronous spontaneous breathing has the potential to aggravate lung injury. During use of airway-pressure-release-ventilation (APRV), the assisted breaths are difficult to measure. We developed an algorithm to differentiate the breaths in a setting of lung injury in spontaneously breathing ewes. We hypothesized that differentiation of breaths into spontaneous, mechanical and assisted is feasible using a specially developed for this purpose algorithm. Ventilation parameters were recorded by software that integrated ventilator output variables. The flow signal, measured by the EVITA® XL (Lübeck, Germany), was measured every 2 ms by a custom Java-based computerized algorithm (Breath-Sep). By integrating the flow signal, tidal volume (VT) of each breath was calculated. By using the flow curve the algorithm separated the different breaths and numbered them for each time point. Breaths were separated into mechanical, assisted and spontaneous. Bland Altman analysis was used to compare parameters. Comparing the values calculated by Breath-Sep with the data from the EVITA® using Bland-Altman analyses showed a mean bias of - 2.85% and 95% limits of agreement from - 25.76 to 20.06% for MVtotal. For respiratory rate (RR) RRset a bias of 0.84% with a SD of 1.21% and 95% limits of agreement from - 1.53 to 3.21% were found. In the cluster analysis of the 25th highest breaths of each group RRtotal was higher using the EVITA®. In the mechanical subgroup the values for RRspont and MVspont the EVITA® showed higher values compared to Breath-Sep. We developed a computerized method for respiratory flow-curve based differentiation of breathing cycle components during mechanical ventilation with superimposed spontaneous breathing. Further studies in humans and optimizing of this technique is necessary to allow for real-time use at the bedside.

Early pulmonary function and mid-term outcome in lung transplantation after ex-vivo lung perfusion - a single-center, retrospective, observational, cohort study.

Outcomes after transplantation of lungs (LuTX) treated with ex-vivo lung perfusion (EVLP) are debated. In a single-center 8 years of retrospective analysis, we compared: donors' and recipients' characteristics, gas exchange and lung mechanics at ICU admission, 3, 6, and 12 months, and patients' survival of LuTX from standard donors compared with EVLP-treated grafts. A total of 193 LuTX were performed. Thirty-one LuTX, out of 50 EVLP procedures, were carried out: 7 from nonheart beating and 24 from extended criteria brain-dead donors. Recipients' characteristics were similar. At ICU admission, compared with standard donors, EVLP patients had worse PaO2 /FiO2 [276 (206; 374) vs. 204 (133; 245) mmHg, P < 0.05], more frequent extracorporeal support (18% vs. 32%, P = 0.053) and longer mechanical ventilation duration [28 days of ventilator-free days: 27 (24; 28) vs. 26 (19; 27), P < 0.05]. ICU length of stay [4 (2; 9) vs. 6 (3; 12) days, P = 0.208], 28-day survival (99% vs. 97%, P = 0.735), and 1-year respiratory function were similar between groups. Log-rank analysis (median follow-up 2.5 years) demonstrated similar patients' survival (P = 0.439) and time free of chronic lung allograft disease (P = 0.484). The EVLP program increased by 16% the number of LuTX. Compared to standard donors, EVLP patients had worse respiratory function immediately after LuTX but similar early and mid-term outcomes.

Quality of Life and Lung Function in Survivors of Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome.

BACKGROUND: Survivors of acute respiratory distress syndrome (ARDS) have long-term impairment of pulmonary function and health-related quality of life, but little is known of outcomes of ARDS survivors treated with extracorporeal membrane oxygenation. The aim of this study was to compare long-term outcomes of ARDS patients treated with or without extracorporeal membrane oxygenation. METHODS: A prospective, observational study of adults with ARDS (January 2013 to December 2015) was conducted at a single center. One year after discharge, survivors underwent pulmonary function tests, computed tomography of the chest, and health-related quality-of-life questionnaires. RESULTS: Eighty-four patients (34 extracorporeal membrane oxygenation, 50 non-extracorporeal membrane oxygenation) were studied; both groups had similar characteristics at baseline, but comorbidity was more common in non-extracorporeal membrane oxygenation (23 of 50 vs. 4 of 34, 46% vs. 12%, P < 0.001), and severity of hypoxemia was greater in extracorporeal membrane oxygenation (median PaO2/FIO2 72 [interquartile range, 50 to 103] vs. 114 [87 to 133] mm Hg, P < 0.001) and respiratory compliance worse. At 1 yr, survival was similar (22/33 vs. 28/47, 66% vs. 59%; P = 0.52), and pulmonary function and computed tomography were almost normal in both groups. Non-extracorporeal membrane oxygenation patients had lower health-related quality-of-life scores and higher rates of posttraumatic stress disorder. CONCLUSIONS: Despite more severe respiratory failure at admission, 1-yr survival of extracorporeal membrane oxygenation patients was not different from that of non-extracorporeal membrane oxygenation patients; each group had almost full recovery of lung function, but non-extracorporeal membrane oxygenation patients had greater impairment of health-related quality of life.

Induction Dosage of Propofol for Repeated Sedations in Children With Hematological Disorders.

Pediatric patients with hematologic malignancies require several procedural sedations by means of propofol infusion. We retrospectively analyzed the medical records of leukemic pediatric patients who had undergone procedural sedations at an Italian tertiary referral center (San Gerardo Hospital, Monza) from January 2011 to November 2013. We retrieved the following: demographics; diagnosis; chemotherapy phase; use of corticosteroids; induction dosage of propofol, fentanyl and/or ketamine; and the type of procedure. We used a multivariate linear mixed model to evaluate the factors affecting induction propofol dose. We analyzed 1459 procedures (59% lumbar punctures, 31% bone marrow aspirations) performed on 96 children (7 [4-10] y old, 24 [16-34] kg, 37% female) admitted for acute lymphoblastic leukemia (80%), lymphoma (11%), and acute myeloid leukemia (7%). The induction propofol dose increased by 0.03 mg/kg per each procedure (P<0.05), from 2.6 (2.0-3.2) to 3.5 (2.6-4.3) mg/kg at the first and the last procedure, respectively. Higher age, weight, and use of ketamine were associated to lower propofol dosage (P<0.01), while combined procedures increased propofol dosage (P<0.01). In a large cohort of leukemic pediatric patients undergoing procedural sedation, the induction dose of propofol was increased over time, regardless of weight, age, use of corticosteroids, diagnosis, and treatment phase.

Safety of anesthesia for children with mucopolysaccharidoses: A retrospective analysis of 54 patients.

BACKGROUND: Complications are common during anesthesia for patients with mucopolysaccharidoses. San Gerardo Hospital (Italy) is a reference center for mucopolysaccharidoses with a dedicated pediatric anesthesia service. AIMS: This study aims to evaluate the safety of anesthesia for mucopolysaccharidoses patients, describe their anesthetic management at our institution, and assess risk factors for complications. METHODS: The anesthetic charts of mucopolysaccharidoses patients admitted from January 1999 to December 2014 were retrospectively analyzed. We retrieved patients' demographics; location and type of the procedure; anesthetic approach airway management and occurrence of difficult intubation and complications and outcome at hospital discharge. A generalized linear mixed model was performed to assess risk factors for complications and difficult intubation. RESULTS: Fifty-four consecutive children were included. The anesthetic charts of 232 procedures (52% radio-diagnostics, 15% orthopedics, 15% ear-nose-throat surgery, 10% neurosurgery, and 8% general surgery) were analyzed. Each patient underwent a median of 4 (1-6) procedures. The median age at the first procedure was 2 (1-5), and overall age was 5 (2-8) years old. One hundred and twenty-five (54%) procedures were performed in remote locations. General anesthesia was utilized for 100 (43%) procedures. No death was recorded. Twenty-one (9%) procedures had respiratory complications. Remote location anesthesia was associated with increased risk for complications (odds ratio 5.405 [1.355-28.571], P = .016). All planned intubations (n = 65) were successful. Nineteen (29%) of those were defined difficult. All emergency intubations (n = 3) failed and were rescued by laryngeal mask airways. Older age was associated with an increased risk of difficult intubation (OR 1.200 [1.019-1.436], P = .028). CONCLUSION: Patients with mucopolysaccharidoses are at high risk for anesthesia-related complications. Remote location anesthesia is associated with increased risk for complications, and older age is associated with increased risk for difficult intubation.