Three Logistic Predictive Models for the Prediction of Mortality and Major Pulmonary Complications after Cardiac Surgery.

Background and Objectives: Pulmonary complications are a leading cause of morbidity after cardiac surgery. The aim of this study was to develop models to predict postoperative lung dysfunction and mortality. Materials and Methods: This was a single-center, observational, retrospective study. We retrospectively analyzed the data of 11,285 adult patients who underwent all types of cardiac surgery from 2003 to 2015. We developed logistic predictive models for in-hospital mortality, postoperative pulmonary complications occurring in the intensive care unit, and postoperative non-invasive mechanical ventilation when clinically indicated. Results: In the "preoperative model" predictors for mortality were advanced age (p < 0.001), New York Heart Association (NYHA) class (p < 0.001) and emergent surgery (p = 0.036); predictors for non-invasive mechanical ventilation were advanced age (p < 0.001), low ejection fraction (p = 0.023), higher body mass index (p < 0.001) and preoperative renal failure (p = 0.043); predictors for postoperative pulmonary complications were preoperative chronic obstructive pulmonary disease (p = 0.007), preoperative kidney injury (p < 0.001) and NYHA class (p = 0.033). In the "surgery model" predictors for mortality were intraoperative inotropes (p = 0.003) and intraoperative intra-aortic balloon pump (p < 0.001), which also predicted the incidence of postoperative pulmonary complications. There were no specific variables in the surgery model predicting the use of non-invasive mechanical ventilation. In the "intensive care unit model", predictors for mortality were postoperative kidney injury (p < 0.001), tracheostomy (p < 0.001), inotropes (p = 0.029) and PaO2/FiO2 ratio at discharge (p = 0.028); predictors for non-invasive mechanical ventilation were kidney injury (p < 0.001), inotropes (p < 0.001), blood transfusions (p < 0.001) and PaO2/FiO2 ratio at the discharge (p < 0.001). Conclusions: In this retrospective study, we identified the preoperative, intraoperative and postoperative characteristics associated with mortality and complications following cardiac surgery.

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

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 (PaO2/FiO2) 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, PaO2/FiO2, 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 PaO2/FiO2, 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.

Intrinsic positive end-expiratory pressure during ventilation through small endotracheal tubes during general anesthesia: incidence, mechanism, and predictive factors.

STUDY OBJECTIVE: To assess the safety of mechanical ventilation and effectiveness of extrinsic positive end-expiratory pressure (PEEP) (PEEPe) in improving peripheral oxygen saturation (SpO2) during direct microlaryngeal laser surgery; to assess the incidence, amount, and nature (dynamic hyperinflation or airflow obstruction) of ensuing intrinsic PEEP (PEEPi); and to find a surrogate PEEPi indicator. DESIGN: Quasiexperimental. SETTING: S. Raffaele Hospital (Milano), November 2009 to December 2010. PATIENTS: Fifty-two adults scheduled for direct microlaryngeal laser surgery. Exclusion criterion is pregnancy. INTERVENTIONS: Twenty-one percent O2 mechanical ventilation through 4.5- to 5.5-mm internal diameter endotracheal tubes; in 29 patients, after measurement of PEEPi, an identical amount of PEEPe was added; and PEEPi. MEASUREMENTS: SpO2, peak (Pawpeak) and plateau (Pawplateau) airway pressure, and end-expiratory carbon dioxide were measured every 5 minutes. Respiratory compliance (Crs) was computed. PEEPi was measured (end-expiratory occlusion method). MAIN RESULTS: PEEPi ≥5 cm H2O occurred in 14 patients (27%) after intubation, in 16 (30%) at the beginning, and in 14 (27.3%) at the end of surgery. Thirty-one patients (59.4%) exhibited PEEPi ≥5 cm H2O on at least 1 time point. PEEPi at the beginning of surgery was positively correlated with Pawplateau, Crs, tidal volume, and body mass index. Body mass index was the only predictor for the occurrence of PEEPi ≥5 cm H2O. At the beginning of surgery, the Pawplateau receiver operating characteristic curve predicting PEEPi ≥5 cm H2O had area under the receiver operating characteristic curve of 0.85; best cutoff value of 15.5 cm H2O (sensitivity, 88.9%; specificity, 75%; correctly classified cases, 86.1%). When PEEPe was applied, in 23 cases (82.1%), total PEEP equaled PEEPe+ PEEPi; in 3 (10.7%), it was lower; and in 2 (7.1%), it was higher. Application of PEEPe increased SpO2 (P< .05) and Crs (P< .05). CONCLUSIONS: During ventilation through small endotracheal tubes, PEEPi (mostly due to dynamic hyperinflation) is common. Hemodynamic complications, barotrauma, and O2 desaturation (reversible with PEEPe) are rare. Pawplateau provided by ventilators is useful in suspecting and monitoring the occurrence of PEEPi and allows detection of lung overdistension as PEEPe is applied.

Optimization of the THP-1 activation assay to detect pharmaceuticals with potential to cause immune mediated drug reactions.

Despite important impacts of systemic hypersensitivity induced by pharmaceuticals, for such endpoint no reliable preclinical approaches are available. We previously established an in vitro test to identify contact and respiratory allergens based on interleukin-8 (IL-8) production in THP-1 cells. Here, we challenged it for identification of pharmaceuticals associated with systemic hypersensitivity reactions, with the idea that drug sensitizers share common mechanisms of cell activation. Cells were exposed to drugs associated with systemic hypersensitivity reactions (streptozotocin, sulfamethoxazole, neomycin, probenecid, clonidine, procainamide, ofloxacin, methyl salicylate), while metformin was used as negative drug. Differently to chemicals, drugs tested were well tolerated, except clonidine and probenecid, with no signs of cytotoxicity up to 1-2mg/ml. THP-1 activation assay was adjusted, and conditions, that allow identification of all sensitizing drugs tested, were established. Next, using streptozotocin and selective inhibitors of PKC-ß and p38 MAPK, two pathways involved in chemical allergen-induced cell activation, we tested the hypothesis that similar pathways were also involved in drug-induced IL-8 production and CD86 upregulation. Results indicated that drugs and chemical allergens share similar activation pathways. Finally, we made a structure-activity hypothesis related to hypersensitivity reactions, trying to individuate structural requisite that can be involved in immune mediated adverse reactions.