Kinetics of Different Blood Biomarkers during Polymyxin-B Extracorporeal Hemoperfusion in Abdominal Sepsis.

INTRODUCTION: Comparison of the marker kinetics procalcitonin, presepsin, and endotoxin during extracorporeal hemoperfusion with polymyxin-B adsorbing cartridge (PMX-HA) has never been described in abdominal sepsis. We aimed to compare the trend of three biomarkers in septic post-surgical abdominal patients in intensive care unit (ICU) treated with PMX-HA and their prognostic value. METHODS: Ninety abdominal post-surgical patients were enrolled into different groups according to the evidence of postoperative sepsis or not. Non-septic patients admitted in the surgical ward were included in C group (control group). ICU septic shock patients with endotoxin levels <0.6 EAA receiving conventional therapy were addressed in S group and those with endotoxin levels ≥0.6 EAA receiving treatment with PMX-HA, besides conventional therapy, were included in SPB group. Presepsin, procalcitonin, endotoxin and other clinical data were recorded at 24 h (T0), 72 h (T1) and 7 days (T2) after surgery. Clinical follow-up was performed on day 30. RESULTS: SPB group showed reduced levels of the three biomarkers on T2 versus T0 (p < 0.001); presepsin, procalcitonin and endotoxin levels decreased, respectively, by 25%, 11%, and 2% on T1 versus T0, and 40%, 41%, and 26% on T2 versus T0. All patients in C group, 73% of patients in SPB group versus 37% of patients in S group survived at follow-up. Moreover, procalcitonin had the highest predictive value for mortality at 30 days, followed by presepsin. CONCLUSION: The present study showed the reliability of presepsin in monitoring PMX-HA treatment in septic shock patients. Procalcitonin showed better predicting power for the mortality riSsk.

Electrical Impedance Tomography during Abdominal Laparoscopic Surgery: A Physiological Pilot Study.

BACKGROUND: Both general anesthesia and pneumoperitoneum insufflation during abdominal laparoscopic surgery can lead to atelectasis and impairment in oxygenation. Setting an appropriate level of external PEEP could reduce the occurrence of atelectasis and induce an improvement in gas exchange. However, in clinical practice, it is common to use a fixed PEEP level (i.e., 5 cmH2O), irrespective of the dynamic respiratory mechanics. We hypothesized setting a PEEP level guided by EIT in order to obtain an improvement in oxygenation and respiratory system compliance in lung-healthy patients than can benefit a personalized approach. METHODS: Twelve consecutive patients scheduled for abdominal laparoscopic surgery were enrolled in this prospective study. The EIT Timpel Enlight 1800 was applied to each patient and a dedicated pneumotachograph and a spirometer flow sensor, integrated with EIT, constantly recorded respiratory mechanics. Gas exchange, respiratory mechanics and hemodynamics were recorded at five time points: T0, baseline; T1, after induction; T2, after pneumoperitoneum insufflation; T3, after a recruitment maneuver; and T4, at the end of surgery after desufflation. RESULTS: A titrated mean PEEP of 8 cmH2O applied after a recruitment maneuver was successfully associated with the "best" compliance (58.4 ± 5.43 mL/cmH2O), with a low percentage of collapse (10%), an acceptable level of hyperdistention (0.02%). Pneumoperitoneum insufflation worsened respiratory system compliance, plateau pressure, and driving pressure, which significantly improved after the application of the recruitment maneuver and appropriate PEEP. PaO2 increased from 78.1 ± 9.49 mmHg at T0 to 188 ± 66.7 mmHg at T4 (p < 0.01). Other respiratory parameters remained stable after abdominal desufflation. Hemodynamic parameters remained unchanged throughout the study. CONCLUSIONS: EIT, used as a non-invasive intra-operative monitor, enables the rapid assessment of lung volume and regional ventilation changes in patients undergoing laparoscopic surgery and helps to identify the "optimal" PEEP level in the operating theatre, improving ventilation strategies.

High-Flow Oxygen Therapy in the Perioperative Setting and Procedural Sedation: A Review of Current Evidence.

High-flow oxygen therapy (HFOT) is a respiratory support system, through which high flows of humidified and heated gas are delivered to hypoxemic patients. Several mechanisms explain how HFOT improves arterial blood gases and enhances patients' comfort. Some mechanisms are well understood, but others are still unclear and under investigation. HFOT is an interesting oxygen-delivery modality in perioperative medicine that has many clinical applications in the intensive care unit (ICU) and the operating room (OR). The purpose of this article was to review the literature for a comprehensive understanding of HFOT in the perioperative period, as well as its uses in procedural sedation. This review will focus on the HFOT definition, its physiological benefits, and their mechanisms, its clinical uses in anesthesia, and when it is contraindicated.

Role of aspirin, beta-blocker, statins, and heparin therapy in septic patients under mechanical ventilation: a narrative review.

Sepsis is the main cause of death among patients admitted to intensive care units. Management of sepsis includes fluid resuscitation, vasopressors, intravenous antimicrobials, source control, mechanical ventilation, and others. New insights into the potential benefits of non-antimicrobial drugs in sepsis have evolved based on the pathophysiology of the disease and the mechanism of action of some drugs, but the findings are still controversial. In this study, we aimed to evaluate the effect of beta-blockers, aspirin, statins, and heparin as adjunctive treatments in septic patients under mechanical ventilation with non-cardiovascular diseases and their effect on mortality. We searched PubMed with relevant keywords (beta-blockers, aspirin, statins, or heparin, and critically ill or sepsis) for the last 10 years and some personal collection of relevant articles, and then we assessed studies according to prespecified inclusion and exclusion criteria. Our results show that beta-blockers, aspirin, and heparin may have promising feedback on reducing mortality. However, new well-controlled, randomized, multicenter studies are needed to confirm that, and multiple issues regarding their usage need to be addressed. On the other hand, the feedback regarding the effectiveness of statins was not as strong as that of the other drugs studied, and we suggest that further research is needed to confirm these results.

Mucopenetration study of solid lipid nanoparticles containing magneto sensitive iron oxide.

In most chronic respiratory diseases, excessive viscous airway secretions oppose a formidable permeation barrier to drug delivery systems (DDSs), with a limit to their therapeutic efficacy for the targeting epithelium. Since mucopenetration of DDSs with slippery technology (i.e. PEGylation) has encountered a reduction in the presence of sticky and complex airway secretions, our aim was to evaluate the relevance of magnetic PEGylated Solid Lipid Nanoparticles (mSLNs) for pulling them through chronic obstructive pulmonary disease (COPD) airway secretions. Thus, COPD sputum from outpatient clinic, respiratory secretions aspirated from high (HI) and low (LO) airways of COPD patients in acute respiratory insufficiency, and porcine gastric mucus (PGM) were investigated for their permeability to mSLN particles under a magnetic field. Rheological tests and mSLN adhesion to airway epithelial cells (AECs) were also investigated. The results of mucopenetration show that mSLNs are permeable both in COPD sputum and in PGM, while HI and LO secretions are always impervious. Parallel rheological results show a different elastic property, which can be associated with different mucus mesostructures. Finally, adhesion tests confirm the role of the magnetic field in improving the interaction of SLNs with AECs. Overall, our results reveal that mesostructure is of paramount importance in determining the mucopenetration of magnetic SLNs.

Immunological effects of glutamine supplementation in polytrauma patients in intensive care unit.

BACKGROUND: In polytrauma intensive care unit (ICU) patients, glutamine (GLN) becomes a "conditionally essential" amino acid; its role has been extensively studied in numerous clinical trials but their results are inconclusive. We evaluated the IgA-mediated humoral immunity after GLN supplementation in polytrauma ICU patients. METHODS: All consecutive patients with polytrauma who required mechanical ventilation and enteral nutrition (EN) provided within 24 h since the admission in ICU at the University Hospital of Foggia from September 2016 to February 2017 were included. Thereafter, two groups were identified: patients treated by conventional EN (25 kcal/kg/die) and patients who have received conventional EN enriched with 50 mg/kg/ideal body weight of alanyl-GLN 20% intravenously. We analysed the plasmatic concentration of IgA, CD3+/CD4+ T helper lymphocytes, CD3+/CD8+ T suppressor lymphocytes, CD3+/CD19+ B lymphocytes, IL-4 and IL-2 at admission and at 4 and 8 days. RESULTS: We identified 30 patients, with 15 subjects per group. IgA levels increased significantly in GLN vs the control group at T0, T4 and T8. CD3+/CD4+ T helper lymphocyte and CD3+/CD8+ T suppressor lymphocyte levels significantly increased in GLN vs the control group at T4 and T8. CD3+/CD19+ B lymphocyte levels increased significantly in GLN vs the control group only at T8. IL-2 and IL-4 levels showed no significant differences when comparing GLN with the control group. CONCLUSIONS: Our study showed that there was an improvement in humoral and cell-mediated immunity with GLN supplementation in polytrauma ICU patients using recommended doses.

Machine learning and predictive models: 2 years of Sars-CoV-2 pandemic in a single-center retrospective analysis.

BACKGROUND: Since January 2020, coronavirus disease 19 (COVID-19) has rapidly spread all over the world. An early assessment of illness severity is crucial for the stratification of patients in order to address them to the right intensity path of care. We performed an analysis on a large cohort of COVID-19 patients (n=581) hospitalized between March 2020 and May 2021 in our intensive care unit (ICU) at Policlinico Riuniti di Foggia hospital. Through an integration of the scores, demographic data, clinical history, laboratory findings, respiratory parameters, a correlation analysis, and the use of machine learning our study aimed to develop a model to predict the main outcome. METHODS: We deemed eligible for analysis all adult patients (age >18 years old) admitted to our department. We excluded all the patients with an ICU length of stay inferior to 24 h and the ones that declined to participate in our data collection. We collected demographic data, medical history, D-dimers, NEWS2, and MEWS scores on ICU admission and on ED admission, PaO2/FiO2 ratio on ICU admission, and the respiratory support modalities before the orotracheal intubation and the intubation timing (early vs late with a 48-h hospital length of stay cutoff). We further collected the ICU and hospital lengths of stay expressed in days of hospitalization, hospital location (high dependency unit, HDU, ED), and length of stay before and after ICU admission; the in-hospital mortality; and the in-ICU mortality. We performed univariate, bivariate, and multivariate statistical analyses. RESULTS: SARS-CoV-2 mortality was positively correlated to age, length of stay in HDU, MEWS, and NEWS2 on ICU admission, D-dimer value on ICU admission, early orotracheal intubation, and late orotracheal intubation. We found a negative correlation between the PaO2/FiO2 ratio on ICU admission and NIV. No significant correlations with sex, obesity, arterial hypertension, chronic obstructive pulmonary disease, chronic kidney disease, cardiovascular disease, diabetes mellitus, dyslipidemia, and neither MEWS nor NEWS on ED admission were observed. Considering all the pre-ICU variables, none of the machine learning algorithms performed well in developing a prediction model accurate enough to predict the outcome although a secondary multivariate analysis focused on the ventilation modalities and the main outcome confirmed how the choice of the right ventilatory support with the right timing is crucial. CONCLUSION: In our cohort of COVID patients, the choice of the right ventilatory support at the right time has been crucial, severity scores, and clinical judgment gave support in identifying patients at risk of developing a severe disease, comorbidities showed a lower weight than expected considering the main outcome, and machine learning method integration could be a fundamental statistical tool in the comprehensive evaluation of such complex diseases.

A Lower Global Lung Ultrasound Score Is Associated with Higher Likelihood of Successful Extubation in Invasively Ventilated COVID-19 Patients.

Lung ultrasound (LUS) can be used to assess loss of aeration, which is associated with outcome in patients with coronavirus disease 2019 (COVID-19) presenting to the emergency department. We hypothesized that LUS scores are associated with outcome in critically ill COVID-19 patients receiving invasive ventilation. This retrospective international multicenter study evaluated patients with COVID-19-related acute respiratory distress syndrome (ARDS) with at least one LUS study within 5 days after invasive mechanical ventilation initiation. The global LUS score was calculated by summing the 12 regional scores (range 0-36). Pleural line abnormalities and subpleural consolidations were also scored. The outcomes were successful liberation from the ventilator and intensive care mortality within 28 days, analyzed with multistate, competing risk proportional hazard models. One hundred thirty-seven patients with COVID-19-related ARDS were included in our study. The global LUS score was associated with successful liberation from mechanical ventilation (hazard ratio [HR]: 0.91 95% confidence interval [CI] 0.87-0.96; P = 0.0007) independently of the ARDS severity, but not with 28 days mortality (HR: 1.03; 95% CI 0.97-1.08; P = 0.36). Subpleural consolidation and pleural line abnormalities did not add to the prognostic value of the global LUS score. Examinations within 24 hours of intubation showed no prognostic value. To conclude, a lower global LUS score 24 hours after invasive ventilation initiation is associated with increased probability of liberation from the mechanical ventilator COVID-19 ARDS patients, independently of the ARDS severity.

A Pilot Study on Electrical Impedance Tomography During CPAP Trial in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia: The Bright Side of Non-invasive Ventilation.

Background: Different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia phenotypes were described that match with different lung compliance and level of oxygenation, thus requiring a personalized ventilator setting. The burden of so many patients and the lack of intensive care unit (ICU) beds often force physicians to choose non-invasive ventilation (NIV) as the first approach, even if no consent has still been reached to discriminate whether it is safer to choose straightforward intubation, paralysis, and protective ventilation. Under such conditions, electrical impedance tomography (EIT), a non-invasive bedside tool to monitor lung ventilation and perfusion defects, could be useful to assess the response of patients to NIV and choose rapidly the right ventilatory strategy. Objective: The rationale behind this study is that derecruitment is a more efficient measure of positive end expiratory pressure (PEEP)-dependency of patients than recruitment. We hypothesized that patients who derecruit significantly when PEEP is reduced are the ones that do not need early intubation while small end-expiratory lung volume (ΔEELV) variations after a single step of PEEP de-escalation could be predictive of NIV failure. Materials and Methods: Consecutive patients admitted to ICU with confirmed SARS-CoV-2 pneumonia ventilated in NIV were enrolled. Exclusion criteria were former intubation or NIV lasting > 72 h. A trial of continuos positive airway pressure (CPAP) 12 was applied in every patient for at least 15 min, followed by the second period of CPAP 6, either in the supine or prone position. Besides standard monitoring, ventilation of patients was assessed by EIT, and end-expiratory lung impedance (ΔEELI) (%) was calculated as the difference in EELI between CPAP12 and CPAP6. Tidal volume (Vt), Ve, respiratory rate (RR), and FiO2 were recorded, and ABGs were measured. Data were analyzed offline using the dedicated software. The decision to intubate or continue NIV was in charge of treating physicians, independently from study results. Outcomes of patients in terms of intubation rate and ICU mortality were recorded. Results: We enrolled 10 male patients, with a mean age of 67 years. Six patients (60%) were successfully treated by NIV until ICU discharge (Group S), and four patients failed NIV and were intubated and switched to MV (Group F). All these patients died in ICU. During the supine CPAP decremental trial, all patients experienced an increase in RR and Ve. ΔEELI was < 40% in Group F and > 50% in Group S. In the prone trial, ΔEELI was > 50% in all patients, while RR decreased in Group S and remained unchanged in Group F. Conclusion: ΔEELI < 40% after a single PEEP de-escalation step in supine position seems to be a good predictor of poor recruitment and CPAP failure.

Management of Intraoperative Mechanical Ventilation to Prevent Postoperative Complications after General Anesthesia: A Narrative Review.

Mechanical ventilation (MV) is still necessary in many surgical procedures; nonetheless, intraoperative MV is not free from harmful effects. Protective ventilation strategies, which include the combination of low tidal volume and adequate positive end expiratory pressure (PEEP) levels, are usually adopted to minimize the ventilation-induced lung injury and to avoid post-operative pulmonary complications (PPCs). Even so, volutrauma and atelectrauma may co-exist at different levels of tidal volume and PEEP, and therefore, the physiological response to the MV settings should be monitored in each patient. A personalized perioperative approach is gaining relevance in the field of intraoperative MV; in particular, many efforts have been made to individualize PEEP, giving more emphasis on physiological and functional status to the whole body. In this review, we summarized the latest findings about the optimization of PEEP and intraoperative MV in different surgical settings. Starting from a physiological point of view, we described how to approach the individualized MV and monitor the effects of MV on lung function.

Use of low-molecular weight heparin, transfusion and mortality in COVID-19 patients not requiring ventilation.

It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation. From the initial cohort of 422 patients, 264 were enrolled. Most (n = 156, 87.7%) received standard LMWH prophylaxis during hospitalization, with no significant difference between medical wards and Intensive Care Unit (ICU). Major or not major but clinically relevant hemorrhages were recorded in 13 (4.9%) patients: twelve in those taking prophylactic LMWH and one in a patient taking oral anticoagulants (p: n.s.). Thirty-nine patients (14.8%) with median age 75 years. were transfused. Hemoglobin (Hb) at admission was significantly lower in transfused patients and Hb at admission inversely correlated with the number of red blood cells units transfused (p < 0.001). In-hospital mortality occurred in 76 (28.8%) patients, 46 (24.3%) of whom admitted to medical wards. Furthermore, Hb levels at admittance were significantly lower in fatalities (g/dl 12.3; IQR 2.4 vs. 13.3; IQR 2.8; Mann-Whitney U-test; p = 0.001). After the exclusion of patients treated by LMWH intermediate or therapeutic doses (n = 32), the logistic regression showed that prophylaxis significantly and independently reduced mortality (OR 0.31, 95% CI 0.13-0.85). Present data show that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH.

SARS-CoV-2 pneumonia succesfully treated with cpap and cycles of tripod position: a case report.

BACKGROUND: Pneumonia induced by 2019 Coronavirus (COVID-19) is characterized by hypoxemic respiratory failure that may present with a broad spectrum of clinical phenotypes. At the beginning, patients may have normal lung compliance and be responsive to noninvasive ventilatory support, such as CPAP. However, the transition to more severe respiratory failure - Severe Acute Respiratory Syndrome (SARS-CoV-2), necessitating invasive ventilation is often abrupt and characterized by a severe V/Q mismatch that require cycles of prone positioning. The aim of this case is to report the effect on gas exchange, respiratory mechanics and hemodynamics of tripod (or orthopneic sitting position) used as an alternative to prone position in a patient with mild SARS-CoV-2 pneumonia ventilated with helmet CPAP. CASE PRESENTATION: A 77-year-old awake and collaborating male patient with mild SARS-CoV-2 pneumonia and ventilated with Helmet CPAP, showed sudden worsening of gas exchange without dyspnea. After an unsuccessful attempt of prone positioning, we alternated three-hours cycles of semi-recumbent and tripod position, still keeping him in CPAP. Arterial blood gases (PaO2/FiO2, PaO2, SaO2, PaCO2 and A/a gradient), respiratory (VE, VT, RR) and hemodynamic parameters (HR, MAP) were collected in the supine and tripod position. Cycles of tripod position were continued for 3 days. The patient had a clinically important improvement in arterial blood gases and respiratory parameters, with stable hemodynamic and was successfully weaned and discharged to ward 10 days after pneumonia onset. CONCLUSIONS: Tripod position during Helmet CPAP can be applied safely in patients with mild SARS-CoV-2 pneumonia, with improvement of oxygenation and V/Q matching, thus reducing the need for intubation.

Mortality and Transfusion Requirements in COVID-19 Hospitalized Italian Patients According to Severity of the Disease.

There is paucity of data on the transfusion need and its impact on the overall mortality in patients with COVID-19. We explored mortality in hospitalized patients with COVID-19 who required transfusions. Information on clinical variables and in-hospital mortality were obtained from medical records of 422 patients admitted to medical wards or the Intensive Care Unit (ICU). In-hospital mortality occurred in 147 (34.8%) patients, 94 (63.9%) of whom were admitted to the ICU. The median fatalities age was 77 years (IQR 14). Overall, 100 patients (60 males) received transfusion during hospitalization. The overall mortality was significantly and independently associated with age, ICU admission, Chronic Kidney Disease (CKD), and the number of transfused Red Blood Cell (RBC) units. Specifically, CKD was associated with mortality in patients admitted to medical wards, whereas the number of transfused RBC units predicted mortality in those admitted to the ICU. Transfusion strongly interacted with the admission to ICU (OR: 9.9; 95% CI: 2.5-40.0). In patients with COVID-19, age is one of the strongest risk factors in predicting mortality independently of the disease's severity. CKD confers a higher risk of mortality in patients admitted to medical wards. In those admitted to the ICU, the more RBC units are transfused, the more mortality increases.

Effectiveness of Combined Strategies for the Prevention of Hypothermia Measured by Noninvasive Zero-Heat Flux Thermometer During Cesarean Section.

Background: Perioperative hypothermia (body temperature <36°C) is a common complication of anesthesia increasing the risk for maternal cardiovascular events and coagulative disorders, and can also influence neonatal health. The aim of our work was to evaluate the impact of combined warming strategies on maternal core temperature, measured with the SpotOn. We hypothesized that combined modalities of active warming prevent hypothermia in pregnant women undergoing cesarean delivery with spinal anesthesia. Methods: Seventy-eight pregnant women were randomly allocated into three study groups receiving warmed IV fluids and forced-air warming (AW), warmed IV fluids (WF), or no warming (NW). Noninvasive core temperature device (SpotOn) measured maternal core temperature intraoperatively and for 30 min after surgery. Maternal mean arterial pressure, incidence of shivering, thermal comfort and newborn's APGAR, axillary temperature, weight, and blood gas analysis were also recorded. Results: Incidence of hypothermia was of 0% in AW, 4% in WF, and 47% in NW. Core temperature in AW was constantly higher than WF and NW groups. Incidence of shivering in perioperative time was significantly lower in AW and WF groups compared with the NW group (p < 0.04). Thermal comfort was higher in both AW and WF groups compared with NW group (p = 0.02 and p = 0.008, respectively). There were no significant differences among groups for the other evaluated parameters. Conclusion: Combined modalities of active warming are effective in preventing perioperative hypothermia. The routine uses of combined AW are suggested in the setting of cesarean delivery.

Circulating Skeletal Troponin During Weaning From Mechanical Ventilation and Their Association to Diaphragmatic Function: A Pilot Study.

Background: Patients with acute respiratory failure (ARF) may need mechanical ventilation (MV), which can lead to diaphragmatic dysfunction and muscle wasting, thus making difficult the weaning from the ventilator. Currently, there are no biomarkers specific for respiratory muscle and their function can only be assessed trough ultrasound or other invasive methods. Previously, the fast and slow isoform of the skeletal troponin I (fsTnI and ssTnI, respectively) have shown to be specific markers of muscle damage in healthy volunteers. We aimed therefore at describing the trend of skeletal troponin in mixed population of ICU patients undergoing weaning from mechanical ventilation and compared the value of fsTnI and ssTnI with diaphragmatic ultrasound derived parameters. Methods: In this prospective observational study we enrolled consecutive patients recovering from acute hypoxemic respiratory failure (AHRF) within 24 h from the start of weaning. Every day an arterial blood sample was collected to measure fsTnI, ssTnI, and global markers of muscle damage, such as ALT, AST, and CPK. Moreover, thickening fraction (TF) and diaphragmatic displacement (DE) were assessed by diaphragmatic ultrasound. The trend of fsTnI and ssTnI was evaluated during the first 3 days of weaning. Results: We enrolled 62 consecutive patients in the study, with a mean age of 67 ± 13 years and 43 of them (69%) were male. We did not find significant variations in the ssTnI trend (p = 0.623), but fsTnI significantly decreased over time by 30% from Day 1 to Day 2 and by 20% from Day 2 to Day 3 (p < 0.05). There was a significant interaction effect between baseline ssTnI and DE [F (2) = 4.396, p = 0.015], with high basal levels of ssTnI being associated to a higher decrease in DE. On the contrary, the high basal levels of fsTnI at day 1 were characterized by significant higher DE at each time point. Conclusions: Skeletal muscle proteins have a distinctive pattern of variation during weaning from mechanical ventilation. At day 1, a high basal value of ssTnI were associated to a higher decrease over time of diaphragmatic function while high values of fsTnI were associated to a higher displacement at each time point.