Impact of CT Scan Phenotypes in Clinical Manifestations, Management and Outcomes of Hospitalised Patients with COVID-19

COVID-19 is such a heterogeneous disease that a one-size-fits-all approach is not recommended, so the management of patients has been based on their clinical and laboratory characteristics. We therefore investigated possible homogeneous groups presenting similar features of lung involvement based on chest CT and laboratory results. We designed a study to identify a possible correlation between CT scan phenotypes, laboratory exams, and clinical outcomes. We retrospectively analysed 120 adult patients with COVID-19 5who underwent chest CT scan during hospitalisation, between March and December 2020 at our COVID-19 Hospital in two different wards: Respiratory Intensive Care Unit (RICU) and Intensive Care Unit (ICU). The analysis of CT scans resulted in the identification of three radiological phenotypes by two blinded pulmonologists (Cohen's κ = 0.9 for Phenotype 1, 0.9 for Phenotype 2 and 0.89 for Phenotype 3), in accordance with what previously described by Robba et al. “Phenotype 1” (PH1) is characterised by modest interstitial oedema with presentation on chest CT of diffuse ground glass opacities (GGO). “Phenotype 2” (PH2) shows predominant consolidation at lung lobes. “Phenotype 3” (PH3) shows a typical CT pattern of moderate-to-severe ARDS, with alveolar oedema. Based on our results, we could hypothesise that phenotype 2 shows a different trend from all the others and would seem to be more related to a coagulopathy, although we cannot exclude the hypothesis that one phenotype evolves from the other. Further studies might focus on the predictive role of D-dimer, and its cut-offs, in delineating the PH2 patients, that could require an early CT scan to avoid excessive pressure support and finally prevent VILI. To further understand the exact basis of the different CT scan phenotype, a longer longitudinal analysis of clinical and laboratory features (e.g., timing of weaning, pressures and FiO2 delivered) in each phenotype and a comparison among them is needed

Patient-Ventilator Asynchronies: Clinical Implications and Practical Solutions

Mechanical ventilation is a supportive treatment commonly applied in critically ill patients. Whenever the patient is spontaneously breathing, the pressure applied to the respiratory system depends on the sum of the pressure generated by the respiratory muscles and the pressure generated by the ventilator. Patient-ventilator interaction is of utmost importance in spontaneously breathing patients, and thus the ventilator should be able to adapt to patient's changes in ventilatory demand and respiratory mechanics. Nevertheless, a lack of coordination between patient and ventilator due to a mismatch between neural and ventilator timing throughout the respiratory cycle may make weaning difficult and lead to prolonged mechanical ventilation. Therefore, appropriate monitoring of asynchronies is mandatory to improve the applied strategies and thus improve patient-ventilator interaction. We conducted a literature review regarding patient-ventilator interaction with a focus on the different kinds of inspiratory and expiratory asynchronies, their monitoring, clinical implications, possible prevention, and treatment. We believe that monitoring patient-ventilator interaction is mandatory in spontaneously breathing patients to understand, by using the available technologies, the type of asynchrony and consequently improve the adaptation of the ventilator to the patient's needs. Asynchronies are relatively frequent during mechanical ventilation in critically ill patients, and they are associated with poor outcomes. This review summarizes the different types of asynchronies and their mechanisms, consequences, and potential management. The development and understanding of monitoring tools are necessary to allow a better appraisal of this area, which may lead to better outcomes for patients

Circulating stem cells, HIF-1, and SDF-1 in septic abdominal surgical patients: randomized controlled study protocol

Abstract Background Sepsis caused by complicated intra-abdominal infection is associated with high mortality. Loss of endothelial barrier integrity, inflammation, and impaired cellular oxygen have been shown to be primary contributors to sepsis. To date, little is known regarding the pathway for the mobilization of endothelial progenitor cells (EPCs) from the bone marrow in sepsis whereas stromal-cell-derived factor 1a (SDF-1a) and hypoxia inducible factor 1 (HIF-1) seem to have a role in the EPC response to hypoxic microenvironments. The aims of the study are: (a) to determine the time course of the levels of circulating EPCs (CD133/CD34), SDF-1a, and HIF-1 in septic patients undergoing major abdominal surgery (group S), (b) to investigate the relationship between CD133/CD34, HIF-1, and SDF-1a, and (c) to investigate the relationship of these factors with the outcome of group S patients treated with standard conventional therapy alone (CT) or with the addition of extracorporeal hemoperfusion therapy (HCT). Methods/design Patients undergoing major abdominal surgery will be allocated into groups: postoperative non-septic patients in an emergency surgical ward (group C) and postoperative septic patients in an intensive care unit (group S). The latter will be randomized to receive CT alone (S1) or with HCT (S2). Healthy volunteers (group H) will be recruited at University Hospital Foggia. Peripheral blood (PB) samples will be collected preoperatively (T0), at 24 h (T1), 72 h (T2), 7 (T3), and 10 (T4) postoperative days in groups S and C, and at T0 in group H. The CD34/133 cells and HIF-1 counts will be determined by flow cytometer analysis. The concentration of SDF-1a in plasma will be calculated by enzyme-linked immunosorbent assay analysis (ELISA). Discussion This prospective randomized clinical trial is designed to investigate circulating stem cells, levels of HIF-1 and SDF-1a, and their interrelationship in septic postoperative abdominal surgical patients treated with CT alone or with HCT. The rationale is that an integrated understanding of the role of hypoxia-related factors and EPCs in PB of septic patients could indicate which molecular processes need to be regulated to recover the innate immunity homeostasis. Understanding the function of EPCs in sepsis may provide innovative diagnostic and therapeutic approaches to improve the prognosis of this syndrome. Trial registration ClinicalTrials.gov: NCT02589535. Registered on 28 October 2015

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

Reference values for coagulation assessment in full-term newborns

Most data in the literature report reduced coagulation activities in the first few days of life with respect to adults and the effects of these differences must be considered when diagnosing and treating haemostatic disorders. Management of pediatric population is further complicated by the lack of age-related reference values and by unreliability of hemostatic tests currently used while an accurate interpretation of results are required to reduce the cases of inappropriate investigation. Thromboelastography (TEG®) is a point-of-care test that provides an efficient analysis of the dynamic viscoelastic properties of whole blood that may provide superior evaluation and management of coagulopathies in newborn. This study was designed to determine reference values for kaolin-activated TEG in full-term healthy newborn by taking small blood samples from the umbilical cord and facilitate accurate interpretation of neonatal TEG results

Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial)

INTRODUCTION: In patients with septic shock, low levels of circulating immunoglobulins are common and their kinetics appear to be related to clinical outcome. The pivotal role of immunoglobulins in the host immune response to infection suggests that additional therapy with polyclonal intravenous immunoglobulins may be a promising option in patients with septic shock. Immunoglobulin preparations enriched with the IgM component have largely been used in sepsis, mostly at standard dosages (250mg/kg per day), regardless of clinical severity and without any dose adjustment based on immunoglobulin serum titres or other biomarkers. We hypothesised that a personalised dose of IgM enriched preparation based on patient IgM titres and aimed to achieve a specific threshold of IgM titre is more effective in decreasing mortality than a standard dose.METHODS AND ANALYSIS: The study is designed as a multicentre, interventional, randomised, single-blinded, prospective, investigator sponsored, two-armed study. Patients with septic shock and IgM titres <60mg/dL will be randomly assigned to an IgM titre-based treatment or a standard treatment group in a ratio of 1:1. The study will involve 12 Italian intensive care units and 356 patients will be enrolled. Patients assigned to the IgM titre-based treatment will receive a personalised daily dose based on an IgM serum titre aimed at achieving serum titres above 100mg/dL up to discontinuation of vasoactive drugs or day 7 after enrolment. Patients assigned to the IgM standard treatment group will receive IgM enriched preparation daily for three consecutive days at the standard dose of 250mg/kg. The primary endpoint will be all-cause mortality at 28 days.ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committees of the coordinating centre (Comitato Etico dell'Area Vasta Emilia Nord) and collaborating centres. The results of the trial will be published within 12 months from the end of the study and the steering committee has the right to present them at public symposia and conferences.TRIAL REGISTRATION DETAILS: The trial protocol and information documents have received a favourable opinion from the Area Vasta Emilia Nord Ethical Committee on 12 September 2019. The trial protocol has been registered on EudraCT (2018-001613-33) on 18 April 2018 and on ClinicalTrials.gov (NCT04182737) on 2 December 2019

Patient-Ventilator Asynchronies: Clinical Implications and Practical Solutions

Mechanical ventilation is a supportive treatment commonly applied in critically ill patients. Whenever the patient is spontaneously breathing, the pressure applied to the respiratory system depends on the sum of the pressure generated by the respiratory muscles and the pressure generated by the ventilator. Patient-ventilator interaction is of utmost importance in spontaneously breathing patients, and thus the ventilator should be able to adapt to patient's changes in ventilatory demand and respiratory mechanics. Nevertheless, a lack of coordination between patient and ventilator due to a mismatch between neural and ventilator timing throughout the respiratory cycle may make weaning difficult and lead to prolonged mechanical ventilation. Therefore, appropriate monitoring of asynchronies is mandatory to improve the applied strategies and thus improve patient-ventilator interaction. We conducted a literature review regarding patient-ventilator interaction with a focus on the different kinds of inspiratory and expiratory asynchronies, their monitoring, clinical implications, possible prevention, and treatment. We believe that monitoring patient-ventilator interaction is mandatory in spontaneously breathing patients to understand, by using the available technologies, the type of asynchrony and consequently improve the adaptation of the ventilator to the patient's needs. Asynchronies are relatively frequent during mechanical ventilation in critically ill patients, and they are associated with poor outcomes. This review summarizes the different types of asynchronies and their mechanisms, consequences, and potential management. The development and understanding of monitoring tools are necessary to allow a better appraisal of this area, which may lead to better outcomes for patients

Peep titration based on the open lung approach during one lung ventilation in thoracic surgery: a physiological study

Abstract Background During thoracic surgery in lateral decubitus, one lung ventilation (OLV) may impair respiratory mechanics and gas exchange. We tested a strategy based on an open lung approach (OLA) consisting in lung recruitment immediately followed by a decremental positive-end expiratory pressure (PEEP) titration to the best respiratory system compliance (CRS) and separately quantified the elastic properties of the lung and the chest wall. Our hypothesis was that this approach would improve gas exchange. Further, we were interested in documenting the impact of the OLA on partitioned respiratory system mechanics. Methods In thirteen patients undergoing upper left lobectomy we studied lung and chest wall mechanics, transpulmonary pressure (PL), respiratory system and transpulmonary driving pressure (ΔPRS and ΔPL), gas exchange and hemodynamics at two time-points (a) during OLV at zero end-expiratory pressure (OLVpre-OLA) and (b) after the application of the open-lung strategy (OLVpost-OLA). Results The external PEEP selected through the OLA was 6 ± 0.8 cmH2O. As compared to OLVpre-OLA, the PaO2/FiO2 ratio went from 205 ± 73 to 313 ± 86 (p = .05) and CL increased from 56 ± 18 ml/cmH2O to 71 ± 12 ml/cmH2O (p = .0013), without changes in CCW. Both ΔPRS and ΔPL decreased from 9.2 ± 0.4 cmH2O to 6.8 ± 0.6 cmH2O and from 8.1 ± 0.5 cmH2O to 5.7 ± 0.5 cmH2O, (p = .001 and p = .015 vs OLVpre-OLA), respectively. Hemodynamic parameters remained stable throughout the study period. Conclusions In our patients, the OLA strategy performed during OLV improved oxygenation and increased CL and had no clinically significant hemodynamic effects. Although our study was not specifically designed to study ΔPRS and ΔPL, we observed a parallel reduction of both after the OLA. Trial registration TRN: ClinicalTrials.gov , NCT03435523 , retrospectively registered, Feb 14 2018