Use of an innovative cuff pressure control and subglottic secretions drainage system in COVID-19 ARDS patients undergoing pronation (preprint)

Anapnoguard endotracheal tubes and control unit were used in 15 patients with COVID-19 acute respiratory distress syndrome. Anapnoguard system provides suction, venting, rinsing of subglottic space and controls cuff pressure detecting air leakage through the cuff. Alpha-amylase and pepsin levels, as oropharyngeal and gastric microaspiration markers, were detected from 85 tracheal aspirates.Oropharyngeal microaspiration occurred in 47 cases (55%). Episodes of gastric microaspiration weren’t detected. There wasn’t correlation in enzyme levels between prone and supine positioning. Ventilator-associated pneumonia (VAP) rate was 40%. The use of the AG system provided effective Pcuff control and SS drainage. Nevertheless, the role of Anapnoguard system in VAP prevention is worthy to be further investigated.

One-Year Prospective Study of Occupational Health in the Intensivists of a COVID-19 Hub Hospital (preprint)

The COVID-19 pandemic has severely tested the physical and mental health of health care workers (HCWs). The various stages of the epidemic have posed different problems; consequently, only a prospective study can effectively describe the changes in the workers’ health. This repeated cross-sectional study is based on a one-year investigation (spring 2020 to spring 2021) of intensive care physicians in one of the two COVID-19 hub hospitals in Central Italy. Changes in their work activity due to the pandemic were studied anonymously together with their perception of organizational justice, occupational stress, sleep quality, anxiety, depression, burnout, job satisfaction, happiness, and intention to quit. In May-June 2021, one year after the baseline, doctors reported an increased workload, isolation at work and in social life, lack of time for physical activity and meditation and compassion fatigue. Stress was inversely associated with the perception of justice in safety procedures and directly correlated with work isolation. Occupational stress was significantly associated with anxiety, depression, burnout, dissatisfaction, and intention to quit. Procedural justice was significantly associated with happiness. Doctors believed vaccinations would help control the problem; however, this positive attitude had not yet resulted in improved mental health. Doctors reported high levels of distress (73%), sleep problems (28%), anxiety (25%), depression (64%). Interventions to correct the situation are urgently needed.

A Machine-learning Parsimonious Multivariable Predictive Model of Mortality Risk in Patients With Covid-19 (preprint)

BackgroundThe COVID-19 pandemic is impressively challenging the healthcare system. Several prognostic models have been validated but few of them are implemented in daily practice. The objective of the study was to validate a machine-learning risk prediction model using easy-to-obtain parameters, potentially available at home, to help identifying patients with COVID-19 who are at higher risk of death.MethodsThe training cohort included all patients admitted to Fondazione Policlinico Gemelli with COVID-19 from March 5, 2020 to November 5, 2020. Afterwards, the model was tested on all patients admitted to the same hospital with COVID-19 from November 6, 2020 to February 5 2021. The primary outcome was in-hospital mortality.The out-of-sample performance of the model was estimated from the training set in terms of Area under the Receiving Operator Curve (AUROC) and classification matrix statistics by averaging the results of 5-fold cross validation repeated 3-times and comparing the results with those obtained on the test set. An explanation analysis of the model, based on the SHapley Additive exPlanations (SHAP), is also presented. To assess the subsequent time evolution, the change in paO2/FiO2 (P/F) at 48 hours after the baseline measurement was plotted against its baseline value.ResultsAmong the 921 patients included in the training cohort, 120 died (13%). Variables selected for the model were age, platelet count, SpO2, blood urea nitrogen (BUN), hemoglobin, C-reactive protein, neutrophil count, and sodium. The results of the 5-fold cross-validation repeated 3-times gave AUROC of 0.87, and statistics of the classification matrix to the Youden index as follows: sensitivity 0.840, specificity 0.774, negative predictive value 0.971. Then, the model was tested on a new population (n=1463) in which the mortality rate was 22.6 %. The test model showed AUROC 0.818, sensitivity 0.813, specificity 0.650, negative predictive value 0.922. Considering the first quartile of the predicted risk score (low-risk score group), the mortality rate was 1.6%, 17.8% in the second and third quartile (high-risk score group) and 53.5% in the fourth quartile (very high-risk score group). The three risk score groups showed good discrimination for the P/F value at admission, and a positive correlation was found for the low-risk class to P/F at 48 hours after admission (adjusted R-squared= 0.48).ConclusionsWe developed a predictive model of death for people with SARS-CoV-2 infection by including only easy-to-obtain variables (abnormal blood count, BUN, C-reactive protein, sodium and lower SpO2). It demonstrated good accuracy and high power of discrimination. The simplicity of the model makes the risk prediction applicable for patients at home, in the Emergency Department, or during hospitalization.

Prolonged Stress Causes Depression in Frontline Workers Facing the COVID-19 Pandemic. A Repeated Cross-Sectional Study (preprint)

The Covid-19 pandemic has severely tested the mental health of frontline health care workers. A repeated cross-sectional study can provide information on how their mental health evolved during the various phases of the pandemic. The intensivists of a COVID-19 hub hospital in Rome were investigated with a baseline survey during the first wave of the pandemic in April 2020 and were contacted again in December 2020, during the second wave. 152 of the 205 eligible workers responded to an online questionnaire designed to measure procedural justice, occupational stress (effort/reward imbalance), sleep quality, anxiety, depression, burnout, job satisfaction, happiness, and turnover intention. Workers reported a further increase in workload and compassion fatigue, which had already risen during the first wave, and a marked reduction in the time devoted to meditation and mental activities. A low level of confidence in the adequacy of safety procedures and the need to work in isolation, together with an increased workload and lack of time for meditation were the most significant predictors of occupational stress in a stepwise linear regression model. Occupational stress was, in turn, a significant predictor of insomnia, anxiety, low job satisfaction, burnout, and intention to leave the hospital. The number of workers manifesting symptoms of depression increased significantly to exceed 60%. Action to prevent occupational risks and enhance individual resilience cannot be postponed.

Prone Position in Intubated, Mechanically Ventilated Patients with Coronavirus Disease-19. (preprint)

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 were 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 Responders if the PaO2/FiO2 ratio increased ≥ 20 mmHg 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 was observed. Seventy-eight % of patients were Responders to prone position. Non-Responders had a more severe respiratory failure and died more often in the ICU (65% vs. 38%, p=0.047).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

Comparative bench study evaluation of a modified snorkeling mask used during COVID-19 pandemia and standard interfaces for Non-Invasive Ventilation (preprint)

Background COVID-19 infection has put enormous pressure on the healthcare systems worldwide and especially on Intensive Care Units (ICUs). In this particular situation, a modified snorkeling mask into a mask for non-invasive continuous positive airway pressure (nCPAP) and non-invasive ventilation (NIV), with the help of 3D printers, has been proposed for clinical use. We designed a bench study to compare a Helmet (H), a Full face mask (RFF) and a modified full face snorkeling mask (MFF) for delivering nCPAP and NIV in pressure support mode (PSV).Methods A mannequin was connected to an active lung simulator. The inspiratory and expiratory variations in airways pressure observed with a high simulated effort (Pmus), were determined relative to the preset CPAP level. NIV was applied in PSV at two simulated respiratory rates and two cycling-off flow thresholds. During the bench study we measured the variables defining patient-ventilator interaction and performance.Results During nCPAP, the MFF presented significantly lower values of ΔPawi and ∆Pawe compared to the other interfaces tested (H and RFF). During NIV, the MFF demonstrated a better patient-ventilator interaction compared to RFF, as shown by significantly shorter Timepress and Delaytrexp (p < 0.01), but no significant differences were found in terms of Delaytrinsp and Timesync between the interfaces tested. At RR 20sim, the MFF presented the shorter ΔPtrigger (p < 0.01), moreover during all the conditions tested the MFF showed the longer PTP 200, 300 and 500 compared to RFF (p < 0.01). A major limitation of MFF is that during NIV with this interface it is possible to reach at maximum 18 cmH2O of peak inspiratory pressure. Over this pressure value, the presence of air leaks determined important asynchrony phenomena. For this reason, our test was limited to one pressure support and PEEP set (PS 10 cmH2O and PEEP 8 cmH2O).Conclusions The modified full face snorkeling mask can be used as an acceptable alternative to other interfaces for both nCPAP and NIV in emergency situations.

Comparative Bench Study Evaluation of a Modified Snorkeling Mask Used During COVID-19 Pandemia and Standard Interfaces for Non-invasive Ventilation. (preprint)

BackgroundCOVID-19 infection has put enormous pressure on the healthcare systems worldwide and especially on Intensive Care Units (ICUs). In this particular situation, a modified snorkeling mask into a mask for non-invasive continuous positive airway pressure (nCPAP) and non-invasive ventilation (NIV), with the help of 3D printers, has been proposed for clinical use. We designed a bench study to compare a Helmet (H), a Full face mask (RFF) and a modified full face snorkeling mask (MFF) for delivering nCPAP and NIV in pressure support mode (PSV).MethodsA mannequin was connected to an active lung simulator. The inspiratory and expiratory variations in airways pressure observed with a high simulated effort (Pmus), were determined relative to the preset CPAP level. NIV was applied in PSV at two simulated respiratory rates and two cycling-off flow thresholds. During the bench study we measured the variables defining patient-ventilator interaction and performance. ResultsDuring nCPAP, the MFF presented significantly lower values of ΔPawi and ∆Pawe compared to the other interfaces tested (H and RFF). During NIV, the MFF demonstrated a better patient-ventilator interaction compared to RFF, as shown by significantly shorter Timepress and Delaytrexp (p<0.01), but no significant differences were found in terms of Delaytrinsp and Timesync between the interfaces tested. At RR 20sim, the MFF presented the shorter ΔPtrigger (p<0.01), moreover during all the conditions tested the MFF showed the longer PTP 200, 300 and 500 compared to RFF (p<0.01). A major limitation of MFF is that during NIV with this interface it is possible to reach at maximum 18 cmH2O of peak inspiratory pressure. Over this pressure value, the presence of air leaks determined important asynchrony phenomena. For this reason, our test was limited to one pressure support and PEEP set (PS 10 cmH2O and PEEP 8 cmH2O).ConclusionsThe modified full face snorkeling mask can be used as an acceptable alternative to other interfaces for both nCPAP and NIV in emergency situations.

Comparative Bench Study Evaluation of a Modified Snorkeling Mask Used During COVID-19 Pandemia and Standard Interfaces for Non-Invasive Ventilation. (preprint)

BackgroundCOVID-19 infection has put enormous pressure on the healthcare systems worldwide and especially on Intensive Care Units (ICUs). In this particular situation, a modified snorkeling mask into a mask for non-invasive continuous positive airway pressure (nCPAP) and non-invasive ventilation (NIV), with the help of 3D printers, has been proposed for clinical use. We designed a bench study to compare a Helmet (H), a Full face mask (RFF) and a modified full face snorkeling mask (MFF) for delivering nCPAP and NIV in pressure support mode (PSV).MethodsA mannequin was connected to an active lung simulator. The inspiratory and expiratory variations in airways pressure observed with a high simulated effort (Pmus), were determined relative to the preset CPAP level. NIV was applied in PSV at two simulated respiratory rates and two cycling-off flow thresholds. During the bench study we measured the variables defining patient-ventilator interaction and performance. ResultsDuring nCPAP, the MFF presented significantly lower values of ΔPawi and ∆Pawe compared to the other interfaces tested (H and RFF). During NIV, the MFF demonstrated a better patient-ventilator interaction compared to RFF, as shown by significantly shorter Timepress and Delaytrexp (p<0.01), but no significant differences were found in terms of Delaytrinsp and Timesync between the interfaces tested. At RR 20sim, the MFF presented the shorter ΔPtrigger (p<0.01), moreover during all the conditions tested the MFF showed the longer PTP 200, 300 and 500 compared to RFF (p<0.01). A major limitation of MFF is that during NIV with this interface it is possible to reach at maximum 18 cmH2O of peak inspiratory pressure. Over this pressure value, the presence of air leaks determined important asynchrony phenomena. For this reason, our test was limited to one pressure support and PEEP set (PS 10 cmH2O and PEEP 8 cmH2O).ConclusionsThe modified full face snorkeling mask can be used as an acceptable alternative to other interfaces for both nCPAP and NIV in emergency situations.

Household Disinfectant Exposure During the COVID-19 Pandemic: A Retrospective Study of the Data from an Italian Poison Control Center (preprint)

Background: Since the beginning of the COVID-19 pandemic it has been recommended that chemical disinfectants are used to protect surfaces. This study aimed to determine whether the number of exposure calls related to household disinfectants (HD) received between January 30, 2020 to May 18, 2020 varied from the same time period in the previous year.Method: A retrospective review of the poison control centers database from the Fondazione Universitario Policlinico Agostino Gemelli IRCCS was conducted. Calls from Italian citizens, hospitals, and general practitioners received during the same time period in 2019 and 2020 were compared.Findings: The center received 1972 exposure calls during the study period. A 5% increase in calls regarding exposure to HDs was noted from 2019 to 2020 (9·8% to 15·2%, p<0.001). The majority of enquiries regarded bleach-containing products, hand sanitizers, ethanol, and hydrogen peroxide. Most calls were received from patients in their homes (n, 259; prevalence, 86%; increase, 107%) and concerned accidental exposure (n, 280; prevalence, 93%; increase, 76%), while cases of intentional exposure decreased (n, 14; prevalence, 5%; decrease, 33%). The main route of exposure was ingestion (n, 170; prevalence, 57%; increase, 45%), but the highest increase was observed in inhalation cases (n, 82; prevalence, 27%; increase, 122%).Interpretation: As the incidence of enquiries regarding products that can represent an important health hazard, when improperly used, increased in 2020 suggests that the COVID-19 public health messaging on the proper use of HDs should be improved.Funding Statement: This work has been supported by Fondi di Ateneo, Linea D1 – Università Cattolica del Sacro Cuore, Grant n. R4124500772 (Recipient: Antonio Oliva). Declaration of Interests: There are no conflicts of interest to declare.Ethics Approval Statement: The authors state that no approval from ethics committee was required.

Noninvasive Ventilatory Support As First-Line Treatment For COVID-19 Critically Ill Patients With Acute Hypoxemic Respiratory Failure (preprint)

Background: Although widely applied, noninvasive ventilatory support (NIVS) efficacy in COVID-19 disease is unknown. Early identification of treatment failure is warranted to avoid delays in endotracheal intubation and protective ventilation. We conducted a study to determine the rate of and factors associated to NIVS failure in critically ill patients with COVID-19 disease, and to compare NIVS failure rate in COVID-19 patients to that of a matched cohort with hypoxemic respiratory failure of other origins. Methods: : All consecutive patients receiving first-line treatment NIVS for hypoxemic respiratory failure due to COVID-19 in the ICU of a University Hospital in Italy up to April 20 th , 2020, were studied: laboratory data were collected on arrival, 28-day outcome was recorded. After one-to-one propensity score matching based on simplified acute physiology (SAPS) II score, age, PaO 2 /FiO 2 and PaCO 2 at arrival, NIVS failure rate in COVID-19 patients was compared to a previously published cohort who received NIVS during hypoxemic respiratory failure from other causes. Results: : Eighty-five patients received first-line treatment with NIVS, mainly with helmet noninvasive ventilation and high-flow nasal cannula. Fifty-two patients (61%) needed endotracheal intubation. Independent predictors of NIVS failure were SAPSII score (adjusted hazard ratio 1.039 [1.018-1.061], <0.001), and serum lactate de-hydrogenase at enrolment (adjusted hazard ratio: 1.002 [1.000-1.004], p=0.013): 88% of patients with SAPSII≥33 and serum lactate de-hydrogenase≥405 Units/Liter needed endotracheal intubation vs. 32% of patients with SAPS<33 and lactate de-hydrogenase<405 Units/Liter. In the propensity-matched cohorts (108 patients), COVID-19 patients showed higher risk of NIVS failure than other causes of hypoxemic respiratory failure (59% vs. 35%, p=0.02), with an adjusted hazard ratio of 2 (CI95% [1.1-3.6], p=0.01). Conclusions: : COVID-19 patients receiving first-line NIVS are burdened by high risk of needing endotracheal intubation: this appears greater than that of patients affected by hypoxemic respiratory failure of other origins. In order to not delay endotracheal intubation, if logistically sustainable, NIVS use in the intensive care unit should be avoided in severe patients (SAPSII score≥33) with serum lactate de-hydrogenase≥405 Units/Liter.

Sarilumab use in severe SARS-CoV-2 pneumonia (preprint)

Importance: Interleukin-6 signal blockade has shown preliminary beneficial effects in treating aberrant host inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Objective: to describe the effect of off-label intravenous use of Sarilumab in patients with severe SARS-CoV-2-related pneumonia. Design: Observational clinical cohort study. Setting: Fondazione Policlinico Universitario A. Gemelli IRCCS as Italian Covid reference center. Participants: Patients with laboratory-confirmed SARS-CoV-2 infection and respiratory distress with PaO2/FiO2 ratio<300 treated with Sarilumab between March 23rd - April 4th, 2020. Date of final follow-up was April 18, 2020. Main outcomes and measures: We describe the clinical outcomes of 53 patients with SARS-CoV-2 severe pneumonia treated with intravenous Sarilumab in terms of pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards setting and of live discharge rate in ICU treated patients as well as in terms of safety. Each patient received Sarilumab 400 mg administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and was followed for at least 14 days, unless previously discharged or dead. No gluco-corticosteroids were used at baseline. Results: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39 (73.6%) were treated in medical wards (66.7% with a single infusion) while 14 (26.4%) in ICU (92.6% with a second infusion). The median PaO2/FiO2 of patients in the Medical Ward was 146(IQR:120-212) while the median PaO2/FiO2 of patients in ICU was 112(IQR:100-141.5), respectively. Within the medical wards, 7(17.9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89.7% of medical inpatients significantly improved (46.1% after 24 hours, 61.5% after 3 days), 70.6% were discharged from the hospital and 85.7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64.2% were discharged from ICU to the ward and 35.8% were still alive at the last follow-up. Overall mortality rate was 5.7% after Sarilumab administration: 1(2.5%) patient died in the Medical Ward whilst 2(14.2%) patients died in ICU, respectively. Conclusions and relevance: IL6-R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical benefit and good safety.