The SARS-CoV-2 pandemic as a source of unprecedented bioethical and biolaw issues: lessons for intensivists.

The following article presents the relevant and unprecedented bioethical and biolaw issues posed by the SARS-COV-2 pandemic and summarizes the initiatives adopted by the Italian Society of Anesthesia and Resuscitation (SIAARTI) as well as by the Veneto Region ICU Network. Since the initial phase of the pandemic, in March 2020, there has been a strong appeal from both SIAARTI and the Veneto Region ICU Network to consider "the appropriate intensive treatment." During the pandemic, the principle of proportionality must be applied, in compliance with the main principle in bioethics. This encompasses the concept of clinical appropriateness, based on the efficacy of the treatment in specific case and context, as well as the concept of ethical appropriateness, which refers to ethical and juridical principles of acceptance of health care. The "appropriate treatment" must never interfere with the withdrawal of patients, who are not eligible for intensive treatments since they would not benefit from them and who are eligible for ordinary treatments that must be maintained, and, where necessary, palliative treatments were initiated. On the other hand, it must not encroach on unreasonable obstinacy. At the end of 2020, the SIAARTI-SIMLA (Italian Society of Insurance and Legal Medicine) document provides healthcare professionals with a tool for responding appropriately to the emergency of the pandemic, in the event of an imbalance between healthcare demand and available resources. The document states that the ICU triage should be based on global evaluation of each patient, taking into account well-defined parameters and stresses that each person potentially eligible for intensive care should have a shared care planning (SCP) stipulated, and, when necessary, a proxy should be nominated. This has illustrated how the biolaw issues encountered by intensivists during the pandemic, such as those relating to consent and refusal to medical treatment, even when it is lifesaving, as well as requests for treatment of unproven clinical efficacy, were subject to appropriate guidelines and solutions through the application of Law 219/2017 (provisions for informed consent and advance directives treatment). Communication with family members and the management of sensitive personal data; the evaluation of "legal capacity" of comprehension and informed decision-making regarding the proposed treatment plan; and the need for emergency medical intervention in the absence of consent are all addressed in light of the relevant regulations and the particular conditions of social isolation induced by the pandemic. The collaborative ICUs network sustained by the Veneto Region has given great prominence to clinical bioethics issues, and as a result, multidisciplinary integration with the help of legal and juridical experts was developed. This has led to an increase in skills in the bioethical field, as well as providing a valuable lesson for the improvement of therapeutic relationships with critically ill patients and their families.

The PROVENT-C19 registry: A study protocol for international multicenter SIAARTI registry on the use of prone positioning in mechanically ventilated patients with COVID-19 ARDS.

BACKGROUND: The worldwide use of prone position (PP) for invasively ventilated patients with COVID-19 is progressively increasing from the first pandemic wave in everyday clinical practice. Among the suggested treatments for the management of ARDS patients, PP was recommended in the Surviving Sepsis Campaign COVID-19 guidelines as an adjuvant therapy for improving ventilation. In patients with severe classical ARDS, some authors reported that early application of prolonged PP sessions significantly decreases 28-day and 90-day mortality. METHODS AND ANALYSIS: Since January 2021, the COVID19 Veneto ICU Network research group has developed and implemented nationally and internationally the "PROVENT-C19 Registry", endorsed by the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care…'(SIAARTI). The PROVENT-C19 Registry wishes to describe 1. The real clinical practice on the use of PP in COVID-19 patients during the pandemic at a National and International level; and 2. Potential baseline and clinical characteristics that identify subpopulations of invasively ventilated patients with COVID-19 that may improve daily from PP therapy. This web-based registry will provide relevant information on how the database research tools may improve our daily clinical practice. CONCLUSIONS: This multicenter, prospective registry is the first to identify and characterize the role of PP on clinical outcome in COVID-19 patients. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of a clinical intervention. Indeed observation-based registries could be effective tools aimed at identifying specific clusters of patients within a large study population with widely heterogeneous clinical characteristics. TRIAL REGISTRATION: The registry was registered (ClinicalTrial.Gov Trials Register NCT04905875) on May 28,2021.

COVID-19 ICU mortality prediction: a machine learning approach using SuperLearner algorithm.

BACKGROUND: Since the beginning of coronavirus disease 2019 (COVID-19), the development of predictive models has sparked relevant interest due to the initial lack of knowledge about diagnosis, treatment, and prognosis. The present study aimed at developing a model, through a machine learning approach, to predict intensive care unit (ICU) mortality in COVID-19 patients based on predefined clinical parameters. RESULTS: Observational multicenter cohort study. All COVID-19 adult patients admitted to 25 ICUs belonging to the VENETO ICU network (February 28th 2020-april 4th 2021) were enrolled. Patients admitted to the ICUs before 4th March 2021 were used for model training ("training set"), while patients admitted after the 5th of March 2021 were used for external validation ("test set 1"). A further group of patients ("test set 2"), admitted to the ICU of IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan, was used for external validation. A SuperLearner machine learning algorithm was applied for model development, and both internal and external validation was performed. Clinical variables available for the model were (i) age, gender, sequential organ failure assessment score, Charlson Comorbidity Index score (not adjusted for age), Palliative Performance Score; (ii) need of invasive mechanical ventilation, non-invasive mechanical ventilation, O2 therapy, vasoactive agents, extracorporeal membrane oxygenation, continuous venous-venous hemofiltration, tracheostomy, re-intubation, prone position during ICU stay; and (iii) re-admission in ICU. One thousand two hundred ninety-three (80%) patients were included in the "training set", while 124 (8%) and 199 (12%) patients were included in the "test set 1" and "test set 2," respectively. Three different predictive models were developed. Each model included different sets of clinical variables. The three models showed similar predictive performances, with a training balanced accuracy that ranged between 0.72 and 0.90, while the cross-validation performance ranged from 0.75 to 0.85. Age was the leading predictor for all the considered models. CONCLUSIONS: Our study provides a useful and reliable tool, through a machine learning approach, for predicting ICU mortality in COVID-19 patients. In all the estimated models, age was the variable showing the most important impact on mortality.

Static compliance and driving pressure are associated with ICU mortality in intubated COVID-19 ARDS.

BACKGROUND: Pathophysiological features of coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) were indicated to be somewhat different from those described in nonCOVID-19 ARDS, because of relatively preserved compliance of the respiratory system despite marked hypoxemia. We aim ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1st day of controlled mechanical ventilation are associated with intensive care unit (ICU) mortality in COVID-19 ARDS. METHODS: Observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28th-April 28th, 2020), who received controlled mechanical ventilation, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of controlled mechanical ventilation were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. RESULTS: A total of 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: (1) Crs was not linearly associated with ICU mortality (p value for nonlinearity = 0.01), with a greater risk of death for values < 48 ml/cmH2O; (2) the association between DP and ICU mortality was linear (p value for nonlinearity = 0.68), and increasing DP from 10 to 14 cmH2O caused significant higher odds of in-ICU death (OR 1.45, 95% CI 1.06-1.99); (3) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95% CI 0.55-1.52). Multivariable analysis confirmed these findings. CONCLUSIONS: Crs < 48 ml/cmH2O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death.

The impact of the SARS-CoV-2 epidemic outbreak on the vascular access team operations after conversion to COVID-19 dedicated hospital.

BACKGROUND: On February 21 2020, in Schiavonia Hospital occurred the first death by COVID-19 in Italy and since this date SARS-CoV-2 caused more than 100,000 deaths in our country. Our hospital was immediately closed and re-opened after 15 days as a reference Covid Hospital. Among services involved in a process of destruction and rebirth there was also the Vascular Access Team. METHODS: We analyzed our Vascular Access Team activity comparing data from the first month (March) in which basically it did not work and data from the following month (April) in which we began to re-build the Team adapting it to the new reality. RESULTS: In all patients admitted to Intensive Care Unit a Centrally Inserted Central Catheter multilumen was placed, but in March only 5.5% of patients admitted to Medicine-Sub-intensive Unit had a catheter different from the short peripheral cannula while in April it was possible to guarantee a more suitable catheter 31.7% of patients admitted to Medicine-Sub-intensive Unit (p < 0.000). In April, compared to March, a significant higher number of Midline were implanted in Medicine-Sub-intensive Unit (36/139 vs 12/238 p < 0.000) where also a higher number of Centrally Inserted Central Catheter and Femoral Inserted Central Catheter were implanted (8/139 vs 1/238 p = 0.003). This change allowed us to implant more vascular accesses in Medicine-Sub-intensive Unit favoring Midline with a longer average duration. Only one patient with Midline developed a catheter vein thrombosis, and in only one patient the device was removed for suspected infection. CONCLUSIONS: The experience we gained will allow us to be more prepared in the future and our experience has highlighted that a structured Vascular Access Team is necessary to respond adequately to COVID-19 patients' needs, to ensure the effectiveness of the maneuver, to reduce complications and to avoid the waste of resources, always working in safe condition.

Pacemaker implantation in a COVID-19 patient. Balancing the patient's needs and the team's risk of exposure.

COVID-19 patients may have cardiovascular complications requiring invasive treatment. Pacemaker implantation procedure may be challenging because of the necessity of personal protective equipment use. We report pacemaker implantation in a 78-year-old man with severe bilateral COVID-19 interstitial pneumonia, a second degree 2:1 atrioventricular block, and concomitant aortic stenosis.

Indications and timing for tracheostomy in patients with SARS CoV2-related.

BACKGROUND: The indications and timing for tracheostomy in patients with SARS CoV2-related are controversial. PURPOSE: In a recent issue published in the European Archives of Otorhinolaryngology, Mattioli et al. published a short communication about tracheostomy timing in patients with COVID-19 (Coronavirus Disease 2019); they reported that the tracheostomy could allow early Intensive Care Units discharge and, in the context of prolonged Invasive Mechanical Ventilation, should be suggested within 7 and 14 days to avoid potential tracheal damages. In this Letter to the Editor we would like to present our experience with tracheostomy in a Hub Covid Hospital. METHODS: 8 patients underwent open tracheostomy in case of intubation prolonged over 14 days, bronchopulmonary overlap infections, and patients undergoing weaning. They were followed up and the number and timing of death were recorded. RESULTS: Two patients died after tracheostomy; the median time between tracheostomy and death was 3 days. A negative prognostic trend was observed for a shorter duration of intubation. CONCLUSION: In our experience, tracheostomy does not seem to influence the clinical course and prognosis of the disease, in the face of possible risks of contagion for healthcare workers. The indication for tracheostomy in COVID-19 patients should be carefully evaluated and reserved for selected patients. Although it is not possible to define an optimal timing, it is our opinion that tracheostomy in a stable or clinically improved COVID-19 patient should not be proposed before the 20th day after orotracheal intubation.