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.

Outcomes of COVID-19 Patients with Severe Hypoxemic Acute Respiratory Failure: Non-Invasive Ventilation vs. Straight Intubation-A Propensity Score-Matched Multicenter Cohort Study.

The best timing for endotracheal intubation in patients with coronavirus disease 2019 (COVID-19) hypoxemic acute respiratory failure (hARF) remains debated. Aim of this study is to compare the outcomes of COVID-19 patients with hARF receiving either a trial of non-invasive ventilation (NIV) or intubated with no prior attempt of NIV ("straight intubation"). All consecutive patients admitted to the 25 participating ICUs were included and divided in two groups: the "straight intubation" group and the "NIV" group. A propensity score matching was performed to correct for biases associated with the choice of the respiratory support. Primary outcome was in-hospital mortality. Secondary outcomes were length of mechanical ventilation, hospital stay and reintubation rate. A total of 704 COVID-19 patients were admitted to ICUs during the study period. After matching, 141 patients were included in each group. No clinically relevant difference at ICU admission was found between groups. In-hospital mortality was significantly lower in the NIV group (22.0% vs. 36.2%), with no significant difference in secondary endpoints. There was no significant mortality difference between patients who received straight intubation and those intubated after NIV failure. In COVID-19 patients with hARF it is worth and safe attempting a trial of NIV prior to intubation.

Outcomes of COVID-19 patients intubated after failure of non-invasive ventilation: a multicenter observational study.

The efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the intensive care unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: (1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and (2) assessing whether the length of NIV application affects patient survival. This observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February-April 2020), who underwent endotracheal intubation after NIV failure. Among the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60-76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06-4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04-1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. In-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality.

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 National Emergency Medical Service Role During the COVID-19 Pandemic in Sierra Leone.

This report describes the main adaptive and transformative changes adopted by the brand-new National Emergency Medical Service (NEMS) to face the novel coronavirus disease 2019 (COVID-19) in Sierra Leone, including ambulance re-distribution, improvements in communication flow, implementation of ad-hoc procedures and trainings, and budget re-allocation. In a time-span of four months, 1,170 COVID-19 cases have been handled by the NEMS through a parallel referral system, while efforts have been made to manage the routine emergencies of the country, causing a substantial intensification of daily activities.