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 impact of COVID-19 pandemic on access to medical services and its consequences on emergency surgery.

Background: On March 9, 2020, the Italian Prime Minister announced the lockdown, which was officially closed on May 4. This extraordinary measure was necessary to contain the COVID-19 pandemic spread in Italy. During this phase, a significant decrease in patients' access to Emergency Department (ED) was observed. Delayed access to treatment determined a delay in the diagnosis of acute surgical conditions, as already documented in other clinical areas, with consequences on surgical outcome and survival. Aim of this study is to provide a detailed description of abdominal urgent-emergent conditions surgically treated and surgical outcomes during the lockdown in a tertiary referral Italian hospital, compared with historical data. Methods: A retrospective review of urgent-emergent patients surgically treated in our department was conducted in order to compare patients' characteristics and surgical outcomes during the period March 9th-May 4th, 2020 with the same period of the previous year. Results: 152 patients were included in our study, 79 patients in 2020 group and 77 patients in 2019. We found no significant differences between the groups regarding ASA score, age, gender, and disease prevalence. Significant differences were found in symptom duration before ER access and abdominal pain as the main symptom in non-traumatic conditions. We also performed a sub-analysis on peritonitis which showed significant differences in: hospital length of stay, presence of colostomy vs. ileostomy, and fatal events in 2020. No differences were found in the use of laparoscopy. Conclusions: While the overall number of ER accesses has decreased in 2020 group, the number of patients surgically treated in emergency-urgency conditions has not decreased. However, those patients waited significantly more before the hospital access. This diagnostic delay was associated with a more severe clinical condition and a consequent significantly worse prognosis.

A new perspective during laryngo-tracheal surgery: the use of an ultra-thin endotracheal tube (Tritube®) and flow-controlled ventilation-a retrospective case series and a review of the literature.

BACKGROUND: Upper airway surgery often poses a challenge to both anesthesiologists and surgeons, as airway access, mechanical ventilation, and surgical difficulties may occur in a tricky combination. To fulfill the need for a tubeless surgery, techniques such as apneic oxygenation or jet ventilation may be used, which carry the risk of several complications. The ultrathin cuffed endotracheal tube Tritube can be used with flow-controlled ventilation (FCV) to provide adequate surgical field and ventilation. To assess the feasibility, safety, and effectiveness of this technique, we describe a series of 21 patients, with various lung conditions, undergoing laryngo-tracheal surgery with FCV delivered via Tritube. Moreover, we perform a narrative systematic review to summarize clinical data on the use of Tritube during upper airway surgery. RESULTS: All patients were successfully intubated in one attempt with Tritube. The median (interquartile range [IQR]) tidal volume was 6.7 (6.2-7.1) mL/kg of ideal body weight, the median end-expiratory pressure was 5.3 (5.0-6.4) cmH2O, and the median peak tracheal pressure was 16 (15-18) cmH2O. The median minute volume was 5.3 (5.0-6.4) L/min. Median global alveolar driving pressure was 8 (7-9) cmH2O. The median maximum level of end-tidal CO2 was 39 (35-41) mmHg. During procedures involving laser, the maximum fraction of inspired oxygen was 0.3, with the median lowest peripheral oxygen saturation of 96% (94-96%). No complications associated with intubation or extubation occurred. In one patient, the ventilator needed to be rebooted for a software issue. In two (10%) patients, Tritube needed to be flushed with saline to remove secretions. In all patients, optimal visualization and accessibility of the surgical site were obtained, according to the surgeon in charge. Thirteen studies (seven case reports, two case series, three prospective observational studies, and one randomized controlled trial) were included in the narrative systematic review and described. CONCLUSIONS: Tritube in combination with FCV provided adequate surgical exposure and ventilation in patients undergoing laryngo-tracheal surgery. While training and experience with this new method is needed, FCV delivered with Tritube may represent an ideal approach that benefits surgeons, anesthesiologists, and patients with difficult airways and compromised lung mechanics.

Perioperative ROTEM and ROTEMplatelet monitoring in a case of Glanzmann's thrombasthenia.

Glanzmann's thrombasthenia is a rare, inherited disease, which consists in abnormality of the glycoprotein IIa/IIIb genes that causes impaired platelet function. Glanzmann's thrombasthenia patients show prolongation of bleeding time and may experience life-threatening hemorrhage after surgery. We present a case of a young woman having Glanzmann's thrombasthenia, who underwent gynecological operation for ovarian cyst. Perioperative monitoring included thromboelastometry with ROTEM and impedance aggregometry with ROTEMplatelet. In this case, despite acceptable ROTEM results after platelet transfusion, ROTEMplatelet was more indicative of hemostatic impairment and reflected the bleeding occurred in the postoperative period. When treating patients with congenital or acquired platelet dysfunction, some intrinsic limits of thromboelastometry to assess platelet function may be overcome with the combined use of a point-of-care device that measures platelet aggregation.

Tranexamic Acid for Trauma Resuscitation in the United States of America.

The utilization of tranexamic acid (TXA) for the management of bleeding trauma patients has been a subject of much debate on both sides of the Atlantic and in Australia. As a result of the large randomized controlled study called the Clinical Randomization of an Antifibrinolytic in Severe Hemorrhage (CRASH-2), there was an initial enthusiasm for the use of TXA to treat bleeding patients. However, the adoption of TXA in the United States was delayed by concerns of "knowledge and evidence gaps" of the CRASH-2 study and because of a lack of mechanistic rationale that would explain the survival benefit noted in the study. Subsequent nonrandomized controlled trials questioned the liberal use of TXA in trauma patients. This narrative review explores the historical as well as clinical and theoretical grounds for the more measured use of TXA in the United States and proposes a clinical and point-of-care guided utilization of TXA, blood components, and adjunctive hemostatic agents in bleeding trauma patients.

Cost-Effectiveness of Dabigatran Exilate in Treatment of Atrial Fibrillation.

BACKGROUND: Dabigatran exilate has emerged as a highly effective tool in treating atrial fibrillation, AF). Its relative convenience in terms of cost and overall utility with respect to other anti-coagulants, however, has not been explored in much detail yet. METHODS AND RESULTS: We run a Markovian disease simulation model based on a cohort of 1000 randomly generated patients which were sub-grouped by average risk of hemorrhage and average risk of stroke to compare treatments with Aspirin, Warfarin and Dabigatran. Quality-adjusted life-year, QALYs) for the patients were projected over up to 30 years with mortality statistics database and properly adjusted after every 5-year survival from the starting date. If managed within the prescribed range, Warfarin offers the highest outcome in terms of QALYs: 7.93 versus 7.61 for the Aspirin treatment and 7.57 for highest dose treatment with Dabigatran. Dabigatran outperformed the other treatments in patients at high risk of major stroke, provided Warfarin was not managed optimally. The incremental cost-effectiveness ratio for Dabigatran versus sub-optimally managed Warfarin was €7,759.48/QALY meaning that every year in perfect health earned with Dabigatran cost less than €8,000 more than the alternative treatment with Warfarin. CONCLUSIONS: The therapy with high-dose Dabigatran proved the most clinically safe solution for patients at high risk of stroke unless Warfarin therapy was excellent.

Management of severe bleeding in a ruptured extrauterine pregnancy: a theragnostic approach.

Haemoperitoneum due to ruptured extrauterine pregnancy is a complication that may occur in the first trimester of pregnancy, but massive haemorrhage with severe shock is rare. When severe bleeding does occur, timely diagnosis and rapid haemostatic treatment are vital. We present the case of a 37-year-old woman with severe bleeding and shock due to ruptured extrauterine pregnancy.Management of the patient consisted of emergency laparotomy, red blood cell transfusion and targeted haemostatic therapy guided by rotational thromboelastometry using the fibrin-based clotting (FIBTEM) assay, (activation with tissue factor with addition of the platelet inhibitor cytochalasin D). As severe hypofibrinogenaemia was apparent, indicated by a FIBTEM maximum clot firmness (MCF) that was not measurable (i.e. < 2 mm) and a plasma fibrinogen level of 0.17 g/l, the patient was treated with 4 g fibrinogen concentrate. Tranexamic acid (1 g) was also administered.Rapid restoration of haemostasis was indicated by the improvement of thromboelastometric parameters (FIBTEM MCF 16 mm) and, later, laboratory coagulation tests (plasma fibrinogen 2.75 g/l), along with cessation of bleeding. No fresh frozen plasma (FFP) was administered. Surgery was successfully completed, and the patient was subsequently discharged 5 days after admission with no further complications. Haemorrhage in extrauterine pregnancy is commonly managed using autologous blood transfusion (via cell salvage) and homologous plasma transfusion. In this case of severe bleeding and shock due to ruptured extrauterine pregnancy, thromboelastometry-guided administration of fibrinogen concentrate enabled rapid restoration of haemostasis, complete avoidance of FFP transfusion and resulted in a successful outcome.

Management of hemorrhage in trauma.

Hemorrhage remains one of the leading causes of trauma-related deaths. Uncontrolled diffuse microvascular bleeding in the course of initial care is common, potentially resulting in exsanguination. Early and aggressive hemostatic intervention increases survival and reduces the incidence of massive transfusion. Thus, timely diagnosis of the underlying coagulation disorders is mandatory. It has been shown that standard coagulation tests do not sufficiently characterize trauma-induced coagulopathy (TIC). This has led to increasing interest in alternatives, such as the viscoelastic test, to diagnose TIC and to provide the basis for a goal-directed hemostatic therapy. The concept of damage control resuscitation (DCR) has been introduced widely in trauma patients with severe bleeding. This strategy addresses important confounders of the coagulation process such as hemodilution, hypothermia, and acidosis; DCR is based on a damage control surgical approach, permissive hypotension, and improvement of hemostatic competence. Many studies have shown benefit in mortality when using high ratios of fresh frozen plasma (FFP) to red blood cells (RBC) as early treatment. However, there is increased awareness that coagulation factor concentrate could be beneficial in the treatment of trauma-induced coagulopathy.

Rotational thromboelastometry analysis and management of life-threatening haemorrhage in isolated craniofacial injury.

Massive haemorrhage from facial fractures is rare but the associated mortality rate is high. Here, we describe a case in which thromboelastometry [rotational thromboelastometry (ROTEM)]-guided administration of prothrombin complex concentrate and fibrinogen concentrate was effective in correcting coagulopathy in a 68-year-old man with serious craniofacial trauma and massive haemorrhage. The patient, a cyclist who collided with a car, was transferred to the emergency department of our hospital with signs of shock and significant bleeding from multiple fractures and soft tissue injuries to the face. Blood gas analysis and standard laboratory tests revealed the presence of anaemia and acidosis, and our massive haemorrhage protocol was initiated. E-FAST and total-body computed tomography scans excluded the possibility of bleeding from other sites. All efforts were directed towards stopping bleeding from craniofacial lesions, but the surgeon experienced difficulty in maintaining haemostasis. ROTEM analysis revealed severe coagulopathy and was indispensable in guiding transfusion: 2 g tranexamic acid, followed by 1000 IU prothrombin complex concentrate, 5 g fibrinogen and 2 U platelet concentrate. Two hours later, ROTEM analysis showed that coagulopathy had been corrected, and haemostasis was confirmed by cessation of bleeding. This report highlights the potential for using ROTEM to guide treatment with fibrinogen and prothrombin complex concentrates in the presence of profuse multifocal bleeding and severe coagulopathy.