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Abstract Emergency general surgeons often provide care to severely ill patients requiring surgical interventions and intensive support. One of the primary drivers of morbidity and mortality is perioperative bleeding. In general, when addressing life threatening haemorrhage, blood transfusion can become an essential part of overall resuscitation. However, under all circumstances, indications for blood transfusion must be accurately evaluated. When patients decline blood transfusions, regardless of the reason, surgeons should aim to provide optimal care and respect and accommodate each patient’s values and target the best outcome possible given the patient’s desires and his/her clinical condition. The aim of this position paper was to perform a review of the existing literature and to provide comprehensive recommendations on organizational, surgical, anaesthetic, and haemostatic strategies that can be used to provide optimal peri-operative blood management, reduce, or avoid blood transfusions and ultimately improve patient outcomes.

Abstract Resembling the morphology of Japanese polyp vessels, the classic form of Takotsubo cardiomyopathy is characterized by the presence of systolic dysfunction of the mid-apical portion of the left ventricle associated with basal hyperkinesia. It is believed that this may be due to a higher density of β-adrenergic receptors in the context of the apical myocardium, which could explain the greater sensitivity of the apex to fluctuations in catecholamine levels. The syndrome is precipitated by significant emotional stress or acute severe pathologies, and it is increasingly diagnosed during the perioperative period. Indeed, surgery, induction of general anaesthesia and critical illness represent potential harmful trigger of stress cardiomyopathy. No universally accepted guidelines are currently available, and, generally, the treatment of TTS relies on health care personal experience and/or local practice. In our daily practice, anaesthesiologists can be asked to manage patients with the diagnosis of new-onset Takotsubo before elective surgery or an emergent surgery in a patient with a concomitant stress cardiomyopathy. Even more, stress cardiomyopathy can arise as a complication during the operation. In this paper, we aim to provide an overview of Takotsubo syndrome and to discuss how to manage Takotsubo during surgery and in anaesthesiologic special settings.

Abstract Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients’ safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts’ opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery.

Background: We estimated the diagnostic accuracy of urinary NGAL for the diagnosis of AKI. Methods: Urinary NGAL and Creatinine were measured daily for up to 3 days. Doppler ultrasonography was performed within 24 h of admission and for the following 3 days. Results: Of the 21 patients, 44% had AKI during their ICU stay. The AKI group presented with higher values of serum Creatinine, renal length, MDRD as well as SAPS II already at admission. Urinary NGAL was significantly higher among patients with AKI and patients AKI-no at T0 (p < 0.0001) and increased steadily on T1 and T2. Urinary NGAL seemed to be a notable diagnostic marker for AKI from the first measurement (T0) with an area under the ROC of 0.93 (95% CI = 0.78–0.99) with a sensitivity of 99%. RRI levels were slightly higher in the AKI group at each time and increased gradually from T0 to T2 but reached statistical significance only at T2 (p = 0.02). Renal length and SAPS II at T0 showed high AuRoc and sensitivity. Conclusions: Urinary NGAL is a valuable marker for AKI in intensive care settings. It seemed that a pre-existing chronic renal disease, the SAPS II and the NGAL at admission represented the principal predictors of AKI.

Abstract Background In the last decades, several adjunctive treatments have been proposed to reduce mortality in septic shock patients. Unfortunately, mortality due to sepsis and septic shock remains elevated and NO trials evaluating adjunctive therapies were able to demonstrate any clear benefit. In light of the lack of evidence and conflicting results from previous studies, in this multidisciplinary consensus, the authors considered the rational, recent investigations and potential clinical benefits of targeted adjunctive therapies. Methods A panel of multidisciplinary experts defined clinical phenotypes, treatments and outcomes of greater interest in the field of adjunctive therapies for sepsis and septic shock. After an extensive systematic literature review, the appropriateness of each treatment for each clinical phenotype was determined using the modified RAND/UCLA appropriateness method. Results The consensus identified two distinct clinical phenotypes: patients with overwhelming shock and patients with immune paralysis. Six different adjunctive treatments were considered the most frequently used and promising: (i) corticosteroids, (ii) blood purification, (iii) immunoglobulins, (iv) granulocyte/monocyte colony-stimulating factor and (v) specific immune therapy (i.e. interferon-gamma, IL7 and AntiPD1). Agreement was achieved in 70% of the 25 clinical questions. Conclusions Although clinical evidence is lacking, adjunctive therapies are often employed in the treatment of sepsis. To address this gap in knowledge, a panel of national experts has provided a structured consensus on the appropriate use of these treatments in clinical practice.

Abstract Background The role of β-blockers in the critically ill has been studied, and data on the protective effects of these drugs on critically ill patients have been repeatedly reported in the literature over the last two decades. However, consensus and guidelines by scientific societies on the use of β-blockers in critically ill patients are still lacking. The purpose of this document is to support the clinical decision-making process regarding the use of β-blockers in critically ill patients. The recipients of this document are physicians, nurses, healthcare personnel, and other professionals involved in the patient’s care process. Methods The Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) selected a panel of experts and asked them to define key aspects underlying the use of β-blockers in critically ill adult patients. The methodology followed by the experts during this process was in line with principles of modified Delphi and RAND-UCLA methods. The experts developed statements and supportive rationales in the form of informative text. The overall list of statements was subjected to blind votes for consensus. Results The literature search suggests that adrenergic stress and increased heart rate in critically ill patients are associated with organ dysfunction and increased mortality. Heart rate control thus seems to be critical in the management of the critically ill patient, requiring careful clinical evaluation aimed at both the differential diagnosis to treat secondary tachycardia and the treatment of rhythm disturbance. In addition, the use of β-blockers for the treatment of persistent tachycardia may be considered in patients with septic shock once hypovolemia has been ruled out. Intravenous application should be the preferred route of administration. Conclusion β-blockers protective effects in critically ill patients have been repeatedly reported in the literature. Their use in the acute treatment of increased heart rate requires understanding of the pathophysiology and careful differential diagnosis, as all causes of tachycardia should be ruled out and addressed first.

Abstract Although the precise clinical indication for initiation of PMX-HA is widely debated in the literature, a proper patient selection and timing of treatment delivery might play a critical role in the clinical course of a specific subphenotype of septic shock (endotoxic shock). In light of this view, since 2019, we have introduced in our clinical practice a diagnostic-therapeutic flowchart to select patients that can benefit the most from the treatment proposed. In addition, we reported in this study our experience of PMX-HA in a cohort of critically ill patients admitted to our intensive care unit (ICU). We analyzed a single centre, retrospective, observational web-based database (extracted from the EUPHAS2 registry) of critically ill patients admitted to the ICU between January 2016 and May 2021 who were affected by endotoxic shock. Patients were divided according to the diagnostic-therapeutic flowchart in two groups: Pre-Flowchart (Pre-F) and Post-Flowchart (Post-F). From January 2016 to May 2021, 61 patients were treated with PMX-HA out of 531 patients diagnosed with septic shock and of these, fifty patients (82%) developed AKI during their ICU stay. The most common source of infection was secondary peritonitis (36%), followed by community-acquired pneumonia (29%). Fifty-five (90%) out of 61 patients received a second PMX-HA treatment, with a statistically significant difference between the two groups (78% of the Pre-F vs. 100% of the Post-F group, p = 0.005). In both groups, between T0 and T120, the Endotoxin Activity Assay (EAA) decreased, while the SOFA score, mean arterial pressure (MAP), and Vasoactive Inotropic Score (VIS) improved with no statistically significant difference. Furthermore, when performing a propensity score matching analysis to compare mortality between the two groups, statistically significant lower ICU and 90-day mortalities were observed in the Post-F group [p = 0.016]. Although in this experienced centre data registry, PMX-HA was associated with organ function recovery, hemodynamic improvement, and current EAA level reduction in critically ill patients with endotoxic shock. Following propensity score-matched analysis, ICU mortality and 90-day mortalities were lower in the diagnostic-therapeutic flowchart group when considering two temporal groups based on strict patient selection criteria and timing to achieve PMX. Further Randomised Control Trials focused on centre selection, adequate training and a flowchart of action when assessing extracorporeal blood purification use should be performed.

Abstract Background Non-traumatic emergency general surgery involves a heterogeneous population that may present with several underlying diseases. Timeous emergency surgical treatment should be supplemented with high-quality perioperative care, ideally performed by multidisciplinary teams trained to identify and handle complex postoperative courses. Uncontrolled or poorly controlled acute postoperative pain may result in significant complications. While pain management after elective surgery has been standardized in perioperative pathways, the traditional perioperative treatment of patients undergoing emergency surgery is often a haphazard practice. The present recommended pain management guidelines are for pain management after non-traumatic emergency surgical intervention. It is meant to provide clinicians a list of indications to prescribe the optimal analgesics even in the absence of a multidisciplinary pain team. Material and methods An international expert panel discussed the different issues in subsequent rounds. Four international recognized scientific societies: World Society of Emergency Surgery (WSES), Global Alliance for Infection in Surgery (GAIS), Italian Society of Anesthesia, Analgesia Intensive Care (SIAARTI), and American Association for the Surgery of Trauma (AAST), endorsed the project and approved the final manuscript. Conclusion Dealing with acute postoperative pain in the emergency abdominal surgery setting is complex, requires special attention, and should be multidisciplinary. Several tools are available, and their combination is mandatory whenever is possible. Analgesic approach to the various situations and conditions should be patient based and tailored according to procedure, pathology, age, response, and available expertise. A better understanding of the patho-mechanisms of postoperative pain for short- and long-term outcomes is necessary to improve prophylactic and treatment strategies.

Abstract Background Diaphragmatic dysfunction is a major factor responsible for weaning failure in patients that underwent prolonged invasive mechanical ventilation for acute severe respiratory failure from COVID-19. This study hypothesizes that ultrasound measured diaphragmatic thickening fraction (DTF) could provide corroborating information for weaning COVID-19 patients from mechanical ventilation. Methods This was an observational, pragmatic, cross-section, multicenter study in 6 Italian intensive care units. DTF was assessed in COVID-19 patients undergoing weaning from mechanical ventilation from 1st March 2020 to 30th June 2021. Primary aim was to evaluate whether DTF is a predictive factor for weaning failure. Results Fifty-seven patients were enrolled, 25 patients failed spontaneous breathing trial (44%). Median length of invasive ventilation was 14 days (IQR 7–22). Median DTF within 24 h since the start of weaning was 28% (IQR 22–39%), RASS score (− 2 vs − 2; p = 0.031); Kelly-Matthay score (2 vs 1; p = 0.002); inspiratory oxygen fraction (0.45 vs 0.40; p = 0.033). PaO2/FiO2 ratio was lower (176 vs 241; p = 0.032) and length of intensive care stay was longer (27 vs 16.5 days; p = 0.025) in patients who failed weaning. The generalized linear regression model did not select any variables that could predict weaning failure. DTF was correlated with pH (RR 1.56 × 1027; p = 0.002); Kelly-Matthay score (RR 353; p

Abstract Several perioperative factors are responsible for the dysregulation or suppression of the immune system with a possible impact on cancer cell growth and the development of new metastasis. These factors have the potential to directly suppress the immune system and activate hypothalamic-pituitary-adrenal axis and the sympathetic nervous system with a consequent further immunosuppressive effect. Anesthetics and analgesics used during the perioperative period may modulate the innate and adaptive immune system, inflammatory system, and angiogenesis, with a possible impact on cancer recurrence and long-term outcome. Even if the current data are controversial and contrasting, it is crucial to increase awareness about this topic among healthcare professionals for a future better and conscious choice of anesthetic techniques. In this article, we aimed to provide an overview regarding the relationship between anesthesia and cancer recurrence. We reviewed the effects of surgery, perioperative factors, and anesthetic agents on tumor cell survival and tumor recurrence.

Abstract Background To assess the usefulness of pre-operative contrast-enhanced transthoracic echocardiography (CE-TTE) and post-operative chest-x-ray (CXR) for evaluating central venous catheter (CVC) tip placements, with trans-esophageal echocardiography (TEE) as gold standard. Methods A prospective single-center, observational study was performed in 111 patients requiring CVC positioning into the internal jugular vein for elective cardiac surgery. At the end of CVC insertion by landmark technique, a contrast-enhanced TTE was performed by both the apical four-chambers and epigastric bicaval acoustic view to assess catheter tip position; then, a TEE was performed and considered as a reference technique. A postoperative CXR was obtained for all patients. Results As per TEE, 74 (67%) catheter tips were correctly placed and 37 (33%) misplaced. Considering intravascular and intracardiac misplacements together, they were detected in 8 patients by CE-TTE via apical four-chamber view, 36 patients by CE-TTE via epigastric bicaval acoustic view, and 12 patients by CXR. For the detection of catheter tip misplacement, CE-TTE via epigastric bicaval acoustic view was the most accurate method providing 97% sensitivity, 90% specificity, and 92% diagnostic accuracy if compared with either CE-TTE via apical four-chamber view or CXR. Concordance with TEE was 79% (p

Abstract Positive end-expiratory pressure (PEEP) may affect arterial wave propagation and reflection, thus influencing ventricular loading conditions. The aim of the study was to investigate the hemodynamic variations in arterial wave reflection (i.e., wave reflection time, augmentation index, left ventricular ejection time, diastolic time, SEVR) associated with the application of increasing levels of PEEP in healthy subjects. We conducted a prospective observational study. Study population was selected from students and staff. Pulse contour wave analysis was performed from the right carotid artery during stepwise increase in PEEP levels (from 0 cmH2O, 5 cmH20, 10 cmH2O) with applanation tonometry. Sixty-two healthy volunteers were recruited. There were no significant changes in heart rate, augmentation index (AIx), left ventricular ejection time, Diastolic time (DT) among all of the different steps. A significant increase of time to the inflection point (Ti) was observed during all steps of the study. Diastolic area under the curve (AUC) divided by systolic-AUC (SEVR) increased from baseline to PEEP = 5 cmH2O, and from baseline to PEEP = 10 cmH2O. AIx and Ti were significantly correlated (directly) at the baseline and during PEEP = 10 cmH2O. Ti and DT were significantly correlated at the baseline and during PEEP = 5 cmH2O. In our preliminary results, low levels of PEEP played a role in the interaction between the heart and the vascular system, apparently mediated by a prolongation of the diastolic phase and a reduction in the systolic work of the heart. Clinical trials registration number: NCT03294928, 19/09/2017.

Abstract Background To produce statements based on the available evidence and an expert consensus (as members of the Lung Ultrasound Working Group of the Italian Society of Analgesia, Anesthesia, Resuscitation, and Intensive Care, SIAARTI) on the use of lung ultrasound for the management of patients with COVID-19 admitted to the intensive care unit. Methods A modified Delphi method was applied by a panel of anesthesiologists and intensive care physicians expert in the use of lung ultrasound in COVID-19 intensive critically ill patients to reach a consensus on ten clinical questions concerning the role of lung ultrasound in the following: COVID-19 diagnosis and monitoring (with and without invasive mechanical ventilation), positive end expiratory pressure titration, the use of prone position, the early diagnosis of pneumothorax- or ventilator-associated pneumonia, the process of weaning from invasive mechanical ventilation, and the need for radiologic chest imaging. Results A total of 20 statements were produced by the panel. Agreement was reached on 18 out of 20 statements (scoring 7–9; “appropriate”) in the first round of voting, while 2 statements required a second round for agreement to be reached. At the end of the two Delphi rounds, the median score for the 20 statements was 8.5 [IQR 8.9], and the agreement percentage was 100%. Conclusion The Lung Ultrasound Working Group of the Italian Society of Analgesia, Anesthesia, Resuscitation, and Intensive Care produced 20 consensus statements on the use of lung ultrasound in COVID-19 patients admitted to the ICU. This expert consensus strongly suggests integrating lung ultrasound findings in the clinical management of critically ill COVID-19 patients.

Abstract On January 2020, the WHO Director General declared that the outbreak constitutes a Public Health Emergency of International Concern. The world has faced a worldwide spread crisis and is still dealing with it. The present paper represents a white paper concerning the tough lessons we have learned from the COVID-19 pandemic. Thus, an international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making. With the present paper, international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making.

Abstract Immunocompromised patients are a heterogeneous and diffuse category frequently presenting to the emergency department with acute surgical diseases. Diagnosis and treatment in immunocompromised patients are often complex and must be multidisciplinary. Misdiagnosis of an acute surgical disease may be followed by increased morbidity and mortality. Delayed diagnosis and treatment of surgical disease occur; these patients may seek medical assistance late because their symptoms are often ambiguous. Also, they develop unique surgical problems that do not affect the general population. Management of this population must be multidisciplinary. This paper presents the World Society of Emergency Surgery (WSES), Surgical Infection Society Europe (SIS-E), World Surgical Infection Society (WSIS), American Association for the Surgery of Trauma (AAST), and Global Alliance for Infection in Surgery (GAIS) joined guidelines about the management of acute abdomen in immunocompromised patients.

Abstract Background Hip fracture is one of the most common orthopedic causes of hospital admission in frail elderly patients. Hip fracture fixation in this class of patients is considered a high-risk procedure. Preoperative physical examination, plasma natriuretic peptide levels (BNP, Pro-BNP), and cardiovascular scoring systems (ASA-PS, RCRI, NSQIP-MICA) have all been demonstrated to underestimate the risk of postoperative complications. We designed a prospective multicenter observational study to assess whether preoperative lung ultrasound examination can predict better postoperative events thanks to the additional information they provide in the form of “indirect” and “direct” cardiac and pulmonary lung ultrasound signs. Methods LUSHIP is an Italian multicenter prospective observational study. Patients will be recruited on a nation-wide scale in the 12 participating centers. Patients aged > 65 years undergoing spinal anesthesia for hip fracture fixation will be enrolled. A lung ultrasound score (LUS) will be generated based on the examination of six areas of each lung and ascribing to each area one of the four recognized aeration patterns—each of which is assigned a subscore of 0, 1, 2, or 3. Thus, the total score will have the potential to range from a minimum of 0 to a maximum of 36. The association between 30-day postoperative complications of cardiac and/or pulmonary origin and the overall mortality will be studied. Considering the fact that cardiac complications in patients undergoing hip surgery occur in approx. 30% of cases, to achieve 80% statistical power, we will need a sample size of 877 patients considering a relative risk of 1.5. Conclusions Lung ultrasound (LU), as a tool within the anesthesiologist’s armamentarium, is becoming increasingly widespread, and its use in the preoperative setting is also starting to become more common. Should the study demonstrate the ability of LU to predict postoperative cardiac and pulmonary complications in hip fracture patients, a randomized clinical trial will be designed with the scope of improving patient outcome. Trial registration ClinicalTrials.gov, NCT04074876. Registered on August 30, 2019.

Abstract High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.

Healthcare-associated infections (HAIs) result in significant patient morbidity and can prolong the duration of the hospital stay, causing high supplementary costs in addition to those already sustained due to the patient’s underlying disease. Moreover, bacteria are becoming increasingly resistant to antibiotics, making HAI prevention even more important nowadays. The public health consequences of antimicrobial resistance should be constrained by prevention and control actions, which must be a priority for all health systems of the world at all levels of care. As many HAIs are preventable, they may be considered an important indicator of the quality of patient care and represent an important patient safety issue in healthcare. To share implementation strategies for preventing HAIs in the surgical setting and in all healthcare facilities, an Italian multi-society document was published online in November 2022. This article represents an evidence-based summary of the document.

PurposeAn increasing number of laryngotracheal complications in mechanically ventilated COVID-19 patients has been reported in the last few months. Many etiopathogenetic hypotheses were proposed but no clear explanation of these complications was identified. In this paper we evaluated the possibility that the tracheal mucosa could be a high viral replication site that could weaken the epithelium itself.MethodsSubjects for the COVID-19 group and the control group were selected retrospectively according to specific criteria. Patients’ basic and clinical data were recorded and analyzed. Tracheal samples of both groups were collected during surgical tracheostomies and then analyzed from a histological and genetic-transcriptional point of view.ResultsFour COVID-19 patients were enrolled in this study and compared with four non-COVID-19 patients. No laryngotracheal complications were identified in both groups. The SARS-CoV-2 was detected in one out of four COVID-19 samples. A subepithelial inflammatory lymphomonocyte infiltrate was observed in all patients but two cases of the COVID-19 group showed vasculitis of small subepithelial vessels associated with foci of coagulative necrosis. Two gene sets (HALLMARK_INFLAMMATORY_RESPONSE and HALLMARK_ESTROGEN_RESPONSE_LATE) were significantly deregulated in COVID-19 patients compared to the control group.ConclusionThe altered inflammatory response of the COVID-19 patients could be another possible explanation of the increasing number of laryngotracheal complications.

This study aims to evaluate clinical correlates of psychiatric comorbidity and length of hospitalization in patients admitted in a general hospital emergency medicine setting. Overall, 160 patients hospitalized for different acute medical pathologies were selected consecutively over 12 months. All subjects were evaluated with proper forms to collect data on medical and psychiatric diagnoses. Levels of C-reactive protein were also measured in all patients. Statistical analyses were conducted with univariate, logistic, and multiple linear regressions. Patients with psychiatric comorbidity had significantly longer hospitalization than did patients with no psychiatric diagnoses (days 10.9±9.5 vs. 6.9±4.5, p

Abstract Objectives To assess the hypothesis that an adjunctive therapy with methylprednisolone and unfractionated heparin (UFH) or with methylprednisolone and low molecular weight heparin (LMWH) are more effective in reducing any-cause mortality in critically-ill ventilated patients with pneumonia from SARS-CoV-2 infection compared to LMWH alone. Trial design The study is designed as a multi-centre, interventional, parallel group, superiority, randomized, investigator sponsored, three arms study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned to one of the three treatment groups in a ratio 1:1:1. Participants Inpatients will be recruited from 8 Italian Academic and non-Academic Intensive Care Units Inclusion Criteria (all required) 1. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) 2. Positive pressure ventilation (either non-invasive or invasive) from > 24 hours 3. Invasive mechanical ventilation from < 96 hours 4. PaO2/FiO2 ratio lower than 150 mmHg 5. D-dimer level > 6 times the upper limit of normal reference range 6. C-reactive Protein > 6-fold upper the limit of normal reference range Exclusion Criteria 1. Age < 18 years 2. On-going treatment with anticoagulant drugs 3. Platelet count < 100.000/mm3 4. History of heparin-induced thrombocytopenia 5. Allergy to sodium enoxaparin or other LMWH, UFH or methylprednisolone 6. Active bleeding or on-going clinical condition deemed at high risk of bleeding contraindicating anticoagulant treatment 7. Recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery 8. Chronic assumption or oral corticosteroids 9. Pregnancy or breastfeeding or positive pregnancy test. In childbearing age women, before inclusion, a pregnancy test will be performed if not available 10. Clinical decision to withhold life-sustaining treatment or “too sick to benefit” 11. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition) 12. Lack or withdrawal of informed consent Intervention and comparator • LMWH group: patients in this group will be administered enoxaparin at standard prophylactic dosage. • LMWH + steroid group: patients in this group will receive enoxaparin at standard prophylactic dosage and methylprednisolone. • UFH + steroid group: patients in this group will receive UFH at therapeutic dosages and methylprednisolone. UFH will be administered intravenously in UFH + steroid group at therapeutic doses. The infusion will be started at an infusion rate of 18 UI/kg/hour and then modified to obtain aPTT Ratio in between the range of 1.5-2.0. aPTT will be periodically checked at intervals no longer than 12 hours. The treatment with UFH will be administered up to ICU discharge. After ICU discharge anticoagulant therapy may be interrupted or switched to prophylaxis with LMWH in the destination ward up to clinical judgement of the attending physician. Enoxaparin will be administered in both LMWH group and LMWH + steroid group at standard prophylactic dose (i.e., 4000 UI once day, increased to 6000 UI once day for patients weighting more than 90 kg). The treatment will be administered subcutaneously once a day up to ICU discharge. After ICU discharge it may be continued or interrupted in the destination ward up to clinical judgement of the attending physician. Methylprednisolone will be administered in both LMWH + steroid group and UHF + steroid group intravenously with an initial bolus of 0,5 mg/kg followed by administration of 0,5 mg/kg 4 times daily for 7 days, 0,5 mg/kg 3 times daily from day 8 to day 10, 0,5 mg/kg 2 times daily at days 11 and 12 and 0,5 mg/kg once daily at days 13 and 14. Main Outcomes Primary Efficacy Endpoint: All-cause mortality at day 28 Secondary Efficacy Endpoints: - Ventilation free days (VFDs) at day 28, defined as the total number of days that patient is alive and free of ventilation (either invasive or non-invasive) between randomization and day 28 (censored at hospital discharge). - Need of rescue administration of high-dose steroids or immune-modulatory drugs; - Occurrence of switch from non-invasive to invasive mechanical ventilation during ICU stay; - Delay from start of non-invasive ventilation to switch to invasive ventilation; - All-cause mortality at ICU discharge and hospital discharge; - ICU free days (IFDs) at day 28, defined as the total number of days between ICU discharge and day 28. - Occurrence of new infections from randomization to day 28; including infections by Candida, Aspergillus, Adenovirus, Herpes Virus e Cytomegalovirus - Occurrence of new organ dysfunction and grade of dysfunction during ICU stay. - Objectively confirmed venous thromboembolism, stroke or myocardial infarction; Safety endpoints: - Occurrence of major bleeding, defined as transfusion of 2 or more units of packed red blood cells in a day, bleeding that occurs in at least one of the following critical sites [intracranial, intra-spinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal], bleeding that necessitates surgical intervention and bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death); - Occurrence of clinically relevant non-major bleeding, defined ad acute clinically overt bleeding that does not meet the criteria for major and consists of any bleeding compromising hemodynamic; spontaneous hematoma larger than 25 cm2, intramuscular hematoma documented by ultrasonography, haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures; haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention or any other bleeding requiring temporary cessation of a study drug. Randomization A block randomisation will be used with variable block sizes (block size 4-6-8), stratified by 3 factors: Centre, BMI (

Abstract The current COVID-19 pandemic underlines the importance of a mindful utilization of financial and human resources. Preserving resources and manpower is paramount in healthcare. It is important to ensure the ability of surgeons and specialized professionals to function through the pandemic. A conscious effort should be made to minimize infection in this sector. A high mortality rate within this group would be detrimental. This manuscript is the result of a collaboration between the major Italian surgical and anesthesiologic societies: ACOI, SIC, SICUT, SICO, SICG, SIFIPAC, SICE, and SIAARTI. We aim to describe recommended clinical pathways for COVID-19-positive patients requiring acute non-deferrable surgical care. All hospitals should organize dedicated protocols and workforce training as part of the effort to face the current pandemic.

Abstract Background Jehovah’s Witnesses represent a tremendous clinical challenge when indicated to liver transplantation because they refuse blood transfusion on religious grounds and the procedure is historically associated with potential massive peri-operative blood loss. We herein describe a peri-operative management pathway with strategies toward a transfusion-free environment with the aim not only of offering liver transplant to selected Jehovah’s Witnesses patients but also, ultimately, of translating this practice to all general surgical procedures. Methods This is a retrospective review of prospective medical records of JW patients who underwent LT at our Institution. The peri-operative multimodal strategy to liver transplantation in Jehovah’s Witnesses includes a pre-operative red cell mass optimization package and the intra-operative use of normovolemic haemodilution, veno-venous bypass and low central venous pressure. Results In a 9-year period, 13 Jehovah’s Witness patients received liver transplantation at our centre representing the largest liver transplant program from deceased donors in Jehovah’s Witnesses patients reported so far. No patient received blood bank products but 3 had fibrinogen concentrate and one tranexamic acid to correct ongoing hyper-fibrinolysis. There were 4 cases of acute kidney injury (one required extracorporeal renal replacement treatment) and one patient needed vasoactive medications to support blood pressure for the first 2 postoperative days. Two patients underwent re-laparotomy. Finally, of the 13 recipients, 12 were alive at the 1 year follow-up interview and 1 died due to septic complications. Conclusions Our experience confirms that liver transplantation in selected Jehovah’s Witnesses patients can be feasible and safe provided that it is carried out at a very experienced centre and according to a multidisciplinary approach.

Abstract Background Tracheostomy is a standard procedure in critically ill patients requiring mechanical ventilation or airway protection for extended periods. The main cause of death is haemorrhage, most commonly owing to a trachea-to-innominate artery fistula, usually requiring surgical treatment. Case presentation Here we report the case of an 83-yr-old woman with a subarachnoid haemorrhage, who incurred a trachea-to-innominate artery transfixion following percutaneous tracheostomy, successfully and conservatively managed by interventional radiology. Conclusions The use of peri-procedural ultrasound examination of the neck can reduce the risk of complications related to vessel anatomical variants. When the tracheostomy is complicated by bleeding, the procedure should be stopped in order to diagnose the vascular iatrogenic injury and to evaluate the best therapeutic approach by a multidisciplinary team.

Abstract Background This study aims to ascertain whether (1) an educational program is sufficient to achieve adequate Diaphragm Ultrasound (DUS) assessments on healthy volunteers and (2) combining a video tutorial with a practical session is more effective in making learners capable to obtain accurate DUS measurements, as opposed to sole video tutorial. Results We enrolledstep 1: 172 volunteers naïve to ultrasound. After watching a video tutorial, a questionnaire was administered and considered to be passed when at least 70% of the questions were correctly answered. Course participants who passed the theoretical test were randomized to either intervention or control group. Learners randomized to the interventional group underwent to a practical training, tutored by an expert, before accessing DUS examination. Participants randomized to the control group directly accessed DUS examination, without any practical training. DUS measurements by learners and tutors were recorded and checked for accuracy, according to predefined criteria. Detection of both acoustic windows and accurate DUS assessment was achieved by 83.7% learners of the intervention group while 3.5% only among controls (p

Abstract Background This pilot study was designed to develop a fully automatic and quantitative scoring system of B-lines (QLUSS: quantitative lung ultrasound score) involving the pleural line and to compare it with previously described semi-quantitative scores in the measurement of extravascular lung water as determined by standard thermo-dilution. Methods This was a prospective observational study of 12 patients admitted in the intensive care unit with acute respiratory distress and each provided with 12 lung ultrasound (LUS) frames. Data collected from each patient consisted in five different scores, four semi-quantitative (nLUSS, cLUSS, qLUSS, %LUSS) and quantitative scores (QLUSS). The association between LUS scores and extravascular lung water (EVLW) was determined by simple linear regression (SLR) and robust linear regression (RLR) methods. A correlation analysis between the LUS scores was performed by using the Spearman rank test. Inter-observer variability was tested by computing intraclass correlation coefficient (ICC) in two-way models for agreement, basing on scores obtained by different raters blinded to patients’ conditions and clinical history. Results In the SLR, QLUSS showed a stronger association with EVLW (R 2 = 0.57) than cLUSS (R 2 = 0.45) and nLUSS (R 2 = 0.000), while a lower association than qLUSS (R 2 = 0.85) and %LUSS (R 2 = 0.72) occurred. By applying RLR, QLUSS showed an association for EVLW (R 2 = 0.86) comparable to qLUSS (R 2 = 0.85) and stronger than %LUSS (R 2 = 0.72). QLUSS was significantly correlated with qLUSS (r = 0.772; p = 0.003) and %LUSS (r = 0.757; p = 0.005), but not with cLUSS (r = 0.561; p = 0.058) and nLUSS (r = 0.105; p = 0.744). Moreover, QLUSS showed the highest ICC (0.998; 95%CI from 0.996 to 0.999) among the LUS scores. Conclusions This study demonstrates that computer-aided scoring of the pleural line percentage affected by B-lines has the potential to assess EVLW. QLUSS may have a significant impact, once validated with a larger dataset composed by multiple real-time frames. This approach has the potentials to be advantageous in terms of faster data analysis and applicability to large sets of data without increased costs. On the contrary, it is not useful in pleural effusion or consolidations.

Abstract Background Extracorporeal carbon dioxide removal is an increasingly used respiratory support technique. As is true of all extracorporeal techniques, extracorporeal carbon dioxide removal needs proper anticoagulation. We report a case of a patient at risk of bleeding complications who was treated with extracorporeal carbon dioxide removal and anticoagulated with a regional technique. Case presentation A 56-year-old Caucasian man with a history of chronic obstructive pulmonary disease exacerbation required extracorporeal carbon dioxide removal for severe hypercapnia and acidosis despite mechanical ventilation. The extracorporeal circuit was anticoagulated using a regional heparin technique to limit the patient’s risk of bleeding due to a low platelet count. The patient underwent 96 h of effective extracorporeal carbon dioxide removal without any adverse events. He was successfully weaned from extracorporeal carbon dioxide removal. During the treatment, no bleeding complications or unexpected circuit clotting was observed. Conclusions The use of regional heparin anticoagulation technique seems to be feasible and safe during extracorporeal carbon dioxide removal.

Subarachnoid hemorrhage (SAH) represents a medical emergency. Unfortunately, diagnosis can be delay due to cardiogenic abnormalities often associated with SAH. Cardiac manifestations are heterogeneous and common in patients with SAH. This phenomenon has not to be underestimated taking into account the devastating consequences of misdiagnosis and delay in the correct diagnosis and in a specific treatment, with serious and life-threatening consequences. We present a case report of an out of hospital ST elevation in a patient with Glasgow coma score of 6. He was primarily managed as an acute coronary syndrome case. However, coronary angiography was normal. After performing a computed tomography scan, the diagnosis of SAH was made.

Even with encouraging recipient outcomes, transplantation using donation after circulatory death (DCD) is still limited. A major barrier to this type of transplantation is the consequences of warm ischemia on graft survival; however, preservation techniques may reduce the consequences of cardiac arrest and provide better organ conservation. Furthermore, DCD in trauma patients could further expand organ donation. We present five cases in which organs were retrieved and transplanted successfully using normothermic regional perfusion (NRP) in trauma patients. Prompt critical care support and surgical treatment allowed us to overcome the acute phase. Unfortunately, owing to the severity of their injuries, all of the donors died. However, the advanced and continuous organ-specific supportive treatment allowed the maintenance of general clinical stability and organ preservation. Consequently, it was possible to retrieve and transplant the donors’ organs. Death was ascertained in accordance with cardio-circulatory criteria, which was followed by NRP. We consider that DCD in trauma patients may represent an important source of organs.

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 (250 mg/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

Introduction Percutaneous tracheostomy (PT) in the intensive care unit (ICU) is a well-established practice that shows a reduced risk of wound infection compared with surgical tracheostomy, thus facilitating mechanical ventilation, nursing procedures, reduction in sedation and early mobilization. Objective This is an observational case-control study that compares the results of PT in ICU patients with coronavirus disease 2019 (COVID-19) prospectively enrolled to a similar group of subjects, retrospectively recruited, without COVID-19. Methods Ninety-eight consecutive COVID-19 patients admitted to the ICU at Pisa Azienda Ospedaliero Universitaria Pisana between March 11th and May 20th, 2020 were prospectively studied. Thirty of them underwent PT using different techniques. Another 30 non-COVID-19 ICU patients were used as a control-group. The main outcome was to evaluate the safety and feasibility of PT in COVID-19 patients. We measured the rate of complications. Results Percutaneous tracheostomy was performed with different techniques in 30 of the 98 COVID-19 ICU patients admitted to the ICU. Tracheostomy was performed on day 10 (mean 10 ± 3.3) from the time of intubation. Major tracheal complications occurred in 5 patients during the procedure. In the control group of 30 ICU patients, no differences were found with regards to the timing of the tracheostomy, whereas a statistically significant difference was observed regarding complications with only one tracheal ring rupture reported. Conclusion Percutaneous tracheostomy in COVID-19 patients showed a higher rate of complications compared with controls even though the same precautions and the same expertise were applied. Larger studies are needed to understand whether the coronavirus disease itself carries an increased risk of tracheal damage.

Abstract Background Lung ultrasound can be used as an alternative to chest radiography (CXR) for the diagnosis and follow-up of various lung diseases in the intensive care unit (ICU). Our aim was to evaluate the influence that introducing a routine daily use of lung ultrasound in critically ill patients may have on the number of CXRs and as a consequence, on medical costs and radiation exposure. Methods Data were collected by conducting a retrospective evaluation of the medical records of adult patients who needed thoracic imaging and were admitted to our academic polyvalent ICU. We compared the number of CXRs and relative costs before and after the introduction of lung ultrasound in our ICU. Results A total of 4134 medical records were collected from January 2010 to December 2014. We divided our population into two groups, before (Group A, 1869 patients) and after (Group B, 2265 patients) the introduction of a routine use of LUS in July 2012. Group A performed a higher number of CXRs compared to Group B (1810 vs 961, P = 0.012), at an average of 0.97 vs 0.42 exams per patient. The estimated reduction of costs between Groups A and B obtained after the introduction of LUS, was 57%. No statistically significant difference between the outcome parameters of the two groups was observed. Conclusions Lung ultrasound was effective in reducing the number of CXRs and relative medical costs and radiation exposure in ICU, without affecting patient outcome.

Abstract Intraoperative transesophageal echocardiography is a minimally invasive monitoring tool that can provide real-time visual information on ventricular function and hemodynamic volume status in patients undergoing liver transplantation. The American Association for the Study of Liver Diseases states that transesophageal echocardiography should be used in all liver transplant candidates in order to assess chamber sizes, hypertrophy, systolic and diastolic function, valvular function, and left ventricle outflow tract obstruction. However, intraoperative transesophageal echocardiography can be used to “visualize” other organs too; thanks to its proximity and access to multiple acoustic windows: liver, lung, spleen, and kidney. Although only limited scientific evidence exists promoting this comprehensive use, we describe the feasibility of TEE in the setting of liver transplantation: it is a highly valuable tool, not only as a cardiovascular monitoring, but also as a tool to evaluate lungs and pleural spaces, to assess hepatic vein blood flow and inferior vena cava anastomosis and patency, i.e., in cases of modified surgical techniques. The aim of this case series is to add our own experience of TEE as a comprehensive intraoperative monitoring tool in the field of orthotopic liver transplantation (and major liver resection) to the literature.

Abstract Background Chest tube positioning is an invasive procedure associated with potentially serious injuries. In the last few years, we have been running a project directed at developing a practical simulator of a surgical procedure taught on our medical training program. The phantom model reconstructs the pleural anatomy, visible by lung ultrasound, used for the assessed performance of the Seldinger technique. The aim of the present study was to investigate the validity of this simulation technology for assessing residents in anesthesia and intensive care medicine; specifically, their skill in positioning a US-guided chest tube drain was tested using the simulator device. The second aim of the paper was to evaluate the learning curve of our residents over their 5-year study course and validate the phantom scoring system. Methods This was a prospective, single-blinded observational study. Participants were recruited from residents in anesthesia and intensive care medicine and divided into two groups: ‘Novice’ and ‘Expert,’ based on the course year attended (years 1, 2, and 3 vs. years 4 and 5, respectively). We asked them to position a chest tube drain in a phantom model, guided by ultrasound, to drain a simulated pleural effusion. Each subject performed two tests that simulated pleural effusions of 4 and 2 cm, respectively. Every step of the maneuver was constantly monitored and the performance scored by the investigators. We then performed a Spearman correlation analysis to evaluate the effect of experience level on the performance of the two groups of residents. Results Thirty-one residents were included in this study: 20 in the Novice group and 11 in the Expert group. The mean performance rating score was 0.75 ± 4.38 for the Novice Group and 5.91 ± 3.75 for the Expert group (p = 0.0026). The Spearman correlation analysis examining the relationship between year of residency and performance rating score confirmed a positive correlation (r = 0.58, p = 0.0006). Post-test trend analysis revealed a statistically significant linear trend for skill growth across time, i.e., course year (p = 0.0022). Conclusions Our simulated procedure using a phantom model of lung anatomy can accurately and reliably be used to assess the skill levels of operators in their ability to drain pleural effusion.

Background. Xenon-in-oxygen is a high density gas mixture and may improve PaO2/FiO2 ratio in morbidly obese patients uniforming distribution of ventilation during anesthesia. Methods. We compared xenon versus sevoflurane anesthesia in twenty adult morbidly obese patients (BMI>35) candidate for roux-en-Y laparoscopic gastric bypass and assessed PaO2/FiO2 ratio at baseline, at 15 min from induction of anaesthesia and every 60 min during surgery. Differences in intraoperative and postoperative data including heart rate, systolic and diastolic pressure, oxygen saturation, plateau pressure, eyes opening and extubation time, Aldrete score on arrival to the PACU were compared by the Mann-Whitney test and were considered as secondary aims. Moreover the occurrence of side effects and postoperative analgesic demand were assessed. Results. In xenon group PaO2-FiO2 ratio was significantly higher after 60 min and 120 min from induction of anesthesia; heart rate and overall remifentanil consumption were lower; the eyes opening time and the extubation time were shorter; morphine consumption at 72 hours was lower; postoperative nausea was more common. Conclusions. Xenon anesthesia improved PaO2/FiO2 ratio and maintained its distinctive rapid recovery times and cardiovascular stability. A reduction of opioid consumption during and after surgery and an increased incidence of PONV were also observed in xenon group.