Anticoagulation and Bleeding during Veno-Venous Extracorporeal Membrane Oxygenation: Insights from the PROTECMO Study.

Rationale: Definitive guidelines for anticoagulation management during veno-venous extracorporeal membrane oxygenation (VV ECMO) are lacking, whereas bleeding complications continue to pose major challenges. Objectives: To describe anticoagulation modalities and bleeding events in adults receiving VV ECMO. Methods: This was an international prospective observational study in 41 centers, from December 2018 to February 2021. Anticoagulation was recorded daily in terms of type, dosage, and monitoring strategy. Bleeding events were reported according to site, severity, and impact on mortality. Measurements and Main Results: The study cohort included 652 patients, and 8,471 days on ECMO were analyzed. Unfractionated heparin was the initial anticoagulant in 77% of patients, and the most frequently used anticoagulant during the ECMO course (6,221 d; 73%). Activated partial thromboplastin time (aPTT) was the most common test for monitoring coagulation (86% of days): the median value was 52 seconds (interquartile range, 39 to 61 s) but dropped by 5.3 seconds after the first bleeding event (95% confidence interval, -7.4 to -3.2; P < 0.01). Bleeding occurred on 1,202 days (16.5%). Overall, 342 patients (52.5%) experienced at least one bleeding event (one episode every 215 h on ECMO), of which 10 (1.6%) were fatal. In a multiple penalized Cox proportional hazard model, higher aPTT was a potentially modifiable risk factor for the first episode of bleeding (for 20-s increase; hazard ratio, 1.07). Conclusions: Anticoagulation during VV ECMO was a dynamic process, with frequent stopping in cases of bleeding and restart according to the clinical picture. Future studies might explore lower aPTT targets to reduce the risk of bleeding.

Metabolic support for patients on extra-corporeal membrane oxygenation.

PURPOSE OF REVIEW: The purpose of the review is to summarize recent research on metabolic support during extracorporeal membrane oxygenation. In this review, we cover the evidence on nutritional supplementation, both the route of supplementation, timing of initiation of supplementation as well as quantities of supplementation needed. In addition, we discuss the recent trend in awake extracorporeal membrane oxygenation (ECMO) and its benefits to patients. RECENT FINDINGS: As ECMO use continues to increase over the last few years, for both cardiovascular as well as respiratory failure, the need to optimize the metabolic states of patients has arisen. Increasing evidence has pointed towards this hitherto unexplored domain of patient care having a large impact on outcomes. Additionally, strategies such as awake ECMO for select patients has allowed them to preserve muscle mass which could aid in a faster recovery. SUMMARY: There is a role of optimal metabolic support in the early recovery of patients on ECMO that is currently under-recognized. Future directions of research that aim to improve post ECMO outcomes must focus on this area.

Antithrombin during veno-venous extracorporeal membrane oxygenation with heparin anticoagulation: A single-center cohort study.

INTRODUCTION: Antithrombin (AT) is a natural anticoagulant essential to enhancing the unfractionated heparin (UFH) anticoagulant effect. Its supplementation in the management of UFH-based anticoagulation during veno-venous extracorporeal membrane oxygenation (VV ECMO) has a strong pathophysiological rationale. METHODS: This is a single-center, retrospective cohort study of adult VV ECMO patients with anticoagulation maintained by UFH targeting an activated partial thromboplastin time (aPTT) of 40-50 s and AT activity >80%. We compare anticoagulation management and survival outcomes between AT subpopulations, defined by a threshold AT activity ≥80%. Linear and logistic regression analyses were used to evaluate the variation in AT activity and its association with ICU survival. RESULTS: In 244 patients enrolled from 2009 to 2022, anticoagulation was maintained by a median heparin dose of 11.4 IU/kg/h [IQR: 8.2-14.7] with a mean aPTT of 46.1 s (±7.3) and AT activity of 88.9% (±17.0). A lower mean aPTT, higher dose of UFH and shorter fraction of time without UFH were associated with higher AT activity (p < .01). Higher AT activity showed a consistent association with ICU survival (for 10% increase of AT, odds ratio for ICU mortality: 0.95; 95% CI 0.93-0.97; p value <.01). CONCLUSIONS: There is a positive association between AT activity and UFH requirements but no significant difference in the rate of bleeding events. A higher mean AT during VV ECMO was associated with ICU survival. Future studies are needed to differentiate between exogenously supplemented versus endogenous AT effect.

Effects of adding the second drainage cannula in severely hypoxemic patients supported with VV ECMO due to COVID-19-associated ARDS.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a recognized method of support in patients with severe and refractory acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 infection. While veno-venous (VV) ECMO is the most common type, some patients with severe hypoxemia may require modifications to the ECMO circuit. In this study, we aimed to investigate the effects of adding a second drainage cannula to the circuit in patients with refractory hypoxemia, on their gas exchange, mechanical ventilation, ECMO settings, and clinical outcomes. METHODS: We conducted an observational retrospective study based on a single-center institutional registry including all consecutive cases of COVID-19 patients requiring ECMO admitted to the Centre of Extracorporeal Therapies in Warsaw between March 1, 2020 and March 1, 2022. We selected patients who had an additional drainage cannula inserted. Changes in ECMO and ventilator settings, blood oxygenation, and hemodynamic parameters, as well as clinical outcomes were assessed. RESULTS: Of 138 VV ECMO patients, 12 (9%) patients met the inclusion criteria. Ten patients (83%) were men, and mean age was 42.2 ± 6.8. An addition of drainage cannula resulted in a significant raise in ECMO blood flow (4.77 ± 0.44 to 5.94 ± 0.81 [L/min]; p = 0.001), and the ratio of ECMO blood flow to ECMO pump rotations per minute (RPM), whereas the raise in ECMO RPM alone was not statistically significant (3432 ± 258 to 3673 ± 340 [1/min]; p = 0.064). We observed a significant drop in ventilator FiO2 and a raise in PaO2 to FiO2 ratio, while blood lactates did not change significantly. Nine patients died in hospital, one was referred to lung transplantation center, two were discharged uneventfully. CONCLUSIONS: The use of an additional drainage cannula in severe ARDS associated with COVID-19 allows for an increased ECMO blood flow and improved oxygenation. However, we observed no further improvement in lung-protective ventilation and poor survival.

Extracorporeal membrane oxygenation for COVID-19 and influenza H1N1 associated acute respiratory distress syndrome: a multicenter retrospective cohort study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has become an established rescue therapy for severe acute respiratory distress syndrome (ARDS) in several etiologies including influenza A H1N1 pneumonia. The benefit of receiving ECMO in coronavirus disease 2019 (COVID-19) is still uncertain. The aim of this analysis was to compare the outcome of patients who received veno-venous ECMO for COVID-19 and Influenza A H1N1 associated ARDS. METHODS: This was a multicenter retrospective cohort study including adults with ARDS, receiving ECMO for COVID-19 and influenza A H1N1 pneumonia between 2009 and 2021 in seven Italian ICU. The primary outcome was any-cause mortality at 60 days after ECMO initiation. We used a multivariable Cox model to estimate the difference in mortality accounting for patients' characteristics and treatment factors before ECMO was started. Secondary outcomes were mortality at 90 days, ICU and hospital length of stay and ECMO associated complications. RESULTS: Data from 308 patients with COVID-19 (N = 146) and H1N1 (N = 162) associated ARDS who had received ECMO support were included. The estimated cumulative mortality at 60 days after initiating ECMO was higher in COVID-19 (46%) than H1N1 (27%) patients (hazard ratio 1.76, 95% CI 1.17-2.46). When adjusting for confounders, specifically age and hospital length of stay before ECMO support, the hazard ratio decreased to 1.39, 95% CI 0.78-2.47. ICU and hospital length of stay, duration of ECMO and invasive mechanical ventilation and ECMO-associated hemorrhagic complications were higher in COVID-19 than H1N1 patients. CONCLUSION: In patients with ARDS who received ECMO, the observed unadjusted 60-day mortality was higher in cases of COVID-19 than H1N1 pneumonia. This difference in mortality was not significant after multivariable adjustment; older age and longer hospital length of stay before ECMO emerged as important covariates that could explain the observed difference. TRIAL REGISTRATION NUMBER: NCT05080933 , retrospectively registered.

Nutrition during extracorporeal life support: A review of pathophysiological bases and application of guidelines.

BACKGROUND: Patients on extracorporeal life support (ECLS), either for respiratory or cardiac support, are at high risk of malnutrition; guidelines on nutrition in critical care have not incorporated solid evidence regarding these settings. The aim of this narrative review is to gather the available evidence in the existing literature and transpose general principles to the ECLS population. METHODS: A literature review of observational and interventional studies on nutrition during ECLS, and evaluation of nutrition guidelines in this perspective. RESULTS: Nutrition is paramount for improving outcomes in ECLS, as well as in critically ill patients. The caloric needs during ECLS can vary according to the severity of the clinical state, sedation, paralysis, and temperature stability. Precise evaluation of energy expenditure by indirect calorimetry is difficult because ECLS is a system dedicated to removing carbon dioxide; however, modified equations composed of carbon dioxide values taken from the membrane lung are available. Guidelines suggest starting early enteral nutrition (EN) with a hypocaloric (70%-80% of the needs) strategy, also in acute states such as septic or cardiogenic shock. Moreover, EN, despite previous concerns, is feasible in prone position, an increasingly adopted strategy during mechanical ventilation. The catabolic state is maximal in these patients, causing a protein and muscular reduction. Therefore, adequate protein delivery should be guaranteed by administering a high protein intake of up to 2 g/kg/day. CONCLUSIONS: Studies on nutrition tailored to ECLS patients are warranted. Early hypocaloric EN with high protein intake, tailored on indirect calorimetry, may be the most appropriate option.

Use of nafamostat mesilate for anticoagulation during extracorporeal membrane oxygenation: A systematic review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) represents an advanced option for supporting refractory respiratory and/or cardiac failure. Systemic anticoagulation with unfractionated heparin (UFH) is routinely used. However, patients with bleeding risk and/or heparin-related side effects may necessitate alternative strategies: among these, nafamostat mesilate (NM) has been reported. METHODS: We conducted a systematic literature search (PubMed and EMBASE, updated 12/08/2021), including all studies reporting NM anticoagulation for ECMO. We focused on reasons for starting NM, its dose and the anticoagulation monitoring approach, the incidence of bleeding/thrombosis complications, the NM-related side effects, ECMO weaning, and mortality. RESULTS: The search revealed 11 relevant findings, all with retrospective design. Of these, three large studies reported a control group receiving UFH, the other were case series (n = 3) or case reports (n = 5). The main reason reported for NM use was an ongoing or high risk of bleeding. The NM dose varied largely as did the anticoagulation monitoring approach. The average NM dose ranged from 0.46 to 0.67 mg/kg/h, but two groups of authors reported larger doses when monitoring anticoagulation with ACT. Conflicting findings were found on bleeding and thrombosis. The only NM-related side effect was hyperkalemia (n = 2 studies) with an incidence of 15%-18% in patients anticoagulated with NM. Weaning and survival varied across studies. CONCLUSION: Anticoagulation with NM in ECMO has not been prospectively studied. While several centers have experience with this approach in high-risk patients, prospective studies are warranted to establish the optimal space of this approach in ECMO.

Inferior vena cava surgical cannulation for infants needing veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: Femoral cannulation for veno-venous extracorporeal membrane oxygenation is challenging in infants because of the diameter of the vein. CASE REPORT: Prolonged ECMO support (67 days) was necessary for an 8-month-old (8 kg) girl with acute respiratory distress syndrome that was caused by H1N1 influenza. After 30 days on ECMO support and using a single 16 Fr double-lumen cannula (internal jugular vein), a second cannula was necessary to ensure adequate flow. This second 12 Fr single-lumen cannula was surgically placed through the right common iliac vein. An excellent flow profile was then achieved and ECMO continued successfully for 37 more days. DISCUSSION: As a lifesaving option, this double caval configuration successfully optimized the flow profile and oxygenation, outweighing the related risks. CONCLUSION: In small children, a surgical approach to the inferior vena cava can be considered safe, especially in those cases where there is a shortage of adequate cannulas, or when central venous access is difficult.

Cutaneous Ulcer Caused by Apixaban Treatment Is Resolved after Replacement with Dabigatran.

Nowadays, novel oral anticoagulants (NOACs) have shown improved safety profile and efficacy compared to vitamin K antagonists in the prevention of thromboembolic events occurring during different pathological conditions. However, there are concerns and safety issues, mostly related to adverse events following interactions with other drugs, in real-world practice. We report the case of an 83-year-old woman who developed a non-bleeding leg ulcer not caused by trauma or other evident pathological conditions after 10 days of treatment with apixaban 5 mg/q.d. She was switched from apixaban to dabigatran and the leg ulcer rapidly improved and completely cicatrized in 40 days. The resolution of the ulcer and the toleration of dabigatran therapy suggest an apixaban-specific reaction; however, the pathological mechanism of ulcer onset is currently unclear. Careful evaluation of hospital databases of Molise region (Southern Italy) hospitals identified two similar cases between 2019 and 2021. These cases underline the necessity of careful post-marketing surveillance, considering the rapidly increasing number of patients treated with NOACs and patient's risk factors such as old age, high polypharmacy rate, co-morbidities, and peculiar genetic background related to NOACs pharmacokinetic features.

Reply to Sagliocco, O.; Betelli, M. Comment on "Fierro et al. Severe Hypotension, Bradycardia and Asystole after Sugammadex Administration in an Elderly Patient. Medicina 2021, 57, 79".

We thank Dr. Sagliocco and Dr. Betelli for their comments [...].

Vitamin D in critical care: where are we now and what is next?

PURPOSE OF REVIEW: To summarize the recent evidence on the role of vitamin D deficiency in critically ill patients and emerging data claiming a role of vitamin D in COVID-19. RECENT FINDINGS: Vitamin D is a strong predictor for worse outcomes in critically ill patients, and as well in COVID-19. The vitamin D content in typical nutrition regimes is lower than what is recommended for the general population. Although its supplementation has been shown to reduce respiratory tract infections, asthma exacerbations and mortality risk in noncritically ill patients, its role in the acute setting is not yet clear. Several small intervention trials have shown interesting results in COVID-19, and larger studies are ongoing. SUMMARY: Although research on this topic is still ongoing, it appears reasonable to recommend at least the standard vitamin dose for the healthy population (600--800 IU of native vitamin D3). Many questions remain on the actual role, the best metabolite, regime, and so forth. However, the role for vitamin D in bone health is clear. Elderly ICU survivors have a high risk for osteoporosis/fractures, so at least in this population, an optimal vitamin D status should be targeted.

Tracheostomy management in patients with severe acute respiratory distress syndrome receiving extracorporeal membrane oxygenation: an International Multicenter Retrospective Study.

BACKGROUND: Current practices regarding tracheostomy in patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome are unknown. Our objectives were to assess the prevalence and the association between the timing of tracheostomy (during or after ECMO weaning) and related complications, sedative, and analgesic use. METHODS: International, multicenter, retrospective study in four large volume ECMO centers during a 9-year period. RESULTS: Of the 1,168 patients treated with ECMO for severe ARDS (age 48 ± 16 years, 76% male, SAPS II score 51 ± 18) during the enrollment period, 353 (30%) and 177 (15%) underwent tracheostomy placement during or after ECMO, respectively. Severe complications were uncommon in both groups. Local bleeding within 24 h of tracheostomy was four times more frequent during ECMO (25 vs 7% after ECMO, p < 0.01). Cumulative sedative consumption decreased more rapidly after the procedure with sedative doses almost negligible 48-72 h later, when tracheostomy was performed after ECMO decannulation (p < 0.01). A significantly increased level of consciousness was observed within 72 h after tracheostomy in the "after ECMO" group, whereas it was unchanged in the "during-ECMO" group. CONCLUSION: In contrast to patients undergoing tracheostomy after ECMO decannulation, tracheostomy during ECMO was neither associated with a decrease in sedation and analgesia levels nor with an increase in the level of consciousness. This finding together with a higher risk of local bleeding in the days following the procedure reinforces the need for a case-by-case discussion on the balance between risks and benefits of tracheotomy when performed during ECMO.

Metabolic and Endocrine Challenges.

This review aims to provide an overview of metabolic and endocrine challenges in the setting of intensive care medicine. These are a group of heterogeneous clinical conditions with a high degree of overlap, as well as nonspecific signs and symptoms. Several diseases involve multiple organ systems, potentially causing catastrophic dysfunction and death. In the majority of cases, endocrine challenges accompany other organ failures or manifest as a complication of prolonged intensive care unit stay and malnutrition. However, when endocrine disorders present as an isolated syndrome, they are a rare and extreme manifestation. As they are uncommon, these can typically challenge both with diagnosis and management. Acute exacerbations may be elicited by triggers such as infections, trauma, surgery, and hemorrhage. In this complex scenario, early diagnosis and prompt treatment require knowledge of the specific endocrine syndrome. Here, we review diabetic coma, hyponatremia, hypercalcemia, thyroid emergencies, pituitary insufficiency, adrenal crisis, and vitamin D deficiency, highlighting diagnostic tools and tricks, and management pathways through defining common clinical presentations.

Hemoperfusion and blood purification strategies in patients with COVID-19: A systematic review.

BACKGROUND: Coronavirus disease-19 (COVID-19) ranges from asymptomatic infection to severe cases requiring admission to the intensive care unit. Together with supportive therapies (ventilation in particular), the suppression of the pro-inflammatory state has been a hypothesized target. Pharmacological therapies with corticosteroids and interleukin-6 (IL-6) receptor antagonists have reduced mortality. The use of extracorporeal cytokine removal, also known as hemoperfusion (HP), could be a promising non-pharmacological approach to decrease the pro-inflammatory state in COVID-19. METHODS: We conducted a systematic review of PubMed and EMBASE databases in order to summarize the evidence regarding HP therapy in COVID-19. We included original studies and case series enrolling at least five patients. RESULTS: We included 11 articles and describe the characteristics of the populations studied from both clinical and biological perspectives. The methodological quality of the included studies was generally low. Only two studies had a control group, one of which included 101 patients in total. The remaining studies had a range between 10 and 50 patients included. There was large variability in the HP techniques implemented and in clinical and biological outcomes reported. Most studies described decreasing levels of IL-6 after HP treatment. CONCLUSION: Our review does not support strong conclusions regarding the role of HP in COVID-19. Considering the very low level of clinical evidence detected, starting HP therapies in COVID-19 patients does not seem supported outside of clinical trials. Prospective randomized data are needed.

Immunological and Hematological Response in COVID-19.

INTRODUCTION: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently and rapidly emerged and developed into a global pandemic. Through the renin-angiotensin system, the virus may impact the lung circulation, but the expression on endothelium may conduct to its activation and further systemic damage. While precise mechanisms underlying these phenomena remain to be further clarified, the understanding of the disease, its clinical course, as well as its immunological and hematological implications is of paramount importance in this phase of the pandemic. METHODS: This review summarizes the evidence gathered until 12 June; electronic databases were screened for pertinent reports on coronavirus and inflammatory and hematological changes. Search was conducted by two independent investigators; keywords used were "SARS-CoV-2," "COVID-19," "inflammation," "immunological," and "therapy." RESULTS: The viral infection is able to trigger an excessive immune response in predisposed individuals, which can result in a "cytokine storm" that presents an hyperinflammation state able to determine tissue damage and vascular damage. An explosive production of proinflammatory cytokines such as TNF-α IL-1ß and others occurs, greatly exaggerating the generation of molecule-damaging reactive oxygen species. These changes are often followed by alterations in hematological parameters. Elucidating those changes in SARS-CoV-2-infected patients could help to understand the pathophysiology of disease and may provide early clues to diagnosis. Several studies have shown that hematological parameters are markers of disease severity and suggest that they mediate disease progression. According to the available literature, the primary hematological symptoms-associated COVID-19, and which distinguish patients with severe disease from patients with nonsevere disease, are lymphocytopenia, thrombocytopenia, and a significant increase in D-dimer levels. CONCLUSIONS: SARS-CoV-2 infection triggers a complex response altering inflammatory, hematological, and coagulation parameters. Measuring these alterations at certain time points may help identify patients at high risk of disease progression and monitor the disease severity.

COVID-19 and Extracorporeal Membrane Oxygenation.

INTRODUCTION: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently and rapidly emerged and developed into a global pandemic. In SARS-CoV-2 patients with refractory respiratory failure, there may be a role for veno-venous extracorporeal membrane oxygenation (V-V ECMO) as a life-saving rescue intervention. METHODS: This review summarizes the evidence gathered until June 12, 2020; electronic databases were screened for pertinent reports on coronavirus and V-V ECMO. Search was conducted by two independent investigators; keywords used were SARS-CoV-2, COVID-19, ECMO, and extracorporeal life support (ECLS). RESULTS: Many patients with COVID-19 experience moderate symptoms and a relatively quick recovery, but others must be admitted into the intensive care unit due to severe respiratory failure and often must be mechanically ventilated. Further deterioration may require institution of extracorporeal oxygenation. Infection mechanisms may trigger "cytokine storm," an inflammatory disorder notable for multi-organ system failure; together with other metabolic and hematological changes, these amplify the changes pertinent to ECMO therapy, often exaggerating blood coagulation disorders. Thirty-two studies were found describing experiences with ECMO in the treatment of COVID-19. Of 4,912 COVID-19 patients, 2,119 (43%) developed ARDS and 2,086 (42%) were transferred to the ICU; 1,015 patients (21%) were treated with ECMO. While in an overall cohort, observed mortality was 640 (13%), the mortality within ECMO subgroups reached up to 34.6% (range 0-100%). CONCLUSION: The efficacy of ECMO treatment for COVID-19 is largely dependent on the expertise of the center in ECLS due to the interplay between the changes in hematological and inflammatory modulators associated with both COVID-19 and ECMO. In order to support gas exchange during early infection with SARS-CoV-2, ECMO has a strong rationale for the treatment of the most critically ill patients. Due to the limited resources during a global pandemic, ECMO should be reserved for only the most severe cases of COVID-19.

Micronutrients in Sepsis and COVID-19: A Narrative Review on What We Have Learned and What We Want to Know in Future Trials.

Sepsis remains the leading cause of mortality in hospitalized patients, contributing to 1 in every 2-3 deaths. From a pathophysiological view, in the recent definition, sepsis has been defined as the result of a complex interaction between host response and the infecting organism, resulting in life-threatening organ dysfunction, depending on microcirculatory derangement, cellular hypoxia/dysoxia driven by hypotension and, potentially, death. The high energy expenditure driven by a high metabolic state induced by the host response may rapidly lead to micronutrient depletion. This deficiency can result in alterations in normal energy homeostasis, free radical damage, and immune system derangement. In critically ill patients, micronutrients are still relegated to an ancillary role in the whole treatment, and always put in a second-line place or, frequently, neglected. Only some micronutrients have attracted the attention of a wider audience, and some trials, even large ones, have tested their use, with controversial results. The present review will address this topic, including the recent advancement in the study of vitamin D and protocols based on vitamin C and other micronutrients, to explore an update in the setting of sepsis, gain some new insights applicable to COVID-19 patients, and to contribute to a pathophysiological definition of the potential role of micronutrients that will be helpful in future dedicated trials.

Severe Hypotension, Bradycardia and Asystole after Sugammadex Administration in an Elderly Patient.

Background and Objectives: Sugammadex is a modified γ-cyclodextrin largely used to prevent postoperative residual neuromuscular blockade induced by neuromuscular aminosteroid blocking agents. Although Sugammadex is considered more efficacious and safer than other drugs, such as Neostigmine, significant and serious complications after its administration, such as hypersensitivity, anaphylaxis and, more recently, severe cardiac events, are reported. Case presentation: In this report, we describe the case of an 80-year-old male with no medical history of cardiovascular disease who was scheduled for percutaneous nephrolithotripsy under general anesthesia. The intraoperative course was uneventful; however, the patient developed a rapid and severe hypotension, asystole and cardiac arrest after Sugammadex administration. Spontaneous cardiac activity and hemodynamic stability was restored with pharmacological therapy and chest compression. The patient was stabilized and discharged uneventfully on postoperative day 10. Conclusions: The potential causes of cardiac arrest after Sugammadex administration have been carefully considered, yet all indications point to Sugammadex as the direct causative agent. On the basis of laboratory and clinical tests, we can exclude among the cause of bradycardia, Kounis syndrome, acute myocardial infarction, coronary spasm and other arrhythmias, but not anaphylaxis. Although Sugammadex is considered an increasingly important option in the prevention of postoperative residual neuromuscular blockade, anesthesiologists should consider it a causative agent of cardiac arrest during surgery. This case highlights the necessity of increased pharmacovigilance and further studies to examine Sugammadex safety and mechanism through which it may cause severe bradycardia, hypotension and cardiac arrest.

Impact of Physical Activity on Disability Risk in Elderly Patients Hospitalized for Mild Acute Diverticulitis and Diverticular Bleeding Undergone Conservative Management.

Background and Objectives: The role of physical activity (PA) in elderly patients admitted to surgical units for mild acute diverticulitis in the development of disability has not been clarified so far. Our aim is to demonstrate the relationship between physical activity and better post-discharge outcomes on disability in elderly population affected by diverticular disease. Materials and Methods: We retrospectively reviewed data of 56 patients (32 Males-24 females) collected from October 2018 and March 2020 at Cardarelli Hospital in Campobasso. We included patients older than 65 yrs admitted for acute bleeding and acute diverticulitis stage ≤II, characterized by a good independence status, without cognitive impairment and low risk of immobilization, as evaluated by activity of daily living (ADL) and the instrumental activity of daily living (IADL) and Exton-Smith Scale. "Physical Activity Scale for the Elderly" (PASE) Score evaluated PA prior to admission and at first check up visit. Results: 30.4% of patients presented a good PA, 46.4% showed moderate PA and 23.2% a low PA score. A progressive reduction in ADL and IADL score was associated with lower physical activity (p value = 0.0038 and 0.0017). We consider cognitive performance reduction with a cut off of loss of more than 5 points in Short Port of ADL and IADL and a loss of more than 15 points on Exton-Smith Scale, (p-value 0.017 and 0.010). In the logistic regression analysis, which evaluated the independent role of PASE in disability development, statistical significance was not reached, showing an Odds Ratio of 0.51 95% CI 0.25-1.03 p value 0.062. Discussion: Reduced physical activity in everyday life in elderly is associated with increased post-hospitalization disability regarding independence, cognitive performance and immobilization. Conclusions: Poor physical performance diagnosis may allow to perform a standardized multidimensional protocol to improve PA to reduce disability incidence.

COVID-19 and ECMO: the interplay between coagulation and inflammation-a narrative review.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presently become a rapidly spreading and devastating global pandemic. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) may serve as life-saving rescue therapy for refractory respiratory failure in the setting of acute respiratory compromise such as that induced by SARS-CoV-2. While still little is known on the true efficacy of ECMO in this setting, the natural resemblance of seasonal influenza's characteristics with respect to acute onset, initial symptoms, and some complications prompt to ECMO implantation in most severe, pulmonary decompensated patients. The present review summarizes the evidence on ECMO management of severe ARDS in light of recent COVID-19 pandemic, at the same time focusing on differences and similarities between SARS-CoV-2 and ECMO in terms of hematological and inflammatory interplay when these two settings merge.