Never Give Up: lesson learned from a severe COVID-19 patient.

We here report the clinical course of a 72-year old Caucasian male (M.A.) admitted for SARS-CoV2 pneumonia at our University Hospital in Modena. A multidisciplinary medical staff composed by different specialists (infectious diseases, pulmonology, intensive care) was in charge for caring and assuming shared clinical decisions

Primjena programa ubrzanog oporavka nakon barijatrijske kirurgije: analiza kliničkih ishoda i isplativosti

Enhanced recovery after surgery (ERAS) programs are perioperative evidencebased interventions that have the purpose of making the perioperative pathway more efficient in safeguarding patient safety and quality of care. Recently, several ERAS components have been introduced in the setting of bariatric surgery (Enhanced Recovery After Bariatric Surgery, ERABS). The aim of the present study was to evaluate clinical efficiency and cost-effectiveness of the implementation of an ERABS program. It was a retrospective case-control study comparing a group of adult obese (body mass index >40) patients treated according to the ERABS protocol (2014-2015) with a historical control group that received standard care (2013-2014) in the General and Emergency Surgery Department, Arcispedale S. Maria Nuova Hospital, Reggio Emilia, Italy. Data on the occurrence of complications, mortality, re-admissions and re-operations were extracted retrospectively from medical case notes and emergency patient admission lists. Length of hospital stay was significantly different between the two cohort patients. In the control group, the mean length of stay was 12.6±10.9 days, whereas in the ERABS cohort it was 7.1±2.9 days (p=0.02). During hospital stay, seven patients in the control group developed surgical complications, including one patient with major complications, whereas in the ERABS group three patients developed minor complications. Economic analysis revealed a different cost distribution between the two groups. On the whole, there were significant savings for almost all the variables taken into consideration, mainly driven by exclusion of using intensive are unit, which is by far more expensive than the average cost of post-anesthesia care unit. Our study confirmed the implementation of an ERABS protocol to have shortened hospital stay and was cost-saving while safeguarding patient safety.Programi ubrzanog oporavka nakon operacije (Enhanced Recovery After Surgery, ERAS) su perioperacijske intervencije zasnovane na dokazima kojima je svrha učiniti perioperacijski tijek učinkovitijim osiguravajući bolesnikovu sigurnost i kvalitetu skrbi. Odnedavno je nekoliko sastavnica programa ERAS uvedeno u okruženje barijatrijske kirurgije (Enhanced Recovery After Bariatric Surgery, ERABS). Cilj ovoga istraživanja bio je procijeniti kliničku učinkovitost i isplativost provođenja programa ERABS. U ovoj retrospektivnoj studiji slučaja i kontrola uspoređena je skupina odraslih pretilih bolesnika (indeks tjelesne mase >40) liječenih prema protokolu ERABS (2014.-2015.) s povijesnom kontrolnom skupinom koja je primala standardnu skrb (2013.-2014.) u Klinici za opću i hitnu kirurgiju, Bolnica Arcispedale S. Maria Nuova, Reggio Emilia, Italija. Podaci o pojavnosti komplikacija, smrtnosti, ponovnom prijmu i ponovljenim operacijama retrospektivno su izvedeni iz bolesničkih kartona i prijamnih lista. Duljina boravka u bolnici značajno se razlikovala među dvjema skupinama bolesnika. U kontrolnoj skupini srednja duljina boravka u bolnici bila je 12,6±10,9 dana, dok je skupini ERABS iznosila 7,1±2,9 dana (p=0,02). Kod prijma se kirurška komplikacija razvila u 7 osoba iz kontrolne skupine; od toga je jedan bolesnik imao teže komplikacije, dok su u skupini ERABS manje komplikacije zabilježene kod 3 bolesnika. Ekonomska analiza pokazala je drukčiju raspoređenost troškova u dvjema skupinama. Sve u svemu, značajne uštede u gotovo svim ispitivanim varijablama uglavnom su nastale zbog isključenja uporabe jedinice intenzivnog liječenja, što je daleko skuplje od prosječnih troškova u jedinici skrbi poslije anestezije. Naše je istraživanje potvrdilo da primjena protokola ERABS skraćuje boravak u bolnici i snižava troškove pritom osiguravajući sigurnost bolesnika

Coagulopathy in liver diseases: complication or therapy?

Coagulopathy in cirrhosis is a composite condition where liver synthetic deficit rebalances coagulation to a parallel reduction of both pro- and anticoagulant factors. Cirrhosis is therefore no longer considered a hypocoagulable state but rather a more unstable hemostatic balance with a lower threshold for tipping toward thrombosis or bleeding. Tendency to bleeding in cirrhosis is due to the reduction in the synthesis of procoagulants and a low platelet count as well as hyperfibrinolysis. Variceal hemorrhage is a frequent bleeding complication in decompensated cirrhosis. However, the possible contribution of coagulopathy as a precipitant or an aggravating factor is poorly documented and further data are required to clarify its real contributing role. Moreover, apart from the gastrointestinal tract, the occurrence of spontaneous and procedure-related bleeding elsewhere in the body, whilst not uncommon, is less than would be expected. By contrast, a large-scale population-based study has shown the propensity towards venous thrombosis in patients with liver diseases. Portal vein thrombosis (PVT) is a critical but frequent event occurring in up to 40% of patients with liver cirrhosis. PVT causes deterioration of the clinical course, the complications of portal hypertension and an increase in post-transplant mortality. The pathogenesis of PVT includes both local alterations, like blood flow reduction and endothelial activation, and systemic derangement. Systemic prohemostatic alterations include high von Willebrand factor, low ADAMTS-13, low levels of anticoagulants (antithrombin, proteins C and S) and increases in procoagulants like factor VIII. Low-molecular-weight heparin such as enoxaparin has proven to be safe and effective in both the treatment and prevention of PVT. In addition, patients in prophylaxis with enoxaparin showed a lower rate of decompensation and a better survival without bleeding complications. In such patients, circulating bacterial DNA, endotoxemia and markers of inflammation were attenuated compared to controls. These results therefore suggest a possible connection between enoxaparin, decrease of endotoxemia and reduction of portal hypertension. The approach to the coagulopathy in patients with liver diseases is changing: while the main goal for clinicians so far has been to reduce the risk of bleeding, the results of these new studies highlight the importance of preventing or treating thrombophilic disorders like PVT to avoid microcirculatory damage and eventually liver decompensation

Perioperative effects of high doses of intraoperative thymoglobulin induction in liver transplantation

Aim: To describe our single-centre experience in liver transplantation (LT) with the infusion of high perioperative thymoglobulin doses. The optimal dosage and timing of thymoglobulin(®) [antithymocyte globulin (ATG)] administration during LT remains controversial. Cytokine release syndrome, haemolytic anaemia, thrombocytopenia, neutropenia, fever and serum sickness are potential adverse effects associated with ATG infusion. Methods: Between December 2009 and December 2010, 16 adult non-randomized patients (ATG group), receiving a liver graft from a deceased donor, received an intraoperative infusion (4-6 h infusion) of thymoglobulin (3 mg/kg, ATG: Thymoglobuline(®)). These patients were compared (case control approach) with 16 patients who had a liver transplant without ATG treatment (control group) to evaluate the possible effects of intraoperative ATG infusion. The matching parameters were: Sex, recipient age (± 5 years), LT indication including viral status, MELD score (± 5 points), international normalized ratio and platelet count (as close as possible). The exclusion criteria for both groups included the following: Multi-organ or living donor transplant, immunosuppressive therapy before transplantation, contraindications to the administration of any thymocyte globulin, human immunodeficiency virus seropositivity, thrombocytopenia [platelet < 50000/μL] or leukopenia [white blood cells < 1000/μL]. The perioperative side effects (haemodynamic alterations, core temperature variations, colloids and crystalloids requirements, and surgical time) possibly related to ATG infusion and the thromboelastographic (TEG) evaluation of the ATG effects on coagulation, blood loss and blood product transfusion were analysed during the operation and the first three postoperative days. Results: Intraoperative ATG administration was associated with longer surgical procedures [560 ± 88 min vs 480 ± 83 min (control group), P = 0.013], an intraoperative core temperature more than 37 °C (50% of ATG patients vs 6.2% of control patients, P = 0.015), major intraoperative blood loss [3953 ± 3126 mL vs 1419 ± 940 mL (control group), P = 0.05], higher red blood cell [2092 ± 1856 mL ATG group vs 472 ± 632 mL (control group), P = 0.02], fresh frozen plasma [671 ± 1125 mL vs 143 ± 349 mL (control group), P = 0.015], and platelet [374 ± 537 mL vs 15.6 ± 62.5 mL (control group), P = 0.017] transfusion, and a higher requirement for catecholamines (0.08 ± 0.07 μg/kg per minutes vs 0.01 ± 0.38 μg/kg per minutes, respectively, in the ATG and control groups) for haemodynamic support. The TEG tracings changed to a straight line during ATG infusion (preanhepatic and anhepatic phases) in 81% of the patients from the ATG group compared to 6.25% from the control group (P < 0.001). Patients from the ATG group compared to controls had higher post-op core temperatures (38 °C ± 1.0 °C vs 37.3 °C ± 0.5 °C; P = 0.02), an increased need of noradrenaline (43.7% vs 6.25%, P = 0.037), received more platelet transfusions (31.5% vs 0%, P = 0.04) and required continuous renal replacement therapy (4 ATG patients vs none in the control group; P = 0.10). ATG infusion was considered the cause of a fatal anaphylactic shock and of a suspected adverse reaction that led to intravascular haemolysis and acute renal failure. Conclusion: The side effects and the coagulation imbalance observed in patients receiving a high dosage of ATG suggest caution in the use of thymoglobulin during LT

Thromboelastographic reference ranges for a cirrhotic patient population undergoing liver transplantation

Aim: To describe the thromboelastography (TEG) "reference" values within a population of liver transplant (LT) candidates that underline the differences from healthy patients. Methods: Between 2000 and 2013, 261 liver transplant patients with a model for end-stage liver disease (MELD) score between 15 and 40 were studied. In particular the adult patients (aged 18-70 years) underwent to a first LT with a MELD score between 15 and 40 were included, while all patients with acute liver failure, congenital bleeding disorders, and anticoagulant and/or antiplatelet drug use were excluded. In this population of cirrhotic patients, preoperative haematological and coagulation laboratory tests were collected, and the pretransplant thromboelastographic parameters were studied and compared with the parameters measured in a previously studied population of 40 healthy subjects. The basal TEG parameters analysed in the cirrhotic population of liver candidates were as follows: Reaction time (r), coagulation time (k), Angle-Rate of polymerization of clot (α Angle), Maximum strenght of clot (MA), Amplitudes of the TEG tracing at 30 min and 60 min after MA is measured (A30 and A60), and Fibrinolysis at 30 and 60 min after MA (Ly30 and Ly60). The possible correlation between the distribution of the reference range and the gender, age, MELD score (higher or lower than 20) and indications for transplantation (liver pathology) were also investigated. In particular, a MELD cut-off value of 20 was chosen to verify the possible correlation between the thromboelastographic reference range and MELD score. Results: Most of the TEG reference values from patients with end-stage liver disease were significantly different from those measured in the healthy population and were outside the suggested normal ranges in up to 79.3% of subjects. Wide differences were found among all TEG variables, including r (41.5% of the values), k (48.6%), α (43.7%), MA (79.3%), A30 (74.4%) and A60 (80.9%), indicating a prevailing trend to hypocoagulability. The differences between the mean TEG values obtained from healthy subjects and the cirrhotic population were statistically significant for r (P = 0.039), k (P < 0.001), MA (P < 0.001), A30 (P < 0.001), A60 (P < 0.001) and Ly60 (P = 0.038), indicating slower and less stable clot formation in the cirrhotic patients. In the cirrhotic population, 9.5% of patients had an r value shorter than normal, indicating a tendency for faster clot formation. Within the cirrhotic patient population, gender, age and the presence of hepatocellular carcinoma or alcoholic cirrhosis were not significantly associated with greater clot firmness or enhanced whole blood clot formation, whereas greater clot strength was associated with a MELD score < 20, hepatitis C virus and cholestatic-related cirrhosis (P < 0.001; P = 0.013; P < 0.001). Conclusion: The range and distribution of TEG values in cirrhotic patients differ from those of healthy subjects, suggesting that a specific thromboelastographic reference range is required for liver transplant candidates

Management of Severe Bleeding in Liver Disease and Transplantation

The concept that patients with cirrhosis are at increased risk of bleeding events is probably out of date. Liver failure is accompanied by multiple changes in the hemostatic system, because of reduced plasma levels of procoagulative and anticoagulative clotting factors synthesized by the intact liver. Thrombocytopenia is very frequent ranking first among the altered hematological tests but Von Willebrand factor is elevated and ADAMTS-13 instead decreased, counterbalancing/compensating in some way the thrombocytopenia. The hemostatic system is then in a delicate balance between prothrombotic and antithrombotic processes. Since the global effect of liver disease on the hemostatic system is complex, patients with end-stage liver disease (ESLD) can experience severe bleeding or, at the opposite, thrombotic complications. Conventional coagulation tests such as prothrombin time (PT) and international normalized ratio (INR) are not able to provide information on the actual coagulation status of the patient as well as to predict possible bleeding or thrombotic events in patients with liver disease. Standard hemostatic tests which are inadequate to evaluate the so-called rebalanced hemostatic profile of the cirrhotic patient may provide misleading information regarding the risk of bleeding: in particular, clinicians have to be aware that unneeded, useless, or even dangerous pro-hemostatic factors might be administered with no demonstrated benefit. Because of the limits of conventional coagulation tests, in recent years, the viscoelastic tests (Thromboelastography/thromboelastomatry) have gained increasing importance. A more dynamic and targeted approach to the overall hemostatic process is at the base of their success providing a visual information on fibrinolysis, on the presence of endogenous heparinoids and tendency to hypercoagulability: these characteristics make these tests ideal for a rapid diagnosis of the type of coagulopathy and for an appropriate choice of the therapeutic option in patients with acute or chronic liver disease

Predictive factors of short term outcome after liver transplantation: A review

Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early post-transplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests (platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores (model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function) have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1(th) and the 5(th) day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients could be greatly improved by using clinically reliable tools to predict early graft function

Transoesophageal echocardiography during liver transplantation

Liver transplantation (LT) has become the standard of care for patients with end stage liver disease. The allocation of organs, which prioritizes the sickest patients, has made the management of liver transplant candidates more complex both as regards their comorbidities and their higher risk of perioperative complications. Patients undergoing LT frequently display considerable physiological changes during the procedures as a result of both the disease process and the surgery. Transoesophageal echocardiography (TEE), which visualizes dynamic cardiac function and overall contractility, has become essential for perioperative LT management and can optimize the anaesthetic management of these highly complex patients. Moreover, TEE can provide useful information on volume status and the adequacy of therapeutic interventions and can diagnose early intraoperative complications, such as the embolization of large vessels or development of pulmonary hypertension. In this review, directed at clinicians who manage TEE during LT, we show why the procedure merits a place in challenging anaesthetic environment and how it can provide essential information in the perioperative management of compromised patients undergoing this very complex surgical procedure