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.

Donor-derived carbapenem-resistant gram-negative bacterial infections in solid organ transplant recipients: Active surveillance enhances recipient safety.

Donor-derived infections (DDIs) caused by carbapenem-resistant gram-negative bacteria (CR-GNB) in solid organ transplant recipients are potentially life-threatening. In this prospective study, we evaluated the incidence, factors associated with transmission, and the outcome of recipients with unexpected CR-GNB DDIs after the implementation of our local active surveillance system (LASS). LASS provides for early detection of unexpected donor CR-GNB infections, prophylaxis of recipients at high risk, and early diagnosis and treatment of DDIs. Whole genome sequencing confirmed DDI. Among 791 recipients, 38 (4.8%) were at high risk of unexpected CR-GNB DDI: 25 for carbapenem-resistant Enterobacterales (CRE) and 13 for carbapenem-resistant Acinetobacter baumannii (CRAB). Transmission did not occur in 27 (71%) cases, whereas DDIs occurred in 9 of 25 of CRE and 2 of 13 of CRAB cases. Incidence of CR-GNB DDI was 1.4%. Recipients of organs with CR-GNB-positive preservation fluid and liver recipients from a donor with CRE infection were at the highest risk of DDI. There was no difference in length of hospital stay or survival in patients with and without CR-GNB DDI. Our LASS contains transmission and mitigates the negative impacts of CR-GNB DDI. Under well-defined conditions, organs from donors with CR-GNB may be considered after a thorough evaluation of the risk/benefit profile.

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.

Right vs left portal branch puncture in TIPS creation with controlled expansion covered stent: comparison of hemodynamic and clinical outcomes.

PURPOSE: To retrospectively compare outcomes of TIPS performed by puncturing left portal vein (LPV) vs right portal vein (RPV) to access the portal system. MATERIALS AND METHODS: One hundred ninety-three consecutive patients underwent TIPS with controlled expansion covered stent by using the LPV (37 patients) or the RPV (156 patients). Patients were followed until the last clinical evaluation, liver transplantation, or death. RESULTS: Demographics and clinical characteristics of the two groups were comparable. The median follow-up was 9.6 months (range 0.1-50.6). Portosystemic pressure gradient (PSG) before TIPS 15.7 mmHg ± 4.7 in RPV group (RPVG) vs 15.4 mmHg ± 4.5 in LPV group (LPVG) (p = 0.725). After TIPS, PSG 6.3 mmHg ± 2.8 in RPVG vs 6.2 mmHg ± 2.2 (p = 0.839). In LPVG, the stent was dilated to 8-mm in 95% of patients vs 77% of RPVG (p = 0.015). Two (5.4%) and 22 (14%) patients underwent TIPS revision in LPVG and RPVG (p = 0.15). The incidence of overt HE was 13% in LPVG and 24% in RPVG (p = 0.177). Rebleeding occurred in 3 of 49 patients (6%) with variceal bleeding as an indication: 2/41 patients (4.9%) in RPVG vs 1/8 patients (12.5%) in LPVG (p = 0.417). Among 126 patients with refractory ascites 20 patients (15.9%) needed paracentesis 3 months after the procedure: 18/101 patients (17.8%) in RPVG vs 2/25 patients (8%) in LPVG (p = 0.231). Thirty-seven patients (19%) died: 32 (21%) in RPVG and 5 (14%) in LPVG (p = 0.337). CONCLUSION: Compared with RPV puncture, in TIPS created through the LPV, the targeted PSG was reached with a smaller stent diameter. However, no significant difference in clinical outcomes was observed. KEY POINTS: • A LPV approach for TIPS creation does not lead to better control of complications of portal hypertension as compared to a RPV approach.

Clinical outcomes of transjugular intrahepatic portosystemic shunt with PTFE-covered stents after liver transplantation and technical results in split and whole liver graft recipients.

OBJECTIVES: To assess the outcomes of transjugular intrahepatic portosystemic shunt (TIPS) creation using PTFE-covered stents in liver transplant (LT) recipients and to analyze the technical result of TIPS creation in split grafts (SG) compared with whole liver grafts (WG). METHODS AND MATERIALS: Single-center, retrospective study, analyzing LT patients who underwent TIPS using PTFE-covered stents. Clinical and technical variables were analyzed. RESULTS: Between 2005 and 2021, TIPS was created using PTFE-covered stents in 48 LT patients at a median of 43 months (range, 0.5-192) after LT. TIPS indications were refractory ascites (RA) in 33 patients (69%), variceal bleeding (VB) in 9 patients (19%), others in 6 (12%). Ten patients (21%) received a SG. Technical success rate was 100% in both groups: in two WG recipients, (5%) a second attempt was required. An unconventional approach (combined transhepatic or transplenic access) was needed in 2 WG (5%) and 2 SG recipients (20%). Two procedure-related death occurred in the WG group. After a median follow-up of 22 months (range, 0,1-144), 16 patients (48%) in the RA group did not require post-TIPS paracentesis, in the VB group rebleeding occurred in 3 patients (33%). Fifteen patients (31%) underwent TIPS revision. Overt hepatic encephalopathy occurred in 14 patients (29%). Patient survival at 6 months, 1 year, and 3 years was 77%, 66%, and 43%, respectively. CONCLUSIONS: The feasibility and safety of TIPS creation in SG are comparable to that of WG. TIPS creation using PTFE-covered stents represents a viable option to treat portal hypertensive complications in LT recipients. KEY POINTS: • TIPS creation using PTFE-covered stents represents a viable option to treat complications of PH in LT recipients. • TIPS creation in LT SG recipients appears to be safe and feasible as in WG. • Results from this study may help to refine the management of LT patients with recurrent portal hypertensive complications encouraging physicians to consider TIPS creation as a treatment option in both SG and WG recipients.

The Effect of Borderline Pulmonary Hypertension on Survival in Chronic Lung Disease.

BACKGROUND: The impact of the new "borderline" hemodynamic class for pulmonary hypertension (PH) (mean pulmonary artery pressure [mPAP], 21-24 mm Hg and pulmonary vascular resistance, [PVR], ≥3 wood units, [WU]) in chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) is unclear. OBJECTIVES: The aim of this study was to assess the effect of borderline PH (BLPH) on survival in COPD and ILD patients. METHOD: Survival was analyzed from retrospective data from 317 patients in 12 centers (Italy, Spain, UK) comparing four hemodynamic groups: the absence of PH (NoPH; mPAP <21 mm Hg or 21-24 mm Hg and PVR <3 WU), BLPH (mPAP 21-24 mm Hg and PVR ≥3 WU), mild-moderate PH (MPH; mPAP 25-35 mm Hg and cardiac index [CI] ≥2 L/min/m2), and severe PH (SPH; mPAP ≥35 mm Hg or mPAP ≥25 mm Hg and CI <2 L/min/m2). RESULTS: BLPH affected 14% of patients; hemodynamic severity did not predict survival when COPD and ILD patients were analyzed together. However, survival in the ILD cohort for any PH level was worse than in NoPH (3-year survival: NoPH 58%, BLPH 32%, MPH 28%, SPH 33%, p = 0.002). In the COPD cohort, only SPH had reduced survival compared to the other groups (3-year survival: NoPH 82%, BLPH 86%, MPH 87%, SPH 57%, p = 0.005). The mortality risk correlated significantly with mPAP in ILD (hazard ratio [HR]: 2.776, 95% CI: 2.057-3.748, p < 0.001) and notably less in COPD patients (HR: 1.015, 95% CI: 1.003-1.027, p = 0.0146). CONCLUSIONS: In ILD, any level of PH portends worse survival, while in COPD, only SPH presents a worse outcome.

Portal vein puncture-related complications during transjugular intrahepatic portosystemic shunt creation: Colapinto needle set vs Rösch-Uchida needle set.

Transjugular portal vein puncture is considered the riskiest step in TIPS creation with possible incidence of portal vein puncture-related complications (PVPC). The Colapinto and the Rösch-Uchida needle sets are two different needle sets currently available. To date, there have been no randomized control trials or systematic reviews which compare the incidence of PVPC when using the two different needle sets. The aim of this literature review is to assess the rate of PVPC associated with the different needle sets used in the creation of TIPS. From the described search, 1500 articles were identified and 34 met the inclusion criteria. Outcome measured was the prevalence of PVPC using the different needle sets. Overall 212 (3.6%) PVPC were reported in 5865 patients; 142 (3.5%) reported in 4000 cases using the Rösch-Uchida set and 70 (3.7%) in 1865 patients using the Colapinto set (p = 0.69). PVPC in TIPS creation are not related to the choice of needle set used in the procedure. To our knowledge, this is the first review of its kind, the results of which support the theory that while the rate of PVPC is influenced by many factors, choice of needle set does not seem to be one of them.

Direct-acting antivirals ability to clear intestinal HCV-RNA in liver transplant patients.

The hepatitis C virus mainly infects the liver but is also able to infect and replicate in other body compartments by creating an extra-hepatic reservoir that may influence the persistence of the infection after transplantation. It is unknown whether antiviral drugs affect the viral extra-hepatic sites. We evaluated the ability of pegylated/interferon + ribavirin and sofosbuvir + ribavirin to clear the virus from the gastrointestinal mucosa of liver-transplanted patients with HCV recurrence after transplantation. A total of 51 liver-transplanted patients, 30 treated with pegylated/interferon + ribavirin (ERA1) and 21 treated with sofosbuvir + ribavirin (ERA2), were enrolled, and blood serum and gastrointestinal tissues analyzed for the presence of HCV-RNA. In the ERA1 group, the 46.6% of patients had a sustained viral response to antiviral treatment, and gastrointestinal biopsies were positive for HCV in 73.3% of cases, 54.5% of responders, and 45.5% of non-responders. In the ERA2 group, the 66.6% had a sustained viral response, and gastrointestinal HCV-RNA was present in the 14.3% of patients, all relapsers. Sofosbuvir + ribavirin cleared the intestinal HCV in 85.7% of patients with recurrent HCV infection, while pegylated/interferon + ribavirin cleared it in 26.6% of treated patients, demonstrating the better effectiveness of new direct antiviral agents in clearing HCV intestinal reservoir.

How can we optimise antifungal use in a solid organ transplant centre? Local epidemiology and antifungal stewardship implementation: A single-centre study.

PURPOSE: We aimed to implement and to assess the impact of the antifungal stewardship programme (AFSp) on prescription appropriateness of antifungals, management and outcomes of candidaemia patients, and antifungal consumption and costs at our solid organ transplant (SOT) institute. METHODS: Local epidemiology of invasive fungal infections (IFIs) from 2009 to 2017 was analysed in order to prepare an effective AFSp, implemented in January 2018. It included suspension of empirical antifungal prescriptions after 72 hours (antifungal time-out), automated alert and infectious disease (ID) consult for empirical prescriptions and for every patient with IFI, and indication for step-down to oral fluconazole when possible. We used process measures and results measures to assess the effects of the implemented programme. RESULTS: The ASFp led to significant improvements in selection of the appropriate antifungal (40.5% in pre-AFS vs 78.6% in post-AFS), correct dosing (51.2% vs 79.8%), correct length of treatment (55.9% vs 75%) and better management of patients with candidaemia. Analysis of prescribed empirical antifungal revealed that defined daily doses (DDDs) per 100 patient days decreased by 36.7% in 2018 compared to the average of pre-AFSp period, with important savings in costs. CONCLUSION: This AFSp led to a better use of antifungal drugs in terms of appropriateness and consumption, with stable clinical and microbiological outcomes in patients with IFI.

The role of endoscopy as non-invasive procedure to manage gastrointestinal complications during extracorporeal membrane oxygenation.

INTRODUCTION: Gastrointestinal bleeding is a life-threatening complication in patients undergoing extracorporeal membrane oxygenation support. Despite data on increased mortality due to gastrointestinal bleeding, there is little data on the treatment of such conditions under extracorporeal membrane oxygenation, and on the possibilities of advanced endoscopic therapy to non-invasively solve these bleeding complications. No clear treatment in the case of extracorporeal membrane oxygenation support is recommended in the guidelines. METHODS: Retrospective observational cohort study including 134 veno-venous extracorporeal membrane oxygenation patients for acute respiratory failure from 2009 to 2018 at IRCCS-ISMETT (Italy). Patients were divided into two groups according to gastrointestinal bleeding episodes and reviewed for type of endoscopic therapy. Gastrointestinal bleeding group was characterized for pre-extracorporeal membrane oxygenation characteristics, management variables-including amount of transfusions and clinical outcomes. RESULTS: Fourteen (14) patients (10.4%) experienced upper (n = 13) or lower (n = 1) gastrointestinal bleeding. Gastrointestinal bleeding and no-gastrointestinal bleeding group had similar characteristics apart from higher creatinine in the gastrointestinal bleeding group (1.9 mg/dL (1.3-4.9) vs 1.2 mg/dL (0.7-1.8), p = 0.03). In 3 of the 14 patients (21%), endoscopy showed no signs of active bleeding (nasogastric or feeding tube decubitus), and no specific intervention was performed. Active bleeding was recognized in 11 of the 14 patients (79 %). No patients died of fatal bleeding in the gastrointestinal bleeding group. Endoscopic therapy was feasible, with a complete bleeding control in all the cases: five Hemospray®, two fibrin glue, two metallic clips, one combined approach metallic clips with epinephrine, and one cyanoacrylate. The extracorporeal membrane oxygenation course was significantly longer in the gastrointestinal bleeding group: 19.5 (15-36) days vs 13.5 (8-25) days, p = 0.01. No significant differences in mortality were found between the two groups (all p values > 0.05). CONCLUSION: Advanced endoscopic therapy during veno-venous extracorporeal membrane oxygenation may contribute to reducing the negative effects on mortality for gastrointestinal bleeding episodes.

Sequential multistenting protocol in biliary stenosis after liver transplantation: a prospective analysis.

BACKGROUND: Biliary complications are a serious source of morbidity after orthotopic and living-related liver transplantation. Endoscopic retrograde cholangiography (ERC) is the gold standard for patients with duct-to-duct anastomosis because it allows a direct approach for interventional procedures. A retrospective study showed results of a sequential multistenting protocol, without stent removal/exchange, with promising results. We conducted a prospective analysis to assess the clinical success, recurrence rate, and adverse event rate related to this protocol. METHODS: From May 2012 to April 2018, all consecutive patients with a diagnosis of anastomotic stenosis following liver transplantation were enrolled in the study, and were followed for a period of at least 6 months after the last ERC. During the first ERC, a maximum number of plastic stents (10 Fr) were placed. In subsequent ERCs, scheduled every 3 months up to a maximum of 1 year, additional stents were inserted, as many as possible, without removing the previously placed stents. RESULTS: From May 2012 to May 2018, 87 patients were included in the study and treated with a sequential multistenting protocol. The mean number of stents placed was 3.7 (SD 1.0). Clinical success (stricture resolution and normalization of cholestasis) was achieved in 86 patients (98.9 %). Seven patients (8.0 %) developed complications. Recurrence was recorded in seven patients (8.0 %) after a mean of 992.7 days (SD 622.1). CONCLUSIONS: This study represents the first prospective demonstration of the efficacy and safety of a sequential multistenting protocol. A key limitation of the study is the lack of a comparative group treated according to the traditional stent exchange approach.

Epidemiology and successful containment of a carbapenem-resistant Enterobacteriaceae outbreak in a Southern Italian Transplant Institute.

INTRODUCTION: Carbapenem-resistant enterobacteriaceae (CRE) infections are difficult to treat and pose a serious threat to solid organ transplant (SOT) recipients. At our institute we observed an infection burden in 2012. METHODS: In order to contain the spread of CRE infections, we established a taskforce to implement guidelines suggested by the Centers for Disease Control and Prevention (CDC) for this type of outbreak. Here, we describe the epidemiology of the outbreak in our SOT population, and the effectiveness of such interventions, by comparing levels of CRE hospital-acquired infection (HAI) pre- and post-task force intervention (from January 2009 to December 2012, and from September 2013 to December 2016, respectively) through a linear regression model. RESULTS: In this study, we included 933 patients who underwent a total of 1017 SOT procedures, 286 of whom had a CRE-positive culture (28.8%), of which 65 (22.7% of CRE positive) developed infection. One-year mortality post-SOT was significantly higher in patients with CRE infection. After the taskforce intervention, the CRE HAI rate in SOT showed a significant inverse trend (event rate: -1.28, CI -1.70 to 0.86; P < 0.01). CONCLUSION: In the paucity of treatment options, the application of CDC measures in our SOT institute contributed significantly to containing CRE infections.

NT-ProBNP and hsTnI: A Multistate Survival Analysis in Outpatients with Reduced Left-Ventricular Ejection Fraction.

Heart failure (HF) with reduced ejection fraction (HFrEF) has a well-known epidemic relevance in western countries. It affects up to 1-2% of patients > 60 years and reaches a prevalence of 12% in octogenarian patients. The role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitive troponin I (hsTnI) in risk stratifying HFrEF patients has been established; at present, evidence is exclusively based on one-time assessments, and the prognostic usefulness of serial biochemical assessments in this population still remains to be determined. We prospectively recruited 226 patients with chronic HFrEF, who were all referred to the Outpatient Clinic of our institution from November 2011 through September 2014. Recruited patients underwent full clinical evaluation with complete history taking and physical examination as well as ECG, biochemical assessment, and standard 2D and Doppler flow echocardiography at the first visit, and then again at each visit during the follow-up, repeated every 6 months. During the follow-up period, cardiovascular (CV) death, which occurred in 16 patients, was not statistically correlated with gender (p = 0.088) or age (p = 0.1636); however, baseline serum levels of NT-proBNP, which were 3 times higher in deceased patients, were significantly related to this clinical event (p = 0.001). We found that NT-proBNP represents a strong and independent predictor of CV outcome; serum levels of hsTnI, which are significantly related to an increased risk of hospitalization, cannot properly predict the relative risk of CV mortality. Our study validates, eventually, the multimarker strategy, which reflects the complexity of the HF pathophysiology.

Trying to identify who may benefit most from future vitamin D intervention trials: a post hoc analysis from the VITDAL-ICU study excluding the early deaths.

BACKGROUND: Vitamin D supplementation has shown promise for reducing mortality in the intensive care setting. As a steroid prohormone with pleiotropic effects, there may be a lag between administration and observing clinical benefit. This secondary analysis of the VITdAL-ICU study sought to explore whether the effect size of vitamin D on mortality was different when study participants who died or were discharged early were excluded. METHODS: The VITdAL-ICU study was a randomized, placebo-controlled trial in critically ill adults who received placebo or 540,000 IU cholecalciferol followed by monthly supplementation. The effect of vitamin D on 28-day mortality was evaluated after exclusion of participants who died or were discharged within 7 days from study drug administration, according to vitamin D concentrations on day 3, using a bivariate analysis adjusted for confounders and in a stepwise multiple analysis. RESULTS: Of 475 study participants, 65 died or were discharged within the first 7 days. In the remaining 410 patients, vitamin D supplementation was associated with a reduction in 28-day mortality [OR 0.58 (95% CI 0.35-0.97) p value = 0.035]. The effect on mortality was not significant after adjusting for age, severity scores, female gender, chronic liver and kidney disease, COPD, diagnosis of the tumor, mechanical ventilation, and vasopressors at enrollment (all p > 0.05). In a multiple model, the mortality reduction by vitamin D supplementation did not remain independently significant [OR 0.61 (95% CI 0.35-1.05) p = 0.075]. Vitamin D metabolite response, in the treatment group, demonstrated that survivors at 28 days, had higher levels of 25-hydroxyvitamin D (34.4 vs 25.4 ng/ml, p = 0.010) and 1,25-dihydroxyvitamin D (107.6 vs 70.3 pg/ml, p = 0.049) on day 3. The increase of plasma metabolites after vitamin D oral supplementation, independent of the baseline value, was associated with lower odds of death [OR 0.48 (95% CI 0.27-0.87) p value = 0.016]. CONCLUSIONS: High-dose vitamin D3 supplementation was associated with a reduction of 28-day mortality in a mixed population of critically ill adults with vitamin D deficiency when excluding patients who died or were discharged within 7 days after study inclusion. However, this survival benefit was not independently confirmed when adjusted for other factors strongly associated with mortality.

A paradigm shift in the intention-to-transplant children with biliary atresia: Outcomes of 101 cases and a review of the literature.

For children with BA who do not benefit from Kasai surgery, the only therapeutic option is liver replacement and transplantation. The very decision to proceed for transplantation is a crucial point in time because it is the first step toward the preparation for the transplantation. The former time point is defined in this analysis as "intent-to-transplant" care pathway. In the life of every BA candidate for liver replacement, this point in time varies and mostly depends on the decision of their primary caring teams-about when to switch from supportive care to transplant, and thus to refer to a transplant center. This intent-to-transplant analysis of a series of 101 consecutive infants that were referred to a single transplant team showed that excellent overall outcome (97% survival) has been achieved overall. However, three deaths occurred that were clearly related to a late referral. This analysis and recent observations from other centers strongly support that the timing for referring these children to a transplant center and/or deciding to list them on the waiting list is currently too late and should be anticipated to what it is currently. This paradigm shift in the intention-to-transplant children is likely necessary for giving a better chance to an increased number of children and impacts positively on the general outcome. Networking and defining new tools for a rapid recognition of the infants who need early transplantation are necessary; centralization of these children may be helpful to achieve better outcomes than currently observed.

Anticoagulation and Transfusions Management in Veno-Venous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: Assessment of Factors Associated With Transfusion Requirements and Mortality.

PURPOSE: We describe an approach for anticoagulation and transfusions in veno-venous-extracorporeal membrane oxygenation (VV-ECMO), evaluating factors associated with higher transfusion requirements, and their impact on mortality. METHODS: Observational study on consecutive adults supported with VV-ECMO for acute respiratory distress syndrome (ARDS). We targeted an activated partial thromboplastin time of 40 to 50 seconds and a hematocrit of 24% to 30%. Univariate and multiple analyses were done to evaluate factors associated with transfusion requirements and the influence of increasing transfusions on mortality during ECMO. RESULTS: In a cohort of 82 VV-ECMO patients (PRedicting dEath for SEvere ARDS on VV-ECMO [PRESERVE] score: 4, Interquartile range [IQR]: 3-5, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction [RESP] score: 2, IQR: 2-4), 76 (92.7%) patients received at least 1 unit of packed red blood cells (PRBCs) during the intensive care unit stay related to ECMO (median PRBC/d 156 mL, IQR: 93-218; median ECMO duration 14 days, IQR: 8-22). A higher requirement of PRBC transfusions was associated with pre-ECMO hematocrit, and with the following conditions during ECMO: platelet nadir, antithrombin III (ATIII), and stage 3 of acute kidney injury (all P < .05). Sixty-two (75.6%) patients survived ECMO. Pre-ECMO hospital stay, PRBC transfusion, and septic shock were associated with mortality (all P < .05). The adjusted odds ratio for each 100mL/d increase in PRBC transfusion was 1.9 (95% confidence interval [CI]: 1.1-3.2, P = .01); for the development of septic shock it was 15.4 (95% CI: 1.7-136.8, P = .01), and for each day of pre-ECMO stay it was 1.1 (95% CI: 1-1.2, P = .04). CONCLUSION: Implementation of a comprehensive protocol for anticoagulation and transfusions in VV-ECMO for ARDS resulted in a low PRBC requirement, and an ECMO survival comparable to data in the literature. Lower ATIII emerged as a factor associated with increased need for transfusions. Higher PRBC transfusions were associated with ECMO mortality. Further investigations are needed to better understand the right level of anticoagulation in ECMO, and the factors to take into account in order to manage personalized transfusion practice in this select setting.

Hemoglobin trigger and approach to red blood cell transfusions during veno-venous extracorporeal membrane oxygenation: the international TRAIN-ECMO survey.

INTRODUCTION: Optimal red blood cell transfusion practice during veno-venous extracorporeal membrane oxygenation (VV ECMO) is still under debate. This survey aimed to assess the Hb trigger (also comparing with other critically ill patients) and major physiologic determinants considered for transfusions during veno-venous extracorporeal membrane oxygenation. METHODS: Voluntary Web-based survey, endorsed by the European Society of Intensive Care Medicine, conducted among VV ECMO pratictioners worldwide. RESULTS: A total of 447 respondents worldwide answered the questionnaire: 277 (61.9%) from Europe, 99 (22.1%) from North America, 36 (8.2%) from Asia and Oceania, and 35 (7.8%) from Central and South America. Among the respondents, 59.2% managed less than 12 venous extracorporeal membrane oxygenation runs/year, 19.4% between 12 and 24 runs/year, and 21.4% more than 24 runs/year. Of the respondents, 54.4% do not use a predefined Hb trigger in veno-venous extracorporeal membrane oxygenation, and, while the rate of adoption of a defined trigger varied worldwide, the effective value of Hb did not differ significantly among macro-regions. In patients on veno-venous extracorporeal membrane oxygenation, the Hb trigger to initiate red blood cell transfusion, was higher than in other critically ill patients: 9.1 ± 1.8 g/dL versus 8.3 ± 1.7 g/dL, p < 0.01. The Hb trigger was lower in centers with more than 24 venous extracorporeal membrane oxygenation runs/year (8.4 mg/dL (95% CI: 7.7-8.9)); (8.9 mg/dL (95% CI: 8.2-9.7)) in centers with between 12 and 24 venous extracorporeal membrane oxygenation runs/year; and (9.6 mg/dL (95% CI: 9.1-10.0)) in centers with fewer than 12 venous extracorporeal membrane oxygenation runs/year (p < 0.01). Several and variable adjunctive parameters are considered in cases of uncertainty for transfusion: the principal are hemodynamic status, SvO2, lactates, and fluid balance. CONCLUSION: Although the use of a predefined Hb trigger is still under-adopted among centers with low or median extracorporeal membrane oxygenation case volume, the majority of respondents use a higher Hb trigger for veno-venous extracorporeal membrane oxygenation patients compared with other critically ill patients. Higher volume centers tolerate lower Hb levels.

Acute rejection after lung transplantation: association between histopathological and CT findings.

PURPOSE: To evaluate the predictive role of computed tomography (CT) on acute rejection in patients who underwent lung transplantation (LT). MATERIALS AND METHODS: Seventy-eight patients who underwent LT were evaluated in our study. The CT scans were reviewed by three different radiologists, who evaluated the findings potentially associated with acute rejection such as air trapping, tree-in-bud, consolidations, crazy paving, ground-glass opacity, bronchiectasis, thickening of intralobular or interlobular septa and presence of pleural effusion. The association between a tissue diagnosis of acute rejection and the above-mentioned CT findings was assessed using a multivariate model of logistic regression. RESULTS: Based on our results, none of the CT findings included in the study, alone or in combination, showed significant statistical association with the diagnosis of acute rejection. CONCLUSION: CT is a very useful technique for the assessment of lung transplant recipients although it has limited accuracy for the assessment of acute rejection. None of the radiological findings considered in our study was significantly associated with histologically proven acute rejection.

The addition of simvastatin administration to cold storage solution of explanted whole liver grafts for facing ischemia/reperfusion injury in an area with a low rate of deceased donation: a monocentric randomized controlled double-blinded phase 2 study.

BACKGROUND: Liver transplantation is the best treatment for end-stage liver disease. The interruption of the blood supply to the donor liver during cold storage damages the liver, affecting how well the liver will function after transplant. The drug Simvastatin may help to protect donor livers against this damage and improve outcomes for transplant recipients. The aim of this study is to evaluate the benefits of treating the donor liver with Simvastatin compared with the standard transplant procedure. PATIENT AND METHODS: We propose a prospective, double-blinded, randomized phase 2 study of 2 parallel groups of eligible adult patients. We will compare 3-month, 6-month, and 12-month graft survival after LT, in order to identify a significant relation between the two homogenous groups of LT patients. The two groups only differ by the Simvastatin or placebo administration regimen while following the same procedure, with identical surgical instruments, and medical and nursing skilled staff. To reach these goals, we determined that we needed to recruit 106 patients. This sample size achieves 90% power to detect a difference of 14.6% between the two groups survival using a one-sided binomial test. DISCUSSION: This trial is designed to confirm the effectiveness of Simvastatin to protect healthy and steatotic livers undergoing cold storage and warm reperfusion before transplantation and to evaluate if the addition of Simvastatin translates into improved graft outcomes. TRIAL REGISTRATION: ISRCTN27083228 .

Risk Factors Associated With Peripheral Neuropathy in Heart Failure Patients Candidates for Transplantation.

INTRODUCTION: Peripheral neuropathy can affect patients with heart failure, though its prevalence is unknown. After heart transplantation, it can influence the postoperative course and quality of life, but screening for neuromuscular disease is not routinely performed. OBJECTIVE: The aim of this study was to identify the factors associated with neuropathy in a population of patients with heart failure who are candidates for heart transplantation. STUDY DESIGN: Data regarding patients' clinical history, including recent hospitalizations, were collected. All patients underwent a complete neurological examination and a neurophysiological protocol including nerve conduction studies and concentric needle electromyography. RESULTS: Thirty-two patients were included in the study, and neuropathy was diagnosed in 10 (31.3%). Neuropathy was associated with the number of admissions ( P = .023; odds ratio [OR]: 1.96) and the total number of days of hospitalization in the year prior to inclusion in the study ( P = .010; OR: 1.03). The majority of hospitalizations occurred in the step-down unit (85%), with acute heart failure the leading cause of admission (42%). CONCLUSIONS: This study shows that neuropathy is frequent in patients with advanced heart failure and that hospitalization for cardiac care, also in the absence of intensive care, is a marker of high risk of neurologic damage. These data can help physicians in selecting and managing candidates for transplantation and can guide decisions on the best immunosuppressive regimen or rehabilitation strategy.