Pain management in liver transplant recipients: a focus on current and future strategies.

Liver transplantation is the only curative treatment option for patients with end-stage liver disease. Anesthesiologists and intensivists are fully involved in this procedure due to the perioperative care focus on hemodynamic, respiratory and metabolic support. However, quite surprisingly, postoperative pain management does not have clinical primary consideration in this class of patients due to a combination of factors including the thought that liver transplantation recipients have less pain and require lower doses of analgesics than patients who undergo other types of major abdominal surgery. Other factors contribute to make the management of postoperative pain somewhat complex in this class of patients: 1) drug pharmacokinetics and metabolism by the new liver is not predictable; 2) the multifactorial nature of liver graft recovery; and 3) the alterations of homeostasis, including circulatory, respiratory and metabolic vulnerability, in the days postoperative period. As a result, post-liver transplantation analgesia is underestimated not only from the clinical point of view but also in the literature and only a few papers deal with the management of postoperative pain in this particular class of patients. Thus, in the experts' opinion paper we aimed to report the possible strategies for managing post-LT pain with a focus on opioids alternatives and possible future developments in this particular clinical setting also in the view that improvements in perioperative care have made it possible to adopt fast track and Enhanced Recovery After Surgery-oriented protocols also in this class of patients.

International Liver Transplantation Society/Society for Advancement of Transplant Anesthesia Consensus Statement on Essential Attributes of a Liver Transplant Anesthesiologist.

BACKGROUND: We sought to establish consensus on the essential skills, knowledge, and attributes that a liver transplant (LT) anesthesiologist should possess in a bid to help guide the further training process. METHODS: Consensus was achieved via a modified Delphi methodology, surveying 15 identified international experts in the fields of LT anesthesia and critical care. RESULTS: Key competencies were identified in preoperative management and optimization of a potential LT recipient; intraoperative management, including hemodynamic monitoring; coagulation and potential crisis management; and postoperative intensive and enhanced recovery care. CONCLUSIONS: This article provides an essential guide to competency-based training of an LT anesthesiologist.

Use of an intraoperative veno-venous bypass during liver transplantation: an observational, single center, cohort study.

BACKGROUND: As previous studies demonstrated conflicting results, we investigated the hemodynamic and renal outcomes of the intra-operative use of a veno-venous bypass during liver transplantation. METHODS: The intraoperative levels of mean artery pressure, cardiac index, inferior vena cava and renal perfusion pressures were compared in liver transplant patients receiving or not the bypass. RESULTS: We enrolled 38 patients: 20 with the bypass and 18 without. No differences characterized the two groups regarding gender (P=0.95), age (P=0.32), BMI (P=0.09), liver disease indicating LT and preoperative serum creatinine levels. Patients with the bypass received more intraoperative fluids (crystalloids and colloids) but with no difference in terms of intraoperative blood products and vasopressors requirements (P=0.33). After clamping of the inferior vena cava, patients with the bypass showed higher mean artery pressure. Simultaneously, pressure in the inferior vena cava below the clamp level sharply increased vs. baseline (P<0.0001) independently of the use of the bypass and remained high until clamp release. Consequently, renal perfusion pressure dropped abruptly (P<0.0001) after vena cava clamping and returned to baseline only upon clamp removal. Overall, 18 subjects developed postoperative acute kidney injury which was equally distributed between patients with (n=9) or without (N.=8) the bypass. CONCLUSIONS: Our data suggest that the use of a veno-venous bypass fails to release the increased renal venous backflow from inferior vena cava clamping resulting in renal congestion with reduced renal perfusion pressure.

Multidrug-resistant infections in solid organ transplant recipients: a focus on risk factors, prevention, and treatment strategies.

Solid organ transplantation is the best therapeutic option for patients with end-stage organ disease and, according to the data from international registries, there has been a steady increase in numbers and results. However, post­transplant infections remain a fearsome complication with, in the last decade, an increasing incidence of episodes due to antibiotic­resistant bacteria and opportunistic agents. In this paper, we summarized the most relevant and updated knowledge concerning infections from multidrug­resistant germs in solid organ transplant recipients, focusing on risk factors, treatment and prevention strategies, and antimicrobial pharmacokinetics relevant to this population of patients.

Intraoperative transfusion management, antifibrinolytic therapy, coagulation monitoring and the impact on short-term outcomes after liver transplantation-A systematic review of the literature and expert panel recommendations.

BACKGROUND: Liver transplantation (LT) is frequently complicated by coagulopathy associated with end-stage liver disease (ESLD), that is, often multifactorial. OBJECTIVES: The objective of this systematic review was to identify evidence based intraoperative transfusion and coagulation management strategies that improve immediate and short-term outcomes after LT. METHODS: PRISMA-guidelines and GRADE-approach were followed. Three subquestions were formulated. (Q); Q1: transfusion management; Q2: antifibrinolytic therapy; and Q3: coagulation monitoring. RESULTS: Sixteen studies were included for Q1, six for Q2, and 10 for Q3. Q1: PRBC and platelet transfusions were associated with higher mortality. The use of prothrombin complex concentrate (PCC) and fibrinogen concentrate (FC) were not associated with reductions in intraoperative transfusion or increased thrombotic events. The use of cell salvage was not associated with hepatocellular carcinoma (HCC) recurrence or mortality. Cell salvage and transfusion education significantly decreased blood product transfusions. Q2: Epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA) were not associated with decreased blood product transfusion, improvements in patient or graft survival, or increases in thrombotic events. Q3: Viscoelastic testing (VET) was associated with decreased allogeneic blood product transfusion compared to conventional coagulation tests (CCT) and is likely to be cost-effective. Coagulation management guided by VET may be associated with increases in FC and PCC use. CONCLUSION: Q1: A specific blood product transfusion practice is not recommended (QOE; low | Recommendation; weak). Cell salvage and educational interventions are recommended (QOE: low | Grade of Recommendation: moderate). Q2: The routine use of antifibrinolytics is not recommended (QOE; low | Recommendation; weak). Q3: The use of VET is recommended (QOE; low-moderate | Recommendation; strong).

The prevention of pressure injuries in the positioning and mobilization of patients in the ICU: a good clinical practice document by the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI).

BACKGROUND: The aim of this document is to support clinical decision-making concerning positioning and mobilization of the critically ill patient in the early identification and resolution of risk factors (primary prevention) and in the early recognition of those most at risk (secondary prevention). The addresses of this document are physicians, nurses, physiotherapists, and other professionals involved in patient positioning in the intensive care unit (ICU). METHODS: A consensus pathway was followed using the Nominal Focus Group and the Delphi Technique, integrating a phase of focused group discussion online and with a pre-coded guide to an individual phase. A multidisciplinary advisory board composed by nine experts on the topic contributed to both the phases of the process, to reach a consensus on four clinical questions positioning and mobilization of the critically ill patient. RESULTS: The topics addressed by the clinical questions were the risks associated with obligatory positioning and therapeutic positions, the effective interventions in preventing pressure injuries, the appropriate instruments for screening for pressure injuries in the ICU, and the cost-effectiveness of preventive interventions relating to ICU positioning. A total of 27 statements addressing these clinical questions were produced by the panel. Among the statements, nine provided guidance on how to manage safely some specific patients' positions, including the prone position; five suggested specific screening tools and patients' factors to consider when assessing the individual risk of developing pressure injuries; five gave indications on mobilization and repositioning; and eight focused on the use of devices, such as positioners and preventive dressings. CONCLUSIONS: The statements may represent a practical guidance for a broad public of healthcare professionals involved in the management of critically ill patients.

Guidelines for Perioperative Care for Liver Transplantation: Enhanced Recovery After Surgery (ERAS) Recommendations.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) is a multimodal, evidence-based, program of care developed to minimize the response to surgical stress, associated with reduced perioperative morbidity and hospital stay. This study presents the specific ERAS Society recommendations for liver transplantation (LT) based on the best available evidence and on expert consensus. METHODS: PubMed and ClinicalTrials.gov were searched in April 2019 for published and ongoing randomized clinical trials on LT in the last 15 y. Studies were selected by 5 independent reviewers and were eligible if focusing on each validated ERAS item in the area of adult LT. An e-Delphi method was used with an extended interdisciplinary panel of experts to validate the final recommendations. RESULTS: Forty-three articles were included in the systematic review. A consensus was reached among experts after the second round. Patients should be screened for malnutrition and treated whenever possible. Prophylactic nasogastric intubation and prophylactic abdominal drainage may be omitted, and early extubation should be considered. Early oral intake, mobilization, and multimodal-balanced analgesia are recommended. CONCLUSIONS: The current ERAS recommendations were elaborated based on the best available evidence and endorsed by the e-Delphi method. Nevertheless, prospective studies need to confirm the clinical use of the suggested protocol.

Solid Organ Transplantation During COVID-19 Pandemic: An International Web-based Survey on Resources' Allocation.

Solid organ transplants (SOTs) are life-saving interventions, recently challenged by coronavirus disease 2019 (COVID-19). SOTs require a multistep process, which can be affected by COVID-19 at several phases. METHODS: SOT-specialists, COVID-19-specialists, and medical ethicists designed an international survey according to CHERRIES guidelines. Personal opinions about continuing SOTs, safe managing of donors and recipients, as well as equity of resources' allocation were investigated. The survey was sent by e-mail. Multiple approaches were used (corresponding authors from Scopus, websites of scientific societies, COVID-19 webinars). After the descriptive analysis, univariate and multivariate ordinal regression analysis was performed. RESULTS: There were 1819 complete answers from 71 countries. The response rate was 49%. Data were stratified according to region, macrospecialty, and organ of interest. Answers were analyzed using univariate-multivariate ordinal regression analysis and thematic analysis. Overall, 20% of the responders thought SOTs should not stop (continue transplant without restriction); over 70% suggested SOTs should selectively stop, and almost 10% indicated they should completely stop. Furthermore, 82% agreed to shift resources from transplant to COVID-19 temporarily. Briefly, main reason for not stopping was that if the transplant will not proceed, the organ will be wasted. Focusing on SOT from living donors, 61% stated that activity should be restricted only to "urgent" cases. At the multivariate analysis, factors identified in favor of continuing transplant were Italy, ethicist, partially disagreeing on the equity question, a high number of COVID-19-related deaths on the day of the answer, a high IHDI country. Factors predicting to stop SOTs were Europe except-Italy, public university hospital, and strongly agreeing on the equity question. CONCLUSIONS: In conclusion, the majority of responders suggested that transplant activity should be continued through the implementation of isolation measures and the adoption of the COVID-19-free pathways. Differences between professional categories are less strong than supposed.

Safety Analysis of 13 Suspicious Deaths in Intensive Care: Ergonomics and Forensic Approach Compared.

OBJECTIVES: Thirteen suspicious deaths occurred in an intensive care unit of Tuscany, Italy, in 2015. All patients developed sudden unexplained coagulopathy leading to severe bleeding. None of them had been prescribed heparin, but supertherapeutic concentrations of heparin were found. After a nurse was arrested on suspicion of murdering Human Factor and Ergonomics (HF/E) experts received a mandate to identify system failures. According to the judgment of the Court of First Instance on April 2019, the nurse was found guilty. METHODS: The HF/E group used a two-pronged safety analysis: understanding the conditions in which the healthcare practitioners were working in the period when the suspicious deaths emerged and reviewing the clinical records. RESULTS: Fourteen patients admitted to the intensive care unit in 2014 and 2015 were selected on the basis of markedly abnormal coagulation tests (n = 13) or a family member's complaint (n = 1). In 13 cases, a massive, abrupt hemorrhage in the presence of an unexpected abnormality of coagulation tests occurred, whereas the fourteenth patient had the only prolongation of coagulation markers without bleeding. All cases examined classified as adverse events related to a coagulation disorder. Human factor and ergonomics analysis identified a number of latent and active failures that contributed to the event and provided a set of important recommendations for safety improvement. CONCLUSIONS: When presented with a manifest, albeit suspected, wrongdoing with lethal consequences for patients, forensic investigators and safety investigators have distinctly different goals and methods. We believe that a memorandum of understanding between HF/E and forensic investigative teams provides an operative framework for allowing co-existence and fosters collaboration. The pursuit of safe care as a new emerging right for patients and balancing the right to legal justice with the right to safer healthcare merit further investigation and discussion.

When Is a Critically Ill Cirrhotic Patient Too Sick to Transplant? Development of Consensus Criteria by a Multidisciplinary Panel of 35 International Experts.

BACKGROUND: Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT). Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility. METHODS: Thirty-five international experts from anesthesiology/intensive care, hepatology, and transplant surgery were surveyed using the Delphi method. More than 70% of similar answers to a question were necessary to define agreement. RESULTS: The panel recommended patient and graft survival at 1 year after LT to define futility. Severe frailty and persistent fever or <72 hours of appropriate antimicrobial therapy in case of ongoing sepsis were considered reasons to delay LT. A simple assessment of the number of organs failing was considered the most appropriate way to decide whether LT should be delayed or denied, with respiratory, circulatory and metabolic failures having the most influence in this decision. The thresholds of severity of organ failures contraindicating LT for which a consensus was achieved were a Pao2/FiO2 ratio<150 mm Hg, a norepinephrine dose >1 µg/kg per minute and a serum lactate level >9 mmol/L. CONCLUSIONS: Our expert panel provides a consensus on the definition of futile LT and on specific criteria for postponing or denying LT. A framework that may facilitate the decision if a patient is too sick for transplant is presented.

Correction to: A year in review in Minerva Anestesiologica 2019. Critical care.

This corrects the article DOI:10.23736/S0375-9393.20.14384-0.

Liver transplantation for acute-on-chronic liver failure.

Acute-on-chronic liver failure (AoCLF) represents a newly defined entity in patients with liver disease leading to multiple organ failures and increased mortality. To date, no universally accepted definition exists, and different academic societies developed guidelines on the early diagnosis and classification of AoCLF. Recently published trials focused on factors associated with a poor outcome and on the development of severity scores aimed to identify patients who may benefit for advanced monitoring and treatment. No specific therapies are demonstrated to improve survival, and liver transplantation (LT) remains the only treatment associated with improved outcome. Our review focuses on current evidence for early diagnosis and prognostication of disease in patients with AoCLF, as well of criteria for intensive care unit admission, indication, and futility markers of LT, as well as bridging therapy and optimal timing of surgery.