Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations.

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU. DESIGN: The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. INTERVENTIONS: In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS: We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence. CONCLUSIONS: Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence.

Impact of the COVID-19 pandemic on American College of Surgeons-Accredited Education Institutes & American Society of Anesthesiologists-Simulation Education Network: Opportunities for interdisciplinary collaboration.

BACKGROUND: The COVID-19 pandemic presented challenges for simulation programs including American College of Surgeons Accredited Education Institutes and American Society of Anesthesiologists Simulation Education Network. American College of Surgeons Accredited Education Institutes and American Society of Anesthesiologists Simulation Education Network leadership were surveyed to identify opportunities to enhance patient safety through simulation. METHODS: Between January and June 2021, surveys consisting of 3 targeted domains: (I) Changing practice; (II) Contributions and recognition; and (III) Moving ahead were distributed to 100 American College of Surgeons Accredited Education Institutes and 54 American Society of Anesthesiologists Simulation Education Network centers. Responses were combined and percent frequencies reported. RESULTS: Ninety-six respondents, representing 51 (51%) American College of Surgeons Accredited Education Institutes, 17 (31.5%) American Society of Anesthesiologists Simulation Education Network, and 28 dually accredited centers, completed the survey. Change of practice. Although 20.3% of centers stayed fully operational at the COVID-19 onset, 82% of all centers closed: 32% were closed less than 3 months, 28% were closed 3 to 6 months, 8% were closed 7 to 9 months, and 32% remained closed as of June 6, 2021. Most impacted activities were large-group instruction and team training. Sixty-nine percent of programs converted in-person to virtual programs. Contributions. The top reported innovative contributions included policies (80%), curricula (80%), and scholarly work (74%), Moving ahead. The respondents' top concerns were returning to high-quality training to best address learners' deficiencies and re-engagement of re-directed training programs. When asked "How the American College of Surgeons/American Society of Anesthesiologists Programs could best assist your simulation center goals?" the top responses were "facilitate collaboration" and "publish best practices from this work." CONCLUSION: The Pandemic presented multiple challenges and opportunities for simulation centers. Opportunities included collaboration between American College of Surgeons Accredited Education Institutes and the American Society of Anesthesiologists Simulation Education Network to identify best practices and resources needed to enhance patient safety through simulation.

Takotsubo syndrome after liver transplantation: An association with intraoperatively administered epinephrine and fentanyl.

Takotsubo syndrome (TTS) can develop after liver transplant (LT), but its predisposing factors are poorly understood. In this study, we aimed to determine if perioperative factors were associated with posttransplant TTS. Adult patients who underwent primary LT between 2006 and 2018 were included. Patients with and without TTS were identified and matched by propensity scores. Of 2181 LT patients, 38 developed postoperative TTS with a mean left ventricular ejection fraction of 25.5% (±7.8%). Multivariable logistic regression revealed two preoperative risk factors (alcoholic cirrhosis and model for end-stage liver disease-sodium scores) for TTS. Post-propensity match analyses showed that TTS patients had significantly higher doses of epinephrine and lower doses of fentanyl during LT compared with non-TTS patients. A higher dose of epinephrine and a lower dose of fentanyl was associated with a higher predicted probability of TTS. All TTS patients had full recovery of cardiac function and had comparable 1-year survival. In conclusion, TTS occurred at a rate of 1.7% after LT and was associated with two pretransplant risk factors. The higher doses of epinephrine and lower doses of fentanyl administered during LT were associated with posttransplant TTS. More studies on the relationship between intraoperative medications and TTS are warranted.

Reliability of simulation-based assessment for practicing physicians: performance is context-specific.

INTRODUCTION: Even physicians who routinely work in complex, dynamic practices may be unprepared to optimally manage challenging critical events. High-fidelity simulation can realistically mimic critical clinically relevant events, however the reliability and validity of simulation-based assessment scores for practicing physicians has not been established. METHODS: Standardised complex simulation scenarios were developed and administered to board-certified, practicing anesthesiologists who volunteered to participate in an assessment study during formative maintenance of certification activities. A subset of the study population agreed to participate as the primary responder in a second scenario for this study. The physicians were assessed independently by trained raters on both teamwork/behavioural and technical performance measures. Analysis using Generalisability and Decision studies were completed for the two scenarios with two raters. RESULTS: The behavioural score was not more reliable than the technical score. With two raters > 20 scenarios would be required to achieve a reliability estimate of 0.7. Increasing the number of raters for a given scenario would have little effect on reliability. CONCLUSIONS: The performance of practicing physicians on simulated critical events may be highly context-specific. Realistic simulation-based assessment for practicing physicians is resource-intensive and may be best-suited for individualized formative feedback. More importantly, aggregate data from a population of participants may have an even higher impact if used to identify skill or knowledge gaps to be addressed by training programs and inform continuing education improvements across the profession.

Major Thromboembolic Complications in Liver Transplantation: The Role of Rotational Thromboelastometry and Cryoprecipitate Transfusion.

BACKGROUND: Although hemorrhage is a major concern during liver transplantation (LT), the risk for thromboembolism is well recognized. Implementation of rotational thromboelastometry (ROTEM) has been associated with the increased use of cryoprecipitate; however, the role of ROTEM-guided transfusion strategy and cryoprecipitate administration in the development of major thromboembolic complications (MTCs) has never been documented. METHODS: We conducted a study on patients undergoing LT before and after the implementation of ROTEM. We defined MTC as intracardiac thrombus, pulmonary embolism, hepatic artery thrombosis, and ischemic stroke in 30 d after LT. We used a propensity score to match patients during the 2 study periods. RESULTS: Among 2330 patients, 119 (4.9%) developed MTC. The implementation of ROTEM was significantly associated with an increase in cryoprecipitate use (1.1 ± 1.1 versus 2.9 ± 2.3 units, P < 0.001) and MTC (4.2% versus 9.5%, P < 0.001). Further analysis demonstrated that the use of cryoprecipitate was an independent risk factor for MTC (odds ratio 1.1, 95% confidence interval 1.04-1.24, P = 0.003). Patients with MTC had significantly lower 1-y survival. CONCLUSIONS: Our study suggests that the implementation of ROTEM and the use of cryoprecipitate play significant roles in the development of MTC in LT. The benefits and risks of cryoprecipitate transfusion should be carefully evaluated before administration.

Screen-Based Simulation for Training and Automated Assessment of Teamwork Skills: Comparing 2 Modes With Different Interactivity.

INTRODUCTION: The need for teamwork training is well documented; however, teaching these skills is challenging given the logistics of assembling individual team members together to train in person. We designed 2 modes of screen-based simulation for training teamwork skills to assess whether interactivity with nonplayer characters was necessary for in-game performance gains or for player satisfaction with the experience. METHODS: Mixed, randomized, repeated measures study with licensed healthcare providers block-stratified and randomized to evaluation-participant observes and evaluates the team player in 3 scenarios-and game play-participant is immersed as the leader in the same 3 scenarios. Teamwork construct scores (leadership, communication, situation monitoring, mutual support) from an ontology-based, Bayesian network assessment model were analyzed using mixed randomized repeated measures analyses of variance to compare performance, across scenarios and modes. Learning was measured by pretest and posttest quiz scores. User experience was evaluated using χ2 analyses. RESULTS: Among 166 recruited and randomized participants, 120 enrolled in the study and 109 had complete data for analysis. Mean composite teamwork Bayesian network scores improved for successive scenarios in both modes, with evaluation scores statistically higher than game play for every teamwork construct and scenario (r = 0.73, P = 0.000). Quiz scores improved from pretest to posttest (P = 0.004), but differences between modes were not significant. CONCLUSIONS: For training teamwork skills using screen-based simulation, interactivity of the player with the nonplayer characters is not necessary for in-game performance gains or for player satisfaction with the experience.

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Cardiovascular, Endocrine, Hematologic, Pulmonary, and Renal Considerations.

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for adults with acute or acute on chronic liver failure in the ICU. DESIGN: The guideline panel comprised 29 members with expertise in aspects of care of the critically ill patient with liver failure and/or methodology. The Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy were followed throughout. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. SETTING: The panel was divided into nine subgroups: cardiovascular, hematology, pulmonary, renal, endocrine and nutrition, gastrointestinal, infection, perioperative, and neurology. INTERVENTIONS: We developed and selected population, intervention, comparison, and outcomes questions according to importance to patients and practicing clinicians. For each population, intervention, comparison, and outcomes question, we conducted a systematic review aiming to identify the best available evidence, statistically summarized the evidence whenever applicable, and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS: In this article, we report 29 recommendations (from 30 population, intervention, comparison, and outcomes questions) on the management acute or acute on chronic liver failure in the ICU, related to five groups (cardiovascular, hematology, pulmonary, renal, and endocrine). Overall, six were strong recommendations, 19 were conditional recommendations, four were best-practice statements, and in two instances, the panel did not issue a recommendation due to insufficient evidence. CONCLUSIONS: Multidisciplinary international experts were able to formulate evidence-based recommendations for the management acute or acute on chronic liver failure in the ICU, acknowledging that most recommendations were based on low-quality indirect evidence.

Intraoperative Hypertension and Thrombocytopenia Associated With Intracranial Hemorrhage After Liver Transplantation.

BACKGROUND: Intracranial hemorrhage (ICH) is a devastating complication. Although hypertension and thrombocytopenia are well-known risk factors for ICH in the general population, their roles in ICH after liver transplantation (LT) have not been well established. METHODS: We performed a retrospective study and hypothesized that intraoperative hypertension and thrombocytopenia were associated with posttransplant ICH. New onset of spontaneous hemorrhage in the central nervous system within 30 days after LT were identified by reviewing radiologic reports and medical records. Risk factors were identified by multivariate logistic regression. Receiver operating characteristic analysis and Youden index were used to find the cutoff value with optimal sensitivity and specificity. RESULTS: Of 1836 adult patients undergoing LT at University of California, Los Angeles, 36 (2.0%) developed ICH within 30 days after LT. Multivariate logistic regression demonstrated that intraoperative mean arterial pressure ≥105 mm Hg (≥10 min) (odds ratio, 6.5; 95% confidence interval, 2.7-7.7; P < 0.001) and platelet counts ≤30 × 10/L (odds ratio, 3.3; 95% confidence interval, 14-7.7; P = 0.006) were associated with increased risk of postoperative ICH. Preoperative total bilirubin ≥7 mg/dL was also a risk factor. Thirty-day mortality in ICH patients was 48.3%, significantly higher compared with the non-ICH group (3.0%; P < 0.001). Patients with all 3 risk factors had a 16% chance of developing ICH. CONCLUSIONS: In the current study, postoperative ICH was uncommon but associated with high mortality. Prolonged intraoperative hypertension and severe thrombocytopenia were associated with postoperative ICH. More studies are warranted to confirm our findings and develop a strategy to prevent this devastating posttransplant complication.

Extracorporeal liver support in patients with liver failure: a systematic review and meta-analysis of randomized trials.

PURPOSE: Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are associated with significant mortality and morbidity. Extracorporeal liver support (ECLS) devices have been used as a bridge to liver transplant; however, the efficacy and safety of ECLS are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of ECLS in liver failure. METHODS: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through March 13, 2019. RCTs comparing ECLS to usual care in ALF or ACLF were included. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence. RESULTS: We identified 25 RCTs (1796 patients). ECLS use was associated with reduction in mortality (RR 0.84; 95% CI 0.74, 0.96, moderate certainty) and improvement in hepatic encephalopathy (HE) (RR 0.71; 95% CI 0.60, 0.84, low certainty) in patients with ALF or ACLF. The effect of ECLS on hypotension (RR 1.46; 95% CI 0.98, 2.2, low certainty), bleeding (RR 1.21; 95% CI 0.88, 1.66, moderate certainty), thrombocytopenia (RR 1.62; 95% CI 1.0, 2.64, very low certainty) and line infection (RR 1.92; 95% CI 0.11, 33.44, low certainty) was uncertain. CONCLUSIONS: ECLS may reduce mortality and improve HE in patients with ALF and ACLF. The effect on other outcomes is uncertain. However, the evidence is limited by risk of bias and imprecision, and larger trials are needed to better determine the effect of ECLS on patient-important outcomes.

Perioperative Considerations in Liver Transplantation.

Liver transplantation (LT) has the potential to cure patients with acute and chronic liver failure as well as a number of hepatic and biliary malignancies. Over time, due to the increasing demand for organs as well as improvements in the survival of LT recipients, patients awaiting LT have become sicker, and often undergo the procedure while critically ill. This trend has made the process of preoperative assessment and planning, intraoperative management, and postoperative management even more crucial to the success of LT programs. Multidisciplinary and specialized teams are essential and include anesthesiologists, surgeons, and intensivists. This article focuses on the preoperative evaluation, intraoperative care, and postoperative management of the liver transplant patient. Management relevant to the critically ill patient is discussed, with a focus on the management of postoperative cardiopulmonary conditions including the care of special populations such as those with hepatopulmonary syndrome and portopulmonary hypertension.

Preoperative beta blockade and severe intraoperative bradycardia in liver transplantation.

Nonselective Beta blockade (NSBB) is commonly prescribed for liver transplantation (LT) candidates, but its impact on intraoperative hemodynamics is not well understood. In this study, we investigated if preoperative NSBB was associated with severe bradycardia during LT and if severe intraoperative bradycardia was associated with 30-day mortality. Adult patients undergoing LT between 2005 and 2014 were included. Propensity matching was used to control selection bias. Intraoperative hemodynamics were compared between patients with and without preoperative NSBB. Univariate and multivariate methods were used in statistical analysis. Of 1452 patients, 370 who received preoperative NSBB were matched in a 1:1 ratio with those who did not. Propensity matching eliminated all significant differences between the two groups. Patients who received preoperative NSBB had a significantly higher incidence of severe intraoperative bradycardia compared with the non-BB group (9.6% vs 3.2%, P = 0.001, OR 2.95, 95% CI 1.42-6.12, P = 0.004). Intraoperative hypotension and postreperfusion syndrome were not significantly different between the two groups. Severe intraoperative bradycardia was associated with increased 30-day mortality. In conclusion, preoperative NSBB was associated with severe intraoperative bradycardia in LT. In patients who receive preoperative NSBB, severe intraoperative bradycardia should be closely monitored in LT. Further studies assessing safety of preoperative NSBB and intraoperative bradycardia in LT are warranted.

Potentially inappropriate liver transplantation in the era of the "sickest first" policy - A search for the upper limits.

Liver transplantation has emerged as a highly efficient treatment for a variety of acute and chronic liver diseases. However, organ shortage is becoming an increasing problem globally, limiting the applicability of liver transplantation. In addition, potential recipients are becoming sicker, thereby increasing the risk of losing the graft during transplantation or in the initial postoperative period after liver transplantation (three months). This trend is challenging the model for end-stage liver disease allocation system, where the sickest candidates are prioritised and no delisting criteria are given. The weighting of the deontological demand for "equity", trying to save every patient, regardless of the overall utility; and "efficiency", rooted in utilitarianism, trying to save as many patients as possible and increase the overall quality of life of patients facing the same problem, has to be reconsidered. In this article we are aiming to overcome the widespread concept of futility in liver transplantation, providing a definition of potentially inappropriate liver transplantation and giving guidance on situations where it is best not to proceed with liver transplantation, to decrease the mortality rate in the first three months after transplantation. We propose "absolute" and "relative" conditions, where early post-transplant mortality is highly probable, which are not usually captured in risk scores predicting post-transplant survival. Withholding liver transplantation for listed patients in cases where liver transplant is not deemed clearly futile, but is potentially inappropriate, is a far-reaching decision. Until now, this decision had to be discussed extensively on an individual basis, applying explicit communication and conflict resolution processes, since the model for end-stage liver disease score and most international allocation systems do not include explicit delisting criteria to support a fair delisting process. More work is needed to better identify cases where transplantation is potentially inappropriate and to integrate and discuss these delisting criteria in allocation systems, following a societal debate on what we owe to all liver transplant candidates.

Venovenous Bypass Is Associated With a Lower Incidence of Acute Kidney Injury After Liver Transplantation in Patients With Compromised Pretransplant Renal Function.

BACKGROUND: Although the hemodynamic benefits of venovenous bypass (VVB) during liver transplantation (LT) are well appreciated, the impact of VVB on posttransplant renal function is uncertain. The aim of this study was to determine if VVB was associated with a lower incidence of posttransplant acute kidney injury (AKI). METHODS: Medical records of adult (≥18 years) patients who underwent primary LT between 2004 and 2014 at a tertiary hospital were reviewed. Patients who required pretransplant renal replacement therapy and intraoperative piggyback technique were excluded. Patients were divided into 2 groups, VVB and non-VVB. AKI, determined by the Acute Kidney Injury Network criteria, was compared between the 2 groups. Propensity match was used to control selection bias that occurred before VVB and multivariable logistic regression was used to control confounding factors during and after VVB. RESULTS: Of 1037 adult patients who met the study inclusion criteria, 247 (23.8%) received VVB. A total of 442 patients (221 patients in each group) were matched. Aftermatch patients were further divided according to a predicted probability AKI model using preoperative creatinine (Cr), VVB, and intraoperative variables into 2 subgroups: normal and compromised pretransplant renal functions. In patients with compromised pretransplant renal function (Cr ≥1.2 mg/dL), the incidence of AKI was significantly lower in the VVB group compared with the non-VVB group (37.2% vs 50.8%; P = .033). VVB was an independent risk factor negatively associated with AKI (odds ratio, 0.1; 95% confidence interval, 0.1-0.4; P = .001). Renal replacement in 30 days and 1-year recipient mortality were not significantly different between the 2 groups. The incidence of posttransplant AKI was not significantly different between the 2 groups in patients with normal pretransplant renal function (Cr <1.2 mg/dL). CONCLUSIONS: In this large retrospective study, we demonstrated that utilization of intraoperative VVB was associated with a significantly lower incidence of posttransplant AKI in patients with compromised pretransplant renal function. Further studies to assess the role of intraoperative VVB in posttransplant AKI are warranted.

Simulation-based Assessment of the Management of Critical Events by Board-certified Anesthesiologists.

BACKGROUND: We sought to determine whether mannequin-based simulation can reliably characterize how board-certified anesthesiologists manage simulated medical emergencies. Our primary focus was to identify gaps in performance and to establish psychometric properties of the assessment methods. METHODS: A total of 263 consenting board-certified anesthesiologists participating in existing simulation-based maintenance of certification courses at one of eight simulation centers were video recorded performing simulated emergency scenarios. Each participated in two 20-min, standardized, high-fidelity simulated medical crisis scenarios, once each as primary anesthesiologist and first responder. Via a Delphi technique, an independent panel of expert anesthesiologists identified critical performance elements for each scenario. Trained, blinded anesthesiologists rated video recordings using standardized rating tools. Measures included the percentage of critical performance elements observed and holistic (one to nine ordinal scale) ratings of participant's technical and nontechnical performance. Raters also judged whether the performance was at a level expected of a board-certified anesthesiologist. RESULTS: Rater reliability for most measures was good. In 284 simulated emergencies, participants were rated as successfully completing 81% (interquartile range, 75 to 90%) of the critical performance elements. The median rating of both technical and nontechnical holistic performance was five, distributed across the nine-point scale. Approximately one-quarter of participants received low holistic ratings (i.e., three or less). Higher-rated performances were associated with younger age but not with previous simulation experience or other individual characteristics. Calling for help was associated with better individual and team performance. CONCLUSIONS: Standardized simulation-based assessment identified performance gaps informing opportunities for improvement. If a substantial proportion of experienced anesthesiologists struggle with managing medical emergencies, continuing medical education activities should be reevaluated.

Liver Transplantation in a Patient With Antiphospholipid Syndrome: A Case Report.

Antiphospholipid syndrome (APS) is an acquired thrombophilic disorder characterized by autoantibodies to cell membrane phospholipids. While altered coagulation can complicate end-stage liver disease, there are few reports describing the perioperative management for liver transplantation in recipients with a preexisting hypercoagulable disorder, such as APS. We present a patient with a history of APS, Budd-Chiari syndrome with cirrhosis, hepatopulmonary syndrome, and heparin-induced thrombocytopenia who underwent liver transplantation complicated by hepatic artery thrombosis. Management included postoperative anticoagulation with a factor Xa inhibitor and, after repeat transplantation, transition to long-term anticoagulation therapy with eventual recovery.

Frequency and Type of Situational Awareness Errors Contributing to Death and Brain Damage: A Closed Claims Analysis.

BACKGROUND: Situational awareness errors may play an important role in the genesis of patient harm. The authors examined closed anesthesia malpractice claims for death or brain damage to determine the frequency and type of situational awareness errors. METHODS: Surgical and procedural anesthesia death and brain damage claims in the Anesthesia Closed Claims Project database were analyzed. Situational awareness error was defined as failure to perceive relevant clinical information, failure to comprehend the meaning of available information, or failure to project, anticipate, or plan. Patient and case characteristics, primary damaging events, and anesthesia payments in claims with situational awareness errors were compared to other death and brain damage claims from 2002 to 2013. RESULTS: Anesthesiologist situational awareness errors contributed to death or brain damage in 198 of 266 claims (74%). Respiratory system damaging events were more common in claims with situational awareness errors (56%) than other claims (21%, P < 0.001). The most common specific respiratory events in error claims were inadequate oxygenation or ventilation (24%), difficult intubation (11%), and aspiration (10%). Payments were made in 85% of situational awareness error claims compared to 46% in other claims (P = 0.001), with no significant difference in payment size. Among 198 claims with anesthesia situational awareness error, perception errors were most common (42%), whereas comprehension errors (29%) and projection errors (29%) were relatively less common. CONCLUSIONS: Situational awareness error definitions were operationalized for reliable application to real-world anesthesia cases. Situational awareness errors may have contributed to catastrophic outcomes in three quarters of recent anesthesia malpractice claims.Situational awareness errors resulting in death or brain damage remain prevalent causes of malpractice claims in the 21st century.