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.

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.

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.

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.

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.

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.

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.

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.

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.

Effect of Performance Deficiencies on Graduation and Board Certification Rates: A 10-yr Multicenter Study of Anesthesiology Residents.

BACKGROUND: This multicenter, retrospective study was conducted to determine how resident performance deficiencies affect graduation and board certification. METHODS: Primary documents pertaining to resident performance were examined over a 10-yr period at four academic anesthesiology residencies. Residents entering training between 2000 and 2009 were included, with follow-up through February 2016. Residents receiving actions by the programs' Clinical Competency Committee were categorized by the area of deficiency and compared to peers without deficiencies. RESULTS: A total of 865 residents were studied (range: 127 to 275 per program). Of these, 215 residents received a total of 405 actions from their respective Clinical Competency Committee. Among those who received an action compared to those who did not, the proportion graduating differed (93 vs. 99%, respectively, P < 0.001), as did the proportion achieving board certification (89 vs. 99%, respectively, P < 0.001). When a single deficiency in an Essential Attribute (e.g., ethical, honest, respectful behavior; absence of impairment) was identified, the proportion graduating dropped to 55%. When more than three Accreditation Council for Graduate Medical Education Core Competencies were deficient, the proportion graduating also dropped significantly. CONCLUSIONS: Overall graduation and board certification rates were consistently high in residents with no, or isolated, deficiencies. Residents deficient in an Essential Attribute, or multiple competencies, are at high risk of not graduating or achieving board certification. More research is needed on the effectiveness and selective deployment of remediation efforts, particularly for high-risk groups.

Myocardial injury in patients with hemodynamic derangements during and/or after liver transplantation.

Myocardial injury, defined as an elevation of cardiac troponin (cTn) resulting from ischemia, is associated with substantial mortality in surgical patients, and its incidence, risk factors, and impact on patients undergoing liver transplantation (LT) are poorly understood. In this study, adult patients who experienced perioperative hemodynamic derangements and had cTn measurements within 30 days after LT between 2006 and 2013 were studied. Of 502 patients, 203 (40.4%) met the diagnostic criteria (cTn I ≥0.1 ng/mL) of myocardial injury. The majority of myocardial injury occurred within the first three postoperative days and presented without clinical signs or symptoms of myocardial infarction. Thirty-day mortality in patients with myocardial injury was 11.4%, significantly higher compared with that in patients without myocardial injury (3.4%, P<.01). Cox analysis indicated the peak cTn was significantly associated with 30-day mortality. Multivariable logistic analysis identified three independent risk factors: requirement of ventilation before transplant (odds ratios (OR) 1.6, P=.006), RBC≥15 units (OR 1.7, P=.006), and the presence of PRS (OR 2.0, P=.028). We concluded that post-LT myocardial injury in this high-risk population was common and associated with mortality. Our findings may be used in pretransplant stratification. Further studies to investigate this postoperative cardiac complication in all LT patients are warranted.

Practice improvements based on participation in simulation for the maintenance of certification in anesthesiology program.

BACKGROUND: This study describes anesthesiologists' practice improvements undertaken during the first 3 yr of simulation activities for the Maintenance of Certification in Anesthesiology Program. METHODS: A stratified sampling of 3 yr (2010-2012) of participants' practice improvement plans was coded, categorized, and analyzed. RESULTS: Using the sampling scheme, 634 of 1,275 participants in Maintenance of Certification in Anesthesiology Program simulation courses were evaluated from the following practice settings: 41% (262) academic, 54% (339) community, and 5% (33) military/other. A total of 1,982 plans were analyzed for completion, target audience, and topic. On follow-up, 79% (1,558) were fully completed, 16% (310) were partially completed, and 6% (114) were not completed within the 90-day reporting period. Plans targeted the reporting individual (89% of plans) and others (78% of plans): anesthesia providers (50%), non-anesthesia physicians (16%), and non-anesthesia non-physician providers (26%). From the plans, 2,453 improvements were categorized as work environment or systems changes (33% of improvements), teamwork skills (30%), personal knowledge (29%), handoff (4%), procedural skills (3%), or patient communication (1%). The median word count was 63 (interquartile range, 30 to 126) for each participant's combined plans and 147 (interquartile range, 52 to 257) for improvement follow-up reports. CONCLUSIONS: After making a commitment to change, 94% of anesthesiologists participating in a Maintenance of Certification in Anesthesiology Program simulation course successfully implemented some or all of their planned practice improvements. This compares favorably to rates in other studies. Simulation experiences stimulate active learning and motivate personal and collaborative practice improvement changes. Further evaluation will assess the impact of the improvements and further refine the program.

Gastroesophageal and hemorrhagic complications associated with intraoperative transesophageal echocardiography in patients with model for end-stage liver disease score 25 or higher.

OBJECTIVE: To investigate major gastroesophageal and hemorrhagic complications that may be related to intraoperative transesophageal echocardiography (TEE) in liver transplant (LT) patients with high model for end-stage liver disease (MELD) score 25 or higher. DESIGN: Retrospective. SETTING: Single institution university setting. PARTICIPANTS: Of 906 transplant recipients, 656 who had MELD score 25 or higher were included for analysis. INTERVENTIONS: Patient demographics, pre- and intraoperative characteristics, and major gastroesophageal and hemorrhagic complications were compared between patients with and without TEE. MEASUREMENTS AND MAIN RESULTS: Sixty-six percent (433 patients) had intraoperative TEE and 34% (223 patients) did not. One patient in the TEE group had a major gastroesophageal complication (Mallory-Weiss tear). Eleven patients required postoperative gastrointestinal consultation. These patients were distributed evenly between the TEE and non-TEE groups. Eighteen (2.8%) had major hemorrhagic complication (defined as bloody nasogastric output>500 mL in 24 hours postoperatively). Multivariate analysis showed alcoholic cirrhosis had 5.3 higher odds of post-transplant gastroesophageal hemorrhage compared with other indications for transplant (95% confidence interval 1.8-15.8, p<0.001). TEE was not associated with an increased likelihood of major hemorrhagic complication after LT. CONCLUSIONS: The authors demonstrated that the incidence of major gastroesophageal and hemorrhagic complications following intraoperative TEE in LT patients with MELD score 25 or higher was low.

Perioperative complications in liver transplantation using donation after cardiac death grafts: a propensity-matched study.

Donation after cardiac death (DCD) is an important source for expanding the donor pool for liver transplantation (LT). Although the long-term outcomes of LT using DCD grafts have been extensively studied, perioperative complications related to DCD grafts are rarely reported. The aim of this study was to determine whether DCD grafts were associated with a higher incidence of postreperfusion complications and worse outcomes in adult LT patients. After institutional review board approval, the medical records of all adult patients who underwent LT at our medical center between 2004 and 2011 were reviewed. Postreperfusion complications and posttransplant outcomes were compared between patients receiving DCD grafts and patients receiving donation after brain death (DBD) grafts. In all, 74 patients received DCD grafts during the study period, and 1369 patients received DBD grafts. An initial comparison showed that many preoperative, prereperfusion, and donor variables in the DCD group differed significantly from those in the DBD group. Propensity matching was chosen so that adjustments could be made for the differences. A postmatching analysis showed that the preoperative, prereperfusion, and donor variables no longer differed between the 2 groups. The postreperfusion requirements for blood products and vasopressors, the posttransplant ventilation times, the incidence of posttransplant acute renal injury, and the 30-day and 1-year patient and graft survival rates were comparable between the 2 groups. However, patients receiving DCD grafts experienced significantly higher rates of hyperkalemia (33.8% versus 18.9%, P < 0.05) and postreperfusion syndrome (PRS; 25.7% versus 12.3%, P < 0.05). In conclusion, after adjustments for preoperative and prereperfusion risks via propensity matching, DCD grafts remained a risk factor for postreperfusion hyperkalemia and PRS. A prophylactic regimen aimed at decreasing postreperfusion hyperkalemia and PRS is recommended for the management of LT using DCD grafts.

Storage age of transfused red blood cells during liver transplantation and its intraoperative and postoperative effects.

BACKGROUND: Recent studies suggest that the storage age of red blood cells (RBCs) may be associated with morbidity and mortality in surgical patients. We studied perioperative effects of RBC storage age in patients undergoing orthotopic liver transplant (OLT). METHODS: Adult patients who received ≥ 5 U of RBCs during OLT between January 2004 and June 2009 were studied. The subjects were divided into two groups according to the mean storage age of RBCs they received: new or old RBCs (stored ≤ 14 or >14 days, respectively). Effects of storage age of transfused RBCs during OLT on intraoperative potassium (K(+)) concentrations, incidence of hyperkalemia (K(+) ≥ 5.5 mmol/L), postoperative morbidity, and patient and graft survival were studied. RESULTS: The mean serum K(+) concentrations and the incidence of hyperkalemia during OLT were significantly associated with storage age of the RBCs. Logistic analysis showed that storage age of RBCs was an independent risk factor for intraoperative hyperkalemia (odds ratios 1.067-1.085, p < 0.001) in addition to baseline K(+) concentration and units of RBCs transfused. Patient and graft survival and postoperative morbidity including postoperative ventilation, reoperation, acute renal dysfunction defined by the RIFLE criteria was not associated with old RBCs. CONCLUSIONS: Transfusion of RBCs stored for a longer time was associated with intraoperative hyperkalemia but not with postoperative adverse outcomes in adult OLT. Prevention and treatment of potentially harmful hyperkalemia should be considered when old RBCs are administered.