Optimal management of perioperative analgesia regarding immediate and short-term outcomes after liver transplantation - A systematic review, meta-analysis and expert panel recommendations.

BACKGROUND: Adequate pain control is essential for patients undergoing liver transplantation (LT). Multiple analgesic strategies have been implemented during the perioperative period. There is no consensus on the optimal perioperative analgesia management. OBJECTIVES: To provide recommendations, on the optimal perioperative analgesia management for LT. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: A systematic review and meta-analysis following PRISMA guidelines and recommendations using GRADE. Studies describing outcomes, morbidity, mortality, pain scores, intensive care unit and hospital length of stay in patients that received different pain management techniques during and after LT were included (CRD42021243282). RESULTS: One thousand nine hundred ten articles were screened, but only two randomized controlled trials, one prospective and six retrospective studies were included. The opioid-avoidance protocols included, thoracic epidural analgesia (TEA), Transversus Abdominis Plane (TAP) block, as well as other non-opioid analgesics, resulted in improved short-term outcomes. Mortality was reduced in this group versus control cohorts (OR = 0.51; CI 0.14, 1.83; P = 0.350), Time to extubation, and intensive care unit LOS were shorter; pain scores after surgery were lower in opioid-avoidance group (percentage decrease, 35%, 12%, and 55%, respectively). However, hospital LOS was longer (percentage increase 8%). CONCLUSIONS: Opioid-avoidance analgesia management for LT results in improved short-term outcomes. (Quality of Evidence; Moderate to low | Grade of Recommendation; Weak). Medications such as acetaminophen(paracetamol), gabapentin, ketamine, tramadol and local anesthesia may be used instead of, or as adjuncts to opioids for postoperative analgesia. Overall evidence remains weak and more robust studies are required.

Hemodynamic Instability During Liver Transplantation in Patients With End-stage Liver Disease: A Consensus Document from ILTS, LICAGE, and SATA.

Hemodynamic instability (HDI) during liver transplantation (LT) can be difficult to manage and increases postoperative morbidity and mortality. In addition to surgical causes of HDI, patient- and graft-related factors are also important. Nitric oxide-mediated vasodilatation is a common denominator associated with end-stage liver disease related to HDI. Despite intense investigation, optimal management strategies remain elusive. In this consensus article, experts from the International Liver Transplantation Society, the Liver Intensive Care Group of Europe, and the Society for the Advancement of Transplant Anesthesia performed a rigorous review of the most current literature regarding the epidemiology, causes, and management of HDI during LT. Special attention has been paid to unique LT-associated conditions including the causes and management of vasoplegic syndrome, cardiomyopathies, LT-related arrhythmias, right and left ventricular dysfunction, and the specifics of medical and fluid management in end-stage liver disease as well as problems specifically related to portal circulation. When possible, management recommendations are made.

Local Anesthetic Toxicity in the Geriatric Population.

This article provides a concise overview of local anesthetic systemic toxicity, its history, mechanisms, risk factors, prevention, clinical presentation, and treatment, with a special emphasis on issues specific to the geriatric population. The authors used MEDLINE, Scopus, and Google Scholar to search for original research articles (human and animal studies), registries data, case reports, review articles, and pertinent online publications using the combinations of the following search terms: local anesthetics, local anesthetic systemic toxicity, intralipid, lipid emulsion, Exparel, ultrasound-guidance, regional anesthesia, lidocaine, bupivacaine, ropivacaine, cocaine, procaine, tetracaine, levobupivacaine, liposomal bupivacaine, lignocaine. Local anesthetic systemic toxicity continues to occur despite the use of putatively less cardiotoxic formulations of local anesthetics and more common use of ultrasound guidance. The elderly appear to be at a disproportionately increased risk for toxicity owing to the presence of relevant comorbidities and decreased muscle mass. Examination of recent case reports involving patients over the age of 65 years demonstrates that inadvertent overdosing is responsible for some cases of local anesthetic systemic toxicity. Elderly patients are at increased risk of local anesthetic systemic toxicity. When considering use of local anesthetics in older patients, special attention should be paid to the presence of systemic disease and muscle wasting. The safety of regional anesthesia and multi-modal analgesia among these at-risk patients will be improved by educating physicians and staff to recognize and manage local anesthetic systemic toxicity.

Local Anesthetic Systemic Toxicity: A Narrative Literature Review and Clinical Update on Prevention, Diagnosis, and Management.

BACKGROUND: The objective of this narrative review of local anesthetic systemic toxicity is to provide an update on its prevention, diagnosis, and management. METHODS: The authors used a MEDLINE search of human studies, animal studies, and case reports and summarize findings following the American Society of Regional Anesthesia and Pain Medicine practice advisories on local anesthetic systemic toxicity. RESULTS: Between March of 2014 and November of 2016, there were 47 cases of systemic toxicity described. Twenty-two patients (47 percent) were treated with intravenous lipid emulsion and two patients (4.3 percent) died. Seizures were the most common presentation. The spectrum of presenting neurologic and cardiovascular symptoms and signs are broad and can be obscured by perioperative processes. Local anesthetic type, dosage, and volume; site of injection; and patient comorbidities influence the rate of absorption from the site of injection and biodegradation of local anesthetics. Consider discussing appropriate dosages as a component of the surgical "time-out." A large-volume depot of dilute local anesthetic can take hours before reaching peak plasma levels. Oxygenation, ventilation, and advanced cardiac life support are the first priorities in treatment. Lipid emulsion therapy should be given at the first sign of serious systemic toxicity with an initial bolus dose of 100 ml for adults weighing greater than 70 kg and 1.5 ml/kg for adults weighing less than 70 kg or for children. CONCLUSION: All physicians who administer local anesthetics should be educated regarding the nature of systemic toxicity and contemporary management algorithms that include lipid emulsion therapy.

Prolonged Pulseless Electrical Activity Cardiac Arrest After Intranasal Injection of Lidocaine With Epinephrine: A Case Report.

Local anesthetic toxicity is a rare but serious complication of local anesthetic administration. Although lidocaine has a safety profile superior to other amide local anesthetics, we report a case of cardiac arrest after intranasal injection of lidocaine. The case involves a 22-year-old healthy woman who experienced pulseless electrical activity shortly after a submucosal injection of 2.2 mg/kg of lidocaine with epinephrine. Resuscitative efforts were unsuccessful until a bolus of intralipid was given. This case emphasizes that even a "low" dose of a less lipophilic drug has the potential for severe toxicity.

Cardiac diseases among liver transplant candidates.

Improvements in early survival after liver transplant (LT) have allowed for the selection of LT candidates with multiple comorbidities. Cardiovascular disease is a major contributor to post-LT complications. We performed a literature search to identify the causes of cardiac disease in the LT population and to describe techniques for diagnosis and perioperative management. As no definite guidelines for preoperative assessment (except for pulmonary heart disease) are currently available, we recommend an algorithm for preoperative cardiac work-up.

The Third American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Local Anesthetic Systemic Toxicity: Executive Summary 2017.

The American Society of Regional Anesthesia and Pain Medicine's Third Practice Advisory on local anesthetic systemic toxicity is an interim update from its 2010 advisory. The advisory focuses on new information regarding the mechanisms of lipid resuscitation, updated frequency estimates, the preventative role of ultrasound guidance, changes to case presentation patterns, and limited information related to local infiltration anesthesia and liposomal bupivacaine. In addition to emerging information, the advisory updates recommendations pertaining to prevention, recognition, and treatment of local anesthetic systemic toxicity. WHAT'S NEW IN THIS UPDATE?: This interim update summarizes recent scientific findings that have enhanced our understanding of the mechanisms that lead to lipid emulsion reversal of LAST, including rapid partitioning, direct inotropy, and post-conditioning. Since the previous practice advisory, epidemiological data have emerged that suggest a lower frequency of LAST as reported by single institutions and some registries, nevertheless a considerable number of events still occur within the general community. Contemporary case reports suggest a trend toward delayed presentation, which may mirror the increased use of ultrasound guidance (fewer intravascular injections), local infiltration techniques (slower systemic uptake), and continuous local anesthetic infusions. Small patient size and sarcopenia are additional factors that increase potential risk for LAST. An increasing number of reported events occur outside of the traditional hospital setting and involve non-anesthesiologists.

Local Anesthetic Systemic Toxicity: A Review of Recent Case Reports and Registries.

This review summarizes presenting features, management, and outcomes of local anesthetic systemic toxicity (LAST) from published cases and those submitted to online registries capturing use of intravenous lipid emulsion (ILE) therapy. The results of single-center and multicenter registries and epidemiologic studies complement this information. Between March 2014 and November 2016, 47 separate cases of LAST were described in 35 peer-reviewed articles. Local anesthetic systemic toxicity events occurred as a result of penile blocks (23%), local infiltration (17%), and upper/lower extremity, torso, and neuraxial blockade. Twenty-two patients (47%) were treated with ILE, and 2 patients (4.3%) died. During the same time period, 11 cases submitted to lipidrescue.org were treated with ILE and survived. The incidence of LAST reported in registries is 0.03% or 0.27 (95% confidence interval, 0.21-0.35) per 1000 peripheral nerve blocks (denominator of 251,325). Seizure (53% and 61% from case reports and registries, respectively) was the most common presenting feature.

Epsilon-Aminocaproic Acid Has No Association With Thromboembolic Complications, Renal Failure, or Mortality After Liver Transplantation.

OBJECTIVES: To examine the role of epsilon-aminocaproic acid (EACA) administered after reperfusion of the donor liver in the incidences of thromboembolic events and acute kidney injury within 30 days after orthotopic liver transplantation. One-year survival rates between the EACA-treated and EACA-nontreated groups also were examined. DESIGN: Retrospective, observational, cohort study design. SETTING: Single-center, university hospital. PARTICIPANTS: The study included 708 adult liver transplantations performed from 2008 to 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: EACA administration was not associated with incidences of intracardiac thrombosis/pulmonary embolism (1.3%) or intraoperative death (0.6%). Logistic regression (n = 708) revealed 2 independent risk factors associated with myocardial ischemia (age and pre-transplant vasopressor use) and 8 risk factors associated with the need for post-transplant dialysis (age, female sex, redo orthotopic liver transplantation, preoperative sodium level, pre-transplant acute kidney injury or dialysis, platelet transfusion, and re-exploration within the first week after transplant); EACA was not identified as a risk factor for either outcome. One-year survival rates were similar between groups: 92% in EACA-treated group versus 93% in the EACA-nontreated group. CONCLUSIONS: The antifibrinolytic, EACA, was not associated with an increased incidence of thromboembolic complications or postoperative acute kidney injury, and it did not alter 1-year survival after liver transplantation.

Adverse cardiac events after orthotopic liver transplantation: a cross-sectional study in 389 consecutive patients.

Current American College of Cardiology/American Heart Association guidelines caution that preoperative noninvasive cardiac tests may have poor predictive value for detecting coronary artery disease in liver transplant candidates. The purpose of our study was to evaluate the role of clinical predictor variables for early and late cardiac morbidity and mortality and the predictive values of noninvasive cardiac tests for perioperative cardiac events in a high-risk liver transplant population. In all, 389 adult recipients were retrospectively analyzed for a median follow-up time of 3.4 years (range = 2.3-4.4 years). Overall survival was 83%. During the first year after transplantation, cardiovascular morbidity and mortality rates were 15.2% and 2.8%. In patients who survived the first year, cardiovascular morbidity and mortality rates were 3.9% and 2%, with cardiovascular etiology as the third leading cause of death. Dobutamine stress echocardiography (DSE) and single-photon emission computed tomography had respective sensitivities of 9% and 57%, specificities of 98% and 75%, positive predictive values of 33% and 28%, and negative predictive values of 89% and 91% for predicting early cardiac events. A rate blood pressure product less than 12,000 with DSE was associated with an increased risk for postoperative atrial fibrillation. Correspondence analysis identified a statistical association between nonalcoholic steatohepatitis/cryptogenic cirrhosis and postoperative myocardial ischemia. Logistic regression identified 3 risk factors for postoperative acute coronary syndrome: age, history of coronary artery disease, and pretransplant requirement for vasopressors. Multivariable analysis showed statistical associations of the Model for End-Stage Liver Disease score and the development of acute kidney injury as risk factors for overall cardiac-related mortality. These findings may help in identifying high-risk patients and may lead to the development of better cardiac tests.

Guided surgical debridement: staining tissues with methylene blue.

Precise surgical debridement of wounds is required to achieve wound closure. The authors describe their experience with a technique using topical methylene blue to facilitate precise surgical debridement. In this technique, methylene blue dye is applied topically to the wound surface at the onset of surgery. The stained wound site is then wiped to remove dye from the surface of normal epithelium; eschar, nonviable tissue, and granulation tissue remain stained. The methylene blue-stained tissue is surgically removed, and the newly debrided surface of the wound is assessed for adequate vascularity and biopsied to verify presence of bacteriologic balance before closure. The authors have used this technique in more than 200 wound debridements during the past year, including acute surgical or traumatic wounds, acute and subacute burn wounds, chronic granulating wounds, partially epithelialized wounds, sinus tracts, and fistulae. No adverse reactions have been noted, even on patients undergoing multiple applications through serial operations. Topical application of methylene blue to wounds with mixed tissue content helps to distinguish between viable and nonviable tissue and between epithelialized and nonepithelialized areas, facilitating more precise and complete wound debridement.