Use of Transesophageal Echocardiography for Liver Transplantation: A Global Comparison of Practice From the ILTS, SATA, and LICAGE.

BACKGROUND: Anesthesiologists frequently use intraoperative transesophageal echocardiography (TEE) to aid in the diagnosis and management of hemodynamic problems during liver transplantation (LT). Although the use of TEE in US centers continues to increase, data regarding international use are lacking. METHODS: This prospective, global, survey-based study evaluates international experience with TEE for LT. Responses from 252 LT (105 US and 147 non-US) centers representing 1789 anesthesiologists were analyzed. RESULTS: Routine use of TEE in the United States has increased in the last 5 y (from 37% to 47%), but only 21% of non-US LT anesthesiologists use TEE routinely. Lack of training (44% US versus 70% non-US) and equipment (9% non-US versus 34% US) were cited as obstacles. Most survey participants preferred not to perform a complete cardiac examination but rather use only 6 of 11 basic views. Although non-US LT anesthesiologists more frequently had additional clinical training than their US counterparts, they had less TEE experience (13% versus 44%) and less frequently, TEE certification (22% versus 35%). Most LT anesthesiologists agreed that TEE certification is essential for proficiency. Of all respondents, 89% agreed or strongly agreed that TEE provides valuable information needed for immediate clinical decision-making, and >86% agreed or strongly agreed that that information could not be derived from other sources. CONCLUSIONS: The use of TEE for LT surgery in the US LT centers is currently higher compared with non-US LT centers. This may become a standard monitoring modality during LT in the near future.

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 "Ice Age" in Cardiac Surgery: Evolution of the "Siberian" Method of Brain Protection During Deep Hypothermic Perfusionless Circulatory Arrest.

Deep hypothermic perfusionless circulatory arrest was the first practical neuroprotective technique used for open-heart surgery. It was refined at the Novosibirsk Medical Research Center in Siberia and was actively used from the mid-1950s until 2001.This review describes the development of this technique and its contribution to our understanding of the dynamic changes in human physiology during induced hypothermia for circulatory arrest without extracorporeal perfusion. Deep hypothermic perfusionless circulatory arrest was an important stepping stone in the development of modern approaches in neuroprotection and monitoring during cardiac surgery.

Acute heart failure after Orthotopic liver transplantation: a case series from one center.

BACKGROUND: Patients undergoing liver transplantation (LT) can develop acute heart failure (HF) in the postoperative period despite having had a normal cardiac evaluation prior to surgery. End-stage liver disease is often associated with underlying cardiac dysfunction which, while not identified during preoperative testing, manifests itself during or immediately after surgery. CASE PRESENTATION: We describe three cases of non-ischemic acute HF developing shortly after LT in patients who had a normal preoperative cardiac evaluation. The challenges associated with both diagnosis and management of acute HF in the setting of a newly implanted graft will be discussed. CONCLUSIONS: Diastolic dysfunction, QTc interval prolongation, and an increase in BNP may be predictive of postoperative HF. Current recommendations for preoperative cardiovascular evaluation of transplant candidates does not include studies examining these risk factors and should be revised. Further investigations are necessary to evaluate these findings.

Perioperative Anesthetic Management of Patients Having Liver Transplantation for Uncommon Conditions.

This review focuses on the perioperative anesthetic management of patients having liver transplantation (LT) performed for several uncommon indications or in combination with rare pathology. Conditions discussed in the article include Alagille syndrome, hypertrophic cardiomyopathy, Gilbert's syndrome, porphyria, Wilson's disease, and Budd-Chiari syndrome. In comparison to other indications, LT in these settings is infrequent because of the low incidence of these pathologies. Most of these conditions (with the exception of Gilbert syndrome) are associated with a high probability of significant perioperative complications and increased mortality and morbidity. Experience in management of these unusual conditions is only gained over time. Developing clinical pathways for patients with these conditions should result in outcomes similar to LT performed for more common indications.

Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats.

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD.

Successful Liver Transplant Complicated by Severe Portopulmonary Hypertension After an Initial Aborted Attempt: Case Report and Review of Treatment Options.

Good right ventricular function and responsiveness to vasodilator therapy are the most important prerequisites for successful liver transplant in patients with portopulmonary hypertension. A patient with portopulmonary hypertension and good right ventricular function presented for deceased-donor liver transplant. Pulmonary arterial pressure was controlled with epoprostenol and sildenafil preoperatively. After anesthesia induction, pulmonary arterial pressure increased significantly and the procedure was aborted. Additional medical treatment included aggressive vasodilator therapy and the transplant was successfully performed 1 month later. During the procedure, elevations in pulmonary arterial pressure responded to a combination of inhaled nitric oxide, intravenous milrinone and nitroglycerin, and optimization of mechanical ventilation.

Hepatic resection is associated with reduced postoperative opioid requirement.

BACKGROUND AND AIMS: Postoperative pain can significantly affect surgical outcomes. As opioid metabolism is liver-dependent, any reduction in hepatic volume can lead to increased opioid concentrations in the blood. The hypothesis of this retrospective study was that patients undergoing open hepatic resection would require less opioid for pain management than those undergoing open pancreaticoduodenectomy. MATERIAL AND METHODS: Data from 79 adult patients who underwent open liver resection and eighty patients who underwent open pancreaticoduodenectomy at our medical center between January 01, 2010 and June 30, 2013 were analyzed. All patients received both general and neuraxial anesthesia. Postoperatively, patients were managed with a combination of epidural and patient-controlled analgesia. Pain scores and amount of opioids administered (morphine equivalents) were compared. A multivariate lineal regression was performed to determine predictors of opioid requirement. RESULTS: No significant differences in pain scores were found at any time point between groups. Significantly more opioid was administered to patients having pancreaticoduodenectomy than those having a hepatic resection at time points: Intraoperative (P = 0.006), first 48 h postoperatively (P = 0.001), and the entire length of stay (LOS) (P = 0.002). Statistical significance was confirmed after controlling for age, sex, body mass index, and American Society of Anesthesiologists physical status classification (adjusted P = 0.006). Total hospital LOS was significantly longer after pancreaticoduodenectomy (P = 0.03). A multivariate lineal regression demonstrated a lower opioid consumption in the hepatic resection group (P = 0.03), but there was no difference in opioid use based on the type of hepatic resection. CONCLUSION: Patients undergoing open hepatic resection had a significantly lower opioid requirement in comparison with patients undergoing open pancreaticoduodenectomy. A multicenter prospective evaluation should be performed to confirm these findings.

Autoimmune conditions are associated with perioperative thrombotic complications in liver transplant recipients: A UNOS database analysis.

BACKGROUND: End stage liver disease (ESLD) is associated with significant thrombotic complications. In this study, we attempted to determine if patients with ESLD, due to oncologic or autoimmune diseases, are susceptible to thrombosis to a greater extent than patients with ESLD due to other causes. METHODS: In this retrospective study, we analyzed the UNOS database to determine the incidence of thrombotic complications in orthotopic liver transplant (OLT) recipients with autoimmune and oncologic conditions. Between 2000 and 2012, 65,646 OLTs were performed. We found 4,247 cases of preoperative portal vein thrombosis (PVT) and 1,233 cases of postoperative vascular thrombosis (VT) leading to graft failure. RESULTS: Statistical evaluation demonstrated that patients with either hepatocellular carcinoma (HCC) or autoimmune hepatitis (AIC) had a higher incidence of PVT (p = 0.05 and 0.03 respectively). Patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and AIC had a higher incidence of postoperative VT associated with graft failure (p < 0.0001, p < 0.0001, p = 0.05 respectively). Patients with preoperative PVT had a higher incidence of postoperative VT (p < 0.0001). Multivariable logistic regression demonstrated that patients with AIC, and BMI ≥40, having had a transjugular intrahepatic portosystemic shunt, and those with diabetes mellitus were more likely to have preoperative PVT: odds ratio (OR)(1.36, 1.19, 1.78, 1.22 respectively). Patients with PSC, PBC, AIC, BMI ≤18, or with a preoperative PVT were more likely to have a postoperative VT: OR (1.93, 2.09, 1.64, 1.60, and 2.01, respectively). CONCLUSION: Despite the limited number of variables available in the UNOS database potentially related to thrombotic complications, this analysis demonstrates a clear association between autoimmune causes of ESLD and perioperative thrombotic complications. Perioperative management of patients at risk should include strategies to reduce the potential for these complications.

Portal Hypertension: An Underestimated Entity?

OBJECTIVE: The aim of this study is to evaluate portal hypertension as an independent risk factor in general surgical procedures. BACKGROUND: Data on the impact of portal hypertension in general surgical outcomes has been limited. Published literature has focused mainly on its effect in liver surgery. The Child Pugh score and Model for End Stage Liver Disease are utilized for surgical risk assessment in liver disease but they do not accurately reflect degree of portal hypertension. METHODS: From 2005 to 2012, patients with esophageal varices (EV) in the National Surgical Quality Improvement Program (NSQIP) formed the portal hypertension cohort, and were case matched to patients without esophageal varices (NEV) based on sex, age, surgery type, and year of operation. Thirty day mortality and morbidity were analyzed using generalized estimating equations for binary outcomes. EV patients were also dichotomized by Model for End Stage Liver Disease (MELD) score (≤15 vs >15) and compared with NEV patients. RESULTS: One thousand five hundred and seventy-four EV patients were matched to 3148 NEV patients. In multivariable analysis, EV patients had a 3.01 higher odds of 30 day mortality (P < 0.001) and 1.28 higher odds of complications (P < 0.001) compared with NEV patients. EV patients with MELD >15 had 4.64 higher odds of death within 30 days (P < 0.001) and had 1.75 higher odds of complications within 30 days (P < 0.001) compared with NEV patients; EV patients with MELD 15 or less had 1.95 higher odds of 30 day mortality (P < 0.001) compared with NEV patients. CONCLUSIONS: Portal hypertension is associated with a significant mortality and morbidity risk in general surgery, and should not be underestimated even in patients with MELD 15 or less where the early mortality risk remained significant.

Effect of cold perfusion and perfluorocarbons on liver graft ischemia in a donation after cardiac death model.

BACKGROUND: Effects of two perfluorocarbon (PFC) formulations (perfluorodecalin emulsion and perfluorodecalin liquid) on the quality of liver graft preservation, in a donation after cardiac death (DCD) rat model, were investigated. The significance of continuous graft perfusion during cold preservation was also explored. MATERIALS AND METHODS: DCD model: 30 min after cardiopulmonary arrest was initiated, livers were excised and flushed with cold University of Wisconsin (UW) solution (± PFC) and preserved in the same solution for 8 h. The study groups were preserved as follows: group 1: no perfusion; group 2: perfusion with UW; group 3: PFC was administered before cardiac arrest and the liver was perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In a baseline group used only for comparison of gene expression, livers were quick-frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations were performed to assess the quality of graft preservation. RESULTS: Significant decreases in downregulation and increases in upregulation of hepatic genes (relative to baseline) were demonstrated in all perfusion groups. This trend was most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a reduction in Caspase 3 activation were found in all perfusion groups. CONCLUSION: Hypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (± PFC) produced superior preservation compared with nonperfusion storage. The observed changes in expression of hepatic genes may represent a protective effect in the DCD model.

Analysis of acute pain scores and skin conductance measurements in infants.

BACKGROUND: Skin conductance (SC) has been previously used to measure acute post-operative pain in adults and older children (>1year old).We have investigated the ability of SC to predict the severity of post-operative pain scores in the exclusively infant population. METHODS: Infants (ages 6-12months) scheduled for elective surgery were recruited for the study. Data for behavioral pain scores and SC values - frequency of electrodermal responses per second (EDR/s), peak and basal levels, were recorded in the post-anesthesia care unit (PACU). Blood samples were collected for genomic studies, including single nucleotide polymorphisms (SNP) in morphine opioid receptor (MOR) A118G and the catechol-O-methyltransferase (COMT) G1947A genes. RESULTS: 31 infants, mean age 8.9months (±1.9); mean weight 8.5kg (±1.1) were included in the final study analysis. With every 0.1 unit increase in peak values noted on SC, the odds of higher pain scores were found to be 5% greater (p=0.03). For predictability of moderate to severe pain, the area under the curve, sensitivity and specificity were 0.64, 90.9% and 51.4% respectively for peak values and 0.66, 54.5% and 79.4% respectively for EDR/s values. Genotyping performed in 16 out of 31 infants demonstrated that the carriers of MOR 118G allele had consistently higher basal SC values in the PACU. CONCLUSION: Peak SC values may serve as indicators of unmitigated pain. Further studies are needed to fully investigate the effect of MOR A118G SNP on the post operative pain scores and SC values in the larger infant population in order to validate both the clinical significance of the skin conductance for routine pain assessment in infants and the observed genetic effect.

Reappraisal of the role of dolasetron in prevention and treatment of nausea and vomiting associated with surgery or chemotherapy.

Chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting are one of the most frequent but also very concerning consequences for patients undergoing chemotherapy or surgical procedures under general anesthesia. There are a variety of mechanisms involved in the activation of nausea and vomiting. Serotonin, a ubiquitous central and peripheral neurotransmitter, is thought to be the predominant mediator of the perception of nausea and triggering of the vomiting response in both the brain and the periphery via the 5-hydroxytryptamine type 3 (5-HT(3)) receptor pathways. 5-HT(3) receptor antagonists disrupt this pathway, largely at the level of the vagal afferent pathways, to decrease nausea and vomiting. This review will focus on dolasetron, an older but sill commonly used 5-HT(3) receptor antagonist and its multimodal mechanism of action, safety and tolerability, patient considerations, and a review of the current literature on its use to combat both chemotherapy-induced and postoperative nausea and vomiting in these two important patient populations.

Use of a third-generation perfluorocarbon for preservation of rat DCD liver grafts.

BACKGROUND: Cold storage in any of the commonly used preservation solutions is not always adequate for donation after cardiac death (DCD) liver grafts due to prolonged warm ischemic time. In this study, we used a third-generation perfluorocarbon (PFC), Oxycyte, for DCD liver graft preservation in a rat model. MATERIALS AND METHODS: Twenty-eight rats (14 in each group) were used. Thirty minutes after cardiopulmonary arrest, livers were harvested and flushed with a cold and pre-oxygenated solution of either University of Wisconsin (UW) or UW + 20% PFC. After 8 h of cold preservation in either of the investigated solutions, liver graft specimens were analyzed for evidence of ischemic injury. Hemotoxylin and eosin staining (H and E), as well as immunohistochemical analysis with anti-cleaved caspase 3 antibody, was performed. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the preservation solution were analyzed at 1 and 8 h during preservation. RESULTS: In the PFC group, the degree of cell congestion, vacuolization and necrosis were all significantly less than in the UW group (P = 0.002-0.004). The number of cells with a positive cleaved caspase 3 antibody reaction was reduced by about 50% in comparison with the UW group (P < 0.006). The AST level in the PFC group was significantly less than in the UW group after 8 h of preservation (P < 0.048). CONCLUSION: The addition of PFC to UW solution significantly decreases the degree of histologic damage in rat DCD liver grafts. This preservation strategy can be potentially helpful for organ preservation after prolonged warm ischemia.

Learning curves of novice anesthesiology residents performing simulated fibreoptic upper airway endoscopy.

BACKGROUND: In various medical and surgical specialties, it is essential to acquire fibreoptic upper airway endoscopy skills for successful endotracheal intubation, especially when faced with a difficult airway. The aim of our study was to evaluate the learning curves of residents performing fibreoptic upper airway endoscopy in the simulation environment. METHODS: Following a standardized video and practice session, 16 residents newly enrolled in the anesthesiology program performed nasal fibreoptic endoscopy of the upper airway (endpoint being the carina) on a high fidelity simulator. Weekly 20-min sessions continued for a period of one month. Each attempt was designated as either a "success" or a "failure" based on the study participant's ability or inability to visualize the carina in ≤60 sec and with ≤five collisions with the simulated mucosal wall. Proficiency was attained when the downward graphical trend of the cumulative sum (CUSUM) analysis crossed two adjacent boundary lines, i.e., an acceptable failure rate was reached. RESULTS: The residents' mean number of attempts at fibreoptic airway endoscopy was 47 (9) with a range of 32-64. Time to visualization of the carina was 51 (36) sec. Three classical patterns of CUSUM trends were observed: proficient (n = 7); not proficient with a downward (improvement) trend (n = 3); and not proficient with an upward (worsening) trend (n = 6). The number of attempts at which proficiency was achieved varied from 27 to 58. CONCLUSION: There is a large variation in the learning curves of residents performing fibreoptic upper airway endoscopy. The training for fibreoptic airway endoscopy should be tailored to the needs of each individual.

Release of cytokines and hemodynamic instability during the reperfusion of a liver graft.

The objectives of this prospective, observational study were (1) to determine whether a transplanted liver graft releases proinflammatory cytokines into the systemic circulation upon reperfusion and (2) to determine whether they contribute to any subsequent hemodynamic instability observed after graft reperfusion (if this release occurs). Blood samples from 17 consecutive patients undergoing liver transplantation were analyzed for cytokines, including tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), IL-2, IL-6, and IL-8. Blood samples were obtained from the radial artery, portal vein, and flush blood (a sample taken from a catheter placed above the infrahepatic inferior vena cava clamp). The amount of catecholamines necessary to maintain a mean arterial pressure between 65 and 75 mm Hg during graft reperfusion was compared with the level of cytokines. A statistical analysis was performed with the least squares method, Kendall's tau-b test, and regression analysis. We demonstrated that flush blood from the liver grafts contained a significant amount and variety of cytokines. Most of these were removed by graft irrigation. The concentration of TNF-α in samples obtained from flush blood at the end of liver irrigation was significantly higher than the concentration in samples obtained from the radial artery (P = 0.0067) or portal vein (P = 0.0003) before reperfusion. This correlated directly with the amount of catecholamines used to treat hemodynamic instability. Although there were increased levels of IL-1ß, IL-2, and IL-8 in the flush blood, there was no statistically significant correlation between the levels of these cytokines and the amount of catecholamines used.