Effects of Extracellular Calcium Concentration on Hepatic Ischemia-Reperfusion Injury in a Rat Model.

OBJECTIVES: Hypocalcemia is frequently identified during liver transplant. However, supplementation of extracellular calcium could induce increased intracellular calcium concentration, as a potential factor for injury to the liver graft. We evaluated the effects of regulating extracellular calcium concentrations on hepatic ischemia-reperfusion injury. MATERIALS AND METHODS: We randomly divided 24 Sprague-Dawley rats into 3 groups: group C received normal saline (n = 8), group L received citrate to induce hypocalcemia (n = 8), and group L-Co received citrate followed by calcium gluconate to ameliorate hypocalcemia (n = 8). Liver enzyme levels and extracellular calcium were measured before surgery, 1 hour after ischemia, and 2 hours after reperfusion. The primary outcome was liver enzyme levels measured 2 hours after reperfusion. In addition, we evaluated intracellular calcium levels, lactate dehydrogenase activity, and histopathological results in liver tissue. RESULTS: Three groups demonstrated significant differences in extracellular calcium concentrations, but intracellular calcium concentrations in liver tissue were not significantly different. Group L showed significantly lower mean arterial pressure than other groups at 1 hour after ischemia (93.6 ± 20.8 vs 69.4 ± 14.2 vs 86.6 ± 10.4 mmHg; P = .02, for group C vs L vs L-Co, respectively). At 2 hours after reperfusion, group L showed significantly higher liver enzymes than other groups (aspartate aminotransferase 443.0 ± 353.2 vs 952.3 ± 94.8 vs 502.4 ± 327.3 U/L, P = .01; and alanine aminotransferase 407.9 ± 406.5 vs 860.6 ± 210.9 vs 333.9 ± 304.2 U/L, P = .02; for group C vs L vs L-Co, respectively). However, no significant difference was shown in lactate dehydrogenase and histological liver injury grade. CONCLUSIONS: Administering calcium to rats with hypocalcemia did not increase intracellular calcium accumulation but instead resulted in less hepatic injury compared with rats with low extracellular calcium concentrations in this rat model study.

Forced-air prewarming prevents hypothermia during living donor liver transplantation: a randomized controlled trial.

Despite various intraoperative thermal strategies, core heat loss is considerable during liver transplantation and hypothermia is common. We tested whether forced-air prewarming prevents hypothermia during liver transplantation. Adult patients undergoing living donor liver transplantation were randomly assigned to non-prewarming group (n = 20) or prewarming group (n = 20). Patients in prewarming group underwent 30-min forced-air warming before anesthetic induction. During surgery, core temperature was measured in the pulmonary artery. The primary outcome was intraoperative hypothermia (< 36.0 °C). The secondary outcomes included plasma lactate concentration. Intraoperative hypothermia risk was significantly lower in prewarming group than in non-prewarming group (60.0% vs. 95.0%, P = 0.020). The difference in hypothermia incidence between groups was greater in the post-induction phase (20.0% vs. 85.0%, P < 0.001) than in the anhepatic or post-reperfusion phase, suggesting that prewarming mainly acts on preventing post-induction core-to-peripheral heat redistribution. Hypothermia duration was significantly shorter in prewarming group (60 [0-221] min vs. 383 [108-426] min, P = 0.001). Lactate concentration decreased during 3 h after graft reperfusion in prewarming group, whereas it continuously increased in non-prewarming group (- 0.19 [- 0.48 to 0.13] mmol/L vs. 1.17 [3.31-0.77] mmol/L, P = 0.034). In conclusion, forced-air prewarming decreases the incidence and duration of intraoperative hypothermia with potential clinical benefit while mainly acting by preventing the core-to-peripheral heat redistribution.Clinical trial registration: Registered at the Clinical Research Information Service ( https://cris.nih.go.kr , [KCT0003230]) on 01/10/2018.

Intraoperative Factors Modifying the Risk of Postoperative Pulmonary Complications After Living Donor Liver Transplantation.

BACKGROUND: The relationship between intraoperative anesthetic management and postoperative pulmonary complications (PPCs) after liver transplantation is not fully understood. We aimed to determine the intraoperative contributors to PPC. METHODS: The retrospectively collected cohort included 605 patients who underwent living donor liver transplantation. PPCs comprised respiratory failure, respiratory infection, pulmonary edema, atelectasis (at least moderate degree), pneumothorax, and pleural effusion (at least moderate degree). The presence and type of PPC were evaluated by 2 pulmonary physicians. Logistic regression analysis was performed to determine the association between perioperative variables and PPC risk. RESULTS: Of the 605 patients, 318 patients (52.6%) developed 486 PPCs. Multivariable analysis demonstrated that PPC risk decreased with low tidal volume ventilation (odds ratio [OR] 0.62 [0.41-0.94], P = 0.023) and increased with greater driving pressure at the end of surgery (OR 1.08 [1.01-1.14], P = 0.018), prolonged hypotension (OR 1.85 [1.27-2.70], P = 0.001), and blood albumin level ≤3.0 g/dL at the end of surgery (OR 2.43 [1.51-3.92], P < 0.001). Survival probability at 3, 6, and 12 mo after transplantation was 91.2%, 89.6%, and 86.5%, respectively, in patients with PPCs and 98.3%, 96.5%, and 93.4%, respectively, in patients without PPCs (hazard ratio 2.2 [1.3-3.6], P = 0.004). Graft survival probability at 3, 6, and 12 mo after transplantation was 89.3%, 87.1%, and 84.3%, respectively, in patients with PPCs and 97.6%, 95.8%, and 92.7%, respectively, in patients without PPCs (hazard ratio 2.3 [1.4-3.7], P = 0.001). CONCLUSIONS: We found that tidal volume, driving pressure, hypotension, and albumin level during living donor liver transplantation were significantly associated with PPC risk. These data may help determine patients at risk of PPC or develop an intraoperative lung-protective strategy for liver transplant recipients.

Effects of 20% albumin infusion therapy during liver transplantation on plasma neutrophil gelatinase-associated lipocalin level: A randomized controlled trial.

The risk of acute kidney injury (AKI) after liver transplantation was lower in patients with serum albumin levels ≥3.0 mg/dL during surgery. We tested whether intraoperative infusion of 20% albumin affects neutrophil gelatinase-associated lipocalin (NGAL) level, a reliable indicator of AKI. We randomly assigned 134 patients undergoing liver transplantation into albumin group (n=70, 20% albumin 200 mL) and the control group (n=66, crystalloid solution 200 mL). The 2 study fluids were infused at 100 mL/h from the start of the anhepatic phase. The primary outcome was plasma NGAL level at 1 hour after graft reperfusion. Albumin level at the start of graft reperfusion was significantly greater in albumin group than in the control group [2.9 (2.4-3.3) g/dL vs. 2.3 (2.0-2.7) g/dL, p <0.001]. The NGAL level at 1 hour after graft reperfusion was not significantly different between the 2 groups [100.2 (66.7-138.8) ng/mL vs. 92.9 (70.8-120.6) ng/mL, p =0.46], and the AKI risk was not either (63.9% vs. 67.8%, adjusted p =0.73). There were no significant differences between the 2 groups regarding hospital readmission within 30 days/90 days after transplantation (32.6% vs. 41.5%, adjusted p =0.19 and 55.0% vs. 55.7%, adjusted p =0.87). Graft survival probability at 30 days/90 days/1 year after transplantation was 90.0%/84.3%/78.6% in albumin group and 97.0%/90.9%/89.4% in the control group [HR=1.6 (0.6-4.0), adjusted p =0.31]. In conclusion, intraoperative infusion of 20% albumin 200 mL increased the albumin level but failed to maintain serum albumin ≥3.0 mg/dL during surgery. The hypertonic albumin therapy did not significantly affect plasma NGAL level and clinical outcomes including AKI.

Improvement of compliance to the Portland intensive insulin therapy during liver transplantation after introducing an application software: a retrospective single center cohort study.

BACKGROUND: The Portland intensive insulin therapy effectively controls acute hyperglycemic change after graft reperfusion during liver transplantation. However, the time-consuming sophistication acts as a barrier leading to misinterpretation and decreasing compliance to the protocol; thus, we newly introduced an application software "Insulin protocol calculator" which automatically calculates therapeutic bolus/continuous insulin doses based on the Portland protocol. METHODS: Of 144 patients who underwent liver transplantation, 74 patients were treated before the introduction of "Insulin protocol calculator" by using a paper manual, and 70 patients were treated by using the application. Compliance was defined as the proportion of patients treated with exact bolus/continuous insulin dose according to the Portland protocol. RESULTS: Compliance was significantly greater in app group than in paper group regarding bolus dose (94.5% and 86.9%, P < 0.001), continuous dose (88.9% and 77.3%, P = 0.001), and both doses (86.6% and 73.8%, P < 0.001). Blood glucose concentration was significantly lower in app group at 3 h (125 ± 17 mg/dl vs. 136 ± 19 mg/dl, P = 0.014) and 4 h (135 ± 22 mg/dl vs. 115 ± 15 mg/dl, P = 0.029) after graft reperfusion. Acute hyperglycemic change during 30 min was more prominent in app group while hyperglycemia incidence was 71.4% vs. 54.1% (P = 0.031). However, hyperglycemia risk was comparable at 2 h (31.4% vs. 31.1%, P = 0.964), and even insignificantly lower in app group at 3 h (7.1% vs. 19.5%, P = 0.184). CONCLUSIONS: Compliance to the Portland protocol was significantly improved after introducing the application software; post-reperfusion hyperglycemia was better controlled. "Insulin protocol calculator" is cost-effective and time-saving with potential clinical benefits.

Intravenous iron injection does not impair liver function in a rat model of cirrhosis.

BACKGROUND: There is a lack of convincing data concerning the safety of iron therapy in patients with advanced liver cirrhosis (LC). This study investigated the hepatic effects of ferric carboxymaltose, an intravenous iron supplement, in a rat model of cirrhosis. METHODS: In total, 45 Sprague-Dawley rats were allocated into three groups: normal rats (control group, n=15), cirrhotic rats receiving intravenous normal saline (LC group, n=15), and cirrhotic rats receiving 20 mg/kg intravenous ferric carboxymaltose (LC-iron group, n=15). LC was induced by twice-weekly intraperitoneal injection of carbon tetrachloride. Biochemical parameters were compared at 0, 2, 14, and 28 days. Additionally, liver tissue samples were extracted from five rats in each group at 2, 14, and 28 days for evaluation of the degrees of hepatic fibrosis and iron deposition. Inflammatory and oxidative stress markers were also compared among groups. RESULTS: Serum alanine transferase levels did not significantly differ between the LC and LC-iron groups at 0 (443±110 vs. 444±117 IU/L, P>0.99), 2 (453±117 vs. 479±136 IU/L, P=0.84), 14 (1,535±1,058 vs. 1,578±711 IU/L, P=0.55), or 28 days (2,067±641 vs. 2,533±914 IU/L, P=0.15). The degree of hepatic fibrosis was comparable between the groups, although hepatic iron accumulation was greater in the LC-iron group than in the LC group. The levels of inflammatory and oxidative stress markers were significantly lower in the LC-iron group than in the LC group. CONCLUSIONS: In our rat model of cirrhosis, the administration of intravenous iron appears safe. However, further preclinical and clinical studies are warranted to confirm the safety and efficacy of intravenous iron in patients with LC or end-stage liver disease.

Blood Salvage and Autotransfusion With Single Leukoreduction Does Not Increase the Risk of Tumor Recurrence After Liver Transplantation for Advanced Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to determine whether autotransfusion of salvaged blood with single leukoreduction is associated with post-transplant tumor recurrence in patients with advanced hepatocellular carcinoma (HCC). BACKGROUND: Previous studies have consistently demonstrated the safety of autotransfusion of salvaged and leukoreduced blood during liver transplantation for HCC. However, the effects of this technique remained unknown for advanced HCC. METHODS: Of 349 patients who underwent living donor liver transplantation for advanced HCC: 74 of 129 without autotransfusion were matched with 74 of 220 with autotransfusion using propensity score based on tumor biology, allogeneic transfusion, and others. Survival analysis was performed with death as a competing risk event. The primary outcome was HCC recurrence. RESULTS: Recipients in autotransfusion group received 811 (497-1247) mL of salvaged blood with single leukoreduction. In the matched cohort, cumulative overall recurrence probability at 1/2/5 years after transplantation was 24.6%/ 38.3%/39.7% for nonautotransfusion group and 16.2%/23.1%/32.5% for autotransfusion group. There were no significant differences between the 2 groups in overall recurrence [hazard ratio (HR) = 0.72 (0.43-1.21)], intrahepatic recurrence [HR = 0.70 (0.35-1.40)], and extrahepatic recurrence [HR = 0.82 (0.46-1.47)]. Also, there were no significant differences in overall death [HR = 0.57 (0.29-1.12)], HCC-related death [HR = 0.59 (0.29-1.20)], and HCC-unrelated death [HR = 0.48 (0.09-2.65)]. CONCLUSIONS: When allogeneic transfusion was matched, autotransfusion was not significantly related to HCC recurrence, with more favorable probabilities for autotransfusion, in patients with advanced HCC. Thus, blood salvage and autotransfusion could be safely used with single leukoreduction, without double-filtered leukoreduction, during liver transplantation for HCC with potential benefits from avoiding allogeneic red blood cell transfusion.

Decrease in the Risk of Posttransplant Hepatocellular Carcinoma Recurrence After the Conversion to Prestorage Leukoreduction for Transfused Red Blood Cells.

BACKGROUND: Prestorage leukoreduction has the advantage over poststorage leukoreduction in reducing leukocyte-derived molecules in red blood cells (RBC) unit, which induce immunomodulation. Our institution newly introduced prestorage leukoreduction, instead of conventional poststorage leukoreduction, for liver transplant recipients since March 2012. In this study, we aimed to evaluate the risk of posttransplant hepatocellular carcinoma (HCC) recurrence after the conversion of poststorage leukoreduction into prestorage leukoreduction for transfused allogeneic RBCs. METHODS: Among 220 patients who underwent living-donor liver transplantation for HCC, 83 of 113 who received only poststorage-leukoreduced RBCs were matched with 83 of 107 who received only prestorage-leukoreduced RBCs using 1:1 propensity score matching based on factors like tumor biology. The primary outcome was overall HCC recurrence. Survival analysis was performed with death as a competing risk event. RESULTS: In the matched cohort, recurrence probability at 1, 2, and 5 years posttransplant was 9.6%, 15.6%, and 18.1% in prestorage group and 15.6%, 21.6%, and 33.7% in poststorage group (hazard ratio [HR], 0.52; 0.28-0.97; P = 0.040). Multivariable analysis confirmed a significance of prestorage leukoreduction (HR, 0.29; 0.15-0.59; P < 0.001). Overall death risk was also lower with prestorage leukoreduction (HR, 0.51; 0.26-0.99; P = 0.049). In subgroup analysis for the unmatched cohort, recurrence risk was significantly lower in prestorage group within the patients who underwent surgery 2 years (HR, 0.24; 0.10-0.61; P = 0.002), 1 year (HR, 0.16; 0.03-0.92; P = 0.040), and 6 months (HR, 0.13; 0.02-0.85; P = 0.034), respectively, before and after the conversion to prestorage leukoreduction. CONCLUSIONS: Our findings suggest a potential benefit of prestorage leukoreduction in reducing the risk of HCC recurrence in liver transplant recipients who received allogeneic RBCs during the perioperative period.

Five-lead Electrocardiography During Living Donor Liver Transplantation: Incidence and Clinical Significance of ST Segment Abnormality.

OBJECTIVES: Five-lead electrocardiography (ECG) is commonly used during liver transplantation, while 3-lead ECG is used during most noncardiac operations. This study aimed to evaluate the incidence and clinical significance of ST segment abnormality during living donor liver transplantation (LDLT) with 5-lead ECG. METHODS: We retrospectively reviewed medical records of patients who received LDLT between May 2018 and May 2019. A total of 109 adult recipients underwent LDLT, and 108 recipients were divided into 2 groups according to whether or not significant ST segment abnormality had occurred at 8 predetermined time points during the operation. ST segment change by more than 1 mm was regarded as significant. RESULTS: Of the 108 recipients, 21 recipients (19.4%) had significant ST segment depression during the operation. No case of significant ST segment elevation was noted. The significant ST segment depression was detected mostly in lead II and V5, and with 2 in combination we could detect 95.2% of significant ST segment change. The significant ST segment depression was frequently observed 1 hour after anhepatic phase and 2 hours after reperfusion. Patient characteristics were not different between the 2 groups. Moreover, the cardiac enzyme (troponin I) measurements, measured immediately after the operation, were not different between the 2 groups. CONCLUSIONS: Although significant ST segment change was frequently observed during LDLT, more studies are required to determine the clinical significance of 5-lead ECG ST segment abnormality during LDLT.

Comparison of Pulmonary Gas Exchange During Kidney Transplantation: Second-Generation Laryngeal Mask Airway vs Endotracheal Tube.

INTRODUCTION: We evaluated whether second-generation laryngeal mask airway (LMA) could provide an adequate pulmonary gas exchange during prolonged abdominal surgery compared to endotracheal tube (ETT) using propensity score matching. METHODS: Of the 257 recipients who underwent living donor kidney transplantation (LDKT), the LMA group and ETT group were matched: 87 of 101 recipients who inserted second-generation LMA were matched with 87 of 156 recipients who inserted ETT. Arterial partial pressure of carbon dioxide (PaCO2) and ratio of arterial partial pressure of oxygen to fractional inspired oxygen (PFR) and intraoperative ventilator parameters were compared between the 2 groups. In addition, we compared incidences of postoperative pulmonary and nonpulmonary complications including hoarseness, vocal cord palsy, nausea, vomiting, arrhythmia, and delirium between the 2 groups. RESULTS: Median anesthesia time was 357 minutes. PaCO2 and PFR were comparable between the 2 groups and did not show group and time interaction. Ventilator parameters during surgery were comparable, and incidences of both postoperative pulmonary and nonpulmonary complications were also comparable between the 2 groups. CONCLUSION: Second-generation LMA could provide an adequate pulmonary gas exchange compared with ETT during LDKT. In terms of pulmonary gas exchange, second-generation LMA could be considered as a suitable alternative to ETT during prolonged abdominal surgery.

Improvement in postoperative pain control by combined use of intravenous dexamethasone with intravenous dexmedetomidine after interscalene brachial plexus block for arthroscopic shoulder surgery: A randomised controlled trial.

BACKGROUND: Intravenous dexamethasone or dexmedetomidine is reported to prolong the duration of analgesia after single-shot interscalene brachial plexus block (ISBPB). However, the effect of co-administration of these agents on the duration of analgesia has not been evaluated. OBJECTIVES: We evaluated the difference in time to first rescue analgesic request between patients receiving co-administered intravenous dexamethasone and dexmedetomidine and patients receiving intravenous dexamethasone alone after single-shot ISBPB for arthroscopic shoulder surgery. DESIGN: A randomised controlled study. SETTING: A single tertiary care centre, study period from August 2017 to January 2018. PATIENTS: Sixty-six patients undergoing arthroscopic shoulder surgery with ISBPB with 15 ml of 0.5% ropivacaine with 1 : 200 000 epinephrine. INTERVENTIONS: We randomly assigned the patients to one of three groups: intravenous 0.9% saline (control), intravenous dexamethasone 0.11 mg kg (D1 group), or co-administered intravenous dexamethasone 0.11 mg kg and intravenous dexmedetomidine 1.0 µg kg (D2 group). MAIN OUTCOME MEASURES: The primary outcome was the time to first rescue analgesic request. RESULTS: The median [interquartile range] time to first rescue analgesic request was significantly longer for the D2 group (66.3 h [23.3 to 72]) than the D1 (17.4 h [14.9 to 36], P = 0.002) and control (10.9 h [10.1 to 12.2], P < 0.001) groups. The D1 and D2 groups both had reduced pain scores, reduced postoperative opioid consumption, less sleep disruption and improved patient satisfaction compared with the control group. There were no significant elevations in blood glucose concentrations in patients receiving dexamethasone (D1 and D2 groups) compared with the control group at postoperative day 1. CONCLUSION: Co-administration of intravenous dexamethasone (0.11 mg kg) with dexmedetomidine (1.0 µg kg) significantly prolonged the time to first rescue analgesic request after single-shot ISBPB in patients undergoing arthroscopic shoulder surgery. TRIAL REGISTRATION: Clinical Trial Registry of Korea; https://cris.nih.go.kr/cris/index.jsp and identifier: KCT0002569.

Portland Intensive Insulin Therapy During Living Donor Liver Transplantation: Association with Postreperfusion Hyperglycemia and Clinical Outcomes.

Many liver transplant recipients experience intraoperative hyperglycemia after graft reperfusion. Accordingly, we introduced the Portland intensive insulin therapy (PoIIT) in our practice to better control blood glucose concentration (BGC). We evaluated the effects of PoIIT by comparing with our conventional insulin therapy (CoIT). Of 128 patients who underwent living donor liver transplantation (LDLT) during the phaseout period of CoIT, 89 were treated with the PoIIT and 39 were treated with CoIT. The primary outcome was hyperglycemia (BGC > 180 mg/dL) during the intraoperative postreperfusion phase. The secondary outcomes were postoperative complications such as infection. The incidence of hyperglycemia (22.5% vs. 53.8%, p = 0.001) and prolonged hyperglycemia for >2 hours (7.9% vs. 30.8%, p = 0.002) was significantly lower in PoIIT group than in CoIT group. A mixed linear model further demonstrated that repeatedly measured BGCs were lower in PoIIT group (p < 0.001). The use of PoIIT was significantly associated with decreases in major infections (OR = 0.23 [0.06-0.85], p = 0.028), prolonged mechanical ventilation (OR = 0.29 [0.09-0.89], p = 0.031), and biliary stricture (OR = 0.23 [0.07-0.78], p = 0.018) after adjustments for age, sex, and diabetes mellitus. In conclusion, the PoIIT is effective for maintaining BGC and preventing hyperglycemia during the intraoperative postreperfusion phase of living donor liver transplantation with potential clinical benefits.

Longer storage of red blood cells does not affect mortality in transfused liver transplant recipients.

BACKGROUND: The characteristics of red blood cell (RBC) products change after 2 weeks of cold storage. It is unclear whether older RBCs affect mortality after liver transplantation. This retrospective cohort study aimed to evaluate the association between the age of transfused RBCs and death after living donor liver transplantation (LDLT). STUDY DESIGN AND METHODS: Of 200 recipients who underwent LDLT, 118 who received RBCs with a mean storage duration of less than 10 days (shorter storage group) were compared with 82 with an RBC mean storage duration of more than 14 days (longer storage group). Key exclusion criteria were transfusion of very fresh RBCs stored for less than 4 days and transfusion of old RBCs in recipients of the shorter storage group. The primary outcome was posttransplant overall death. Survival analysis was performed using the Cox model. RESULTS: Mean RBC storage duration was 7 days in the shorter storage group and 17 days in the longer storage group. Death probability at 1, 2, and 5 years posttransplant was 5.1%, 7.6%, and 13.6% in the shorter storage group, respectively, and 6.1%, 8.5%, and 13.5% in the longer storage group. Death risk was comparable between the two groups in univariable (hazard ratio [HR] 1.00, 95% confidence interval [CI], 0.47-2.16, p = 0.991) and multivariable (HR 1.07, 95% CI, 0.46-2.50, p = 0.882) analyses. Graft failure risk was also comparable (HR 1.04, 95% CI, 0.50-2.18, p = 0.916). Hepatocellular carcinoma recurrence probability at 1, 2, and 5 years was 10.8%, 15.4%, and 23.1%, respectively, in the shorter storage group and 11.4%, 15.9%, and 20.7% in the longer storage group (HR 0.84, 95% CI, 0.37-1.89, p = 0.670). No significant differences were observed regarding graft regeneration/function, vascular/biliary complications, acute kidney injury, surgical site infection, or rejection (p > 0.05). CONCLUSIONS: No evidence was found that transfusion of old RBCs contributes to death after LDLT.

Intraoperative management of liver transplant recipients having severe renal dysfunction: results of 42 cases.

PURPOSE: Whereas continuous renal replacement therapy (CRRT) has been utilized during liver transplantation (LT), there was a lack of evidence to support this practice. We investigated the adverse events at the perioperative periods in recipients of LT who received preoperative CRRT without intraoperative CRRT. METHODS: We retrospectively reviewed medical records of adult patients (age ≥ 18 years) who received LT between December 2009 and May 2015. Perioperative data were collected from the recipients, who received preoperative CRRT until immediately before LT, because of refractory renal dysfunction. RESULTS: Of 706 recipients, 42 recipients received preoperative CRRT. The mean (standard deviation) Model for end-stage liver disease score were 49.6 (13.4). Twenty-six point two percent (26.2%) of recipients experienced the serum potassium > 4.5 mEq/L before reperfusion and treated with regular insulin. Thirty-eight point one percent (38.1%) of recipients were managed with sodium bicarbonate because of acidosis (base excess < -10 mEq/L throughout LT). All patients finished their operations without medically uncontrolled complications such as severe hyperkalemia (serum potassium > 5.5 mEq/L), refractory acidosis, or critical arrhythmias. Mortality was 19% at 30 day and 33.3% at 1 year. CONCLUSION: Although intraoperative CRRT was not used in recipients with severe preoperative renal dysfunction, LT was safely performed. Our experience raises a question about the need for intraoperative CRRT.

Sarcopenia as a predictor of post-transplant tumor recurrence after living donor liver transplantation for hepatocellular carcinoma beyond the Milan criteria.

To evaluate the association between sarcopenia and tumor recurrence after living donor liver transplantation (LDLT) in patients with advanced hepatocellular carcinoma (HCC), we analyzed 92 males who underwent LDLT for treating HCC beyond the Milan criteria. Sarcopenia was defined when the height-normalized psoas muscle thickness was <15.5 mm/m at the L3 vertebra level on computed tomography based on an optimum stratification method using the Gray's test statistic. Survival analysis was performed with death as a competing risk event. The primary outcome was post-transplant HCC recurrence. The median follow-up time was 36 months. There was a 9% increase in recurrence risk per unit decrease in height-normalized psoas muscle thickness. Twenty-six (36.1%) of 72 sarcopenic recipients developed HCC recurrence, whereas only one (5.0%) of 20 non-sarcopenic recipients developed HCC recurrence. Recurrence risk was greater in sarcopenic patients in univariable analysis (hazard ratio [HR] = 8.06 [1.06-16.70], p = 0.044) and in multivariable analysis (HR = 9.49 [1.18-76.32], p = 0.034). Greater alpha-fetoprotein and microvascular invasion were also identified as independent risk factors. Incorporation of sarcopenia improved the model fitness and prediction power of the estimation model. In conclusion, sarcopenia appears to be one of the important host factors modulating tumor recurrence risk after LDLT for advanced HCC.

Incidence and clinical significance of hyperfibrinolysis during living donor liver transplantation.

: We evaluated the incidence and clinical significance of hyperfibrinolysis during living donor liver transplantation (LDLT) using viscoelastic coagulation tests. We retrospectively reviewed adult LDLT recipients from February 2010 to February 2015. Hyperfibrinolysis was defined when clot lysis index [LY60 = (MA - A60)/MA × 100, %] was less than 85, where A60 is the clot amplitude at 60 min after maximum amplitude (MA) occurred. Viscoelastic coagulation tests were performed six times (T1: immediately after anesthetic induction, T2: end of preanhepatic phase, T3: 1 h after anhepatic phase, T4: 5 min after reperfusion, T5: 1 h after reperfusion, and T6: 3 h after reperfusion). One hundred-ten recipients were included in final analysis. Hyperfibrinolysis was uncommon in preanhepatic phase (0% at T1 and 4.5% at T2) and aggravated during anhepatic phase and peaked immediately after reperfusion, 18% at T3 and 71% at T4. However, hyperfibrinolysis nearly disappeared 1 h after reperfusion and did not recur; 0.9% at T5 and 0% at T6. Hyperfibrinolysis was not predicted from preoperative demographics and coagulation profiles. However, the degree of coagulation profile derangements and intraoperative blood loss was greater in the hyperfibrinolysis group. During LDLT, hyperfibrionlysis frequently occurred at anhepatic phase and immediately after reperfusion, but it was resolved during postreperfusion phase.

Risk of Post-transplant Hepatocellular Carcinoma Recurrence Is Higher in Recipients of Livers From Male Than Female Living Donors.

OBJECTIVE: To evaluate the relationship between donor sex and hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation. BACKGROUND: HCC shows a male predominance in incidence and recurrence after tumor resection due to sex differences in hepatic sex hormone receptors. There have been no studies evaluating the importance of donor sex on post-transplant HCC recurrence. METHODS: Of 384 recipients of livers, from living donors, for HCC: 104/120 who received grafts from female donors were matched with 246/264 who received grafts from male donors using propensity score matching, with an unfixed matching ratio based on factors like tumor biology. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. RESULTS: The median follow-up time was 39 months. Before matching, recurrence probability at 1/2/5 years after transplantation was 6.1/9.7/12.7% in recipients with female donors and 11.7/19.2/25.3% in recipients with male donors. Recurrence risk was significantly higher with male donors in univariable analysis (hazard ratio [HR] = 2.04 [1.15-3.60], P = 0.014) and multivariable analysis (HR=2.10 [1.20-3.67], P = 0.018). In the matched analysis, recurrence risk was also higher with male donors (HR=1.92 [1.05-3.52], P = 0.034): both in intrahepatic recurrence (HR=1.92 [1.05-3.51], P = 0.034) and extrahepatic recurrence (HR=1.93 [1.05-3.52], P = 0.033). Multivariable analysis confirmed the significance of donor sex (HR=2.08 [1.11-3.91], P = 0.023). Interestingly, the significance was lost when donor age was >40 years. Two external cohorts validated the significance of donor sex. CONCLUSIONS: Donor sex appears to be an important graft factor modulating HCC recurrence after living donor liver transplantation.

Comparison of intrathecal morphine and surgical-site infusion of ropivacaine as adjuncts to intravenous patient-controlled analgesia in living-donor kidney transplant recipients.

INTRODUCTION: This prospective observational study compared the postoperative analgesic effectiveness of intrathecal morphine (ITM) and surgical-site infusion (SSI) of ropivacaine as adjuncts to intravenous (IV) patient-controlled analgesia (PCA) (fentanyl) in living-donor kidney transplant recipients. METHODS: Patients undergoing living-donor kidney transplantation who received ITM or SSI in addition to IV PCA were included. Rescue analgesia was achieved with IV meperidine as required. The primary outcome, measured using the Numeric Pain Rating Scale (NRS), was pain at rest and when coughing. Patients were assessed for 48 hours after surgery. RESULTS: A total of 53 patients (32 ITM, 21 SSI) were included in the study. The ITM group showed significantly lower NRS scores, at rest and when coughing, for up to 12 and eight hours. NRS scores were comparable between the groups at other times. The ITM group had significantly less postoperative systemic opioid requirement in the first 24 hours, but there was no significant difference between the systemic opioid consumption of the groups on postoperative Day 2. In the ITM group, 3 (9.4%) patients presented with bradypnoea and 1 (3.1%) with excessive sedation in the first 12 postoperative hours. More patients in the ITM group developed pruritus requiring treatment during the first 24 hours. There were no differences between the groups in other outcomes (e.g. nausea/vomiting, change in pulmonary or kidney functions). CONCLUSION: Compared with SSI, ITM reduced immediate postoperative pain and IV opioid consumption on postoperative Day 1 after living-donor kidney transplantation, but at the cost of increased pruritus and respiratory depression.

Spinal activity of interleukin 6 mediates myelin basic protein-induced allodynia.

Mechanosensory fibers are enveloped by myelin, a unique multilamellar membrane permitting saltatory neuronal conduction. Damage to myelin is thought to contribute to severe pain evoked by innocuous tactile stimulation (i.e., mechanical allodynia). Our earlier (Liu et al., 2012) and present data demonstrate that a single injection of a myelin basic protein-derived peptide (MBP84-104) into an intact sciatic nerve produces a robust and long-lasting (>30days) mechanical allodynia in female rats. The MBP84-104 peptide represents the immunodominant epitope and requires T cells to maintain allodynia. Surprisingly, only systemic gabapentin (a ligand of voltage-gated calcium channel α2δ1), but not ketorolac (COX inhibitor), lidocaine (sodium channel blocker) or MK801 (NMDA antagonist) reverse allodynia induced by the intrasciatic MBP84-104. The genome-wide transcriptional profiling of the sciatic nerve followed by the bioinformatics analyses of the expression changes identified interleukin (IL)-6 as the major cytokine induced by MBP84-104 in both the control and athymic T cell-deficient nude rats. The intrasciatic MBP84-104 injection resulted in both unilateral allodynia and unilateral IL-6 increase the segmental spinal cord (neurons and astrocytes). An intrathecal delivery of a function-blocking IL-6 antibody reduced the allodynia in part by the transcriptional effects in large-diameter primary afferents in DRG. Our data suggest that MBP regulates IL-6 expression in the nervous system and that the spinal IL-6 activity mediates nociceptive processing stimulated by the MBP epitopes released after damage or disease of the somatosensory nervous system.

Safety of the Use of Blood Salvage and Autotransfusion During Liver Transplantation for Hepatocellular Carcinoma.

OBJECTIVE: To determine whether autotransfusion of red blood cells (RBCs) salvaged during liver transplantation is associated with the recurrence of hepatocellular carcinoma (HCC). BACKGROUND: Blood salvage is widely used during liver transplantation to reinfuse salvaged autologous RBCs and reduce allogeneic transfusion. However, the reintroduction of cancer cells via autotransfusion is a major concern in HCC patients. METHODS: Among 397 patients who underwent living-donor liver transplantation for HCC, 97 of 114 recipients without intraoperative autotransfusion were matched with 222 of 283 recipients with intraoperative autotransfusion with unfixed matching ratio using the propensity score based on age, sex, allogeneic transfusion, immunosuppression, tumor biology, and others. Competing risks Cox regression was used to compare HCC recurrence risk of the 2 paired groups. RESULTS: Recipients in autotransfusion group received 1177 ±â€Š1318 mL of salvaged RBCs during surgery. A leukocyte depletion filter was used for all autotransfused RBCs. Cumulative HCC recurrence rate at 1, 2, and 5 years after transplantation were 10.4% (5.3%-17.6%), 19.1% (11.6%-28.0%), and 24.1% (15.2%-34.0%) for nonautotransfusion group and 10.8% (7.2%-15.4%), 14.9% (10.5%-20.0%), and 20.3% (14.9%-26.4%) for autotransfusion group, respectively. Autotransfusion versus nonautotransfusion group was not significantly different in overall recurrence [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.47-1.53, P = 0.579] and intrahepatic recurrence (HR 0.75, 95% CI 0.36-1.56) or extrahepatic recurrence (HR 1.00, 95% CI 0.49-2.04). CONCLUSIONS: We found no evidence of a significant impact of autotransfusion on posttransplant HCC recurrence. Thus, salvaged and filtered RBCs could be used in HCC patients undergoing liver transplantation with potential benefits from avoiding allogeneic RBCs transfusion and its complications.