Eye Protection in Liver Transplantation Patients Under General Anesthesia.

BACKGROUND: Opsite (Smith & Nephew, Hull, UK) is widely used in wound care but its use in eye protection against corneal abrasion during major surgery is rarely reported. The purpose of the current study is to compare the effectiveness of using Opsite in eye protection with either wet gauze alone or with wet gauze following application of eye ointment in patients undergoing living donor liver transplantation (LDLT). METHODS: This is a prospective, double-blinded, randomized controlled trial. Forty-one patients undergoing liver transplantation were enrolled. One eye of each patient was protected with sterile gauze soaked with normal saline solution and covered with Opsite. Duratears (ALCON, Fort Worth, Tex, United States) ointment was applied to the other eye before covering it with sterile wet gauze and Opsite (ointment group). The corneal examination was carried out after fluorescein staining before and at the end of surgery by the same doctor. A Student t-test and a χ2 test were used for the statistical analyses. RESULTS: Forty-one patients with 82 eyes were observed in this study. No corneal epithelial defects were found in either the normal saline group or the ointment group. CONCLUSION: Opsite combined with wet gauze with or without additional eye ointment provided 100% protection against corneal abrasion in patients undergoing LDLT.

The Correlation Between CVP and SVV and Intraoperative Minimal Blood Loss in Living Donor Hepatectomy.

BACKGROUND: Blood loss during liver surgery is found to be correlated with central venous pressure (CVP). The aim of the current retrospective study is to find out the cutoff value of CVP and stroke volume variation (SVV), which may increase the risk of having intraoperative blood loss of more than 100 mL during living liver donor hepatectomies. METHOD AND PATIENTS: Twenty-seven adult living liver donors were divided into 2 groups according to whether they had intraoperative blood loss of less (G1) or more than 100 mL (G2). The mean values of the patients' CVP and SVV at the beginning of the transaction of the liver parenchyma was used as the cutoff point. Its correlation to intraoperative blood loss was evaluated using the χ2 test; P < .001 was regarded as significant. RESULTS: The cutoff points of CVP and SVV were 8 mm Hg and 13% respectively. The odds ratio of having blood loss exceeding 100 mL was 91.25 (P < .001) and 0.36 (P < .001) for CVP and SVV, respectively. CONCLUSION: CVP less than 5 mm Hg, as suggested by most authors, is not always clinical achievable. Our results show that a value of less than 8 mm Hg or SVV 13% is able to achieve a minimal blood loss of 100 mL during parenchyma transaction during a living donor hepatectomy. Measurements used to lower the CVP or increased SVV in our serial were intravenous fluids restriction and the use of a diuretic.

Predictive Risk Factors in the Development of Intraoperative Hyperkalemia in Adult Living Donor Liver Transplantation.

BACKGROUND: Hyperkalemia, defined as a serum potassium level higher than 5 mEq/L, is common in the liver transplantation setting. Severe hyperkalemia may induce fatal cardiac arrhythmias; therefore, it should be monitored and treated accordingly. The aim of the current retrospective study is to evaluate and indentify the predictive risk factors of hyperkalemia during living-donor liver transplantation (LDLT). METHODS AND PATIENTS: Four hundred eighty-seven adult LDLT patients were included in the study. Intraoperative serum potassium levels were monitored at least five times during LDLT; patients with a potassium level higher than 5 mEq/L were included in group 1, and the others with normokalemia in group 2. Patients' categorical characteristics and intraoperative numeric variables with a P value <.1 were selected into a multiple binary logistic regression model. In multivariate analysis, a P value of <.05 is regarded as a risk factor in the development of hyperkalemia. RESULTS: Fifty-one of 487 (10.4%) patients had hyperkalemia with a serum potassium level higher than 5.0 mEq/L during LDLT. Predictive factors with P < .1 in univariate analysis (Table 1), such as anesthesia time, preoperative albumin level, Model for End-stage Liver Disease score, preoperative bilirubin level, amount of blood loss, red blood cell (RBC) and fresh frozen plasma transfused, 5% albumin administered, hemoglobin at the end of surgery, and the amount of furosemide used, were further analyzed by multivariate binary regression. Results show that the anesthesia time, preoperative serum albumin level, and RBC count are determinant risk factors in the development of the hyperkalemia in our LDLT serials. CONCLUSION: Prolonged anesthesia time, preoperative serum albumin level, and intraoperative RBC transfusion are three determinant factors in the development of intraoperative hyperkalemia, and close monitoring of serum potassium levels in patients with abovementioned risk factors are recommended.

Transitional Study of Patient-Controlled Analgesia Morphine With Ketorolac to Patient-Controlled Analgesia Morphine With Parecoxib Among Donors in Adult Living Donor Liver Transplantation: A Single-Center Experience.

BACKGROUND: In this study, as our center transitions from using patient-controlled analgesia (PCA) morphine with intravenous (IV) ketorolac to PCA morphine with IV parecoxib, the two regimens are compared in terms of quality of pain control. METHODS: Post-operative pain management sheets were collected retrospectively among the living donors of liver transplantation during this transitional period. Group parecoxib was given plain PCA morphine. A single dose of IV parecoxib 40 mg was given 30 minutes before the end of surgery. Group ketorolac was given PCA morphine pre-mixed ketorolac with a concentration of 1.87 mg/mL. Daily and total morphine consumption, Visual Analog Score (VAS), and number of rescue attempts made up to 3 post-operative days, together with satisfaction score and incidence of side effects of PCA usage, were analyzed and compared by means of the Mann-Whitney U test; a value of P < .05 was regarded as significant, and data are given as mean ± SD. RESULTS: Fifty patients were analyzed; group 1 comprised 21 patients and group 2 comprised 29 patients. There was no difference between group 1 and group 2 in terms of daily VAS. PCA morphine requirements were significantly lower at day 2 and day 3 in group 1. However, the total overall morphine usage and satisfactory score was not statistically different (P = .863, P = .052). CONCLUSIONS: A single dose of IV parecoxib 40 mg can provide satisfactory pain control when paired with PCA morphine for donors undergoing living donor liver transplantation. The use of parecoxib in the multimodal analgesia regimen has similar efficacy, with possibly less morphine consumption, when compared with ketorolac.

Effects of Pre-Existing Liver Disease on Acute Pain Management Using Patient-Controlled Analgesia Fentanyl With Parecoxib After Major Liver Resection: A Retrospective, Pragmatic Study.

BACKGROUND: The aim of this study was to compare the outcomes of pain management with the use of patient-controlled analgesia (PCA) fentanyl with IV parecoxib between patients with healthy liver with patients with diseased liver undergoing major liver resection. METHODS: Patients with healthy liver undergoing partial hepatectomy as liver donors for liver transplantation (group 1) and patients with liver cirrhosis (Child's criteria A) undergoing major liver resection for hepatoma (group 2) were identified retrospectively. Both groups routinely received post-operative IV PCA fentanyl and a single dose of parecoxib 40 mg. They were followed up for 3 days or until PCA fentanyl was discontinued post-operatively. Daily Visual Analog Scale, PCA fentanyl usage, rescue attempts, and common drug side effects were collected and analyzed with the use of SPSS version 20. RESULTS: One hundred one patients were included in the study: 54 in group 1, and 47 in group 2. There were no statistical differences between the two groups in terms of the daily and total fentanyl usage, VAS resting, and incidence of itchiness. The rate of rescue analgesia on post-operative day (POD) 1 was lower in group 2, with a value of P = .045. VAS dynamics were better on POD 1 and 2 for group 2, with P = .05 and P = .012, respectively. CONCLUSIONS: We found that combining a single dose of IV parecoxib 40 mg with PCA fentanyl is an easy and effective method of acute pain control after major liver resection. We propose the careful usage of post-operative fentanyl and parecoxib in patients with diseased liver, given the difference in effect as compared with healthy liver.

Can coronary vein size predict hemodynamic instability during inferior vena cava clamping in liver transplantation?

OBJECTIVE: This study aimed to determine whether coronary vein size can serve as a predictor of hemodynamic instability during inferior vena cava clamping in living-donor liver transplantations. METHODS: Fifty-two patients' hemodynamic data before and after clamping were retrospectively analyzed and compared with the use of linear regression and repeated measurement. Data included arterial blood pressure, heart rate, central venous pressure, cardiac output, cardiac index, stroke volume, stroke volume variation, and systemic vascular resistance. RESULTS: The values of hemodynamic parameters at 1, 3, 10, and 30 minutes after clamping were compared with baseline data. All changes were found to be significant when the presence of the coronary vein was not considered. When the coronary vein was taken into consideration, linear regression analysis showed that only the percentage changes of cardiac index; stroke volume at 1, 3, and 10 minutes; and systemic vascular resistance at 1 minute after portal and inferior vena cava clamping were significantly correlated with the presence of the coronary vein. CONCLUSIONS: Coronary vein size is a weak predictor of hemodynamic tolerability and instability during portal vein and inferior vena cava clamping in this kind of surgery.

The change of respiratory compliance before and after removal of ascites in living donor liver transplantation.

BACKGROUND: The study's purpose was to evaluate the effects of total removal of the asictes through laparotomy on the lung function of adult patients undergoing living donor liver transplantation. BASIS PROCEDURE: One hundred eleven patients were reviewed retrospectively. Patients were grouped into 3 groups: GI had ascites <1000 mL, GII between 1000 and 4000 mL, and GIII >4000 mL. The respiratory compliance (RC), end-tidal carbon dioxide (EtCO2), peak and plateau airway pressures, tidal volume, and ventilator modes used were compared from 5 minutes before to 20 minutes after laparotomy, by using linear regression and repeated measurements. The changes in the RC among groups were tested using one-way analysis of variance (ANOVA), whereas the changes in percentage of the RC in the same group were tested using paired Student t test. MAIN FINDINGS: The changes in RC before and 10 minutes after laparotomy and total removal of the ascites were 45 ± 12 to 47 ± 13, 39 ± 9 to 43 ± 6, and 24 ± 8 to 43 ± 12 mL/cm H2O for GI, GII, and GIII, respectively. Linear regression analysis showed that the R(2) of the RC 20 minutes after removal of the ascites was 0.645. Pressure cycled ventilation (PCV) used in GIII significantly increased the tidal volume and low end tidal CO2 after laparotomy. CONCLUSIONS: Removal of the ascites in patients undergoing living donor liver transplantation (LDLT) tended to improve the RC in all groups, but significant change was only noted in patients with massive ascites (GIII). Resetting of the ventilator is required to prevent hyperventilation when the PCV mode is used in GIII.

Effect of university of wisconsin and histidine-tryptophan-ketoglutarate preservation solutions on blood potassium levels of patients undergoing living-donor liver transplantation.

BACKGROUND: The potassium content of University of Wisconsin solution (UW) is 125 mEq/L and that of histidine-tryptophan-ketoglutarate solution (HTK) only 9 mEq/L. The aim of the present study was to analyze their effects to change potassium levels on reperfusion among patients undergoing living-donor liver transplantation. METHODS: Anesthesia records of adult living-donor liver transplant patients were reviewed retrospectively. Patients received liver graft preserved in UW were grouped in group I (GI) and HTK in group II (GII). The potassium levels in the anheptic phase were compared with those 5 minutes after reperfusion using paired Student t tests. P values of <.05 were regarded to be significant. RESULTS: Eighty-five GI patients showed the potassium significantly decreased from 3.76±0.70 to 3.60±0.74, whereas the change among 355 GII patients was almost unremarkable: 4.00±0.57 to 3.96±0.06 mEq/L. CONCLUSIONS: Although UW contains a higher potassium content, it seems to have no negative impact on changes in serum potassium levels; in contrast it decreased the potassium level significantly at 5 minutes after reperfusion. Both preservation solutions maintain the patients' potassium levels within the normal range.

Comparison of postoperative morphine requirements in healthy living liver donors, patients with hepatocellular carcinoma undergoing partial hepatectomy, and liver transplant recipients.

OBJECTIVE: To retrospectively evaluate postoperative morphine requirements in healthy living donors undergoing partial hepatectomy and patients with end-stage hepatocellular carcinoma or end-stage liver disease undergoing liver transplantation. PATIENTS AND METHODS: The study included all patients who received intravenous patient-controlled analgesia after partial hepatectomy or liver transplantation from May 2008 to February 2009. Patients were divided into 3 groups according to type of surgery: group 1, healthy living liver donors undergoing graft procurement; group 2, patients with liver cirrhosis due to chronic hepatitis B virus or hepatitis C virus infection and hepatocellular carcinoma undergoing hepatectomy; and group 3, patients with end-stage liver disease undergoing living-donor liver transplantation. Data including patient age, morphine use, and visual analog scale score on postoperative days (PODs) 1, 2, and 3 were compared between groups using 2-way analysis of variance. P<.05 was considered significant. Values are given as mean (SD). RESULTS: Morphine requirement was significantly lower only in group 3 on POD 1. No difference in visual analog scale score between groups was observed postoperatively. CONCLUSION: Although others have reported decreased morphine requirements on PODs 1, 2, and 3, our results indicated that morphine requirements were significantly less only on POD 1.

Decreased fresh gas flow cannot compensate for an increased operating room temperature in maintaining body temperature during donor hepatectomy for living liver donor hepatectomy.

BACKGROUND: The purpose of this study was to compare the effect of various combinations of fresh gas flow (FGF) of anesthesia and different ambient operation room temperatures (ORT) on changes in nasopharyngeal temperature (NT) among living donors undergoing partial hepatectomy. METHODS: The anesthesia records of 167 patients were reviewed retrospectively. The patients were allocated into 4 groups: GI (n=37): isoflurane in 2 L FGF and at typical ambient ORT (19 degrees C-21 degrees C); GII (n=11) isoflurane in 1 L FGF and 1 L air at typical ORT; GIII (n=31) isoflurane in 0.5 L FGF at typical ORT; and GIV (n=88) isoflurane in 0.5 L FGF at ORT of 24 degrees C. The changes in NT were compared using a two-way repeated measure analysis of variance (ANOVA) followed by Bonferroni post hoc tests. RESULTS: Changes of NTs of GIV were significantly higher compared with the other 3 groups, whereas the changes of NTs were the same among GI, GII, and GIII. CONCLUSION: FGF of different volumes seemed to have no significant effect on intraoperative changes of NT in regular ORT. Low-flow anesthesia combined with ORT of 24 degrees C provided significantly higher NTs at all measured points compared with GI, GII, and GIII.

Low-dose dantrolene is effective in treating hyperthermia and hypercapnia, and seems not to affect recovery of the allograft after liver transplantation: case report.

Dantrolene is the drug of choice in treatment of malignant hyperthermia. However, dantrolene is hepatotoxic; thus prolonged use is not recommended in patients with active hepatic disease such as acute hepatitis or active cirrhosis because it may result in fatal hepatic failure. Use of dantrolene in a patient with end-stage liver disease undergoing liver transplantation (LTx) in whom suspected malignant hyperthermia developed has been reported rarely. Its effect on the liver allograft, which has sustained cold, warm, and reperfusion injuries, is currently unknown. We report a case in which low-dose dantrolene administered intravenously during LTx was effective in treating hyperthermia, hypercapnia, and hyperkalemia. Furthermore, its reported hepatotoxic effect seemed to not affect recovery of the allograft after LTx.

Vascular stents in the management of portal venous complications in living donor liver transplantation.

To evaluate the efficacy of stent placement in the treatment of portal vein (PV) stenosis or occlusion in living donor liver transplant (LDLT) recipients, 468 LDLT records were reviewed. Sixteen (10 PV occlusions and 6 stenoses) recipients (age range, 8 months-59 years) were referred for possible interventional angioplasty (dilatation and/or stent) procedures. Stent placement was attempted in all. The approaches used were percutaneous transhepatic (n = 10), percutaneous transsplenic (n = 4), and intraoperative (n = 2). Technical success was achieved in 11 of 16 patients (68.8%). The sizes of the stents used varied from 7 mm to 10 mm in diameter. In the five unsuccessful patients, long-term complete occlusion of the PV with cavernous transformation precluded catherterization. The mean follow-up was 12 months (range, 3-24). The PV stent patency rate was 90.9% (10/11). Rethrombosis and occlusion of the stent and PV occurred in a single recipient who had a cryoperserved vascular graft to reconstruct the PV during the LDLT operation. PV occlusion of >1 year with cavernous transformation seemed to be a factor causing technical failure. In conclusion, early treatment of PV stenosis and occlusion by stenting is an effective treatment in LDLT. Percutaneous transhepatic and transsplenic, and intraoperative techniques are effective approaches depending on the situation.

Effects of different operating room temperatures on the body temperature undergoing live liver donor hepatectomy.

OBJECTIVE: We sought to compare the effects of operation room temperature (ORT) at typical ambient environment (19-21 degrees C) and ORT at 24 degrees C on the core temperature of patients undergoing living donor hepatectomy. METHODS AND PATIENTS: Sixty-two patients undergoing living donor hepatectomy were divided into 2 groups. In group I (n = 31), surgery was performed at typical ambient ORT, and in group II (n = 31) in ORT at 24 degrees C. Anesthesia and measures to prevent heat loss, except ORT, were all the same. Nasopharyngeal temperature (NT) was recorded after anesthesia induction, then hourly until completion of the operation. Changes in NTs were analyzed as well as patient age, weight, anesthetic duration, blood loss, intravenous fluids, total urine output, and pre- and postoperative hemoglobin and hematocrit values. The Mann-Whitney U test was used for comparisons between groups. RESULTS: The patient's characteristics between groups were not statistically different. However, a significantly higher core temperature was noted in group II compared with group I. Increased ORT from 19 to 21 degrees C to 24 degrees C resulted in an increased core temperature of at least 0.5 degrees C during living donor hepatectomy.

Bispectral index monitoring in healthy, cirrhotic, and end-stage liver disease patients undergoing hepatic operation.

The purpose of this study was to assess factors influencing the end-tidal concentrations of isoflurane within a bispectral index (BIS) range of 45-55 among healthy live liver donors (n = 11), chronic hepatitis B patients undergoing hepatectomy hepatocellular carcinoma (n = 10), and end-stage liver disease patients undergoing liver transplantation (n = 7). Patients data collected prospectively were compared among the groups using one-way analysis of variance as well as univariate and multivariate techniques. The results showed that end-stage liver disease patients required the least end-tidal isoflurane concentration. Patients with hepatocellular carcinoma with cirrhosis required intermediate end-tidal isoflurane concentrations; healthy live liver donors required the highest end-tidal isoflurane concentrations to provide sufficient anesthetic depth, as monitored by a target BIS (range, 45-55). Upon multivariate analysis, liver function was the only significant factor influencing the likelihood of lowering the end-tidal isoflurane concentration by 4 hours after anesthesia induction (P = .026). In conclusion, we recommend a preset target BIS within the range of 45-55 to monitor the depth of anesthesia during partial hepatectomy and liver transplantation because end-tidal isoflurane concentration requirements are different for patients with various liver status. This strategy may protect the patients from intraoperative recall or anesthesia over-depth as a consequence of insufficient or overdose of anesthesia, respectively.

Induction of indoleamine 2,3-dioxygenase in livers following hepatectomy prolongs survival of allogeneic hepatocytes after transplantation.

OBJECTIVES: Indoleamine 2,3-dioxygenase (IDO), which catalyzes the breakdown of tryptophan into kyneurenine, has immunologic significance for the induction of maternal tolerance and liver allograft tolerance by inhibiting T-cell activation. In the present study, we compared survival of syngeneic or allogeneic hepatocytes in livers with or without hepatectomy. Subsequently, we investigated gene expression and localization of IDO in the recipient liver. METHODS: DA and Fisher 344 rats were used in the following experimental groups: group 1, DA hepatocytes transplanted into hepatectomized Fisher 344 rats; group 2, Fisher 344 hepatocytes transplanted into hepatectomized Fisher 344 rats; group 3, DA hepatocytes transplanted into nonhepatectomized Fisher 344 rats; and group 4, Fisher 344 hepatocytes transplanted into nonhepatectomized Fisher 344 rats. After transplantation, the surviving cells were evaluated on day 5. The IDO signal of the recipient liver was detected by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: In the hepatectomized groups subjected to allogeneic or syngeneic hepatocyte transplantation, the number of surviving hepatocytes was greater than in the nonhepatectomized group after transplantation. The IDO signals (RT-PCR) in the hepatectomized groups were stronger than those in the nonhepatectomized groups. Immunohistochemistry demonstrated that the IDO signal is located in liver antigen-presenting cells, such as Kupffer cells or dendritic cells, and not expressed in hepatocytes. CONCLUSIONS: Our results demonstrated that IDO is induced in antigen-presenting cells of hepatectomized livers by which subsequently transplanted cells may be protected from rejection by inhibiting indirect or direct recognition of donor antigen and further T-cell activation.

Anesthesia management in a patient with an abdominal aortic aneurysm undergoing liver transplantation: a case report.

We describe the anesthetic management in a 56-year old man with hepatocellular carcinoma and cirrhosis who underwent liver transplantation (LT). Pretransplantation workup showed a 3-cm wide by 10-cm long infrarenal abdominal aortic aneurysm (AAA) with chronic dissection. He subsequently underwent living donor LT. The total operative time was 12 hours. The systolic blood pressure was maintained at normal levels. Severe hypertension was not noted. Hypotension noted during the anhepatic phase was managed with increased volume infusion and small doses (0.1 mg) of intravenous phenylephrine. Metabolic acidosis and ionized hypocalcemia were corrected accordingly. Total blood loss was 460 mL. Blood or blood products were not given. The intravascular volume was replaced with 1400 mL of 5% albumin and 10,610 mL of crystalloid. Extubation was performed in the intensive care unit at 12 hours after the operation. The postoperative course was unremarkable. The patient is alive at 3 years after LT. Patients with AAA undergoing LT present a challenge to the anesthesiologist because among the risk factors for rupture, blood pressure is the only factor under his or her control during the operation. If blood loss can be kept to a minimum and hemodynamic stability achieved, a chronically small dissected AAA may not be a contraindication to LT.

The reaction of posttransplant denervated liver on the hemorrhagic shock in rats.

OBJECTIVE: The aims of the study were to determine the effects of denervation on the function of the liver transplantation as a blood reservoir and to define its vulnerability to ischemic-reperfusion (I/R) injury after hemorrhagic shock. MATERIALS AND METHODS: Hemorrhagic shock with a mean arterial blood pressure (MAP) of 40 to 50 mm Hg was induced by withdrawing blood at a rate of approximately 1 mL/min among 10 posttransplant denervated rats and 10 sham rats for 1 hour. The rats were then resuscitated by retransfusing the drawn blood with sacrifice under deep anesthesia at 1 hour after resuscitation. The total amount of blood required to achieve hemorrhagic shock was compared between groups as well as the vulnerability and reactions of the posttransplant denervated liver to I/R injury after hemorrhagic shock as assessed by gene expressions of c-jun, c-fos, tumor necrosis factor (TNF)-alpha, interleukin (IL)6, IL-10, and heat-shock protein 70 (HSP70). RESULTS: The volume of blood that had to be drawn to reach a MAP of 40 to 50 mm Hg was not significantly different between the groups. One hour of hemorrhagic shock followed by resuscitation resulted in significant increases in the genes expression of c-fos, TNF-alpha, IL-6, IL-10, and HSP70 in comparison to the control values, but no difference was observed between experimental and sham groups. CONCLUSION: We suggest that the function of the liver as a blood reservoir and the gene expressions of c-fos and pro- and anti-inflammatory cytokines, as well as the protective protein HSP70 in response to I/R injury, were not altered by liver transplantation.

The role of a nuclear protein, histone H1, on signalling pathways for the maturation of dendritic cells.

We have demonstrated previously that liver allograft tolerance is associated with the immunosuppressive activity of anti-histone H1 autoreactive antibodies induced in the serum of liver transplantation. Furthermore, we and others have shown that nuclear proteins such as histone H1 and high mobility group box 1 play an important role in maturation of dendritic cells (DCs), although the precise mechanisms are still unknown. In the present study, we focus upon the significance of histone H1 on DCs in terms of the intracellular signalling pathway of DCs. Our immunostaining and immunoblot studies demonstrated that histone H1 was detected in cytoplasm and culture supernatants upon the activation of DCs. Histone H1 blockage by anti-histone H1 antibody down-regulated the intracellular activation of mitogen-activated protein kinases (MAPKs) (p38) and IkappaBalpha of DCs, and inhibited DC activity in the proliferation of CD4+ T cells. On the other hand, the addition of histone H1 without endotoxin stimulation up-regulated major histocompatibility complex class II, the CD80 and CD86 surface markers of DCs and the activation of MAPKs (p38 and extracellular-regulated kinase 1/2) and IkappaBalpha. These results suggest that the translocation of histone H1 from nuclei to cytoplasm and the release of their own histone H1 are necessary for the maturation of DCs and the activation for T lymphocytes.