Continuous versus intermittent thermodilution cardiac output measurement during orthotopic liver transplantation

We evaluated intermittent and continuous thermodilution cardiac output data in 12 patients undergoing orthotopic liver transplantation. Measurements were performed at 16 predefined time points between induction of anaesthesia and 3 h after reperfusion of the liver graft. Cardiac output measurements yielded 192 data pairs (intermittent cardiac output range: 1.8–18.9 l.min⁻¹, continuous cardiac output range: 3.3–20.0 l.min⁻¹). During most of the procedure the correlation between intermittent and continuous cardiac output measurements was significant ( r  = 0.87, p < 0.0001), accompanied with a bias of −0.240 l.min⁻¹ and a degree of precision of 1.789 l.min⁻¹ (< 10.0 l.min⁻¹: 1.137 l.min⁻¹, ≥10.0 l.min⁻¹: 2.220 l.min⁻¹). However, in the early phases after caval clamping and after reperfusion, accuracy was not acceptable. Only during these phases did the difference between the mean values of pulmonary artery blood temperature and rectal temperature increase (after caval clamping) or decrease (after reperfusion). In conclusion, despite acceptable levels of accuracy and precision between intermittent and continuous cardiac output measurement under stable conditions, both methods showed markedly decreased accuracy and precision in the early phases after caval clamping and after reperfusion, possibly owing to increased thermal noise.     

Evolving experience with prevention and treatment of splenic artery syndrome after orthotopic liver transplantation

Impaired hepatic arterial perfusion after orthotopic liver transplantation (OLT) may lead to ischemic biliary tract lesions and graft‐loss. Hampered hepatic arterial blood flow is observed in patients with hypersplenism, often described as arterial steal syndrome (ASS). However, arterial and portal perfusions are directly linked via the hepatic arterial buffer response (HABR). Recently, the term ‘splenic artery syndrome’ (SAS) was coined to describe the effect of portal hyperperfusion leading to diminished hepatic arterial blood flow. We retrospectively analyzed 650 transplantations in 585 patients. According to preoperative imaging, 78 patients underwent prophylactic intraoperative ligation of the splenic artery. In case of postoperative SAS, coil‐embolization of the splenic artery was performed. After exclusion of 14 2nd and 3rd retransplantations and 83 procedures with arterial interposition grafts, SAS was diagnosed in 28 of 553 transplantations (5.1%). Twenty‐six patients were treated with coil‐embolization, leading to improved liver function, but requiring postinterventional splenectomy in two patients. Additionally, two patients with SAS underwent splenectomy or retransplantation without preceding embolization. Prophylactic ligation could not prevent SAS entirely (n = 2), but resulted in a significantly lower rate of complications than postoperative coil‐embolization. We recommend prophylactic ligation of the splenic artery for patients at risk of developing SAS. Post‐transplant coil‐embolization of the splenic artery corrected hemodynamic changes of SAS, but was associated with a significant morbidity.     

Additional techniques adopted for major vascular anastomoses during orthotopic liver transplantation

(Received for publication on July 3, 1997; accepted on Mar. 10, 1998)     

胃黏膜pH监测在肝移植围术期应用的研究

目的 探讨胃黏膜pH监测应用于肝移植术围术期的临床意义.方法 30例原位肝移植病人,分别于术前(Tn)、无肝前期30min(T1)、无肝期5 min(T2)、无肝期30 min(T3)、新肝期5 min(T4)、新肝期30 min(T5)、新肝期60 min(T6)、术毕(T7)测定MAP、PCWP、CI、HR、CVP、pHi、Pg-PaCO2、pHa等指标.结果 与术前相比,在无肝期和新肝期5 min、30min时,MAP、pHi、pHa均下降(P<0.05),以新肝期5 min为最低点,而Pg-PaCO2、HR则增高(P<0.05),CVP、PCWP、CI在无肝期下降(P<0.05 ～0.01),在新肝期5 min,30 min则升高(P<0.05).所有指标在新肝期60 min基本恢复至术前水平(P>0.05).结论 肝移植期间出现剧烈的血流动力学波动,无肝期和新肝初期胃黏膜pH明显下降,提示胃肠道灌注不足和缺血缺氧.pHi监测能及时发现胃黏膜缺血缺氧,以便临床采取相应措施,减少并发症.     

Assessment of ventricular contractile function during orthotopic liver transplantation

Hemodynamic alterations are a well-known phenomenon that influence the outcome of orthotopic liver transplantation (OLT). Whether or not myocardial dysfunction, which has various causes, contributes to this instability is still debated. Previous transesophageal echocardiography (TEE) studies have presented controversial data, not leading to final clarification. This is mainly because the impact of other contributing factors (inotropic support, alternating preload conditions and temperature) remained unaccounted for. We therefore measured the left ventricular shortening fraction (LVSF), a parameter reflecting myocardial contractility, in 10 consecutive patients undergoing OLT without veno-venous bypass. We measured during preparation (PP), during the anhepatic (AP) phase and the immediate reperfusion phase (RP). During the AP we observed a significant decrease of LVSF which never fell to subnormal levels in the majority of our patients, whereas during the RP, LVSF returned to PP values. These findings support the assumption that myocardial function is influenced by OLT, but that it plays only a minor role in the occurrence of hemodynamic instability, which could mainly be attributed to volume fluctuations.Abbreviations AP Anhepatic phase - CI Cardiac index - EF Ejection fraction - HR Heart rate - LVSF Left ventricular fractional shortening - MAP Mean arterial pressure - OLT Orthotopic liver transplantation - PP Preparation phase at hemodynamic stability - RP Reperfusion - TEE Transesophageal echocardiography     

The reticuloendothelial system and hepatocyte function in orthotopic liver transplantation

The reticuloendothelial system function, especially phagocytic activity, and hepatocyte function were investigated in dogs undergoing an orthotopic liver transplantation. The donor's phagocytic index, measured by a lipid emulsion test, was higher in the Survivor group which survived more than 3 days after transplantation (0.063±0.008 vs 0.024±0.002; mean ± standard error of the mean (SEM),P<0.01). There was a statistically significant difference in the phagocytic index between the survivor and nonsurvivor groups. However, the hepatocyte function at an early phase after transplantation, indicated by the arterial ketone body ratio, hepaplastin test and lecithin cholesterol acyltransferase level, did not distinguish the Survivor group from the Nonsurvivor group at all. In the survivor group, the hepaplastin test and the lecithin cholesterol acyltransferase level were significantly decreased after liver transplantation, namely from 155±15% to 58±5% and from 57±12 unit/ml to 19±1 unit/ml on the 2nd day after transplantation (P<0.01,P<0.05), respectively. On the other hand, the reticuloendothelial system (RES) function, as estimated by the phagocytic index and serum complement activity (CH 50), demonstrated no change throughout the experimental period. The present study therefore demonstrated that the operative results might be affected by the phagocytic activity.     

Biliary-type cytokeratin pattern in a canine isolated perfused liver transplantation model

BACKGROUND: Ischemia-reperfusion (I/R) injury in liver transplantation units and the influence of I/R injury on bile flow dynamics is being intensely investigated in various animal models, but the expression of intracellular intermediate filaments of biliary type as an early sign of cholestasis has not been yet explored. METHODS: We studied the hepatic elimination kinetics of indocyanine green (ICG), an exclusively biliary excreted cholephilic dye, and the functional and morphological integrity of liver cells in a canine liver transplantation model following I/R. During reperfusion following cold ischemia, we evaluated the ICG excretion curves, biochemical signs of liver damage, the bile canaliculus of the hepatocytes by electron microscopy, and the expression of intermediate filaments of cytokeratin type by immunohistochemistry. RESULTS: Impairment of the biliary ICG excretion was directly related to ischemia time, but hepatocellular ICG uptake and bile flow rate were not significantly reduced. Liver enzymes increased as early as 6 h of ischemia and hepatocytes showed an increase of the bile canaliculus area. This was correlated to a membranous to cytoplasmatic staining of the cytoskeleton of the hepatocytes. CONCLUSIONS: To the best of our knowledge, this is the first evidence of cholestatic changes starting early following cold ischemia in a canine isolated perfused liver transplantation model despite prompt recovery of the bile flow.     

Splanchnic circulation is maintained during passive hyperventilation in orthotopic liver recipients

BACKGROUND: Mechanical hyperventilation is an established treatment to reduce brain edema and intracranial pressure in patients with encephalopathia caused by acute liver failure. Hyperventilation and ensuing hypocarbia may also affect central and systemic circulation and thereby influence graft performance in patients following orthotopic liver transplantation (OLT). METHODS: We measured the effects of normocapnia and hypocapnia on systemic hemodynamics, gastric tonometry, as a marker of splanchnic oxygenation, and the indocyanine green kinetic, as a global marker of graft function, in humans post OLT. RESULTS: Hyperventilation was performed to a PaCO2 of 4.2 +/- 0.4 kPa (31 +/- 3.4 mm Hg) for about 1 h in 14 liver transplant recipients. Systemic hemodynamics as well as indices of splanchnic oxygenation and indocyanine green kinetics remained statistically unchanged. CONCLUSION: We did not observe any statistically significant circulatory effects or changes in indocyanine green kinetics in liver transplant recipients in the immediate OLT postoperative period caused by short-term mechanical hyperventilation.     

原位肝移植围术期肺血管通透性和肺功能的变化

目的 研究非静脉转流原位肝移植术(OLT)围术期胸内血容量、肺血管通透性、肺氧合功能及肺内分流的改变以及相互关系.方法 18例终末期肝病患者行OLT,监测不同时点血流动力学参数、胸腔内血容积指数(ITBVI)、血管外肺水(EVLW)、血管外肺水指数(EVLWI)、肺血管通透性(PVPI)等指标.同时根据血气分析,计算肺泡一动脉氧分压差(A-aDO2)、肺内分流率(Qs/Qt)变化.结果 ITBVI在下腔静脉阻断15 min后逐渐下降(P<0.05),而在新肝期15 min立刻明显升高(P<0.05),术后30 h内逐渐恢复至术前水平.PVPI在下腔静脉阻断15 min时明显增加(P<0.05),而当新肝期15 min时明显降低(P<0.01).A-aDO2在新肝早期较诱导后5 min明显下降(P<0.05).Qs/Qt在新肝期后各时点均较诱导后5 min明显增高(P<0.05),术后10 h逐渐恢复.ITBVI与Qs/Qt明显相关(r=0.291,P<0.01),与A-aDO2呈负相关(r=-0.271,P<0.01).结论 OLT患者在围术期肺血管通透性有明显改变.新肝灌注后ITBVI的增加可能是影响了肺功能的主要原因,而肺毛细血管的通透性的改变及血管外肺水增加并不如预计的明显.     

Hemodynamic and metabolic effects of transjugular intrahepatic portosystemic shunt (TIPS) during anesthesia for orthotopic liver transplantation

Recently, the tranjugular intrahepatic portosystemic shunt (TIPS) has been advocated as a safe bridge to orthotopic liver transplantation (OLT). We retrospectively studied 53 consecutive cirrhotic patients who underwent OLT: 27 patients with TIPS were compared to 26 controls. Hemodynamic and oxyphoretic data (Fick method) were collected during six phases of OLT. There were no significant differences in demographic data and Child-Pugh class, nor in surgical time and blood product requirements before the anhepatic phase between TIPS patients and controls. In the TIPS group, we observed a marked hyperdynamic profile with a lower systemic vascular resistance index, higher cardiac index, and depressed oxygen consumption before native liver removal. During the same period, the TIPS group developed a greater acidosis and was treated with a larger amount of Na-HCO₃. Following the anhepatic phase, no differences between the two groups were detected. All transplantations were successful, and no complications related to TIPS were observed. These results seem to be the consequence of a reduced liver function reserve with a direct hemodynamic effect due to the TIPS.     

Assessment of liver graft function and regeneration by galactosyl-human serum albumin (99mTc-GSA) liver scintigraphy in adult living-donor liver transplantation

Abstract: Background: In adult living‐donor liver transplantation (LDLT), the assessment of the graft functional reserve is very important. We evaluated the graft functional reserve by technetium‐99m‐diethylenetriaminepenta‐acetic acid‐galactosyl‐human serum albumin (^99mTc‐GSA) liver scintigraphy. Patients and method: From May 2003 to September 2006, ^99mTc‐GSA studies were performed in 27 adult recipients on two, four wk after LDLT, the receptor index [ratio of liver to heart‐plus‐liver radioactivity at 15 minutes (LHL15)] (LHL15) was calculated. Recipients were divided into two groups according to LHL15 on two wk after LDLT (group H; >0.935, group L; <0.935). Liver functional tests and recipients’ background parameters were evaluated between the two groups. Result: Group L accompanied higher preoperative model for end‐stage liver disease (MELD) score (p = 0.038), lower graft‐recipient weight ratio (GRWR) (p = 0.032) and older donor age (p = 0.003) compared with group H. There was no significant difference in the graft regeneration rate between two groups. The three‐yr cumulative survival rate was 76.1% in group L and 88.9% in group H. Conclusion: In LDLT, LHL15 has the potential to assess the graft function and predict the recipients’ outcome. Graft function after LDLT may be related closely to the pretransplant MELD score, GRWR, and donor age.     

ICG-R15、iMELD及CLD评分在预测肝细胞癌术后肝功能不全程度中的作用及相关性研究

目的 以术后肝功能不全程度为标准来研究术前吲哚氰绿15 min内滞留率（indocyanine green retention rate at 15 minute,ICG-R15）、综合的终末期肝病模型评分（the integrated model for end-stage liver disease scores,iMELD）和慢性肝功能不全评分（chronic liver dysfunction scores, CLD）三者之间的相关性.方法 回顾性分析61例行手术切除的原发性肝细胞肝癌患者的临床资料,根据肝功能不全程度分为轻、中、重三组,利用脉冲式色素浓度分析法（pulse dyedensitonmetry,PDD）行吲哚氰绿（indocyanine green,ICG）排泄试验,同时计算患者的iMELD及CLD评分.结果 随着术后肝功能不全程度的递增,ICG-R15及CLD评分逐渐升高,差异具有统计学意义（P＜0.05）;ICG-R15与CLD评分相关性明显强于ICG-R15与iMELD评分的相关性（r=0.65,r=0.49）.结论 ICG-R15与CLD评分正向相关性明显强于iMELD评分.     

肝移植术后呼吸功能监测和并发症处理

目的 摸索肝移植术后呼吸功能监测和维持的规律，提高肝移植术后管理质量。方法 分析5例原位肝移植病人在术后ICU期间经历的呼吸系统并发症和常见问题。结果 4例肝移植术后出现各种呼吸道并发症19例次，包括肝肺综合征、胸腔积液、肺不张、肺充血、肺间质水肿、感染及呼吸道出血。结论 呼吸机的使用和呼吸功能的监控是肝移植术后管理的重要环节。了解肝移植术后呼吸系统病理生理学改变的规律和特殊性，对于病人安全渡过ICU阶段至关重要。     

小体积肝移植和辅助性原位小体积肝移植治疗猪急性肝功能衰竭的近期疗效观察

目的观察小体积肝移植和辅助性原位小体积肝移植治疗猪急性肝功能衰竭的近期疗效。方法急性肝功能衰竭猪随机分为3组接受肝移植治疗:A组行全肝移植(n=5);B组行小体积肝移植(n=5);C组行辅助性原位小体积肝移植(n=5)。各组动物开腹后即刻、切脾后即刻和再灌注后30 min分别监测门静脉压力,并观察术后生化指标变化、病理改变和1周生存率。结果A、B和C三组的移植肝重量与受体体重之比分别为(2．44±0．30)％、(0．76±0．02)％和(0．75±0．03)％。再灌注后30 min,B组移植肝门静脉压力显著高于其它两组(A:B:C=13．3:17．5:12．2 cmH2O, P<0．01),C组原肝门静脉压力显著高于移植肝门静脉压力(14．3:12．2 cmH2O,P<0．05)。A组和C组术后第2天起血清天冬氨酸转氨酶、总胆红素、凝血酶原时间、乳酸和血氨水平明显下降,术后第7天基本恢复至正常水平。B组术后上述生化指标一直维持在较高的水平,术后第2～4天明显高于其它两组(P<0．01)。A组、B组和C组1周生存率分别为100％、20％和80％,B组明显低于其它两组(P<0．05)。结论辅助性原位小体积肝移植治疗急性肝功能衰竭近期疗效优于小体积肝移植,术中不必干预原肝门静脉。     

原位肝移植术中应用高渗氯化钠羟乙基淀粉40注射液进行容量治疗的临床研究

目的探讨高渗氯化钠羟乙基淀粉40注射液(复方高渗液)应用于原位肝移植术中容量治疗的效果。方法选择2011年3月至2012年1月在广州军区广州总医院收治的15例行经典非转流原位肝移植的患者。肝移植术中当血红蛋白值与术前相差大于20g/L时,即经静脉输注复方高渗液,速度20～30ml/min,给药总剂量不超过500ml。在给药前(T0),给完药后即刻(T1)、10min(T2)、20min(T3)、30min(T4)、60min(T5)共6个时间点,分别测量平均动脉压(mean arterial pressure,MAP)、心率(heart rate,HR)、全心舒张末期容积指数(global end-diastolic volume index,GEDVI)、胸腔内血容积指数(intra thoracic bloodvolume index,ITBI)、血管外肺水指数(extra vascular lungwater index,EVLI)、每搏输出量(stroke volume,SV)、每搏输出量变异度(strokevolumevariation,SVV)。结果与T0比较,T1、T2、T3、T4和T5时间点的MAP明显升高(P<0.05或P<0.01);与T1比较,T3、T4时间点的MAP亦显著升高(P<0.05或P<0.01)。与T0比较,T1、T2、T3时间点的GEDVI、ITBI显著升高(均为P<0.05)。与T0比较,T1时间点的EVLI明显升高(P<0.05)。与T0比较,T1、T2时间点的SV显著升高,而T1～T4时间点的SVV则明显降低(P<0.05或P<0.01)。结果显示,患者用药后血流动力学方面达到了临床容量复苏的效果。结论复方高渗液能迅速使肝移植术中低血容量患者的血压恢复正常,为后续治疗赢得了时间,提高了容量复苏的成功率。     

Changes in circulating levels of atrial natriuretic factor (ANF) during orthotopic liver transplantation in humans

Abstract Atrial natriuretic factor (ANF) is a 28 amino acid peptide secreted by the atrial cardiocytes. Clearance is via the lung (50%) and the liver (25%). The main stimulus to ANF secretion is atrial distension but vasoconstrictors, sympathetic stimulation, catecolamines and tachycardia are able to enhance its circulating blood levels. ANF blood concentrations were measured during orthotopic liver transplantation in six postnecrotic cirrhotic patients. Significant increases in ANF blood levels occurred at the end of the anhepatic phase ( P ≤ 0.02 vs baseline) associated with low cardiac filling pressures ( P ≤ 0.02 vs baseline) and increased systemic vascular resistances ( P ≤ 0.02 vs preanhepatic phase). Aldosterone blood levels showed a similar behaviour, increasing significantly ( P ≥ 0.001 vs baseline) at the end of the anhepatic phase. ANF fell after reperfusion of the graft and returned towards baseline values at the end of the procedure. Since most of the total body clearance of ANF is performed by the lungs, its sharp increase at the end of the anhepatic phase could be considered a counterregulatory response to vasoconstricting stimulation and to fluid-paring mechanisms in the presence of relative hypovolaemia. Its decrease after reperfusion could be related to volume normalization and partly to the enhanced clearance performed by the newly grafted liver.     

活体肝移植进展与展望（2000-2020）

活体肝移植比公民逝世后器官捐献肝移植操作更为复杂,围手术期评估及技术实施直接影响供体安全和受体预后。目前,行活体肝移植时,供体选择应遵循“自愿、知情、无害”伦理原则,利用影像学评估供肝质量、解剖结构及残肝体积;受体选择时优先考虑良性终末期肝病病人,而选择肝癌病人应考虑肿瘤分期;移植物选择应满足不同受体的“移植物-受体重量比”标准,对于<3岁的儿童,其比值在2%~4%为宜;在传统开放手术供肝获取经验基础上,腹腔镜供肝获取技术发展与挑战并存;术中各管道重建时,管道条件、匹配程度及通畅性是移植技术的关键;供受体血型不相容时,应用利妥昔单抗可起到减少并发症及改善预后作用;术后精细化管理,尽量减少免疫抑制剂用量以期减少其药物相关副反应。尽管存在诸多问题,相信随着外科技术的进步,医生对肝脏解剖认识的加深及移植物再生血流动力学的理解,活体肝移植技术会更加完备、更加安全。作为公民逝世后器官捐献肝移植的重要补充,活体肝移植将为更多终末期肝病病人提供有效治疗手段。     

Risk factors and criteria predicting early graft loss after adult-to-adult living donor liver transplantation

Background

Because deceased liver donors are scarce, adult-to-adult living donor liver transplantation (LDLT) is considered a suitable alterative. However, LDLT grafts are usually partial, resulting in a higher risk of early graft loss (EGL). The aim of the present study was to identify the risk factors and criteria predicting EGL after LDLT.

Methods

We retrospectively analyzed 178 consecutive adults who underwent LDLT. The recipients were divided into two groups as follows: group I, wherein patients showed graft survival longer than 3 mo after LDLT (n = 164), and group II, wherein graft loss occurred within 3 mo after transplantation (n = 14).

Results

Univariate analysis showed various risk factors; however, only the preoperative model for end-stage liver disease score, the presence of obvious pretransplant portal hypertension, and intraoperative blood loss were identified as independent predictors of EGL by multivariate analysis. After LDLT, significant differences were observed between the groups in the fold change in total bilirubin levels over postoperative day (POD) 1 (TBIL-f1) and in the international normalized ratio over POD 1 (INR-f1). The combination of TBIL-f1 and INR-f1 on POD 10 was found to be a strong EGL predictor. Furthermore, a minimum indocyanine green (ICG) clearance rate constant K (m-K_ICG) <0.100/min after POD 3 was found to be the strongest predictor of EGL (sensitivity, 100%; specificity, 97.2%).

Conclusions

The postoperative m-K_ICG and combination of TBIL-f1 and INR-f1 on POD 10 were useful predictors of EGL; moreover, m-K_ICG was superior and is expected to be especially useful for ensuring timely retransplantation.