In Vivo Evaluation of the Ameliorating Effects of Small-Volume Resuscitation with Four Different Fluids on Endotoxemia-Induced Kidney Injury.

Acute kidney injury associated with renal hypoperfusion is a frequent and severe complication during sepsis. Fluid resuscitation is the main therapy. However, heart failure is usually lethal for those patients receiving large volumes of fluids. We compared the effects of small-volume resuscitation using four different treatment regimens, involving saline, hypertonic saline (HTS), hydroxyethyl starch (HES), or hypertonic saline hydroxyethyl starch (HSH), on the kidneys of rats treated with lipopolysaccharide (LPS) to induce endotoxemia. LPS injection caused reduced and progressively deteriorated systemic (arterial blood pressure) and renal hemodynamics (renal blood flow and renal vascular resistance index) over time. This deterioration was accompanied by marked renal functional and pathological injury, as well as an oxidative and inflammatory response, manifesting as increased levels of tumor necrosis factor-α, nitric oxide, and malondialdehyde and decreased activity of superoxide dismutase. Small-volume perfusion with saline failed to improve renal and systemic circulation. However, small-volume perfusion with HES and HSH greatly improved the above parameters, while HTS only transiently improved systemic and renal hemodynamics with obvious renal injury. Therefore, single small-volume resuscitation with HES and HSH could be valid therapeutic approaches to ameliorate kidney injury induced by endotoxemia, while HTS transiently delays injury and saline shows no protective effects.

Ulinastatin prevents acute lung injury led by liver transplantation.

BACKGROUND: Little is known regarding the effect of ulinastatin (UTI) on acute lung injury (ALI) induced by orthotopic liver transplantation. This study aims to investigate the protective effect of UTI on ALI induced by orthotopic autologous liver transplantation (OALT) in a rat model and to explore the potential underlying mechanism. MATERIALS AND METHODS: Rats were randomly allocated into the following four groups (n = 8 each): (i) sham control group (group sham); (ii) model group (underwent OALT) (group model); (iii) low-dose UTI-treated group (group u1), with UTI (50 U/g) administered intravenously both before the portal vein was occluded and after liver reperfusion started; and (iv) high-dose UTI-treated group (group uh), with UTI (100 U/g) given in the same way as group ul. The lung pathologic parameters, lung water content, and levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, malondialdehyde (MDA), superoxide dismutase (SOD) activity, RanBP-type and C3HC4-type zinc finger-containing protein 1 (RBCK1), and peroxiredoxin-2 (Prx-2) were assessed 8 h after OALT was performed. RESULTS: According to histology, there was severe damage in the lung of group model accompanied by increases in the TNF-α, IL-1ß, IL-6, and MDA levels and decreases in SOD activity and the expression of RBCK1 and Prx-2. UTI treatment significantly reduced the pathologic scores, lung water content, and TNF-α, IL-1ß, IL-6, and MDA levels while restoring the SOD activity and expression of RBCK1 and Prx-2. Furthermore, compared with group u1, treatment with a high dose of UTI resulted in a better protective effect on the lung when assessed by the TNF-α, IL-1ß, IL-6, and MDA levels and SOD activity. CONCLUSIONS: UTI dose-dependently attenuates ALI that is induced by OALT in this rat model, which is mainly due to the suppression of the inflammatory response and oxidant stress, which may, in turn, be mediated by the upregulation of RBCK1 and Prx-2 expression.

Relationship between the expression of Toll-like receptor 2 and 4 in mononuclear cells and postoperative acute lung injury in orthotopic liver transplantation.

BACKGROUND: The aim of this study was to investigate the potential relationship between the dynamic expression of Toll-like receptor 2 and 4 (TLR2/4) in peripheral blood mononuclear cells as well as changes in serum concentration of inflammatory factors and acute lung injury (ALI) in patients after orthotopic liver transplantation (OLT). METHODS: The peripheral blood samples of 27 patients (23 men and 4 women with ASA III to IV) who received OLT were collected for measurement of TLR2/4 at T1 (after induction of anesthesia), T2 (25 minutes after anhepatic phase), T3 (3 hours after graft reperfusion) and T4 (24 hours after graft reperfusion). The expression of TLR2/4 in mononuclear cells was measured by flow cytometry. The serum concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA). Twenty-seven patients were assigned to ALI group (n = 9) and non-ALI group (n = 18) according to the diagnostic criteria of ALI. The expression of TLR2/4 in the ALI group or non-ALI group was analyzed. RESULTS: Compared to the non-ALI group, the volumes of blood loss, ascites, total output and transfused red blood cells were higher in the ALI group, and the anhepatic phase lasted longer (P < 0.05, P < 0.01). The expression of TLR2/4 in mononuclear cells increased significantly at T3 and T4, and serum concentrations of TNF-alpha, IL-1beta and IL-8 increased significantly too. There was no significant difference in Child-Turcotte-Pugh (CTP) scores between the ALI group and non-ALI group (P > 0.05). The expression of TLR2/4 in mononuclear cells increased significantly at T3 and T4 in the ALI group (P < 0.05, P < 0.01). A positive correlation was noted between the expression of TLR4 in mononuclear cells and the serum concentrations of TNF-alpha, IL-1beta (P = 0.041, P = 0.046) in the ALI group. In the non-ALI group, statistical results showed that the expression level of TLR2/4 in mononuclear cells was not significantly different during the peri-operative period of OLT (besides TLR4 expression at T4). Compared to the non-ALI group, the increasing amplitude of TLR2/4 expression in mononuclear cells was more significant in the ALI group. The patients whose TLR2/4 expression in mononuclear cells exceeded that at T1 by one time were more likely to suffer from ALI (P = 0.013), with a relative risk of 16. CONCLUSION: The expression level of TLR2/4 in mononuclear cells increases significantly in the peri-operative period of OLT, and it may be a high risk factor for occurrence of postoperative ALI.

[Change in mixed venous oxygen saturation in patients in perioperative periods of orthotopic liver transplantation and its clinical implication].

OBJECTIVE: To observe the changes in mixed venous oxygen saturation(SvO(2))during perioperative periods of orthotopic liver transplantation (OLT), and explore its clinical significances. METHODS: Twenty patients in terminal stage of hepatic cirrhosis were scheduled for OLT under combined general anesthesia. Vigilance monitor (Edwards, USA) was employed to monitor perioperative SvO(2), oxygen delivery (DO(2)), oxygen consumption(VO(2)), oxygen extraction rate (ERO(2)) and body temperature, cardiac output (CO), and mean arterial blood pressure (MAP). RESULTS: Compared with the preoperative stage, SvO(2) elevated during 15 minutes of anhepatic stage (P<0.05), but decreased significantly during 30 minutes compared to that during 15 minutes of anhepatic stage. Then it was elevated significantly at 30 minutes after the reperfusion of the graft and at the end of operation (all P<0.05). Both DO(2) and VO(2) were decreased significantly during the anhepatic phase (both P<0.05), and increased significantly after graft reperfusion (all P<0.05); ERO(2) increased significantly after graft reperfusion (P<0.05). The level of SvO(2) was correlated with VO(2) significantly at each stage (all P<0.05), but not with DO(2) and hemoglobin (all P<0.05). SvO(2) was correlated well with CO before operation (P<0.05), but not at the other time points (all P>0.05). CONCLUSION: Monitoring SvO(2) continually is of clinical significance in patients during OLT.

Changes of nitric oxide and endothelin, thromboxane A2 and prostaglandin in cirrhotic patients undergoing liver transplantation.

AIM: To investigate the perioperative changes of nitric oxide (NO) and endothelin (ET), thromboxane A2 (TXA2) and prostaglandin (PGI2) during liver transplantation in end-stage liver disease patients. METHODS: Twenty-seven patients with end-stage cirrhosis undergoing liver transplantation were enrolled in this prospective study. Blood samples were obtained from superior vena at five different surgical stages. Plasma concentrations of nitrate and nitrite were determined to reflect plasma NO levels. Plasma levels of ET-1,6-keto-PGF1 alpha and thromboxane B2 (TXB2), the latter two being stable metabolites of PGI2 and TXA2 respectively, were measured. RESULTS: The NO level decreased significantly after vascular cross-clamping and increased significantly at 30 min after reperfusion. While the ET levels at 30 min after clamping and after reperfusion were significantly elevated. The ratio of NO/ET decreased significantly at 30 min after vascular cross-clamping and at the end of surgery. The PGI2 level and the TXA2 during liver transplantation were significantly higher than the baseline level, but the ratio of TXA2/PGI2 decreased significantly at 30 min after clamping. CONCLUSION: NO/ET and TXA2/PGI2 change during liver transplantation. Although the precise mechanism remains unknown, they may play a role in the pathobiology of a variety of liver transplant-relevant processes.

[Changes in pulmonary gas exchange and intrapulmonary shunt during orthotopic liver transplantation with non-venovenous bypass].

OBJECTIVE: To study the changes in pulmonary gas exchange and intrapulmonary shunt during orthotopic liver transplantation (OLT) with non-venovenous bypass. METHODS: Nineteen American Society of Anesthesiologists (ASA) III-IV patients (male 17, female 2) with terminal liver diseases were enrolled for study. Their age ranged from 25-67 years. Anesthesia was induced with midazolam 0.05 mg/kg, propofol 0.5-1.0 mg/kg, fentanyl 4 microg/kg, with vecuronium 0.1 mg/kg, and it was maintained with isoflurane inhalation, fentanyl and vecuronium. All patients were mechanically ventilated with 100% O(2) during operation. After induction of anesthesia, Swan-Ganz catheter was inserted via right internal jugular vein. Cardiac output (CO), mixed venous oxygen saturation and core venous temperature were continuously monitored with continuous cardiac output monitor, and electrocardiogram (ECG), central venous pressure (CVP), pulmonary arterial wedge pressure (PAWP), pulse oxygen saturation (SpO(2)) and end-tidal carbon dioxide tension (P(ET)CO(2)) were also continuously monitored during operation. Radial artery was cannulated for continuous direct blood pressure monitoring. Arterial and mixed venous blood samples were taken after induction of anaesthesia, and partial pressure of oxygen (PaO(2)), partial pressure of carbon dioxide (PaCO(2)), and cardiac index(CI) were determined after induction of anaesthesia, 30 minutes before anhepatic stage, 30 minutes during anhepatic stage, 30 minutes during neohepatic stage and at the end of operation. Alveolar-arterial oxygen partial pressure difference (P(A-a)O(2)) and intrapulmonary shunt (Qs/Qt) were calculated according to the standard formula. RESULTS: After induction of anaesthesia, when the inspired oxygen flow (FiO(2)) was 1.00, PaO(2) was only (385.0+/-56.4) mm Hg (1 mm Hg=0.133 kPa), P(A-a)O(2) and Qs/Qt were all higher than normal values. There were no significant changes 30 minutes before anhepatic stage as compared with that after induction of anaesthesia. CO, CI and Qs/Qt were decreased significantly during anhepatic stage compared with that after induction of anaesthesia. PaO(2), PaCO(2), CO and CI were increased and P(A-a)O(2) decreased significantly, but there were no significant changes in Qs/Qt 30 minutes during neohepatic stage. CI and CO increased and Qs/Qt decreased significantly at the end of operation, but there were no significant difference in PaO(2), PaCO(2) and P(A-a)O(2). CONCLUSION: There are obvious changes in pulmonary gas exchange and intrapulmonary shunt during OLT with non-veno-venous bypass.

[Changes in hemodynamics and nitric oxide/endothelin-1 during liver transplantation in patients with cirrhosis].

OBJECTIVE: To study the systemic and pulmonary hemodynamic changes of patients with cirrhosis during liver transplantation and evaluate the role of nitric oxide (NO) and endothelin-1(ET-1). METHODS: Twenty-four patients with cirrhosis at terminal stage underwent modifying piggy-back liver transplantation. Hemodynamic parameters including cardiac index (CI), arterial blood pressure (ABP) and pulmonary arterial pressure (PAP) were monitored continuously. NO and ET-1 levels were measured by radioimmunoassay. Blood samples were obtained from superior vena cava at induction of anesthesia (T1), 10 minutes before vascular cross clamping (T2), 30 minutes after vascular cross clamping (T3), 30 minutes after reperfusion of the new liver (T4), and at the end of surgery (T5). RESULTS: (1) Mean arterial blood pressure (MABP) lowered significantly in the early stage of anhepatic period and neohepatic period (P<0.05 or P<0.01). (2) Central venous pressure (CVP), mean pulmonary arterial pressure (MPAP) and pulmonary arterial wedge pressure (PAWP) lowered significantly during anhepatic period. They rose significantly after graft reperfusion, and remained at a high level with respect to the baseline level (P<0.05). (3) CI declined significantly during anhepatic period and increased 10 minutes after reperfusion of new liver. (4) Systemic vascular resistance index and pulmonary vascular resistance index increased during anhepatic period and were higher than the baseline level 15 minutes after reperfusion. SVRI was lower than baseline level 30 minutes after reperfusion. (5) Compared with the baseline level, NO decreased significantly after vascular cross-clamping and elevated 30 minutes after reperfusion. ET levels were significant elevated 30 minutes after clamping and after reperfusion (P<0.05). CONCLUSION: Significant hemodynamic changes occur in patients with cirrhosis during liver transplantation, and pulmonary hypertension develops during neohepatic period. The role of elevated contents of NO and ET-1 after reperfusion needs further study.

[Changes in oxygen metabolism in hepatitis B gravis in peri-operative stages of orthotopic liver transplantation].

OBJECTIVE: To investigate the changes in oxygen metabolism in peri-operative stages in hepatitis B gravis and non-hepatitis B gravis undergoing orthotopic liver transplantation (OLT). METHODS: Twelve patients undergoing OLT for hepatitis B gravis (experimental group) and 10 patients without hepatitis B gravis (control group) were enrolled for study. Anesthesia was induced by propofol, fentanyl and vecuronium bromide, and maintained with isoflurane. Arterial catheter was inserted into the left radial artery. Swan-Ganz catheter was inserted through the right internal jugular vein. Arterial partial pressure of oxygen (PaO(2)), mixed venous partial pressure of oxygen (PvO(2)), arterial oxygen content (CaO(2)), mixed venous oxygen content (CvO(2)), arterial-venous oxygen content difference (Ca-vO(2)), oxygen delivery (DO(2)), index of oxygen delivery (DO(2)I), oxygen consumption (VO(2)), index of oxygen consumption (VO(2)I), index of oxygen extract (O(2)EI), oxygen extract rate (O(2)ER) were determined before skin incision (T1), 10 minutes before anhepatic phase (T2), 25 minutes after liver was removed (anhepatic phase, T3), 30 minutes in neohapitic phase (T4), and the end of operation (T5). RESULTS: (1) In the experimental group, PvO(2) increased, Ca-vO(2) decreased, DO(2) and VO(2) showed no change, and O(2)EI and O(2)ER decreased in T2. In preanhepatic period, PvO(2) increased, Ca-vO(2) decreased, DO(2) and VO(2) did not change. In anhepatic period, DO(2), DO(2)I, VO(2) and VO(2)I decreased obviously, DO(2) decreased by 43%, while VO(2) decreased by 21%, and O(2)ER increased obviously. In reperfusion period, PaO(2) and PvO(2) increased, CaO(2) and Ca-vO(2) decreased, DO(2) and DO(2)I increased, VO(2) and VO(2)I recovered to base level. After termination of operation, PvO(2), DO(2), DO(2)I were still high. (2) In the control group: PvO(2) increased, O(2)EI and O(2)ER decreased, but no significant changes were found in DO(2) and VO(2) in T2. DO(2), DO(2)I, VO(2), and VO(2)I all decreased in T3, while DO(2) reduced by 25% and VO(2) reduced by 12%. In T4, PvO(2), DO(2) and DO(2)I all increased, while Ca-vO(2), VO(2) and VO(2)I reached the pre-operative levels in T4. DO(2) and DO(2)I levels were higher than those of pre-operation in T5. CONCLUSION: The decrease in DO(2) is more obvious than VO(2) in anhepatic period during OLT in hepatitis B gravis patients. In neohepatic period, DO(2) increases while VO(2) returns to base level.

[Significance of hemodynamic changes and monitoring value of patients with severe hepatitis during perioperative orthotopic liver transplantation].

OBJECTIVE: To observe the hemodynamic changes of the patients with severe hepatitis during orthotopic liver transplantation (OLT). METHODS: Ten patients with severe hepatitis received liver transplantation. The pulmonary artery catheter was inserted into right jugular vein and an arterial line was put in the left radial artery. Hemodynamics parameters including cardiac output (CO), arterial blood pressure (ABP), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), cardiac index (CI) at different time points were observed. RESULTS: During the operation, HR was increased, and ABP was significantly decreased at the beginning of anhepatic period and neo-hepatic period. Central venous pressure (CVP) was significantly decreased during anhepatic period and profoundly increased in the early neo-hepatic phase, then declined to normal range progressively. Pulmonary capillary wedge pressure (PCWP) changed in accordance with the variation of pulmonary arterial pressure (PAP). Both of them were significantly decreased during anhepatic period and profoundly increased in the early neo-hepatic phase. SVR was at a lower level before operation, and gradually increased during anhepatic period, then significantly declined at the beginning of anhepatic period. PVR had the most marked changes during the neo-hepatic period, gradually decreased to the pre-operation level after significant elevation at the early neo-hepatic phase. Left ventricular stroke work index (LVSWI) was profoundly declined from the beginning of anhepatic period to the 1 minute after neo-hepatic phase, then progressively increased. Right ventricular stroke work index (RVSWI) was significantly decreased during anhepatic period, then progressively increased during neo-hepatic period. CO and CI maintained at a higher level, significantly declined during anhepatic period compared with pre-anhepatic period and gradually increased to a higher level than peri-operation. CONCLUSION: Remarkable changes in hemodynamics of patients with severe hepatitis during liver transplantation are found especially at the early phase of anhepatic and neo-hepatic, while CO maintained at a higher level, together with a complicated changes in SVRI. Monitoring hemodynamics during peri-operation has its value to prevent and manage cardiac insufficiency and low blood volume.