Anesthesia And Goal-guided Hemodynamic Management Of The Organ Transplant Patients With DCD Liver Supported By ECMO

In the 21st century, with the progressing of liver transplantation technology, liver transplantation has become the only way to cure patients with end-stage liver disease. But the shortage of organ has always been a global challenge. In recent years, China launched donation after cardiac death (DCD), and become the direction of transplant organ donation in China.Hemodynamic goal-directed therapy oriented management by determining the goal directed, selecting the appropriate indicators of hemodynamic monitoring, and making a diagnosis and treatment about accurate equilibrium of supply and demand of oxygen to reach the ultimate objective of this hemodynamic management，In the course of hemodynamic optimization management in our choice of priority monitoring means can provide us the correct information about these patients, whether timely and reliable information, how to help our decision-making and treatment. For low-risk operation, the monitoring of the noninvasive parameters eg.NIBP, CVP, HR etc.is enough.but the monitoring has been far from enough for the high-risk operation eg.liver transplantation, so we choose PICCO2 as the hemodynamic monitoring methods. But a more accurate monitoring means can improve the prognosis, unless you can choose the right treatment, so we adopted the PICCO2 monitoring to optimize the anesthesia induction.During liver transplantation surgery, hemodynamic volatility, organ ischemia-reperfusion injury, massive bleeding and changes in clotting mechanisms would damage the new liver, even lead to graft failure. However, before obtaining graft organ, DCD donor have to go through a period of hypo-perfusion even no perfusion, and during which occurs a series of pathophysiological changes in intracellular because of decreased blood flow and oxygen deficiency. To minimize the impact, we apply extracorporeal membrane oxygenation (ECMO) in the process of organ obtaining. ECMO is mainly used in the patients with respiratory insufficiency and cardiac dysfunction in clinic, to improve hypoxemia and organ blood perfusion effectively. However, ECMO is a form of bypass, and has some indications. ECMO can make warm ischemia time shorter, but because of its non-physiological intervention on donor and pathophysiological changes, there will be many kinds of complications.We hope to discuss the physiological and pathological change trend in peri operation period of liver transplantation patients by the clinic research of anesthesia and goal-guided hemodynamic management of the organ transplant patients with DCD liver supported by ECMO, and how to provide reference about the evaluation of early effect of transplantation.Part 1 The hemodynamic management of goal-directed therapy about the anesthesia induction of the liver transplantation with DCD donorObjectiveDuring the period of anesthesia induction and intubation, patients would react strongly. For critically ill patients, they would stimulate cardiovascular system and cause hemodynamic fluctuating. After hemodynamic goal-directed therapy management, we can accurately analyze the influence of hemodynamic parameters based on dynamic monitoring, and make diagnosis and treatment timely. Dexmedetomidine has central anti-sympathetic effects, and has approximate natural sleep sedation, and some analgesic effect. This study is to investigate the effect of dexmedetomidine on the hemodynamic response to the induction of general anesthesia and tracheal intubation with PiCCO2.Materials and Methods24 patients (including liver cancer 10 cases, liver cirrhosis 12 cases, acute liver failure 2 cases) undergoing liver transplantation were enrolled in this study with Narcotrend monitoring anesthesia depth. Before anesthesia induction, anesthesiologist inserted at femoral artery under local anesthesia PiCCO tube and connected to PiCCO monitor, and recorded invasive arterial pressure, heart rate (HR), pulse indicator continuous cardiac index (PCCI), systemic vascular resistance index (SVRI), global ejection fraction (GEF), central venous pressure (CVP), extravascular lung water (EVLW). According to random number table, they were assigned to DEX group (an initial dose of 0.5μg/kg for 10 min, followed by a continuous infusion of 0.5 μg/kg/h, n=12) and control group (an initial dose of the same amount of 0.9% sodium chloride, n=12). Anesthesia was induced with propofol and remifentanil using a target-controlled infusion system. The initial target propofol and remifentanil effective concentration were 3.0μg/ml and 3.0ng/ml respectively, followed by intravenous injection with 0.15mg/kg cisatracurium. Intubation was carried out until the TCI system reached the effective concentration. MAP, HR, PCCI, SVRI, GEF, EVLW, CVP and NT were recorded at time points of pre-Dex(T0), post-Dex(T1), TCI system reached the effective concentration(T2), intubation(T3), 1min after intubation(T4),3min after intubation(T5),5min after intubation(T6).Use IBM SPSS20.0 statistical software for statistical analysis. Use repeated measures analysis of variance. The mean and standard deviation of each data were expressed by χ±s, P<0.05 was considered statistically significant.ResultsThere was no difference between the two groups in the number of MAP、HR、 PCCI、EVLW、SVRI、CVP at TO (P>0.05). Compared with T0, the difference was statistically significant about PCCI at T11 in group DP(P=0.008), but the difference was statistically significant about GEF. There was statistically significant about ELVW at time T1～T6 compared with time T0(P<0.05).Compared with T0, there was statistically significant about HR、SVRI、PCCI and GEF at T2 (P<0.05). Compared with T0, there was statistically significant about MAP, HR and NI at T3 and T4(P<0.05). There was statistically significant about EVLW at all the time compared with each other. The EVLW in group DP was drop gradually(F=3.468, P=0.043), and which was rising gradually(F=2.111, P=0.137) in group NS. Compared with two groups, there was statistically significant about EVLW at all the time. Tl(t=-2.628, P=0.015), T2(t=-3.543, P=0.002), T3(t=-4.776, P< 0.001), T4(t=-3.604, P=0.002), T5(t=-3.937, P=0.001), T6 (t=-4.347, P<0.001)。DiscussionMaintain the same propofol remifentanil target controlled concentration and the depth of anesthesia induction, the use of a loading dose of Dex 0.5 mu g/kg for anesthesia induction of orthotopic liver transplantation in patients with general anesthesia will help to achieve the goal of GDT instead of aggravating hemodynamic fluctuations. Dexmedetomidine administration during anesthetic induction may be useful, because it suppresses the decrease in MAP, and blunts the cardiovascular response to tracheal intubation, but also increases SVRI and reduces EVLW. Therefore, goal-directed therapy of hemodynamic monitoring will provide the most direct reference for the best scheme about anesthesia induction.Part 2 The relationship of the narcotrend index change and early recovery of liver function undergoing classic orthotopic liver transplantationBackgroundThe efficacy of liver transplantation mainly depends on if the graft could restore sooner once the graft liver blood circulation established. Percutaneous liver biopsy even some other could damage the new liver. MELD classification which is depended on serum creatinine, bilirubin, INR and other indicators, is susceptible to non-liver disease factors, which will directly impact the determination of liver disease. ICG (indocyanine green or indocyanine green) test can reflect hepatic blood flow and the secretion of hepatic cells, but the result is greatly affected by hepatic blood flow, and is not suitable for all patients. In recent years, our department using Narcotrend grade monitoring during liver transplantation surgery to guide anesthesia, reduce anesthetics consumption and shorten recovery time has made a significant clinical effect. During monitoring process, we found that after opening the new liver vascular, the low concentration of narcotic drugs which was needed in the non-liver period to maintain the anesthesia depth was continued. And with the time going, NT value gradually increased. We increased the target concentration until the NT value reached the predetermined value. We recorded the time from opening the new liver vascular to deepening anesthesia, and found the magnitude of the time value varied widely. This study is to investigate the relationship of the narcotrend index change and early recovery of liver function undergoing classic orthotopic liver transplantation.Materials and Methods38 patients with end-stage liver disease undergoing liver transplantation were enrolled in this study, and the ASA stage was Ⅱ～Ⅲ. All patients were general anesthesia, and maintained with total intravenous target-controlled infusion. The target propofol and remifentanil effective concentration were 3.0-4.5μg/ml and 3.0-4.0ng/ml respectively. Patients were monitored by Narcotrend regularly after arriving the operating room, and the depth of anesthesia was maintained by Narcotrend between D2 with E1 stage(20-46). Anesthesiologist use vasoactive drugs appropriatly to maintain hemodynamic stability. The NT value was the basic value when portal vein was opened. The narcotrend index was monitored and TCI target controlled concentration remained unchanged after the portal vein opening. When the narcotrend index was rising higher than 20, anesthesia was deepened and time (S) was recorded. The weight, age, intraoperative blood loss and urine, monitoring indicators such as INR, ALT, AST, CRE 2 days after liver transplantation, the days stayed in ICU and hospital, ECMO running time, non-liver time, and cold ischemia time were recoreded.This study uses IBM and SPSS20.0 statistical software for statistical analysis. The mean and standard deviation of each data were expressed by χ±S，p<0.05 was considered statistically significant, we will use Pearson correlation test to process bivariate normality test variables and use Spearman correlation test to process which are not the bivariate normality test variables.ResultsTo further investigate whether there is a linear regression relationship between the various elements and S, we first choose the main elements to establish eight regression models, then add relevant element one by one (table 2-3). Then we will add all the elements into the model to investigate the linear regression relationship between all the elements of S. The results showed that:on the background which the confidence interval was 95% and significance was 0.05, only Model 1 (time S and AST) was significant of all above regression model.All Regression model variance analysis showed that:the results of T-test were that P values were all less than 0.05, and we could consider the regression coefficients of the above model were meaningful.The results of regression analysis between all elements and the S:on the background which the confidence interval was 95% and significance was 0.05, the regression coefficient R of the regression model did not have a significant meaning.Variance analysis of regression model showed that this model did not exist significant regression relationship.All factors for main effects regression model showed that only AST had a significant relationship with S (in the case of controlling other variables, t value was 2.673, the significance level was 0.014, the regression coefficient was 0.518).Of all above model, only Regression model one was significant. Therefore, we believe that Regression model one could better explain the factors influencing S.Model 1 can be described as:S= 72.497***+0.558*** AST R square=.312, sig.= 000T (20.975 4.036)DiscussionThe study found that the indicators of serum liver enzyme before and after anhepatic period were often unable to truly reflect the recovery of liver function, which may be the surgical trauma, bieeding, and frequent replacement capacity lead in serum enzyme spectroscopy losing objectivity, even appearing liver function "better" illusion.The trend of NT value is simple and quantify, and is applicable to clinical practice. It is not only used to guide choosing anesthetic drugs, adjusting anesthesia depth, but also help us understand the early recovery of DCD liver from the side. And compared with other biochemical markers of liver and kidney function, NT value is not affected by external factors, but we need further study to confirm if the NT value has some relationship with cell function examinations.There was a significant relationship between the time S and the indicators for liver function (especially AST) 2 days after operation, so we could estimate how the new liver recovery by the time S. During the cold ischemia period of the graft, the time S provided us a reference index to know the liver conditions. If the time S was significant longer, indicated that the liver function was inhibited and did not work normally after restoring the blood flow of liver, which maybe because the donor, the procedure of obtaining organ, or the surgery. So we should find the ways sooner, including careful use of narcotic drugs, early artificial liver replacement therapy for DCD liver recovery gaining more time.Of course, the time S could not replace intraoperative monitoring indicators of liver function totally, but it would become an acceptable way to predict new liver function in clinic, because it was hardly to find a simply and non-invasive mean to predict the recovery of the graft in the early new liver after opening (within 3 hours), and clinical and biochemical monitoring indicators were influenced by heavy blood and transfusion even though important.The study found a positive correlation between ECMO and ALT, which shows the length of time of ECMO running affected the new graft. In addition, patients with abnormal coagulation prolonged ICU stay, which was consistent with the clinical observation. The study also found that there was a certain relationship between blood loss and postoperative renal function. When the blood loss increased, the renal tissue perfusion pressure would decrease, and so does the glomerular filtration rate. Compared with preoperative level, the CRE of 1,2, and 3 days after operation were significant increased, indicating that postoperative renal function was injuried. Some patients’ serum CRE were more than 133μmol/L, which is the cute renal failure diagnostic criteria, and the incidence in the first was 2.6% after operation, then rised to 31.6% in the next day. The Correlation analysis results showed that postoperative CRE level especially the first day after operation, had a strong correlation with the preoperative, suggesting renal function before liver transplantation did influence postoperstive renal function.The study found that DCD graft cold ischemia time and non-liver time were not related with postoperative liver and kidney function. This may be because of the further optimization of ECMO application of DCD organ procurement, and cold ischemic time is much shorter compared to the previous. Our department control the liver cold ischemia time within 5 hours (including non-hepatic period of time), usually 3-4 hours basically to reduce the damage on sinusoidal endothelial cells and hepatocytes, and decrease IPGF and PGNF. And our study confirmed the importance of limiting ischemia time again.Part 3 The all kinds of monitoring indicators after DCD donor liver transplantation backed by EC MOObjectivePatients after liver transplatation is usually transported to the ICU, and the treatment time is generally 2 to 5 days, of which the first three days is the most important. Then the surgeons decided to continue treatment in the ICU or return to the general ward depended on these days situation. Therefore, we choose several key indicators including liver function, kidney function, blood coagulation and other monitoring indicators for three days, and want to how to develop.Materials and Methods38 patients with end-stage liver disease undergoing liver transplantation were enrolled in this study,21 of who were hepatic carcinoma and 17 were cirrhosis. The ASA of all them was Ⅱ～Ⅲ, and preoperative cardiopulmonary function was normal. All patients were general anesthesia, and maintained with total intravenous target-controlled infusion, adjusting the anesthesia depth according to the different surgical stages. Venous blood samples were collected in the preoperative(TO), 24h(Tl),48h(T2),72(T3) after the operation, testing INR, AST, ALT, TBIL and creatinine after centrifugation. Use IBM SPSS20.0 statistical software for statistical analysis. Use repeated measures analysis of variance. The mean and standard deviation of each data were expressed by χ±s, P<0.05 was considered statistically significant.ResultsCompared with each time, there was statistically significant about AST (F=15.817, P<0.001). Compared with T0, there was statistically significant about AST at T1-T2 (P<0.05). Compared with T0, there was not statistically significant about AST at T3.Compared with each time, there was statistically significant about ALT (F=8.705, P<0.001). Compared with T0, there was statistically significant about ALT at T1-T2 (P<0.05). Compared with T0, there was not statistically significant about ALT at T3.Compared with each time, there was statistically significant about CRE (F=22.105, P<0.001). Compared with T0, there was statistically significant about CRE at T1-T3 (P<0.05), and postoperative CRE increased significantly. Compared with Tl, there was statistically significant about ALT at T2 and T3(P<0.05).There was statistical correlation between the INR values of TO and T1(r=0.666, P<0.001). There was statistical correlation between the INR values of T1 and T3(r=0.341, P=0.036). There was statistical correlation between the INR values of T2 and T3(r=0.734, P<0.001). There was not statistical correlation among the other values.There was statistical correlation compared with each other about TBIL values (P <0.01).There was statistical correlation between the AST values of T1 and T2(r=0.619, P< 0.001). There was statistical correlation between the AST values of T2 and T3(r=0.618, P<0.001). There was statistical correlation between the ALT values of T2 and T3(r=0.363, P=0.025). There was statistical correlation between the CRE values of TO and T1(r=0.473, P=0.003).There was statistical correlation among the values of T1, T2 and T3.ConclusionCompared with pre-operation, coagulation after liver transplantation was in a low hypercoagulable state with lack of coagulation factors and fibrinolysis, and began to slowly improve on the third day. In addition, postoperative coagulation status significantly correlated with preoperative status, it showed that the preoperative coagulation influences the postoperative recovery.Postoperative liver function also appears different situations. TBIL, ALT and AST were sharply increased compared with pre-operation. The liver function started to recover slowly in all, especially the next day after the operation, even hot-cold ischemia, anesthesia and surgery, reperfusion injury all could damage the new liver.Acute renal failure is the result of multiple factors, which releated to the preoperative, intraoperative and postoperative problems, and mainly because of pre-renal and renal. Therefore, the patients undergoing liver transplantation should adjust renal function early before operation, and closely monitor creatinine and the volume of urine during the procedure.