| IntroductionSince the first success case of liver transplantation in the beginning the 1960s', hepatic transplantation already has 40 years history. Along with the improvement of the surgical skill and the treatment of immune repulsion , and the understanding about the complications of postoperative, the success ratio of the liver transplantation has been increased gradually. But the complications of postoperative still unceasingly occurred and which was attached importance day by day. The remote organ damage which resulted from hepatic transplantation is one of the key points at present researches.The rate of neurological complications of postoperative liver transplantation was 8 to 47%, average about 20%. The cerebral complication was mainly occurred at the early time of postoperative. The success of transplantation and patients healing was influenced seriously.The neurological complications after transplantation could be attributed to several reasons such as metabolism disorder, surgical injury, stress, ischemia reperfusion injury, the brain damage caused by late-stage hepatic disease, postoperative rejection and the use of immunosuppressive agents. But the mechanisms of neurological complications after transplantation are still not clear.In patients with liver failure, massive liver injury may be associated with a rapid development of cerebral dysfunction including hepatic encephalopathy (HE) and cerebral edema. Several theories concerning the pathogenesis of HE have been put forward, but it remains unknown whether changes in the cerebral circulation precede or follow cerebral dysfunction. Normally, the cerebral circulation is regulated by arterial carbon dioxide tension and metabolism to secure an adequate supply of oxygen and glucose to the brain. Changes in arterial pressure only have a minor influence on CBF, that is cerebralautoregulation. In patients with tulminant tailure and in some patients with cirrhosis, CBF autoregulation is absent. The pathophysiological mechanism of impaired CBF autoregulation remains unknown, but it could be caused by toxic substances released from the failing liver. If loss of CBF autoregulation is of pathophysiological importance in the development of FIE and cerebral edema, it must be assumed that CBF autoregulation has been reestablished shortly after hepatic recovery resulting from liver transplantation.Previously, concerning cerebral hemodynamics of late-stage hepatic disease, and the cerebral blood flow (CBF) influenced by Orthotopic liver transplantation (OLT), the impaired cerebral autoregulation and cerebral hemodynamics during OLT were concentrated more. But little was attached importance to the CBF alteration after transplantation, especially two weeks after operation that the neurological complications occur frequently, and the relationship between restoration of liver function, cerebral function, prognosis and CBF.In this research we monitored CBF velocity (CBFV) of OLT by transcranial Doppler ultrasonography (TCD), looking for the rule of the CBFV alteration after transplantation, searching the possiblerelationship between liver function, prognosis and CBFV, in hope of providing the material for clinical therapeutics and finding a way to lower the neurological complications after operation, then enhance the success ratio of liver transplantation.Materials and methods1. Materials: 35 patients (29 males and 6 females, median age 43 yr, range from 5 to 65 yr) undergoing OLT consecutively admitted to our Liver Transplantation Unit between August 2005 and January 2006 were observed. 27 with liver cirrhosis caused by Hepatitis B, 4 with primary carcinoma of liver, 1 with cholangiocarcinoma, 1 with Wilson's disease, 1 with Caroli's disease, and 1 with congenital emphraxis of choledochus.2. Methods:2.1. Cerebral Blood Flow Velocity: Mean CBFV of the bilateral middle cerebral artery (MCA) was measured by transcranial Doppler ultrasonography (Companion2021-III, EME, Germany) at 46 to 60 mm of depth transtemporal window by a 2-MHz probe. When the temporal window was inadequate, the transorbital approach was used to measure the contralateral MCA at 80 to 92mm of depth. Ascertained the blood vessel by Quechenstedt test, and recording the velocity of systolic peak(Vs), end of diastolic (Vd), mean blood flow velocity (Vm) and the pulsatility index (PI).2.2. Neurological examination: routine evaluated the consciousness (with Glasgow coma score, GCS), pupil and light reflex, muscular force and tension, tendon reflex and the Babinski's sign. At the same time observed the convulsion postoperative.2.3. A catheter was inserted into a radial artery for blood sampling and monitoring of mean arterial pressure (MABP) (Baxter transducer, Unden, Holland), The MABP was displayed by a Anesthesia-CMS2001 monitor (Agilent, American). Arterial carbon dioxide tension (PaCO2) was kept between 35 and 45 mmHg.2.4. The severity of liver disease was determined according to the Child-Pugh score. The assignment of patients to Child class A, B, or C was based on the values of serum albumin, bilirubin, and prothrombin time, on ultrasound assessment of the presence and degree of ascites, and on an estimate of encephalopathy.2.5. Hepatic encephalopathy (HE): The level of HE (grades I-IV) was evaluated by final report of the Working Party at the 11* World Congresses of Gastroenterology about Hepatic encephalopathy-definition, nomenclature, diagnosis, and quantification, which includethe symptom, sign and the electroencephalogram. And the electroencephalogram was measured by the electroenphalograph (Belight, EB Neuro company, Italian) and fixed the electrodes of eight-lead according to international 10-20' rule and traced ten minutes. 2.6. For statistical analysis, CBFV, PI, GCS and MABP, PaCO2, the data of liver function were compared preoperative, the 1st, 3rd, 5*, 7th and 14th day of postoperative.3. Anesthesia: Radial artery was cannulated and Swan-Ganz catheter was placed via right internal jugular vein. ECG, MABP, HR, CVP, MPAP, cardiac output (CO), SpO2, PE1CO2 and T were monitored during operation. Anesthesia was induced with midazolam O.lmg/kg, fentanyl 5~10ug/kg, scopolamine 0.6mg and vecuronium O.lmg/kg, and maintained with isoflurane 0.5%~1.0% and propofol infusion (l~2mg/kg.h) in combination with intermittent i.v. boluses of midazolam, fentanyl and vecuronium, adjusted to maintain a constant depth of anesthesia as assessed by hemodynamics. The patients was mechanically ventilated after tracheal intubation, PetCO2 was maintained between 35~45mmHg, SpO2 was maintained at 100%.4. Statistics: The results are presented as medians and standard deviations. SPSS 10.0 statistical software was adopted. For comparison,the analysis of variance and paired t-test were used when appropriate. PO.05 was considered significant. And we used the bivariate correlation analysis to analyze the relation of all factors.Results26 patients without HE, 7 with HE I-II, 2 with HE III-IV;and according to the Child-Pugh score, Child A is thirteen, B is fourteen, and Child C is seven;GCS is 15 in 29 patients, ^12 in 6 patients;5 patients have convulsion postoperative. Two patients died at the seventh day of postoperative, therefore that participated the two weeks continuous examination is thirty-three.GCS decreased to the lowest level at the first day of postoperative, and returned to normal at the 5th day, later than the CBFV restoration. Analysis the changes of consciousness postoperative according the difference of GCS preoperative: A minority of the normal consciousness patients the GCS decreased at the 1st day, and returned to normal at the 3rd day. Whereas all of unconsciousness patients decreased at the 1st day, the extent was large, furthermore only 2 patients returned to normal at the 3 day, 2 died at the 7 day, and 2 patients were somnolent all through the two weeks postoperative. The ratio of the convulsion in unconsciousness patients was much higher than the consciousness.The MABP was kept constantly and the PaCO2 was kept in normal all patients within 30 minutes that the CBFV was measured. The results were displayed as follow:1. Statistics the all 35 patients: CBFV decreased to the lowest level at the first day of postoperative, compared to the preoperative (baseline), decreasing 10.02cm/s, the statistic difference was significant (P<0.05) in contrast to the baseline and the 3rd, 5th, 7th, 14th day postoperative. Returned to the baseline value and kept constantly from the 3rd day.The value of PI increased to the highest level (PI=1.01±0.22), P<0.05 compared with baseline and the 3rd, 5th, 7th, 14th day of postoperative, and still higher in the 3rd day, but returned to the baseline in the 5th day.Alanine and aspartate aminotransferase (ALT and AST) both increased to the highest level in the 1st day of postoperative, and decreased gradually, AST returned to normal after two week.2. Analyze according to the Child-Pugh score preoperative: all patients CBFV decreased and PI increased in the 1st day, but the changes in Child A was little, and was obvious in both B and C, the differences were significant in statistics (P<0.05). In Child B PI was still high (P<0.05 with pre-operation) in the 3rd day then returned to normalgradually;Contrast to others, the value of PI in Child C was already higher pre-operation, and continuously high in length time of postoperative, returned approximately to normal two weeks after operation. The data of liver function including ALT and AST, increased to the highest level in 1st day of postoperative, and returned to normal gradually, 53.85%, 78.57% patients of Child A, B returned to normal in ALT two weeks after operation, AST is 100% and 64.29%, the alteration of serum total bilirubin (TB) is similar. But the alteration of ALT and TB decreased slowly in Child C.3. Analyze according to the severity of HE: Pre-operation CBFV of the patients with HE was slower than that of without HE (group A). CBFV in the 1st day decreased obviously in contrast to preoperative all patients (P<0.05), but patients without HE and with HE HI (group B) both returned to baseline in a short time, and those with HE III-IV (group C) increased continuously from the 3rd day. Pre-operation PI of group C was much higher than that of group A and B, the variance was significant in statistics (P<0.01). In the 1st day of postoperative the value of PI increased in two groups of A and B, then decreased to normal level, but that of the group C post-operation was lower than pre-operation. ALT and AST in group A and B both increased to the highest level inthe 1st day then returned to normal, two weeks after OLT the ratio of ALT returning to normal each is 33.33 and 12.50 per cent, and the AST is 70.83 and 25.00 per cent, but the alteration of group C was irregular. TB of all three groups decreased gradually.4. Analyze according to the GCS preoperative: The CBFV of the unconsciousness patients was lower than that of the consciousness preoperative and the 1st day, the variance is significant (PO.05), and returned at the 3rd day. But the consciousness patients kept constantly pre-/post-operation.5. Eight patients (22.86%) the CBFV in the 3rd day postoperative was much higher than the baseline, which was demonstrated cerebral hyperperfusion in association with reperfiision of the liver graft. In this research the CBFV increased 28.17% in the 3rd day, and the patients with good prognosis returned to normal quickly, two patients increased continuously until death, five fold of baseline in the highest level, one patients increased mildly in the 3rd, 5* day of, but decreased sharply in the 7th day, taking on the spectrum of intracranial hypertension, and PI=2.2.In addition, 4 in above 8 patients was unconsciousness, and 3 patients died in a short time. The value of CBFV in unconsciousnesspatients was higher than the consciousness (P<0.05), furthermore the persistent time of the cerebral hyperperfusion was longer, the former was two weeks and the later returned to normal at the 5 day. The ratio of cerebral hyperperfusion in convulsion patients was higher than that of the without.6. Correlation analysis: According to "Pearson" coefficient, the CBFV is negative correlation with PI, TB, convulsion, the severity of the liver function and HE;the value of PI is negative correlation with CBFV, GCS, but positive with TB, ALT, AST, convulsion, the severity of the liver function and HE;the consciousness is negative correlation with PI, TB, ALT, AST, the severity of the liver function and HE;the convulsion is positive correlation with PI, TB, ALT, the severity of liver function and HE, but negative with the CBFV and GCS.Conclusion1. The CBFV of OLT in the 1st day of postoperative is lower than that of preoperative, and the alteration is much more in the patients with HE and seriously impaired live function. And most of patients return to normal three to five days after operation, earlier than the restoring of liver function, earlier than the HE and consciousness too.2. Cerebral hyperperfusion in association with reperfusion of the livergraft exists in a percentage of patients. But the prognosis of patients that the CBFV returning to normal in a short time is good, and that increasing continuously is bad. All of the latter are with HE and seriously impaired live function.3. The consciousness regain slowly in unconsciousness patients of preoperative, and these patients take on frequently cerebral hyperperfusion in association with reperfusion of the liver graft frequently, the time of cerebral hyperperfusion is longer, the ratio of neurological complications is higher and the prognosis is bad.4. Correlation analysis: CBFV is negative correlation with PI, TB, convulsion, the severity of the liver function and HE;the consciousness is negative correlation with PI, TB, ALT, AST, the severity of the liver function and HE;the convulsion of postoperative is negative correlation with the CBFV and GCS, but positive with PI, TB, ALT, the severity of liver function and HE.3. TCD is a noninvasive, bedside, safe, economical and repeatable method, which can' be used to measure the CBFV of the OLT patients effectively.4. Perioperative monitoring the CBFV of OLT patients, in combination with the neurological examination, the severity of the liver function andHE, could provide the material for clinical therapeutics and finding a way to lower the neurological complications after transplantation, and assist to evaluate the prognosis.
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