Liver Transplant Patients Rocuronium Clinical Pharmacodynamic Study

Objective To study dose-response relationship of rocuronium in patients with severe liver dysfunction undergoing orthotopic liver transplantation during intravenous balanced anesthesia.Methods Rocuronium was administered to 20 patients undergoing orthotopic liver transplantation (Child-Pugh Class C) and 20 healthy patients for an elective procedure. Patients were randomly allocated to received an initial dose of rocuronium: 100, 150, 200, or 250μg/kg. The response of adductor pollicis to train-of-four (TOF) stimulation of unlar nerve were monitored. The relationship between probit-transformed depression of first twitch height of TOF and the logarithm dose of rocuronium was analyzed using linear regression and ED₅₀, ED₉₀, ED₉₅ was calculated, respectively. The onset time was recorded.Results The two groups were comparable with regard to age, weight and hemocrit, but plasma albumin was significantly lower in patients undergoing orthotopic liver transplantation than that in healthy patients. No statistically significant differences were found in the slope, intercept, ED₅₀ , ED₉₀and ED₉₅ values between two groups. The average onset time was significantly longer in liver transplantation group than that in healthy patient group, especially when the initial doses of rocuronium were 200 and 250μg/kg.Conclusions During intravenous balanced anesthesia, severe liver dysfunction (Child-Pugh Class C) did not change the dose-response relationship of rocuronium, but significantly delayed the onset time of rocuronium.Objective To compare the changes of continuous infusion rates of rocuronium and atracurium during three stages of orthotopic liver transplantation in humans.Methods 20 male patients undergoing liver transplantation were randomly assigned to two comparable groups of 10 patients each to receive a continuous infusion of rocuronium or atracurium under intravenous balanced anesthesia. The response of adductor pollicis to train-of-four (TOF) stimulation of unlar nerve were monitored. The infusion rates of rocuronium and atracurium were adjusted to maintain T1/Tc ratio between 2-10%. The total dose of each drug given during each of the three phases of OLT was recorded.Results Rocuronium requirement, which were 0.468±0.167 mg/kg·h during the paleohepatic phase, decreased significantly during the anhepatic phase to 0. 303±0. 134 mg/kg·h and return to the initial values at the neohepatic period (0.429±0.130 mg/kg · h);whereas atracuruim requirements remained unchanged during the three stages.Conclusions This study showed that the exclusion of the liver from the circulation results in the significantly reduced requirement of rocuronium while the requirement of atracurium is not changed, which suggests that the liver is ofmajor importance in the clearance of rocuronium. A continuous infusion of atracurium with constant rate can provide stable neuromuscular blockade during the three stages of OLT.Objective To investigate the effect of renal function on the diagnostic value of rocuronium to assess early postoperative graft liver function during liver transplantation.Methods 49 patients undergoing orthotopic liver transplantation were divided into two groups according to the preoperative renal function: normal renal function group (Group N, 28 cases) and renal failure group (Group F, 21 cases). All patients were given rocuronium 0. 6mg/kg during induction and 15 minutes after reperfusion of the allograft. The response of adductor pollicis to train-of-four stimulation of unlar nerve were monitored and the time from injection of rocuronium to T1 return to 25% of baseline (clinical duration time) were recorded. The patients in two groups were divided into two subgroups which consisted of patients with immediate normal liver function and with early postoperative liver dysfunction according to early postoperative liver function, respectively. Early postoperative liver dysfunction was determined by peak serum aspirate aminotransferase and alanine aminotransferase levels >2000U/L, and prothrombin time >16s.Results The clinical duration time during neohepatic period in Group F was prolonged compared with Group N (84±21 vs 66±18min, P<0. 01) . 4 patients matchedthe diagnostic standard of early postoperative liver dysfunction in each groups. Early postoperative liver function testing using the clinical duration of >80min has a sensitivity of 75% and a specificity of 83% in Group N, while using the clinical duration of >95min has a sensitivity of 75% and a specificity of 76% in Group F. The area under ROC curve was not statistically different between the two groups (0.927+0.032 for Group N, 0.794+0.085 for Group F).Conclusions Using rocuronium to assess early postoperative graft liver function during liver transplantation in patients with normal renal function may have high diagnostic value, but the value may be decreased when used in patients with renal failure, which needs larger sample study to confirm.