The Lack Of Histamine Release And Dose-respose Relationship Of Cisatracurium Besilate Made In China

Objective:This study was designed to evaluate the histamine release and dose-response relationship of cisatracurium besilate made in China.Methods:Thirty-six ASA gradeⅠ～Ⅱpatients,undergoing elective surgery,were randomly divided into 3 groups in which patients received a single bolus of either cisatracurium besilate 0.10, 0.20 or 0.30mg/kg.Anesthesia was induced with midazolam 0.05～0.08mg/kg,etomidate 0.2～0.3mg/kg and fentanyl 3～5μg/kg.Each of three groups of patients received intravenous bolus of 0.10,0.20 or 0.30mg/kg of cisatracurium besilate respectively when patients fell asleep and their hemodynamics were stable.The MAP and HR were recorded during anesthesia when getting into the operating room(t₁), befor(t₂),after 1min(t₃),3min(t4),5min(t₅),7min(t₆),10min(t₇)the administration of muscle relaxant.The matching dose(500mg:1mg) of propofol and remifentanil were continuously pumped to maintain anesthesia.When T₁ inhibion to 75%of the baseline value arrived, conditions of intubation were appraised and recorded.Times to T₁ inhibion to 25%,50%,75%,100%of the baseline value,times to 25%,95%of recovery,times to T₄/T₁≥0.7 and the recovery index(25%～75%) were recored.Venous blood samples were obtained before(T₁) and at 3min(T₂) and at 5min(T₃) after the administration of muscle relaxant for determination of plasma histamine concentrations.Result:1.There was no significant difference in sex,age, weight and the intubating conditions among the three groups. 2.Time to T₁ 75%inhibition of the baseline value in groupâ…¡,â…¢was significantly shorter than that in groupâ… (P＜0.05),which in groupâ…¢was also significantly shorter than that in groupâ…¡(P＜0.05). Time to maximum suppression from 75%inhibition of the T₁ response in groupâ…¢was significantly shorter than that in groupâ… andâ…¡(P＜0.01),which in groupâ…¡was also significantly shorter than that in groupâ… (P＜0.05).Time to 25%,95%recovery of the T₁ response,time to no response of TOF and time to T₄/T₁＞0.7 in groupâ…¡were significantly longer than that in groupâ… (P＜0.05), which in groupâ…¢were also significantly longer than that in groupâ… andâ…¡(P＜0.05).However,the extent of maximum suppression of the T₁ response and the recovery index(25%～75%) were no significant difference among these groups(P＞0.05).3.The HR and the MAP at t₂ were no significant difference from that at t₁ in three groups respectively(P＞0.05),and they at t₃～t₇ were also no significant difference from that at t₂ in three groups(P＞0.05). On the three curve graphs of HR changes,the HR at t₂ were slower than that at t₁,which then had been going faster and faster gradually until the HR at t₄～t₇ almost went back to the baseline value at t₁;On the three curve digrams of MAP changes,the MAP at t₂ got lower than that at t1,which at t₃ went up higher than that at t₂.Meanwhile, the MAP at t₄～t₇ went back to the baseline lever at t₁ gradually; None of all patients used atropine to raise the HR or required therapy for hypotension.4.The plasma histamine concentrations changes at T₂ and T₃ after the administration of relaxant as compared with those before induction were not significantly different in the three groups respectively(P＞0.05),which were higher at T₂ and T₃ than those at T₁, though;On the three trendline graphs of plasma histamine concentrations changes,The plasma histamine concentrations at T₂ were uptrend and then got back to the baseline value at T₃;Among the three groups,the plasma histamine concentration at T₂ in groupâ…¢was higher than that in groupâ… andâ…¡which in groupâ…¡was also higher than that in groupâ… ,but these differences were not significant (P＞0.05);Actually the skin of one patient in groupâ…¡and one patient in groupâ…¢turned up flush or constant redness(＞120s) when they received intravenous bolus of muscle relaxant but no further cutaneous reactions were observed.Conclusions:(1) In total intravenous anesthesia(TIVA),the time of onset of cisatracurium besilate made in China was significantly shorter,and the time to recovery of neuromuscular block was significantly longer.However,the recovery index changes were not significantly different.(2)2～6×ED₉₅ of cisatracurium besilate made in China does not cause any significant changes either in histamine release nor in hemodynamics.