Abnormal Cisatracurium Pharmacodynamics and Pharmacokinetics among Patients with Severe Aortic Regurgitation during Anesthetic Induction

Abstract Background This study was designed to examine whether severe aortic regurgitation will affect the pharmacodynamics (PD) and pharmacokinetics (PK) of cisatracurium during anesthetic induction. Method s A total of 32 patients were divided into two groups: the AR group (n=16) and the control group (n=16). Arterial blood samples were drawn before and at 1, 2, 4, 6, 8, 10, 16 and 20 minutes after intravenous injection of 0.15mg/kg cisatracurium. TOF tests were applied to determine the onset time of maximal muscle relaxation. The concentration of cisatracurium in plasma was determined by high-performance liquid chromatography. Results The onset time to maximal neuromuscular block was prolonged from 2.07±0.08 minutes to 4.03±0.14 minutes, which indicated that the PD responses to cisatracurium were significantly delayed in the AR group (P<0.05) compared to the control group. A conventional two-compartment PK model showed a higher plasma concentration of cisatracurium among the AR group with markedly reduced intercompartment transfer rate (K 12 = 0.19±0.02 and K 21 = 0.11±0.01 in the AR group vs. K 12= 0.26±0.01 and K 21 = 0.19±0.01 in the control group, P<0.01) compared to the control group. Conclusion Backward blood flow during diastole in severe AR impaired distribution of cisatracurium from the central compartment to the peripheral compartment, which accounted for the lagged PD responses. Findings in this study underlie the importance of neuromuscular blockade monitoring among patients with severe aortic regurgitation during anesthetic induction.