Jiayi Liu1,2, Chunying Lu1,3, Qirong Zou1, Sheng Wang4, Xuemei Peng1. 1. Department of Anesthesiology, First Affiliated Hospital of Jinan University, Guangzhou, China. 2. Department of Anesthesiology, Guangzhou Sun Yat-sen Memorial Hospital Sun Yat-sen University, Guangzhou, China. 3. Department of Anesthesiology, Guangdong No.2 Provincial People's Hospital, Guangzhou, China. 4. Department of Anesthesiology, the Guangdong Provincial People's Hospital (Guangdong Provincial Cardiovascular Institute).
Abstract
AIM: The aim of the current study was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of cisatracurium in patients with severe mitral valve regurgitation (MR) during the anaesthetic induction period. METHODS:Thirty patients in the clinical trial were divided into two groups: the MR group (n = 15) and the control group (n = 15). Arterial blood samples were obtained before (time 0) and at 1, 2, 4, 6, 8, 10, 15 and 20 min after intravenous injection of 0.15 mg kg-1 cisatracurium. The degree of neuromuscular block was measured by train of four (TOF) testing. The concentration of cisatracurium in the plasma was determined by high-performance liquid chromatography. A conventional two-compartment model and integrated PK/PD model were applied to PK and PD data analysis, respectively. RESULTS: The results of PK model fitting demonstrated that severe MR reduced the distribution rate of cisatracurium from the central to peripheral compartment, resulting in a higher concentration of the drug in the plasma. The time to the maximal neuromuscular blocking effect of cisatracurium was delayed in the MR group (2.08 min in the control group vs. 4.12 min in the MR group). The PK/PD model indicated that the distribution rate of cisatracurium from the blood to the effect compartment was decreased in the MR group. CONCLUSIONS: The present study suggested that the PK and PD of cisatracurium were significantly altered in patients with severe MR. The study has the potential to improve the safety of anaesthetic induction in patients with severe MR through accurate prediction of the PD responses of cisatracurium using the established PK/PD model.
RCT Entities:
AIM: The aim of the current study was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of cisatracurium in patients with severe mitral valve regurgitation (MR) during the anaesthetic induction period. METHODS: Thirty patients in the clinical trial were divided into two groups: the MR group (n = 15) and the control group (n = 15). Arterial blood samples were obtained before (time 0) and at 1, 2, 4, 6, 8, 10, 15 and 20 min after intravenous injection of 0.15 mg kg-1 cisatracurium. The degree of neuromuscular block was measured by train of four (TOF) testing. The concentration of cisatracurium in the plasma was determined by high-performance liquid chromatography. A conventional two-compartment model and integrated PK/PD model were applied to PK and PD data analysis, respectively. RESULTS: The results of PK model fitting demonstrated that severe MR reduced the distribution rate of cisatracurium from the central to peripheral compartment, resulting in a higher concentration of the drug in the plasma. The time to the maximal neuromuscular blocking effect of cisatracurium was delayed in the MR group (2.08 min in the control group vs. 4.12 min in the MR group). The PK/PD model indicated that the distribution rate of cisatracurium from the blood to the effect compartment was decreased in the MR group. CONCLUSIONS: The present study suggested that the PK and PD of cisatracurium were significantly altered in patients with severe MR. The study has the potential to improve the safety of anaesthetic induction in patients with severe MR through accurate prediction of the PD responses of cisatracurium using the established PK/PD model.
Authors: Gregg W Stone; Alec S Vahanian; David H Adams; William T Abraham; Jeffrey S Borer; Jeroen J Bax; Joachim Schofer; Donald E Cutlip; Mitchell W Krucoff; Eugene H Blackstone; Philippe Généreux; Michael J Mack; Robert J Siegel; Paul A Grayburn; Maurice Enriquez-Sarano; Patrizio Lancellotti; Gerasimos Filippatos; Arie Pieter Kappetein Journal: J Am Coll Cardiol Date: 2015-07-21 Impact factor: 24.094
Authors: Lars B Holst; Nicolai Haase; Jørn Wetterslev; Jan Wernerman; Anne B Guttormsen; Sari Karlsson; Pär I Johansson; Anders Aneman; Marianne L Vang; Robert Winding; Lars Nebrich; Helle L Nibro; Bodil S Rasmussen; Johnny R M Lauridsen; Jane S Nielsen; Anders Oldner; Ville Pettilä; Maria B Cronhjort; Lasse H Andersen; Ulf G Pedersen; Nanna Reiter; Jørgen Wiis; Jonathan O White; Lene Russell; Klaus J Thornberg; Peter B Hjortrup; Rasmus G Müller; Morten H Møller; Morten Steensen; Inga Tjäder; Kristina Kilsand; Suzanne Odeberg-Wernerman; Brit Sjøbø; Helle Bundgaard; Maria A Thyø; David Lodahl; Rikke Mærkedahl; Carsten Albeck; Dorte Illum; Mary Kruse; Per Winkel; Anders Perner Journal: N Engl J Med Date: 2014-10-01 Impact factor: 91.245
Authors: R C Prielipp; D B Coursin; P E Scuderi; D L Bowton; S R Ford; V J Cardenas; J Vender; D Howard; E J Casale; M J Murray Journal: Anesth Analg Date: 1995-07 Impact factor: 5.108
Authors: Wen-Chih Wu; Tracy L Schifftner; William G Henderson; Charles B Eaton; Roy M Poses; Georgette Uttley; Satish C Sharma; Michael Vezeridis; Shukri F Khuri; Peter D Friedmann Journal: JAMA Date: 2007-06-13 Impact factor: 56.272
Authors: Stephen Ph Alexander; Eamonn Kelly; Neil Marrion; John A Peters; Helen E Benson; Elena Faccenda; Adam J Pawson; Joanna L Sharman; Christopher Southan; O Peter Buneman; William A Catterall; John A Cidlowski; Anthony P Davenport; Doriano Fabbro; Grace Fan; John C McGrath; Michael Spedding; Jamie A Davies Journal: Br J Pharmacol Date: 2015-12 Impact factor: 8.739