This study aims to determine the pharmacodynamics (PD) effect (measured by cardiovascular depression) of propofol during anesthesia induction period on morbidly obese (MO) patients. Four hemodynamics indexes [i.e., three indexes about blood pressure and cardiac output (CO)] representing cardiovascular function were measured. Pharmacokinetic/pharmacodynamic (PK/PD) modeling was performed by population analysis to obtain PD parameters. Two propofol dosing scalars, namely, dosing based on total body weight (TBW) or lean body weight (LBW), were used for MO subjects. The PD data were well described by a PK/PD model. Blood pressure and CO were rapidly decreased within one minute after intravenous injection of propofol (2 mg/kg). TBW group showed significantly lower blood pressure and CO values at and 1 min after propofol administration compared with the control group, whereas the control and LBW groups had similar PD profiles. In addition, the propofol EC50 value was significantly decreased in MO patients, whereas all other PD parameters were similar between control and MO subjects. This change indicated that propofol potency and/or sensitivity was increased in MO subjects. For MO patients, dosing of propofol based on LBW rather than TBW would be a safer choice due to a less cardiovascular depression effect.
Keywords: Cardiovascular depression; Morbidly obese; Pharmacodynamics; Population analysis; Propofol.
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