Pharmacokinetic and pharmacodynamics of intravenous dexmedetomidine in morbidly obese patients undergoing laparoscopic surgery.

Abstract

This study was designed to investigate the pharmacokinetics and pharmacodynamics of dexmedetomidine in morbidly obese patients undergoing laparoscopic surgery. Morbidly obese (body mass index ≥40kg/m2) and normal weight patients scheduled for elective laparoscopic surgery were included (n=8, each group). After baseline hemodynamic measurement, dexmedetomidine 1μg/kg was administered over 10min. General anesthesia was induced with propofol 1.5mg/kg and fentanyl 4μg/kg 20min after completion of dexmedetomidine infusion; the lungs were mechanically ventilated after tracheal intubation. The pharmacokinetics of dexmedetomidine was analyzed by a noncompartment model. Hemodynamic data and peripheral oxygen saturation (SpO2) were measured up to 30 min after starting dexmedetomidine infusion. Sedation level was measured with the Observer's Assessment of Alertness/Sedation (OAA/S) scale. Peak plasma concentration, area under the curve to infinity, elimination half-life, and apparent volume of distribution were significantly larger in morbidly obese than in normal weight patients (3.75±0.56 vs. 2.54±0.32µg/l, P<0.001; 2174±335 vs. 1594±251ngh/l, P<0.001; 225±55 vs. 158±53min, P=0.02; 310±63 vs. 164±41 l, P<0.001, respectively). Although clearance was also higher in obese patients than in normal body weight patients (58.6±10.7 vs. 44.9±9.0 l/h, P=0.02), it was lower in obese patients than in normal body weight patients after normalization to total body weight (0.47±0.07 vs. 0.64±0.09 l/h/kg, P<0.001). There were no differences in systolic or diastolic blood pressure or heart rate between the two groups within the 30min. Sedation level was deeper and SpO2 was lower in morbidly obese than in normal weight patients. More patients in the morbidly obese patient group experienced deeper sedation after the start of the dexmedetomidine infusion (P<0.05). The pharmacokinetics and pharmacodynamics of dexmedetomidine are significantly different in morbidly obese patients compared with normal weight patients. Level of sedation was significantly deeper, and oxygen saturation was significantly lower, in morbidly obese than in normal weight patients, probably resulting from higher plasma concentration after infusion of 1.0µg/kg. ClinicalTrials.gov (NCT01864187), https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=1&cx=-jg9qo4 .