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A4143
October 27, 2015
1:00:00 PM - 3:00:00 PM
Room Hall B2-Area E
Dexmedetomidine Pharmacokinetics in Morbidly Obese Patients
Weifeng Tu, Ph.D., Dongxu Zhou, M.B., Zhitao Li, M.B., Biyun Chen, M.B., Liuxun Li, M.B., Liuxun Liu, M.B., Zhaoxin Zheng, M.B., Bo Xu, M.D.
The General Hospital of Guangzhou Military Command, Guangzhou, China
Disclosures: W. Tu: None. D. Zhou: None. Z. Li: None. B. Chen: None. L. Li: None. L. Liu: None. Z. Zheng: None. B. Xu: None.
Background: The α -adrenergic agonist dexmedetomidine is a sedative and can be used as an adjunct to anesthetics. However, the impact of obesity on dexmedetomidine pharmacokinetics has not been specifically examined. The goal of this study was to investigate the influence of morbid obesity on dexmedetomidine pharmacokinetics.

Methods: Eight morbidly obese subjects and eight matched normal weight subjects undergoing elective laparoscopic gastric surgery were included in the study. Dexmedetomidine 1μg /kg based on total body weight (TBW) was infused i.v. over 10 min before induction of anesthesia. Arterial blood samples for the measurement of plasma concentrations of dexmedetomidine were collected for 8 h after starting the infusion. Pharmacokinetic variables were determined using nonlinear mixed effects modeling (NONMEM program). Cardiorespiratory responses and sedation were recorded for 8 h.

Result:Plasma concentrations (C ) and area under the concentration-time curve (AUC ) were 47.64% (3.75±0.56 VS 2.54±0.32 μg/L, P<0.05) and 34.82% (130.43±20.07 VS 95.61±15.08 μg/L, P<0.05) higher in the morbidly obese patients. The volume of distribution (V ) and clearance (CLz) were increased by 89.53% (310.36±63.08 VS 163.75±40.91 L, P<0.05) and 30.51% (58.64±10.66 VS 44.93±9.00 L/h, P0.05) in two groups, and the TBW-normalized clearance (CLz/TBW) was 36.17% lower (0.47±0.07 VS 0.64±0.09 L, P<0.05) in contrast. The elimination half-time (t ) was 42.38% longer (225.19±55.54 VS 158.16±52.90 min, P<0.05) in the morbidly obese patients. Cardiovascular responses and sedation have no significant difference between two groups, but more obvious respiratory depression was found in the morbidly obese group.

Conclusion:The essential finding of the study is that pharmacokinetic of dexmedetomidine is appreciably different in morbidly obese versus normal weight subjects. To reach a certain plasma concentration, morbidly obese patients evidently need smaller initial doses of dexmedetomidine than the normal weight patients, as morbidly obese patients have a larger volume of distribution of the drug than normal weight patients. Clinically this means dexmedetomidine dosing regimens should be based on lean body weight (LBW) or ideal body weight (IBW) but not TBW.

References:

1. Ingrande J, Lemmens HJ: Anesthetic Pharmacology and the Morbidly Obese Patient. Curr Anesthesiol Rep 2013; 3: 10-17

2. Dere K, Sucullu I, Budak ET, Yeyen S, Filiz AI, Ozkan S, Dagli G: A comparison of dexmedetomidine versus midazolam for sedation, pain and hemodynamic control, during colonoscopy under conscious sedation. Eur J Anaesthesiol 2010; 27: 648-52

3. Tufanogullari B, White PF, Peixoto MP, Kianpour D, Lacour T, Griffin J, Skrivanek G, Macaluso A, Shah M, Provost DA: Dexmedetomidine infusion during laparoscopic bariatric surgery: the effect on recovery outcome variables. Anesth Analg 2008; 106: 1741-8

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