Bo Xu1, Dongxu Zhou2,3, Li Ren2,4, Steven Shulman5, Xingan Zhang2, Ming Xiong6. 1. Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, 510010, China. xubo333@hotmail.com. 2. Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, 510010, China. 3. Department of Anesthesiology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, 441021, China. 4. Department of Anesthesiology, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, 519000, China. 5. Department of Anesthesiology, Rutgers-NJMS, Newark, NJ, 07101, USA. 6. Department of Anesthesiology, Rutgers-NJMS, Newark, NJ, 07101, USA. xiong@njms.rutgers.edu.
Abstract
BACKGROUND: This study was designed to investigate the pharmacokinetics and pharmacodynamics of dexmedetomidine in morbidly obese patients undergoing laparoscopic surgery. METHODS: Morbidly obese (body mass index ≥40 kg/m2) and normal weight patients scheduled for elective laparoscopic surgery were included (n = 8, each group). After baseline hemodynamic measurement, dexmedetomidine 1 μg/kg was administered over 10 min. General anesthesia was induced with propofol 1.5 mg/kg and fentanyl 4 μg/kg 20 min 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. RESULTS: 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 ± 0.32 µg/l, P < 0.001; 2174 ± 335 vs. 1594 ± 251 ng h/l, P < 0.001; 225 ± 55 vs. 158 ± 53 min, 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 30 min. 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). CONCLUSION: 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 1.0 µg/kg. CLINICAL TRIAL NUMBER, REGISTRY URL: ClinicalTrials.gov (NCT01864187), https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=1&cx=-jg9qo4 .
BACKGROUND: This study was designed to investigate the pharmacokinetics and pharmacodynamics of dexmedetomidine in morbidly obesepatients undergoing laparoscopic surgery. METHODS: Morbidly obese (body mass index ≥40 kg/m2) and normal weight patients scheduled for elective laparoscopic surgery were included (n = 8, each group). After baseline hemodynamic measurement, dexmedetomidine 1 μg/kg was administered over 10 min. General anesthesia was induced with propofol 1.5 mg/kg and fentanyl 4 μg/kg 20 min 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. RESULTS: 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 ± 0.32 µg/l, P < 0.001; 2174 ± 335 vs. 1594 ± 251 ng h/l, P < 0.001; 225 ± 55 vs. 158 ± 53 min, P = 0.02; 310 ± 63 vs. 164 ± 41 l, P < 0.001, respectively). Although clearance was also higher in obesepatients than in normal body weight patients (58.6 ± 10.7 vs. 44.9 ± 9.0 l/h, P = 0.02), it was lower in obesepatients 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 30 min. Sedation level was deeper and SpO2 was lower in morbidly obese than in normal weight patients. More patients in the morbidly obesepatient group experienced deeper sedation after the start of the dexmedetomidine infusion (P < 0.05). CONCLUSION: The pharmacokinetics and pharmacodynamics of dexmedetomidine are significantly different in morbidly obesepatients 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 1.0 µg/kg. CLINICAL TRIAL NUMBER, REGISTRY URL: ClinicalTrials.gov (NCT01864187), https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=1&cx=-jg9qo4 .
Authors: Utkarsh Kohli; Pratik Pandharipande; Mordechai Muszkat; Gbenga G Sofowora; Eitan A Friedman; Mika Scheinin; Alastair J J Wood; E Wesley Ely; Rachel F Tyndale; Leena Choi; C Michael Stein; Daniel Kurnik Journal: Eur J Clin Pharmacol Date: 2012-01-21 Impact factor: 2.953
Authors: Luis I Cortínez; Brian J Anderson; Nick H G Holford; Valentina Puga; Natalia de la Fuente; Hernán Auad; Sandra Solari; Fidel A Allende; Mauricio Ibacache Journal: Eur J Clin Pharmacol Date: 2015-09-26 Impact factor: 2.953
Authors: Burcu Tufanogullari; Paul F White; Mariana P Peixoto; Daniel Kianpour; Thomas Lacour; James Griffin; Gary Skrivanek; Amy Macaluso; Mary Shah; David A Provost Journal: Anesth Analg Date: 2008-06 Impact factor: 5.108
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