右美托咪啶在病态肥胖患者腹腔镜手术中的药代动力学和药效学
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Remifentanil added to sufentanil-sevoflurane anesthesia suppresses hemodynamic and metabolic stress responses to intense surgical stimuli more effectively than high-dose sufentanil-sevoflurane alone
目的
本研究旨在探讨右美托咪啶在病态肥胖患者腹腔镜手术中的药代动力学和药效学。
方 法
纳入16例行腹腔镜手术的重度肥胖患者(体重指数≥40 kg/m2)和正常体重患者，每组8例。测定基础血液动力学指标后，右美托咪啶1μg/kg，10 min内泵注。右美托咪啶静脉输注20 min后，异丙酚1.5mg/kg+芬太尼4μg/kg诱导全麻，气管插管后行机械通气，采用非房室模型分析右美托咪啶的药代动力学。右美托咪啶输注开始，连续测量血液动力学和外周氧饱和度（SpO2）30分钟 。采用警觉/镇静评分量表（OAA/s）评定镇静水平。
结 果
病态肥胖患者血浆峰浓度、曲线下面积、消除半衰期、表观体积明显大于正常体重患者（分别为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）。虽然肥胖患者的清除率也高于正常体重患者（58.6 ± 10.7 vs. 44.9 ± 9.0 l/h, P = 0.02），但肥胖患者标准化体重低于正常患者体重（0.47 ± 0.07 vs. 0.64 ± 0.09 l/h/kg, P < 0.001）。30分钟内两组收缩压、舒张压、心率无明显差异。与正常体重患者相比，在病态肥胖中镇静程度较深，SpO2较低。病态肥胖组使用右美托咪啶后，更多患者出现更深程度的镇静(P < 0.05)。
结 论
与正常体重组相比，病态肥胖患者右美托咪啶的药代动力学和药效学有显着性差异。重度肥胖患者的镇静水平明显高于正常体重患者，血氧饱和度明显低于正常体重患者，这可能是由于1.0 µg/kg泵注后血浆浓度较高所致。
原始文献摘要
Pharmacokinetic and pharmacodynamics of intravenous dexmedetomidine in morbidly obese patients undergoing laparoscopic surgery.J Anesth. 2017 Dec;31(6):813-820. doi: 10.1007/s00540-017-2399-y. Epub 2017 Aug 21. Xu B, Zhou D,Ren L
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.
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