Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48109-5048, USA.
Anesth Analg. 2012 Feb;114(2):297-302. doi: 10.1213/ANE.0b013e31823ede22. Epub 2011 Dec 13.
Morbid obesity affects the pharmacokinetics and pharmacodynamics of anesthetics, which may result in inappropriate dosing. We hypothesized that obesity significantly alters the minimum alveolar concentration (MAC) for isoflurane and sevoflurane. To test this hypothesis, we used a rodent model of human metabolic syndrome developed through artificial selection for inherent low aerobic capacity runners (LCR) and high aerobic capacity runners (HCR). The LCR rats are obese, display phenotypes homologous to those characteristic of human metabolic syndrome, and exhibit low running endurance. In contrast, HCR rats have high running endurance and are characterized by improved cardiovascular performance and overall health.
Male and female LCR (n = 10) and HCR (n = 10) rats were endotracheally intubated and maintained on mechanical ventilation with either isoflurane or sevoflurane. A bracketing design was used to determine MAC; sensory stimulation was induced by tail clamping. An equilibration period of 30 minutes was provided before and between the consecutive tail clamps. Two-tailed parametric (unpaired t test) and nonparametric (Mann-Whitney test) statistics were used for the comparison of MAC between LCR and HCR rats. The data are reported as mean ± sd along with the 95% confidence interval. A P value of <0.05 was considered statistically significant.
The MAC for isoflurane in LCR rats (1.52% ± 0.13%) was similar to previously reported isoflurane-MAC for normal rats (1.51% ± 0.12%). The HCR rats showed a significantly higher isoflurane-MAC (1.90% ± 0.19%) than did the LCR rats (1.52% ± 0.13%) (P = 0.0001). The MAC for sevoflurane was not significantly different between LCR and HCR rats and was similar to the previously published sevoflurane-MAC for normal rats (2.4% ± 0.30%). There was no influence of sex on the MAC of either isoflurane or sevoflurane.
Obesity and associated comorbidities do not affect anesthetic requirements as measured by MAC in a rodent model of metabolic syndrome. By contrast, high aerobic capacity is associated with a higher MAC for isoflurane and may be a risk factor for subtherapeutic dosing.
病态肥胖会影响麻醉的药代动力学和药效动力学，从而导致用药不当。我们假设肥胖会显著改变异氟醚和七氟醚的肺泡最低有效浓度（MAC）。为了验证这一假设，我们使用了一种通过人工选择开发的人类代谢综合征啮齿动物模型，该模型通过选择固有低有氧能力的跑步者（LCR）和高有氧能力的跑步者（HCR）。LCR 大鼠肥胖，表现出与人类代谢综合征特征相似的表型，并表现出低耐力跑步能力。相比之下，HCR 大鼠具有高耐力跑步能力，其心血管性能和整体健康状况得到改善。
雄性和雌性 LCR（n = 10）和 HCR（n = 10）大鼠行气管内插管，并使用异氟醚或七氟醚机械通气维持。采用加框设计来确定 MAC；通过夹尾刺激来诱导感觉刺激。在连续夹尾之前和之间提供 30 分钟的平衡期。使用双尾参数（未配对 t 检验）和非参数（Mann-Whitney 检验）统计方法比较 LCR 和 HCR 大鼠之间的 MAC。数据以平均值 ± sd 以及 95%置信区间报告。P 值 <0.05 被认为具有统计学意义。
LCR 大鼠的异氟醚 MAC（1.52%±0.13%）与之前报道的正常大鼠异氟醚-MAC（1.51%±0.12%）相似。HCR 大鼠的异氟醚-MAC 显著高于 LCR 大鼠（1.90%±0.19%）（P = 0.0001）。LCR 和 HCR 大鼠的七氟醚 MAC 无显著差异，与之前报道的正常大鼠七氟醚-MAC（2.4%±0.30%）相似。性别的差异对异氟醚或七氟醚的 MAC 没有影响。
在代谢综合征的啮齿动物模型中，肥胖症和相关的合并症不会影响麻醉药的需求，这是通过 MAC 来衡量的。相比之下，高有氧能力与异氟醚的较高 MAC 相关，可能是治疗剂量不足的一个风险因素。
