Lemmens Hendrikus J M, Saidman Lawrence J, Eger Edmond I, Laster Michael J
Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA.
Anesth Analg. 2008 Dec;107(6):1864-70. doi: 10.1213/ane.0b013e3181888127.
Few studies have determined the effect of obesity on inhaled anesthetic pharmacokinetics. We hypothesized that the solubility of potent inhaled anesthetics in fat and increased body mass index (BMI) in obese patients interact to increase anesthetic uptake and decrease the rate at which the delivered (FD) and inspired (FI) concentrations of an inhaled anesthetic approach a constantly maintained alveolar concentration (end-tidal or FA). This hypothesis implies that the effect of obesity would be greater with a more soluble anesthetic such as isoflurane versus desflurane.
In 107 ASA physical status I-III patients, anesthesia was induced with propofol, tracheal intubation facilitated with neuromuscular blockade, and ventilation controlled with 50% nitrous oxide in oxygen to maintain end-tidal carbon dioxide concentrations between 35 and 45 mm Hg. Isoflurane or desflurane was administered in a 1 L/min inflow rate at FD concentrations sufficient to maintain FA at 0.6 minimum alveolar anesthetic concentration (0.7% or 3.7%, respectively). FD, FI, and FA were measured 5, 10, 20, 40, 60, 90, 120,150, and 180 min after starting potent inhaled anesthetic delivery.
Fifty-nine patients received isoflurane and 48 received desflurane. BMI ranged between 18 and 63 kg/m(2) and demographic variables did not differ between anesthetic groups. For isoflurane, FD/FA or FI/FA weakly (but significantly) correlated with BMI at 9/18 time points whereas for desflurane FD/FA or FI/FA correlated significantly with BMI at only one time point (P < 0.01). After dividing each group into nonobese (BMI < 30) and obese (BMI > or = 30) patients, with isoflurane, FD/FA or FI/FA was higher in obese patients at four time points whereas there was no difference between nonobese and obese patients for desflurane. Patients receiving isoflurane took longer to respond to command after discontinuing anesthesia but obesity did not increase or decrease awakening time for either isoflurane or desflurane. When BMI was used to normalize FI/FA and FD/FA the median values for isoflurane consistently exceeded the median value for desflurane by factors ranging from 3 to 5, values comparable to the ratios of their blood/gas (3.1), muscle/gas (4.6), and fat/gas (5.4) partition coefficients.
BMI modestly affects FD/FA and FI/FA, and this effect is most apparent for an anesthetic having a greater solubility in all tissues. An increased BMI increases anesthetic uptake and, thus, the need for delivered anesthetic to sustain a constant alveolar anesthetic concentration, particularly with a more soluble anesthetic. However, the increase with an increased body mass is small.
很少有研究确定肥胖对吸入麻醉药药代动力学的影响。我们假设,强效吸入麻醉药在脂肪中的溶解度以及肥胖患者体重指数(BMI)的增加相互作用,会增加麻醉药摄取,并降低吸入麻醉药的输送浓度(FD)和吸入浓度(FI)接近持续维持的肺泡浓度(呼气末或FA)的速率。该假设意味着,与地氟烷相比,肥胖对溶解度更高的麻醉药如异氟烷的影响更大。
对107例美国麻醉医师协会(ASA)身体状况I-III级的患者,用丙泊酚诱导麻醉,使用神经肌肉阻滞剂辅助气管插管,并通过在氧气中加入50%氧化亚氮进行通气控制,以维持呼气末二氧化碳浓度在35至45 mmHg之间。以1 L/min的流速给予异氟烷或地氟烷,FD浓度足以将FA维持在0.6最低肺泡麻醉浓度(分别为0.7%或3.7%)。在开始给予强效吸入麻醉药后5、10、20、40、60、90、120、150和180分钟测量FD、FI和FA。
59例患者接受异氟烷,48例患者接受地氟烷。BMI在18至63 kg/m²之间,各麻醉组的人口统计学变量无差异。对于异氟烷,FD/FA或FI/FA在9/18个时间点与BMI呈弱(但显著)相关,而对于地氟烷,FD/FA或FI/FA仅在一个时间点与BMI显著相关(P < 0.01)。将每组患者分为非肥胖(BMI < 30)和肥胖(BMI >或= 30)患者后,使用异氟烷时,肥胖患者在四个时间点的FD/FA或FI/FA较高,而使用地氟烷时,非肥胖和肥胖患者之间无差异。接受异氟烷的患者在停止麻醉后对指令的反应时间较长,但肥胖并未增加或减少异氟烷或地氟烷的苏醒时间。当用BMI对FI/FA和FD/FA进行标准化时,异氟烷的中位数始终比地氟烷的中位数高出3至5倍,这些值与它们的血/气(3.1)、肌肉/气(4.6)和脂肪/气(5.4)分配系数的比值相当。
BMI适度影响FD/FA和FI/FA,这种影响在所有组织中溶解度更高的麻醉药中最为明显。BMI增加会增加麻醉药摄取,因此需要输送更多麻醉药以维持恒定的肺泡麻醉浓度,尤其是对于溶解度更高的麻醉药。然而,随着体重增加的变化很小。