Sevoflurane has been reported as a good option for anaesthesia management of obese patients . Nonetheless, obesity markedly affects the cardiovascular and respiratory systems, resulting in increased circulating volume and resting cardiac output , and decreased functional residual capacity (FRC) and total lung capacity . These changes in respiratory and cardiovascular function, as well as the increased body size and different proportion of lean and fat tissues in body composition can potentially affect the wash-in and wash-out kinetics of inhalation anaesthetics in obese patients . Since no data were available in the literature, we conducted a prospective, case-control study to evaluate the effects of morbid obesity on wash-in and wash-out kinetics of sevoflurane.
Our study was approved by our Institutional Ethics Committee and written informed consent obtained from patients. The wash-in and wash-out kinetics of sevoflurane were determined in seven obese, ASA II-III patients undergoing laparoscopic silicone-adjustable gastric banding. These kinetics were compared from measurements in seven non-obese patients (actual body weight ranging within ±10% of ideal body weight) undergoing laparoscopic cholecystectomy, and matched with respect to sex, age and co-existing diseases. Morbid obesity was defined as a body mass index (BMI) >35 kg m−2, calculated as body weight (kg) divided by height squared (m2). Patients with hypoventilation syndrome, chronic obstructive lung disease, myocardial infarction and congestive heart failure were excluded.
After oral premedication with diazepam (0.1 mg kg−1), general anaesthesia was induced with fentanyl (1 mg kg−1) and thiopental (6 mg kg−1) intravenously (i.v.); in the obese patients, doses were referred to ideal body weight. Endotracheal intubation was facilitated with succinylcholine (1 mg kg−1 i.v.), and further muscle relaxation provided with atracurium (0.4 mg kg−1 h−1). Intermittent positive pressure ventilation of the lungs was applied using a Servo-900C® lung ventilator with a non-rebreathing system and a fresh gas flow of 15 L min−1 (Siemens, Germany). During all measurements the ventilator was set to a tidal volume of 10 mL kg−1, a ventilatory frequency of 12 breaths min−1, and an inspiratory to expiratory time ratio of 1 : 2, using an oxygen/air mixture (FiO2 = 0.5), while supplemental boluses of thiopental or fentanyl were given as indicated in order to maintain blood pressure and heart rate values within ±20% of baseline.
After adequate placement of an endotracheal tube and stabilization of the ventilation variables, sevoflurane 2% was given for 30 min via a non-rebreathing circuit, while ports permitted sampling of inspired (FI), and end-tidal (FA) gases . The end-tidal of inhalation agent was measured using an infrared gas analyser (RGM 5250®; Ohmeda Medical, Wisconsin, USA) previously calibrated according to the manufacturer's instructions. The wash-in kinetics of sevoflurane was determined by recording, every 5 min, the end-tidal concentration from the first breath for 30 min; then surgery started.
General anaesthesia was then maintained with sevoflurane 1.5-2% in an oxygen/air mixture (FiO2 = 0.5), while fentanyl 50 μg boluses were given to maintain arterial pressure and heart rate within ±20% of baseline values. After the last skin suture, the end-tidal sevoflurane concentration was recorded from five consecutive breaths before discontinuation; then the end-tidal sevoflurane concentration was recorded at 30 s intervals from 0 to 5 min after discontinuation. The fresh gas flow and ventilatory parameters were set at the same values of the wash-in period and maintained constant throughout the wash-out period.
Data were analysed with a two-way analysis of variance for repeated measures, while t-test for unpaired data was used for inter-group comparisons. P < 0.05 was considered significant. Mean age was 39 ± 6 yr for patients in the obese group and 39 ± 7 yr for those in the non-obese group; while six females and one male were enrolled in each group. Obese patients had a mean BMI of 42 (±4) kg m−2, while the non-obese group had a mean BMI of 22 (±3) kg m−2. No differences in the end-tidal concentration of sevoflurane required during anaesthesia maintenance and in the CO2 end-tidal concentrations were reported between the two groups throughout the study. Haemodynamic variables were stable throughout in both groups, without differences between the two study groups during either wash-in or wash-out kinetic determinations (data are not presented). The alveolar to inspiratory fraction (FA/FI) was higher in obese patients 1 min after starting the administration of sevoflurane (Fig. 1a); but no further differences were observed between obese and non-obese patients. The wash-out curve of sevoflurane (FA/FA0) was slower in obese patients compared with non-obese ones, and the FA/FA0 ratio was higher in obese patients from 0.5 to 2.5 min after discontinuation of sevoflurane administration (Fig. 1b). No differences in the FA/FA0 ratio were reported between the two groups of patients, 5 min after sevoflurane had been discontinued.
A possible explanation for the more rapid increase of the FA/FI ratio observed in obese patients during the first minute of administration could be related to the reduction of FRC induced by obesity , since the wash-in kinetics of inhalation agents is hastened with reduced FRC . On the contrary, the wash-out kinetics of sevoflurane elimination was slightly slower in obese than non-obese patients. The rate of FA/FA0 decrease of an inhalation agent is governed by lung ventilation and delivery of the anaesthetic to the lungs from the body tissue, which is determined by the solubility of the drug, cardiac output and venous-to-alveolar anaesthetic partial pressure difference . Even though the blood/gas partition coefficient of sevoflurane is very small (0.69), its tissue/blood partition coefficient is relatively large ; consequently, it may be speculated that the increased amount of sevoflurane taken up by fat tissue in the obese patients could delay the wash-out kinetics compared to non-obese patients by increasing the anaesthetic delivery to the lung from the body tissues after discontinuation. This could be also partly related to the increase in cardiac output induced by obesity .
Even though significant, the observed differences in wash-in and wash-out kinetics of sevoflurane between obese and non-obese patients are minimal, short lasting and, reasonably, without clinically relevant effects on awakening time, since 5 min after sevoflurane discontinuation no differences were observed between obese and non-obese patients. Although body mass has been demonstrated significantly to affect the pharmacokinetic properties of inhalation agents , results of this prospective, case-control study suggest that obesity results in minimal and not clinically relevant effects on the wash-in and wash-out curves of sevoflurane.
Department of Anesthesiology; Vita-Salute University of Milano; IRCCS San Raffaele Hospital; Milan, Italy
1. Torri G, Casati A, Albertin A, et al.
A prospective randomized comparison between isoflurane or sevoflurane anesthesia for laparoscopic gastric banding in morbidly obese patients. J Clin Anesth
2. Palmieri V, de Simone G, Arnett DK, et al.
Relation of various degrees of body mass index in patients with systemic hypertension to left ventricular mass, cardiac output, and peripheral resistance (the hypertension genetic epidemiology network study). Am J Cardiol
3. Pelosi P, Croci M, Ravagnan I, Vicardi P, Gattinoni L. Total respiratory system, lung, and chest wall mechanics in sedated paralyzed postoperative morbidly obese patients. Chest
4. Wahrenbrock EA, Eger II EI, Laravuso RB, Maruschak G. Anesthetic uptake - of mice and man (and whales). Anesthesiology
5. Yasuda N, Lockhart SH, Eger II EI, et al.
Comparison of kinetics of sevoflurane and isoflurane in humans. Anesth Analg
6. Pelosi P, Croci M, Ravagnan I, et al.
The effects of body mass on lung volumes, respiratory mechanics, and gas exchange during general anesthesia. Anesth Analg
7. Yasuda N, Targ AG, Eger EI II. Solubility of I-653, sevoflurane, isoflurane, and halothane in human tissues. Anesth Analg