title: Obesity modestly affects inhaled anesthetic kinetics in humans.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA. hlemmens@stanford.edu
authors.forename: Hendrikus J M
authors.initials: HJ
authors.lastname: Lemmens
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Saidman
authors.forename: Edmond I
authors.initials: EI
authors.lastname: Eger
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Laster
mesh_terms: D000328:Adult; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics*; D015992:Body Mass Index; D000077335:Desflurane; D004058:Diffusion; D005260:Female; D006801:Humans; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*
chemical_list: D018685:Anesthetics, Inhalation; D000077335:Desflurane; D007530:Isoflurane