title: First pass lung uptake of bupivacaine: effect of acidosis in an intact rabbit lung model.
abstract: The first pass uptake, metabolism and recovery of bupivacaine were examined in an intact rabbit lung model using a multiple indicator technique with rapid sequential sampling. The rabbits were allocated to an acidotic group (pH 7.0-7.1) (n = 8) and a control group (n = 10) with normal pH. Bupivacaine recovery rates were not significantly different: median 93.2% (range 48.9-116.5%) and 94.5% (54.9-123.1%) in control and acidotic groups, respectively. Median peak percentage fractional concentrations of bupivacaine were greater in the acidotic group: 6.22% (2.5-7.65%) vs 4.1% (2.5-6.7%) (P less than 0.05). Median maximum instantaneous pulmonary percentage extraction was less in the acidotic animals than in animals with normal pH: 81.2% (47.1-91.9%) vs 91.0% (82.6-94.5%) (P less than 0.01). Median normalized mean percentage transit time was less in the acidotic group (245.3% (163.4-465.3%)) than in the control group (423.9% (313.9-740.4%)) (P less than 0.01). There was no evidence for bupivacaine metabolism by the lung. The results suggest that acidosis reduced bupivacaine lung uptake and increased its rate of passage through the lung, but did not influence overall drug recovery rates. This has clinical implications for bupivacaine related cardiac and cerebral toxicity.
authors.affiliation: Nuffield Department of Anaesthetics, Oxford.
authors.forename: M G
authors.initials: MG
authors.lastname: Palazzo
authors.forename: E A
authors.initials: EA
authors.lastname: Kalso
authors.forename: E
authors.initials: E
authors.lastname: Argiras
authors.forename: R
authors.initials: R
authors.lastname: Madgwick
authors.forename: J W
authors.initials: JW
authors.lastname: Sear
mesh_terms: D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002045:Bupivacaine / Q000097:blood / Q000493:pharmacokinetics*; D002302:Cardiac Output / Q000502:physiology; D008168:Lung / Q000378:metabolism*; D008954:Models, Biological; D011817:Rabbits
chemical_list: D002045:Bupivacaine