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.

Intravenous Lipid Emulsion for Levobupivacaine Intoxication in Acidotic and Hypoxaemic Pigs

“…There are at least two major reasons why this kind of acidosis worsens the cardiotoxicity of local anaesthetics: one is iontrapping into the cardiac tissue 25 and another is decreased binding of the compound in blood allowing enhanced tissue uptake 26 , and consequently increased binding of the local anaesthetic to sodium channels 19 . The decreased first-pass lung uptake of local anaesthetics because of acidosis, experimentally shown in rabbits 27 , may be a third separate mechanism of enhanced toxicity.…”

Drug handling by the lungs

“…In isolated rat lungs, the ®rst-pass retention of bupivacaine, measured by a double-indicator dilution technique, was small (6±7%), despite an initial peak extraction of 81±91%. 74 Others have shown extensive pulmonary uptake (®rst-pass retention up to 81%) in the lungs of rabbits. 97 102 There could be signi®cant differences between species in the pulmonary uptake of bupivacaine.…”

“…In rabbit lungs, a decrease in the acidity of the blood (pH 7.0±7.1) reduced pulmonary extraction and caused a 50% increase in the median peak bupivacaine concentration in the ef¯uent blood after bolus injection. 74 Pulmonary uptake of bupivacaine decreases with increasing dose, repeated administration and pretreatment with propranolol. 97 Pulmonary metabolism of bupivacaine appears to be very small.…”