Newborn Tissue Concentrations of Bupivacaine following Maternal Epidural Administration during Labor in Guinea Pigs

Abstract

Newborn plasma concentrations of maternally administered bupivacaine are often measured, but it is unclear how well they reflect tissue concentrations. Bupivacaine (0.25%) was administered epidurally (0.12 ml/kg) 10 min prior to labor induction in 6 term-pregnant guinea pigs. Plasma, brain, heart and liver samples were obtained for bupivacaine analysis from newborns (n = 22) after spontaneous delivery. Liver bupivacaine concentrations were 2–3 times greater than those in the plasma, brain, and heart. A similar pattern of tissue concentrations was seen in a smaller number of newborns delivered by cesarean section. Liver bupivacaine concentration decreased with drug-delivery interval in littermates, while heart and brain concentrations showed no relationship with drug-delivery interval. Blood gases of newborns reflected acidosis, which may have influenced tissue drug concentrations. Under conditions of the study, bupivacaine concentrations in heart and brain, potential sites of bupivacaine action, were lower than those observed in a peripheral blood sample.

Determination of bupivacaine tissue concentration in human biopsy samples using high‐performance liquid chromatography with mass spectrometry

“…Repeated freezing and thawing for three times did not affect the stability of local anesthetics. The results are congruent with the literature where bupivacaine and lidocaine proved to be very stable in tissues and in different solvents (Cho et al, 2017; Golub et al, 1998; Scherpenisse & Bergwerff, 2007; Siddareddy et al, 2017).…”

“…The determination coefficients (R 2 ) were higher than 0.9957 for bupivacaine determination from all tested human tissues which demonstrates good linearity of all calibration curves, while the lack‐of‐fit test showed adequacy of obtained models (Table 2). The concentration range tested in our study covers the clinically relevant concentrations of bupivacaine in the μg g −1 range which are significantly higher than those tested in previous studies that determined the traces of bupivacaine in different animal tissues in the ng g −1 range (Cho et al, 2017; Golub et al, 1998).…”

“…We developed and tested a method for determination of bupivacaine tissue concentration in human adipose, muscle, neural, connective and cartilage tissue biopsy samples. Compared with previous studies that developed methods to determine local anesthetic tissue concentrations, we used human tissues and significantly smaller tissue samples (500 mg) that are expected to be obtained during tissue biopsy (Cho et al, 2017; Golub et al, 1998; Keegan et al, 1996; Scherpenisse & Bergwerff, 2007). The method was tested in the concentration range of 0.16 to 100.00 μg g −1 because the estimated minimal effective tissue concentrations of local anesthetics are in the μg g −1 range (Keegan et al, 1996; McDonald et al, 2002).…”

“…Furthermore, because bupivacaine and lidocaine are amphipathic molecules that have known interactions with biological membranes and could accumulate at the interphase between polar and non‐polar solvents (Högberg et al, 2007; Tsuchiya & Mizogami, 2013), we tested whether local anesthetics will substantially accumulate at the acetonitrile/ n ‐hexane interphase during acid extraction (Figure 2B). Approximately 30% of bupivacaine and 36% of lidocaine accumulated at the acetonitrile/ n ‐hexane interphase; therefore, in contrast to other liquid–liquid extraction methods of local anesthetics from tissue samples (Cho et al, 2017; Golub et al, 1998; Scherpenisse & Bergwerff, 2007), we decided to include the collection of acetonitrile/ n ‐hexane interphase during the extraction process.…”

“…HPLC was successfully employed for determination of mepivacaine concentrations in equine synovial tissue and bone samples (Keegan et al, 1996). Similarly, bupivacaine concentrations in heart, liver and brain tissues of neonatal guinea pigs were determined using GC–MS (Golub et al, 1998), while bupivacaine and tricaine concentrations in beef, porcine and fish meat samples were determined using HPLC–MS (Cho et al, 2017; Scherpenisse & Bergwerff, 2007). To date, there is no analytical method for determination of bupivacaine concentration across the wide concentration range (from minimally tissue effective concentrations to tissue concentrations expected at injection site) in very small biopsy samples of different human tissues with markedly diverse compositions.…”