FACTORS INFLUENCING PRECIPITATION OF pH-ADJUSTED BUPIVACAINE SOLUTIONS

Abstract

Solutions of bupivacaine precipitate when bicarbonate is added. This limits the clinical use of pH-adjustment in optimizing bupivacaine activity. In this study four different bupivacaine solutions were studied with the addition of sodium bicarbonate at 4 degrees C or 20 degrees C. Bupivacaine concentrations remained unchanged after pH-adjustment. Least crystallization was observed with bupivacaine solutions containing a small amount of sodium bicarbonate and stored at 4 degrees C.

Alkalinization of amide local anaesthetics by addition of 1% sodium bicarbonate solution

“…While in the present study examination of the alkalinized solution using microscopy both before and after centrifugation, failed to demonstrate evidence of precipitate formation, previous studies using particle counters have demonstrated an increased number of particles up to 25 μm after alkalinization of similar local anaesthetic solutions to a pH of ≅7 [12,13]. However, particulate numbers have never exceeded the numbers set by the USP for small volume injections [14].…”

The Polyanalgesic Consensus Conference (PACC): Recommendations for Intrathecal Drug Delivery: Guidance for Improving Safety and Mitigating Risks

“…Prior to that admixture, the patient received IT morphine monotherapy for seven years. Bupivacaine is known to precipitate in the presence of sodium bicarbonate , but this was unlikely in this case. In addition, bupivacaine has been shown to be stable in admixture with opioids and clonidine .…”

Identification of the precipitate in alkalinized solutions of mepivacaine and bupivacaine at 37 oC

“…In clinical practice, solutions equilibrate at 37 °C when they are injected into body tissues. The pKa of local anaesthetics decreases with temperature (4–6). Thus, the relative amount of free base increases with temperature at constant pH.…”