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Alkalinization and Precipitation Characteristics of 0.2% Ropivacaine
  1. Paul D. Fulling, M.D. and
  2. Robert A. Peterfreund, M.D., Ph.D.
  1. From the Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
  1. Reprint requests: Robert A. Peterfreund, M.D., Ph.D., Department of Anesthesia and Critical Care, Massachusetts General Hospital, Clinics 314D, 55 Fruit St, Boston, MA 02114.

Abstract

Background and Objectives Alkalinization of local anesthetics has been used to increase the speed of onset of nerve blocks. However, alkalinization of local anesthetic solutions may cause precipitation, thereby decreasing bioavailability and anesthetic activity. Alkalinization of ropivacaine has not been described. This laboratory study assessed the alkalinization and precipitation characteristics of ropivacaine.

Methods Aliquots (2 mL) of commercially available ropivacaine (Naropin, 0.2%; Astra Pharmaceutical, West-borough, MA) were alkalinized with increasing amounts (0.01, 0.02, 0.04 mL) of sodium bicarbonate (8.4%) and immediately monitored for pH change and onset of visible precipitation at room temperature. We then alkalinized ropivacaine with sodium bicarbonate and measured the amount of precipitate that accumulated after various incubation times.

Results The pH of ropivacaine increases with the addition of small amounts of bicarbonate. The calculated percentage of nonionized ropivacaine increased from 0.3% to greater than 30% with alkalinization from pH of 5.51 to 7.63. Drug loss to precipitation increased with higher doses of bicarbonate, reaching 25% to 30% of the total ropivacaine. Even with a low dose of bicarbonate (0.1 mL bicarbonate/20 mL ropivacaine), precipitation increased with time of incubation, reaching a plateau at 20 minutes.

Conclusions A laboratory evaluation that establishes the alkalinization characteristics of ropivacaine is a prerequisite for designing a clinical study of alkalinized ropivacaine. In our experiment, low doses of bicarbonate produced significant increases in the proportion of nonionized ropivacaine with only modest precipitation. There would be a low likelihood of substantial drug precipitation if the mixture was administered within 5 to 10 minutes after alkalinization. These results indicate that alkalinized ropivacaine should not be used for infusions and that ropivacaine should not be alkalinized until just before use.

  • Ropivacaine
  • Local anesthetics
  • Alkalinization
  • pH adjustment

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Footnotes

  • Presented in part in abstract form at the American Society of Anesthesiologists Annual Meeting, October 19, 1998, Orlando, FL.

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