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M.I. Triana, R. Jones, III, J.C. MacDonald, R. Glickman; Formulation of an Optimized Local Anesthetic for Ophthalmic Procedures . Invest. Ophthalmol. Vis. Sci. 2005;46(13):472.
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Purpose:Sodium bicarbonate 8.4% (NaHCO3) is added to local anesthetic solutions to improve the comfort of injection, hasten the onset of action, and prolong the duration of action. Bupivacaine 0.75% (BUP) has a long duration of action. Alkalinization is limited by the formation of a precipitate that is toxic to tissue. Lidocaine 2% (LID) has a shorter onset of action, remains precipitate–free when alkalinized, but is limited by a shorter duration of action. Ophthalmologists use a 50:50 mixture of BUP and LID (BL50) to obtain the benefits of both. Alkalinization of individual anesthetic agents has been studied. To date, no study has quantified the amount of NaHCO3 that can be added to BL50 without forming a precipitate. Moreover, no study has considered tromethamine (THAM) as an alternative to NaHCO3. Methods: The pH of BUP, LID, BL50, NaHCO3, sodium acetate 16.4% (NaOAc), and 0.3 M THAM were measured. In separate beakers, 10 ml aliquots of BUP or BP50 were studied in triplicate. Small increments of NaHCO3, NaOAc, or THAM were added to each of the beakers. The pH was measured while visually monitoring for clouding or dense precipitate (dp) formation. Optimal ratios of alkalinizing agent to anesthetic were determined. Results: BUP pH=5.11, LID pH=5.99, BL50 pH=6.00, NaHCO3 pH=9.08, NaOAc pH=8.69, and THAM pH=11.03. Alkalinization of 10 ml BUP resulted as follows: NaHCO3: clouded at pH 6.76 (25 µl) and formed a dp at pH 6.81 (30 µl); NaOAc: clouded at pH 6.87 (960 µl) and formed a dp at pH 6.94 (1600 µl); THAM: clouded at pH 6.68 (20 µl) and formed a dp at pH 6.93 (80 µl). Alkalinization of 10 ml of BL50 resulted as follows: NaHCO3: clouded at pH 6.93 (50 µl) and formed a dp at pH 7.02 (70 µl); NaOAc: remained clear with an addition of 1520 µl (pH 6.78); THAM: clouded at pH 6.96 (50 µl) but did not form a dp at pH 7.0 (60 µl). Conclusions: BUP alone should not be alkalinized with NaHCO3 or THAM due to precipitate formation. NaOAc could theoretically be used with BUP at a ratio of 1.5:10 ml to form an alkalinized, precipitate–free (optimized) BUP–only injection. In comparison, BL50 was easier to alkalinize. Only 0.4 ml of NaHCO3 was needed to create an optimized solution with BL50 (pH 6.83). Small volumes of NaOAc did not adequately raise the pH, so it was eliminated as a potential alkalinizing agent. Finally, 0.4 ml of THAM was needed to create an optimized solution with BL50 (pH 6.88). In conclusion, the maximum pH of optimized BL50 is 6.8 and can be obtained by adding 0.4 ml of NaHCO3 or THAM to 10 ml of BL50. THAM does not raise serum Na+ or K+ and may be useful in patients with hypernatremia.
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