Introduction Amino-amide local anesthetics precipitate when mixed with some commonly used adjuvants, carrying the risk of perineural or vascular crystal deposition. The aim of this study was to evaluate whether crystallization occurs with routinely used local anesthetic–adjuvant combinations and if a relation with the solution’s pH exists.
Methods All substances used in this trial were first visually investigated undiluted under tenfold magnification. Grade of crystallization was assessed using a 6 point grading system.
Ropivacaine (0.2%, 0.75% and 1%) and bupivacaine (0.25% and 0.5%) were mixed in a 1:1 solution with the following adjuvants: dexamethasone, dexmedetomidine, clonidine, fentanyl, sodium bicarbonate 8.4% and sodium chloride 0.9%. Subsequently, ropivacaine (0.2% and 0.75%) and bupivacaine (0.25% and 0.5%) were mixed with adjuvants in concentrations commonly used in clinical practice and then serially assessed at several time points up to 1 hour. pH of all substances/combinations was assessed and correlated with crystallization grade.
Results All pure substances—except the reference standards sterile water and triamcinolon—showed crystallization grades ranging from grade 1 to grade 4. Addition of adjuvants lead to variable, unpredictable changes in crystal depositions. Addition of sodium bicarbonate 8.4% produced heavy crystallization in all combinations. Grade of crystallization was weakly positively related to the pH of the solution in 1:1 mixtures and clinically relevant concentrations, but not in pure substances.
Discussion Our study showed that crystallization is present in pure local anesthetics and may be increased or decreased by admixture of adjuvants. Higher pH of mixtures was weakly associated with more crystallization. Further research is necessary to translate these findings into clinical practice.
- anesthesia, local
- pain management
Data availability statement
Data are available on reasonable request. Raw data/full-resolution images are available on request.
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Contributors EH is the guarantor for this work. EH, OS, TS and LG developed the research protocol. EH, OS, GP, SM and LG performed laboratory tests. GP, TS and LG provided methodological consultation. EH, TS and LG wrote the initial draft of the manuscript. All authors reviewed the manuscript. All authors helped revise the manuscript. EH, OS and LG finalized the initial and revised manuscripts.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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