Microscopic Evaluation of Crystallization Dynamics in 0.25% Levobupivacaine Mixed with Common Regional Anaesthesia Adjuvants: An in vitro Compatibility Study.
- 1Republican Scientific Centre of Emergency Medicine, Department of Anaesthesiology and Reanimation, Tashkent, Uzbekistan.
Abstract
Objective
To investigate the crystallization dynamics of 0.25% levobupivacaine when combined with common regional anaesthesia adjuvants.Methods
This in vitro study examined mixtures of 0.25% levobupivacaine with dexamethasone (20:1), 25% magnesium sulfate (20:1.5), dexmedetomidine (20:1), 8.4% sodium bicarbonate (10:1), and adrenaline (1:100,000). The study protocol was an in vitro investigation. Since no human or animal subjects were involved, the study was exempt from formal ethics committee approval. An institutional waiver was obtained from the Ministry of Health of the Republic of Uzbekistan Research Administration of the Republican Scientific Emergency Medical Centre (ref no: 03-05/119, date: 15.01.2026). All mixtures were incubated at 37 °C and examined under light microscopy (40× magnification) immediately, at 15 minutes, and at 1 hour. Crystallization onset, crystal count, and crystal size were quantified. For accurate dimensional analysis, a stage micrometer was used to calibrate the digital imaging software, and a calibrated scale bar was superimposed on each micrograph. Statistical analyses were performed using IBM SPSS Statistics for Windows, version 30.0 (IBM Corp., Armonk, NY, USA). Overall changes across the three matched assessment times were evaluated using the Friedman test. Significant omnibus results were followed by paired Wilcoxon signed-rank tests with Holm adjustment for multiple comparisons. All tests were two-sided, and a P value <0.05 was considered statistically significant.Results
Solutions containing sodium bicarbonate and dexamethasone demonstrated the earliest onset of crystallization. Sodium bicarbonate (10:1) produced immediate and massive precipitation. Levobupivacaine-dexamethasone mixtures showed progressive crystallization, with particle counts exceeding 100 per field for particles larger than 10 μm within 60 minutes. Adrenaline, magnesium sulfate, and dexmedetomidine showed significantly lower crystal densities than those of alkaline mixtures.Conclusion
Based on the present in vitro findings, adding either 8.4% sodium bicarbonate or dexamethasone to 0.25% levobupivacaine produced rapid, substantial crystallization, suggesting a physicochemical incompatibility under the tested conditions. These findings suggest that direct admixture of these agents with levobupivacaine in the same syringe should be approached with caution pending confirmation in clinical studies.
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BibTeX
@article{sharipova2026microscopic,
title = {{Microscopic Evaluation of Crystallization Dynamics in 0.25% Levobupivacaine Mixed with Common Regional Anaesthesia Adjuvants: An in vitro Compatibility Study.}},
author = {Visolat Sharipova and Shoira Yuldosheva and Ivan Fokin},
journal = {Turkish journal of anaesthesiology and reanimation},
year = {2026},
month = oct,
doi = {10.4274/tjar.2026.262399},
url = {https://europepmc.org/article/MED/42969300},
note = {CC BY},
}
RIS
TY - JOUR
TI - Microscopic Evaluation of Crystallization Dynamics in 0.25% Levobupivacaine Mixed with Common Regional Anaesthesia Adjuvants: An in vitro Compatibility Study.
AU - Visolat Sharipova
AU - Shoira Yuldosheva
AU - Ivan Fokin
PY - 2026
DA - 2026/10/01
JO - Turkish journal of anaesthesiology and reanimation
DO - 10.4274/tjar.2026.262399
UR - https://europepmc.org/article/MED/42969300
AB - Objective To investigate the crystallization dynamics of 0.25% levobupivacaine when combined with common regional anaesthesia adjuvants.Methods This in vitro study examined mixtures of 0.25% levobupivacaine with dexamethasone (20:1), 25% magnesium sulfate (20:1.5), dexmedetomidine (20:1), 8.4% sodium bicarbonate (10:1), and adrenaline (1:100,000). The study protocol was an in vitro investigation. Since no human or animal subjects were involved, the study was exempt from formal ethics committee approval. An institutional waiver was obtained from the Ministry of Health of the Republic of Uzbekistan Research Administration of the Republican Scientific Emergency Medical Centre (ref no: 03-05/119, date: 15.01.2026). All mixtures were incubated at 37 °C and examined under light microscopy (40× magnification) immediately, at 15 minutes, and at 1 hour. Crystallization onset, crystal count, and crystal size were quantified. For accurate dimensional analysis, a stage micrometer was used to calibrate the digital imaging software, and a calibrated scale bar was superimposed on each micrograph. Statistical analyses were performed using IBM SPSS Statistics for Windows, version 30.0 (IBM Corp., Armonk, NY, USA). Overall changes across the three matched assessment times were evaluated using the Friedman test. Significant omnibus results were followed by paired Wilcoxon signed-rank tests with Holm adjustment for multiple comparisons. All tests were two-sided, and a P value <0.05 was considered statistically significant.Results Solutions containing sodium bicarbonate and dexamethasone demonstrated the earliest onset of crystallization. Sodium bicarbonate (10:1) produced immediate and massive precipitation. Levobupivacaine-dexamethasone mixtures showed progressive crystallization, with particle counts exceeding 100 per field for particles larger than 10 μm within 60 minutes. Adrenaline, magnesium sulfate, and dexmedetomidine showed significantly lower crystal densities than those of alkaline mixtures.Conclusion Based on the present in vitro findings, adding either 8.4% sodium bicarbonate or dexamethasone to 0.25% levobupivacaine produced rapid, substantial crystallization, suggesting a physicochemical incompatibility under the tested conditions. These findings suggest that direct admixture of these agents with levobupivacaine in the same syringe should be approached with caution pending confirmation in clinical studies.
SN - 2667-677X
SN - 2667-6370
ER -