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"Anesthetics"

Original Articles
Crystallization of Local Anesthetics When Mixed With Corticosteroid Solutions
Hyeoncheol Hwang, Jihong Park, Won Kyung Lee, Woo Hyung Lee, Ja-Ho Leigh, Jin Joo Lee, Sun G. Chung, Chaiyoung Lim, Sang Jun Park, Keewon Kim
Ann Rehabil Med 2016;40(1):21-27.   Published online February 26, 2016
DOI: https://doi.org/10.5535/arm.2016.40.1.21
Objective

To evaluate at which pH level various local anesthetics precipitate, and to confirm which combination of corticosteroid and local anesthetic crystallizes.

Methods

Each of ropivacaine-HCl, bupivacaine-HCl, and lidocaine-HCl was mixed with 4 different concentrations of NaOH solutions. Also, each of the three local anesthetics was mixed with the same volume of 3 corticosteroid solutions (triamcinolone acetonide, dexamethasone sodium phosphate, and betamethasone sodium phosphate). Precipitation of the local anesthetics (or not) was observed, by the naked eye and by microscope. The pH of each solution and the size of the precipitated crystal were measured.

Results

Alkalinized with NaOH to a certain value of pH, local anesthetics precipitated (ropivacaine pH 6.9, bupivacaine pH 7.7, and lidocaine pH 12.9). Precipitation was observed as a cloudy appearance by the naked eye and as the aggregation of small particles (<10 µm) by microscope. The amount of particles and aggregation increased with increased pH. Mixed with betamethasone sodium phosphate, ropivacaine was precipitated in the form of numerous large crystals (>300 µm, pH 7.5). Ropivacaine with dexamethasone sodium phosphate also precipitated, but it was only observable by microscope (a few crystals of 10–100 µm, pH 7.0). Bupivacaine with betamethasone sodium phosphate formed precipitates of non-aggregated smaller particles (<10 µm, pH 7.7). Lidocaine mixed with corticosteroids did not precipitate.

Conclusion

Ropivacaine and bupivacaine can precipitate by alkalinization at a physiological pH, and therefore also produce crystals at a physiological pH when they are mixed with betamethasone sodium phosphate. Thus, the potential risk should be noted for their use in interventions, such as epidural steroid injections.

Citations

Citations to this article as recorded by  
  • Efficacy of different routes of dexamethasone administration for preventing rebound pain following peripheral nerve blocks in adult surgical patients: a systematic review and network meta‐analysis
    Jeetinder K. Makkar, Narinder Pal Singh, Bisman J. K. Khurana, Janeesha K. Chawla, Preet M. Singh
    Anaesthesia.2025; 80(6): 704.     CrossRef
  • Physicochemical stability of mixtures of non-steroidal anti-inflammatory drugs such as ketorolac and diclofenac and antiemetics such as ondansetron and ramosetron: an in vitro study
    Chung Hun Lee
    The Korean Journal of Pain.2025; 38(2): 103.     CrossRef
  • Perineural dexamethasone: A bad habit that is hard to break
    Alessandro De Cassai, Serkan Tulgar, Burhan Dost
    Journal of Perioperative Practice.2025;[Epub]     CrossRef
  • A comparative evaluation of the effect of addition of 8 mg dexamethasone to 2% lignocaine with adrenaline in mandibular third molar surgery: a split mouth randomised double blind study
    P. Poorna, Premalatha Shetty, Veerbhadra Kalyani, Sameep Shetty, Madhusudan Upadya, Prasanna Mithra
    Frontiers in Oral Health.2024;[Epub]     CrossRef
  • Lights and shadows on the use of adjuvants in fascial block
    Pierfrancesco FUSCO, Francesca DE SANCTIS, Emanuele NAZZARRO, Carla STECCO, Raffaele PERNA, Rita COMMISSARI, Walter CIASCHI, Gian M. PETRONI
    Minerva Anestesiologica.2024;[Epub]     CrossRef
  • Steroids and Local Anesthetics Used in Musculoskeletal Disorders
    Chang-Won Moon
    Clinical Pain.2024; 23(2): 57.     CrossRef
  • Buprenorphine has a concentration-dependent cytotoxic effect on equine chondrocytes in vitro
    Gabriel Castro-Cuellar, Jeannette Cremer, Chin-Chi Liu, Patricia Queiroz-Williams, Chiara Hampton, Britta Sigrid Leise
    American Journal of Veterinary Research.2023; : 1.     CrossRef
  • Precipitation of sugammadex with nicardipine and labetalol: A laboratory research
    Jiwon Han, Ah‐Young Oh
    Fundamental & Clinical Pharmacology.2023; 37(5): 1006.     CrossRef
  • Various Injectable Agents for Neuromusculoskeletal Pain and Ultrasound-Guided Injection
    Yong-Soon Yoon, Kwang Jae Lee
    Clinical Pain.2023; 22(2): 88.     CrossRef
  • Cauda equina syndrome after unilateral medial branch blocks of the lower lumbar zygapophyseal joints
    Zied Zaghdoudi, Sam Eldabe, Sue Copley, Haythem Abbes, Philippe Temperli, Eric Buchser
    Pain Practice.2022; 22(6): 582.     CrossRef
  • Neurologic Complication Due to Crystallization After Drug Interaction Between Alkalized Lidocaine and Ropivacaine: A Case Report and in vitro Study
    Afang Zhu, Lijian Pei, Wei Liu, Wencong Cheng, Yu Zhang, Yuguang Huang
    Frontiers in Medicine.2022;[Epub]     CrossRef
  • Crystallization of ropivacaine and bupivacaine when mixed with different adjuvants: a semiquantitative light microscopy analysis
    Elisabeth Hoerner, Ottokar Stundner, Guenther Putz, Thorsten Steinfeldt, Simon Mathis, Lukas Gasteiger
    Regional Anesthesia & Pain Medicine.2022; 47(10): 625.     CrossRef
  • Interaction between Dexamethasone, Ropivacaine, and Contrast Media Used in Interventional Pain Treatment: Considerations in Safety
    Yeon Ju Kim, Yeon-Dong Kim, Hyungtae Kim, Dong Ji Ahn, Ha-Jung Kim, Won Uk Koh, Young-Jin Ro
    Medicina.2022; 58(12): 1871.     CrossRef
  • Analgesic Effect of the Topical Use of Dexamethasone in Ultrasound-Guided Axillary Brachial Plexus Blockade: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study
    Aikaterini Chazapi, Panagiotis Lepetsos, Zoe Gambopoulou, Ioanna Siafaka, Erifylli Argyra, Athina Vadalouka
    Cureus.2021;[Epub]     CrossRef
  • Safety of epidural steroids: a review
    Min Soo Lee, Ho Sik Moon
    Anesthesia and Pain Medicine.2021; 16(1): 16.     CrossRef
  • Evaluation of the in vitro effects of local anesthetics on equine chondrocytes and fibroblast-like synoviocytes
    Ditte M. T. Adler, Jeppe F. Frellesen, Christoffer V. Karlsen, Line D. Jensen, Anne S. Q. Dahm, Lise C. Berg
    American Journal of Veterinary Research.2021; 82(6): 478.     CrossRef
  • Non-Particulate Steroids (Betamethasone Sodium Phosphate, Dexamethasone Sodium Phosphate, and Dexamethasone Palmitate) Combined with Local Anesthetics (Ropivacaine, Levobupivacaine, Bupivacaine, and Lidocaine): A Potentially Unsafe Mixture
    Eun Joo Choi, Dong-Hyun Kim, Woong Ki Han, Ho-Jin Lee, Imhong Kang, Francis Sahngun Nahm, Pyung-Bok Lee
    Journal of Pain Research.2021; Volume 14: 1495.     CrossRef
  • Effect of intravenous dexamethasone on the duration of postoperative analgesia for popliteal sciatic nerve block: a randomized, double-blind, placebo-controlled study
    Byung-Gun Kim, Woojoo Lee, Jang Ho Song, Chunwoo Yang, Gyung A Heo, Hongseok Kim
    Korean Journal of Anesthesiology.2021; 74(4): 317.     CrossRef
  • Fluoroscopy-guided spine injections: establishing a successful service in your radiology department or practice
    Swati Deshmukh, Jonathan Youngner, Ankur Garg
    Skeletal Radiology.2020; 49(3): 475.     CrossRef
  • Intravenous patient-controlled analgesia: in vitro stability profiles of mixtures containing fentanyl, hydromorphone, oxycodone, nefopam, ondansetron, and ramosetron
    Chung Hun Lee, Ah Rahn Kim, Mi Kyoung Lee, Jung Suk Oh, Dong Kyu Lee, Sang Sik Choi
    Journal of Analytical Science and Technology.2020;[Epub]     CrossRef
  • The Simplified Science of Corticosteroids for Clinicians
    Daniel J. Kaplan, Jonathan D. Haskel, David J. Kirby, David A. Bloom, Thomas Youm
    JBJS Reviews.2020; 8(11): e20.00038.     CrossRef
  • Are patients more likely to have hip osteoarthritis progression and femoral head collapse after hip steroid/anesthetic injections? A retrospective observational study
    F. Joseph Simeone, Joao R. T. Vicentini, Miriam A. Bredella, Connie Y. Chang
    Skeletal Radiology.2019; 48(9): 1417.     CrossRef
  • Trends in steroid agent and diluent choices for epidural steroid injections: a survey of Spine Intervention Society physicians
    Nathan Clements, Darrell Vydra, Daniel M. Cushman, Ameet Nagpal, Jonathan Julia, Patricia Zheng, Zachary L. McCormick
    Regional Anesthesia & Pain Medicine.2019; 44(8): 809.     CrossRef
  • Clinical effectiveness of single dose of intravenous dexamethasone on the duration of ropivacaine axillary brachial plexus block: the randomized placebo-controlled ADEXA trial
    Jean-Christophe Clement, Guillaume Besch, Marc Puyraveau, Tommy Grelet, David Ferreira, Lucie Vettoretti, Sébastien Pili-Floury, Emmanuel Samain, Francis Berthier
    Regional Anesthesia & Pain Medicine.2019; 44(3): e100035.     CrossRef
  • Dilution and microfiltration of particulate corticosteroids for spinal epidural injections: impact on drug concentration and agglomerate formation
    A. Alcántara Guardado, G. Cooper, A. Weightman, R. Spiess, A.D.L. Baker
    Anaesthesia.2019; 74(12): 1551.     CrossRef
  • Safe Injectate Choice, Visualization, and Delivery for Lumbar Transforaminal Epidural Steroid Injections: Evolving Literature and Considerations
    Patricia Zheng, Byron J. Schneider, David J Kennedy, Zachary L. McCormick
    Current Physical Medicine and Rehabilitation Reports.2019; 7(4): 414.     CrossRef
  • Intra-articular Corticosteroid Injections for Symptomatic Knee Osteoarthritis: What the Orthopaedic Provider Needs to Know
    Cody L. Martin, James A. Browne
    Journal of the American Academy of Orthopaedic Surgeons.2019; 27(17): e758.     CrossRef
  • Safety and Complications of Cervical Epidural Steroid Injections
    Byron J. Schneider, Simone Maybin, Eric Sturos
    Physical Medicine and Rehabilitation Clinics of North America.2018; 29(1): 155.     CrossRef
  • Cervical Epidural Steroid Injection
    Lawrence McLean House, Kevin Barrette, Ryan Mattie, Zachary L. McCormick
    Physical Medicine and Rehabilitation Clinics of North America.2018; 29(1): 1.     CrossRef
  • Ultrasound-Guided Percutaneous Needle Fasciotomy after Steroid Injection for Dupuytren's Contracture
    Jae-Sung Yoo, Kang Heo, Seong-Jun Kim, Kwang-Hee Park, Jong-Pil Kim
    Archives of Hand and Microsurgery.2018; 23(1): 28.     CrossRef
  • Safety and Risk Mitigation for Cervical Transforaminal Epidural Steroid Injections
    Byron J. Schneider, Simone Maybin
    Current Physical Medicine and Rehabilitation Reports.2017; 5(4): 186.     CrossRef
  • Mixing local anaesthetics, corticosteroid, and ketorolac tromethamine leads to no extreme pH or precipitation
    M. Q. H. Leow, K. S. Chua, S. C. Tay
    Journal of Hand Surgery (European Volume).2017; 42(9): 963.     CrossRef
  • Analysis of efficacy of adding dexamethasone to ropivacaine in oral surgery
    Simona Stojanović
    Acta stomatologica Naissi.2017; 33(76): 1754.     CrossRef
  • Delayed Onset Paraparesis Complicating Epidural Steroid Injection with Underlying Spinal Dural Arteriovenous Fistula
    Kartavya Sharma, Vibhash D Sharma
    Pain Management.2016; 6(5): 421.     CrossRef
  • 9,983 View
  • 184 Download
  • 32 Web of Science
  • 34 Crossref
The Effect and Safety of Steroid Injection in Lumbar Spinal Stenosis: With or Without Local Anesthetics
Sung Hyuk Song, Gi Hyeong Ryu, Jin Woo Park, Ho Jun Lee, Ki Yeun Nam, Hyojun Kim, Seung Yeon Kim, Bum Sun Kwon
Ann Rehabil Med 2016;40(1):14-20.   Published online February 26, 2016
DOI: https://doi.org/10.5535/arm.2016.40.1.14
Objective

To compare the long-term effect and safety of an epidural steroid injection in spinal stenosis patients, with or without local anesthetics.

Methods

Twenty-nine patients diagnosed with spinal stenosis were included and randomly divided into two groups. Translaminar epidural and selective nerve root spinal injection procedures were performed using steroids mixed with local anesthetics or normal saline. The effects of spinal injection procedures were measured with visual analogue scale (VAS) and functional rate index (FRI). These measurements were performed before injection, at 1 month after injection and at 3 months after injection. The occurrence of side effects was investigated each time.

Results

The VAS and FRI scores were significantly reduced in both the local anesthetics group and normal saline group at 1 and 3 months after the injection. However, there was no significant difference in VAS and FRI score reduction between the two groups each time. Side effects are not noted in both groups.

Conclusion

The spinal injection procedures using steroids mixed either with local anesthetics or normal saline have an effect in reducing pain and improving functional activities. However, there was no significant difference between the two groups in relation to side effects and the long-term effects of pain and function.

Citations

Citations to this article as recorded by  
  • Real-Time MR-Guided Lumbosacral Periradicular Injection Therapy Using a 0.55 T MRI System: A Phantom Study
    Saher Saeed, Jan Boriesosdick, Arwed Michael, Nina Pauline Haag, Julian Schreck, Denise Schoenbeck, Matthias Michael Woeltjen, Julius Henning Niehoff, Christoph Moenninghoff, Jan Borggrefe, Jan Robert Kroeger
    Diagnostics.2025; 15(11): 1413.     CrossRef
  • Factfinders for patient safety: Epidural steroid injection in patients with lumbar spinal stenosis
    George Christolias, Aditya Raghunandan, Byron J. Schneider, Kunj Amin, David Hao, Jaymin Patel
    Interventional Pain Medicine.2024; 3(4): 100444.     CrossRef
  • A comparison between effectiveness of gluteal trigger point and epidural steroid injection in lumbosacral canal stenosis patients: a randomized clinical trial
    Sana Sadat Khoshnazar, Hamid Reza Farpour, Reza Shahriarirad
    British Journal of Neurosurgery.2023; 37(5): 1117.     CrossRef
  • Differentiating Lumbar Spinal Etiology from Peripheral Plexopathies
    Marco Foreman, Krisna Maddy, Aashay Patel, Akshay Reddy, Meredith Costello, Brandon Lucke-Wold
    Biomedicines.2023; 11(3): 756.     CrossRef
  • Safety of Epidural Hyaluronic Acid Injections in Managing the Symptoms of Lumbar Foraminal Stenosis: A Prospective Preliminary Study
    Piotr Godek, Kuba Ptaszkowski
    Journal of Clinical Medicine.2023; 12(6): 2359.     CrossRef
  • Intralesional corticosteroid injections are less painful without local anesthetic: a double-blind, randomized controlled trial
    Danny Zakria, James R. Patrinely, Anna K. Dewan, Sharon E. Albers, Lee E. Wheless, Aleta N. Simmons, Brian C. Drolet
    Journal of Dermatological Treatment.2022; 33(4): 2034.     CrossRef
  • Assessing the impact of adding bupivacaine on immediate and delayed post-procedure pain scores in interlaminar epidural steroid injections
    Cody R. Quirk, Anthony Onofrio, James T. Patrie, Nicholas C. Nacey
    Skeletal Radiology.2022; 51(1): 161.     CrossRef
  • Non-operative treatment for lumbar spinal stenosis with neurogenic claudication: an updated systematic review
    Carlo Ammendolia, Corey Hofkirchner, Joshua Plener, André Bussières, Michael J Schneider, James J Young, Andrea D Furlan, Kent Stuber, Aksa Ahmed, Carol Cancelliere, Aleisha Adeboyejo, Joseph Ornelas
    BMJ Open.2022; 12(1): e057724.     CrossRef
  • Do steroid injections to the peripheral nerve increase perineural fibrosis? An animal experimental study
    Mustafa ÇELİKTAŞ, Semih Kivanc OLGUNER, Kivilcim ERDOGAN, Remzi ÇAYLAK, Kenan DAĞLIOĞLU
    Journal of Surgery and Medicine.2022; 6(2): 181.     CrossRef
  • Recent Domestic and International Trends on Non-Surgical Treatment of Lumbar Spinal Stenosis
    Mi-Hyun Kim, K.M.D., Eun-Sang Park, Hyeon-Ho Hwang, Yeo-Gyeong Lee, Geum-Ju Song, Mi-Ri Kwon, Jun-Hyuk Kang
    Journal of Korean Medicine Rehabilitation.2021; 31(3): 1.     CrossRef
  • Short-Term Efficacy of Epidural Injection of Triamcinolone Through Translaminar Approach for the Treatment of Lumbar Canal Stenosis
    Saeed Sabbaghan, Elham Mirzamohammadi, Maryam Ameri Mahabadi, Farshad Nikouei, Farhad Rahbarian, Susan Ahmadichaboki, Samira Eftekhari, Maryam Zamankhani, Amir Aghaie Aghdam
    Anesthesiology and Pain Medicine.2020;[Epub]     CrossRef
  • Interventional Approaches to Low Back Pain
    Ariana M. Nelson, Geeta Nagpal
    Clinical Spine Surgery: A Spine Publication.2018; 31(5): 188.     CrossRef
  • Lumbale Radikulopathie: Klinik steht vor Bildgebung
    Franz Xaver Glocker
    Deutsches Ärzteblatt Online.2018;[Epub]     CrossRef
  • 5,495 View
  • 50 Download
  • 8 Web of Science
  • 13 Crossref
The Effects of Topical Anesthetic Ointment to the Pain during Electromyographic Examination.
Jang, Seong Ho , Lee, Kang Hee
J Korean Acad Rehabil Med 1998;22(6):1279-1283.

Objectives: To investigate the effects of topical anesthetic ointment (lidocaine 2.5%⁢prilocaine 2.5%) to the pain during electromyographic examination

Method: Thirty-two adults without known neurological disorders were studied. The needle Electromyography (EMG) of flexor carpi radialis (FCR) muscle and the motor and sensory conduction studies of median nerve were performed after the application of topical anesthetic ointment in one upper extremity and compared to the other side upper extremity without anesthesia. The intensity of pain was assessed with the Visual Analog Scale (VAS) and the characteristics of pain was evaluated with the modified short-form McGill pain questionnaire.

Results: The VAS score of the needle EMG of FCR muscle in the anesthetized side was significantly lower to that of the non-anesthetized side (P<0.01). And the characteristics of pain were shooting (10 cases, 31.3%), or throbbing (6 cases, 18.8%) in the anesthetized side and dull (13 cases, 40.6%), or numb (7 cases, 21.9%) in the non-anesthetized side. The VAS scores of the sensory and motor nerve conduction study of median nerve were not significantly different in both sides.

Conclusion: The application of topical anesthetic ointment decreases the intensity and changes the characteristics of pain during the needle EMG.

  • 1,707 View
  • 9 Download
Clinical Analysis on the Efficacy of Epidural Injections in Low Back Pain Patient.
Park, Young Jae , Kim, Mi Jung , Lee, Sang Gun
J Korean Acad Rehabil Med 1998;22(2):269-273.

The purpose of this study is to evaluate the efficacy of epidural injections with steroids and local anesthetics for the low back pain patients.

Two hundred fifty patients with low back pain and sciatica were selected for the study. The patients were treated with the epidural injection of steroid(Depo-medrol) weekly for 2 weeks and local anesthetics(lidocaine and bupivacaine) daily via epidural catheter. The efficacy of epidural injections was assessed with the Visual Analog Scale(VAS) on pre- and 2weeks post-epidural injections. The VAS scores of pre- and post-epidural injections were 6.14⁑2.14 and 3.65⁑1.93(p<0.05) respectively. The VAS scores were not different by the disease subgroups(p>0.05). By the main symptoms, VAS scores were reduced prominently in patients with the pseudoclaudication symptom after post-epidural injections.

In conclusion, epidural injections of steroid and local anesthetics are effective for patients with a low back pain and sciatica in the short term. Further prospective long-term follow up studies will be necessary in the future.

  • 1,403 View
  • 6 Download
Skeletal Muscle Changes Following Injection of Local Anesthetics.
Kwon, Hee Kyu , Park, Youn Hyung , Na, Jin Kyung , Lee, Hang Jae
J Korean Acad Rehabil Med 1997;21(1):140-145.

To investigate the skeletal muscle changes, intramuscular injections of local anesthetics were performed using animal, Sprague-Dawley rat.

The experiments were composed of two procedures, experiment I and II. In experi ment I, single injection was performed using 0.4 cc of 1 and 2% of procaine and lidocaine.

In experiment II, repeated injection of 0.4 cc of 2% lidocaine on weekly bases 3 times were performed.

The experimental rats were divided into five groups in experiment I: Four experimental groups 40(10 rats for each local anesthetics) and Control 10 and were divided into two groups in experiment II: Experimental group 8 and Control 4. The muscle biopsies were performed in 15 minutes, 2, 4, 8 and 16 days after injection in two experiments.

No muscle fiber changes were shown in control group, and 1~2 % procaine, and 2% lidocaine injected groups of experiment I and control group of experiment II. In the groups of single and repeated injections of 2% lidocaine, muscular inflammatory changes were shown on 2 and 4 days after injection. The changes were more extensive in the group of repeated injections. The inflammatory reaction was usually abated on 8 days after injection and the muscles appeared to be normal in quality and quantity on 16 days after injection. These histopathologic results indicated reversible muscular changes.

Although the muscular changes are reversible after local anesthetics injection, the concentration of local anesthetics and injection interval should be considered to minimize the muscle fiber changes in the repeated injections.

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