Pharmacokinetic Analysis of Bupivacaine in the Presence and Absence of Perineural Dexamethasone in Axillary Blockade

NCT05359731 | Completed Phase 4 DMC

• 1 other identifier: OAIC 1249/22
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will conduct a prospective, randomized, double-blinded study using an axillary brachial plexus block in patients undergoing elective surgery of the distal forearm and hand to characterize and describe the pharmacokinetics of bupivacaine associated with perineural dexamethasone. The pharmacokinetic analysis will be performed by measuring bupivacaine plasma levels at different time intervals after the blockade (15, 30, 45, 60, and 90 minutes), allowing comparison between 2 different groups: Bupivacaine (B) and Bupivacaine-dexamethasone (BD). Thus, the hypothesis is that plasma levels of bupivacaine during the first 90 minutes after a blockade are lower in the presence of perineural dexamethasone, suggesting a decrease, at least initially, in systemic absorption from the injection site.

Conditions

Analgesia; Acute Pain; Upper Extremity Injury

Keywords

Dexamethasone; Nerve Block; Adjuvant; Pharmacokinetic Analysis

Outcome Measures

Primary Outcomes (1)

• Maximum plasma concentration (Cmax) of bupivacaine

  Maximum plasmatic level of bupivacaine

  0 to 90 minutes after the ending time of local anesthetic injection

Secondary Outcomes (17)

• Plasmatic concentration of bupivacaine at 15 minutes

  15 minutes after the ending time of local anesthetic injection

• Plasmatic concentration of bupivacaine at 30 minutes

  30 minutes after the ending time of local anesthetic injection

• Plasmatic concentration of bupivacaine at 45 minutes

  45 minutes after the ending time of local anesthetic injection

• Plasmatic concentration of bupivacaine at 60 minutes

  60 minutes after the ending time of local anesthetic injection

• Plasmatic concentration of bupivacaine at 90 minutes

  90 minutes after the ending time of local anesthetic injection

Study Arms (2)

Perineural Bupivacaine

ACTIVE COMPARATOR

Bupivacaine without Dexamethasone in axillary brachial plexus blockade

Drug: Bupivacaine Hydrochloride

Perineural Bupivacaine plus Dexamethasone

EXPERIMENTAL

Bupivacaine with Dexamethasone in axillary brachial plexus blockade

Drug: Bupivacaine Hydrochloride with Dexamethasone

Interventions

Bupivacaine Hydrochloride DRUG

Patients will receive a total volume of 30 ml of bupivacaine 0.5% in an axillary block with a double puncture.

Perineural Bupivacaine

Bupivacaine Hydrochloride with Dexamethasone DRUG

Patients will receive a total volume of 30 ml of bupivacaine 0.5% with Dexamethasone 4 mg in an axillary block with a double puncture.

Perineural Bupivacaine plus Dexamethasone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• American Society of Anesthesiologists classification 1-2
• Real weight between 80 and 100 kg
• Body mass index between 20 and 30

You may not qualify if:

• Adults who are not capable of giving their own consent
• Medical history or physical findings of pre-existing neuropathy
• Coagulopathy (assessed by history and physical examination and, if deemed clinically necessary, by blood work up i.e. platelets ≤ 100, International Normalized Ratio ≥ 1.4 or prothrombin time ≥ 50)
• Renal failure (assessed by history and physical examination and, if deemed clinically necessary, by blood work up i.e. creatinine ≥ 100)
• Hepatic failure (assessed by history and physical examination and, if deemed clinically necessary, by blood work up i.e. transaminases ≥ 100)
• Allergy to local anesthetics (LAs)
• Pregnancy
• Previous surgery in the axillary region of the surgical side

Sponsors & Collaborators

• University of Chile: lead

Study Sites (1)

Hospital Clínico Universidad de Chile

Santiago, Metropolitan, Chile

Location

Related Publications (13)

• Desai N, Albrecht E, El-Boghdadly K. Perineural adjuncts for peripheral nerve block. BJA Educ. 2019 Sep;19(9):276-282. doi: 10.1016/j.bjae.2019.05.001. Epub 2019 Jul 6. No abstract available.

  PMID: 33456903 BACKGROUND

• Leurcharusmee P, Aliste J, Van Zundert TC, Engsusophon P, Arnuntasupakul V, Tiyaprasertkul W, Tangjitbampenbun A, Ah-Kye S, Finlayson RJ, Tran DQ. A Multicenter Randomized Comparison Between Intravenous and Perineural Dexamethasone for Ultrasound-Guided Infraclavicular Block. Reg Anesth Pain Med. 2016 May-Jun;41(3):328-33. doi: 10.1097/AAP.0000000000000386.

  PMID: 27015546 BACKGROUND

• Aliste J, Leurcharusmee P, Engsusophon P, Gordon A, Michelagnoli G, Sriparkdee C, Tiyaprasertkul W, Tran DQ, Van Zundert TC, Finlayson RJ, Tran DQH. A randomized comparison between intravenous and perineural dexamethasone for ultrasound-guided axillary block. Can J Anaesth. 2017 Jan;64(1):29-36. doi: 10.1007/s12630-016-0741-8. Epub 2016 Sep 23.

  PMID: 27663451 BACKGROUND

• Heesen M, Klimek M, Imberger G, Hoeks SE, Rossaint R, Straube S. Co-administration of dexamethasone with peripheral nerve block: intravenous vs perineural application: systematic review, meta-analysis, meta-regression and trial-sequential analysis. Br J Anaesth. 2018 Feb;120(2):212-227. doi: 10.1016/j.bja.2017.11.062. Epub 2017 Nov 22.

  PMID: 29406171 BACKGROUND

• Albrecht E, Kern C, Kirkham KR. A systematic review and meta-analysis of perineural dexamethasone for peripheral nerve blocks. Anaesthesia. 2015 Jan;70(1):71-83. doi: 10.1111/anae.12823. Epub 2014 Aug 14.

  PMID: 25123271 BACKGROUND

• Shishido H, Kikuchi S, Heckman H, Myers RR. Dexamethasone decreases blood flow in normal nerves and dorsal root ganglia. Spine (Phila Pa 1976). 2002 Mar 15;27(6):581-6. doi: 10.1097/00007632-200203150-00005.

  PMID: 11884905 BACKGROUND

• Gonzalez AP, Bernucci F, Pham K, Correa JA, Finlayson RJ, Tran DQ. Minimum effective volume of lidocaine for double-injection ultrasound-guided axillary block. Reg Anesth Pain Med. 2013 Jan-Feb;38(1):16-20. doi: 10.1097/AAP.0b013e3182707176.

  PMID: 23146999 BACKGROUND

• Kirkham KR, Jacot-Guillarmod A, Albrecht E. Optimal Dose of Perineural Dexamethasone to Prolong Analgesia After Brachial Plexus Blockade: A Systematic Review and Meta-analysis. Anesth Analg. 2018 Jan;126(1):270-279. doi: 10.1213/ANE.0000000000002488.

  PMID: 28922230 BACKGROUND

• Souza MCO, Marques MP, Duarte G, Lanchote VL. Analysis of bupivacaine enantiomers in plasma as total and unbound concentrations using LC-MS/MS: Application in a pharmacokinetic study of a parturient with placental transfer. J Pharm Biomed Anal. 2019 Feb 5;164:268-275. doi: 10.1016/j.jpba.2018.10.040. Epub 2018 Oct 23.

  PMID: 30399533 BACKGROUND

• Tran DQ, Dugani S, Dyachenko A, Correa JA, Finlayson RJ. Minimum effective volume of lidocaine for ultrasound-guided infraclavicular block. Reg Anesth Pain Med. 2011 Mar-Apr;36(2):190-4. doi: 10.1097/AAP.0b013e31820d4266.

  PMID: 21270721 BACKGROUND

• Bravo D, Aliste J, Layera S, Fernandez D, Leurcharusmee P, Samerchua A, Tangjitbampenbun A, Watanitanon A, Arnuntasupakul V, Tunprasit C, Gordon A, Finlayson RJ, Tran DQ. A multicenter, randomized comparison between 2, 5, and 8 mg of perineural dexamethasone for ultrasound-guided infraclavicular block. Reg Anesth Pain Med. 2019 Jan;44(1):46-51. doi: 10.1136/rapm-2018-000032.

  PMID: 30640652 BACKGROUND

• Ferraro LHC, Takeda A, Barreto CN, Faria B, Assuncao NA. [Pharmacokinetic and clinical effects of two bupivacaine concentrations on axillary brachial plexus block]. Braz J Anesthesiol. 2018 Mar-Apr;68(2):115-121. doi: 10.1016/j.bjan.2017.09.001. Epub 2017 Oct 16.

  PMID: 29042063 BACKGROUND

• Bravo D, Aguilera G, Giordano A, Layera S, Erpel H, Mora D, Ramirez C, Jara A, Aliste J. Bupivacaine pharmacokinetics in the absence or presence of perineural dexamethasone in axillary blockade. Br J Anaesth. 2026 Jan 16:S0007-0912(25)00894-3. doi: 10.1016/j.bja.2025.12.009. Online ahead of print.

  PMID: 41547610 DERIVED

MeSH Terms

Conditions

Agnosia; Acute Pain; Arm Injuries

Interventions

Bupivacaine; Dexamethasone

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pain; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: A research assistant (licensed anesthesiologist) will prepare the local anesthetic solutions and will add the study drug following the randomization order. The operator, patient and investigator assessing the block will be blinded to group allocation.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 28, 2022
• First Posted: May 4, 2022
• Study Start: June 28, 2022
• Primary Completion: April 17, 2023
• Study Completion: April 24, 2023
• Last Updated: October 17, 2023

Record last verified: 2023-10

Locations

CL (1)