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

Analgesia Clinical Trial

Official title:

Pharmacokinetic Analysis of Bupivacaine in the Presence and Absence of Perineural Dexamethasone in Axillary Brachial Plexus Blockade for Distal Forearm and Hand Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05359731
• Other study ID #: OAIC 1249/22
• Status: Completed
• Phase: Phase 4
• Start date: June 28, 2022
• Est. completion date: April 24, 2023

Study information

• Verified date: October 2023
• Source: University of Chile
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 24, 2023
• Est. primary completion date: April 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• American Society of Anesthesiologists classification 1-2

• Real weight between 80 and 100 kg

• Body mass index between 20 and 30

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Acute Pain
• Analgesia
• Arm Injuries
• Upper Extremity Injury

Intervention

Drug:
• Bupivacaine Hydrochloride
Patients will receive a total volume of 30 ml of bupivacaine 0.5% in an axillary block with a double puncture.
• Bupivacaine Hydrochloride with Dexamethasone
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.

Locations

Country	Name	City	State
Chile	Hospital Clínico Universidad de Chile	Santiago	Metropolitan

Sponsors (1)

Lead Sponsor	Collaborator
University of Chile

Country where clinical trial is conducted

Chile, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum plasma concentration (Cmax) of bupivacaine	Maximum plasmatic level of bupivacaine	0 to 90 minutes after the ending time of local anesthetic injection
Secondary	Plasmatic concentration of bupivacaine at 15 minutes	Plasmatic level of bupivacaine 15 minutes after local anesthetic injection (ng/ml)	15 minutes after the ending time of local anesthetic injection
Secondary	Plasmatic concentration of bupivacaine at 30 minutes	Plasmatic level of bupivacaine 30 minutes after local anesthetic injection (ng/ml)	30 minutes after the ending time of local anesthetic injection
Secondary	Plasmatic concentration of bupivacaine at 45 minutes	Plasmatic level of bupivacaine 45 minutes after local anesthetic injection (ng/ml)	45 minutes after the ending time of local anesthetic injection
Secondary	Plasmatic concentration of bupivacaine at 60 minutes	Plasmatic level of bupivacaine 60 minutes after local anesthetic injection (ng/ml)	60 minutes after the ending time of local anesthetic injection
Secondary	Plasmatic concentration of bupivacaine at 90 minutes	Plasmatic level of bupivacaine 90 minutes after local anesthetic injection (ng/ml)	90 minutes after the ending time of local anesthetic injection
Secondary	Time to obtain the maximum plasma concentration of bupivacaine (Tmax)	Time in minutes in which the maximum plasmatic level of bupivacaine is reached	0 to 90 minutes after the ending time of local anesthetic injection
Secondary	Area under the curve of plasma concentration versus time at 90 minutes (AUC90)	Area under the curve at 90 minutes	0 to 90 minutes after the ending time of local anesthetic injection
Secondary	Sensory and motor block score	The sensorimotor block will be assessed every 5 minutes until 30 minutes after the end of local anesthetic injection using a 16-point composite score evaluating sensory and motor block of musculocutaneous, medium, radial, and ulnar nerves.; Sensation will be assessed with ice in each nerve territory with a 0 to 2 point scale. 0= no block, patients can feel cold; 1= analgesic block, the patient can feel touch but not cold; 2= anesthetic block, the patient cannot feel cold or touch.; The motor function will be assessed for each nerve with a 0 to 2 points scale where 0= no motor block; 1= paresis; 2= paralysis.; Successful blocks at 30 minutes correlate with a final score ( sum of all individual sensory and motor scores) of at least 14 points out of 16.	30 minutes after the ending time of local anesthetic injection
Secondary	Block onset time	Time required to reach a minimal sensorimotor composite score of 14 points out of a maximum of 16 points. The sensorimotor score is described in outcome 9.	30 minutes after the ending time of local anesthetic injection
Secondary	Incidence of successful block	Percentage of blocks with a minimal sensorimotor composite score of 14 points out of a maximum of 16 points at 30 minutes after the injection	30 minutes after the ending time of local anesthetic injection
Secondary	Motor block duration	The elapsed period in minutes between the ending time of the local anesthetic injection and the time of return of hand and fingers movement.	48 hours after the ending time of local anesthetic injection
Secondary	Sensory block duration	The elapsed period in minutes between the ending time of the local anesthetic injection and the time of the return of hand and fingers sensation	48 hours after the ending time of local anesthetic injection
Secondary	Analgesic block duration	The elapsed period in minutes between the ending time of the local anesthetic injection and the time of the first sensation of pain in the surgical area	48 hours after the ending time of local anesthetic injection
Secondary	Intensity of pain during block procedure	Evaluated with the Numeric Rating Scale for Pain. This scale is graduated from 0 to 10 points. A 0-point score represents the absence of pain, and a 10-points score represents the worst imaginable pain. Patients will be asked to rate their pain verbally with this scale. The blinded assessor will register the score reported.	During the execution of the nerve blockade
Secondary	Block performance time	Sum of: 1- the acquisition time of the ultrasonographic image. and 2- the time to perform the block itself (from the skin anesthesia to the end of local anesthetic injection)	From the skin anesthesia to the end of local anesthetic injection
Secondary	Incidence of nerve block side effects	Determined by the presence of paresthesia, local anesthetic systemic toxicity, vascular puncture after the block.	From the skin anesthesia to the end of local anesthetic injection
Secondary	Persistent neurologic deficit	Presence of persistent sensory or motor postoperative deficit.	7 days after surgery