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

Study Overview
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Brief Summary
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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.

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

Conditions
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Analgesia, Acute Pain, Upper Extremity Injury

Intervention / Treatment
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* Drug: Bupivacaine Hydrochloride
* Drug: Bupivacaine Hydrochloride with Dexamethasone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Perineural Bupivacaine<br>Bupivacaine without Dexamethasone in axillary brachial plexus blockade | Drug: Bupivacaine Hydrochloride<br>* Patients will receive a total volume of 30 ml of bupivacaine 0.5% in an axillary block with a double puncture.<br>|
| Experimental: Perineural Bupivacaine plus Dexamethasone<br>Bupivacaine with Dexamethasone in axillary brachial plexus blockade | Drug: Bupivacaine Hydrochloride with Dexamethasone<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of bupivacaine | Maximum plasmatic level of bupivacaine | 0 to 90 minutes after the ending time of local anesthetic injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Persistent neurologic deficit | Presence of persistent sensory or motor postoperative deficit. | 7 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dexamethasone, Nerve Block, Adjuvant, Pharmacokinetic Analysis