Bupivacaine Pharmacokinetics in Ultrasound-guided Axillary Brachial Plexus Block.

NCT ID: NCT02755532

Last Updated: 2016-04-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-31

Study Completion Date

2015-10-31

Brief Summary

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Introduction: The risk of systemic toxicity when using bupivacaine is a persistent problem, making its pharmacokinetic study crucial to the safety of regional anesthesia (RA). Little evidence exists regarding the effect of different concentrations of this drug on peak plasma levels. The present study compares two bupivacaine concentrations to establish how the concentration and exchange area affect the peak plasma level of this drug during axillary brachial plexus block. Latency and postoperative analgesia periods were also compared.

Methods: 32 patients were randomly assigned to two groups. In the 0.25% group, 10 ml of 0.25% bupivacaine was injected per nerve; in the 0.5% group, 5 ml of 0.5% bupivacaine was injected per nerve. Peripheral blood samples were collected every 15 min during the first hour and every 30 min during the second hour to establish serum level dosage. High-performance liquid chromatography coupled with mass spectrometry was used for the analysis.

Detailed Description

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Conditions

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Pharmacokinetics Anesthetics, Local

Keywords

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Pharmacokinetics Bupivacaine Axillary brachial plexus block

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Bupivacaine 0,25%

Routine surgical procedure monitoring with an electrocardiogram, sphygmomanometer, and pulse oximeter was performed. One experienced anesthesiologist performed an ultrasound guided axillary brachial plexus block (S Series, FUJIFILM Sonosite, Seattle, USA) with the patient in the supine position. Local anesthetic injection was performed on each nerve identified in this pathway (i.e., the radial nerve, the ulnar nerve, the median nerve, and the musculocutaneous nerve) In the group bupicavaine 0.25%, 10 ml of 0.25% bupivacaine was injected into each nerve, for a total of 40 ml per patient.

Group Type ACTIVE_COMPARATOR

Bupivacaine 0,25%

Intervention Type DRUG

Venous blood samples were collected prior to blocking , every 15 min during the first hour after completion of the blocking and every 30 min during the second hour after completion using an exclusive cannula. Then, 5 ml was drawn off and was stored in two EDTA tubes (BD, Franklin Lakes, NJ, USA). The EDTA tubes were centrifuged at 3,500xg for 10 min to obtain the blood plasma. This plasma was then stored in cryogenic tubes in a freezer at -80 °C until the time of the analysis. A high-performance liquid chromatography apparatus (Shimadzu, Kyoto, Japan) coupled to a Bruker mass spectrometer (MS), model Amazon (USA), with electrospray source ionization and a sequential mass spectrometry system (MS/MS) were used for the analysis. After obtaining the precursor ion, a fragment was obtained via a collision-induced dissociation process. The following molecular ions were selected: 289.0 m/z==\>140.1 m/z. The methodology was validated according to the international FDA recommendations.

Bupivacaine 0,5%

Routine surgical procedure monitoring with an electrocardiogram, sphygmomanometer, and pulse oximeter was performed. One experienced anesthesiologist performed an ultrasound guided axillary brachial plexus block (S Series, FUJIFILM Sonosite, Seattle, USA) with the patient in the supine position. Local anesthetic injection was performed on each nerve identified in this pathway (i.e., the radial nerve, the ulnar nerve, the median nerve, and the musculocutaneous nerve). In the group bupivacaine 0.5% , 5 ml of 0.5% bupivacaine was injected into each nerve, for a total of 20 ml per patient.

Group Type ACTIVE_COMPARATOR

Bupivacaine 0,5%

Intervention Type DRUG

Venous blood samples were collected prior to blocking , every 15 min during the first hour after completion of the blocking and every 30 min during the second hour after completion using an exclusive cannula. Then, 5 ml was drawn off and was stored in two EDTA tubes (BD, Franklin Lakes, NJ, USA). The EDTA tubes were centrifuged at 3,500xg for 10 min to obtain the blood plasma. This plasma was then stored in cryogenic tubes in a freezer at -80 °C until the time of the analysis. A high-performance liquid chromatography apparatus (Shimadzu, Kyoto, Japan) coupled to a Bruker mass spectrometer (MS), model Amazon (USA), with electrospray source ionization and a sequential mass spectrometry system (MS/MS) were used for the analysis. After obtaining the precursor ion, a fragment was obtained via a collision-induced dissociation process. The following molecular ions were selected: 289.0 m/z==\>140.1 m/z. The methodology was validated according to the international FDA recommendations.

Interventions

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Bupivacaine 0,25%

Venous blood samples were collected prior to blocking , every 15 min during the first hour after completion of the blocking and every 30 min during the second hour after completion using an exclusive cannula. Then, 5 ml was drawn off and was stored in two EDTA tubes (BD, Franklin Lakes, NJ, USA). The EDTA tubes were centrifuged at 3,500xg for 10 min to obtain the blood plasma. This plasma was then stored in cryogenic tubes in a freezer at -80 °C until the time of the analysis. A high-performance liquid chromatography apparatus (Shimadzu, Kyoto, Japan) coupled to a Bruker mass spectrometer (MS), model Amazon (USA), with electrospray source ionization and a sequential mass spectrometry system (MS/MS) were used for the analysis. After obtaining the precursor ion, a fragment was obtained via a collision-induced dissociation process. The following molecular ions were selected: 289.0 m/z==\>140.1 m/z. The methodology was validated according to the international FDA recommendations.

Intervention Type DRUG

Bupivacaine 0,5%

Venous blood samples were collected prior to blocking , every 15 min during the first hour after completion of the blocking and every 30 min during the second hour after completion using an exclusive cannula. Then, 5 ml was drawn off and was stored in two EDTA tubes (BD, Franklin Lakes, NJ, USA). The EDTA tubes were centrifuged at 3,500xg for 10 min to obtain the blood plasma. This plasma was then stored in cryogenic tubes in a freezer at -80 °C until the time of the analysis. A high-performance liquid chromatography apparatus (Shimadzu, Kyoto, Japan) coupled to a Bruker mass spectrometer (MS), model Amazon (USA), with electrospray source ionization and a sequential mass spectrometry system (MS/MS) were used for the analysis. After obtaining the precursor ion, a fragment was obtained via a collision-induced dissociation process. The following molecular ions were selected: 289.0 m/z==\>140.1 m/z. The methodology was validated according to the international FDA recommendations.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* candidates for elective surgery of the distal forearm and hand for whom brachial plexus anesthesia and analgesia were indicated.
* physical status of I or II according to American Society of Anesthesiologists (ASA) criteria
* body mass index (BMI) of less than 35 kg/m2
* Signed the free and informed consent document.

Exclusion Criteria

* cognitive impairment
* infection at the block puncture site
* coagulopathy
* history of bupivacaine allergy
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fundação de Amparo à Pesquisa do Estado de São Paulo

OTHER_GOV

Sponsor Role collaborator

Federal University of São Paulo

OTHER

Sponsor Role lead

Responsible Party

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Leonardo Henrique Cunha Ferraro

PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Leonardo HC Ferraro, PhD

Role: PRINCIPAL_INVESTIGATOR

Federal University of São Paulo

References

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Cohen LS, Rosenthal JE, Horner DW Jr, Atkins JM, Matthews OA, Sarnoff SJ. Plasma levels of lidocaine after intramuscular administration. Am J Cardiol. 1972 Apr;29(4):520-3. doi: 10.1016/0002-9149(72)90442-0. No abstract available.

Reference Type RESULT
PMID: 5016830 (View on PubMed)

Mulroy MF. Systemic toxicity and cardiotoxicity from local anesthetics: incidence and preventive measures. Reg Anesth Pain Med. 2002 Nov-Dec;27(6):556-61. doi: 10.1053/rapm.2002.37127. No abstract available.

Reference Type BACKGROUND
PMID: 12430104 (View on PubMed)

Rosenberg PH, Veering BT, Urmey WF. Maximum recommended doses of local anesthetics: a multifactorial concept. Reg Anesth Pain Med. 2004 Nov-Dec;29(6):564-75; discussion 524. doi: 10.1016/j.rapm.2004.08.003.

Reference Type BACKGROUND
PMID: 15635516 (View on PubMed)

Liu SS, Ortolan S, Sandoval MV, Curren J, Fields KG, Memtsoudis SG, YaDeau JT. Cardiac Arrest and Seizures Caused by Local Anesthetic Systemic Toxicity After Peripheral Nerve Blocks: Should We Still Fear the Reaper? Reg Anesth Pain Med. 2016 Jan-Feb;41(1):5-21. doi: 10.1097/AAP.0000000000000329. No abstract available.

Reference Type RESULT
PMID: 26650424 (View on PubMed)

Vasques F, Behr AU, Weinberg G, Ori C, Di Gregorio G. A Review of Local Anesthetic Systemic Toxicity Cases Since Publication of the American Society of Regional Anesthesia Recommendations: To Whom It May Concern. Reg Anesth Pain Med. 2015 Nov-Dec;40(6):698-705. doi: 10.1097/AAP.0000000000000320.

Reference Type RESULT
PMID: 26469367 (View on PubMed)

Dillane D, Finucane BT. Local anesthetic systemic toxicity. Can J Anaesth. 2010 Apr;57(4):368-80. doi: 10.1007/s12630-010-9275-7. Epub 2010 Feb 12.

Reference Type RESULT
PMID: 20151342 (View on PubMed)

Lee LA, Posner KL, Cheney FW, Caplan RA, Domino KB. Complications associated with eye blocks and peripheral nerve blocks: an american society of anesthesiologists closed claims analysis. Reg Anesth Pain Med. 2008 Sep-Oct;33(5):416-22. doi: 10.1016/j.rapm.2008.01.016.

Reference Type RESULT
PMID: 18774510 (View on PubMed)

Auroy Y, Narchi P, Messiah A, Litt L, Rouvier B, Samii K. Serious complications related to regional anesthesia: results of a prospective survey in France. Anesthesiology. 1997 Sep;87(3):479-86. doi: 10.1097/00000542-199709000-00005.

Reference Type RESULT
PMID: 9316950 (View on PubMed)

Takeda A, Ferraro LH, Rezende AH, Sadatsune EJ, Falcao LF, Tardelli MA. Minimum effective concentration of bupivacaine for axillary brachial plexus block guided by ultrasound. Braz J Anesthesiol. 2015 May-Jun;65(3):163-9. doi: 10.1016/j.bjane.2013.11.007. Epub 2015 Feb 16.

Reference Type RESULT
PMID: 25925026 (View on PubMed)

Other Identifiers

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Bupvacaine Pharmacokinetic

Identifier Type: -

Identifier Source: org_study_id