Pharmacokinetics of Levobupivacaine After Cesarean Section

NCT02852720 | Completed Phase 4

• 1 other identifier: 160605003
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Transversus abdominis plane (TAP) block provides effective analgesia and is now a standard of care for analgesia after cesarean section. There is no information on levobupivacaine pharmacokinetics post TAP after pregnancy. Objective: Generate a pharmacokinetic levobupivacaine model and its effect on the electrocardiogram (ECG). Method: The investigators will study 12 healthy term pregnant patients, scheduled for elective cesarean section under spinal anesthesia. A bilateral TAP block is performed with 20 ml 0.25% levobupivacaine with epinephrine 5 ug/ml. Sensory block will be assessed at 1-2-6 and 12 hours post puncture. 2 ml of venous blood will be obtained at 2-5-10-30-45-60-90 and 180 minutes. With a Holter machine we will study the effect of levobupivacaine plasma levels and the QTc changes. Expected results: 1) Plasma levobupivacaine levels; 2) Changes in QTc .

Conditions

Pain, Postoperative

Keywords

Pharmacokinetics; levobupivacaine; Pregnancy; Cesarean section; Electrocardiography

Outcome Measures

Primary Outcomes (1)

• Levobupivacaine free plasma levels

  Plasma levobupivacaine will be assessed at defined timepoints after TAP block

  180 minutes

Secondary Outcomes (1)

• EKG

  12 hours

Study Arms (1)

Pharmacokinetics

EXPERIMENTAL

A bilateral TAP block will be performed with 20 ml levobupivacaine 0,25% and epinephrine (5ug/ml). After the blockade, venous blood samples will be taken on predefined times.

Drug: Levobupivacaine; Procedure: Spinal anesthesia; Procedure: Peripheral vein canulation; Procedure: Ultrasonography; Device: Holter

Interventions

Levobupivacaine DRUG

After the block procedure, 2 ml blood samples will be taken in defined times to determine the plasma blood levels of levobupivacaine.

Also known as: Chirocaine

Pharmacokinetics

Spinal anesthesia PROCEDURE

Spinal anesthesia in the L3-L4 or L4-L5 interspace with hyperbaric bupivacaine 0,75% 1,4 ml plus 20 ug fentanyl to achieve a bilateral anesthetic level of T4 determined by pinprick.

Also known as: Subarachnoid anesthesia

Pharmacokinetics

Peripheral vein canulation PROCEDURE

An intravenous (18-gauge) catheter will be placed under local anesthesia for co hydration and a second IV catheter for venous sampling

Also known as: Intravenous catheter

Pharmacokinetics

Ultrasonography PROCEDURE

TAP blocks will be performed using a ultrasound Sonosite M-Turbo US machine (Sonosite Inc, Washington) with an L38x 10-5 megahertz (MHz), 38-mm broadband linear array probe.

Also known as: Ultrasound

Pharmacokinetics

Holter DEVICE

A portable 12-lead Holter (NorthEast Monitoring®, Boston, USA) will record continuously the electrocardiogram (ECG) after the TAP block, for 24 hrs.

Also known as: Continuous electrocardiogram

Pharmacokinetics

Eligibility Criteria

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

You may qualify if:

• Term pregnant patients
• American Society of Anesthesiologists physical status I or II, scheduled for elective cesarean section.

You may not qualify if:

• Allergy/sensitivity to the local anaesthetic
• Significant renal or liver dysfunction.

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (1)

Hospital Clinico Universidad Catolica de Chile

Santiago, RM, 8330024, Chile

Location

Related Publications (8)

• Bardsley H, Gristwood R, Baker H, Watson N, Nimmo W. A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers. Br J Clin Pharmacol. 1998 Sep;46(3):245-9. doi: 10.1046/j.1365-2125.1998.00775.x.

  PMID: 9764965 BACKGROUND

• Gerbershagen HJ, Aduckathil S, van Wijck AJ, Peelen LM, Kalkman CJ, Meissner W. Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures. Anesthesiology. 2013 Apr;118(4):934-44. doi: 10.1097/ALN.0b013e31828866b3.

  PMID: 23392233 BACKGROUND

• McDonnell JG, Curley G, Carney J, Benton A, Costello J, Maharaj CH, Laffey JG. The analgesic efficacy of transversus abdominis plane block after cesarean delivery: a randomized controlled trial. Anesth Analg. 2008 Jan;106(1):186-91, table of contents. doi: 10.1213/01.ane.0000290294.64090.f3.

  PMID: 18165577 BACKGROUND

• Weiss E, Jolly C, Dumoulin JL, Meftah RB, Blanie P, Laloe PA, Tabary N, Fischler M, Le Guen M. Convulsions in 2 patients after bilateral ultrasound-guided transversus abdominis plane blocks for cesarean analgesia. Reg Anesth Pain Med. 2014 May-Jun;39(3):248-51. doi: 10.1097/AAP.0000000000000088.

  PMID: 24682078 BACKGROUND

• Corvetto MA, Echevarria GC, De La Fuente N, Mosqueira L, Solari S, Altermatt FR. Comparison of plasma concentrations of levobupivacaine with and without epinephrine for transversus abdominis plane block. Reg Anesth Pain Med. 2012 Nov-Dec;37(6):633-7. doi: 10.1097/AAP.0b013e31826c330a.

  PMID: 23038415 BACKGROUND

• Karlsson MO, Sheiner LB. The importance of modeling interoccasion variability in population pharmacokinetic analyses. J Pharmacokinet Biopharm. 1993 Dec;21(6):735-50. doi: 10.1007/BF01113502.

  PMID: 8138894 BACKGROUND

• Ikeda Y, Oda Y, Nakamura T, Takahashi R, Miyake W, Hase I, Asada A. Pharmacokinetics of lidocaine, bupivacaine, and levobupivacaine in plasma and brain in awake rats. Anesthesiology. 2010 Jun;112(6):1396-403. doi: 10.1097/ALN.0b013e3181d9cc54.

  PMID: 20460991 BACKGROUND

• Lacassie HJ, Rolle A, Cortinez LI, Solari S, Corvetto MA, Altermatt FR. Pharmacokinetics of levobupivacaine with epinephrine in transversus abdominis plane block for postoperative analgesia after Caesarean section. Br J Anaesth. 2018 Aug;121(2):469-475. doi: 10.1016/j.bja.2018.02.070.

  PMID: 30032887 DERIVED

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Levobupivacaine; Anesthesia, Spinal; High-Energy Shock Waves; Electrocardiography, Ambulatory

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bupivacaine; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Anesthesia, Conduction; Anesthesia; Anesthesia and Analgesia; Ultrasonic Waves; Sound; Radiation, Nonionizing; Radiation; Physical Phenomena; Electrocardiography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Monitoring, Ambulatory; Monitoring, Physiologic

Study Officials

• Hector J Lacassie, MD

  Pontificia Universidad Catolica de Chile

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: July 27, 2016
• First Posted: August 2, 2016
• Study Start: December 15, 2016
• Primary Completion: February 15, 2017
• Study Completion: February 15, 2017
• Last Updated: February 16, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

CL (1)