A Pilot Study to Investigate Plasma Bupivacaine Concentrations in Children Receiving Total Intravenous Anaesthesia and Caudal Analgesia

Phase 1

Completed

• Conditions: Anesthesia
• Interventions: Drug: sevoflurane; Drug: propofol

• Registration Number: NCT01216007
• Lead Sponsor: University of British Columbia

Brief Summary

The objective of this pilot study is to compare plasma \[bupivacaine\] between two groups of paediatric patients under general anaesthesia who will all receive regional caudal anaesthesia with bupivacaine: group 1 will receive TIVA and group 2 will receive a volatile anaesthetic.

Detailed Description

Hypothesis:

The investigators hypothesize that there will be a detectable difference in free plasma \[bupivacaine\] between these two treatment groups, with lower free plasma \[bupivacaine\] in the TIVA group.

Background:

Local anesthetics (LA) are frequently administered intra-operatively, in combination with general anaesthesia, for pain management in children. Although highly effective in this regard, LAs possess a narrow margin of safety. High plasma levels can cause toxicity in both the central nervous system (CNS) and the cardiovascular system (CVS) and may result from either the correct placement of an excessive dose or an inadvertent intravenous (IV) injection of a correct dose.

Specific Objectives:

The objective of this pilot study is to compare plasma \[bupivacaine\] between two groups of paediatric patients under general anaesthesia who will all receive regional caudal anaesthesia with bupivacaine: group 1 will receive TIVA and group 2 will receive a volatile anaesthetic.

Methods:

Induction of anesthesia: The TIVA group will receive the BCCH standard regimen comprising induction with propofol 5 mg/kg and remifentanil 2.5 mcg/kg, followed by maintenance infusion of propofol 200-400 mcg/kg/min and remifentanil 0.1-0.2 mcg/kg/min. Total cumulative Intralipid® doses will be recorded at times of caudal injection and blood sampling. The volatile anesthesia group will undergo inhalational induction with sevoflurane in oxygen, followed by maintenance with a volatile agent of the anesthesiologist's choice. In both groups, airway management will be at the discretion of the anesthesiologist. Standard minimum monitoring will be applied. A caudal epidural will then be performed using a standard technique.

Administration of caudal analgesia and whole blood sampling: A caudal dose of 1 ml/kg of 0.25% bupivacaine (2.5 mg/kg) with 1 in 200 000 epinephrine will be administered at time zero (T0). Venous blood samples of 5 ml will be obtained from a second indwelling IV cannula 15 (T1) and 30 (T2) min after caudal injection. These will be collected into EDTA-containing tubes by the PART research assistant and transferred to the BCCH pharmacy research technician (blinded to anesthetic technique) for analysis. Blood samples will be immediately centrifuged. The extracted plasma will be frozen at -850C. Total and free bupivacaine plasma concentrations will be determined using high-pressure liquid chromatography (HPLC) and ultrafiltration.

Data Analysis:

This pilot study will have two primary outcome measures, total and free plasma bupivacaine concentrations. These data will be presented as mean (± SD) at T1 and T2. Normal distribution will be tested by histogram plot. Between-group (TIVA vs. volatile anaesthesia) comparisons of total and free plasma bupivacaine levels will be performed using appropriate analyses of variance. This analysis will determine if there is a detectable difference in plasma concentrations between the TIVA and volatile anaesthesia groups. These data will then be used in a power calculation to determine necessary group sizes for a future randomized controlled trial (RCT) study. Statistical analysis will be conducted using Analyse-It® (Analyse-It Software, Leeds, UK) in consultation with a statistician (Clinical Research Statistical Unit).

Study Timeline

• Study First Submitted: 2010-08-30
• Study Start: 2010-10
• Study First Submitted QC: 2010-10-06
• Study First Posted: 2010-10-07
• Primary Completion: 2012-10
• Study Completion: 2012-10
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-22
• Last Update Posted: 2017-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Inhalational	sevoflurane	Inhalational/volatile general anesthetic
TIVA	propofol	TIVA

Primary Outcome Measures

Name	Time	Method
Total and free plasma bupivacaine concentrations		5 mL blood sample will be obtained at 15 and 30min. Total and free plasma bupivacaine concentrations

Trial Locations

Locations (1)

BC Children's Hospital, Department of Anesthesia; 🇨🇦 Vancouver, British Columbia, Canada