A Pilot Study to Investigate Plasma Bupivacaine Concentrations in Children Receiving Total Intravenous Anaesthesia and Caudal Analgesia
Condition: Anesthesia
Study type: Interventional
Phase: Phase 1/Phase 2

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).
    

Intervention name(s): propofol; sevoflurane
Intervention type(s): Drug; Drug
Intervention description(s): In the TIVA group, IV access will be obtained as per BCCH routine, with caregiver present. 2% lidocaine 1 mg/kg will be administered via IV to prevent venous pain before induction of anaesthesia with propofol, as per BCCH standard. Induction of anaesthesia will be achieved with an IV bolus of propofol 5 mg/kg and remifentanil 2.5 mcg/kg. Anaesthesia will be maintained with an infusion of propofol 200-400 mcg/kg/min and remifentanil 0.1-0.2 mcg/kg/min. Once the subject is under general anaesthesia, the anaesthesiologist will place a second IV cannula, specifically for the collection of blood samples. This cannula will not be in the same limb as the propofol infusion.; In the volatile anaesthesia group, induction of anaesthesia will be achieved with inhalation of sevoflurane (5-8% in O2/air). Maintenance of anaesthesia will continue with a volatile agent of the anaesthesiologist's choice.
Intervention MeSH terms: Propofol; Sevoflurane
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Diagnostic
Keywords: Plasma; bupivacaine; concentration; caudal; epidural; TIVA; Inhalational; anesthesia; Caudal epidural