None listed
Conditions
Brief summary
We aim to develop a population pharmacokinetic model for lidocaine administration by intravenous infusion and identify clinically important covariates by conducting a prospective, single-centre, exploratory interventional study. It is anticipated that this project will provide data to inform a model which will facilitate accurate and potentially safer dosing of intravenous lidocaine. We plan to recruit 40 female adult patients undergoing breast reconstruction surgery. Patients will receive a bolus dose of lidocaine followed by an intravenous infusion. Dosing will be calculated using lean body weight and based on the dosing protocol approved and used in the LOLIPOP Pilot Trial (1) which has proven it to be safe and feasible. As an additional safety feature, we will be using half the dose of that used in LOLIPOP. This is because, unlike the LOLIPOP Trial, pain is not one of our outcome measures. Our primary aim of examining serial serum lidocaine concentrations and the potential formulation of a pharmacokinetic model is achievable at these lower doses. Lidocaine samples will be taken at hourly intervals throughout the duration of the infusion, and twice postoperatively between 8 and 26 hours of ceasing the infusion Current research (including the LOLIPOP Trial) is focussed on the analgesic properties of intravenous lidocaine. Several studies have already demonstrated a reduction in pain scores and a decrease in peri-operative opioid consumption. The goal of intravenous infusion is to establish and maintain therapeutic plasma concentrations of 0.5-5 mcg/mL, whilst avoiding higher doses that may result in toxicity. Lidocaine has complex pharmacokinetics and demonstrates non-linear (time-dependent) pharmacokinetics with prolonged infusion, including increasing plasma concentrations and prolonging elimination half-life. Establishing a population-based pharmacokinetic model will facilitate a dosing regimen that maintains plasma lidocaine concentrations within a safe therapeutic window. This will improve the safety of intravenous lidocaine infusion by decreasing the risks of systemic toxicity, and potentially improve its efficacy by maintaining effective therapeutic plasma levels. [1] Toner A.J. BMA, Schug S.A., Corcoran T.B. A pilot multicentre randomised controlled trial of lidocaine infusion in women undergoing breast cancer surgery. Anaesthesia. 2021. ClinicalTrials.gov registration ID: NCT05072314
Interventions
Intraoperative intravenous bolus and infusion of lidocaine during breast reconstructive surgery.
Drug: Lidocaine 2%
Suitable candidates will be given an intravenous bolus dose of Lidocaine followed by an infusion for the duration of their surgery according to the following dosing parameters:
1) Intravenous bolus of (2.5mg/kg/LBW)/2 [2% lidocaine]
2) Intraoperative infusion of (3.33mg/kg/hr/LBW)/2 [2% lidocaine]
Lean body weight= (9270 x weight)/ (8780 + (244 x BMI))8
where BMI = total body we
Intraoperative intravenous bolus and infusion of lidocaine during breast reconstructive surgery. Drug: Lidocaine 2% Suitable candidates will be given an intravenous bolus dose of Lidocaine followed by an infusion for the duration of their surgery according to the following dosing parameters: 1) Intravenous bolus of (2.5mg/kg/LBW)/2 [2% lidocaine] 2) Intraoperative infusion of (3.33mg/kg/hr/LBW)/2 [2% lidocaine] Lean body weight= (9270 x weight)/ (8780 + (244 x BMI))8 where BMI = total body weight/ (height in metres) = W / H2 W = total body weight in kg H = height in metres. Ideal body weight is capped at 68Kg. The values entered into the Alaris PK pump program MUST be double checked against the printout from the drug dosing module by the research coordinator with the attending anaesthetist. The bolus and infusion will be commenced at induction of anaesthesia and the infusion will be ceased at the completion of surgery. The exact duration of infusion is therefore dependent on operative considerations. The dose of the intervention is determined by each individual patient's lean body weight. The attending Anaesthetist will be responsible for the administration of the intravenous lidocaine. Patients will be under the constant supervision of an Anaesthetist throughout the duration of the infusion. Samples to determine serum lidocaine concentrations will be taken at hourly intervals for the duration of the infusion, once in the Postoperative Anaesthetic Care Unit (PACU) and twice more between 8 and 26 hours post cessation of the infusion.
Sponsors
Royal Perth Hospital
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
• Adult biological female patient aged >=18 and <80 years old • Undergoing remote breast reconstructive surgery with a unilateral or bilateral DIEP (or other myocutaneous) flap • ASA physical status 1-3
Exclusion criteria
• Inability to provide informed consent – impaired cognition. Where consent cannot be obtained in English, an interpreter should be used to obtain informed consent • Pregnancy • History of epilepsy • History of anaphylaxis, sensitivity or known contraindication to lidocaine or other amide local anaesthetics, including patients with porphyria and methaemaglobinaemia • Baseline HR <50bpm or SBP <100mmHg • Acute coronary event within the last 3 months • Cardiac Conduction abnormalities including: Heart block (all degrees), Bundle Branch Block or Fascicular Block, Prolonged QT interval, Wolf Parkinson White Syndrome, channellopathy (e.g. Brugada Syndrome). A preoperative ECG is not mandatory. • Abnormal serum sodium and/or potassium concentrations • Active liver disease or abnormal liver function tests • Medications within the last 7 days which affect lidocaine metabolism (amiodarone, beta blockers, cimetidine, fluoroquinolones, fluvoxamine, imidazoles, macrolides, verapamil, HIV drugs • Cardiac Failure • Severe renal disease (CrCl <30ml/min or dialysis dependent) • Recruitment into LOLIPOP or any other Trial • Planned regional anaesthesia/analgesia technique • Co-administration of lidocaine within 24 hours of surgery (e.g. lidocaine patch)
Outcome results
None listed