Pharmacokinetic Study of Intravenous Lidocaine in Young and Elderly Patients (ElderLIDO_1)

Aging is accompanied by a gradual alteration in the functional reserve of several organs and a change in body composition that can affect the pharmacokinetics, response, and safety profile of medications. Lidocaine is a local anesthetic used daily in perineural or intravenous administration to reduce the need for opioids. Although its analgesic efficacy is well-established, there is currently only one older study regarding the pharmacokinetics and pharmacokinetic-pharmacodynamic (PK-PD) relationship of lidocaine in healthy elderly patients. In this study, conducted with a small sample size (13 subjects over 64 years old and 24 young subjects under 38 years old) and using a low bolus of 25 mg, the half-life of lidocaine was increased by 59% and clearance was decreased by 35% in elderly male subjects without significant differences in females. However, the recommendations for intravenous administration of lidocaine for analgesic purposes are the same for all: a bolus of 1 to 2 mg/kg followed by continuous administration of 1.5 to 2 mg/kg/h. Morphine sparing is particularly important in elderly patients due to their increased sensitivity to adverse effects. With this study, the investigators aim to define the optimal dose to administer in elderly subjects, in order to optimize analgesia while remaining within the therapeutic range to limit the adverse effects of lidocaine.

Study Overview

• Status: Recruiting
• Conditions: Anesthesia
• Intervention / Treatment: Other: Pre-inclusion; Other: Inclusion; Drug: Lidocaine; Other: Pharmacokinetic study of intravenous lidocaine; Other: Pain; Other: adverse effects/events; Biological: biological blood test

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Marie LE NAOU; Phone Number: 0299282555; Email: marie.lenaou@chu-rennes.fr
• Study Contact Backup: Name: Pauline Rouxel, MD; Phone Number: 0299266724; Email: pauline.rouxel@chu-rennes.fr

Study Locations

• France
  • Rennes, France, 35000
    • Recruiting
    • CHU de Rennes - Hôpital Sud
    • Contact: Marie LE NAOU; Phone Number: 0299282555; Email: marie.lenaou@chu-rennes.fr
    • Principal Investigator: Pauline Rouxel, MD
    • Contact: Pauline Rouxel; Phone Number: 0299266724; Email: pauline.rouxel@chu-rennes.fr
  • CHU De Rennes
    • Rennes, CHU De Rennes, France, 35033
      • Not yet recruiting
      • CHU de Rennes - Hopital Pontchaillou
      • Contact: Pauline Rouxel, MD
      • Principal Investigator: Pauline Rouxel, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

CI1 - Adult participant (≤ 40 years old) and (≥ 70 years old). CI2 - Undergoing abdominal, digestive, hepatic, urological, or gynecological surgery with an expected duration > 2 hours.

CI3 - Covered by a social security plan. CI4 - Provided with both oral and written information about the protocol and has signed informed consent to participate in this research.

Exclusion Criteria:

NC1 - Allergy to lidocaine or any of its excipients.

NC2 - Presence of comorbidities that may alter lidocaine pharmacokinetics, such as:

• Heart failure (ejection fraction < 45%).
• Renal failure (creatinine clearance < 15 ml/min).
• Hepatic failure (prothrombin time < 15%).
• Body Mass Index (BMI) > 30.

NC3 - Long-term treatment with an antiarrhythmic drug.

NC4 - Ongoing treatment with strong CYP 1A2 inhibitors (e.g., Ciprofloxacin, Fluvoxamine) and/or CYP 1A2 inducers (e.g., Carbamazepine, Modafinil, Ritonavir).

NC5 - Use of peripheral or neuraxial regional anesthesia or local anesthetic infiltration.

NC6 - Known pregnancy or ongoing breastfeeding.

NC7 - Adult under legal protection (e.g., judicial safeguard, guardianship, or tutelage) or deprived of liberty.

NC8 - Participation in another interventional study.

EXCLUSION CRITERIA

EC1 - Any eligibility criterion that is no longer met between the signing of consent and the day of surgery.

EC2 - Participant with no blood sample for pharmacokinetics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: elderly patients; Adult participant ≥ 70 years old	Other: Pre-inclusion; Information and presentation of the proposed study to participants during the anesthesia consultation scheduled prior to surgery, including provision of the information document and consent form. Trial participants will have at least 2 days to decide whether or not to take part in the trial.; Other: Inclusion; Participants will be welcomed according to the usual process in the digestive, hepatic, urological, or gynecological surgery service. The inclusion visit will coincide with the pre-anesthesia visit during which the absence of contraindications for starting the study will be verified, particularly the occurrence of any health changes since the anesthesia visit that would contraindicate anesthesia or lidocaine administration. During this visit, participant consent will be obtained. The informed consent form must be signed no later than the morning of the intervention. For women of childbearing age, the absence of current pregnancy will be verified orally for each participant included. A pregnancy test may be performed if the participant so wishes, but a systematic test is not justified.; Drug: Lidocaine; Induction of anesthesia will be at the discretion of the attending anesthesiologist, with a lidocaine bolus of 2 mg/kg administered over 1 minute, followed by a continuous IV infusion of 2 mg/kg/h.; Other: Pharmacokinetic study of intravenous lidocaine; Blood samples of 3 mL will be collected in heparinized tubes without gel of 4 ml at 30, 60 and 120 minutes after the start of lidocaine infusion, then every two hours during surgery, and two finals samples at 15 and 60 minutes after the infusion stops.; Other: Pain; . Maximal pain reported in the post-anesthesia care unit (PACU) and maximal pain at rest and with movement at 24 hours post-extubation will be recorded.; Other: adverse effects/events; Any adverse effects/events will be documented from the start of lidocaine administration until 24 hours post-extubation,; Biological: biological blood test; A biological blood test, not performed in routine practice, will be carried out to measure the following parameters: albumin, ASAT, ALAT, PAL, GammaGT, total and conjugated bilirubin, creatinine, with calculation of GFR.
Other: Young patients; Adult participant ≤ 40 years old)	Other: Pre-inclusion; Information and presentation of the proposed study to participants during the anesthesia consultation scheduled prior to surgery, including provision of the information document and consent form. Trial participants will have at least 2 days to decide whether or not to take part in the trial.; Other: Inclusion; Participants will be welcomed according to the usual process in the digestive, hepatic, urological, or gynecological surgery service. The inclusion visit will coincide with the pre-anesthesia visit during which the absence of contraindications for starting the study will be verified, particularly the occurrence of any health changes since the anesthesia visit that would contraindicate anesthesia or lidocaine administration. During this visit, participant consent will be obtained. The informed consent form must be signed no later than the morning of the intervention. For women of childbearing age, the absence of current pregnancy will be verified orally for each participant included. A pregnancy test may be performed if the participant so wishes, but a systematic test is not justified.; Drug: Lidocaine; Induction of anesthesia will be at the discretion of the attending anesthesiologist, with a lidocaine bolus of 2 mg/kg administered over 1 minute, followed by a continuous IV infusion of 2 mg/kg/h.; Other: Pharmacokinetic study of intravenous lidocaine; Blood samples of 3 mL will be collected in heparinized tubes without gel of 4 ml at 30, 60 and 120 minutes after the start of lidocaine infusion, then every two hours during surgery, and two finals samples at 15 and 60 minutes after the infusion stops.; Other: Pain; . Maximal pain reported in the post-anesthesia care unit (PACU) and maximal pain at rest and with movement at 24 hours post-extubation will be recorded.; Other: adverse effects/events; Any adverse effects/events will be documented from the start of lidocaine administration until 24 hours post-extubation,; Biological: biological blood test; A biological blood test, not performed in routine practice, will be carried out to measure the following parameters: albumin, ASAT, ALAT, PAL, GammaGT, total and conjugated bilirubin, creatinine, with calculation of GFR.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of lidocaine	Plasma concentration of lidocaine at steady state ( at 60 min from initial lidocaine bolus)	at 60 min from initial lidocaine bolus

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clearance	Other pharmacokinetic parameters of lidocaine: clearance	Day 0
Area under the curve	Other pharmacokinetic parameters of lidocaine: area under the curve (AUC)	Day 0
plasma half-life	Other pharmacokinetic parameters of lidocaine: plasma half-life	Day 0
Volume of distribution	Other pharmacokinetic parameters of lidocaine: volume of distribution.	Day 0
Free concentration	Free concentration of lidocaine.	Day 0
Total morphine-equivalent consumption	Total morphine-equivalent consumption at 24 hours post-extubation.	24 hours post-extubation.
Maximal pain reported in the post-anesthesia care unit (PACU)	Maximal pain reported in the post-anesthesia care unit (PACU) assessed using the Numerical Rating Scale (NRS) for pain (Numerical scale from 0 to 10 (0: no pain, 10: worst pain ever experienced))	Day 0
Maximal pain at rest in the 24h post-extubation	Maximal pain at rest in the 24h post-extubation, assessed using the Numerical Rating Scale (NRS) for pain. (Numerical scale from 0 to 10 (0: no pain, 10: worst pain ever experienced))	24 hours post-extubation
Maximal pain with movement in the 24h post-extubation	Maximal pain with movement in the 24h post-extubation, assessed using the Numerical Rating Scale (NRS) for pain (Numerical scale from 0 to 10 (0: no pain, 10: worst pain ever experienced))	24 hours post-extubation
Frequency of adverse effects	Frequency of adverse effects attributable to lidocaine at 24 hours post-extubation.	24 hours post-extubation
Number of adverse effects	Number of adverse effects attributable to lidocaine at 24 hours post-extubation.	24 hours post-extubation

Collaborators and Investigators

• Sponsor: Rennes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: December 13, 2024
• First Submitted That Met QC Criteria: January 24, 2025
• First Posted (Actual): January 27, 2025

Study Record Updates

• Last Update Posted (Actual): May 2, 2025
• Last Update Submitted That Met QC Criteria: April 29, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Lidocaine
• Other Study ID Numbers: 35RC23_9774_07_ElderLIDO_1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No