Overview

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.

Eligibility

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