Anesthesia
Conditions
Brief summary
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.
Interventions
OTHERPre-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.
OTHERInclusion
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.
DRUGLidocaine
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.
OTHERPharmacokinetic 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.
OTHERPain
. 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.
OTHERadverse effects/events
Any adverse effects/events will be documented from the start of lidocaine administration until 24 hours post-extubation,
BIOLOGICALbiological 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.
Sponsors
Rennes University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentration of lidocaine | at 60 min from initial lidocaine bolus | Plasma concentration of lidocaine at steady state ( at 60 min from initial lidocaine bolus) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clearance | Day 0 | Other pharmacokinetic parameters of lidocaine: clearance |
| Area under the curve | Day 0 | Other pharmacokinetic parameters of lidocaine: area under the curve (AUC) |
| plasma half-life | Day 0 | Other pharmacokinetic parameters of lidocaine: plasma half-life |
| Volume of distribution | Day 0 | Other pharmacokinetic parameters of lidocaine: volume of distribution. |
| Free concentration | Day 0 | Free concentration of lidocaine. |
| Total morphine-equivalent consumption | 24 hours post-extubation. | Total morphine-equivalent consumption at 24 hours post-extubation. |
| Maximal pain reported in the post-anesthesia care unit (PACU) | Day 0 | 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)) |
| Maximal pain at rest in the 24h post-extubation | 24 hours 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)) |
| Maximal pain with movement in the 24h post-extubation | 24 hours 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)) |
| Frequency of adverse effects | 24 hours post-extubation | Frequency of adverse effects attributable to lidocaine at 24 hours post-extubation. |
| Number of adverse effects | 24 hours post-extubation | Number of adverse effects attributable to lidocaine at 24 hours post-extubation. |
Countries
France
Outcome results
None listed