Patients Eligible for Elective Lower Extremity Femoral Nerve Surgery, Knee Arthroscopic Surgery
Conditions
Brief summary
This prospective, sequential dose-finding clinical observational study aims to estimate the median effective concentration (EC50) and the 95% effective concentration (EC95) of liposomal bupivacaine for ultrasound-guided femoral nerve block. Sensory and motor block endpoints are evaluated separately at 30 minutes after block placement using a modified up-and-down (sequential allocation) design, with trial termination after eight reversal points.
Detailed description
This prospective clinical observational, sequential dose-finding study is designed to determine the effective concentrations of liposomal bupivacaine for ultrasound-guided femoral nerve block in patients undergoing lower limb surgery or related procedures. All patients receive ultrasound-guided femoral nerve block performed by an experienced anesthesiologist using a standardized technique. A fixed injection volume of liposomal bupivacaine is administered, while the drug concentration is adjusted according to a modified up-and-down sequential method. The concentration for each subsequent participant is determined based on the response of the preceding participant. Following a positive response, the concentration is decreased; following a negative response, the concentration is increased by a pre-specified step size. The study is terminated after eight reversal points (crossovers) are observed. To independently characterize sensory and motor block dose-response relationships, participants are allocated into two endpoint-specific observation groups: Sensory block group Sensory function in the femoral nerve distribution is assessed 30 minutes after block placement using standardized sensory testing. Complete loss of sensation at 30 minutes is defined as a positive response, while preserved sensation is defined as a negative response. Motor block group Motor function of the quadriceps muscle is evaluated 30 minutes after block placement using a standardized motor strength assessment. Complete loss of quadriceps muscle strength or paralysis at 30 minutes is defined as a positive response, while preservation of motor function is defined as a negative response. The primary objective of this study is to estimate the EC50 and EC95 of liposomal bupivacaine for: femoral nerve sensory blockade, and femoral nerve motor blockade, based on sequential allocation data and appropriate dose-response modeling. Secondary objectives include describing the differential sensory-motor block profile of liposomal bupivacaine and evaluating its clinical feasibility and safety for femoral nerve block applications. All patients are monitored for block-related adverse events, including signs of local anesthetic systemic toxicity, nerve injury, and other complications throughout the perioperative period.
Interventions
Liposomal bupivacaine administered for ultrasound-guided femoral nerve block at varying concentrations using a modified up-and-down sequential dose-finding design.
Sponsors
Hainan Medical College
The Second Affiliated Hospital of Hainan Medical University
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Adults aged 18 to 85 years * Scheduled for elective unilateral lower limb surgery * Unilateral ultrasound-guided femoral nerve block clinically indicated as part of routine perioperative anesthesia and analgesia management * Ability to clearly distinguish between the blocked (operated) limb and the contralateral (non-blocked) limb for sensory and pain assessments * Ability to understand the study procedures and provide written informed consent * Ability to cooperate with sensory and motor assessments, including visual analog scale (VAS) scoring and quadriceps muscle strength testing
Exclusion criteria
* Known allergy or hypersensitivity to bupivacaine, amide-type local anesthetics, or any component of liposomal bupivacaine * Infection at or near the planned injection site * Coagulopathy or clinically significant bleeding disorder, or anticoagulant/antiplatelet therapy incompatible with peripheral nerve block * Pre-existing neurological deficits, neuropathy, or motor weakness affecting either lower limb that could interfere with sensory or motor assessments * Severe hepatic dysfunction or other conditions that increase the risk of local anesthetic systemic toxicity * Pregnancy or breastfeeding * Emergency surgery * Inability to complete study assessments or comply with study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| EC50 and EC95 for femoral nerve sensory block | 30 minutes after femoral nerve block placement | The median effective concentration (EC50) and the 95% effective concentration (EC95) of liposomal bupivacaine for ultrasound-guided femoral nerve sensory blockade are estimated using a modified up-and-down sequential dose-finding design. Sensory block is assessed 30 minutes after block placement in the femoral nerve distribution on the blocked side, including the anterior thigh (anterior femoral cutaneous nerve territory) and the medial aspect of the lower leg (saphenous nerve territory). Sensory testing is performed using pinprick testing and/or cold stimulation with an ether-soaked cotton swab, with the contralateral non-blocked limb used as an internal control. Sensory block is graded as follows: 0 = no block (sensation identical to the non-blocked limb); 1 = partial block (reduced sensation); 2 = complete block (absence of pain sensation). A positive sensory response is defined as a sensory block score of 2. |
| EC50 and EC95 for femoral nerve motor block | 30 minutes after femoral nerve block placement | The median effective concentration (EC50) and the 95% effective concentration (EC95) of liposomal bupivacaine for ultrasound-guided femoral nerve motor blockade, estimated using a modified up-and-down sequential dose-finding design. Motor function is evaluated immediately after sensory assessment by assessing quadriceps muscle strength. Patients are instructed to perform a straight leg raise in the supine position or actively extend the knee. Muscle strength is graded using the Medical Research Council (MRC) scale (0-5). Motor function preservation is defined as an MRC score ≥4. A positive motor response (motor block) is defined as an MRC score ≤3, indicating clinically significant weakness or paralysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative pain intensity assessed by VAS | 2, 6, 12, 24, and 48 hours postoperatively | Postoperative pain intensity is assessed using the Visual Analog Scale (VAS, 0-10, where 0 indicates no pain and 10 indicates the worst imaginable pain). VAS scores are recorded separately for the operated (blocked) limb and the contralateral (non-blocked) limb. Pain assessments are performed at 2, 6, 12, 24, and 48 hours after surgery to evaluate postoperative pain progression and potential differences between limbs following femoral nerve block with liposomal bupivacaine. |
| Postoperative movement-evoked pain assessed by VAS | Postoperative day 1 and day 2 | Movement-evoked pain is assessed using the Visual Analog Scale (VAS, 0-10). VAS scores are recorded during active movement of the operated limb on postoperative day 1 and postoperative day 2 to evaluate pain associated with mobilization following femoral nerve block. |
| Quadriceps muscle strength after surgery | Postoperative day 1 and day 2 | Quadriceps muscle strength on the operated side is evaluated using the Medical Research Council (MRC) muscle strength scale (0-5). Assessments are performed on postoperative day 1 and postoperative day 2 to evaluate recovery of motor function following femoral nerve block. |
| Length of hospital stay | From the date of surgery until hospital discharge, assessed up to 30 days postoperatively. | Length of hospital stay is defined as the number of days from the date of surgery to the date of hospital discharge. |
| Time to first ambulation after surgery | From the end of surgery until the first out-of-bed ambulation, assessed up to 72 hours postoperatively. | Time to first ambulation is defined as the time interval from the end of surgery to the patient's first out-of-bed ambulation with or without assistance. |
| Intraoperative heart rate | From skin incision to the end of surgery, assessed continuously during the intraoperative period. | Intraoperative heart rate is continuously monitored and recorded during surgery to assess intraoperative physiological stability. |
| Intraoperative mean arterial pressure | From skin incision to the end of surgery, assessed continuously during the intraoperative period. | Intraoperative mean arterial pressure is continuously monitored and recorded during surgery to assess intraoperative hemodynamic stability. |
Countries
China
Contacts
CONTACTDr.chen
Outcome results
None listed