Estimation of Effective Dose 95 (ED95) of Intrathecal Isobaric 2-chloroprocaine (2-CP) Based on the Height (cm) of a Patient Undergoing Ambulatory Knee Arthroscopy

Study Overview
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Brief Summary
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In ambulatory surgery, the choice of the local anesthetic used is essential. The ideal local anesthetic must allow a quick installation of the spinal block, a duration of the sensory block adapted to the surgery with a minimum of side effects. These side effects include bradycardia, hypotension and block failure during the intraoperative period; bladder retention, transient neurological disorders during the post-operative period. The achievement of kinetic objectives associated with a reduction in side effects is related to the choice of local anesthetic and the dose administered. However, there are interindividual pharmacokinetic variations that make it difficult to predict the effective dose and the unfortunate occurrence of side effects. In this context, the height of the patient is a criterion involved in the level, the duration of the sensitive motor block and therefore the side effects The local anesthetic of the amino ester family, isobaric 2-chloroprocaine (2-CP) has been successfully used for spinal anesthesia since several decades. With a short duration of action, it is preferred to other anesthetics for the short-term outpatient surgeries. However, the effective dose 95 (ED95) of intrathecal isobaric 2-CP is currently unknown. The purpose of this prospective study is to determine the ED95 of the spinal 2-CP using the continuous re-evaluation method (Continual Reassessment Method) (CRM) based on patient's height

Official Title
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Estimation of Effective Dose 95 (ED95) of Intrathecal Isobaric 2-chloroprocaine (2-CP) Based on the Height (cm) of a Patient Undergoing Ambulatory Knee Arthroscopy : Dose-finding Study Based on the Continual Reassessment Method (CRM)

Conditions
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Knee Arthroscopy

Intervention / Treatment
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* Drug: Isobaric 2-chloroprocaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed informed consent scheduled outpatient knee arthroscopy between 18 and 80 years old American Society of Anesthesiologists physical status (ASA) < III Height between 150 and 195 cm Exclusion Criteria: cardiac pathology (such as heart failure, aortic stenosis) coagulation disorder (International Normalized Ratio (INR) > 1.3, platelets<80.000/mm3) known allergy to local anaesthetics central and peripheral neuropathies patient's refusal

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1 : Height 150-165 cm<br>Dose-finding study with 4 subjects per dose and a maximum of 40 patients by cohort. The cohort 1 includes patients whose the height is between 150 and 165 cm. To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), isobaric 2-chloroprocaine will be administrated at the dose initial of 40 mg in the cohort 1 for the first 4 subjects. For the next subjects, the doses to administrate will vary 5 mg (0.5 ml) and will be determined by the Continual Reassessment Method (CRM) according to the observed responses in the previous subjects. Doses will be staggered from 25 to 50 mg for cohort 1. | Drug: Isobaric 2-chloroprocaine<br>* The doses of isobaric 2-chloroprocaine will be administrated intrathecally and will be adjusted according to the observed responses in the previous subjects.<br>* Other names: Ampres 10mg/ml;|
| Cohort 2 : Height 166-180 cm<br>Dose-finding study with 4 subjects per dose and a maximum of 40 patients by cohort. The cohort 2 includes patients whose the height is between 166 and 180 cm. To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), isobaric 2-chloroprocaine will be administrated at the dose initial of 45 mg in the cohort 2 for the first 4 subjects. For the next subjects, the doses to administrate will vary 5 mg (0.5 ml) and will be determined by the Continual Reassessment Method (CRM) according to the observed responses in the previous subjects. Doses will be staggered from 30 to 55 mg for cohort 2. | Drug: Isobaric 2-chloroprocaine<br>* The doses of isobaric 2-chloroprocaine will be administrated intrathecally and will be adjusted according to the observed responses in the previous subjects.<br>* Other names: Ampres 10mg/ml;|
| Cohort 3 : Height 181-195 cm<br>Dose-finding study with 4 subjects per dose and a maximum of 40 patients by cohort. The cohort 3 includes patients whose the height is between 166 and 180 cm. To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), isobaric 2-chloroprocaine will be administrated at the dose initial of 50 mg in the cohort 3 for the first 4 subjects. For the next subjects, the doses to administrate will vary 5 mg (0.5 ml) and will be determined by the Continual Reassessment Method (CRM) according to the observed responses in the previous subjects. Doses will be staggered from 35 to 60 mg for cohort 3. | Drug: Isobaric 2-chloroprocaine<br>* The doses of isobaric 2-chloroprocaine will be administrated intrathecally and will be adjusted according to the observed responses in the previous subjects.<br>* Other names: Ampres 10mg/ml;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success or failure of anesthesia | The anesthesia will be considered as a success if there is an extension of the sensory block to the Th12 dermatome after inflation of the tourniquet, absence of pain during tourniquet inflation, incision and overall surgery. Or the anesthesia will be considered as a failure if there is an absence of extension of the sensory block at the Th12 dermatome, pain at the tourniquet inflation, at the incision, or during surgery. | perioperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum level of sensory block assessed as loss of sensation to pinprick, cold | The level of sensory block will be assessed as loss of sensation to pinprick and cold at 5, 10, 20 and 30 minutes after the intrathecal injection (corresponding to time 0), every 10 minutes in the Post Anesthesia Care Unit (PACU) and every 30 minutes after PACU discharge. | Until complete release of sensory block (up to 5 hours after surgery) | 
| Level of motor block assessed by the Bromage score | The level of motor block will be determined at 5, 10, 20 and 30 minutes after intrathecal injection (corresponding to time 0) and every 10 minutes in the post-anesthesia care unit (PACU). The level of motor block will be assessed by using the Bromage Scale. | Until complete release of motor block (up to 5 hours after surgery) | 
| Side-effects (nausea, vomiting) | Nausea and vomiting are treated in the PACU and the post operative unit. | up to 5 hours after surgery | 
| Pain as assessed by Visual Analog Scale | Pain levels will be determined at tourniquet inflation, incision, every 10 minutes in the post-anesthesia care unit (PACU), every 30 minutes after PACU discharge and 24h after the surgery at home (by phone). Visual Analog pain score (scale = 0 no pain; 10= worst pain imaginable) | up to 24 hours after surgery | 
| End time of sensory block | The patient is asked to note the time at which he/she feels that he/she has regained a strictly normal sensitivity | Until complete release of sensory block (up to 5 hours after surgery) | 
| Time to void | The time to obtain the first micturition will be noted. | up to maximum 5 hours after surgery | 
| Bladder volume before first micturition | An evacuating bladder catheterization is performed when a bladder volume greater than 600 mL, confirmed by a Bladderscan device, is associated with the following signs and/or symptoms: hypogastric pain, anuria or overflow urination. | up to maximum 5 hours after surgery | 
| Time to eligibility for discharge defined by complete regression of sensory block | Time of discharge of the patient from the hospital. | up to maximum 5 hours after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spinal anesthesia, Knee Arthroscopy, Chloroprocaine, Height, Effective Dose (ED95), Continual Reassessment Method (CRM)