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

• ClinicalTrials.gov Identifier: NCT03882489
• Recruitment Status: Completed
• First Posted: March 20, 2019
• Last Update Posted: October 7, 2019
• Sponsor: Centre Hospitalier Universitaire Saint Pierre
• Collaborator: Hôpital de Braine-l'Alleud
• Information provided by (Responsible Party): Centre Hospitalier Universitaire Saint Pierre

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment
Knee Arthroscopy	Drug: Isobaric 2-chloroprocaine

Study Design

• Study Type: Observational
• Actual Enrollment: 120 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: 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)
• Actual Study Start Date: April 11, 2019
• Actual Primary Completion Date: August 16, 2019
• Actual Study Completion Date: August 17, 2019

Groups and Cohorts

Group/Cohort	Intervention/treatment
Cohort 1 : Height 150-165 cm; 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; The doses of isobaric 2-chloroprocaine will be administrated intrathecally and will be adjusted according to the observed responses in the previous subjects.; Other Name: Ampres 10mg/ml
Cohort 2 : Height 166-180 cm; 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; The doses of isobaric 2-chloroprocaine will be administrated intrathecally and will be adjusted according to the observed responses in the previous subjects.; Other Name: Ampres 10mg/ml
Cohort 3 : Height 181-195 cm; 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; The doses of isobaric 2-chloroprocaine will be administrated intrathecally and will be adjusted according to the observed responses in the previous subjects.; Other Name: Ampres 10mg/ml

Outcome Measures

Primary Outcome Measures :

1. Success or failure of anesthesia [ Time Frame: perioperative ]

   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.

Secondary Outcome Measures :

1. Maximum level of sensory block assessed as loss of sensation to pinprick, cold [ Time Frame: Until complete release of sensory block (up to 5 hours after surgery) ]
   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.
2. Level of motor block assessed by the Bromage score [ Time Frame: Until complete release of motor block (up to 5 hours after surgery) ]
   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.
3. Side-effects (nausea, vomiting) [ Time Frame: up to 5 hours after surgery ]
   Nausea and vomiting are treated in the PACU and the post operative unit.
4. Pain as assessed by Visual Analog Scale [ Time Frame: up to 24 hours after surgery ]
   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)
5. End time of sensory block [ Time Frame: Until complete release of sensory block (up to 5 hours after surgery) ]
   The patient is asked to note the time at which he/she feels that he/she has regained a strictly normal sensitivity
6. Time to void [ Time Frame: up to maximum 5 hours after surgery ]
   The time to obtain the first micturition will be noted.
7. Bladder volume before first micturition [ Time Frame: up to maximum 5 hours after surgery ]
   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.
8. Time to eligibility for discharge defined by complete regression of sensory block [ Time Frame: up to maximum 5 hours after surgery ]
   Time of discharge of the patient from the hospital.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Adult patients undergoing ambulatory knee arthroscopy under the spinal anesthesia

Criteria

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

Contacts and Locations

Locations

Belgium

Braine-l'Alleud Hospital

Braine-l'Alleud,, Belgium, 1420

Sponsors and Collaborators

Centre Hospitalier Universitaire Saint Pierre

Hôpital de Braine-l'Alleud

Investigators

• Principal Investigator: Emmanuel Guntz, MD, PhD; Université Libre de Bruxelles (ULB), Braine-l'Alleud Hospital
• Principal Investigator: Emmanuel Guntz; Université Libre de Bruxelles (ULB), Braine-l'Alleud Hospital

More Information

Publications:

Yu X, Zhang F. The effect of parturient height on the median effective dose of intrathecally administered ropivacaine. Ann Saudi Med. 2016 Sep-Oct;36(5):328-333.

Förster JG, Rosenberg PH, Harilainen A, Sandelin J, Pitkänen MT. Chloroprocaine 40 mg produces shorter spinal block than articaine 40 mg in day-case knee arthroscopy patients. Acta Anaesthesiol Scand. 2013 Aug;57(7):911-9. doi: 10.1111/aas.12107. Epub 2013 Mar 25.

FOLDES FF, McNALL PG. 2-Chloroprocaine: a new local anesthetic agent. Anesthesiology. 1952 May;13(3):287-96.

Yoos JR, Kopacz DJ. Spinal 2-chloroprocaine: a comparison with small-dose bupivacaine in volunteers. Anesth Analg. 2005 Feb;100(2):566-572. doi: 10.1213/01.ANE.0000143356.17013.A1.

Gonter AF, Kopacz DJ. Spinal 2-chloroprocaine: a comparison with procaine in volunteers. Anesth Analg. 2005 Feb;100(2):573-579. doi: 10.1213/01.ANE.0000143380.36298.4A.

Casati A, Fanelli G, Danelli G, Berti M, Ghisi D, Brivio M, Putzu M, Barbagallo A. Spinal anesthesia with lidocaine or preservative-free 2-chlorprocaine for outpatient knee arthroscopy: a prospective, randomized, double-blind comparison. Anesth Analg. 2007 Apr;104(4):959-64.

• Responsible Party: Centre Hospitalier Universitaire Saint Pierre
• ClinicalTrials.gov Identifier: NCT03882489
• Other Study ID Numbers: B076201836762
• First Posted: March 20, 2019
• Last Update Posted: October 7, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Centre Hospitalier Universitaire Saint Pierre:

spinal anesthesia; Knee Arthroscopy; Chloroprocaine; Height; Effective Dose (ED95); Continual Reassessment Method (CRM)

Additional relevant MeSH terms:

Chloroprocaine; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents