Clinical trial NCT03365752
Conditions: Knee Arthroscopy
Sponsor: Hospital for Special Surgery, New York
Start date: 2018-06-24; Completion date: 2021-02-04
Enrollment: 39 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Outpatient knee surgeries with duration of less than one hour pose a challenge to the use of spinal anesthesia given that traditional agents remain in effect for 2-3 hours, thus creating a mismatch between length of surgery and anesthetic resolution. The investigators hypothesize that the use of chloroprocaine can combine the benefits of a short spinal anesthetic while avoiding the side effects of a general anesthetic, thus promoting earlier discharge.

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None
Interventions: intervention 1: Chloroprocaine intervention 2: Mepivacaine intervention 3: General Anesthetics
Intervention descriptions: intervention 1: A spinal anesthetic with 2% chloroprocaine (2cc or 40 mg) will be performed intervention 2: A spinal anesthetic with 1.5% Mepivacaine (3cc or 45 mg) will be performed intervention 3: General anesthetics will be administered intravenously

Protocol documents:
Prot_SAP_000.pdf: 
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Page 1 of 17 
 
 
 
 
 
 
 
 
 
A Comparison Study to Facilitate Earlier Discharge: 
Spinal Versus General Anesthesia for Outpatient 
Knee Surgeries, a Randomized Controlled Study   
 
 
FUNDER: 
Department of Anesthesiology,  
Hospital for Special Surgery 
PROTOCOL NO.: 
IRB #2017-1547 
DATE: 
2/4/2021 
 
 
 
 
 
 
 
 
This document contains the confidential information of the Hospital for Special Surgery.  It is provided to you and your company’s personnel for 
review.  Your acceptance of this document constitutes an agreement that you will not disclose the information contained herein to others without 
the prior written consent of the Hospital for Special Surgery.  No other use or reproduction is authorized by Hospital for Special Surgery, nor does 
the Hospital for Special Surgery assume any responsibility for unauthorized use of this protocol. 


 
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TABLE OF CONTENTS 
TABLE OF CONTENTS................................................................................................................... 2 
PROTOCOL SYNOPSIS.................................................................................................................. 3 
1.0     INTRODUCTION .................................................................................................................... 4 
    2.0 
PRODUCT DESCRIPTION………………………..……………………………………………….4 
3.0      OBJECTIVE OF CLINICAL STUDY ...................................................................................... 4 
4.0      STUDY HYPOTHESIS ........................................................................................................... 4 
5.0      STUDY DESIGN .................................................................................................................... 4 
5.1 
Study Duration ................................................................................................................ 4 
5.2 
Endpoints ....................................................................................................................... 4 
5.2.1 
Primary Endpoint ...................................................................................................... 4 
5.2.2 
Secondary Endpoints ................................................................................................ 4 
5.2.3 
Safety Evaluations. ................................................................................................... 4 
5.3 
Study Site ....................................................................................................................... 4 
6.0        STUDY POPULATION ......................................................................................................... 4 
6.1 
Number of Subjects ........................................................................................................ 4 
6.2 
Inclusion Criteria............................................................................................................. 5 
6.3 
Exclusion Criteria: .......................................................................................................... 5 
    6.4        Randomization………………………………………………………………………………..5 
7.0         PROCEDURES .................................................................................................................... 5 
7.1 
Surgical Procedure ......................................................................................................... 5 
 
7.1.1. Investigational Product Administration………………………………………………. .…..5 
7.2 
Imaging Procedure ......................................................................................................... 5 
7.3 
Medical Record Requirements ....................................................................................... 5 
7.4 
Data Collection ............................................................................................................... 5 
    7.5        Schedule of Assessments……………………………………………………..…………….. 6 
7.6 
Radiological Evaluations ................................................................................................ 7 
7.7 
Clinical Evaluations ........................................................................................................ 7 
 
7.7.1. Revision Surgery………………………………………………………………………. .……7 
8.0         STATISTICAL ANALYSIS .................................................................................................. 7 
9.0         ADVERSE EVENT ASSESSMENT ..................................................................................... 7 
9.1 
Adverse Event (AE) ........................................................................................................ 7 
9.2 
Serious Adverse Events (SAE) ...................................................................................... 7 
9.3 
Subsequent Surgical Interventions Definitions .............................................................. 7 
9.4 
Adverse Event Relationship ........................................................................................... 7 
9.5 
Adverse Event Recording .............................................................................................. 7 
9.6 
Adverse Event Reporting ............................................................................................... 7 
10.0         INVESTIGATOR RESPONSIBILITIES, RECORD AND REPORTS ................................ 7 
10.1 
Subject Consent and Information ................................................................................... 7 
10.2 
Subject Data Protection ................................................................................................. 7 
10.3 
Staff Information ............................................................................................................. 8 
10.4 
Protocol Reviews............................................................................................................ 8 
10.5 
Investigator Records ...................................................................................................... 8 
10.6 
Investigator Reports ....................................................................................................... 8 
 11.0  
REFERENCES……………………………………………………………….………………….8 
APPENDIX A: Case Report Forms .............................................................................................. 9 


 
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PROTOCOL SYNOPSIS 
Protocol Title: 
A Comparison Study to Facilitate Earlier Discharge: Spinal 
Versus General Anesthesia for Outpatient Knee Surgeries, a 
Randomized Controlled Study   
Protocol Number: 
2017-1547 
Protocol Date: 
2/4/2021 
Sponsor: 
The Department of Anesthesiology, Hospital for Special Surgery 
Principal 
Investigator: 
David Kim, MD 
Products: 
2% preservative-free Chloroprocaine (Phase II); Mepivacaine 
(Phase II) 
Objective: 
Outpatient knee surgeries with duration of less than one hour 
poses a challenge to the use of spinal anesthesia given that 
traditional agents remain in effect for 2-3 hours, thus creating a 
mismatch between length of surgery and anesthetic resolution. 
Spinal mepivacaine is mostly used at our institution for these 
surgeries but the prolonged duration of the block in the PACU 
impedes earlier discharge. Patients do not like prolonged PACU 
stays due to slow recovery from spinal anesthesia. Many 
centers instead use general anesthesia (GA). While GA has the 
advantage of less surgery/anesthesia time ratio mismatch, the 
adverse effects of nausea, vomiting, prolonged emergence and 
pain control may contribute to lengthened discharge. Approved 
for spinal use in Europe in 2012, chloroprocaine is proven to be 
an effective local anesthetic with the advantage of faster block 
resolution, averaging 60 to 90 minutes. The intervention we are 
studying is whether chloroprocaine is a superior alternative to 
mepivacaine and general anesthesia in providing surgical 
anesthesia. We hypothesize that the use of chloroprocaine can 
combine the benefits of a short spinal anesthetic while avoiding 
the side effects of a general anesthetic, thus promoting earlier 
discharge. 
Study Design: 
Randomized Controlled Clinical Trial 
Enrollment: 
33/132 
Subject Criteria: 
1. Written informed consent obtained from subject and 
ability for subject to comply with the requirements of the 
study 


 
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2. Subjects scheduled for knee arthroscopy that is 
anticipated to be less than one hour 
 
3. Age 18 to 80 years 
 
4. Ability to follow study protocol 
 
5. English speaking (secondary outcomes include 
questionnaires validated in English only) 
Study Duration: 
6/24/2018 – 2/4/2021 
Data Collection: 
• 
Collection timepoints: Pre-op, POD 0, POD 1, POD 3, 
POD 7 
• 
Sources: EPIC, medical records, and patient  
Outcome 
Parameters: 
• 
The primary outcome will be time until ready for 
discharge, defined as duration from the PACU arrival to 
the time the patient has reached PADSS discharge 
criteria. 
• 
Secondary outcomes: induction time, time of emergence, 
time of resolution of spinal, time of ambulation, time of 
micturition, incidence of urinary retention, incidence of 
transient neurologic symptoms, incidence of neurologic 
deficits/neuropraxia, incidence of side effects related to 
spinal anesthesia, incidence of block failure, incidence of 
opioid related side effects, incidence of PDPH, incidence 
of emergence delirium /delayed emergence, incidence of 
sore throat, incidence of drowsiness, incidence of PONV, 
NRS Pain Scores, opioid consumption, time of discharge 
from PACU, time of meeting discharge criteria, patient 
satisfaction with intraoperative anesthesia and pain 
control, ORSDS, length of PACU stay, length of 
operative time, QoR-15. 
Statistical Analysis: 
Proposed analysis (e.g., student’s t-test, ANOVA, chi-square, 
regression, etc.): 
1. Three pairwise two-sample t-tests or Wilcoxon rank-sum 
tests 
2. Alpha level: 0.05/3 = 0.0167 (two-sided) 
3. Beta or power level: 80% power 
 
 
 


 
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1.0 INTRODUCTION 
Ideally for ambulatory surgeries, the local anesthetic used for spinals would be safe with 
minimal side effects, be effective for surgical anesthesia, and be of short duration to not 
impede PACU discharges. For almost two decades, our department has been using 
mepivacaine as the local anesthetic of choice for shorter cases (duration of 150 minutes or 
less). It has fewer incidences of transient neurologic symptoms (TNS) in comparison to 
lidocaine, and is of shorter duration than bupivacaine. Recently, preservative-free 
chloroprocaine spinals have been reported to provide effective surgical anesthesia of 40 to 
90 minutes (shorter than mepivacaine), depending on the dose given (30-60 mg), and have 
lower incidences of TNS (0-1.9%) than mepivacaine. It has been used as the safe and 
better alternative for short cases at other institutions. A recent randomized controlled trial 
compared 3 drugs for spinal anesthesia (chloroprocaine, lidocaine, bupivacaine) and found 
faster time until resolution of motor and sensory block with chloroprocaine (Teunkens et al 
RAPM 2016). This study involved 99 patients, and did not have a group of mepivacaine 
spinals, so there is still interest in comparing chloroprocaine in regards to safety and efficacy 
with the most commonly used local anesthetic used for ambulatory cases in our institution—
mepivacaine.  
 
Since June 2016, our department has been using 2-chloroprocaine for spinal anesthesia, 
specifically for cases of short duration (less than one hour). At several academic institutions 
in the U.S., including Columbia, Virginia Mason Medical Center, and New York University 
Hospital, chloroprocaine has been used for spinal anesthesia for the past 5-10 years. 
However, 2-chloroprocaine use in spinal anesthesia has had a controversial past. In the 
1980’s, devastating neurologic deficits have been reported on inadvertent subarachnoid 
injection of epidural doses of CP, leading the FDA to not approve its use as a spinal 
anesthetic. It was hypothesized the preservatives (bisulphite and EDTA) and/or excessive 
dosage were responsible for the neurotoxicity of CP. Newer formulations have been made in 
early 2000’s, which are preservative-free and have recently been approved for spinal use in 
Europe since 2012. To keep FDA antiquated policies in perspective, isobaric mepivacaine, 
which we have been using at HSS for over 20 years, is still not approved for spinal use. 
 
Since its approval for use in Europe, there have been a resurgence in the number of 
chloroprocaine studies. Recent studies - (volunteer, retrospective and prospective) have 
verified the safety and efficacy of preservative-free CP, especially for ambulatory surgeries. 
According to clinicaltrials.gov, there are 11 registered studies using chloroprocaine spinals, 
two of which are in the US (Vanderbilt, Columbia). We are currently conducting a 
retrospective study, in collaboration with NYU Hospital/Hospital for Joint Disease, to confirm 
that the use of this local anesthetic is safe, and efficacious, especially since it is being used 
in an off-label manner. Our preliminary review has validated that chloroprocaine spinal 
anesthesia at these two institutions were safe and effective in providing surgical anesthesia. 
After examining 452 charts at HSS, we have found no incidence of TNS, which is 
significantly less than mepivacaine (6.4-7.4%), with no incidence of neuropraxia and urinary 


 
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retention. We believe chloroprocaine is not only safe to be used but is also the ideal spinal 
anesthetic to use for short procedures. 
 
There have been studies comparing the most efficient and safe methods of facilitating 
earlier discharge, comparing general with different spinal local anesthetics. Studies have 
touted the quicker recovery from general anesthesia, but none were compared to the use of 
a short spinal anesthetic like chloroprocaine. This prospective study will be the first to 
compare general anesthesia with chloroprocaine and mepivacaine spinals (our current 
institution standard) after ambulatory knee arthroscopic surgeries. Our primary outcome will 
be time to reach PACU discharge criteria. We believe the chloroprocaine spinal will be 
superior to both general anesthesia and the mepivacaine spinal in sending the patients 
earlier from the PACU. 
2.0 PRODUCT DESCRIPTION 
Chloroprocaine has been approved as a spinal anesthetic in Europe since 2012 and several 
institutions have adopted chloroprocaine as a safer spinal anesthetic alternative in the 
United States. 
3.0 OBJECTIVE OF CLINICAL STUDY 
Outpatient knee surgeries with duration of less than one hour poses a challenge to the use 
of spinal anesthesia given that traditional agents remain in effect for 2-3 hours, thus creating 
a mismatch between length of surgery and anesthetic resolution. Spinal mepivacaine is 
mostly used at our institution for these surgeries but the prolonged duration of the block in 
the PACU impedes earlier discharge. Patients do not like prolonged PACU stays due to 
slow recovery from spinal anesthesia. Many centers instead use general Anesthesia (GA). 
While GA has the advantage of less surgery/anesthesia time ratio mismatch, the adverse 
effects of nausea, vomiting, prolonged emergence and pain control may contribute to 
lengthen discharge. Approved for spinal use in Europe in 2012, chloroprocaine is proven to 
be an effective local anesthetic with the advantage of faster block resolution, averaging 60 
to 90 minutes. The intervention we are studying is whether chloroprocaine is a superior 
alternative to mepivacaine and general anesthesia in providing surgical anesthesia. We 
hypothesize that the use of chloroprocaine can combine the benefits of a short spinal 
anesthetic while avoiding the side effects of a general anesthetic, thus promoting earlier 
discharge. 
4.0 STUDY HYPOTHESES 
Outpatient knee surgery patients receiving chloroprocaine spinal anesthesia will be ready for 
PACU discharge earlier than patients receiving mepivacaine spinal anesthesia or general 
anesthesia.  
 
 


 
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5.0 STUDY DESIGN 
 
5.1 
Study Duration 
Total duration of subject participation will be one week. The total duration of the study is 
expected to be 9 months. 
5.2 
Endpoints 
5.2.1 
Primary Endpoint 
• 
Time until ready for discharge, defined as duration from the PACU arrival to the 
time the patient has reached PADSS discharge criteria. 
5.2.2 
Secondary Endpoints 
• 
Induction time (from time out to induction end) 
• 
Time of emergence (from “end of procedure time” to “room out time”) 
• 
Time of resolution of spinal (defined as time of intrathecal injection to full resolution 
of motor and sensory): Motor resolution will be measured using the modified 
bromage score (0= able to move hips, knees and ankles; 1= able to move two of 
three; 2= able to move only one of three; 3= no movement); Sensory will be 
measured using perceived touch of normal sensation on lateral aspect of the foot 
(considered to be S1). RA will assess every 15 minutes until resolution starting at 
PACU arrival. 
• 
Time of ambulation (defined as time of intrathecal injection to ambulation) 
• 
Time of micturition (defined as time of intrathecal injection to micturition) 
• 
Incidence of urinary retention (requiring urinary catheterization) 
• 
Incidence of transient neurologic symptoms (defined as unilateral or bilateral back 
and buttock pain radiating to the legs) (RA phone call on POD 1 and POD 3) 
• 
Incidence of neurologic deficits/neuropraxia (not related to operative site or surgery) 
(RA phone call on POD 1 and POD 3) 
• 
Incidence of side effects related to spinal anesthesia (hypotension, bradycardia, 
urinary retention) (intraop and postop) [Hypotension defined as <30% SBP, 
bradycardia defined as HR <45) 
• 
Incidence of block failure (measured by conversion to GA). Time of GA conversion 
(beginning of case or after one hour) 
• 
Incidence of opioid related side effects (nausea, sedation, pruritus) 
• 
Incidence of PDPH (defined as positional headache, relieved when laying flat) 
• 
Incidence of emergence delirium /delayed emergence (defined as longer than 30 
minutes from procedure end to extubation) 
• 
Incidence of sore throat 
• 
Incidence of drowsiness 
• 
Incidence of PONV 
• 
NRS Pain Scores: NRS questionnaire (Pre-op, PACU, POD 1, POD3) 
o NRS pain in PACU (at rest and activity, measured every 15 minutes) 


 
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o Worst and average pain in PACU asked at PACU discharge 
o Current NRS pain in PACU 3 hours post PACU arrival if patient is not yet 
discharged 
• 
Opioid consumption (total amount in PACU, total amount intraop, number of patients 
requiring IV rescue analgesia for NRS >7, POD1, POD 3) 
• 
Time of discharge PACU (actual) 
• 
Time of meeting discharge criteria (PADSS checklist will be made, RA will assess 
every 15 minutes) 
• 
Patient Satisfaction (PACU discharge) with intraoperative anesthesia and pain 
control (Scale of 0 to 10, 0 being very dissatisfied, 10 being extremely satisfied) 
• 
ORSDS (PACU discharge) 
• 
Length of PACU stay 
• 
Length of operative time (from incision to wound closure: from Epic) 
• 
QoR-15 (quality of recovery score questionnaires) (Pre-op, POD 1, POD 3, and POD 
7 via phone) 
 
5.3 
Study Sites 
This study will take place at the main campus of the Hospital for Special Surgery.  
6.0 STUDY POPULATION 
6.1 
Number of Subjects 
The maximum number of subjects we plan to enroll in this study is 132.  
6.2 
Inclusion Criteria 
Subjects of either gender will be included if they: 
 
1. Written informed consent obtained from subject and ability for subject to 
comply with the requirements of the study. 
2. Subjects scheduled for knee arthroscopy that is anticipated to be less than 
one hour 
3. Age 18 to 80 years 
4. Ability to follow study protocol 
5. English speaking (secondary outcomes include questionnaires validated in 
English only) 
 
6.3 
Exclusion Criteria 
Subjects will be excluded from the study if they: 
 
1. Younger than 18 years old or older than 80 years old 
2. Allergy or intolerance to one of the study medications 


 
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3. Chronic gabapentin/pregablin use (regular use for longer than 3 months) 
4. Chronic opioid use (taking opioids for longer than 3 months) 
5. Patient unable to undergo a spinal anesthetic due to any of the following: 
a. Lack of patient cooperation 
b. Difficulties with positioning 
c. Increased intracranial pressure 
d. Hypovalemia 
e. Indeterminate neurologic disease 
f. Coagulopathy 
g. Anticoagulant status 
h. Infection at the site of the needle insertion 
i. 
Severe spinal deformity 
6. Patient unable to undergo LMA/GA due to any of the following: 
a. Inability to open mouth 
b. Complete upper airway obstruction 
c. Increased risk of aspiration: patients who have not fasted before 
d. administration of anesthesia, upper gastrointestinal bleed 
e. Suspected or known abnormalities in supraglottic anatomy 
f. Need for high airway pressures 
7. Patient refusal to spinal anesthesia or LMA/GA 
8. Subjects who are pregnant or breastfeeding. All female subjects of reproductive 
potential must have a negative pregnancy test 
9. Non-English speakers 
6.4 
Randomization 
A total of 132 subjects will be randomly assigned to one of the three groups (preservative-
free 2-chloroprocaine, Mepivacaine, GA/LMA) in a 1:1:1 ratio. The randomization schedule 
is created using Statistical Analysis System (SAS) software by a member of the Healthcare 
Research Institute not otherwise involved in the trial. After entry into the study, the 
pharmacist will provide the medication that will be used for the study. The randomization 
schedule will be created up IRB approval and prior to start of study enrollment. A computer-
generated randomization table will be generated by a statistician. Randomization will be 
carried out by the pharmacist who will provide the medication to the research team. The 
Anesthesiology Research Administrators will ensure that the randomization is carried out. 
The research assistant and patient will be blinded to which group the study patient is in. 
7.0 PROCEDURES 
7.1 
Surgical Procedure 
Pre-operatively: 
After obtaining consent, baseline measurements will be taken and the subject will be 
randomized to a treatment group. Demographic information, QoR-15 (quality of recovery 


 
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score questionnaire), and current NRS scores at rest and with movement will be 
documented. Research assistant and subjects will be blinded from treatment. 
 
Intra-op: 
All groups may be given 5mg midazolam, ondansetron 4mg, ketorolac 30mg, famotidine 
20mg, and dexamethasone 4mg. Propofol will be administered intraoperatively as outlined 
below. Subject will be monitored intra-operatively according to American Society of 
Anesthesiologists Standards for Basic Anesthetic Monitoring. The spinal injection and the 
surgical procedure will be performed in a setting with immediate availability of emergency 
medications and equipment for treating cardiovascular and respiratory adverse events. 
Intra-op opioid consumption will be documented. IV Tylenol will be ordered at end of case 
or PACU arrival. 
 
Post-op: If not ordered/administered intra-op, IV Tylenol will be ordered while in PACU. The 
following post-operative analgesia may be ordered: Tramadol 50 mg; Tramadol 100 mg; 
Oxycodone 5 mg for break through pain; IV rescue hydromorphone 0.5 mg x2 q5 min (1 mg 
total) for NRS pain >7. The following post-operative anti-emetics may be ordered: 
Metoclopramide 10 mg PRN; Scopolamine patch PRN (if all IV anti-emetics fail). 
 
PACU Visit: 
Following surgery, subjects will be assessed in the PACU (1-2 hours after induction). The 
following information will be collected:  
• 
Post anesthesia Discharge Scoring System (PADSS) criteria (assessed by RA 
every 15 minutes until criteria are met) 
• 
Anesthesia intra-operative notes collected by non-blinded RA 
• 
Current NRS score at rest and with movement every 15 minutes starting at 
PACU arrival until patient reaches PADSS discharge criteria, and once 3 post 
PACU arrival if patient has not yet been discharged 
• 
Average NRS score with movement and at rest while in the PACU (asked at 
PACU discharge) 
• 
Worst NRS score while in the PACU (asked at PACU discharge) 
• 
Opioid consumption 
• 
Opioid Related Symptom Distress Scale (ORSDS) survey 
• 
Time of emergence (from "end of procedure time" to "room out time") 
• 
Time of spinal resolution (defined as time of intrathecal injection to full resolution 
of motor and sensory) (motor measured using the modified bromage score: 0 = 
able to move hips, knees, and ankles, 1=able to move two of three, 2= able to 
move only one of three, 3= no movement. Sensory measured using perceived 
touch of normal sensation on lateral aspect of the foot (considered to be S1), RA 
to assess every 15 minute until resolution. 
• 
Time of PACU arrival 
• 
Time of ambulation (defined as time of intrathecal injection until time of first 
ambulation) 
• 
Time of micturition (Defined as time of intrathecal injection until time of first 
micturition) 
• 
Time of PACU discharge (actual, documented in EPIC) 
• 
Time of PACU stay (PACU arrival until PACU discharge) 
• 
Incidence of urinary retention, transient neurologic symptoms (TNS), side effects 
(nausea, drowsiness, puritis), post-operative dural puncture headache (PDPH), 


 
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emergence delirium/delayed emergence, sore throat, drowsiness and 
postoperative nausea and vomiting (PONV) 
• 
RA will ask subjects: "Do you have any back or buttock pain that is radiating to 
one or both legs? Do you have a headache that gets worse when you sit up or 
stand?" If subject responds 'yes' to either of these questions, the RA will notify 
the PI and attending anesthesiologist who administered the spinal anesthetic (as 
is standard nursing protocol for positive findings on their POD 1 phone calls) 
• 
Incidence of hypotension and bradycardia: 
o Hypotension defined as blood pressure <30% SBP 
o Bradycardia defined as heart rate <45 bpm 
 
Subjects will likely be discharged on the day of surgery. Subsequent visits will occur via 
phone or electronically. 
 
7.1.1 
Investigational Product Application 
 
Group 1- Preservative-free 2% Chloroprocaine(2CP) spinal group: 
Subject will receive an initial bolus of intravenous propofol (0.1-0.15 mg/kg) titrated to 
desired clinical effect. While monitoring cardio respiratory function, propofol will be 
administered as a slow infusion for maintenance of anesthesia at a rate of 25-50 
mcg/kg/min. Intermittent boluses of 10-20 mg to titrate to the desired sedation level at the 
anesthesiologist’s discretion. A spinal anesthetic with preservative-free 2% chloroprocaine 
(2cc or 40 mg) will be performed. 
 
Group 2- 1.5% Mepivacaine spinal group: 
Subject will receive an initial bolus of intravenous propofol (0.1-0.15 mg/kg) titrated to 
desired clinical effect. While monitoring cardio respiratory function propofol will be 
administered as a slow infusion for maintenance of anesthesia at a rate of 25-50 
mcg/kg/min. Intermittent boluses of 10-20 mg to titrate to the desired sedation level at the 
anesthesiologist’s discretion. A spinal anesthetic with 1.5% Mepivacaine (3cc or 45 mg) will 
be performed. 
 
Group 3- General Anesthesia: 
Subject will receive an initial bolus of intravenous propofol (1.5-2.5 mg/kg) for anesthesia 
induction. Subsequently a laryngeal mask airway (LMA) will placed. Anesthesia will be 
maintained using propofol infusion (100-200 mcg/kg/min) and fentanyl (given at 25 mcg 
increments at a total of 200 mcg) at the discretion of the anesthesiologist. Additionally, 
intermittent boluses will be given in increments of 25-50 mg when changes in vital signs 
indicate a response to surgical stimulation or light anesthesia. No inhalation agents or 
nitrous will be used. 
 
7.2 
Data Collection 
The following data will be collected (sources include Epic, medical records, and 
patient): 
 
Pre-operative/Baseline 
• 
DOB 


 
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• 
Race 
• 
Gender 
• 
Name 
• 
Current NRS Pain Scores at rest and with movement  
• 
QoR-15 
 
Surgical procedure/Intra-Op 
• 
Opioid consumption  
• 
Date of surgery 
• 
Type of surgery 
 
PACU 
• 
Opioid consumption  
• 
Incidence of back pain  
• 
Average NRS Pain Scores at rest and with movement  
• 
Worse NRS pain score while in PACU 
 
POD 0 
• 
Current NRS Pain Scores at rest and with movement  
• 
ORSDS 
• 
Blinding assessment  
• 
Patient satisfaction  
• 
Induction time (time out to induction end) 
• 
Time of emergence (“end of procedure time” to “room out time”) 
• 
Time of spinal resolution (Motor/sensory exam) 
• 
Time of ambulation  
• 
Time of micturition 
• 
Incidence of urinary retention  
• 
Incidence of TNS 
• 
Incidence of neurological deficits/neuropraxia 
• 
Incidence of side effects 
• 
Incidence of PDPH 
• 
Incidence of emergence delirium/delayed emergence  
• 
Incidence of sore throat 
• 
Incidence of drowsiness  
• 
Incidence of PONV 
• 
Time of discharge  
• 
Time of meeting discharge criteria  
• 
Time of PACU arrival  
 
POD 1 
• 
Current NRS Pain Scores at rest and with movement  
• 
Opioid consumption 
• 
ORSDS 
• 
Incidence of TNS 
• 
Incidence of neurological deficits/neuropraxia 
• 
Incidence of PDPH 


 
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• 
Incidence of back pain  
• 
Qor-15 (phone) 
• 
Average NRS score at rest and with movement  
 
POD 3 
• 
Current NRS Pain Scores at rest and with movement  
• 
Opioid consumption 
• 
Incidence of TNS 
• 
Incidence of neurological deficits/neuropraxia 
• 
Incidence of PDPH 
• 
Incidence of back pain  
• 
QoR-15 (phone) 
• 
Average NRS score at rest and with movement  
 
POD 7 
• 
QoR-15 (phone) 
 
 
 
 
 
 


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7.3 
Schedule of Assessments 
 
* = First 20 subjects (5 in each treatment arm) enrolled as part of study pilot group 
**=Patient will be re-evaluated by the investigator as per standard follow-up post-operatively at a minimum interval of 6 weeks and 12 weeks post-
operatively 
Procedures 
Pre-Op 
Surgery 
6 Weeks 
± 2 weeks 
12 Weeks 
± 2 weeks 
6 Months 
± 4 weeks 
1 Year 
± 8 Weeks 
2 Years 
± 8 Weeks 
Revision 
Surgery** 
Informed Consent & Eligibility 
Review 
X 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
History 
SOC 
 
SOC 
SOC 
SOC 
SOC 
SOC 
SOC 
Physical Exam 
SOC 
 
SOC 
SOC 
SOC 
SOC 
SOC 
SOC 
Routine X-rays 
SOC 
 
SOC 
SOC 
SOC 
SOC 
SOC 
 
Lumbar MRI 
SOC 
 
 
X* 
 
 
 
 
Routine Lumbar CT Scan 
SOC 
 
 
 
 
 
 
 
Patient-reported Outcomes 
SOC 
 
SOC 
SOC 
SOC 
SOC 
SOC 
SOC 
Pain Medication Assessment 
SOC 
SOC 
SOC 
SOC 
SOC 
SOC 
SOC 
SOC 
Work and Functional Assessment 
SOC 
SOC 
SOC 
SOC 
SOC 
SOC 
SOC 
SOC 
Adverse Event Assessment 
 
X 
X 
X 
X 
X 
X 
X 
Ease of Dissection Scoring 
 
 
 
 
 
 
 
X 
Histological Analysis Scoring 
 
 
 
 
 
 
 
X 


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8.0 STATISTICAL ANALYSIS 
 
The primary outcome (time until ready for PACU discharge) will be compared between the 
chloroprocaine, mepivacaine, and general anesthesia groups with three pairwise two-
sample t-tests or Wilcoxon rank-sum tests, depending upon the distribution of the data. 
Effect size will be presented as difference in means or Wilcoxon-Mann-Whitney odds with 
95% confidence intervals. Continuous secondary outcomes measured at a single time point 
will be analyzed in the same manner as the primary outcome. Categorical secondary 
outcomes measured at a single time point will be compared between groups using χ2 or 
Fisher’s exact tests, with effect sizes presented as risk differences and relative risks with 
95% confidence intervals. Outcomes measured at multiple time points will be analyzed 
using regression based on a generalized estimating equations (GEE) approach. A 
treatment by time interaction term will be included in all GEE models regardless of 
corresponding P value. 
 
Balance on demographics and baseline characteristics will be assessed by calculating 
standardized differences (difference in means or proportions divided by the pooled standard 
deviation) between groups. Balance will be assessed using two thresholds: (1) 1.96 x 
(2/44)1/2 = 0.42 and (2) 0.2 (Austin 2009). All analyses will be performed on an intention-to-
treat basis. 
 
References 
(1) Austin PC. Balance diagnostics for comparing the distribution of baseline covariates 
between treatment groups in propensity-score matched samples. Stat Med 2009; 28: 3083- 
107. 
9.0 ADVERSE EVENT ASSESSMENT 
All Adverse Events (AEs) will be reported in the final study report. Definitions for Adverse 
Event (AE) used in this study are listed below and are based on FDA and international 
guidelines: 
 
9.1 
Adverse Event (AE) 
Any untoward or unfavorable medical occurrence in a participant, including any 
abnormal sign (for example, abnormal physical exam or laboratory finding), 
symptom, or disease, temporally associated with the participant’s participation in the 
research, whether or not considered related to the participant’s participation in the 
research. 
9.2 
Serious Adverse Events (SAE) 
Adverse events that result in any of the following outcomes: death, a life-threatening 
adverse event, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant incapacity or substantial disruption of the ability to conduct 
normal functions, or a congenital anomaly/birth defect. Important medical events that 
may not result in death, be life-threatening, or require hospitalization may be 
considered serious when, based upon appropriate medical judgment, they may 
jeopardize the participant and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. 


 
Protocol Number: 2017-1547  
Version Date: 2/4/2021 
 
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9.3 
Adverse Event Reporting 
Any adverse event(s) or deviation(s) from this protocol will be brought to the attention of the 
PI, and will be recorded and reported to the IRB.  
10.0 INVESTIGATOR RESPONSIBILITIES, RECORD AND REPORTS 
 
10.1 Subject Consent and Information 
Potential subjects will be screened prior to day of scheduled surgery based on inclusion and 
exclusion criteria reviewed in the subject's medical record. After discussion of the study with 
the surgeon, eligible subjects will be approached on the day of surgery prior to surgery and 
invited to participate in the study. Informed consent will be obtained from all subjects before 
conduct of any study-related procedures. 
 
11.0 REFERENCES 
 
1. Camponovo, C. Spinal 1% 2-Chloroprocaine versus general anesthesia for ultra-short outpatient 
procedures: a retrospective analysis. Acta Biomed. 2014 Dec 17; 85(3): 265-8. 
2. Lacasse MA, Roy JD, Forget J, Vandenbroucke F, Seal RF, Beauliu D, McCormack M, 
Massicotte L. Comparison of bupivacaine and 2-chloroprocaine for spinal anesthesia for 
outpatient surgery: a double-blind randomized trial. Can J Anesth. 2011; 58: 384-391 
3. Zayas VM1, Liguori GA, Chisholm MF, Susman MH, Gordon MA. Dose response 
relationships for isobaric spinal mepivacaine using the combined spinal epidural technique. 
Anesth Analg. 1999 Nov;89(5):1167-71. 
4. YaDeau JT1, Liguori GA, Zayas VM. The incidence of transient neurologic symptoms 
after spinal anesthesia with mepivacaine. Anesth Analg. 2005 Sep;101(3):661-5 
5. Hejtmanek MR1, Pollock JE. Chloroprocaine for spinal anesthesia: a retrospective 
analysis. Acta Anaesthesiol Scand. 2011 Mar;55(3):267-72. doi: 10.1111/j.1399- 
6576.2010.02371.x 
6. Kouri M, Kopacz DJ. Spinal 2-Chloroprocaine: a comparison with lidocaine in 
volunteers. Anesth Analg. 2004; 98(1):75-80 
7. Goldblum E, Atchabahian A. The use of 2-chloroprocaine for spinal anesthesia. Acta 
Anaesthesiologica Scandinavica 2013; 57: 545-552. 
8.Teunkens A, Vermeulen K, Gerven EV, Fieuws S, Van de Velde M, Rex S, “Comparison 
of 2-Chloroprocaine, Bupivacaine, and Lidocaine for Spinal Anesthesia in Patients 
Undergoing Knee Arthroscopy in an Outpatient Setting A Double-Blind Randomized 
Controlled Trial” RAPM Vol 41, No 5 Sept-Oct 2016: 577-583 
9. Liu SS, Strodtbeck W, Richman J, Wu Christopher, “A Comparison of Regional Versus 
General Anesthesia for Ambulatory Anesthesia: A Meta-Analysis of Randomized Controlled 
Trials. Anesth Analg 2005 Dec;101(6):1634-42 
10. Mulroy M, Larkin K, Hodgson P, Helman J, Pollock J, Liu SS “A Comparison of Spinal, 
Epidural, and General Anesthesia for Outpatient Knee Arthroscopy” Anesth Analg: October 
2000 - Volume 91 - Issue 4 - p 860–864 
11. Gebhardt V, Monnard M, Weiss C, Schmittner M. “Discharge times for knee arthroscopy 
in spinal vs general anesthesia. Cen Euro Journ of Medicine June 2014, Vol 9, Issue 3, 
pp446-454 
12. Kim D, Kahn R, Lee A, Lin E, Ortolan S, Yadeau J, “Early experience with 2- 
Chloroprocaine for spinal anesthesia: a retrospective analysis at two institutions” . IRB 


 
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Version Date: 2/4/2021 
 
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approved, 8/22/2016 
13.Ivie R, Fu P, Maniker R “Chloroprocaine spinal compared to general anesthesia for 
outpatient knee arthroscopy : A retrospective analysis. ASRA 2015, abstract poster 
presentation 
14. Memtsoudis SG, Kuo C, Ma Y, Edwards A, Mazumdar M, Liguori G. Changes in 
anesthesia-related factors in ambulatory knee and shoulder surgery: United States 1996-2006. 
RAPM. 2011. Jul-Aug; 36(4): 327:31