Comparison of Lidocaine Versus Bupivacaine Spinal Anesthesia in Total Hip Arthroplasty: A Randomized, Double-Blind, Prospective Study
Phase: PHASE4
Conditions: Total Hip Arthroplasty
Sponsor: Thomas L Bradbury

Comparison of Lidocaine versus Bupivacaine Spinal Anesthesia in Total Hip
Arthroplasty: A Randomized, Double-Blind, Prospective Study
NCT02818894
Date: April 26, 2017
IRB00083867

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Spinal anesthesia is commonly used in total hip arthroplasty (THA). This will be the 
first randomized, double-blind, prospective study to compare lidocaine to bupivacaine 
spinal anesthesia in THA patients. The objective of this study is to compare the two 
spinal anesthesia treatments with the primary outcome of transient neurological 
symptoms (TNS). The study will be conducted on healthy adult volunteers who are 
indicated for THA and agree to have spinal anesthesia. All patients will be 
randomized by a computer program and will receive either lidocaine or bupivacaine 
spinal anesthesia prior to their THA. Prospectively collected data will be obtained 
from the patient charts. In addition to TNS, other outcomes include urinary retention, 
hypotension, ambulation and length of hospital stay. We predict there will be no 
difference between lidocaine and bupivacaine spinal anesthesia in THA patients with 
respect to TNS and other outcome measures. 
INTRODUCTION/BACKGROUND

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A. Specific Aims
Most surgeons would agree total hip arthroplasty (THA) is one of the most 
successful surgical interventions. However, when it comes to the type of anesthesia to 
improve THA outcomes, surgeons do not agree. General anesthesia has been shown to be 
associated with increases in adverse events, increased operating room times and increased 
length of stay [Basques,Helwani]. Therefore, more surgeons are turning to spinal 
anesthesia for better pain control, decreased need for narcotics resulting in less nausea, 
sooner recovery of bowel function, and faster participation in physical therapy. All of 
these factors can lead to a sooner discharge from the hospital, which would lead to 
significant cost savings. 
Transient neurological symptoms (TNS) are a concern of using spinal anesthesia 
and have been shown to occur up to 16-40% of the time with lidocaine [Ligouri, 
Capelleri, Hodgson, Keld]. There is no known cause of TNS. Symptoms have been 
described as pain, dysesthesia, or both that occur in the legs or buttocks and urinary 
retention after recovery from spinal anesthesia. Intensity of pain varies but can be quite 
severe. Symptoms can appear in a few hours, for up to 24 hours after surgery [Pollock]. 
The risk of developing TNS after spinal anesthesia with lidocaine has been shown 
to be higher when compared to other anesthetics [Zaric]. Lidocaine is the most widely 
used anesthetic due to its rapid onset, intense nerve blockade, and short duration of 
action. The use of spinal anesthesia with lidocaine has been shown in knee arthroscopy, 
general surgery, and obstetric literature [Valanne, Cappelleri, Ben-David B, Casati, 
Philip]. 
However, it is unknown whether there are differences between patients who 
undergo spinal anesthesia with lidocaine versus bupivacaine in THA. This knowledge is 
important because it has been shown that bupivacaine spinal anesthesia is more effective 
than lidocaine with minimal adverse effects [Gozdemir]. A large randomized, prospective 
study is needed to prove the difference between the two types of anesthesia. 
The primary goal of this study is to evaluate the incidence of TNS between 
lidocaine and bupivacaine spinal anesthesia in THA patients. This will be done through 
examination of the patient records prospectively and telephone questionnaire after 
randomization to lidocaine or bupivacaine spinal anesthesia in THA patients. 
Specific Aim 1: To determine the incidence of TNS after spinal anesthesia with lidocaine 
versus bupivacaine in THA patients. 
Hypothesis: There will be no difference in TNS after surgery between lidocaine and 
bupivacaine spinal anesthesia in THA patients.
Specific Aim 2: To compare urinary retention after spinal anesthesia with lidocaine 
versus bupivacaine in THA patients. 
Hypothesis: There will be no difference in urinary retention after surgery between 
lidocaine and bupivacaine spinal anesthesia in THA patients.
Specific Aim 3: To compare timing of ambulation after spinal anesthesia with lidocaine 
versus bupivacaine in THA patients. 

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Hypothesis: There will be no difference in timing of ambulation after surgery between 
lidocaine and bupivacaine spinal anesthesia in THA patients.
Specific Aim 4: To compare incidence of hypotension after spinal anesthesia with 
lidocaine versus bupivacaine in THA patients. 
Hypothesis: There will be no difference in incidence of hypotension between lidocaine 
and bupivacaine spinal anesthesia in THA patients.
Specific Aim 5: To compare length of hospital stay after spinal anesthesia with lidocaine 
versus bupivacaine in THA patients. 
Hypothesis: There will be no difference in length of hospital stay between lidocaine and 
bupivacaine spinal anesthesia in THA patients.
RESEARCH DESIGN
This is a single-center, prospective, randomized, double-blind study to evaluate the 
effectiveness of spinal anesthesia with lidocaine versus bupivacaine in subjects 
undergoing total hip arthroplasty. A total of 93 subjects per group will be enrolled in this 
study. All subjects will be blinded to treatment. Subjects screened at the  
 
c who meet the inclusion criteria, will be offered 
participation on the study.
          Adult patients, age 18-90 years old who satisfy the inclusion criteria and do not 
meet the exclusion criteria will be enrolled. The enrollment period for this study is one 
year. Demographics obtained will be age, sex, height, weight, laterality and body-mass 
index (BMI).
    Randomization: Patients will be randomized in a blocked fashion to receive either 
lidocaine or bupivicaine.  Randomization will occur after informed consent has been 
obtained from the patients and after the surgeon has completed the preoperative screening 
examination.  To minimize potential patient bias, each patient will be counseled that both 
anesthesia techniques are used in standard clinical practice.  Patients will be blinded to 
their randomization until all study visits have been completed. The randomization module 
in REDCap, a secure, web based application for building and managing online surveys 
and databases, will be used to randomize the patients.  A 1:1 block randomization model 
will be created by the clinical research coordinator.  Each block will contain a random 
sequence of numbers in groups of twenty (i.e. 1 = lidocaine, 2 = bupivicaine). This 
sequence will be used to allocate patients to treatment groups.  The investigators will be 
blinded to the allocation sequence.

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SOURCE OF RESEARCH MATERIAL
Source of Research Material
Standard of Care? 
(Y/N)
Demographics [i. e., age, sex, height, weight, laterality and 
body-mass index (BMI)]
Y
Case Report Form (CRF) 
N
History and physical exam
Y
Spinal Anesthesia Medication
Y
Preoperative Time
Y
Intraoperative Time
Y
Postoperative Time
Y
Time of PACU discharge
Y
Time of ambulation
Y
Vital Signs
Y
Urinary retention (intermittent catheter or foley catheterization)
Y
Date of admission
Y
Date of discharge
Y
TNS
Y
The following data for the study will be obtained from the subject’s inpatient medical 
chart: 
Demographics [i. e., age, sex, height, weight and body-mass index (BMI)]. 
TNS: during hospital stay and questionnaire after discharge
Urinary retention: use of intermittent catheter or foley catheter
Hypotension: defined as systolic blood pressure <90mmHg
Operating Room Times: preoperative, intraoperative, postoperative
Length of Stay: calendar days in the hospital
Ambulation: Timing of ambulation during hospital stay
All data will be entered on a case report form (CRF), which will not have any identifiable 
patient information on it, only the patient’s study number and initials will appear. 
Inclusion and Exclusion Criteria
Inclusion criteria: Subjects meeting all of the following may continue in the 
study: 
Subject must be at least 18 years of age and no older than 90 years of age; 
of either sex
Radiographic evidence of symptomatic osteoarthritis in one or bilateral 
hips. Osteoarthritis will be defined as pain with weight-bearing at the hip 
articulation together with radiographic findings as described below. 
Indicated for total hip arthroplasty
Agreement to undergo spinal anesthesia for surgery

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Exclusion criteria: Subjects meeting any of the following will be withdrawn from 
the study
Patient refusal to undergo spinal anesthesia
Patients with a known history of lumbar or sacral spinal fusion. 
Patients with a known history of prostate, urological, or kidney surgery. 
Patients who need monitoring of urine output during surgery (including 
patients with conﬁrmed renal disease, renal failure, chronic renal 
insufﬁciency, or an indwelling catheter at the time of surgery).
Current infection at site of injection
Women of child-bearing potential who are on Medicare (child-bearing 
potential will be determined prior to surgery per Anesthesia standard of 
care)
Hypovolemia
Indeterminate neurologic disease
Allergy or hypersensitivity to the study medications
Currently taking any anti-coagulation medications or coagulopathic
Increased intracranial pressure
Subject is unable to make his/her own decision regarding the informed 
consent
Subject is unable to read/understand English
Subject Screening Procedures.  History and physical examination, hip radiographs, 
indication for total hip arthroplasty.
Description of the Recruitment and Consent Process
Potential study participants will be identified in the Emory Orthopaedic and Spine 
Center outpatient clinic by the study team (Principal Investigator (PI), Co-Investigator (Co-
I), or research coordinator). The patient’s history and physical examinations and hip 
radiographs will be evaluated to determine if the inclusion/exclusion criteria are met. 
Subjects will have the study procedures, risks and benefits explained to them by a study team 
member (PI, Co-I, and/or research coordinator). The patient will be given the opportunity to 
read the informed consent and given time to ask questions prior to consenting for the study. 
Once the subject has read the consent form and had time to ask questions, they should be 
asked to explain their understanding of the requirements of the study. Subjects should be 
asked to voluntarily sign the consent form. The subject must be able to self-consent to be 
eligible. The following procedures will be conducted and documented for all subjects:
Informed Consent/HIPAA Authorization form (ICF/HIPAA form)
Evaluation of compliance with inclusion and exclusion criteria
Known Medication allergies 
Subjects who sign the ICF/HIPAA Form and who agree to the study procedures may 
be enrolled in the study. Following subject enrollment, if it is determined by the 
investigators that he/she does not meet inclusion/exclusion criteria, or a medical situation 
arises that causes the subject to be unable to continue in the study, the patient will be 

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withdrawn from the study and considered enrolled, but “withdrawn by primary 
investigator.”  Subjects may choose to withdraw at any time.
There is no plan to compensate enrolled subjects for their participation in the study.
Drugs, Dietary Supplements, Biologics, or Devices.  
Patients in the intervention arms will receive one dose of either lidocaine or 
bupivacaine spinal, per Anesthesia standard of care for spinal anesthesia. The equipment 
is included in a tray that includes a 24 gauge pencil point spinal needle with introducer, 
and 22 gauge Quinke needle that are both 3.5 inches long. The approach will be either 
midline or paramedian with the patient sitting or lateral per Anesthesiologist preference 
and based on the patient. 
Medications: 
1. Bupivacaine: 0.75% hyperbaric in dextrose. Dose is primarily dependent on 
patient height 7.5-9mg </= 5 feet tall to 15mg >/= 6 feet tall.
2. Lidocaine: 2% isobaric. Dose is primarily height dependent 40mg for </= to 5 
feet tall to 100mg >/= 6 feet tall.
3. Any additive medications to assist with pain control will be at the discretion 
of the Anesthesiologist and will be recorded for comparison. Additive 
medication will be per standard anesthesia protocol
The administration of either treatment will occur in a double-blinded 
fashion. Neither the patient receiving the medication nor the surgeon or investigators 
collecting study outcome data will be aware of whether or not the patient received lidocaine 
or bupivacaine. Due to patient safety concerns, the Anesthesiologist will not be blinded. 
Both treatment groups will receive a standard postoperative total hip arthroplasty 
pathway.   
Study Procedures/Research Interventions
Potential study subjects will be identified in the Emory Orthopaedics and Spine 
Center clinic by history and physical and hip radiographs. A protocol approved 
investigator or research coordinator will approach the potential subject and briefly 
explain the study. Following the subject’s agreement to participate in the study and 
attainment of proper consent, the subject’s baseline Case Report Form (CRF) will be 
completed. The Inclusion/Exclusion Criteria outlined in this protocol should be reviewed 
for determination of subject eligibility and continuance in the study. For female subjects, 
a negative pregnancy test will be obtained to continue in the study. Only when eligibility 
has been determined, will the subject be allowed to participate in the planned study 
procedures. Final eligibility will be determined by the PI or Co-I.

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Study Day/Period
Assessment
Screening Op
Day
POD 
#1
POD
#2
POD
#3
POD
#4
1 week 
post-op
2 week
post-op
History/Physical Exam     
x
Hip Radiographs
x
Pregnancy test (females-if 
needed)
x
Informed Consent Discussion
x
Demographics [i. e., age, sex, 
height, weight, laterality and 
body-mass index (BMI)]
x
Randomization
x
Study drug
x
Admission Date
x
Preop Time
x
Intraop Time
x
Postop Time
x
Vitals
x
x
x
x
x
Ambulation
x
x
x
x
x
Anesthesia Duration
Urinary retention
x
x
x
x
x
TNS: weakness, numbness, 
parasthesias, etc.
x
x
x
x
x
x
x
Discharge date
x
x
x
x
x
TNS Evaluation
The duration of the anesthesia, defined as the time until the subject had normal 
sensation and was able to lift both extremities, will be recorded. The subject will be 
contacted on the first and third postoperative days by the study team, who are blinded to 
the anesthetic used and only informed of the subjects’ data and telephone number. 
Following a prepared questionnaire [APPENDIX B], the study team member will ask 
about symptoms of TNS and pain not associated with the operation area. The subject will 
be asked to specify the location of the symptoms and grade the complaints after a verbal 
analogue scale from 0 to 10, with zero as no discomfort and ten as unbearable discomfort. 
The subject will be asked about the time to full mobilization and time of first voiding.
Another follow-up call will be made within 7 and 14 days post-operatively. If any 
subject continues to have symptoms, further follow-up evaluation will proceed on a case-
by-case basis until the problem resolved, the subject is unable or unwilling to be 
contacted again, or the primary physician requests no further follow-up calls by the study 
team. The remaining data points will be prospectively obtained from the inpatient chart 
and recorded on the CRF. 

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Data Collection
A subject key listing name, medical record number (MRN), age, sex, study number and 
treatment received will be kept in electronic format, as well as in the research binder stored 
in a secure locked file cabinet.
Radiographs will be obtained at the initial clinic visit per standard of care. 
Demographic data, including height, weight, BMI, sex, laterality and age, at the initial 
clinic visit will be recorded on the CRF. During the subject’s inpatient hospitalization, 
study treatment, vital signs, TNS, ambulation, urinary retention and length of stay will be 
recorded on the CRF. All data collected on the CRF will be kept in REDCap as well as in 
the research binder. The CRF will not have any identifiable subject information, only the 
study number and subject’s initials.
Data from the paper CRFs will be entered into an electronic database in REDCap 
by a study team member. The database will be made available to all investigators 
electronically. Data analysis will be performed by the investigators which will also be 
performed on a password enabled computer. There will be no patient identifiers in the 
data provided to the investigators, only the subject number. 
Primary (i.e., primary outcome variables) and secondary endpoints
Primary: TNS
Secondary: Need for supplemental anesthesia (ie- conversion to general anesthesia), urinary 
retention, urinary incontinence, hypotension, ambulation, length of stay
Confounders: Height, weight, BMI, gender, age, laterality
Sample size and power considerations:  The primary outcome for the THA intent-to-
treat trial will be TNS [APPENDIX B].  Previous studies suggest the incidence of TNS 
after spinal anesthesia in patients treated with bupivacaine as <5% and 16-40% in 
patients treated with lidocaine.  For example, TNS incidence among 150 women that 
underwent gynecologic or obstetric procedures and received 0.5% bupivacaine was less 
than 1% on postoperative day 3 (1 of 150 with TNS; Hampl et al). TNS incidence was 
approximately 3% (1/30; 95% confidence interval: 0.6% to 16.7%) in patients 
undergoing inguinal hernia, appendectomy, varicose vein or minor orthopedic operations 
(Gozdemir et al).
A sample size of 93 patients per treatment group achieves 90% statistical power 
to detect a difference between the two treatment group proportions of 0.15 (Table 1).  
The proportion of patients in the bupivacaine group that report TNS over the 2-week 
study period is assumed to be 0.20 under the null hypothesis and 0.05 under the 
alternative hypothesis. The proportion of patients in the lidocaine group (control arm) 
that report TNS over the 2-week study period is assumed to be 0.20.  The test statistic 
used is the two-sided Z test with pooled variance (significance level = 0.05).
An intent-to-treat design will be followed and all subjects will continue to be 
followed with all scheduled outcome evaluations until the end of the study, death of the 
subject or subject refusal.  Subjects may be withdrawn from their randomly assigned 
treatment for considerations of subject safety.  No interim analyses are planned.

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Table 1. Sample Size and Power Considerations for the Lidocaine versus Bupivacaine 
Spinal Anesthesia THA trial (primary outcome: Transient Neurologic Symptoms, TNS)
p1=proportion of patients reporting TNS during the 2-week study period in the 
Bupivacaine group and p2=proportion of patients reporting TNS during the 2-week study 
period in the Lidocaine group.
Statistical analysis
The primary analyses of the data will be performed according to subjects’ original 
treatment assignment (i.e., intention-to-treat analyses) and all data from all subjects 
randomized will be included in the final analysis.  TNS rates will be estimated and 
compared using 2 approaches.  First, the overall TNS rates (as a simple fraction for each 
treatment group) will be compared between treatment groups using a χ
2 test.  Confidence 
intervals (95%) will be calculated for TNS rates within each study cohort and for the 
observed treatment difference in TNS rates.  Second, TNS rates by treatment group and 
time on study (at discharge, 1-week post-op and 2-weeks post-op) will be estimated and 
compared by performing a generalized estimating equations (GEE) analysis using SAS 
Proc Genmod with an exchangeable correlation structure for the repeated measures 
within the participant (binomial-logit model).  The statistical model provides estimates of 
the percentages of patients with TNS by treatment arm and time on study.  The model-
based estimates are unbiased with unbalanced and missing data, so long as the missing 
data are non-informative (missing completely at random). Results will be summarized 
with TNS rates and 95% confidence intervals.  A P value ≤0.05 will be considered 
statistically significant for the main effects (treatment and time on study) and interaction 
factor (treatment arm by time on study) from the repeated measures analysis. 
A potential problem in any of the above analyses is missing data.  Missing data 
cause the usual statistical analysis of complete or all available data to be subject to bias.  
Since the required follow-up for this clinical trial is only 2-weeks we expect no lost to 
follow-up for the primary endpoint, TNS.  Every effort will be made to minimize missing 
data on outcomes and covariates.  There are no universally applicable methods for 
handling missing data.  If missing data becomes an issue then we will conduct sensitivity 
analyses to encompass different scenarios of assumptions and discuss consistency or 
discrepancy among them.
Bupivacaine, 
p1
Lidocaine, 
p2
Difference 
(p
2-p
1)
# 
Participants 
per Group
Statistical 
Power
0.05
0.30
.25
42
90%
0.05
0.25
.15
61
90%
0.05
0.20
.15
93
90%
0.05
0.15
.10
188
90%
0.05
0.10
.08
582
90%
0.10
0.30
.20
78
90%

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Data and Safety Monitoring and Reporting
Oversight of the progress and safety of the trial will be provided by the primary 
investigator.  Adverse events are not anticipated, but any occurring will be documented 
and reported according to Emory Institutional Review Board (IRB) policies and 
procedures. 
Confidentiality will be protected by utilizing a code number as the only identifier 
for each subject and the master list will be kept in an excel spreadsheet on a password 
protected, encrypted computer access limited to the primary investigator and study team. 
All Case Report Forms (CRFs) will be completed and entered in a secure, password 
protected database within a reasonable time frame.  All CRFs will be reviewed and 
electronically signed by the PI.  Completed paper CRFs and other identifiable study 
documents will be stored securely in a locked filing cabinet in a locked office.  
The principal investigator will be responsible for reviewing protocol compliance, 
data collection and verification. The PI will also review the data after the first 60 
participants to note any changes, safety issues, and/or unanticipated problems.
RISKS/BENEFITS ASSESSMENT 
In the event of a serious adverse event or the subject develops a severe adverse 
reaction, they may be withdrawn by the investigators due to safety concerns. The 
research coordinator would go to the patient key to identify the patient number and 
withdraw the patient from the study.
            Risks to the patient include exposure of personally identifiable information. 
Measures to reduce this risk will include a subject key listing the name, last four digits of 
social security number, subject number (randomly assigned) and treatment received will 
be kept with the research assistant in the Emory Orthopaedics and Spine Center Clinic in 
a research folder, locked in a cabinet. Only the research coordinator will have access to 
this key, none of the investigators will not have access to this information. Physical risks 
apply to the adverse reactions to the medication as listed. This study involves injection of 
a spinal anesthesia and may cause TNS, hypotension, urinary retention or infection. 
There may be additional risks that are unknown at this time. Prior to enrollment, all 
included subjects will receive counseling regarding the risks of the study.  
            Subjects may benefit from the study by reducing the use of narcotics leading to 
better function postoperatively and earlier discharge, reducing costs for the hospital.
ADVERSE EVENTS, UNANTICIPATED PROBLEMS, AND DEVIATIONS
Adverse events may occur with the use of spinal anesthesia using lidocaine or 
bupivacaine which include: headache, weakness, numbness, tingling, pain, infection. The 
risks in this study are the same as any patient undergoing THA with spinal anesthesia. 

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in the supine position. Hyperbaric lidocaine 5% versus hyperbaric bupivacaine 
0.5%. Acta Anaesthesiologica Scandinavica 2000;44(3):285-290.
6. Pollock J. Transient neurologic symptoms: Etiology, risk factors, and 
management. Regional Anesthesia and Pain Medicine 2002;27(6):581-586.
7. Zaric D, Christiansen C, Pace N, Punjasawadwong Y. Transient neurologic 
symptoms after spinal anesthesia with lidocaine versus other local anesthetics: A 
systematic review of randomized, controlled trials. Anesth & Analg 
2005;100(6):1811-1816. 
8. Valanne J, Korhonen A-M, Jokela R, Ravaska P, Korttila K. Selective spinal 
anesthesia: A comparison of hyperbaric bupivacaine 4mg versus 6mg for 
outpatient knee arthroscopy. Anesth & Analg 2001;93(6):1377-1379. 
9. Cappelleri G, Aldegheri, G, Danelli, G, Marchetti C, Nuzzi M, Iannandrea G, 
Casati A. Spinal Anesthesia with Hyperbaric Levobupivacaine and Ropivacaine 
for Outpatient Knee Arthroscopy: A Prospective, Randomized, Double-Blind 
Study. Anesth Analg 2005;101:77–82.
10.Ben-David B, DeMeo P, Lucyk C, Solosko D. A comparison of minidose 
lidocaine-fentanyl spinal anesthesia and local anesthesia/propofol infusion for 
outpatient knee arthroscopy. Anesth & Analg 2001;93(2):319-325.
11.Casati A, Moizo E, Marchetti C, Vinciguerra F. A prospective, randomized, 
double-blind comparison of unilateral spinal anesthesia with hyperbaric 
bupivacaine, ropivacaine, or levobupivacaine for inguinal herniorrhaphy. Anesth 
& Analg 2004;99(5):1387-1392.
12.Philip J, Sharma SK, Gottumukkala VNR, Perez BJ, Slaymaker EA, Wiley J. 
Transient neurologic symptoms after spinal anesthesia with lidocaine in obstetric 
patients. Anesth & Analg 2001;92(2):405-409.
13.Hampl KF, Schneider MC, Ummenhofer W, Drewe J. Transient neurolgic 
symptoms after spinal anesthesia. Regional Anesthesia and Pain Management 
1995;81:1148-53.
14.Gozdemir M, Muslu B, Sert H, Usta B, Demircioglu RI, Karatas OF, Surgit O. 
Transient neurological symptoms after spinal anesthesia with levobupivacaine 
5mg/ml or lidocaine 20mg/ml. Acta Anaesthesiol Scand 2010;54:59-64.
APPENDIX A
Case Report Form from REDCap
APPENDIX B
Transient Neurological Symptoms Checklist/Survey:

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