Comparison of Loss of Resistance Technique With Air Versus Saline to Identify Epidural Space for Combined Spinal Epidural Labor Analgesia
Phase: PHASE2
Conditions: Pain Relief
Sponsor: Wake Forest University Health Sciences

 
 
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Protocol: 
Comparison of Loss of Resistance Technique with Air versus 
Saline to Identify Epidural Space for Combined Spinal Epidural 
Labor Analgesia 
  
 
Principal Investigators: Peter Pan, MD  
 
Background and Significance:  
Combined spinal epidural labor analgesia is a common form of labor pain relief method that 
provides rapid onset of labor pain relief with the first dose of medicine and also an epidural 
catheter is inserted for continuous administration of epidural medication throughout the duration 
of labor.   In combined spinal epidural labor analgesia technique, an epidural is inserted first after 
numbing the skin with local anesthetic.  When the epidural space is identified by the epidural 
needle, then a spinal needle is inserted through the epidural needle into the spinal fluid space.  
When a drop of clear spinal fluid return through the spinal needle, the spinal space is identified 
and then the first dose of medicine is administered through the spinal needle, after which, the 
spinal needle is removed and an epidural catheter is inserted into the epidural space for 
additional medication as needed.  When the epidural needle is inserted initially to identify the 
epidural space, anesthesiologists typically attach to the epidural needle a syringe with 2-3 mL of 
air or saline.  The air or saline is used to help identifying the epidural space.  Both air and saline 
are commonly used and it is not clear and debatable which is a better method to identify the 
epidural space when the combined spinal epidural labor analgesia is performed.  Some clinicians 
believe air is a better choice because when a drop of clear fluid returned from the spinal needle 
during the combined spinal epidural technique, it would be clear that it is from the spinal fluid 
since no saline and only air has been used in the syringe, and the first dose of medicine can be 
administered via the spinal needle.  However, other clinicians believe saline is better because it 
allows easier and more reliable identification of the epidural space and that the saline would not 
interfere with the spinal fluid return from the spinal space during combined spinal epidural labor 
analgesia.  To date, no studies have compared the outcome and success of combined spinal labor 
analgesia between using saline versus air for identifying the epidural space.  The goal of this 
study is to compare whether air or saline makes a difference in success and outcomes of the 
combined spinal epidural labor analgesia.  The results of this study may provide information on 
better choice of technique for obtaining combined spinal labor analgesia. A total of 350 labor 
patients will be enrolled at Forsyth Medical Center. 
 
Obese patients present significant challenges for the anesthesia care providers.  Neuraxial 
anesthesia is preferred over general anesthesia for Cesarean Section.  In obese patients placement 
of spinal or epidural anesthesia is complicated by diminished landmarks and increased depth of 
the epidural and subarachnoid space.  The ability to identify the epidural or subarachnoid space 
is more likely due to misdirection than inadequate needle length.  In spinal anesthesia, a short 
introducer needle is used first and a spinal needle is inserted via the introducer to locate the 
subarachnoid space.  In combined spinal epidural anesthesia technique, an epidural needle 
(longer than the standard introducer used in spinal anesthesia) is inserted first, and the spinal 
needle is inserted into the subarachnoid space via the epidural needle after epidural space is 
identified by the epidural needle.  Both spinal and combined spinal epidural techniques are 
commonly used for cesarean section anesthesia.  Many experienced anesthesia care providers 

 
 
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may have difficulty locating the spinal space with a standard short introducer and a small gauge 
spinal needle in obese patients and find that misdirection and time for placement of anesthesia is 
less when an epidural needle is used to identify tissue plans.  The use of an epidural needle also 
allows the threading of an epidural catheter after spinal anesthesia is administered using a 
combined spinal epidural technique.  This catheter provides additional security to the patient in 
the event of a prolonged operation or postoperative bleeding. To date, no studies have compared 
the time and success for placement of spinal anesthesia via standard spinal versus combined 
spinal epidural (CSE) technique in obese patients scheduled for Cesarean deliveries.  The results 
of this study may provide anesthesia provider information on better choice of technique for 
obtaining subarachnoid anesthesia in obese patients undergoing cesaraean deliveries. 
 
Purpose: 
 
The purpose of this study is to document the success rate and outcomes of combined spinal 
epidural labor analgesia when saline or air is used to identify the epidural space during the 
combined spinal epidural labor analgesia.  Additional objectives of this study are to quantify the 
any complications and pain relief and satisfaction assessed by pain scores via randomized visual 
and verbal analog scores. 
 
Hypothesis: 
Use of saline in combined spinal epidural labor analgesia during identification of epidural space 
does not increase the failure rate of combined spinal epidural labor analgesia when compared to 
the use of air. 
 
Patient Population: 
 
The patient population will consist of 350 women aged 18 years or older, weighing less than or 
equal to 250 lbs, and request neuraxial labor analgesia.  Emancipated minors may also be 
enrolled in this protocol.  Exclusion criteria will be American Society of Anesthesiologists 
physical status greater than II. 
 
Procedures and Methods: 
 
Demographic data including patient’s age, height, weight, gestation, medications and history of 
previous epidurals or spinals will be recorded.  Patients will be randomized into one of two 
treatment groups (Group Air or Group Saline) according to a table of random numbers. The 
patient will be placed in the sitting position and a midline approach will be used as in usual 
practice. Combined spinal epidural labor analgesia will be performed in the usual manner, with 
group Air using 3 mL of air and group Saline using 3mL of saline in the syringe for identifying 
the epidural space during the combined spinal epidural labor analgesia placement.  After positive 
fluid return from the spinal needle, a standard of care acceptable usual dose of labor analgesic 
will be administered at the discretion of the anesthesiologist providing the care.  Typically 10-20 
mcg of fentanyl with or without bupivacine 1-2.5mg will be administered.   The patients and data 
interpreters will be blinded to the treatment group; however, the anesthesiologist performing the 
procedure will not be blinded.  Standard of care monitoring data will be recorded as usual, and 
level of pain relief will be obtained via pain scores by visual and verbal pain scores.  

 
 
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RANDOMIZATION AND TREATMENT: Patients will be randomized to have the anesthesiologist 
using saline or air for identifying epidural space during placement of the combined spinal 
epidural labor analgesia using standard loss of resistance technique. The chance of using air or 
saline is each 50%.  The patients, data interpreters and analyzers will be blinded as to which 
group the patient is assigned to. 
 
Confidentiality: All information obtained while you are in this study, as well as related hospital 
records, will be made available to the research staff and other regulatory authorities including the 
Food and Drug Administration (FDA).  All information will be treated in a confidential manner 
and although the results of this research project may be presented at meetings or in publications, 
you will only referred to by number and your identity will not be disclosed in those 
presentations. 
 
SAFETY MEASURES:  Standard monitoring will be applied in the labor room as in usual clinical 
practice at Forsyth Medical Center.  Unless other untowards effects are observed from the 
techniques, no additional monitoring will not be instituted. 
 
OUTCOME MEASURES: The primary outcome measure will be the success or failure of the 
combined spinal epidural labor analgesia.  Secondary outcome measures are any complication or 
side effects.  
 
Benefits and Risks: 
 
There may be no potential benefits from participating in this study other than more frequent 
assessment and observation.  It is not known which technique actually provide the more 
favorable outcomes but both techniques are commonly used in clinical practice. The usual risks 
of combined spinal epidural labor analgesia include but not limited to : headache, failure of the 
spinal or epidural, intravenous catheter insertion and the extremely rare risks of bleeding, 
infection, nerve damage, paralysis, hypotension, high spinal block and even death rarely.  All 
these risks are explained by the anesthesiologist participating or providing anesthetic care as part 
of the risk of neuraxial block. 
 
 
Statistics and Data Analysis: 
 
Data will be presented as mean (SD) or median as appropriate.  Pain VAS scores will be 
examined, following tests for normality, by repeated measures two-way ANOVA in most study 
designs. Incidence data will be analyzed by Chi-Square or Fishers Exact Test. In the case of 
subject drop out, both intent to treat and completed treatment analyses will be performed.  
Continuous data will be compared by unpaired t-test and ANOVA.  Assuming a difference in 
success rate of 95% versus 85% between the two groups, a sample size of 160/group is required 
to achieve a power of 0.8 and an alpha of 0.05.  An estimate of 175/ groups or 350 total 
evaluable subjects will be enrolled in this study. 
 

 
 
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Human Subject 
 
This study will be performed in the Sara Lee Women’s Center at Forsyth Medical Center, which 
includes monitoring and resuscitation equipment and trained nursing support staff. All studies 
will be approved by the IRB and written informed consent obtained. The Project Investigators 
have all performed similar studies in patients. The purpose of the study and all risks will be 
discussed with each subject, and all questions will be answered prior to obtaining written 
informed consent. Risks to be discussed include discomfort with needle and catheter insertion, 
risk of postdural puncture headache and spinal needle insertion. The usual side effects and risks 
of spinal and combined spinal-epidural anesthesia apply.  These include itching, nausea, 
hypotension, unilateral pain relief, small risk of spinal tap, headache, bleeding, infection, venous 
catheter, high block or inadequate block.  All data acquired will remain confidential with no 
reference to individuals in publications.   
 
Data Safety Monitoring Plan 
 
These monitoring will be performed with a data safety monitoring board (Laura Dean, MD and 
David Merrill, PhD., MD), who are not involved in the study.  Data and adverse events will be 
reported to these individuals, and reviewed on a regular basis.  Adverse events will also be 
reported to the IRB.   Serious adverse events will be reported to all of these groups and the data 
safety monitoring individuals within 24 hr and the trials halted until feedback is obtained from 
each. 
 
References: 
 
Evron S, Sessler D, Sadan O, Boaz M, Glezerman M, Ezri T.  Identification of the epidural 
space: Loss of resistance with air, lidocaine, or the combination of air and lidocaine.  Anesth 
Analg 2004; 99:245-50. 
 
Scott DB. Identification of the epidural space: loss of resistance to air or saline ? Reg Anesth 
1997; 22:1-2. 
 
Russell R. Loss of resistance to saline is better than air for obstetric epiduals.  Int J Obstet Anesth 
2001; 10:302-6. 
 
Iwama H. Injection volume of saline with loss of resistance method may affect the spread of 
epidural anesthesia.  Anesthesiology 1997; 86:507-8. 
 
Okutomi T, Hoka S. Epidural saline solution prior to local anaesthetic produces differential 
nerve block.  Can J Anaesth 1998;45:10:91-3.