Clinical trial NCT03027661
Conditions: Pain, Postoperative
Keywords: para-cervical block laparoscopic hysterectomy
Sponsor: University of Tennessee
Start date: 2017-08-01; Completion date: 2018-06-30
Enrollment: 41 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a prospective randomized controlled trial in which patients that are scheduled to undergo a laparoscopic hysterectomy would be allocated to one of two groups: Paracervical block with local anesthetic (bupivacaine 0.5%), or placebo. This would be achieved using block randomization. The intervention would be performed after the patient is under general anesthesia, prior to starting the surgery. Patients would be consented in the office or preoperative area (before receiving sedatives). As far as the intervention itself, it would consist of injecting 5 mL of 0.5% bupivacaine into the cervical stroma at 3 and 9 o'clock, which is standard technique for para-cervical block. The remainder of the procedure will then continue in a regular fashion. Alternatively, patients in the control group will be injected with 5 mL of normal saline. The surgeon would be blinded as to patient allocation. Research staff will have previously prepared the formulations (saline or bupivacaine) and have sent them to the operating room prior to beginning the procedure depending on assigned group. At the end of the case, pain will be assessed using a visual analogue scale with a range from 0 to 10 by one of the researches who will also be blinded to the group. This will be done at 30 and 60 minutes after surgical stop time. Additional pain control in the postanesthesia care unit (PACU) will be standardized to all patients.

Hypothesis:

Performing a para-cervical block with local anesthetic prior to a laparoscopic hysterectomy significantly reduces pain after the procedure

Detailed description:
Specific aims:

-Determine if infiltrating the cervical stroma with local anesthetic prior to performing a hysterectomy will reduce postoperative pain scores, and hence increase patient satisfaction.

Secondary aims:

* Determine if there is a difference in baseline pain depending on additional procedures performed, and their response to the paracervical block.
* Determine if there is a difference in response to paracervical block based on history of cesarean deliveries or uterine weight.

Background/Significance:

Hysterectomy is one of the most common surgical procedures performed in the United States, with more than 600,000 done annually. Over the last decade, there has been major changes in regards to the surgical approach utilized. With the advent of laparoscopy and robotic surgery, the rate of procedures done vaginally or abdominally has decreased significantly. One of the major drivers to this change is the demand for a faster recovery and decreased postoperative discomfort. Additionally, several adjuvant methods such as a TAP (transverse abdominal plain) block, ERAS (expedited recovery after surgery) pathway, etc. have been developed in order to minimize pain after surgery and hence increase patient satisfaction. Paracervical block is a particular technique that has been evaluated in multiple studies as a way to reduce pain after vaginal surgery. Studies have been successful in demonstrating an improvement in pain scores after these types of procedures. However, to our knowledge, there has never been follow-up to evaluate this method during the laparoscopic approach, with or without robotic assistance. The rationale of why this technique may be beneficial during a hysterectomy is that after infiltrating the cervical stroma with local anesthetic, it will diffuse towards the pelvic sidewalls via the lymphatic and capillary systems, which would allow for the anesthetic agent to come in direct contact with the nerve plexuses that innervate the pelvic structures. Safety of the technique has been proven over the years, given that it is widely used during office procedures that involve manipulation of the cervix. Although much of the focus regarding reducing postoperative pain has been centered on the abdominal wall and port sites, it is undeniable that a significant portion of pain actually arises from the pelvic surgical site; particularly since laparoscopic trocars have become smaller, resulting in less trauma. Our aim is to determine if infiltrating the cervical stroma with local anesthetic prior to performing a hysterectomy will reduce postoperative pain scores, and hence increase patient satisfaction.

Methods

Study design

This is a prospective randomized controlled trial in which patients that are scheduled to undergo a laparoscopic hysterectomy would be allocated to one of two groups: Paracervical block with local anesthetic (bupivacaine 0.5%), or placebo. This would be achieved using block randomization. The intervention would be performed after the patient is under general anesthesia, prior to starting the surgery. Patients would be consented in the office or preoperative area (before receiving sedatives). As far as the intervention itself, it would consist of injecting 10 mL of 0.5% bupivacaine into the cervical stroma at 3 and 9 o'clock, which is standard technique for para-cervical block. The remainder of the procedure will then continue in a regular fashion. Alternatively, patients in the control group will be injected with 10 mL of normal saline. The surgeon would be blinded as to patient allocation. The formulations (saline or bupivacaine) will be previously prepared in a syringe in the operating room by a member of the research time prior to beginning the procedure. At the end of the case, pain will be assessed using a visual analogue scale with a range from 0 to 10 (Wong-Baker faces - appendix 1) by one of the researches who will also be blinded to the group. This will be done at 30 and 60 minutes after surgical stop time. Additional pain control in the PACU will be standardized to all patients.

Study Subjects

Subjects will be selected based mainly on the fact they are undergoing a hysterectomy.

Sample Size

Investigators expect to detect a 25% reduction in pain reported on the visual analogue scale (VAS). Based on previous publications, it was determined that the mean VAS pain score after a laparoscopic hysterectomy is 5 with a standard deviation of 1.5. In order to detect the expected change after the proposed intervention, with a significance level of 5% and a power of 80%, a sample of 46 patients is required.

Data Collection

Data points to be collected are as follows:

* Age
* BMI
* Operating time
* History of cesarean deliveries
* Preoperative indication for surgery (pain, prolapse, tumor, bleeding, etc)
* Procedures performed (if ovaries/tubes were removed, if robotic assistance was used, if any additional procedures that are exceptions from the exclusion criteria were performed).
* Specimen weight
* Uterine pathology
* Pain score at 30 minutes (see appendix 1 for Wong-Baker scale)
* Pain score at 60 minutes
* Number of days in the hospital (zero if discharged on same-day)

Data Handling

A master key will be generated during randomization. It will contain patient initials and medical record number, and an individual code. Only the primary investigator will have access to this master key. A separate de-identified database using the individual code as index will be used for collection of all data points. The data that can be collected on the day of surgery (baseline characteristics, operating time, pain scores, etc) will be collected that day using a standardized form (appendix 2). This will later be transferred to the de-identified database. Using the master key, investigators will research pathology reports when available to complete final data points (uterine weight, histology, etc).

The data-collection sheets will be destroyed as soon as they are transferred into the de-identified database.

Data Analysis

Investigators will use T-Student tests to assure groups are homogenous to age, BMI, operating time, history of cesarean deliveries, and uterine weight. ChiSquare and Ancova analysis will be utilized to determine if there is a significant difference in reported pain scores between groups. Investigators will also stratify subjects based on uterine weight, history of cesarean delivery, additional procedures, etc. and determine if this has an effect on the reported pain scores.

Time Frame

Investigators expect to be able to consent and enroll at least two patients per week (average range of hysterectomy procedures per week from the surgeons that will participate is 5-10). Investigators expect the data collection phase to span over 30 weeks approximately.

Strength/Innovation

Patient satisfaction is a center point in today's healthcare. Faster recovery with less discomfort is not only standard of care, but may also translate into major economic advantages, such as less narcotic use and a decreased rate of postoperative admission. Using this technique as an adjuvant treatment for pain after laparoscopic hysterectomies has never been explored. There is data published for similar procedures, which demonstrates a clear benefit. If this study demonstrates significant improvement in pain scores, it has the potential to change standard of care for pain control during hysterectomy procedures.

Limitations

The main confounding factors are difference in operating style between surgeons and baseline surgical characteristics (large uteri that may require more dissection and tissue manipulation, etc.). To control for this investigators are only recruiting patients from 3 surgeons who have a similar operating technique. In addition to this, investigators are documenting operating time and specimen weight, which can be used to compare both groups and assure that they are homogeneous to these potential confounders. Further analysis will also be made specifically stratifying the data based on these characteristics.

Risks

The risks of the procedure are minimal. Regarding possible adverse reactions to the local anesthetic, there is no additional risk given that this is already routinely administered during surgery. Patients will be screened to confirm they do not have a history of allergies to the medication. Possible reactions include hypotension, bradycardia, headaches, tremors, etc. The paracervical block is routinely performed in the office setting before most invasive procedures involving the cervix, and risks are minimal, similar to those involving any subdermal injection. Possible risks include bleeding from injection site.

There is also the potential risk of accidental disclosure of the health information that will be collected.

Benefits

This study may find new methods of improving postoperative analgesia for patients undergoing minimally invasive hysterectomy procedures which may lead to less narcotic use, faster discharge from hospital, and greater satisfaction.

Costs

There is no additional costs. Local anesthetic and saline are products that are routinely used during all laparoscopic hysterectomy surgeries. The additional operating time it would take to perform the block is also negligible, since it is a procedure that can be accomplished in less than 2 minutes.

Arms: arm 1: Injection of 10 mL of 0.9% sodium chloride into the cervical stroma divided between 3 and 9 o'clock arm 2: Injection of 10 mL of 0.5% bupivacaine into the cervical stroma divided between 3 and 9 o'clock.
Interventions: intervention 1: Bupivacaine intervention 2: 0.9% Sodium Chloride
Intervention descriptions: intervention 1: Inject 10 mL of 0.5% bupivacaine into cervical stroma intervention 2: Inject 10 mL of 0.9% NaCl into cervical stroma

Protocol documents:
Prot_SAP_000.pdf: 
1 
 
Latest approval:  December 21 2017 
 
 
Title:   
Para-cervical block prior to laparoscopic hysterectomy as an adjuvant treatment to reduce 
postoperative pain. 
 
 
Project Summary:  
Hysterectomy is one of the most common surgical procedures performed in the United States.  
Adequate analgesia and a faster recovery from surgery have become key factors that have taken the 
front stage in recent years.  Increased use of minimally invasive techniques as well as the 
implementation of adjuvant treatments such as TAP-block are examples of strategies that have come 
into play in order to reduce postoperative pain scores and hasten recovery.  We propose the use of a 
paracervical block with bupivacaine performed prior to a hysterectomy as a method to further reduce 
postoperative pain.  This is a prospective, blinded randomized controlled trial in which patients that are 
scheduled to undergo a laparoscopic hysterectomy would be allocated to one of two groups: 
Paracervical block with local anesthetic (bupivacaine 0.5%), or placebo.  After the patient is placed under 
anesthesia, 10 mL of 0.5% bupivacaine would be injected into the cervical stroma at 3 and 9 o’clock, 
which is standard technique for para-cervical block. The remainder of the procedure will then continue 
in a regular fashion. Alternatively, patients in the control group will be injected with 10 mL of normal 
saline. The surgeon would be blinded as to patient allocation.  At the end of the case, pain will be 
assessed using a visual analogue scale with a range from 0 to 10 by one of the researches who will also 
be blinded to the group. This will be done at 30 and 60 minutes after surgical stop time. Additional pain 
control in the PACU will be standardized to all patients.  We will use T-Student tests to assure groups are 
homogenous to age, BMI, operating time, history of cesarean deliveries, and uterine weight.  Chi-square 
and Ancova analysis will be utilized to determine if there is a significant difference in reported pain 
scores between groups.  We will also stratify subjects based on uterine weight, history of cesarean 
delivery, additional procedures, etc. and determine if this has an effect on the reported pain scores. 
 
 
 
Hypothesis: 
Performing a para-cervical block with local anesthetic prior to a laparoscopic hysterectomy significantly 
reduces pain after the procedure. 
 


2 
 
Specific aims: 
Determine if infiltrating the cervical stroma with local anesthetic prior to performing a hysterectomy will 
reduce postoperative pain scores, and hence increase patient satisfaction. 
 
Secondary aims: 
Determine if there is a difference in baseline pain depending on additional procedures 
performed, and their response to the paracervical block. 
Determine if there is a difference in response to paracervical block based on history of cesarean 
deliveries or uterine weight. 
 
Background/Significance: 
Hysterectomy is one of the most common surgical procedures performed in the United States, with 
more than 600,000 done annually.  Over the last decade, there has been major changes in regards to the 
surgical approach utilized.  With the advent of laparoscopy and robotic surgery, the rate of procedures 
done vaginally or abdominally has decreased significantly.   One of the major drivers to this change is the 
demand for a faster recovery and decreased postoperative discomfort.  Additionally, several adjuvant 
methods such as a TAP (transverse abdominal plain) block, ERAS (expedited recovery after surgery) 
pathway, etc. have been developed in order to minimize pain after surgery and hence increase patient 
satisfaction.  Paracervical block is a particular technique that has been evaluated in multiple studies as a 
way to reduce pain after vaginal surgery.  Studies have been successful in demonstrating an 
improvement in pain scores after these types of procedures.  However, to our knowledge, there has 
never been follow-up to evaluate this method during the laparoscopic approach, with or without robotic 
assistance.  The rationale of why this technique may be beneficial during a hysterectomy is that after 
infiltrating the cervical stroma with local anesthetic, it will diffuse towards the pelvic sidewalls via the 
lymphatic and capillary systems, which would allow for the anesthetic agent to come in direct contact 
with the nerve plexuses that innervate the pelvic structures.  Safety of the technique has been proven 
over the years, given that it is widely used during office procedures that involve manipulation of the 
cervix.  Although much of the focus regarding reducing postoperative pain has been centered on the 
abdominal wall and port sites, it is undeniable that a significant portion of pain actually arises from the 
pelvic surgical site; particularly since laparoscopic trocars have become smaller, resulting in less trauma.  
Our aim is to determine if infiltrating the cervical stroma with local anesthetic prior to performing a 
hysterectomy will reduce postoperative pain scores, and hence increase patient satisfaction. 
 
 
Methods 
Study design 
This is a prospective randomized controlled trial in which patients that are scheduled to undergo 
a laparoscopic hysterectomy would be allocated to one of two groups: Paracervical block with local 
anesthetic (bupivacaine 0.5%), or placebo.  This would be achieved using block randomization.  The 


3 
 
intervention would be performed after the patient is under general anesthesia, prior to starting the 
surgery.  Patients would be consented in the office or preoperative area (before receiving sedatives).  As 
far as the intervention itself, it would consist of injecting 10 mL of 0.5% bupivacaine into the cervical 
stroma at 3 and 9 o’clock, which is standard technique for para-cervical block.  The remainder of the 
procedure will then continue in a regular fashion.   Alternatively, patients in the control group will be 
injected with 10 mL of normal saline.  The surgeon would be blinded as to patient allocation.  The 
formulations (saline or bupivacaine) will be previously prepared in a syringe in the operating room by a 
member of the research time prior to beginning the procedure.   At the end of the case, pain will be 
assessed using a visual analogue scale with a range from 0 to 10 (Wong-Baker faces – appendix 1) by one 
of the researches who will also be blinded to the group.  This will be done at 30 and 60 minutes after 
surgical stop time.  Additional pain control in the PACU will be standardized to all patients.  
 
Study Subjects 
 
Subjects will be selected based mainly on the fact they are undergoing a hysterectomy. 
 
Inclusion criteria: 
 
Undergoing laparoscopic hysterectomy with or without salpingoophorectomy 
for benign indications 
 
Undergoing laparoscopic hysterectomy with robotic assistance with or without 
salpingoophorectomy for benign indications 
 
Between 18 and 60 years of age 
 
 
Exclusion criteria: 
 
Intraoperative detection of malignancy 
 
Undergoing additional procedures at the time of surgery (except prophylactic 
McCall culdoplasty/uterosacral ligament suspension, excision of endometriosis, 
appendectomy, cystoscopy) 
 
Inability to perform paracervical block due to anatomic abnormalities 
(absent/flush cervix) 
 
Known allergy/sensitivity to bupivacaine 
 
Intraoperative bowel injury, bladder injury, ureter injury or major vessel injury 
that required repair.  
 
 
 
Sample Size 
Based on previous publications, it was determined that the expected mean pain score 
on postoperative day 0 after a TLH was 6 on the VAS, with a SD of 2. (10, 11) In order to detect 


4 
 
at least a 40% reduction in postoperative pain between groups, with a significance level of 5% 
and a power of 80%, a sample of 32 was required. 
Data Collection 
 
Data points to be collected are as follows: 
 
Age 
 
BMI 
 
Operating time 
 
History of cesarean deliveries 
 
Preoperative indication for surgery (pain, prolapse, tumor, bleeding, etc) 
 
Procedures performed (if ovaries/tubes were removed, if robotic assistance was 
used, if any additional procedures that are exceptions from the exclusion 
criteria were performed). 
 
Specimen weight 
 
Uterine pathology 
 
Pain score at 30 minutes (see appendix 1 for Wong-Baker scale) 
 
Pain score at 60 minutes 
 
Number of days in the hospital (zero if discharged on same-day) 
 
Data Handling 
 
A master key will be generated during randomization.  It will contain patient 
initials and medical record number, and an individual code.  Only the primary 
investigator will have access to this master key.   
A separate de-identified database using the individual code as index will be used 
for collection of all data points.  The data that can be collected on the day of surgery 
(baseline characteristics, operating time, pain scores, etc) will be collected that day 
using a standardized form (appendix 2).  This will later be transferred to the de-
identified database.  Using the master key, we will research pathology reports when 
available to complete final data points (uterine weight, histology, etc).   
The data-collection sheets will be destroyed as soon as they are transferred into 
the de-identified database. 
 
 
Data Analysis 
We will use T-Student tests to assure groups are homogenous to age, BMI, 
operating time, history of cesarean deliveries, and uterine weight.  ChiSquare and 
Ancova analysis will be utilized to determine if there is a significant difference in 
reported pain scores between groups.  We will also stratify subjects based on uterine 


5 
 
weight, history of cesarean delivery, additional procedures, etc. and determine if this 
has an effect on the reported pain scores. 
 
Time Frame 
We expect to be able to consent and enroll at least two patients per week (average 
range of hysterectomy procedures per week from the surgeons that will participate is 5-
10).  We expect the data collection phase to span over 30 weeks approximately. 
 
Strength/Innovation 
Patient satisfaction is a center point in today’s healthcare.  Faster recovery with less 
discomfort is not only standard of care, but may also translate into major economic 
advantages, such as less narcotic use and a decreased rate of postoperative admission.  
Using this technique as an adjuvant treatment for pain after laparoscopic 
hysterectomies has never been explored.  There is data published for similar 
procedures, which demonstrates a clear benefit.  If this study demonstrates significant 
improvement in pain scores, it has the potential to change standard of care for pain 
control during hysterectomy procedures. 
 
Limitations 
The main confounding factors are difference in operating style between surgeons and 
baseline surgical characteristics (large uteri that may require more dissection and tissue 
manipulation, etc.).  To control for this we are only recruiting patients from 3 surgeons 
who have a similar operating technique.  In addition to this, we are documenting 
operating time and specimen weight, which can be used to compare both groups and 
assure that they are homogenous to these potential confounders.   Further analysis will 
also be made specifically stratifying the data based on these characteristics.   
 
 
 
Risks 
The risks of the procedure are minimal.  Regarding possible adverse reactions to the 
local anesthetic, there is no additional risk given that this is already routinely 
administered during surgery.  Patients will be screened to confirm they do not have a 
history of allergies to the medication.  Possible reactions include hypotension, 
bradycardia, headaches, tremors, etc.    


6 
 
The parcervical block is routinely performed in the office setting before most invasive 
procedures involving the cervix, and risks are minimal, similar to those involving any 
subdermal injection. Possible risks include bleeding from injection site. 
There is also the potential risk of accidental disclosure of the health information that will 
be collected.   
 
Benefits 
This study may find new methods of improving postoperative analgesia for patients 
undergoing minimally invasive hysterectomy procedures which may lead to less narcotic 
use, faster discharge from hospital, and greater satisfaction. 
 
Costs 
There is no additional costs.  Local anesthetic and saline are products that are routinely 
used during all laparoscopic hysterectomy surgeries.  The additional operating time it 
would take to perform the block is also negligible, since it is a procedure that can be 
accomplished in less than 2 minutes.   
 
References 
 
1. Acton JN, Salfinger SG, Tan J, Cohen PA. Outcomes of Total Laparoscopic Hysterectomy 
Using a 5-mm Versus 10-mm Laparoscope: A Randomized Control Trial. J Minim Invasive 
Gynecol. 2016;23(1):101-6. 
2. Centini G, Calonaci A, Lazzeri L, et al. Parenterally administered moderate sedation and 
paracervical block versus general anesthesia for hysteroscopic polypectomy: a pilot study 
comparing postoperative outcomes. J Minim Invasive Gynecol. 2015;22(2):193-8. 
3. Donnez O, Donnez J, Dolmans MM, Dethy A, Baeyens M, Mitchell J. Low Pain Score After 
Total Laparoscopic Hysterectomy and Same-Day Discharge Within Less Than 5 Hours: 
Results of a Prospective Observational Study. J Minim Invasive Gynecol. 2015;22(7):1293-9. 
4. Golembiewski J, Dasta J. Evolving Role of Local Anesthetics in Managing Postsurgical 
Analgesia. Clin Ther. 2015;37(6):1354-71. 
5. Long JB, Eiland RJ, Hentz JG, et al. Randomized trial of preemptive local analgesia in vaginal 
surgery. Int Urogynecol J Pelvic Floor Dysfunct. 2009;20(1):5-10. 
6. Mercier RJ, Zerden ML. Intrauterine anesthesia for gynecologic procedures: a systematic 
review. Obstet Gynecol. 2012;120(3):669-77. 
7. Ng A, Swami A, Smith G, Davidson AC, Emembolu J. The analgesic effects of intraperitoneal 
and incisional bupivacaine with epinephrine after total abdominal hysterectomy. Anesth 
Analg. 2002;95(1):158-62, table of contents. 


7 
 
8. O'neal MG, Beste T, Shackelford DP. Utility of preemptive local analgesia in vaginal 
hysterectomy. Am J Obstet Gynecol. 2003;189(6):1539-41. 
9. Penninx JP, Mol BW, Bongers MY. Endometrial ablation with paracervical block. J Reprod 
Med. 2009;54(10):617-20. 
10. Skensved H. Combining Paracervical Block With a Complete Fundal Block Significantly 
Reduces Patients' Perception of Pain During Radio-Frequency Endometrial Ablation in an 
Office Setting. J Minim Invasive Gynecol. 2015;22(6S):S45. 
11. Tangsiriwatthana T, Sangkomkamhang US, Lumbiganon P, Laopaiboon M. Paracervical local 
anaesthesia for cervical dilatation and uterine intervention. Cochrane Database Syst Rev. 
2013;(9):CD005056. 
12. ACOG Committee Opinion No. 444: choosing the route of hysterectomy for benign disease. 
Obstet Gynecol. 2009;114(5):1156-8. 
13. Wong-Baker FACES Foundation (2016). Wong-Baker FACES® Pain Rating Scale. Retrieved 
11/10/2016 with permission from http://www.WongBakerFACES.org. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 1 
Wong-Baker FACES Pain Rating Scale (Used with permission) 
 
 


8 
 
 
 
Appendix 2 
Example of data collection form 
 
 


9 
 
Name: 
 
 
Age: MRN: 
BMI: 
 
# of CDEL: 
0 
1 
2 
3 
4 
>4 
Indication(s) for surgery: 
AUB 
Pelvic pain 
Prolapse 
Fibroids 
 
Other:______________________ 
Additional procedures performed: 
Oophorectomy 
Excision of endometriosis  
Vaginal vault suspension 
Minilap for tissue extraction 
 
Robotic Assistance YES  NO 
 
Pain at 30 minutes:  
 
0      1      2      3      4      5     6      7      8      9      10 
 
Pain at 60 minutes: 
 
0      1      2      3      4      5     6      7      8      9      10 
 
Days in hospital:   
0    1    2    3    >3 
Pathology: 
No abnormalities 
Adenomyosis 
Endometriosis 
Leiomyoma 
Other:_________ 
 
Spec weight: 
 
_______grams 
Operating time: 
 
______minutes