Uterine Cervical Dysplasia
Conditions
Brief summary
Women undergoing a LEEP procedure who receive lidocaine buffered with sodium bicarbonate for their cervical block will experience less injection pain than women who receive plain lidocaine.
Detailed description
Specific aims: 1. To determine whether buffering the agent used for intracervical anesthetic at the time of cervical loop excision reduces injection-related pain. (Hypothesis: buffering significantly reduces injection-related pain.) 2. To determine whether other components of pain from LEEP (procedural pain, and cramping) can be reduced by buffering of intracervical anesthetic among women undergoing cervical loop excision. (Hypothesis: only injection pain will be reduced by buffering, as procedural pain will be reduced by lidocaine equally in both arms and cramping will not be reduced in either arm.) Background: Although cervical cancer rates have been dramatically reduced by Pap test screening and the eradication of precursors, more than 100,000 U.S. women develop premalignant cervical lesions each year that require treatment (1). The cervical loop electrosurgical excision procedure (LEEP) is the most common therapy for CIN among U.S. gynecologists. LEEP is performed using one or more 1-2 cm electrosurgical diathermy loops to excise involved and at-risk cervical epithelium including underlying stroma containing glands. Destroying this tissue eliminates cells infected with human papillomavirus, the proximate cause of cervical cancer, and radically reduces the risk of later developing cervical cancer (2, 3). LEEP is usually performed as an outpatient procedure using intracervical anesthesia, most commonly combining lidocaine as an anesthetic agent with epinephrine as a hemostatic agent; final hemostasis is achieved using electrosurgical fulguration and topical hemostatic agents (4). Prior literature has suggested that pain from LEEP has 3 components: pain from injection of the anesthetic combination, pain from the excision, and cramping from reflex uterine contractions (5). While cramping can be controlled with oral nonsteroidal anti-inflammatory agents, injection and procedural pain are not. Most women categorize the pain of LEEP as 3-7 on a 0-10 Likert scale (5, 6). Studies of dermal and ocular anesthesia and bone marrow biopsy have found that buffering of acidic local anesthetic agents reduces injection pain (7-14), with up to 66% reduction in pain and significant results in randomized trials involving 30-50 participants. However, the use of buffered lidocaine has not yet been tested for LEEPs. The principal investigator has used both forms of anesthesia and considers both acceptable forms of therapy; he is unaware of any evidence to support the superiority of either arm.
Interventions
DRUGsodium bicarbonate buffered lidocaine
8.4% sodium bicarbonate will be mixed with lidocaine in a 1:10 ratio prior to mixing with epinephrine and injecting into the cervix.
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* antecedent biopsy read as * cervical intraepithelial neoplasia (CIN) grade 2 or 3 or microinvasive cancer * adenocarcinoma in situ * persistent CIN 1 * antecedent pap read as * high grade squamous intraepithelial lesion * atypical glandular cells * persistent low grade squamous intraepithelial lesion
Exclusion criteria
* anatomy unsuitable for safe office loop excision based on operator judgement * inability to tolerate procedure under local anesthesia * pregnancy * age less than 18 years * inability to understand spoken or written English * refusal of consent * prisoner * mental incapacity * anticoagulant or antiplatelet therapy, or known bleeding diathesis * use of analgesics other than over the counter medications(OTC meds include NSAIDS or Tylenol) within 7 days of scheduled LEEP
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Injection Pain Score (Mean) | Within 30 minutes of completion of procedure | A Likert visual analog scale will be used to document each study participant's level of pain experienced during injection of the cervical block. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote no pain were considered to have marked 0 mm. |
| Injection Pain Score (Median) | Within 30 minutes of completion of the procedure | A Likert visual analog scale will be used to document each study participant's level of pain experienced during injection of the cervical block. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote no pain were considered to have marked 0 mm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Mean) | Within 30 minutes of completion of procedure | A Likert visual analog scale will be used to determine the overall pain experienced by each study participant including injection pain, procedural pain, and cramping. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote no pain were considered to have marked 0 mm. |
| Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Median) | Within 30 minutes of completion of procedure | A Likert visual analog scale will be used to determine the overall pain experienced by each study participant including injection pain, procedural pain, and cramping. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote no pain were considered to have marked 0 mm. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lidocaine Arm Women in this arm will receive plain lidocaine with epinephrine injected into their cervix prior to the LEEP procedure. | 24 |
| Buffered Lidocaine Women in this arm will receive sodium bicarbonate buffered lidocaine mixed with epinephrine injected into their cervix prior to the LEEP procedure.
sodium bicarbonate buffered lidocaine: 8.4% sodium bicarbonate will be mixed with lidocaine in a 1:10 ratio prior to mixing with epinephrine and injecting into the cervix. | 28 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Didn't complete questionnaire correctly | 4 | 0 |
Baseline characteristics
| Characteristic | Buffered Lidocaine | Total | Lidocaine Arm |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 52 Participants | 24 Participants |
| Age, Continuous | 32.3 years STANDARD_DEVIATION 7.6 | 32.4 years STANDARD_DEVIATION 9.2 | 32.4 years STANDARD_DEVIATION 10.3 |
| Anesthetic volume (in mL) >10 mL | 2 participants | 3 participants | 1 participants |
| Anesthetic volume (in mL) 10 mL | 15 participants | 26 participants | 11 participants |
| Anesthetic volume (in mL) 6-9 mL | 11 participants | 23 participants | 12 participants |
| Ectocervical loop size (in mm) 15 x 12 | 7 participants | 10 participants | 3 participants |
| Ectocervical loop size (in mm) 20 x 12 | 16 participants | 29 participants | 13 participants |
| Ectocervical loop size (in mm) Other | 5 participants | 13 participants | 8 participants |
| Endocervical loop size (in mm) 10 x 10 | 11 participants | 16 participants | 5 participants |
| Endocervical loop size (in mm) 10 x 8 | 0 participants | 1 participants | 1 participants |
| Endocervical loop size (in mm) 15 x 12 | 0 participants | 2 participants | 2 participants |
| Estimated blood loss (in mL) 0 mL | 6 participants | 9 participants | 3 participants |
| Estimated blood loss (in mL) >10 mL | 5 participants | 10 participants | 5 participants |
| Estimated blood loss (in mL) 1-5 mL | 8 participants | 17 participants | 9 participants |
| Estimated blood loss (in mL) 6-10 mL | 9 participants | 16 participants | 7 participants |
| Indication AIS | 1 participants | 2 participants | 1 participants |
| Indication CIN 2 | 7 participants | 11 participants | 4 participants |
| Indication CIN 3 | 15 participants | 26 participants | 11 participants |
| Indication HSIL | 4 participants | 12 participants | 8 participants |
| Indication Persistent CIN 1 | 1 participants | 1 participants | 0 participants |
| Number of passes 1 | 11 participants | 17 participants | 6 participants |
| Number of passes 2 | 12 participants | 24 participants | 12 participants |
| Number of passes 3+ | 5 participants | 11 participants | 6 participants |
| Parity 0 | 6 participants | 9 participants | 3 participants |
| Parity 1 | 7 participants | 12 participants | 5 participants |
| Parity 2+ | 15 participants | 31 participants | 16 participants |
| Procedure type Ectocervix and endocervix | 11 participants | 19 participants | 8 participants |
| Procedure type Ectocervix only | 17 participants | 33 participants | 16 participants |
| Race/Ethnicity, Customized African American | 12 participants | 25 participants | 13 participants |
| Race/Ethnicity, Customized Hispanic/Latina | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Other | 1 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized White | 14 participants | 24 participants | 10 participants |
| Region of Enrollment United States | 28 participants | 52 participants | 24 participants |
| Sex: Female, Male Female | 28 Participants | 52 Participants | 24 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 28 | 0 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 |
Outcome results
Primary
Injection Pain Score (Mean)
A Likert visual analog scale will be used to document each study participant's level of pain experienced during injection of the cervical block. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote no pain were considered to have marked 0 mm.
Time frame: Within 30 minutes of completion of procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lidocaine Arm | Injection Pain Score (Mean) | 25 units on a scale | Standard Deviation 19 |
| Buffered Lidocaine | Injection Pain Score (Mean) | 19 units on a scale | Standard Deviation 17 |
p-value: 0.13Wilcoxon (Mann-Whitney)
Primary
Injection Pain Score (Median)
A Likert visual analog scale will be used to document each study participant's level of pain experienced during injection of the cervical block. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote no pain were considered to have marked 0 mm.
Time frame: Within 30 minutes of completion of the procedure
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lidocaine Arm | Injection Pain Score (Median) | 26 units on a scale |
| Buffered Lidocaine | Injection Pain Score (Median) | 18 units on a scale |
p-value: 0.13Wilcoxon (Mann-Whitney)
Secondary
Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Mean)
A Likert visual analog scale will be used to determine the overall pain experienced by each study participant including injection pain, procedural pain, and cramping. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote no pain were considered to have marked 0 mm.
Time frame: Within 30 minutes of completion of procedure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lidocaine Arm | Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Mean) | Injection pain | 25 units on a scale | Standard Deviation 19 |
| Lidocaine Arm | Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Mean) | Procedure pain | 27 units on a scale | Standard Deviation 18 |
| Lidocaine Arm | Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Mean) | Cramping pain | 19 units on a scale | Standard Deviation 16 |
| Buffered Lidocaine | Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Mean) | Injection pain | 19 units on a scale | Standard Deviation 17 |
| Buffered Lidocaine | Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Mean) | Procedure pain | 19 units on a scale | Standard Deviation 17 |
| Buffered Lidocaine | Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Mean) | Cramping pain | 18 units on a scale | Standard Deviation 16 |
Secondary
Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Median)
A Likert visual analog scale will be used to determine the overall pain experienced by each study participant including injection pain, procedural pain, and cramping. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote no pain were considered to have marked 0 mm.
Time frame: Within 30 minutes of completion of procedure
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lidocaine Arm | Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Median) | Injection pain | 26 units on a scale |
| Lidocaine Arm | Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Median) | Procedure pain | 25 units on a scale |
| Lidocaine Arm | Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Median) | Cramping pain | 19 units on a scale |
| Buffered Lidocaine | Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Median) | Injection pain | 18 units on a scale |
| Buffered Lidocaine | Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Median) | Cramping pain | 14 units on a scale |
| Buffered Lidocaine | Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Median) | Procedure pain | 13 units on a scale |