Buffered Lidocaine for Loop Electrosurgical Excision Procedures (LEEPs)

A Randomized Trial of Buffered vs Nonbuffered Lidocaine With Epinephrine for Cervical Loop Excision

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.

Study Overview

• Status: Completed
• Conditions: Uterine Cervical Dysplasia
• Intervention / Treatment: Drug: Non-buffered lidocaine; Drug: sodium bicarbonate buffered 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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lidocaine Arm; Women in this arm will receive plain lidocaine with epinephrine injected into their cervix prior to the LEEP procedure.	Drug: Non-buffered lidocaine
Experimental: Buffered Lidocaine; Women in this arm will receive sodium bicarbonate buffered lidocaine mixed with epinephrine injected into their cervix prior to the LEEP procedure.	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Within 30 minutes of completion of procedure
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.	Within 30 minutes of completion of the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Within 30 minutes of completion of procedure
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.	Within 30 minutes of completion of procedure

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: L. Stewart Massad, M.D., Washington University School of Medicine

Publications and helpful links

General Publications

• Orlinsky M, Hudson C, Chan L, Deslauriers R. Pain comparison of unbuffered versus buffered lidocaine in local wound infiltration. J Emerg Med. 1992 Jul-Aug;10(4):411-5. doi: 10.1016/0736-4679(92)90269-y.
• Ruegg TA, Curran CR, Lamb T. Use of buffered lidocaine in bone marrow biopsies: a randomized, controlled trial. Oncol Nurs Forum. 2009 Jan;36(1):52-60. doi: 10.1188/09.ONF.52-60.
• Sharma T, Gopal L, Shanmugam MP, Bhende P, George J, Samanta TK, Mukesh BN. Comparison of pH-adjusted bupivacaine with a mixture of non-pH-adjusted bupivacaine and lignocaine in primary vitreoretinal surgery. Retina. 2002 Apr;22(2):202-7. doi: 10.1097/00006982-200204000-00011.
• Fitton AR, Ragbir M, Milling MA. The use of pH adjusted lignocaine in controlling operative pain in the day surgery unit: a prospective, randomised trial. Br J Plast Surg. 1996 Sep;49(6):404-8. doi: 10.1016/s0007-1226(96)90011-9.
• Burns CA, Ferris G, Feng C, Cooper JZ, Brown MD. Decreasing the pain of local anesthesia: a prospective, double-blind comparison of buffered, premixed 1% lidocaine with epinephrine versus 1% lidocaine freshly mixed with epinephrine. J Am Acad Dermatol. 2006 Jan;54(1):128-31. doi: 10.1016/j.jaad.2005.06.043.
• Younis I, Bhutiani RP. Taking the 'ouch' out - effect of buffering commercial xylocaine on infiltration and procedure pain - a prospective, randomised, double-blind, controlled trial. Ann R Coll Surg Engl. 2004 May;86(3):213-7. doi: 10.1308/003588404323043382.
• Masters JE. Randomised control trial of pH buffered lignocaine with adrenaline in outpatient operations. Br J Plast Surg. 1998 Jul;51(5):385-7. doi: 10.1054/bjps.1997.0293.

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: July 28, 2011
• First Submitted That Met QC Criteria: July 28, 2011
• First Posted (Estimate): July 29, 2011

Study Record Updates

• Last Update Posted (Estimate): July 28, 2014
• Last Update Submitted That Met QC Criteria: June 26, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Cervical Diseases; Uterine Diseases; Precancerous Conditions; Carcinoma in Situ; Cervical Intraepithelial Neoplasia; Uterine Cervical Dysplasia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine
• Other Study ID Numbers: 201104269