Use of Nitrous Oxide for Pain and Anxiety Management During Cervical Cerclage Removal

Official title

Use of Nitrous Oxide for Pain and Anxiety Management During Cervical Cerclage Removal- A Multicenter Randomized Controlled Study

Overview

The goal of this clinical trial is to determine whether inhaled nitrous oxide can reduce pain and anxiety during cervical cerclage removal compared with standard care. Cervical cerclage removal is commonly performed in the outpatient setting during the third trimester of pregnancy and may be associated with discomfort and anxiety despite being a brief procedure. The study will include pregnant women aged 18 years or older undergoing elective cervical cerclage removal at 36 weeks of gestation or later. The main questions the study aims to answer are: * Does inhaled nitrous oxide reduce pain during cervical cerclage removal? * Does inhaled nitrous oxide reduce anxiety during the procedure? * Does the use of nitrous oxide improve overall patient satisfaction during cerclage removal? Researchers will compare women receiving inhaled nitrous oxide to those receiving standard care without analgesia, as routinely practiced in the participating institutions, in order to determine whether nitrous oxide improves pain control and patient experience during the procedure. Participants will: * Be randomly assigned to receive either inhaled nitrous oxide (50% nitrous oxide / 50% oxygen) or standard care without analgesic treatment during cervical cerclage removal. * Undergo the procedure according to routine clinical practice in the participating centers. * Complete questionnaires assessing pain and anxiety, including a visual analog scale (VAS) for pain and the State-Trait Anxiety Inventory (STAI). * Have routine clinical data recorded from their medical records, including maternal vital signs and any procedure-related side effects.

Detailed description

Cervical insufficiency is a recognized risk factor for spontaneous preterm birth, which remains a major cause of perinatal morbidity and mortality worldwide. Cervical cerclage is an established intervention used in carefully selected patients to reduce the risk of preterm birth.

While cerclage placement is typically performed under anesthesia in the operating room, cerclage removal is usually carried out in the outpatient setting during the late third trimester of pregnancy. Despite being a brief procedure, many patients experience pain, discomfort, and anxiety during cerclage removal. Evidence regarding optimal pain management strategies for this procedure remains limited, and most patients currently undergo cerclage removal without analgesia.

Nitrous oxide (N₂O) is an inhaled gas with well-established analgesic and anxiolytic properties. It has a rapid onset and offset of action and a favorable safety profile. Nitrous oxide is widely used in obstetrics, particularly for labor analgesia, and has also been used for pain management during minor medical procedures. However, its use specifically for cervical cerclage removal has not been well studied.

This study is a multicenter randomized controlled trial designed to evaluate whether inhaled nitrous oxide reduces pain and anxiety during elective cervical cerclage removal. Participants will be randomly assigned in a 1:1 ratio to receive either inhaled nitrous oxide (50% nitrous oxide / 50% oxygen) during the procedure or standard care without analgesic treatment, as routinely practiced in the participating institutions. Randomization will be stratified by site and implemented using sequentially numbered sealed envelopes opened immediately prior to the procedure.

All procedures will be performed according to routine clinical practice in the participating centers. Maternal and procedural data will be collected from medical records, including procedure duration, maternal vital signs, and any reported side effects such as nausea, dizziness, or headache. Pain intensity will be assessed using a 0-100 mm visual analog scale (VAS), and anxiety levels will be evaluated using the State-Trait Anxiety Inventory (STAI). Additional outcomes will include maternal heart rate during the procedure and patient satisfaction with the procedure.

This trial aims to determine whether inhaled nitrous oxide can effectively reduce pain and anxiety during cervical cerclage removal. The findings of this study may provide evidence to support improved pain management strategies for this procedure and may contribute to enhancing patient experience during cerclage removal.

Interventions

• Drug Inhaled nitrous oxide
  Inhaled nitrous oxide (50% nitrous oxide / 50% oxygen) administered via a demand-valve mask during cervical cerclage removal. The system includes a one-way valve and is self-administered by the patient, who holds the mask and inhales as needed. The device is identical to the equipment routinely used for labor analgesia in the participating institutions and is operated and monitored by trained midwives experienced in nitrous oxide administration. Nitrous oxide inhalation begins following instruc

Primary outcome measures

• Pain intensity during cervical cerclage removal [Time frame: 3-5 minutes following completion of the procedure]

Secondary outcome measures (8)

• Difference between expected pain and experienced pain [Time frame: Baseline (prior to procedure) and 3-5 minutes following completion of the procedure]
• Procedure duration [Time frame: During procedure]
• Change in maternal heart rate during procedure [Time frame: Baseline measurement prior to the procedure and continuous monitoring during the procedure]
• Change in anxiety level (STAI) [Time frame: Baseline (before procedure) and 3-5 minutes after completion of the procedure]
• Patient satisfaction [Time frame: 3-5 minutes after completion of the procedure]
• Adverse events [Time frame: During procedure]
• Conversion to neuraxial or general anesthesia [Time frame: During the procedure]
• Physician-rated procedural difficulty [Time frame: 3-5 minutes following completion of the procedure]

Eligibility criteria

Inclusion criteria

• Age ≥18 years
• Women at ≥34 weeks of gestation
• Singleton or twin pregnancy
• Ability to understand, sign informed consent, and complete questionnaires

Exclusion criteria

• Triplet or higher-order pregnancy
• Contraindications to nitrous oxide use
• Fetal monitoring category 2 or higher
• Maternal body temperature >38°C
• Significant vaginal bleeding
• Severe preeclampsia
• Cerclage removal under general anesthesia
• Language or cognitive barrier
• Baseline pain >3 on VAS scale, prior to the procedure

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Israel · 4 centers

• Kaplan Medical Center — Rehovot
• Edith Wolfson Medical Center — Holon
• Meir Medical Center — Kfar Saba
• Rabin Medical Center — Petah Tikva

Publications

• Teichman Y. and Mellik H. (1976). "State-Trait Anxiety Inventory," Tel-Aviv University, Ramot Press
• American College of Emergency Physicians. Managing Acute Pain in the ED - Nitrous Oxide. ACEP // Nitrous Oxide (viewed July 2021)
• Spielberger, C., Gorsuch, R., & Lushene, R. (1970). Manual for the State-Trait Anxiety Inventory
• Rosen MA. Nitrous oxide for relief of labor pain: a systematic review. Am J Obstet Gynecol. 2002 May;186(5 Suppl Nature):S110-26. doi: 10.1067/mob.2002.121259. PMID 12011877
• Del Valle Rubido C, Solano Calvo JA, Rodriguez Miguel A, Delgado Espeja JJ, Gonzalez Hinojosa J, Zapico Goni A. Inhalation analgesia with nitrous oxide versus other analgesic techniques in hysteroscopic polypectomy: a pilot study. J Minim Invasive Gynecol. 2015 May-Jun;22(4):595-600. doi: 10.1016/j.jmig.2015.01.005. Epub 2015 Jan 14. PMID 25596171
• Stewart RD. Nitrous oxide sedation/analgesia in emergency medicine. Ann Emerg Med. 1985 Feb;14(2):139-48. doi: 10.1016/s0196-0644(85)81077-5. PMID 4038592
• Veger ML, van Iterson J, Bakx R, Ridderikhof ML. The Role of Nitrous Oxide in Minor Pediatric Procedures in the Emergency Department: A Systematic Review. J Pediatr Surg. 2024 Jun;59(6):1154-1162. doi: 10.1016/j.jpedsurg.2023.12.026. Epub 2024 Jan 14. PMID 38368199
• Pain Management for In-Office Uterine and Cervical Procedures: ACOG Clinical Consensus No. 9. Obstet Gynecol. 2025 May 15;146(1):161-177. doi: 10.1097/AOG.0000000000005911. PMID 40373312

Identifiers

NCT: NCT07491874 · 0034-26-KMC1-C

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗