Original research article| Volume 95, ISSUE 3, P239-244, March 2017

Nitrous oxide for pain management during in-office hysteroscopic sterilization: a randomized controlled trial



      To evaluate whether inhaled nitrous oxide with oxygen (N2O/O2) is associated with less pain compared to oral sedation for pain management during in-office hysteroscopic sterilization.

      Study design

      This double blinded randomized controlled trial enrolled women undergoing in-office hysteroscopic sterilization. All participants received pre-procedure intramuscular ketorolac and a standardized paracervical block. The intervention group also received N2O/O2 via a nasal mask titrated to a maximum 70%:30% mixture by a nurse during the procedure and placebo pills pre-procedure and the active control group received inhaled O2 during the procedure and 5/325 mg hydrocodone/acetaminophen and 1 mg lorazepam pre-procedure. The primary outcome was maximum procedure pain on a 100 mm Visual Analog Scale (VAS with anchors at 0 = no pain and 100 = worst imaginable pain) assessed 3–5 min post procedure. Thirty women per treatment arm were required to detect a clinically significant pain difference of 20 mm.


      Seventy-two women, 36 per study arm, were randomized. Mean age of participants was 34.1±5.7 years and mean BMI was 30.1±6.6 kg/m2. Mean maximum procedure pain scores were 22.8±27.6 mm and 54.5±32.7 mm for intervention and control groups, respectively (p<.001). Most study participants (97%) stated N2O/O2 should be offered for gynecologic office procedures and 86% would pay for it if not a covered benefit.


      N2O/O2 decreased pain with in-office hysteroscopic sterilization compared to oral sedation and is an effective pain management option for this procedure.


      Given its safety and favorable side effect profile, N2O/O2 can be used for pain management for in-office hysteroscopic sterilization and adds a safe, easily administered option to currently available strategies.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Contraception
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Jones J
        • Mosher W
        • Daniels K
        Current contraceptive use in the United States, 2006-2010, and changes in patterns of use since 1995.
        Natl Health Stat Report. 2012; : 1-25
        • Kraemer DF
        • Yen PY
        • Nichols M
        An economic comparison of female sterilization of hysteroscopic tubal occlusion with laparoscopic bilateral tubal ligation.
        Contraception. 2009; 80: 254-260
        • Hopkins MR
        • Creedon DJ
        • Wagie AE
        • Williams AR
        • Famuyide AO
        Retrospective cost analysis comparing Essure hysteroscopic sterilization and laparoscopic bilateral tubal coagulation.
        J Minim Invasive Gynecol. 2007; 14: 97-102
        • Nichols M
        • Carter JF
        • Fylstra DL
        • Childers MA
        Comparative study of hysteroscopic sterilization performed in-office versus a hospital operating room.
        J Minim Invasive Gynecol. 2006; 13: 447-450
        • Levie MD
        • Chudnoff SG
        Prospective analysis of office-based hysteroscopic sterilization.
        J Minim Invasive Gynecol. 2006; 13: 98-101
        • Ogburn T
        • Espey E
        Transcervical sterilization: past, present, and future.
        Obstet Gynecol Clin N Am. 2007; 34 ([viii]): 57-72
        • Levie M
        • Weiss G
        • Kaiser B
        • Daif J
        • Chudnoff SG
        Analysis of pain and satisfaction with office-based hysteroscopic sterilization.
        Fertil Steril. 2010; 94: 1189-1194
        • Arjona JE
        • Mino M
        • Cordon J
        • Povedano B
        • Pelegrin B
        • Castelo-Branco C
        Satisfaction and tolerance with office hysteroscopic tubal sterilization.
        Fertil Steril. 2008; 90: 1182-1186
        • Jensen MP
        • Martin SA
        • Cheung R
        The meaning of pain relief in a clinical trial.
        J Pain. 2005; 6: 400-406
        • Thiel JA
        • Lukwinski A
        • Kamencic H
        • Lim H
        Oral analgesia vs intravenous conscious sedation during Essure micro-insert sterilization procedure: randomized, double-blind, controlled trial.
        J Minim Invasive Gynecol. 2011; 18: 108-111
        • Chudnoff S
        • Einstein M
        • Levie M
        Paracervical block efficacy in office hysteroscopic sterilization: a randomized controlled trial.
        Obstet Gynecol. 2010; 115: 26-34
        • Isley MM
        • Jensen JT
        • Nichols MD
        • Lehman A
        • Bednarek P
        • Edelman A
        Intrauterine lidocaine infusion for pain management during outpatient transcervical tubal sterilization: a randomized controlled trial.
        Contraception. 2012; 85: 275-281
        • Al-Zahrani AM
        • Wyne AH
        • Sheta SA
        Comparison of oral midazolam with a combination of oral midazolam and nitrous oxide-oxygen inhalation in the effectiveness of dental sedation for young children.
        J Indian Soc Pedod Prev Dent. 2009; 27: 9-16
        • Wood M
        The safety and efficacy of intranasal midazolam sedation combined with inhalation sedation with nitrous oxide and oxygen in paediatric dental patients as an alternative to general anaesthesia.
        SAAD Dig. 2010; 26: 12-22
        • Burnweit C
        • Diana-Zerpa JA
        • Nahmad MH
        • Lankau CA
        • Weinberger M
        • Malvezzi L
        • et al.
        Nitrous oxide analgesia for minor pediatric surgical procedures: an effective alternative to conscious sedation?.
        J Pediatr Surg. 2004; 39 (discussion -9): 495-499
        • Tobias JD
        Applications of nitrous oxide for procedural sedation in the pediatric population.
        Pediatr Emerg Care. 2013; 29: 245-265
        • Young A
        • Ismail M
        • Papatsoris AG
        • Barua JM
        • Calleary JG
        • Masood J
        Entonox(R) inhalation to reduce pain in common diagnostic and therapeutic outpatient urological procedures: a review of the evidence.
        Ann R Coll Surg Engl. 2012; 94: 8-11
        • Faddy SC
        • Garlick SR
        A systematic review of the safety of analgesia with 50% nitrous oxide: can lay responders use analgesic gases in the prehospital setting?.
        Emerg Med J. 2005; 22: 901-908
        • McKinnon KD
        Prehospital analgesia with nitrous oxide/oxygen.
        CMAJ. 1981; 125: 836-840
        • Descamps MJ
        • Gwilym S
        • Weldon D
        • Holloway V
        Prospective audit of emergency department transit times associated with entonox analgesia for reduction of the acute, traumatic dislocated shoulder.
        Accid Emerg Nurs. 2007; 15: 223-227
        • Baskett PJ
        Use of entonox in the ambulance service.
        Br Med J. 1970; 2: 41-43
        • Zacny JP
        • Hurst RJ
        • Graham L
        • Janiszewski DJ
        Preoperative dental anxiety and mood changes during nitrous oxide inhalation.
        J Am Dent Assoc. 2002; 133: 82-88
        • Becker DE
        • Rosenberg M
        Nitrous oxide and the inhalation anesthetics.
        Anesth Prog. 2008; 55 (quiz 31–2): 124-130
        • Sherwood ER
        • Williams CG
        • Prough DS
        Townsend: Sabiston textbook of surgery.
        Elsevier, 2012
        • O'Sullivan I
        • Benger J
        Nitrous oxide in emergency medicine.
        Emerg Med J. 2003; 20: 214-217
        • Collado V
        • Nicolas E
        • Faulks D
        • Hennequin MA
        Review of the safety of 50% nitrous oxide/oxygen in conscious sedation.
        Expert Opin Drug Saf. 2007; 6: 559-571
        • Clark MS
        • Campbell SA
        • Clark AM
        Technique for the administration of nitrous oxide/oxygen sedation to ensure psychotropic analgesic nitrous oxide (PAN) effects.
        Int J Neurosci. 2006; 116: 871-877
        • DeLoach LJ
        • Higgins MS
        • Caplan AB
        • Stiff JL
        The visual analog scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale.
        Anesth Analg. 1998; 86: 102-106
        • Spielberger CD
        • Gorsuch RL
        • Lushene RE
        Manual for the State-Trait Anxiety Inventory.
        Palo Alto Consulting Psychologist's Press, 1970
        • Rowbotham MC
        What is a “clinically meaningful" reduction in pain?.
        Pain. 2001; 94: 131-132
      1. Practice guidelines for sedation and analgesia by non-anesthesiologists.
        (Accessed at) ([on June 15, 2015])
      2. Guidelines for the use of sedation and general anesthesia by dentists 2012.
        (Accessed at) ([on June 15, 2015])