Lumbar Puncture in Emergency Under Nitrous OXide (LENOX)

Impact of 50% Nitrous Oxide Inhalation on Pain Induced by Lumbar Puncture in Emergency: a Double-blind Randomized Controlled Trial.

Lumbar puncture (LP) is a frequent exam that can cause pain and anxiety. In a scheduled setting, it has been shown that nitrous oxide use during the procedure was able to reduce both pain and anxiety. The goal of this trial is to confirm these results in a more heterogeneous group of patients having a LP, in an emergency setting.

Study Overview

• Status: Unknown
• Conditions: Pain; Anxiety
• Intervention / Treatment: Drug: Fixed 50:50 mixture of nitrous oxide and oxygen; Other: Placebo

Detailed Description

Nitrous oxide (N2O) has analgesic and anxiolytic properties that are known for more than a century. Nonetheless, it's use during lumbar puncture in adults has only been investigated in a scheduled setting.Thus, this study is designed to evaluate the analgesic effect of N2O on the pain induced during lumbar puncture.

Patients with urgent lumbar puncture realized for diagnosis purposes will be randomized in 2 groups. One group will inhale N2O for the 5 minutes before the puncture and during the rest of the procedure. The second group will inhale compressed air during the same period. Neither the investigator realizing the lumbar puncture, nor the patient will know which type of gaz they are inhaling (double-blinding).

The maximal pain level that occurred during the procedure will be evaluated on a Numerical Rating Scale (NRS). NRS will also be used to evaluate the maximal anxiety induced by the procedure.

• Study Type: Interventional
• Enrollment (Anticipated): 88
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Auvergne Rhône-Alpes
    • Clermont-Ferrand, Auvergne Rhône-Alpes, France, 63000
      • Recruiting
      • CHU de Clermont-Ferrand
      • Contact: Lise LACLAUTRE, MD-PhD; Email: promo_interne_drci@chu-clermontferrand.fr
      • Sub-Investigator: Ludovic MIRAILLET, MD-PhD
      • Sub-Investigator: Jeannot SCHMIDT, MD-PhD
      • Sub-Investigator: Julien RACONNAT, MD-PhD
      • Sub-Investigator: Farés MOUSTAFA, MD-PhD
      • Sub-Investigator: Christine CARRIAS, MD-PhD
      • Sub-Investigator: Nicolas DUBLANCHET, MD-PhD
      • Sub-Investigator: Sandra TAZE, MD-PhD
      • Sub-Investigator: Sonia AJIMI, MD-PhD
      • Sub-Investigator: Marjolaine BOREL, MD-PhD
      • Sub-Investigator: Marine MONDET, MD-PhD
      • Sub-Investigator: Mathilde QUINTY, MD-PhD
      • Sub-Investigator: Marie VALETTE, MD-PhD
      • Sub-Investigator: Thomas FLEUCHOT, MD-PhD
      • Sub-Investigator: Mélissa FLEURY, MD-PhD
      • Sub-Investigator: Virginie GOULVIN, MD-PhD
      • Sub-Investigator: Bastien MALOSSANE, MD-PhD
      • Sub-Investigator: Vincent MARQUET, MD-PhD
      • Sub-Investigator: Rémi MARTEL, MD-PhD
      • Sub-Investigator: Marion PONCET, MD-PhD
      • Sub-Investigator: Marie THOMAS, MD-PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult patients coming in emergency service who need a lumbar puncture in emergency for a diagnostic purpose
• at least 18
• affiliated to the French state healthcare insurance system
• able to give consent to participation

Exclusion Criteria:

• Previous use of nitrous oxide (medical or recreational)
• Contra-indication to nitrous oxide use
• Face mask phobia
• Stage II obesity (BMI > 35)
• Hemodynamic instability and/or any case when coagulation results cannot be waited
• Cognitive condition defined by a previous Mini Mental State Examination < 24/30
• Confusion or any consciousness disorder that might interfere with judgment or consent
• Patient unable to communicate verbally
• Patient placed under a legal protection measure (tutorship, curatorship or a mandate)
• Any medical condition that might contra-indicate medical research, in physician's opinion

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nitrous oxyde; will inhale experimental treatment throughout the entire procedure (50% N2O - 50% 02)	Drug: Fixed 50:50 mixture of nitrous oxide and oxygen; Gaz inhalation will start 5 minutes before the puncture and will be continued until the end of the procedure.
Placebo Comparator: Placebo; will inhale medical air throughout the entire procedure (22% O2 + N2 Q.S.)	Other: Placebo; inhale medical air (22% O2 - 78% N2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal pain perceived during the lumbar puncture evaluated using a simple numeric 0-10 pain scale	Maximal level of pain during lumbar puncture. The patient will be asked to circle the digit that best describes the maximal level of pain felt during the procedure. If the patient is too painful and/or is incapacitated, the collection notebook will be fulfilled by the care provider after asking the following question: "On a scale of 0 to 10, 0 being the absence of pain and 10 the maximal pain you can imagine, what is the digit best describing the maximal pain you felt during the procedure?"	2-3 minutes after the end of gas inhalation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal anxiety perceived during lumbar puncture evaluated using a simple numeric 0-10 scale	Proportion of patients with significant anxiety	2-3 minutes after the end of gas inhalation
Side effects	Every side effect reported by the patients attributable to gas inhalation during the procedure up to emergency service discharge. Presence, intensity and reversibility will be recorded	From the beginning of gas inhalation to a minimum of 2 hours later
Spinal puncture duration	Comparison of LP duration between both groups measured in minutes (from the beginning of gas inhalation to needle removal).	2-3 minutes after the end of lumbar puncture
Number of attempts before successful LP	Comparison of number of attempts needed to get spinal fluid, defined as number of needle removals for a single exam.	2-3 minutes after the end of lumbar puncture
Patient Satisfaction	overall satisfaction based on a 0-10 score and proportion of patients that would accept another lumbar puncture in the same conditions	2-3 minutes after the end of gas inhalation
Blinding quality	Assessment of blinding in clinical trials (according to Bang et al. 2004)	2-3 minutes after the end of gas inhalation
Induced cost	supplementary cost induced by the use of nitrous oxide inhalation for a total of 88 patients throughout the study (gas and consumables such as masks and pipes)	through study completion, an average 4 months

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Université d'Auvergne; Inserm U1107, NeuroDol

Publications and helpful links

General Publications

• Bang H, Ni L, Davis CE. Assessment of blinding in clinical trials. Control Clin Trials. 2004 Apr;25(2):143-56. doi: 10.1016/j.cct.2003.10.016.
• Koscielniak-Nielsen Z, Hesselbjerg L, Brushoj J, Jensen MB, Pedersen HS. EMLA patch for spinal puncture. A comparison of EMLA patch with lignocaine infiltration and placebo patch. Anaesthesia. 1998 Dec;53(12):1218-22. doi: 10.1046/j.1365-2044.1998.00608.x.
• Herres J, Chudnofsky CR, Manur R, Damiron K, Deitch K. The use of inhaled nitrous oxide for analgesia in adult ED patients: a pilot study. Am J Emerg Med. 2016 Feb;34(2):269-73. doi: 10.1016/j.ajem.2015.10.038. Epub 2015 Oct 24.
• Lavi R, Yarnitsky D, Rowe JM, Weissman A, Segal D, Avivi I. Standard vs atraumatic Whitacre needle for diagnostic lumbar puncture: a randomized trial. Neurology. 2006 Oct 24;67(8):1492-4. doi: 10.1212/01.wnl.0000240054.40274.8a. Erratum In: Neurology. 2007 Feb 27;68(9):711. Yernitzky, D [corrected to Yarnitsky, D].
• Lukas A, Niederecker T, Gunther I, Mayer B, Nikolaus T. Self- and proxy report for the assessment of pain in patients with and without cognitive impairment: experiences gained in a geriatric hospital. Z Gerontol Geriatr. 2013 Apr;46(3):214-21. doi: 10.1007/s00391-013-0475-y.
• Moisset X, Ruet A, Brochet B, Planche V, Jaffeux P, Gilleron V, Ong N, Clavelou P. Who Performs Lumbar Puncture, How Many Do They Perform, How and Why? A Retrospective Study of 6,594 Cases. Eur Neurol. 2016;76(1-2):8-11. doi: 10.1159/000447452. Epub 2016 Jun 24.
• Moisset X, Sia MA, Pereira B, Taithe F, Dumont E, Bernard L, Clavelou P. Fixed 50:50 mixture of nitrous oxide and oxygen to reduce lumbar-puncture-induced pain: a randomized controlled trial. Eur J Neurol. 2017 Jan;24(1):46-52. doi: 10.1111/ene.13127. Epub 2016 Sep 25.

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2019
• Primary Completion (Anticipated): April 1, 2020
• Study Completion (Anticipated): September 1, 2020

Study Registration Dates

• First Submitted: May 2, 2019
• First Submitted That Met QC Criteria: May 6, 2019
• First Posted (Actual): May 8, 2019

Study Record Updates

• Last Update Posted (Actual): February 20, 2020
• Last Update Submitted That Met QC Criteria: February 18, 2020
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Pain; Anxiety; Emergency; Nitrous oxide; Spinal puncture
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Emergencies; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Anesthetics, Inhalation; Nitrous Oxide
• Other Study ID Numbers: RBHP 2018 MOISSET; 2018-001296-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No