Lumbar Puncture in Emergency Under Nitrous OXide (LENOX)

• ClinicalTrials.gov Identifier: NCT03941990
• Recruitment Status: Unknown
• First Posted: May 8, 2019
• Last Update Posted: February 20, 2020
• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Inserm U1107, NeuroDol; Université d'Auvergne
• Information provided by (Responsible Party): University Hospital, Clermont-Ferrand

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pain; Anxiety	Drug: Fixed 50:50 mixture of nitrous oxide and oxygen; Other: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 1:1 randomization to receive experimental treatment (50% N2O - 50% O2) or placebo (Medical Air: 22% O2 - 78% N2).
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Masking Description: double blinding, gas bottles are in undistinguishable boxes, and each gas mask will be filled with odorous ink masking the sweet flavour of N2O. Neither the patient nor the person doing the LP and/or the evaluation of pain and anxiety will know the treatment used
• Primary Purpose: Treatment
• Official Title: Impact of 50% Nitrous Oxide Inhalation on Pain Induced by Lumbar Puncture in Emergency: a Double-blind Randomized Controlled Trial.
• Actual Study Start Date: November 27, 2019
• Estimated Primary Completion Date: April 2020
• Estimated Study Completion Date: September 2020

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Maximal pain perceived during the lumbar puncture evaluated using a simple numeric 0-10 pain scale [ Time Frame: 2-3 minutes after the end of gas inhalation ]
   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?"

Secondary Outcome Measures :

1. Maximal anxiety perceived during lumbar puncture evaluated using a simple numeric 0-10 scale [ Time Frame: 2-3 minutes after the end of gas inhalation ]
   Proportion of patients with significant anxiety
2. Side effects [ Time Frame: From the beginning of gas inhalation to a minimum of 2 hours later ]
   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
3. Spinal puncture duration [ Time Frame: 2-3 minutes after the end of lumbar puncture ]
   Comparison of LP duration between both groups measured in minutes (from the beginning of gas inhalation to needle removal).
4. Number of attempts before successful LP [ Time Frame: 2-3 minutes after the end of lumbar puncture ]
   Comparison of number of attempts needed to get spinal fluid, defined as number of needle removals for a single exam.
5. Patient Satisfaction [ Time Frame: 2-3 minutes after the end of gas inhalation ]
   overall satisfaction based on a 0-10 score and proportion of patients that would accept another lumbar puncture in the same conditions
6. Blinding quality [ Time Frame: 2-3 minutes after the end of gas inhalation ]
   Assessment of blinding in clinical trials (according to Bang et al. 2004)
7. Induced cost [ Time Frame: through study completion, an average 4 months ]
   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)

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Lise LACLAUTRE, Dr; (0)473754963; promo_interne_drci@chu-clermontferrand.fr

Locations

France

CHU de Clermont-Ferrand; Recruiting

Clermont-Ferrand, Auvergne Rhône-Alpes, France, 63000

Contact: Lise LACLAUTRE, MD-PhD promo_interne_drci@chu-clermontferrand.fr

Principal Investigator: Xavier MOISSET, MD-PhD

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

Sponsors and Collaborators

University Hospital, Clermont-Ferrand

Inserm U1107, NeuroDol

Université d'Auvergne

More Information

Publications:

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.

Bang H, Ni L, Davis CE. Assessment of blinding in clinical trials. Control Clin Trials. 2004 Apr;25(2):143-56.

Koscielniak-Nielsen Z, Hesselbjerg L, Brushøj 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.

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. Erratum in: Neurology. 2007 Feb 27;68(9):711. Yernitzky, D [corrected to Yarnitsky, D].

Lukas A, Niederecker T, Günther 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.

• Responsible Party: University Hospital, Clermont-Ferrand
• ClinicalTrials.gov Identifier: NCT03941990
• Other Study ID Numbers: RBHP 2018 MOISSET; 2018-001296-20 ( EudraCT Number )
• First Posted: May 8, 2019
• Last Update Posted: February 20, 2020
• Last Verified: May 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Clermont-Ferrand:

Spinal puncture; Nitrous oxide; Pain; Anxiety; Emergency

Additional relevant MeSH terms:

Emergencies; Disease Attributes; Pathologic Processes; Nitrous Oxide; Anesthetics, Inhalation; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents