The 50:50 Nitrous Oxide vs 2% Lidocaine Challenge

The 50:50 Nitrous Oxide Challenge: A Prospective Randomised Trial - Needle, Meet Your Match

The main goal of the project is to assess pain levels and patient comfort during the administration of a 50:50 Nitrous Oxide/Oxygen gas mixture, in comparison to the same parameters under the standard method used at our institution, which includes injecting a local anaesthetic at the site of planned puncture for central venous catheterisation.

Study Overview

• Status: Recruiting
• Conditions: Anxiety; Acute Pain; Central Venous Catheter
• Intervention / Treatment: Drug: Nitrous Oxide-Oxygen; Drug: Lidocaine 2% Injectable Solution

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ana Cvetkovic, MD,PhD; Phone Number: +381 11 2067 100; Email: ana.cvetkovic@ncrc.ac.rs

Study Locations

• Serbia
  • Savski Venac
    • Belgrade, Savski Venac, Serbia, 11000
      • Recruiting
      • Institute for Oncology and Radiology of Serbia
      • Contact: Ana Cvetković, MD, PhD; Phone Number: +381 11 2067 100; Email: ana.cvetkovic@ncrc.ac.rs
      • Contact: Andrej Jokić, MD; Phone Number: +381 11 2067 100; Email: anestezija@ncrc.ac.rs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subjects who have not previously received Nitrous Oxide.
• Subjects of both sexes, aged between 18 and 65 inclusive.
• Subjects who have signed informed consent with full disclosure; no study-related procedure may begin until the subject signs the consent form.

Exclusion Criteria:

• Infection at the planned puncture site.
• Pregnancy.
• Intracranial hypertension.
• Vitamin B12 deficiency.
• Hemodynamic instability.
• BMI over 35.
• Glasgow Coma Scale (GCS) score less than 15.
• Presence of chronic pain.
• Neurological disorders.
• Hematologic disorders.
• More than two attempts at venous puncture (Subject Withdrawal Criterion).
• Subject experienced an adverse event requiring early discontinuation (Subject Withdrawal Criterion).
• Withdrawal of consent by the subject (Subject Withdrawal Criterion)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nitrous Oxide Group; This will be the experimental group in which the patients will receive a mixture of gases to assess the efficacy of the treatment compared to the control.	Drug: Nitrous Oxide-Oxygen; After placing the patient in the appropriate supination + Trendelenburg position, the operative field (neck and subclavian region) is prepared using antiseptic measures.Five minutes before needle insertion, a mask connected to a 50:50 Nitrous Oxide/Oxygen cylinder with a flow rate of 6 liters per minute is placed on the patient's face and held by the patient. The mask has a valve that opens only when the patient creates negative pressure during inhalation.The patient is instructed to breathe spontaneously; the mask is removed once the catheter is inserted into the target vein or after cessation of painful stimulation.; Other Names: Experimental Treatment
Active Comparator: Lidocaine 2%; The control group receiving the standard of care for this intervention.	Drug: Lidocaine 2% Injectable Solution; After placing the patient in the appropriate supination + Trendelenburg position, the operative field (neck and subclavian region) is prepared using antiseptic measures. Then, under ultrasound control, the most favorable central vein for puncture is determined (v. jugularis interna or v. subclavia) and a 25-gauge needle is used to infiltrate the skin and subcutaneous tissue above the selected vein with local anesthetic. Five minutes after infiltration, puncture of the selected vein is performed using the Seldinger technique. Continuous communication with the patient is maintained throughout the procedure.; Other Names: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity During Needle Insertion	Assessed using a standard Numeric Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst imaginable pain). Higher scores indicate greater pain intensity.	At the time of needle insertion
Pain Intensity During Catheter Placement	Assessed using a standard Numeric Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst imaginable pain). Higher scores indicate greater pain intensity.	During catheter placement
Pain Intensity Post-Intervention	Assessed using a standard Numeric Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst imaginable pain). Higher scores indicate greater pain intensity.	2 minutes after gas inhalation (Treatment 1) or 2 minutes post-intervention (Treatment 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Anxiety Score	Assessed using a standard Numeric Rating Scale (NRS) ranging from 0 (no anxiety) to 10 (worst imaginable anxiety). Higher scores indicate greater anxiety levels.	Post-intervention (at the conclusion of the central venous catheterization procedure)
Patient Satisfaction Score	Assessed using a Numeric Rating Scale (NRS) where patients rate their overall satisfaction with the anesthetic method. The scale ranges from 0 (completely unsatisfied) to 4 (completely satisfied). Higher scores indicate greater satisfaction.	Post-intervention (at the conclusion of the central venous catheterization procedure)
Incidence of Treatment-Related Adverse Events	Percentage of participants experiencing specific adverse events, including nausea/vomiting, unpleasant dreams, paresthesias, dizziness, and euphoria, as recorded by subjective patient reports.	From the start of the intervention through 30 minutes post-procedure

Collaborators and Investigators

• Sponsor: Institute for Oncology and Radiology of Serbia
• Investigators: Principal Investigator: Ana Cvetković, MD, PhD, Institute for Oncology and Radiology of Serbia

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2025
• Primary Completion (Estimated): June 6, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: May 25, 2026
• First Submitted That Met QC Criteria: May 25, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Mental Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Anxiety Disorders; Acute Pain; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Lidocaine
• Other Study ID Numbers: 01-1/2025/1264

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no current plan to share individual participant data to external registries.

Drug and device information, study documents

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