Cocaine, Lidocaine/xylometazoline and Saline for Nasal Analgesia

Comparison of Cocaine, Lidocaine/xylometazoline and Saline for Intranasal Analgesia - a Blinded Triple Crossover Study

When performed by trained personnel nasotracheal intubation is a safe and effective technique for attaining a secure airway in preparation for surgery of the head and neck. The procedure can be deemed necessary due to the nature of the surgical procedure or considerations in regard to the patient's comorbidities. For a certain group of patients with expected difficult airways, the procedure is done whilst they are awake and aided by fiberoptics.

For these awake patients, extra precautions must be taken to ensure the procedure is conducted with minimal pain and discomfort. The pain and discomfort arises from the mechanical manipulation of the nasal mucosa and can be alleviated in part by means of topical analgesia as well as through decongestion, providing more space within the nasal cavity. For these purposes, several drugs in varying combinations and dosages are used, but no single drug choice is universally recommended.

Cocaine is one of these appropriate drugs. It is a magistral formula used especially due to its unique combination of both vasoconstrictive and analgesic properties. Concerns have though been raised regarding cocaine's potential toxicity and alternative medications are continuously sought after.

A combination of lidocaine and xylometazoline can also be used for preparation of the nose prior to awake nasal fiberoptic intubation. Lidocaine contributes with its analgesic effect whilst xylometazoline functions as the vasoconstrictor.

The investigators wish to compare the analgesic effects of cocaine and lidocaine/phenylephrine to each other and saline when subjectively scored on a visual analogue scale of 0-100 mm immediately after simulated awake nasal intubation on healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Analgesia
• Intervention / Treatment: Drug: Cociane hydrochloride 4%; Drug: Lidocaine 4%; Drug: Xylometazoline 0.1%; Drug: Saline 0.9%

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years
• Proficient in spoken and written Danish
• Healthy volunteers (no active diagnoses)
• Negative hCG (human chorionic gonadotropin) urine stix for women of childbearing potential

Exclusion Criteria:

• Known nasal malformation
• Known coagulopathy
• Current antithrombotic treatment
• Self-reported epistaxis occurring more than once a month
• Symptoms of a common cold within the past week
• Hypersensitivity to local anaesthetics of amide type or any of the excipients
• Hypertension
• Narrow-angle glaucoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cocaine; 2 mL 4% cocaine hydrochloride	Drug: Cociane hydrochloride 4%; 2 mL of 4% cocaine
Active Comparator: Xylometazoline and lidocaine; 1.5 mL of 4% lidocaine and 0.5 mL 0.1% xylometazoline	Drug: Lidocaine 4%; 1.5 mL of 4% lidocaine; Drug: Xylometazoline 0.1%; 0.5 mL of xylometazoline 0.1%
Placebo Comparator: Saline; 2 ml of 0,9% saline solution	Drug: Saline 0.9%; 2 mL of saline 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain regarding the procedure	Self reported pain on a visual analogue scale of 0-100 mm	Immediately following the procedure of 10 cm insertion of a 6.0 nasal endotracheal tube

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain regarding the procedure	Self reported pain on a visual analogue scale of 0-100 mm	One minute after the procedure of insertion of a 6.0 nasal endotracheal tube
Volume	Volume within both nasal cavities measured with acoustic rhinometry	5 minutes before drug administration and 1, 3, 5, 7 and 9 minutes after drug administration
Fiberoptic endoscopy	Preferred nasal cavity based on a comparison of the degree of vasoconstriction of the nasal mucosa evaluated by fiberoptic endoscopy assessed by ENT-specialist	Fiberoptic endoscopy performed 10 minutes before drug administraion and 10 minutes after drug administration
Drug test detection	Concentraion of cocaine and cocaine's main metabolite benzoylecgonine in blood and saliva samples respectively	15 minutes before drug administration and 1, 2 and 3 hours after drug administration
Heart rate	Measurement of heart rate	5 minutes before drug administration and 1, 2, 3, 4 and 5 minutes after drug administration
Blood pressure	Measurement of mean arterial blood pressure	5 minutes before drug administration and 1, 2, 3, 4 and 5 minutes after drug administration
Patient-centred questions	The degree of discomfort and unpleasentness of taste of the drug administration on a scale of 1-10 and whether they felt exaltation after drug administration.	15 minutes after drug administration

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Mo H Larsen, MD, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Actual): August 27, 2024
• Study Completion (Actual): August 27, 2024

Study Registration Dates

• First Submitted: May 29, 2024
• First Submitted That Met QC Criteria: June 3, 2024
• First Posted (Actual): June 5, 2024

Study Record Updates

• Last Update Posted (Actual): September 27, 2024
• Last Update Submitted That Met QC Criteria: September 26, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Perceptual Disorders; Agnosia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Respiratory System Agents; Vasoconstrictor Agents; Nasal Decongestants; Lidocaine; Xylometazoline
• Other Study ID Numbers: 2023-506644-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No