Xylometazoline and Cocaine for Nasal Vasoconstriction

Comparison of the Effect of Xylometazoline and Cocaine on Epistaxis When Administered as Local Vasoconstrictors Prior to Nasal Intubation

The objective of this study is to compare xylometazoline and cocaine's effect on minimizing epistaxis when administered as a local vasoconstrictor prior to nasal intubation.

The investigators hypothesize that there will be a lower bleeding score in the group receiving xylometazoline as compared with the group receiving cocaine.

Study Overview

• Status: Completed
• Conditions: Epistaxis
• Intervention / Treatment: Drug: Xylometazoline 0,1%; Drug: Cocaine 4%

Detailed Description

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. Upon intubation the nasal mucosa must be sufficiently lubricated and decongested in order to minimize the risk of epistaxis. For this purpose several topical agents are suggested, the most common being adrenaline, cocaine and oxymetazoline/xylometazoline in varying combinations and dosages. As such, no broad consensus or guidelines currently exist on a single recommended drug for the prevention of epistaxis induced by nasal intubation.

In 1990 Katz et. al performed a study comparing three interventions: cocaine, lidocaine with epinephrine and oxymetazoline in regard to the prevention of epistaxis on nasotracheal intubation. This study included 14 patients in each of their three groups and the authors concluded that oxymetazoline and cocaine were equally effective. However, due to their limited sample size that study was clearly inconclusive, and the investigators wish to repeat such a comparison.

The trial drug xylometazoline is commonly used in Danish operating rooms under the registered trademark Zymelin. It is an adrenergic drug typically used for decongestion of the nose and its local vasoconstrictive effect occurs after a few minutes and lasts 10-12 hours. The drug is readily available without prescription and in theory the patient could administer this themselves on their way to surgery. Oxymetazoline used by Katz et. al and xylometazoline used in Danish hospitals have similar decongestive effects as oxymetazoline is a derivative of xylometazoline. The two drugs share pharmacodynamics varying only on receptor subtype affinity in their direct action on alpha-adrenergic receptors in the arterioles of the nasal mucosa. Both drugs result in vasoconstriction that leads to decreased blood flow and thereby decongests the nose.

The second trial drug cocaine is also routinely used. It is a magistral formula used especially due to its unique combination of both vasoconstrictive and analgesic properties. It is a potent vasoconstrictor through its ability to inhibit the reuptake and metabolism of catecholamines, which then in greater concentration produce adrenergic effects. Uniquely cocaine also binds to and blocks axonal membrane sodium channels, thus interfering with the propagation of action potentials and thereby exerting an analgesic effect. When administered in doses thought to avoid systemic effects, cocaine is a safe local anesthetic agent. The recommended dosage varies considerably throughout the literature with safe doses ranging between 1.5-3.0 mg/kg.

The investigators wish to compare the effects of xylometazoline and cocaine regarding their prevention of epistaxis during and immediately after nasal intubation.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet, Copenhagen University Hospital

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:

• Age ≥ 18 years
• Scheduled for nasal intubation
• Proficient in spoken and written Danish

Exclusion Criteria:

• Intubation to be done on awake patient

• Pregnancy

  • Women of childbearing potential must produce a negative hCG urine stix to participate

• Known symptomatic coronary artery disease

  • As declared by patient or noted in the patient's file

• Untreated hypertension

  • As declared by patient or noted in the patient's file
  • Not taking antihypertension drugs

• Hypersensitivity to the active substance or to any of the excipients of Zymelin

  • As declared by patient or noted in the patient's file

• Closed-angle glaucoma

  • As declared by patient or noted in the patient's file

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Xylometazoline; Xylometazoline 0,1% as nasal solution given immediately prior to nasal intubation	Drug: Xylometazoline 0,1%; 1 ml of 0,1% xylometazoline diluted with 1 ml of 0,9% isotonic saline solution given as a nasal spray; Other Names: Zymelin
Active Comparator: Cocaine; Cocaine 4% as nasal solution given immediately prior to nasal intubation	Drug: Cocaine 4%; 2 ml of 4% cocaine given as a nasal spray; Other Names: Cocaine hydrochloride 4%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding score	Evaluation of epistaxis measured on a predefined scale of 0-3: 0. No sign of bleeding; Blood only on the tracheal tube; Pooling of blood in the pharynx; Bleeding to the extent that it complicates intubation	Immediately following nasal intubation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Qualitative measurements of cocaine's main metabolite benzoylecgonine in saliva	For cocaine-group only, saliva samples will be obtained and analyzed on the DrugTest 5000 machine used by the Danish Police Force in order to evaluate pharmacokinetics.	Immediately prior to nasal intubation, 60 minutes after administration of cocaine and 24 hours after administration of cocaine.
Quantitative measurements of cocaine in whole blood.	In the cocaine group only, blood samples will be drawn and analyzed for the presence of cocaine in order to evaluate pharmacokinetics.	Immediately prior to nasal intubation, 60 minutes after administration of cocaine and 24 hours after administration of cocaine.

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2022
• Primary Completion (Actual): March 21, 2023
• Study Completion (Actual): March 22, 2023

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: April 12, 2022
• First Posted (Actual): April 19, 2022

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 24, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: epistaxis; nasal intubation; vasoconstriction
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Hemorrhage; Otorhinolaryngologic Diseases; Signs and Symptoms, Respiratory; Nose Diseases; Epistaxis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Anesthetics, Local; Respiratory System Agents; Dopamine Uptake Inhibitors; Vasoconstrictor Agents; Nasal Decongestants; Cocaine; Xylometazoline
• Other Study ID Numbers: 89303200; 2021-000691-11 (EudraCT Number); H-21028051 (Other Identifier: Regional Committee on Health Research Ethics)

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