Rapydan Topical Anaesthesia for Arterial Cannulation

Arterial Catheterization Clinical Trial

Official title:

Lidocaine/Tetracaine Patch (Rapydan) for Topical Anaesthesia Before Arterial Access: A Double-blind, Randomized Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01494311
• Other study ID #: 2010/1046
• Status: Completed
• Phase: Phase 4
• First received: December 15, 2011
• Last updated: March 15, 2013
• Start date: March 2011
• Est. completion date: October 2011

Study information

• Verified date: March 2013
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Ethikkommission
• Study type: Interventional

Clinical Trial Summary

Arterial catheterization is painful and is associated with patient stress and anxiety. Analgesia is usually provided by subcutaneous injection of local anesthetic. An alternative is topical anaesthesia, such as Rapydan which is a novel topical anesthetic patch containing 70 mg each of lidocaine and tetracaine. We therefore tested the hypothesis that Rapydan patch analgesia is non-inferior to subcutaneous local anesthetic.

Description:

Many clinical procedures including arterial and venous punctures, percutaneous venous catheter insertion, lumbar puncture, and dermatological procedures are associated with pain and consequent patient discomfort.1-2 With the exception of venopuncture, arterial puncture is the most common invasive procedure performed on critically ill patients. Also, it is often necessary before induction of anaesthesia for invasive measurements of blood pressure and collection of arterial blood samples in patients undergoing major cardiac surgery. Injection of local anesthetics before insertion causes intra-dermal turgor and can trigger local vasoconstriction, both of which reduce puncture success rate.

An alternative approach is to use topical anesthesia for percutaneous procedures. However, intact skin presents a significant barrier to topical anesthetic preparations. Therefore, topical anesthetic preparations typically must be applied under occlusive dressings for 45-60 minutes before vascular access — which is often longer than is clinically practical.

Rapydan (also known as Synera in the United States) is a novel topical anesthetic patch that contains 70 mg each of lidocaine and tetracaine. The central area of each Rapydan patch consists of a Controlled Heat Assisted Drug Delivery pod which is designed to allow for application just 20 minutes before percutaneous procedures. However, the efficacy of Rapydan topical analgesia has yet to be quantified for the more intense pain resulting from arterial puncture. We thus compared routine analgesia (subcutaneous injection with 0.5 ml of 1% lidocaine) with heated lidocaine/tetracaine patches. Specifically, we tested the hypothesis that lidocaine/tetracaine patch analgesia is non-inferior to that provided by subcutaneous lidocaine injection for insertion of arterial catheters.

Ninty patients undergoing elective major cardiac surgery were included in this prospective, double blind clinical trial. Patients were randomly assigned to receive either a lidocaine/tetracaine patch, followed by subcutaneous injection 0.5 ml of normal saline solution or placebo patch, looking identically to the Rapydan patch and subsequent subcutaneous injection of 0.5 ml of lidocaine 1%. Pain during arterial catheterization using 100-mm-long visual analog scale (VAS) was the primary outcome. Other outcomes were pain during anesthetic/saline injection and plasma tetracaine concentrations.

VAS pain scores during arterial puncture were comparable in both groups and Rapydan was non-inferior to subcutaneous lidocaine. Pain scores at the time of subcutaneous injection were significantly lower (better) in patients assigned to the lidocaine/tetracaine patch than to lidocaine (P = 0.001). Plasma tetracaine concentrations never exceeded the detection limit of 25 ng/ml at any time in any patient.

Both the lidocaine/tetracaine patch and subcutaneous injection of lidocaine provided comparable pain control during arterial catheter insertion. Subcutaneous lidocaine caused discomfort during injection whereas the lidocaine/tetracaine patch required placement 20 minutes before the procedure. Given adequate time, the patch provided better overall analgesia by obviating the need for subcutaneous infiltration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: October 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Patients having elective valve-replacement or coronary artery bypass grafting requiring arterial access before induction of anaesthesia.

Exclusion Criteria:

• analgesic use within 24 hours before surgery

• injury or infection at the planned puncture site

• known allergy to local anesthetics

• drug abuse

• alcoholism or psychiatric disorders

• childbearing potential without adequate birth control

• abnormal Allen's test

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Arterial Catheterization

Intervention

Drug:
• Lidocaine/tetracaine patch
The lidocaine/tetracaine patch topical anesthetic patch contains 70 mg each of lidocaine and tetracaine. The central area of each patch consists of a Controlled Heat Assisted Drug Delivery pod which is designed to warm the skin to 26-34°C, theoretically enhancing drug absorption and allowing application just 20 minutes before percutaneous procedures. A active or placebo patch was placed on each patient's wrist in the region of the maximum radial artery pulsation. After 20 minutes, the patch was removed.
• Placebo Patch
A placebo patch was placed on each patient's wrist in the region of the maximum radial artery pulsation. After 20 minutes, the patch was removed.
• Subcutaneous injection of 0.5 ml Lidocain 1%
After removing the patch, a blinded investigator injected 0.5 ml of 1% lidocaine solution. Three minutes after injection, an attempt was made to cannulate the radial artery with a 20-gauge catheter.
• Subcutaneous injection of saline
After removing the patch, a blinded investigator injected 0.5 ml saline solution. Three minutes after injection, an attempt was made to cannulate the radial artery with a 20-gauge catheter.

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna
Canada	Population Health Research Institute, McMaster University	Hamilton	Ontario
United States	Cleveland Clinic Department of Outcomes Research	Cleveland	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Medical University of Vienna	Population Health Research Institute, The Cleveland Clinic

Countries where clinical trial is conducted

United States,  Austria,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain during arterial catheterization	After finishing the puncture procedure, patients were asked to rate their worst pain during subcutaneous injection, during insertion of arterial cannula, and one minute after catheter insertion using a 100-mm-long visual analog scale (VAS). The use of a VAS to measure pain and discomfort has been validated in the several settings of chronic pain, acute postoperative pain, and acute non-surgical pain.	During and minutes after arterial cannula insertion, day 1.	No
Secondary	Pain during annethetic/saline injection.	After finishing the puncture procedure, patients were asked to rate their worst pain during subcutaneous injection, during insertion of arterial cannula, and one minute after catheter insertion using a 100-mm-long visual analog scale (VAS).	During and minutes after injection, day 1.	No
Secondary	Blood concentration of plasma tetracaine	Blood for measurement of plasma tetracaine concentrations sampled: 1) before patch application; 2) 15 minutes after patch application; 3) immediately after successful arterial puncture; 4) 30 minutes after patch application; and, 5) 60 minutes after patch application. Only blood samples from patients assigned to the tetracaine/lidocaine patch were analyzed.	Minutes before and after patch application, day 1.	Yes
Secondary	Patient Satisfaction	Patients also subjectively rated their procedure-related satisfaction on a four-point scale: 0 = unsatisfied; 1 = moderately satisfied; 2 = satisfied; and, 3 = very satisfied.	At conclusion of procedure, day 1.	No
Secondary	Investigator's evaluatuion of pain during catheter insertion	Investigators who were unaware of the randomization estimated each patient's pain intensity at the time of catheter insertion on a four-point scale with 0 indicating no pain and 3 indicating severe pain.	At conclusion of procedure, day 1.	No
Secondary	Difficulty of puncture	The difficulty of the puncture was assessed using a 5-point scale with 1 being insertion at first attempt through 5 which indicated failure to insert the catheter.	During catheter insertion, day 1.	No
Secondary	Number of punctrue attempts	The number of puncture attempts were documented by the investigator.	During catheter insertion, day 1.	No
Secondary	Incidence of edema and erthema at the patch site	After the patches were removed an investigator, blinded to the study randomization, evaluated the treatment sites for skin reactions including edema and erythema using a 5-point Likert scale (1 = none; 5 = vigorous).	Evaluated immediately after patch removed, day 1.	Yes