Rapydan Topical Anaesthesia for Arterial Cannulation

This study has been completed.
Sponsor:
Collaborators:
The Cleveland Clinic
Population Health Research Institute
Information provided by (Responsible Party):
Kurt Rutzler, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01494311
First received: December 15, 2011
Last updated: March 15, 2013
Last verified: March 2013

December 15, 2011
March 15, 2013
March 2011
June 2011   (final data collection date for primary outcome measure)
Pain during arterial catheterization [ Time Frame: During and minutes after arterial cannula insertion, day 1. ] [ Designated as safety issue: No ]
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.
Pain during arterial catheterization [ Time Frame: During and minutes after arterial cannula insertion. ] [ Designated as safety issue: No ]
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.
Complete list of historical versions of study NCT01494311 on ClinicalTrials.gov Archive Site
  • Pain during annethetic/saline injection. [ Time Frame: During and minutes after injection, day 1. ] [ Designated as safety issue: No ]
    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).
  • Blood concentration of plasma tetracaine [ Time Frame: Minutes before and after patch application, day 1. ] [ Designated as safety issue: Yes ]
    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.
  • Patient Satisfaction [ Time Frame: At conclusion of procedure, day 1. ] [ Designated as safety issue: No ]
    Patients also subjectively rated their procedure-related satisfaction on a four-point scale: 0 = unsatisfied; 1 = moderately satisfied; 2 = satisfied; and, 3 = very satisfied.
  • Investigator's evaluatuion of pain during catheter insertion [ Time Frame: At conclusion of procedure, day 1. ] [ Designated as safety issue: No ]
    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.
  • Difficulty of puncture [ Time Frame: During catheter insertion, day 1. ] [ Designated as safety issue: No ]
    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.
  • Number of punctrue attempts [ Time Frame: During catheter insertion, day 1. ] [ Designated as safety issue: No ]
    The number of puncture attempts were documented by the investigator.
  • Incidence of edema and erthema at the patch site [ Time Frame: Evaluated immediately after patch removed, day 1. ] [ Designated as safety issue: Yes ]
    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).
  • Pain during annethetic/saline injection. [ Time Frame: During and minutes after injection. ] [ Designated as safety issue: No ]
    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).
  • Blood concentration of plasma tetracaine [ Time Frame: Minutes before and after patch application ] [ Designated as safety issue: No ]
    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.
  • Patient Satisfaction [ Time Frame: At conclusion of procedure. ] [ Designated as safety issue: No ]
    Patients also subjectively rated their procedure-related satisfaction on a four-point scale: 0 = unsatisfied; 1 = moderately satisfied; 2 = satisfied; and, 3 = very satisfied.
  • Investigator's evaluatuion of pain during catheter insertion [ Time Frame: At conclusion of procedure. ] [ Designated as safety issue: No ]
    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.
  • Difficulty of puncture [ Time Frame: During catheter insertion ] [ Designated as safety issue: No ]
    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.
  • Number of punctrue attempts [ Time Frame: During catheter insertion. ] [ Designated as safety issue: No ]
    The number of puncture attempts were documented by the investigator.
  • Incidence of edema and erthema at the patch site [ Time Frame: Evaluated immediately after patch removed. ] [ Designated as safety issue: Yes ]
    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).
Not Provided
Not Provided
 
Rapydan Topical Anaesthesia for Arterial Cannulation
Lidocaine/Tetracaine Patch (Rapydan) for Topical Anaesthesia Before Arterial Access: A Double-blind, Randomized Trial

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.

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.

Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Supportive Care
Arterial Catheterization
  • 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.
    Other Names:
    • Rapydan
    • Synera, 76667213
  • Drug: 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.
  • Drug: 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.
  • Drug: 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.
  • Active Comparator: Placebo patch and lidocaine injection
    Fourty-five patients were randomly assigned to receive a placebo patch, looking identically to the Rapydan patch and subsequent subcutaneous injection of 0.5 ml of lidocaine 1%.
    Interventions:
    • Drug: Placebo Patch
    • Drug: Subcutaneous injection of 0.5 ml Lidocain 1%
  • Experimental: Lidocaine/tetracaine patch
    Fourty-five patients were randomly assigned to receive a lidocaine/tetracaine patch, followed by subcutaneous injection 0.5 ml of normal saline solution.
    Interventions:
    • Drug: Lidocaine/tetracaine patch
    • Drug: Subcutaneous injection of saline
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
90
October 2011
June 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 90 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Austria,   Canada
 
NCT01494311
2010/1046
Yes
Kurt Rutzler, Medical University of Vienna
Medical University of Vienna
  • The Cleveland Clinic
  • Population Health Research Institute
Not Provided
Medical University of Vienna
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP