Efficacy of 50% Nitrous Oxide/50% Oxygen Gas Premix in Chronic Leg Ulcer Debridement

Study Overview
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Brief Summary
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Adequate analgesia in serial chronic leg ulcer debridement can be difficult to achieve. A common analgesia method is the topical administration of local anesthetics directly onto the wound. However, complete wound debridement is often hampered by insufficient analgesia leading to interruption of the actual debridement and fragmentation of treatment into more frequent serial debridement sessions. Alternatively, the inhalation of an nitrous oxide/oxygen (N2O/O2) gas premix could be used for analgesia. In this study, the investigators have compared the analgesic method of an eutectic mixture of topically administered lidocaine/prilocaine cream (EMLA®) with the inhalation of an equimolar 50% N2O/50% O2 gas premix (Kalinox®) in serial leg ulcer debridement.

Detailed Description
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Study design: Prospective, controlled, single-center, cross-over design study. The study protocol was approved by the local ethical committee. Study setting/participants: The study is performed in a highly specialized secondary care vein center. Patients with chronic foot and leg ulcer disease that are scheduled for repetitive ulcer debridement are eligible for the study and included into the study provided that written informed consent is obtained and no exclusion criteria are present. Debridement procedure: For debridement, disposable sterile scalpel blades, ring curettes, and sterilized reusable scissors and forceps are used. The intended sharp mechanical debridement is proceeded as long as it is tolerated by the patient or terminated as planned. It will immediately be discontinued if the patient asks for it due to intolerable pain or discomfort. Analgesia methods: For analgesia during debridement, either a topically administered eutectic mixture of 5% lidocaine/prilocaine (EMLA®) or an inhaled premix of 50% nitrous oxide/50% oxygen (Kalinox®) are used. The 5% lidocaine/prilocaine cream is administered as a thick layer directly onto the wound with a scoop and the wound is sealed with a polyurethane foil. After 30 minutes of exposure time, the foil is removed and debridement is started immediately. For analgesia with the inhaled 50% nitrous oxide/50% oxygen premix, the patient is asked to hold an inhalation rebreather mask with on-demand-valve tightly placed onto the face after being instructed on how to inhale the gas premix. After 3 minutes of exposure time to the gas premix, debridement is started immediately. Gas inhalation is sustained until final wound dressing is applied. During the entire procedure with each analgesia method, vital signs such as non-invasive blood pressure, heart rate and peripheral oxygen saturation (SpO2) are be recorded. Allocation of the analgesia regimen: After study enrollment, patients are consecutively numbered starting at one. Even numbered patients have the first debridement done with topical administration of lidocaine/prilocaine cream, followed by inhaled nitrous oxide/oxygen premix for the second debridement, and again followed in an alternating way by both tested analgesia methods up to a maximum of 4 interventions. Uneven numbered patients receive inhaled nitrous oxide/oxygen premix first, followed by topical lidocaine/prilocaine cream. After 4 debridement in total with 2 sets of each analgesia method, the study period for each single patient will be secluded. A maximum of 4 data sets per patient will be brought to data analysis. Outcome measures: Primary outcome is the change of pain perception from baseline (1 minute before debridement) to time point of maximum debridement/wound profoundness (up to 10 minutes after start of debridement) as measured by the visual analogue scale (VAS). Secondary outcomes are change of pain perception from time point of maximum debridement/wound profoundness to 5 minutes after debridement as measured by the visual analogue scale (VAS), duration of treatment session, duration of debridement, achievement of treatment goal (completion), subjective general perception of analgesia quality during debridement (patient comfort). Baseline characteristics are gender, age, ulcer etiology, time passed between initial ulcer diagnosis and first debridement, wound emergence in terms of suspected trigger for ulcer development, and wound size.

Official Title
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Efficacy of Inhaled 50% Equimolar Nitrous Oxide/Oxygen Gas Premix (Kalinox®) as Compared to Topically Administered 5% Eutectic Mixture of Lidocaine/Prilocaine (EMLA®) in Chronic Leg Ulcer Debridement

Conditions
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Chronic Leg Ulcer

Intervention / Treatment
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* Procedure: N2O/O2 analgesia
* Procedure: Lidocaine/Prilocaine analgesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of chronic leg ulcer persisting for more than six weeks despite initial conservative treatment; written informed consent Exclusion Criteria: Other chronic wounds than leg ulcers Peripheral polyneuropathy Non-specified peripheral sensibility disorders Allergies or contraindications against the study agents Lack of informed consent Pregnancy or breast feeding Anticipated need for less than two surgical debridement

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: N2O/O2 analgesia<br>Wound debridement under analgesia with N2O/O2 premix. | Procedure: N2O/O2 analgesia<br>* Analgesia for ulcer debridement procedure is provided by the inhalation of N2O/O2 gas premix.<br>* Other names: Kalinox® analgesia;Procedure: Lidocaine/Prilocaine analgesia<br>* Analgesia for ulcer debridement procedure is provided by topically administered lidocaine/prilocaine cream.<br>* Other names: EMLA® analgesia;|
| Active Comparator: Lidocaine/Prilocaine analgesia<br>Wound debridement under analgesia with eutectic mixture of 5% lidocaine/prilocaine. | Procedure: N2O/O2 analgesia<br>* Analgesia for ulcer debridement procedure is provided by the inhalation of N2O/O2 gas premix.<br>* Other names: Kalinox® analgesia;Procedure: Lidocaine/Prilocaine analgesia<br>* Analgesia for ulcer debridement procedure is provided by topically administered lidocaine/prilocaine cream.<br>* Other names: EMLA® analgesia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Pain Level as Measured by Visual Analogue Scale (VAS) | Change of measured VAS between Time Point Baseline, which is 1 Minute Before Start of Surgical Debridement, and Time Point End of Surgical Debridement, which is at Maximum Wound Profoundness and up to 10 Minutes after Start of Surgical Debridement. | Change of VAS from Time Point Baseline 1 Minute before Start of Surgical Debridement at Time Point End of Surgical Debridement up to 10 Minutes after Start of Surgical Debridement | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Pain Level as Measured by Visual Analogue Scale (VAS) | Change of measured VAS between Time Point End of Surgical Debridement, which is at Maximum Wound Profoundness during Debridement, and Time Point 5 Minutes after Surgical Debridement. | Change of VAS from Time Point End of Surgical Debridement at Time Point 5 Minutes After Surgical Debridement | 
| Overall Duration of Treatment Session | Time Patient Spent in Outpatient Clinic for Treatment Session | From Admission to Discharge up to 60 Minutes | 
| Duration of Wound Debridement | Total Procedure Time of Debridement | From Start to End of Debridement up to 10 Minutes | 
| Achievement of Treatment Goal | Surgeon's Judgement whether Debridement was Completed as Planned or Interrupted Prematurely due to Pain and/or Patient Discomfort. | From Start to End of Debridement up to 10 Minutes | 
| Overall Analgesia Quality | Patient's Subjective Perception of Analgesia Quality within the Time Frame of Debridement. | From Start to End of Debridement up to 10 Minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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debridement, analgesia