Adrenaline Reduces Ecchymoses and Hematomas and Improves Quality of Life After Classic Saphenous Vein Stripping (ARESQOLSAVES)

The Role of Adrenaline in the Reduction of Subcutaneous Ecchymoses and Hematomas and in the Improvement of the Quality of Life of Patients After Classic Great Saphenous Vein Stripping

Aim of the present study is to investigate the efficiency of adrenaline (epinephrine) used locally in reducing and avoiding post-operative formation of subcutaneous ecchymoses and hematomas, in comparison with traditional practice of hemostasis, and to assess improvement in the quality of life of subjects undergoing classic great saphenous vein stripping, who received or did not receive adrenaline as a local hemostatic.

Study Overview

• Status: Completed
• Conditions: Venous Stasis; Venous Insufficiency of Leg; Venous Reflux; Ecchymosis; Venous Disease; Bruising; Venous Insufficiency (Chronic)(Peripheral); Subcutaneous Haematoma
• Intervention / Treatment: Procedure: Great saphenous vein stripping and varicectomies; Drug: Epinephrine Topical; Drug: normal saline

Detailed Description

Introduction Quality of life of subjects undergoing classic great saphenous vein stripping is analogous of the gravity of subcutaneous ecchymoses and hematomas formation, as a result of surgical interventions during open surgery, when the great saphenous vein is being removed. Adrenaline (epinephrine) is a potent vasoconstrictor, whose local hemostatic ability has already been documented and applied in many medical specialties. Aim of the present study to investigate the efficiency of adrenaline (epinephrine) used locally in reducing and avoiding post-operative formation of subcutaneous ecchymoses and hematomas, in comparison with traditional practice of hemostasis, and to assess improvement in the quality of life of subjects undergoing classic great saphenous vein stripping, who received or did not receive adrenaline as a local hemostatic.

Material-Methods 40 subjects diagnosed with chronic venous insufficiency (CVI) and/or varicose veins of the lower limbs of varied clinical gravity (CEAP classification II & III), admitted in the department of Vascular Surgery for open surgical management, i.e. great saphenous vein stripping +/- removal of varicosities, will be enrolled after signing an informed consent for their participation in the study. They will be then randomized into 3 separate groups: Group A - great saphenous vein stripping with local adrenaline use for hemostasis Group B - great saphenous vein stripping with local normal saline use for hemostasis Group C - great saphenous vein stripping with traditional hemostatic practice Study subjects will be followed-up after surgery, and in each group measurement of ecchymoses (small 2-5mm2 and large >5mm2) and hematomas (medium 0,2-1cm and large >1cm) will be performed by using ImageJ software after digital high-resolution photographing on 1st, 8th and 14th post-operative days. Quality of life of subjects will be assessed pre-operatively and 1 month post-operatively, by using SF-36 and CIVIQ-2 questionnaires for QoL in CVI.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • South Aegean
    • Rhodes, South Aegean, Greece, 85133
      • Department of Vascular Surgery, Andreas Papandreou General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-80 years
• CVI CEAP Class II or III
• Informed consent signed

Exclusion Criteria:

• Age <18 or >80 years
• CVI CEAP Class I or IV (venous ulcers)
• Allergy to adrenaline history
• No informed consent signed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group A; Group A - great saphenous vein stripping with local adrenaline use for hemostasis	Procedure: Great saphenous vein stripping and varicectomies; Removal of the great saphenous vein (partially - from just below the knee up to the saphenofemoral junction) by two 3cm skin and subcutaneous fat incisions and the introduction of a conventional vein stripper device, under general or epidural/regional anesthesia. Removal of varicose veins of the lower limb by 0,5cm skin incisions and the use of a conventional phlebectomy stainless steel hook. Mechanical hemostasis by direct compression of the thigh for 10 minutes.; Other Names: Saphenectomy; Drug: Epinephrine Topical; Use of epinephrine/adrenaline solution 1:1000 topically; Other Names: Adrenaline solution 1:1000 topical/local use
SHAM_COMPARATOR: Group B; Group B - great saphenous vein stripping with local normal saline use for hemostasis	Procedure: Great saphenous vein stripping and varicectomies; Removal of the great saphenous vein (partially - from just below the knee up to the saphenofemoral junction) by two 3cm skin and subcutaneous fat incisions and the introduction of a conventional vein stripper device, under general or epidural/regional anesthesia. Removal of varicose veins of the lower limb by 0,5cm skin incisions and the use of a conventional phlebectomy stainless steel hook. Mechanical hemostasis by direct compression of the thigh for 10 minutes.; Other Names: Saphenectomy; Drug: normal saline; Use of normal saline solution NaCl 0,9% topically; Other Names: NaCl 0,9% topical/local use
SHAM_COMPARATOR: Group C; Group C - great saphenous vein stripping with traditional hemostatic practice	Procedure: Great saphenous vein stripping and varicectomies; Removal of the great saphenous vein (partially - from just below the knee up to the saphenofemoral junction) by two 3cm skin and subcutaneous fat incisions and the introduction of a conventional vein stripper device, under general or epidural/regional anesthesia. Removal of varicose veins of the lower limb by 0,5cm skin incisions and the use of a conventional phlebectomy stainless steel hook. Mechanical hemostasis by direct compression of the thigh for 10 minutes.; Other Names: Saphenectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subcutaneous ecchymoses number 1d-postop	The absolute number of subcutaneous ecchymoses on the operated limb on 1st post-operative day	24 hours post-operatively
Subcutaneous ecchymoses number 8d-post-op	The absolute number of subcutaneous ecchymoses on the operated limb on 8th post-operative day	192 hours post-operatively
Subcutaneous ecchymoses number 14d-post-op	The absolute number of subcutaneous ecchymoses on the operated limb on 14th post-operative day	336 hours post-operatively
Subcutaneous hematomas number 1d-postop	The absolute number of subcutaneous hematomas in the operated limb on 1st post-operative day	24 hours post-operatively
Subcutaneous hematomas number 8d-postop	The absolute number of subcutaneous hematomas in the operated limb on 8th post-operative day	192 hours post-operatively
Subcutaneous hematomas number 14d-postop	The absolute number of subcutaneous hematomas in the operated limb on 14th post-operative day	336 hours post-operatively
Subcutaneous ecchymoses total area 1d-postop	The total area in mm2 of subcutaneous ecchymoses in the operated limb on 1st post-operative day	24 hours post-operatively
Subcutaneous ecchymoses total area 8d-postop	The total area in mm2 of subcutaneous ecchymoses in the operated limb on 8th post-operative day	192 hours post-operatively
Subcutaneous ecchymoses total area 14d-postop	The total area in mm2 of subcutaneous ecchymoses in the operated limb on 14th post-operative day	336 hours post-operatively
Subcutaneous hematomas total area 1d-postop	The total area in mm2 of subcutaneous hematomas in the operated limb on 1st post-operative day	24 hours post-operatively
Subcutaneous hematomas total area 8d-postop	The total area in mm2 of subcutaneous hematomas in the operated limb on 8th post-operative day	192 hours post-operatively
Subcutaneous hematomas total area 14d-postop	The total area in mm2 of subcutaneous hematomas in the operated limb on 14th post-operative day	336 hours post-operatively
QoL-SF36 preop	Quality of life assessment based on the 36-Item Short Form Survey (SF-36) questionnaire preoperatively. It is an often-used, well-researched, self-reported measure of health. It stems from a study called the Medical Outcomes Study. It taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health. The eight scaled scores, which are the weighted sums of the questions in their section are directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.	24 hours pre-operatively
QoL-SF36 1month-postop	Quality of life assessment based on the 36-Item Short Form Survey (SF-36) questionnaire 30 days post-operatively. It is an often-used, well-researched, self-reported measure of health. It stems from a study called the Medical Outcomes Study. It taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health. The eight scaled scores, which are the weighted sums of the questions in their section are directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.	30 days post-operatively
QoL-CIVIQ2 preop	Quality of life assessment based on the ChronIc Venous Insufficiency quality of life Questionnaire version 2 (CIVIQ-2) questionnaire preoperatively. The CIVIQ was developed and validated (relevance, acceptability, reliability, construct validity, and sensitivity) by French researchers in 1996. The CIVIQ is a 20-item self-reported instrument that includes four categories of questions: physical (4 items), psychological (9 items), social (4 items), and pain (3 items). Its score ranges from 0, the worst score, to 100, the best. There are five possible answers (from 1 to 5) to describe each symptom and the sensation of discomfort. The second version, the CIVIQ-2 (where 2 denotes the second draft of the same questionnaire), provides a global score covering all aspects of the questionnaire and weighs the categories equally.	24 hours pre-operatively
QoL-CIVIQ2 1month post-op	Quality of life assessment based on the CIVIQ-2 questionnaire 1 month post-operatively. Quality of life assessment based on the ChronIc Venous Insufficiency quality of life Questionnaire version 2 (CIVIQ-2) questionnaire preoperatively. The CIVIQ was developed and validated (relevance, acceptability, reliability, construct validity, and sensitivity) by French researchers in 1996. The CIVIQ is a 20-item self-reported instrument that includes four categories of questions: physical (4 items), psychological (9 items), social (4 items), and pain (3 items). Its score ranges from 0, the worst score, to 100, the best. There are five possible answers (from 1 to 5) to describe each symptom and the sensation of discomfort. The second version, the CIVIQ-2 (where 2 denotes the second draft of the same questionnaire), provides a global score covering all aspects of the questionnaire and weighs the categories equally.	30 days post-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HCT preop	Hematocrit (HCT) measured pre-operatively, in percentage (%).	24 hours pre-operatively
HCT postop	Hematocrit (HCT) measured post-operatively, in percentage (%).	24 hours post-operatively
Hgb preop	Hemoglobin (Hgb) measured pre-operatively, in mg/dL.	24 hours pre-operatively
Hgb postop	Hemoglobin (Hgb) measured post-operatively, in mg/dL.	24 hours post-operatively
WBC preop	White blood cells (WBC) count measured pre-operatively, in K/mcL.	24 hours pre-operatively
WBC postop	White blood cells (WBC) count measured post-operatively, in K/mcL.	24 hours post-operatively
PLT preop	Platelet count (PLT) measured pre-operatively, in K/mcL.	24 hours pre-operatively
PLT postop	Platelet count (PLT) measured post-operatively, in K/mcL.	24 hours post-operatively
FIB preop	Fibrinogen (FIB) measured pre-operatively, in mg/dL.	24 hours pre-operatively
FIB postop	Fibrinogen (FIB) measured post-operatively, in mg/dL.	24 hours post-operatively
ESR preop	Erythrocyte sedimentation rate on the 1st hour, measured pre-operatively, in millimeters (mm).	24 hours pre-operatively
ESR postop	Erythrocyte sedimentation rate on the 1st hour, measured post-operatively, in millimeters (mm).	24 hours post-operatively
CRP preop	Serum C-reactive protein (CRP) measured pre-operatively, in mg/L.	24 hours pre-operatively
CRP postop	Serum C-reactive protein (CRP) measured post-operatively, in mg/L.	24 hours post-operatively
Experienced pain preop	Pain experienced pre-operatively assessed by a numeric rating pain scale (0-10). Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain. It is for adults and children 10 years old or older. 0 indicates no pain, 5 moderate and 10 worst possible pain.	24 hours pre-operatively
Experienced pain 1d-postop	Pain experienced pre-operatively assessed by a numeric rating pain scale (0-10). Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain. It is for adults and children 10 years old or older. 0 indicates no pain, 5 moderate and 10 worst possible pain.	24 hours post-operatively
Experienced pain 8d-postop	Pain experienced pre-operatively assessed by a numeric rating pain scale (0-10). Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain. It is for adults and children 10 years old or older. 0 indicates no pain, 5 moderate and 10 worst possible pain.	192 hours post-operatively
Experienced pain 14d-postop	Pain experienced pre-operatively assessed by a numeric rating pain scale (0-10). Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain. It is for adults and children 10 years old or older. 0 indicates no pain, 5 moderate and 10 worst possible pain.	336 hours post-operatively

Collaborators and Investigators

• Sponsor: Junior Doctors Network-Hellas
• Collaborators: Andreas Papandreou Rhodes General Hospital; Hellenic Red Cross Hospital
• Investigators: Principal Investigator: Konstantinos Roditis, MD, MSc, JDN-Hellas / Department of Vascular Surgery, Hellenic Red Cross Hospital; Study Chair: Dimitrios Mavros, MD, MSc, PhD, Department of Vascular Surgery, Andreas Papandreou General Hospital

Publications and helpful links

General Publications

• Furuya T, Tada Y, Sato O. A new technique for reducing subcutaneous hemorrhage after stripping of the great saphenous vein. J Vasc Surg. 1992 Sep;16(3):493-4. doi: 10.1016/0741-5214(92)90389-p. No abstract available.
• Nisar A, Shabbir J, Tubassam MA, Shah AR, Khawaja N, Kavanagh EG, Grace PA, Burke PE. Local anaesthetic flush reduces postoperative pain and haematoma formation after great saphenous vein stripping--a randomised controlled trial. Eur J Vasc Endovasc Surg. 2006 Mar;31(3):325-31. doi: 10.1016/j.ejvs.2005.08.006. Epub 2005 Oct 19.
• Pappa E, Kontodimopoulos N, Niakas D. Validating and norming of the Greek SF-36 Health Survey. Qual Life Res. 2005 Jun;14(5):1433-8. doi: 10.1007/s11136-004-6014-y.
• Andreozzi GM, Cordova RM, Scomparin A, Martini R, D'Eri A, Andreozzi F; Quality of Life Working Group on Vascular Medicine of SIAPAV. Quality of life in chronic venous insufficiency. An Italian pilot study of the Triveneto Region. Int Angiol. 2005 Sep;24(3):272-7.
• Kim H, Hwang K, Yun SM, Kim DJ. Usage of Epinephrine Mixed With Lidocaine in Plastic Surgery. J Craniofac Surg. 2020 May/Jun;31(3):791-793. doi: 10.1097/SCS.0000000000006156.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 10, 2015
• Primary Completion (ACTUAL): May 14, 2016
• Study Completion (ACTUAL): June 10, 2016

Study Registration Dates

• First Submitted: February 9, 2021
• First Submitted That Met QC Criteria: February 12, 2021
• First Posted (ACTUAL): February 17, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 18, 2021
• Last Update Submitted That Met QC Criteria: February 17, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: hemostasis; ecchymosis; venous disease; chronic venous insufficiency; venous reflux; adrenaline; haematoma; epinephrin; great saphenous vein; saphenectomy; saphenous vein stripping
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Hematologic Diseases; Leg Ulcer; Skin Ulcer; Hemorrhage; Blood Coagulation Disorders; Skin Manifestations; Varicose Veins; Varicose Ulcer; Venous Insufficiency; Hematoma; Ecchymosis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Epinephrine
• Other Study ID Numbers: ARES-QOL-SAVES

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