CTRI Number |
CTRI/2017/08/009548 [Registered on: 30/08/2017] Trial Registered Prospectively |
Last Modified On: |
14/12/2018 |
Post Graduate Thesis |
No |
Type of Trial |
Interventional |
Type of Study
|
Drug |
Study Design |
Randomized, Parallel Group, Active Controlled Trial |
Public Title of Study
|
How does a sleeping medicine influence the blood particles during knee surgery |
Scientific Title of Study
|
To study the effect of dexmedetomidine on Ischemia-reperfusion injury after tourniquet release in patients undergoing total knee arthroplasty |
Trial Acronym |
None |
Secondary IDs if Any
|
Secondary ID |
Identifier |
Nil |
NIL |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
Name |
Vanita Ahuja |
Designation |
Associate Professor |
Affiliation |
Department of Anaesthesia and Intensive care |
Address |
GMCH Sector 32
Chandigarh GMCH Sector 32 Chandigarh CHANDIGARH 160030 India |
Phone |
09646121649 |
Fax |
|
Email |
vanitaanupam@gmail.com |
|
Details of Contact Person Scientific Query
|
Name |
Vanita Ahuja |
Designation |
Associate Professor |
Affiliation |
Department of Anaesthesia and Intensive care |
Address |
GMCH Sector 32
Chandigarh GMCH Sector 32 Chandigarh CHANDIGARH 160030 India |
Phone |
09646121649 |
Fax |
|
Email |
vanitaanupam@gmail.com |
|
Details of Contact Person Public Query
|
Name |
Vanita Ahuja |
Designation |
Associate Professor |
Affiliation |
Department of Anaesthesia and Intensive care |
Address |
GMCH Sector 32
Chandigarh GMCH Sector 32 Chandigarh CHANDIGARH 160030 India |
Phone |
09646121649 |
Fax |
|
Email |
vanitaanupam@gmail.com |
|
Source of Monetary or Material Support
|
Department of Anaesthesia and Intensive care
GMCH Sector 32 Chandigarh |
|
Primary Sponsor
|
Name |
Department of Anaesthesia and Intensive care |
Address |
GMCH Sector 32 Chandigarh |
Type of Sponsor |
Government medical college |
|
Details of Secondary Sponsor
|
|
Countries of Recruitment
|
India |
Sites of Study
|
No of Sites = 1 |
Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
Vanita Ahuja |
Department of Anaesthesia and Intensive Care |
Government Medical College and Hospital Sector 32
Chandigarh Chandigarh CHANDIGARH |
09646121649
vanitaanupam@gmail.com |
|
Details of Ethics Committee
|
No of Ethics Committees= 1 |
Name of Committee |
Approval Status |
Institutional Ethics Committee (GMCH Chandigarh) |
Approved |
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
Modification(s)
|
Health Type |
Condition |
Patients |
(1) ICD-10 Condition: O||Medical and Surgical, Undergoing knee replacement surgery , |
|
Intervention / Comparator Agent
|
Type |
Name |
Details |
Comparator Agent |
GA with propofol |
GA with propofol and saline infusion |
Comparator Agent |
GA with sevoflurane |
GA with sevoflurane and saline infusion |
Intervention |
Intravenous dexmedetomidine bolus and GA with propofol |
GA with propofol and dexmedetomidine infusion |
Comparator Agent |
Intravenous dexmedetomidine bolus and GA with sevoflurane |
GA with sevoflurane and dexmedtomidine infusion |
|
Inclusion Criteria
|
Age From |
18.00 Year(s) |
Age To |
60.00 Year(s) |
Gender |
Both |
Details |
American Society of Anaesthesiologists physical status I and II
|
|
ExclusionCriteria |
Details |
Patients with significant cardiorespiratory, hepatic, renal, haematological and neurological dysfunction
Patients on beta blockers, anticonvulsants, or any other centrally acting medications
Anticipated difficult airway
Pregnancy and lactation
Patient allergic to the study drug
Alcohol or substance abuse
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
Blinding/Masking
|
Participant and Investigator Blinded |
Primary Outcome
|
Outcome |
TimePoints |
malondialdehyde levels |
baseline
1 minute pior to tourniquet deflation
5 minute and 30 minutes after tourniquet deflation |
|
Secondary Outcome
|
Outcome |
TimePoints |
Total anti oxidant status
Arterial blood gas analysis
Total tramadol consumption
Sevoflurane consumption
Haemodynamics |
baseline
1 minute pior to tourniquet deflation
5 minute and 30 minutes after tourniquet deflation |
|
Target Sample Size
|
Total Sample Size="100" Sample Size from India="100"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
Phase of Trial
|
Post Marketing Surveillance |
Date of First Enrollment (India)
|
01/12/2017 |
Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
Date of First Enrollment (Global) |
Date Missing |
Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
Estimated Duration of Trial
|
Years="2" Months="6" Days="15" |
Recruitment Status of Trial (Global)
|
Not Applicable |
Recruitment Status of Trial (India) |
Not Yet Recruiting |
Publication Details
|
Not yet |
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
|
Role of tourniquet
application in lower limb surgery has dual benefits. It not only provides a
bloodless filed to the surgeon but is an essential component of patient blood
management strategies.1 During limb surgery, re-establishment of
blood flow tourniquet deflation causes transient increase in end-tidal carbon
dioxide and decrease in mean arterial blood pressure, temperature, and central
venous oxygen tension. This also induces a paradoxical extension of ischaemic
damages mediated by oxygen free radicals, known as the Ischaemia-reperfusion
injury (IRI).2 IRI causes the release of free oxygen radicals initiate the production
of malondialdehyde (MDA), through the lipid peroxidation of cellular membranes.
Following lipid peroxidation, the antioxidant enzyme system is activated
against reactive oxygen species (ROS) and attempts to protect cells from
oxidative damage. There is a balance between the scavenging capacity of
antioxidant
enzymes and ROS.3 Because of this
balance, the total antioxidant capacity (TAC) measurement is a sensitive indicator
of the overall protective effects of the antioxidants.5-7
Currently, the preventive role of ischaemic
preconditioning (IPC) is being considered in patients scheduled for total knee
arthroplasties (TKA). The authors evaluated twenty patients scheduled for TKA
and randomized them as IPC versus placebo. The muscle biopsies of patients in
IPC group demonstrated a protective genomic response and increased oxidative
stress defense mechanism as compared to placebo.8 However, IPC may
not be possible in all the extremity surgeries.
Literature
describes, effective role of a 2 receptor agonist in
prevention of release of catecholamine but is inconclusive with regard to IRI effects.
In an adult study, brachial plexus anesthesia via axillary approach was performed for
upper-limb surgeries. In the dexmedetomidine group, a continuous infusion of
dexmedetomidine (1 microg/kg for 10 minutes, followed by 0.5 mg kg-1 h-1 was used until the end of surgery, whereas the
control group received an equivalent volume of saline. Venous blood samples
were obtained before brachial plexus anesthesia, at 1 minute before tourniquet
release, and 15 minutes after tourniquet release for biochemical analysis. Dexmedetomidine significantly
attenuated plasma hypoxanthine production in the ischemia and plasma MDA
production in the reperfusion periods. Blood creatine phosphokinase and uric
acid levels were significantly lower in the dexmedetomidine group compared with
those in the control group after reperfusion.14 Recently, Bostankolu
and coworkers reported the effects of dexmedetomidine on tourniquet-induced IRI
in lower extremity surgeries performed under GA with sevoflurane in adult
patients. Dexmedetomidine infusion versus normal saline was infused at a rate
of 0.1μg/kg/minute (-1) for 10 minutes prior to induction and then at
0.7μg/kg/hour(-1) until 10 minutes before the end of the operation. Baseline
blood samples, at 1 minute before tourniquet release and at 5 and 20 minutes
after tourniquet release (ATR) reported decreased MDA levels when compared with
the basal values and returned to baseline values at 20 minutes after tourniquet
release. Dexmedetomidine did not have an additional protective role during
routine general anesthesia.15.
The
present study will be a prospective, randomized, placebo controlled trial.
Sample size calculation: In a previous study investigating the
tourniquet-induced IRI in lower-extremity operations and assuming that the
use of dexmedetomidine would result in 20% reduction in plasma MDA, the
present study will require a sample size of 20 patients per group to
achieve a power of 80% and α error of 0.05.10 To compensate for possible
dropouts, we will enroll 25 patients per group
After
approval of the protocol by Institutional Ethics Committee and written informed
consent, 100 patients of either sex scheduled to undergo elective TKA under
epidural analgesia + GA will be enrolled.
Arterial line insertion and blood samples
Following induction of GA, an anaesthesiologist under
strict asepsis will perform arterial line insertion with 20 G arterial cannula.
A base line arterial sample of 1 ml will be taken for arterial blood gases
(ABG) including lactate and serum sample of 3 ml for MDA. Repeat samples will
be taken at 1 minute before tourniquet deflation, 5 minutes and 30 minutes
following tourniquet deflation.
Group allocation of the
patients
Using computer generated random number table, patients will
then be randomly allocated to one of the following four groups. Allocation
concealment will be done using coded sealed opaque envelopes and decoding will
be done at the end of the study.
Group I: (n = 25) GA
maintenance with propofol 3-5 mg kg-1 hr-1
to maintain an entropy value of 40-60 +
IV dexmedetomidine 0.5 μg kg-1 bolus
in 10 ml normal saline (NS) over 10 minutes, followed by infusion at the rate
0.5μg kg-1 hr-1 ( @10 ml
hr-1 )
.
Group II: (n =25) GA
maintenance with propofol 3-5 mg kg-1 hr-1 to maintain an
entropy value of 40-60 + IV 10 ml NS bolus over 10 minutes, followed by
infusion of NS @10 ml hr-1.
Group III: (n =25) GA
maintenance with sevoflurane 0.4-2% to maintain an entropy value of 40-60 + IV
dexmedetomidine 0.5μg kg-1 bolus in 10 ml NS over 10 minutes,
followed by infusion at the rate 0.5μg kg-1 hr-1 ( @ 10 ml hr-1 ).
Group IV: (n =25) GA
maintenance with sevoflurane 0.4-2% to maintain an entropy value of 40-60 + IV
10 ml NS bolus over 10 minutes, followed by infusion of NS @10 ml hr-1.
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