Title of the proposed research project:

A comparative study investigating the effectiveness of the gekoTM medical

device versus intermittent pneumatic compression in prevention of venous
thromboembolism in postoperative patients with hip fractures

SUMMARY

Background:

Neuromuscular electrostimulation devices prevent venous stasis by stimulation of muscle

contractions in the lower leg hence ES is now considered a valuable method for VTE
prevention.1,2,3,4 The gekoTM device (Firstkind ltd) is a small, disposable, internally powered
NMES device with well tolerated and highly effective parameters (27 mA, 1 Hz, 70-560
microsecond pulse width) which prevents stasis in the deep veins of the calf (Griffin et al,
2016) by activation of foot and calf muscle pumps via stimulation of the peroneal nerve. As
the mechanism is plausible and the device is considered safe, it is approved by the UK
National Institute for Health and Care Excellence (NICE) for VTE prophylaxis. It has been
shown to be more effective than standardly used IPC and may also be a more cost effective
method5. This study aims to quantify the effectiveness of gekoTM as compared to IPC in
improving venous blood flow and velocity which are considered as surrogate methods to
assess prevention of thromboembolism6,7,8.

Novelty:

Traditionally chemical prophylaxis has been used for patients with risk of thrombosis. Hip
fracture surgery patients are considered to be at high risk of thromboembolism. But drug
dependent prophylaxis is expensive and may not be suitable for all patients9,10. Among
mechanical methods Intermittent pneumatic compression has been extensively used for VTE
prophylaxis. IPC Devices have been shown to have poor patient compliance and
ineffectiveness in preventing pelvic thrombi. Furthermore, the size, weight and the need for
and external power source, pump, and attached tubing further limit the application of
IPCs11,12. Recently, the UK National Institute for Health and Care Excellence (NICE) issued a
medical technology guidance (NICE MTG19) permitting the use of the gekoTM device for
DVT prophylaxis. This study aims to add high quality evidence for its use as till now there
have been only limited number of small studies conducted using modern day devices.

Objectives:

To compare the effects of gekoTM and IPC in postoperative hip fracture surgery patients in
terms of

I) Femoral vein Flow volume (ml/min)

II) Femoral vein Peak flow velocity (cm/sec)
III) Cost to patient for 4 days ( 96 hrs)

Methods:

Randomized controlled trial with patients randomized to experimental group1 and

experimental group 2. Experimental group 1 will receive gekoTM stimulation and
experimental group 2 will receive intermittent pneumatic compression for 4 days post
operatively. Comparison of femoral vein venous flow and flow velocity measured by
ultrasound will be done on fifth day.
Average cost of DVT prophylaxis with Geko and IPC will be calculated for each patient.

Expected outcome: Greater increase in blood flow and velocity by gekoTM electrical
stimulation as compared to IPC.
Lower cost to patient for using gekoTM as compared to IPC

Keywords: venous thromboembolism

deep vein thrombosis
electrical stimulation
gekoTM
hip fractures
cost effective technology

Abbreviations: VTE- venous thromboembolism

DVT- deep vein thrombosis
IPC- intermittent pneumatic compression
ES- electrical stimulation
NICE- UK National Institute for Health and Care Excellence

BACKGROUND :

Deep venous thrombosis is a potential and life-threatening risk factor for patients suffering
from hip fracture and surgical fixation. It is estimated that 20 million cases of lower extremity
DVT occur in the USA alone and account for the vast majority of pulmonary embolism each
year 13,14. Major orthopaedic surgeries of the lower limbs are a high risk for the development
of DVT and its incidence has been reported to range from 6 to 75%16,17,18. It has been
reported that venous return may be reduced to half after administration of anaesthesia which
may even reduce to one seventh of its preoperative value15.The risk of developing DVT in
patients with fractures of the proximal femur not receiving thromboprophylaxis is 37% 19 .
Several trials have also shown that risk of DVT was highest in the immediate postoperative
period and diminishes with increasing mobility 20,21,22. The formation of clots within the vein
lumen is the result of interplay of various factors. Virchow described these factors as 1.
Stasis of blood flow 2. Endothelial injury 3. Hypercoagulability.
Neuromuscular electrostimulation devices prevent venous stasis by stimulation of muscle
contractions in the lower leg and might be an alternative method for VTE prevention. The
gekoTM device (Firstkind ltd) is a small, disposable, internally powered NMES device (27
mA, 1 Hz, 70-560 microsecond pulse width) which prevents stasis in the deep veins of the
calf (griffin et al, 2016) by activation of foot and calf muscle pumps via stimulation of the
peroneal nerve. As the mechanism is plausible and the device is considered safe, it is
approved by NICE for VTE prophylaxis. As VTE prophylaxis using IPC is not possible in all
patients with hip fractures gekoTM device can be used as an alternative. It is small( 149mm
x 42mm x 11mm), lightweight (18 g), self adhesive .It does not restrict movement of the
knee. The device is intended to be used for up to 24 hrs before being replaced.
The primary device fitting location positions the head of the device to the side of the knee
over the top of the fibula, with the tail wrapping to the rear of the leg below the crease of the
knee. Alternative fitting locations align the head of the device placed on one leg or on both
legs simultaneously. The device aims to imitate the effect normally achieved by walking by
emitting an electrical impulse which stimulates the common peroneal nerve. This in turn
leads to contraction of the calf muscle, aiding the emptying of veins in the lower limbs and
increasing blood circulation to the heart.
The relative risk pertaining to NMES / MEST devices may not apply to the gekoTM device
since the devices produce vey different types of muscle contractions with earlier devices
causing painful contractions ,requiring use of anaesthesia Reported limitations of current
NMES devices include difficult placement of electrodes23, length of electrode to-lead
connector23skin reactions23, discomfort due to stimulation of sensory nerves25 and multiple
wire connections increasing the risk of errors24.

Literature review :

Several studies have demonstrated that ES is able to increase venous velocity and flow in
healthy participants. Moreover , the technique increases arterial and microcirculatory blood
flow, together with a significant decrease in tissue plasminogen activator antigen indicating
increased fibrinolytic activity. Two recent systemic reviews demonstrated that there is
moderate quality evidence to support ES over no prophylaxis in a clinical setting for
preventing VTE28,29,30,31. The gekoTM device significantly increases superficial femoral vein
blood flow and velocity. It is compact, lightweight, and portable because it requires no
external power source or cords. When compared to IPC, in two studies, the gekotm device
was superior in increasing both venous and arterial femoral blood volume in healthy
volunteers by 101% and 75%, respectively26 and microcirculatory flux by 400%27.
Intermittent contraction of the muscles that dorsiflex the foot through ES of the common
peroneal nerve is thought to compress the leg veins and improve venous return in a similar
way to the skeletal muscle pump action whilst walking. .In healthy volunteers, it increases
femoral vessel peak velocity (cm/second) to 216%, ejected volume per
stimulus(ml)to113%and volume flow during muscle contraction to 36% 31,32. In patients with
claudication, the geko™ device has been shown to be statistically significant in increasing
venous and arterial volume and microcirculatory flow after just 60 minutes of stimulation 33.
Venous volume flow increased by 0⋅034 l/minute (mean) in the active limb compared to
0⋅002 l/minute (mean) in the passive limb [P <0⋅001]; arterial volume flow increased by 0⋅68
l/minute (mean) compared to the passive limb, 0⋅004l/minute (mean) [P <0⋅001], and
microcirculatory flow increased by 22⋅25 flux units (mean) [P <0⋅001] 33.For patients with
CVI, the geko™device was used for4–6 hours per day for 6 weeks, compared to baseline,
increased the mean femoral vein peak velocity by 60% (P=0⋅05), the time averaged peak
velocity (TAMV) by 27% (P=0⋅07), volume flowby51%(P=0⋅15)and reduced oedema by16%
(P <0⋅05)34,35, with incremental improvements linked to the length of time (6 weeks) that the
device was used. The gekoTM device was well tolerated, with most participants reporting only
‘mild discomfort’ while using the device6. The device presents a number of advantages over
previous ES devices. Indirect muscle stimulation via the nerve allows muscle contraction to
be effected using a much lower level of stimulus than direct muscle stimulation. This means
that a given level of contraction is considerably more tolerable to the patient. The branching
of the common peroneal nerve distal to the knee results in contraction of a whole complex of
lower leg muscles, including those muscles responsible for foot dorsiflexion, and stabilisers6.
Dorsiflexion has been shown to provide more effective blood pumping than plantar flexion8.
This gives a more effective evacuation (by distension) of the valved vessels of the calf than
by contraction of the gastrocnemius muscle. Previous ES devices delivered a train of
multiple electrical pulses to the muscle, to give a tetanic contraction over a period of
approximately 0.5 to 1 second. This was then relaxed and repeated at regular intervals. A
dose-ranging study have found that prolonged tetanic contraction produced no further
venous flow after the initial momentary contraction, as the vein was already empty36. This led
to the adoption of a charge-balanced stimulus comprising a single pulse with duration < 1ms
delivered every second. As well as providing optimal blood pumping, this proved much more
tolerable to the user, and consumed substantially less power. The short duration of muscle
contractions places very little metabolic demand on the musculature, and so prolonged use
does not lead to muscle fatigue. The reductions in power consumption enable the device to
be powered from a single button-cell battery; this allows the design of a miniature, integral
device comprising battery, control circuit, and adhesive electrodes which can be directly
applied to the patient with no wires or separate box . This has obvious advantages in terms
of convenience, electrical safety and patient ambulation. Furthermore, the application of the
device to the common peroneal nerve, remote from the muscle pumps, permits its use in a
cast.

Intermittent pneumatic compression caused 51% (p = 0.002), 5% (ns) and 3% (ns) median
increases in venous peak velocity, time-averaged maximum velocity and volume flow,
respectively; neuromuscular electrical stimulator stimulation caused a 103%, 101% and
101% median increases in the same parameters (all p = 0.002). The benefit was lost upon
deactivation. Intermittent pneumatic compression did not improve arterial haemodynamics.
Neuromuscular electrical stimulator caused 11%, 84% and 75% increase in arterial
parameters (p < 0.01). Laser Doppler readings taken from the leg were increased by
neuromuscular electrical stimulator (p < 0.001), dropping after deactivation. For intermittent
pneumatic compression, the readings decreased during use but increased after cessation.
Hand flux signal dropped during activation of both devices, rising after cessation11.
On basis of all this it is time to have a study with sufficient number of subjects to quantify the
better performance of geko over IPC in post operative Hip fracture surgery patients .

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Novelty/Innovation:

Use of mechanical agents like elastic stockings and IPC in VTE prophylaxis has been the
norm. Limitations of IPC include improper fitting, inappropriate use of device, peroneal nerve
injury, discomfort and excessive heating under inflatable cuffs. Elastic stockings are
associated with poor compliance and complications such as skin ulcers and blisters. The
role of NMES in venous thromboprophylaxis has been investigated since the 1960s but did
not gain popularity due to antiquated technology which only permitted its use in
anaesthetized patients. In addition the widespread use of LMWH , GCS and IPC led to a
loss of interest in this technology. Transcutaneous electrical muscular stimulation targets the
musculatureof the lower extremities directly with the goal of promoting venous blood flow to
treat leg edema and prevent venous thrombosis .Direct muscular electrical stimulation
increases venous blood flow but requires higher voltage stimuli and is difficiult for patients to
tolerate. Moreover direct muscle stimulation is less effective at evoking a response because
only one muscle group is targerted. Conversly recruiting multiple muscle groups in the lower
extremity by targeting motor nerves is more beneficial and tolerable The recent medical
technology guidance (NICE MTG19) issued by UK NICE for use of the gekoTM device for
thromboprophylaxis has brought the focus to this technique and more evidence based
research is needed to validate the results and bring about a revolutionary change in
standard VTE and hip fracture care.

Study Objectives:

To compare the effects of IPC and GEKOTM es device in post operative hip fracture
surgery patients on

1. Lower limb Venous flow (superficial femoral vein)

i)volume flow(ml/min)

ii)peak velocity(cm/sec)

2. cost to patient for 4days (96 hrs)

Methodology :
I)Study Design : experimental

Randomized controlled trial

ii) inclusion criteria

post operative adult patient with hip fracture

age greater than 18 years
both genders

iii) exclusion criteria

patients with cardiac pacemaker

epilepsy
Open wound on site of device application

iv) intervention

gekoTM is a small disposable self adhesive band containing two electrodes and a stimulator
with an integral battery which provides approximately 48 hrs of operation. It is applied to the
lower leg on the skin overlying the common peroneal nerve. It produces a current of 27 ma
at a frequency of 1 hz which results in a single ankle dorsiflexor muscle twitch every second.
An isometric muscle contraction of the tibialis anterior and peroneus longus, peroneus
brevis, extensor hallucis longus ,extensor hallucis brevis , extensor digitorum longus,
peroneus tertius,extensor digitorum brevis and the medial gastrocnemius occurs .The
extensor muscles are then activated with an additional stretch of the antagonistic flexor
muscles , which pull in a distal direction dorsiflexion , compressing the flexor muscles by the
facial envelopes. Pulse width can be varied between 7 settings (70, 100, 140, 200, 280, 400
and 560 microseconds) and is adjusted to produce a slight visible movement of the foot. The
passive motion of the flexor muscle acts as a calf muscle pump, which may enhance venous
stasis and oedema and influencing muscle oxygenation. This will be applied to post
operative patients on day one in experimental group 1. Machine will be replaced after 48 hrs
when battery dies down. Next machine will be applied for the next 48 hrs.

In Experimental group 2 IPC will be applied on first postoperative day and continued for 4
days.

On Day 5 ultrasound will be done by radiologist who will be blinded to which group the
patient is coming from.
Femoral vein Flow and peak velocity will be checked

The study shall be carried out in the Division of Trauma Surgery and Critical Care, Jai
Prakash Naryan Apex Trauma Center , AIIMS , New Delhi . The study shall be initiated only
after due ethical clearance has been attained. Informed consent shall be taken from all the
recruiting patients.

ii. Sample Size:

50 patients in each group .Significant number to show effects

iii Project Implementation Plan

Enrollment : patients meeting inclusion criteria will be enrolled into experimental group and
control group on an alternate basis in order of their admission. Allocator will be blinded to
intervention being done in each group. Informed consent will be taken.

Intervention :post operatively patient in experimental group will be put on gekoTM stimulation
for 4 days
Patients in control group will be put on IPC for 4 days

Data collection
Ultrasound will be done on day 5 at superficial femoral vein by radiologist. Radiologist will be
blinded to group allocation. Effort will be made to ensure this by asking patient not to reveal
in which study arm he or she was. Assessor will be guided not to ask for it and a
supervisor will ensure the same to happen.

Iv Ethics Review:

Ethical clearance applied for

v. Data collection & statistical analysis plan:

Intervention and data collection done for 18 months and analysis for 6 months.
Stastical analysis at AIIMS Biostastics department.

10.Expected Outcomes:

Greater increase in venous flow and peak velocity as compared to IPC at lower
cost

11.Limitations of this study

12.Future plans based on expected outcomes if any

Introduction of ES based thromboprophylaxis as part of standard care of patients

with hip fractures postoperatively

13.Timelines:

Patient Recruitment, Intervention and data collection done for 18 months and
analysis for 6 months

14.Institutional Support:

IPC and ultrasound provided by institute

All permanent staff from institute.

15.Budget:

5 lakhs which include

Cost of gekoTM device

Stationary items