Onpulse TM technology and the geko TM device: The development of a novel system for the prevention of venous thromboembolism

Transcription

1 Onpulse TM technology and the geko TM device: The development of a novel system for the prevention of venous thromboembolism Tucker AT, Bain DS Jawad H, Bain DS, Dawson H, Adams K, Elnahhas T, Johnston A Centre for Clinical Pharmacology, The William Harvey Research Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London The Ernest Cooke Clinical Microvascular Unit, St Bartholomew s hospital, The Barts Healthcare Trust. a.t.tucker@qmul.ac.uk

2 Current DVT Prophylaxis Pharmacological Mechanical ( IPC / GEC) Disadvantages Active Bleeding Allergic Reactions Risk of VTE persists for weeks or months after hospital discharge Drug interactions with several substances e.g. Antibiotics, foods Clinical supervision Skin Damage / Pain / Ulceration Uncomfortable to wear Size Weight External power source necessity Poor Compliance Expense IPC; Intermittent Pneumatic Compression GEC; Graduated Elastic Compression stockings

3 NMES reduces DVT rates Lindstrom et al, (British Journal of Surgery, 1982) The two prophylactic methods (electrical stimulation, and Dextran 40) have similar effects on the incidence of postoperative thromboembolism. The stimulation method has certain advantages due to its safety and simplicity. Kostin et al, (Khirurgiia, 1993) Electrostimulation of the leg muscles during and after operative intervention is an effective method for the prevention of postoperative thrombosis of the deep veins of the lower limbs. Czyrny et al, (Vascular, 2010) Short-term electrical stimulation is at least as effective as knee-high intermittent pneumatic compression in increasing popliteal and femoral blood flow velocity as the potential to be an effective method of deep venous thrombosis prophylaxis.

4 Aims of Onpulse NMES Prophylaxis To develop a novel technique of transcutaneous electrical nerve stimulation To Enhance acceptability & compliance To Enhance blood flow of the lower limbs To Reduce venous stasis To Provide enhanced DVT prophylaxis Initially to provide options where existing technologies are contraindicated

5 OnPulse TM Mechanisms of Action Electrode pair Gently stimulate the common peroneal nerve located within the popliteal fossa - + Activate the muscle pumps of the lower leg

6 Aims of the Thrive-1 Study Determination of optimal stimulation settings Current Frequency Pain & discomfort assessments To focus further development of the OnPulse TM technology

7 Thrive-1 Experimental design 30 subjects - 2 visits Sitting Position Baseline (respiration) recordings were taken at rest 10 dorsiflexions = Theoretical maximum venous emptying 15 sequential electrical nerve stimulations varying in Amplitude & Frequency were applied for 5 minutes, each followed by 10 minutes rest Low amplitude + low frequency The table shows programmes 1-15 used, with the combination of Amplitude & Frequency at each stimulation programme High amplitude + high frequency

8 % change from baseline % change from baseline THRIVE-1 Results Femoral Vein velocity - Ultrasound Femoral vein volume flow - Ultrasound Hz 3Hz 5Hz Hz 3Hz 5Hz Applied Current (ma) Venous blood velocity increased significantly in the stimulated leg at all stimulations compared to baseline Responses within normal physiological responses of dorsiflexion Correlation to f (R=0.88) and ma (R=0.79) Applied Current (ma) Increase in venous blood volume flow in the stimulated leg at all stimulations compared to baseline No significant change in mean vessel diameter throughout study (p=0.47) Correlation to f (R=0.82) and ma (0.77) Mean ± SEM

9 % change from baseline % of 10 sequential Dorsiflexions THRIVE-1 Results LDF flux ~ microcirculatory velocity PPG ~ venous volume in dorsal foot vein Hz 3Hz 5Hz Hz 3Hz 5Hz Applied Current (ma) Dorsum of foot LDF flux (rbc x velocity) Increased up to ~ 1000% in stimulated leg compared to resting baseline Correlation to frequency R=0.93, p< Mean ± SEM Applied Current (ma) Dorsal foot vein dc-ppg measures venous volume Changes in signal relate to venous emptying Correlation to ma R=0.79, p<0.001

10 Vascular Ultrasound Assessment Visualization of increased blood flow volume, velocity and waveform

11 Vascular Ultrasound Assessment Visualization of increased blood flow volume, velocity and waveform Superficial Femoral Artery: At Rest Superficial Femoral Artery: Device Active Infilling ~50cm/s ~100cm/s Prevention of diastolic flow reversal

12 Visual Analogue Score Verbal Rating Score Comfort & Tolerability of Thrive VAS = Visual Analogue Score VRS = Verbal Rating Score Programme VAS VRS The device was well tolerated with both visual and verbal rating scores at minimal sensation for most settings

13 Summary 4 x Increase in blood flow & velocity in superficial femoral vein Significant increase in frequency of cephalad venous blood flow 2 x Increase in velocity in the femoral artery The reverse flow components of the pulse wave arterial flow waveform are abolished Reverse flow in the superficial femoral artery is due to high resistance of the peripheral vessels Enhanced flow throughout the cardiac cycle suggests a significant reduction in peripheral vascular resistance

14 Aims of the Study II Further evaluate the effectiveness of the device in enhancing lower limb blood flow Investigate the effect on specific blood coagulation markers Further explore subjects acceptability and tolerability Confirm the potential application for prevention of DVT and other vascular disorders

15 Methodology II 10 Subjects Visit 1- Stimulation Study Visit 2- Control Study Unilateral Electrical Stimulation (25 ma, 3Hz, 600 µs) 5 min/15 min Vascular & Micro-vascular Assessments at 0,1,2,3 & 4 Hours No Stimulation Oxygen Levels Skin Blood Flow Blood Pressure Ultrasound Measurements Blood Coagulation Discomfort Questionnaire

16 Results II Control Velocity Device Active Velocity Arterial (ns) Arterial (ns) Venous (ns) Venous (P 0.001)

17 Results II Control Volume Device Active Volume Arterial (p 0.05 ) Arterial (p 0.05 ) Venous (P 0.001) Venous (ns)

18 Results II Control Microcirculation Device Active Microcirculation Stimulated (p ) Left Leg (ns) Right leg (ns) Passive (ns)

19 Results II Control Blood Pressure Device Active Blood Pressure SBP (ns) SBP (p ) DBP (P 0.001) DBP (ns)

20 Control Tissue Plasminogen Activator Antigen Results II Device Active Tissue Plasminogen Activator Antigen Arm (p ) Arm (ns) Right Leg (ns) Left Leg (P 0.001) Passive (ns) Right Leg (p 0.001)

21 Visual Analogue and Verbal Rating Score The device was well tolerated with both visual and verbal rating scores at minimal sensation.

22 Study III geko TM device 10 Subjects Subjects lie supine for 30 min. Devices fitted bilaterally in sequential manner (active 30min / 10 min rest) geko HF geko LF IPC Flowtron IPC Kendall SCD Assessments Performed Microcirculatory Velocity TcPO2 %SPO2 Discomfort Questionnaire US Measurements Blood Pressure

23 Mean Volume Flow, ml/min geko v IPC Venous Volume Mean venous blood volume flow measurement, p Bottom of the box = 25 th percentile, centre of the box = median (50th percentile), top of the box = 75 th percentile, vertical lines = extremes of values within 1.5 times the IQR. Asterisks = outliers. Middle line across = Baseline median Venous Blood Volume Flow GekoHF GekoLF Baseline Device IPCHF IPCKendall

24 Mean Volume Flow, ml/min geko v IPC Arterial Volume Mean Arterial blood volume flow measurement, p Bottom of the box = 25 th percentile, centre of the box = median (50th percentile), top of the box = 75 th percentile, vertical lines = extremes of values within 1.5 times the IQR. Asterisks = outliers. Middle line across = Baseline median 600 Arterial Volume Flow GekoHF GekoLF Baseline Device IPCHF IPCKendall

25 Mean Velocity, cm/sec geko v IPC Venous Velocity Mean Venous Velocity, p Bottom of the box = 25 th percentile, centre of the box = median (50th percentile), top of the box = 75 th percentile, vertical lines = extremes of values within 1.5 times the IQR. Asterisks = outliers. Middle line across = Baseline median. Venous Velocity Baseline GekoHF GekoLF IPCHFDeflate Device IPCHFInflate IPCKDeflate IPCKInflate

26 Mean Velocity, cm/sec geko v IPC Arterial Velocity Mean Arterial Velocity, p Bottom of the box = 25 th percentile, centre of the box = median (50th percentile), top of the box = 75 th percentile, vertical lines = extremes of values within 1.5 times the IQR. Asterisks = outliers. Middle line across = Baseline median Arterial Velocity Baseline GekoHF GekoLF IPCHFDeflate IPCHFInflate IPCKDeflate IPCKInflate Device

27 Mean LDF, Flux Units geko v IPC LDF Laser Doppler Fluxmetry, p Bottom of the box = 25 th percentile, centre of the box = median (50th percentile), top of the box = 75 th percentile, vertical lines = extremes of values within 1.5 times the IQR. Asterisks = outliers. Middle line across = Baseline median. 100 Laser Doppler Flowmetry (LDF) Geko HS Geko LS Baseline IPC HF IPC Kendle Device

28 Study Summary In a direct controlled comparison between the geko TM neuromuscular stimulator and to Intermittent Pneumatic Compression (IPC), the geko TM device elicited: Superior enhancement of venous volume At least equivalent peak venous velocity Superior arterial volume and peak velocity Superior microcirculatory blood flow

29 Conclusions Literature demonstrated NMES is effective in DVT prophylaxis OnPulse technology and the geko device: An effective NMES methodology Very well tolerated Significant enhancement of lower limb blood flow Efficiently reduces stasis Significant opportunity for DVT prophylaxis

30 Overview of Features & Benefits Portable, wearable micro-device, weighs 16g Superior blood velocity & volume equal to 50-70% of walking Silent Operation Easy-to-fit Daily disposable Provides full mobility to recovering patient

31 geko TM Operation Indication (Thrombosis) One button Positioning aid