Electrical stimulation of the foot can increase blood flow out of the leg. This increased blood flow can prevent blood clots from forming in the leg veins. Blood clots in the leg veins can break off and form life-threatening blood clots in the lungs.

Intermittent external pneumatic (air) compression of the foot is already used to increase blood flow in at risk patients.

Hypothesis: Electrical stimulation of the foot increases blood flow out of the legs to the same degree as intermittent external pneumatic (air) compression of the foot.

BACKGROUND

Venous thrombosis and pulmonary embolism or venous thromboembolism (VTE) are important complications of medical and surgical conditions that are associated with prolonged immobilization [1,2]. Immobilization is also a major contributor to the increased risk of VTE associated with prolonged air travel [3,4,5].

There is widespread under utilization of prophylaxis for VTE following major surgical procedures [6,7] either by anticoagulation or physical methods. This practice continues despite good evidence that the risk of VTE continues for weeks after major orthopedic as well as other types of surgery. In certain specific situations there has been a marked improvement in proper prophylaxis, both directly post-surgical and out of hospital, such as following total hip arthroplasty [8]. Overall, however, under prophylaxis continues to be a problem, particularly after hospital discharge, largely because there is no safe and convenient method for continuing prophylaxis in the convalescing patient. This applies not only to surgical patients, but also to other patients with immobilizing conditions including cerebral vascular accidents, and major head and neck trauma.

Increasing venous blood flow velocity is a well-established method of reducing stasis and thus has the potential to prevent thrombosis. Physical methods that increase blood flow in the leg veins are effective for reducing venous thrombosis in high-risk hospitalized medical and surgical patients. However, physical devices have not been evaluated for out of hospital prevention of VTE, but based on their efficacy in the immobilized patient during the early post-operative period, they should be effective in preventing delayed thrombosis.

A number of devices designed to increase venous blood flow velocity have been shown to reduce the incidence of post-surgical venous thrombosis. These devices include high intensity electrical calf stimulation during surgery, graduated compression stockings and intermittent pneumatic compression.

All methods have limitations for out of hospital use. High intensity electrical calf muscle stimulation causes discomfort in the conscious patient and therefore can only be used during general anesthesia. External pneumatic compression can cause arterial ischemia [9]; it requires alternating current, is cumbersome and can only be used while the patient is fully immobilized. Additionally, external pneumatic compression is ineffective for preventing recurrent VTE in obese patients [15]. Graduated compression stockings do not fit all leg shapes and improper application can cause complications. Thus, alternative convenient methods are needed which can be used both in the immobilized and partly mobile patient, particularly after hospital discharge. An illustrative clinical situation is total hip or knee arthroplasty. Recent studies have shown that the risk period for post-operative thrombosis after elective hip surgery extends for up to three months after the patient is discharged from hospital, and for approximately 30 days after major knee surgery [11,12]. Based on the prolonged duration of risk after hospital discharge, it is recommended that prophylaxis with either low molecular weight heparin (LMWH) or warfarin should be continued for up to 35 days following elective hip replacement. Both of these anticoagulants have limitations for out-of-hospital use. LMWH must be administered by subcutaneous injection and warfarin requires laboratory monitoring. Fondaparinux, a new synthetic factor Xa inhibitor, must also be given subcutaneously. Anticoagulants can also be expensive.

The ideal device for out of hospital use should have the following characteristics: it should be safe, effective, portable, easy to use, inexpensive, and able to be worn while the patient is recumbent, sitting, standing or walking. Such requirements are necessary during convalescence from operation when the patient spends considerable periods of time in and out of bed before becoming fully mobile. They are also important requirements for thromboprophylaxis during prolonged travel.

Of the various physical methods available currently, compression stockings are the only type that can be used during recumbency and walking. Compression stockings, however, cannot be adapted to fit all legs, may be improperly applied and have a tendency to slip down the leg. Additionally compression stockings can cause edema of the legs and superficial thrombophlebitis [13,14].

We have attempted to overcome the limitations of currently available physical devices by mild electrical stimulation of the plantar muscles of the feet. Each electrical discharge elicits a foot twitch that causes the intrinsic foot muscles to contract. This contraction compresses the plantar plexus of veins, and thereby increases venous velocity in the popliteal and femoral veins that is transmitted proximally up the leg veins.

A plantar foot stimulation device can be inserted into a sock and can be battery operated. It has the potential to be worn while immobile, standing or walking with assistance, and would thus be suitable for use throughout convalescence after immobilization. Foot stimulation can be used alone or in conjunction with anticoagulation.

Our initial research has shown that mild electrical stimulation of the plantar foot muscles provides a promising method of preventing VTE [16]. The observed increase in blood flow was comparable to that produced by the more traditional calf stimulation.

The aim of this new study is to determine if, over a 4 hour period, mild electrical stimulation of the plantar foot muscles increases venous blood flow velocity to the same degree as intermittent pneumatic compression of the foot in both obese and non-obese subjects. If this study is successful, electrical foot stimulation should be considered a possible safe and effective method of long term venous thromboembolism prophylaxis lasting several weeks.

SUBJECTS AND METHODS

IRB approval and informed consent will be obtained from all subjects. Forty healthy subjects (N = 40) between the ages of 50 to 80 will participate in the study. Half of the subjects (N = 20) will be non-obese with a Body Mass Index (BMI) < 30. The other half of the subjects (N = 20) will be obese with a BMI > 30. Exclusion criterion will include a prior history of deep vein thrombosis or pulmonary embolism, or any trauma or surgery involving any part of the lower extremities.

All subjects will receive therapy applied to one lower extremity with the other lower extremity serving as a control. Subjects will receive electrical foot stimulation and intermittent pneumatic compression of one foot. Subjects will receive either therapy at one session and the other therapy at a second session at least 48 hours later. The right or left leg of each subject will be randomly assigned as the same control leg for both studies. The type of therapy given at the first session will also be randomly assigned.

The study will otherwise follow the protocol used in our initial study of electrical foot stimulation [16]. Subjects will be seated for 4 hours in chairs placed at a fixed distance apart. Subjects will be constantly monitored throughout the study to ensure that they remained seated. Subjects will be allowed to use a bathroom located several feet away only twice during the 4 hour period. During the 4 hour study period subjects will be offered a maximum of 16 ounces of fluid and a normal lunch.

Electrical foot stimulation will consist of surface electrodes placed on the sole of the foot over the plantar muscle group. Electrical stimulation will be delivered by The Focus™ Neuromuscular Stimulation System, Empi, Inc., St. Paul, MN. The crucial stimulus parameters are: biphasic symmetrical square wave at 50 pulses per second, phase duration of 300 microseconds, a starting ramp up time of 2 seconds and a finishing ramp down time of 2 seconds per stimulation cycle, and a stimulation cycle of 12 seconds “on” and 48 seconds “off” per minute. Stimulation will be increased to an intensity just sufficient to create a slight visible muscle twitch. This level of intensity caused no evident discomfort in any of the subjects in our first study [16]. Subjects will be continually monitored throughout this study for any indication of discomfort.

Intermittent pneumatic compression of the foot will consist of external intermittent pneumatic compression. A Tyco Healthcare Kendall Novamedix A-V impulse system® Model 6060 (Mansfield, MA 02048) will be used. Operating parameters: 130mmHg impulse pressure with a 3 second impulse duration; “Program Preset 1” for deep vein thrombosis prophylaxis. The compression will follow the approved standard patient protocol used at our institution detailed in “Utilization of Intermittent Pneumatic Compression (IPC) Stockings for DVT Prophylaxis [17-19].”

Popliteal and femoral venous blood flow velocities will be measured bilaterally using a doppler ultrasound device at 0, 15, 120, and 240 minutes. The person evaluating the doppler ultrasound will be blinded as to the limb receiving either pneumatic compression or electrical stimulation. Immediately following completion of each 4 hour session of electrical foot stimulation or pneumatic compression, subjects will be asked to complete a brief questionnaire regarding their acceptance and tolerance of electrical stimulation or pneumatic compression.

STATISTICAL ANALYSIS

The study will follow a repeated measures design. A mixed linear model will be fit to blood flow results using the PROC MIXED procedure of SAS version 8.2.10 Factors in the model include therapy received (electrical foot stimulation, pneumatic foot compression, control), time of measurement, and BMI (obese, non-obese). Linear contrasts will be used to test specific hypotheses of interest. Standard diagnostic plots will be used to assess model fit and transformations of the data may be considered to meet statistical requirements. Questionnaire results will be evaluated using Chi-square tests, again using SAS, version 8.2. P-values less than 0.05 will be considered significant.

REFERENCES

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9. Hull RD, Raskob GE, Gent M, et al., Effectiveness of intermittent pneumatic leg compression for preventing deep vein thrombosis after total hip replacement. JAMA, 1990;263:2313-2317.

10. SAS Procedure Guide, Version 6. Cary, NC: SAS Institute Inc., 1990.

11. White RH, Romano PS, Zhou H, Rodrigo J, Bargar W. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med. 1998;158:1525-1531.

12. Eikelboom JW, Quinlan DJ, Doulketis JD. Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomized trials. Lancet. 2001;358:9-15.

13. Amarigiri SV, Lees, TA. Elastic compression stockings for prevention of deep vein thrombosis. Cochrane Database Syst Rev. 2000;3:CD001484.

14. Scurr JH, Machin SJ, Bailey-King S, Mackie IJ, McDonald S, Coleridge Smith, PD. Frequency and prevention of symptomless deep-vein thrombosis in long-haul flights: a randomised trial. Lancet. 2001;357:1485-1489.

15. White RH, Gettner S, Newman JM, Trauner KB, Romano PS. Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty. N Engl J Med 2000;343:1758-64.

16. Kaplan RE, Czyrny JJ, Fung TS, Unsworth JD, Hirsh J. Electrical foot stimulation and implications for the prevention of venous thromboembolic disease. Thromb Haemost.2002;88:200-4.

17. Current Opinion in Pulmonary Medicine. Lippincott. Williams and Wilkins, Inc. 2000, 314-320.

18. Ressel N, Genevieve. ACOG practice bulletin on preventing deep vein thrombosis and pulmonary embolism. American Family Physician 2001.

19. Utilization of Intermittent Pneumatic Compression (IPC) Stockings for DVT Prophylaxis. Erie County Medical Center Healthcare Network Policy and Procedure(s). Effective Date: 3/2003.

Accepts Healthy Volunteers

Inclusion Criteria:

• Healthy volunteers

Exclusion Criteria:

• Venous or arterial disease of the lower limbs
• Cardiac pacemaker
• Known allergy to materials of surface electrodes
• Neurologic disorder
• Lower extremity fracture history
• History of joint replacement surgery
• Anticoagulation therapy other than aspirin