Intermittent Pneumatic Compression Devices
Number: 0500
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses intermittent pneumatic compression devices.
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Medical Necessity
- Aetna considers full-leg or half-leg pneumatic compression devices for home use medically necessary durable medical equipment (DME) for the treatment of chronic venous insufficiency of the legs of members who have venous stasis ulcers that have failed to heal after a 6-month trial of conservative therapy directed by the treating physician. The trial of conservative therapy must include a compression bandage system or compression garment, appropriate dressings for the wound, exercise, and elevation of the limb.
- When a pneumatic compression device is determined to be medically necessary, a non-segmented device or segmented device without manual control of the pressure in each chamber is generally considered adequate to meet the clinical needs of the member.
- A segmented device with manual control of the pressure in each chamber is considered medically necessary only if there is clear documentation of medical necessity in the individual case.
- A segmented device with manual control of the pressure in each chamber is considered medically necessary only when there is documentation that the individual has unique characteristics that prevent satisfactory pneumatic compression treatment using a non-segmented device with a segmented appliance/sleeve or a segmented device without manual control of the pressure in each chamber.
- Aetna considers intermittent pneumatic compression devices (e.g., the Venowave VW5) of the lower extremities medically necessary DME to stimulate circulation and reduce the chances of deep venous thromboses for members who are bedridden due to trauma, orthopedic surgery, neurosurgery or other circumstances preventing ambulation. Note: the presence of a cast or splint, the use of an assistive device (e.g., walker, crutches), or non-weightbearing status alone due to injury or surgery are not considered "bedridden" for the purpose of this policy.
- Aetna considers a single patient use intermittent pneumatic compression device (e.g., the VenaPro Vascular Therapy System) not medically necessary.
- For persons with a medically necessary inflatable compression garment (e.g., Flowtron Compression Garment, Jobst Pneumatic Compressor), a pump needed to inflate the compression garment is considered medically necessary.
Note: This CPB does not apply to hot and cold therapy; for hot and cold therapy, see CPB 0297 - Cryoanalgesia and Therapeutic Cold.
- Aetna considers full-leg or half-leg pneumatic compression devices for home use medically necessary durable medical equipment (DME) for the treatment of chronic venous insufficiency of the legs of members who have venous stasis ulcers that have failed to heal after a 6-month trial of conservative therapy directed by the treating physician. The trial of conservative therapy must include a compression bandage system or compression garment, appropriate dressings for the wound, exercise, and elevation of the limb.
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Experimental, Investigational, or Unproven
The following procedures are considered experimental, investigational, or unproven because the effectiveness of these approaches has not been established:
- Intermittent pneumatic trunk compression for the prevention of thrombosis following orthopedic surgery
- Intermittent pneumatic compression (IPC) devices for the following (not an all-inclusive list):
- Enhancement of Achilles tendon rupture healing
- Enhancement of fracture and soft-tissue healing
- Management of edema following femoro-popliteal bypass surgery
- Prophylaxis of venous thromboembolism in neurosurgical procedures that do not prevent ambulation
- Rehabilitation for distal radial fractures
- Treatment of critical limb ischemia
- Treatment of end-stage renal disease
- Treatment of intermittent claudication
- Treatment of lower limb lymphedema in persons with type 2 diabetes mellitus
- Treatment of peripheral arterial occlusive disease/arterial insufficiency
- Treatment of post-thrombotic syndrome
- Treatment of restless legs syndrome
- Treatment of sensory impairment in the upper limb following stroke
- Treatment of upper extremity lymphedema following surgery
- Treatment of upper extremity vascular ulcers.
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Related Policies
- CPB 0069 - Lymphedema - for Aetna's policy on pneumatic compression devices for arm lymphedema
- CPB 0297 - Cryoanalgesia and Therapeutic Cold
- CPB 0482 - Compression Garments for the Legs
Background
Gradient elastic stockings, such as those made by Jobst, Sigvaris, Juzzo, or Medi, are generally viewed as the principle means of preventing complications of chronic venous insufficiency. Intermittent pneumatic compression devices compress the leg and/or foot and ankle and act as a pump to improve circulation in the lower extremities. Pneumatic compression devices consist of an inflatable garment for the leg and an electrical pneumatic pump that fills the garment with compressed air. The garment is intermittently inflated and deflated with cycle times and pressures that vary between devices.
Intermittent pneumatic compression (IPC) boots are generally accepted as a method for preventing deep venous thromboses (DVT) and complications of venous stasis in persons after trauma, orthopedic surgery, neurosurgery, or who for other reasons are unable to walk.
Use of the IPC device has expanded to ambulatory persons who suffer from chronic venous insufficiency (CVI) of the legs and consequent edema, stasis dermatitis, ulcerations, and cellulitis. CVI of the legs is caused by abnormalities of the venous wall and valves, leading to obstruction or reflux of blood flow in the veins.
A systemic review of the literature concluded that the effectiveness of the addition of IPC in treatment of venous leg ulcers is unknown. The systemic review identified 3 small, randomized controlled trials (RCTs) of IPC; all of these trials were different in design. Upon pooling of the results, using a random effects model, the reviewers found no difference in healing rates. The review concluded that “[t]hree small [randomized controlled trials] found no evidence of a significant effect on healing with intermittent pneumatic compression in conjunction with compression bandages.”
There is no evidence that IPC devices are superior to gradient compression stockings in preventing complications of chronic venous disease. Compliance with gradient compression stockings has been shown to be essential to their effectiveness; the stockings do not work unless they are worn. There are no studies, however, that have demonstrated that compliance with IPC devices is significantly greater than compliance with gradient compression stockings.
The A-V Impulse System Foot Pump and the KCI Plexipulse are brands of IPC boots on the market; others include those manufactured by Jobst, Chattanooga, Kendal, and Nutech.
The Canadian Coordinating Office of Health Technology Assessment (2004) concluded that “EPC [external pneumatic compression] reduces the risk of DVT for patients who cannot walk due to trauma, joint surgery or neurosurgery. There is still limited evidence, however, supporting the effect of EPC on the healing of venous ulcers and other disorders resulting from chronic VI [venous insufficiency]”.
Current evidence supporting the use of pneumatic compression devices in peripheral arterial disease is limited to small pilot studies with short-term follow up. In a pilot study (n = 30), Ramaswami et al (2005) examined the usefulness of rapid, high-pressure, intermittent pneumatic calf and foot compression (IPCFC) in patients with stable intermittent claudication. These investigators concluded that “IPCFC improves walking distance in patients with stable intermittent claudication. The combination of IPCFC with other treatment such as risk-factor modification and daily exercise may prove useful in patients with peripheral arterial occlusive disease. It may be a useful first line of therapy in patients with disabling claudication who are unfit for major reconstructive surgery. Improved walking on long-term follow-up and experience from different centers may establish a role for this treatment modality in the future”.
Kakkos et al (2005) compared the effect of unsupervised exercise, supervised exercise and IPCFC on the claudication distance, lower limb arterial hemodynamics and quality of life of patients with intermittent claudication (n = 34). These researchers concluded that IPCFC achieved improvement in walking distance comparable with supervised exercise. Long-term results in a larger number of patients will provide valuable information on the optimal treatment modality of intermittent claudication.
Khanna et al (2008) stated that current methods of fracture care use various adjuncts to try and decrease time to fracture union, improve fracture union rates and enhance functional recovery; and one such modality is IPC. These researchers performed a literature review on this approach. A total of 16 studies on the use of IPC in fracture and soft-tissue healing were identified. These studies demonstrated that IPC facilitates both fracture and soft-tissue healing with rapid functional recovery. The authors concluded that IPC appears to be an effective modality to enhance fracture and soft-tissue healing. Moreover, they noted that the number of subjects in human studies is small, and adequately powered RCTs are needed to produce stronger clinically relevant evidence.
In a prospective, randomized, double-blinded, sham-controlled trial, Lettieri and Eliasson (2009) evaluated the effectiveness of pneumatic compression devices (PCDs) as a non-pharmacologic treatment for restless legs syndrome (RLS). Subjects wore a therapeutic or sham device prior to the usual onset of symptoms for a minimum of 1 hour daily. Measures of severity of illness, quality of life, daytime sleepiness, and fatigue were compared at baseline and after 1 month of therapy. A total of 35 subjects were enrolled. Groups were similar at baseline. Therapeutic PCDs significantly improved all measured variables more than shams. Restless legs severity score improved from 14.1 +/- 3.9 to 8.4 +/- 3.4 (p = 0.006) and Johns Hopkins restless legs scale improved from 2.2 +/- 0.5 to 1.2 +/- 0.7 (p = 0.01). All quality of life domains improved more with therapeutic than sham devices (social function 14 % versus 1 %, respectively; p = 0.03; daytime function 21 % versus 6 %, respectively, p = 0.02; sleep quality 16 % versus 8 %, respectively, p = 0.05; emotional well-being 17 % versus 10 %, respectively, p = 0.15). Both Epworth sleepiness scale (6.5 +/- 4.0 versus 11.3 +/- 3.9, respectively, p = 0.04) and fatigue (4.1 +/- 2.1 versus 6.9 +/- 2.0, respectively, p = 0.01) improved more with therapeutic devices than sham devices. Complete relief occurred in 1/3 of subjects using therapeutic and in no subjects using sham devices. The authors concluded that PCDs resulted in clinically significant improvements in symptoms of RLS in comparison to the use of sham devices and may be an effective adjunctive or alternative therapy for RLS. Moreover, the authors stated that before PCD therapy is ready for more wide-spread use, it will be important to see validating studies in various populations of RLS patients.
In a prospective, randomized trial, te Slaa et al (2011) examined the effects of IPC for the treatment and prevention of post-reconstructive edema following femoro-popliteal bypass surgery. Patients were assigned to one of two groups. All patients suffered from peripheral arterial disease, and all were subjected to autologous femoro-popliteal bypass reconstruction. Patients in group 1 used a compression stocking (CS) above the knee exerting 18 mm Hg (class I) on the leg post-operatively for 1 week (day and night). Patients in group 2 used IPC on the foot post-operatively at night for 1 week. The lower leg circumference was measured pre-operatively and at 5 post-operative time points. A multi-variate analysis was done using a mixed model analysis of variance. A total of 57 patients were analyzed (n = 28 for CS; n = 29 for IPC). Indications for operation were severe claudication (CS 13; IPC 13), rest pain (10/5), or tissue loss (7/11). Re-vascularization was performed with either a supra-genicular (CS 13; IPC 10) or an infra-genicular (CS 15; IPC 19) autologous bypass. Leg circumference increased on day 1 (CS/IPC): 0.4 %/2.7 %, day 4 (2.1 %/6.1 %), day 7 (2.5 %/7.9 %), day 14 (4.7 %/7.3 %), and day 90 (1.0 %/3.3 %) from baseline (pre-operative situation). On days 1, 4, and 7 there was a significant difference in leg circumference between the 2 treatment groups. The authors concluded that edema following femoro-popliteal bypass surgery occurs in all patients. For the prevention and treatment of edema following femoro-popliteal bypass surgery, the use of a class I CS proved superior to treatment with IPC. The authors concluded that the use of CS remains the recommended practice following femoro-popliteal bypass surgery.
Pfizenmaier et al (2005) noted that ischemic vascular ulcerations of the upper extremities are an uncommon and frequently painful condition most often associated with scleroderma and small vessel inflammatory diseases. Digital amputation has been advocated as primary therapy because of the poor outcome with medical care. Intermittent pneumatic compression pump therapy can improve ulcer healing in lower extremity ischemic ulcerations; however, the value of this treatment in upper extremity ischemic ulcerations is not known. This observational pilot study consisted of a consecutive series of 26 patients with 27 upper extremity ischemic vascular ulcers seen at the Mayo Gonda Vascular Center from 1996 to 2003. Inclusion criteria were documented index of ulcer size and follow-up ulcer size and use of the IPC pump as adjunctive wound treatment. Twenty-six of 27 ulcers (96 %) healed with the use of the IPC pump. Mean baseline ulcer size was 1.0 cm2 (SD = 0.3 cm2) and scleroderma was the underlying disease in 65 % (17/26) of cases. Laser Doppler blood flow in the affected digit was 7 flux units (normal greater than 100). The mean ulcer duration before IPC treatment was 31 weeks. The average pump use was 5 hours per day. The mean time to wound healing was 25 weeks. Twenty-five of 26 patients reported an improvement in wound pain with pump use. The authors concluded that intensive IPC pump use is feasible and associated with a high rate of healing in upper extremity ischemic ulcers. Furthermore, they stated that prospective, RCTs of IPC is needed to determine whether IPC treatment improves wound healing compared to standard medical care.
Handoll et al (2006) examined the effects of rehabilitation interventions in adults with conservatively or surgically treated distal radial fractures. These investigators searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (December 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2005), MEDLINE, EMBASE, CINAHL, AMED, PEDro, OTseeker and other databases, conference proceedings and reference lists of articles. No language restrictions were applied. Randomized or quasi-RCTs evaluating rehabilitation as part of the management of fractures of the distal radius sustained by adults. Rehabilitation interventions such as active and passive mobilization exercises, and training for activities of daily living, could be used on their own or in combination, and be applied in various ways by various clinicians. The authors independently selected and reviewed trials. Study authors were contacted for additional information. No data pooling was done. A total of 15 trials, involving 746 mainly female and older patients, were included. Initial treatment was conservative, involving plaster cast immobilization, in all but 27 participants whose fractures were fixed surgically. Though some trials were well-conducted, others were methodologically compromised. For interventions started during immobilization, there was weak evidence of improved hand function for hand therapy in the days after plaster cast removal, with some beneficial effects continuing 1 month later (1 trial). There was weak evidence of improved hand function in the short-term, but not in the longer term (3 months), for early occupational therapy (1 trial), and of a lack of differences in outcome between supervised and unsupervised exercises (1 trial). For interventions started post-immobilization, there was weak evidence of a lack of clinically significant differences in outcome in patients receiving formal rehabilitation therapy (4 trials), passive mobilization (2 trials), ice or pulsed electromagnetic field (1 trial), or whirlpool immersion (1 trial) compared with no intervention. There was weak evidence of a short-term benefit of continuous passive motion (post-external fixation) (1 trial), IPC (1 trial) and ultrasound (1 trial). There was weak evidence of better short-term hand function in participants given physiotherapy than in those given instructions for home exercises by a surgeon (1 trial). The authors concluded that the available evidence from RCTs is insufficient to establish the relative effectiveness of the various interventions used in the rehabilitation of adults with fractures of the distal radius.
In a preliminary study, Cambier et al (2003) evaluated the effectiveness of IPC in treating sensory impairments in the hemiplegic upper limb in stroke patients. A total of 23 stroke patients were enrolled in this RCT that compared the application of IPC with a passive treatment strategy. The experimental group (n = 11) received standard physiotherapy combined with IPC treatment (10 cycles of 3 mins with a peak of 40 mmHg) for their hemiplegic upper limb. The control group (n = 12) received supplementary to their conventional physiotherapy a placebo treatment, namely sham short-wave therapy on the hemiplegic shoulder for 30 mins. Sensory impairments were clinically assessed at 3 occasions over a period of 4 weeks using the Nottingham Sensory Assessment scale. Both groups improved in somato-sensation over time, but the experimental group improved more than the control group (p = 0.036) or 81.1% improvement versus 30.9 %. The authors concluded that the use of IPC in the rehabilitation of stroke patients may be of clinical importance for the restoration of sensory function. Drawbacks of this study included small sample size and short follow-up period.
Doyle et al (2010) examined the effects of interventions that target upper limb sensory impairment after stroke. These investigators searched the Cochrane Stroke Group Trials Register (last searched October 8, 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 1), MEDLINE (1966 to January 2009), EMBASE (1980 to January 2009), and 6 further electronic databases to January 2009. They also hand-searched relevant journals, contacted authors in the field, searched doctoral dissertation databases, checked reference lists, and completed citation tracking. Randomized controlled trials and controlled trials comparing interventions for sensory impairment after stroke with no treatment, conventional treatment, attention placebo or with other interventions for sensory impairment were included in this analysis. Two review authors selected studies, assessed quality and extracted data. They analyzed study data using mean differences and odds ratios as appropriate. The primary outcome was sensory function; and secondary outcomes included upper limb function, activities of daily living, impact of stroke and quality of life as well as adverse events. These researchers included 13 studies, with a total 467 participants, testing a range of different interventions. Outcome measures included 36 measures of sensory impairment and 13 measures of upper limb function. All but 2 studies had unclear or high-risk of bias. While there is insufficient evidence to reach conclusions about the effects of interventions included in this review, 3 studies provided preliminary evidence for the effects of some specific interventions, including mirror therapy for improving detection of light touch, pressure and temperature pain; a thermal stimulation intervention for improving rate of recovery of sensation; and IPC intervention for improving tactile and kinesthetic sensation. These researchers could not perform meta-analysis due to a high-degree of clinical heterogeneity in both interventions and outcomes. The authors concluded that there is insufficient evidence to support or refute the effectiveness of the described interventions in improving sensory impairment, upper limb function, or participants' functional status and participation. Moreover, they stated that there is a need for more well-designed, better-reported studies of sensory rehabilitation.
The American College of Chest Physicians’ evidence-based clinical practice guidelines on “Antithrombotic and thrombolytic therapy for ischemic stroke” (Lansberg et al, 2012) provided recommendations on the use of anti-thrombotic therapy in patients with stroke or transient ischemic attack (TIA). These investigators generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence. In patients with acute ischemic stroke, these researchers recommended IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 hrs (Grade 1A) or 4.5 hrs (Grade 2C) of symptom onset; these investigators suggested intra-arterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 hrs (Grade 2C); they suggested against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and they recommended early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, the authors suggested the use of prophylactic-dose heparin or IPC devices (Grade 2B) and suggested against the use of elastic compression stockings (Grade 2B). In patients with a history of non-cardioembolic ischemic stroke or TIA, they recommended long-term treatment with aspirin (75 to 100 mg once-daily), clopidogrel (75 mg once-daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no anti-platelet therapy (Grade 1A), oral anti-coagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended anti-platelet regimens, the authors suggested clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation, they recommended oral anti-coagulation over no anti-thrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B).
Zhao and colleagues (2012) noted that total hip replacement (THR) is an effective treatment for reducing pain and improving function and quality of life in patients with hip disorders. While this operation is very successful, DVT and pulmonary embolism (PE) are significant complications after THR. Different types of IPC devices have been used for thrombosis prophylaxis in patients following THR. Available devices differ in compression garments, location of air bladders, patterns of pump pressure cycles, compression profiles, cycle-length, duration of inflation time and deflation time, or cycling mode such as automatic or constant cycling devices. Despite the widely accepted use of IPC for the treatment of arterial and venous diseases, the relative effectiveness of different types of IPC systems as prophylaxis against thrombosis after THR is still unclear. In a Cochrane review, these investigators evaluated the comparative safety and effectiveness of different IPC devices with respect to the prevention of venous thromboembolism in patients after THR. The Cochrane Peripheral Vascular Diseases Group Trials Search Coordinator searched the Specialized Register (May 2012), CENTRAL (2012, Issue 4), MEDLINE (April Week 3 2012) and EMBASE (Week 17 2012). Clinical trial databases were searched for details of ongoing and unpublished studies. Reference lists of obtained articles were also screened. There were no limits imposed on language or publication status. Randomized and quasi-RCTs were eligible for inclusion. Two review authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreement was resolved by discussion or, if necessary, referred to a third review author. Only 1 quasi-RCT with 121 study participants comparing 2 types of IPC devices met the inclusion criteria. The authors found no cases of symptomatic DVT or PE in either the calf-thigh compression group or the plantar compression group during the first 3 weeks after the THR. The calf-thigh pneumatic compression was more effective than plantar compression for reducing thigh swelling during the early post-operative stage. The strength of the evidence in this review was weak as only 1 trial was included and it was classified as having a high-risk of bias. The authors concluded that there is a lack of evidence from RCTs to make an informed choice of IPC device for preventing venous thromboembolism (VTE) following THR. They stated that more research is needed, ideally a multi-center, properly designed RCT including a sufficient number of participants. Clinically relevant outcomes such as mortality, imaging-diagnosed asymptomatic VTE and major complications must be considered.
Dennis et al (2013) evaluated the effectiveness of IPC to reduce the risk of DVT in patients who have had a stroke. The CLOTS 3 trial is a multi-center parallel group randomized trial assessing IPC in immobile patients (i.e., who cannot walk to the toilet without the help of another person) with acute stroke. These researchers enrolled patients from day 0 to day 3 of admission and allocated them via a central randomization system (ratio 1:1) to receive either IPC or no IPC. A technician who was masked to treatment allocation did a compression duplex ultrasound (CDU) of both legs at 7 to 10 days and, wherever practical, at 25 to 30 days after enrolment. Care-givers and patients were not masked to treatment assignment. Patients were followed up for 6 months to determine survival and later symptomatic VTE. The primary outcome was a DVT in the proximal veins detected on a screening CDU or any symptomatic DVT in the proximal veins, confirmed on imaging, within 30 days of randomization. Patients were analyzed according to their treatment allocation. Between December 8, 2008, and September 6, 2012, a total of 2,876 patients were enrolled in 94 centers in the United Kingdom. The included patients were broadly representative of immobile stroke patients admitted to hospital and had a median age of 76 years (IQR 67 to 84). The primary outcome occurred in 122 (8.5 %) of 1,438 patients allocated IPC and 174 (12.1 %) of 1,438 patients allocated no IPC; an absolute reduction in risk of 3.6 % (95 % confidence interval [CI]: 1.4 to 5.8). Excluding the 323 patients who died before any primary outcome and 41 without any screening CDU, the adjusted odds ratio (OR) for the comparison of 122 of 1,267 patients versus 174 of 1,245 patients was 0.65 (95 % CI: 0.51 to 0.84; p = 0·001). Deaths in the treatment period occurred in 156 (11 %) patients allocated IPC and 189 (13 %) patients allocated no IPC died within the 30 days of treatment period (p = 0.057); skin breaks on the legs were reported in 44 (3 %) patients allocated IPC and in 20 (1 %) patients allocated no IPC (p = 0.002); falls with injury were reported in 33 (2 %) patients in the IPC group and in 24 (2 %) patients in the no-IPC group (p = 0.221). the authors concluded that IPC is an effective method of reducing the risk of DVT and possibly improving survival in a wide variety of patients who are immobile after stroke.
It is interesting to note that an UpToDate review on “Prevention of venous thromboembolic disease in medical patients” (Pai and Douketis, 2014) states that “Data on the efficacy and safety of IPCs are limited. However, one large randomized trial in patients with stroke suggested that IPCs reduce the incidence of VTE [Dennis et al, 2013]. A multicenter, randomized trial of 2,876 immobile patients with acute stroke (CLOTS 3) reported that, compared to no device, IPC use was associated with a lower rate of VTE at 30 days (12 versus 8.5 percent; absolute risk reduction 3.6 percent; 95% CI 1.4 to 5.8) without altering mortality (13 versus 11 percent). While use of low molecular weight heparin was similar in both groups (32 versus 30 percent), more patients in the IPC group wore compression stockings (15 versus 6 percent) which may have biased results in favor of IPC use”.
Ye et al (2018) examined various definitions of immobility used in recent pharmacological thromboprophylaxis clinical trials. PubMed and relevant references from articles/reviews from 2008 to 2016 were searched. RCTs and other clinical studies involving adult hospitalized medical patients in acute care hospital settings that used the term immobility were selected. Two investigators independently abstracted data in duplicate, and accuracy was checked by a third investigator. Twenty-one clinical studies were included. There was heterogeneity among individual VTE risk factors, with respect to the definition of immobility in medical inpatients in these trials. Thirteen studies utilized objective criteria to define ‘‘immobility’’ including duration (12 studies) and distance or time walked (6 studies). In contrast, 7 studies focused principally on subjective definitions (ie, describing the nature of immobility rather than specifying its quantitative measurement). Three RCTs vaguely defined the level of patient’s immobility after hospitalization. The authors concluded that despite the well-known effectiveness of pharmacological thromboprophylaxis for the prevention of VTE in acutely ill medical patients, there is no current consensus on how to define immobility. The heterogeneous nature of definitions of immobility has led to uncertainty about the importance of immobility in VTE risk assessment models. Although clinical studies have incorporated varying definitions of immobility into their inclusion criteria, immobility as a specific VTE risk factor has not been clearly defined.
Kwak et al (2017) conducted a retrospective comparative study to evaluate intermittent pneumatic compression (IPC) for the prevention of VTE after total hip arthroplasty. A total of 379 adult patients were included of which 233 patients were in the intervention group and 146 patients in the control group. All patients took low-dose aspirin for 6 weeks after surgery. IPC was applied to both legs just after surgery and maintained all day until discharge. When a symptom or a sign suspicious of VTE, such as swelling or redness of the foot and ankle, Homans' sign, and dyspnea was detected, computed tomography (CT) angiogram or duplex ultrasonogram was performed. For both groups, patients were excluded if they were younger than 17 years, taking anticoagulant stronger than aspirin for any reason, had history of previous VTE, could not take aspirin for any reason, and were followed up for less than 3 months after surgery. Both calves were compressed all day long except when patients were out of bed. All patients started active leg muscle contraction exercise when recovered from anesthesia and started crutch walking as soon as possible. Patients were discharged when they could walk with a walker or crutches. Until 3 months after surgery, symptomatic VTE occurred in three patients in the IPC group and in 6 patients in the control group. The incidence of VTE was much lower in the IPC group (1.3%) than in the control group (4.1%), but the difference was not statistically significant. Complications associated with the application of IPC were not detected in any patient. Patients affected by VTE were older and hospitalized longer than the unaffected patients. The incidence of VTE in the IPC group was less than 30% of that in the control group. The authors concluded that IPC might be an effective and safe method for the prevention of postoperative VTE. Limitations include retrospective study with a relatively small number of cases and only the patients with suspicious symptoms or signs were examined by CT or US.
Critical Limb Ischemia
In a systematic review, Abu Dabrh and associates (2015) synthesized the existing evidence about various non-revascularization-based therapies used to treat patients with severe or critical limb ischemia (CLI) who are not candidates for surgical revascularization. These investigators searched multiple databases through November 2014 for RCTs and non-randomized studies comparing the effect of medical therapies (prostaglandin E1 and angiogenic growth factors) and devices (pumps and spinal cord stimulators). They reported ORs and 95 % Cis of the outcomes of interest pooling data across studies using the random effects model. These researchers included 19 studies that enrolled 2,779 patients; none of the non-revascularization-based treatments was associated with a significant effect on mortality. Intermittent pneumatic compression (OR, 0.14; 95 % CI: 0.04 to 0.55) and spinal cord stimulators (OR, 0.53; 95 % CI: 0.36 to 0.79) were associated with reduced risk of amputation. A priori established subgroup analyses (combined versus single therapy; randomized versus non-randomized) were not statistically significant. The authors concluded that very low-quality evidence, mainly due to imprecision and increased risk of bias, suggested that IPC and spinal cord stimulators may reduce the risk of amputations; and evidence supporting other medical therapies is insufficient.
Moran and colleagues (2015) stated that IPC is designed to aid wound healing and limb salvage for patients with CLI who are not candidates for revascularisation. These researchers conducted a systematic review of the literature to identify and critically appraise the evidence supporting its use in this population. A search was conducted in Embase, MEDLINE and clinical trial registries up to the end of March 2013. No date or language restrictions were applied. Quality assessment was performed by 2 investigators independently. Quality was assessed using the Cochrane risk of bias tool and the NICE case-series assessment tool. Two controlled before-and-after (CBA) studies and 6 case series were identified. One retrospective CBA study involving compression of the calf reported improved limb salvage and wound healing (OR 7.00, 95 % CI: 1.82 to 26.89, p < 0.01). One prospective CBA study involving sequential compression of the foot and calf reported statistically significant improvements in claudication distances and SF-36 quality of life scores. No difference in all-cause mortality was found. Complications included pain associated with compression, as well as skin abrasion and contact rash as a result of the cuff rubbing against the skin. All studies had a high risk of bias. The authors concluded that the limited available results suggested that IPC may be associated with improved limb salvage, wound healing and pain management. However, they stated that in the absence of additional well-designed analytical studies examining the effect of IPC in CLI, this treatment remains unproven.
Enhancement of Achilles Tendon Rupture Healing
Abdul Alim and colleagues (2018) noted that adjuvant IPC during leg immobilization following Achilles tendon rupture (ATR) has been shown to reduce the risk of DVT. These researchers examined if IPC can also promote tendon healing. A total of 150 patients with surgical repair of acute ATR were post-operatively leg-immobilized and prospectively randomized. Patients were allocated for 2 weeks of either adjuvant IPC treatment (n = 74) or treatment-as-usual (n = 74) in a plaster cast without IPC. The IPC group received 6 hours daily bilateral calf IPC applied under an orthosis on the injured side. At 2 weeks post-operatively, tendon healing was assessed using micro-dialysis followed by enzymatic quantification of tendon callus production, procollagen type I (PINP) and type III (PIIINP) N-terminal propeptide, and total protein content. A total of 14 IPC and 19 cast patients (control group) consented to undergo micro-dialysis. During weeks 3 to 6, all subjects were leg-immobilized in an orthosis without IPC. At 3 and 12 months, patient-reported outcome was assessed using reliable questionnaires (ATRS and EQ-5D). At 12 months, functional outcome was measured using the validated heel-rise test. At 2 weeks post-rupture, the IPC-treated patients exhibited 69 % higher levels of PINP in the ruptured Achilles tendon (AT) compared to the control group (p = 0.001). Interestingly, the IPC-treated contralateral, intact AT also demonstrated 49 % higher concentrations of PINP compared to the non-treated intact AT of the plaster cast group (p = 0.002). There were no adverse events (AEs) observed associated with IPC. At 3 and 12 months, no significant (n.s.) differences between the 2 treatments were observed using patient-reported and functional outcome measures. The authors concluded that patients in post-operative lower limb immobilization after ATR demonstrated a significantly enhanced early healing response when using adjuvant calf IPC for 2 weeks. They noted that that IPC in addition to exert a prophylactic effect against DVT also may be a viable and effective treatment to prevent immobilization-induced impairments on the healing process. Moreover, they stated that further studies should examine if prolonged IPC usage during the whole immobilization time could shorten the time to recovery and optimize final outcome.
The authors stated that a potential drawback of this study was that they could not conclude the exact time length that the enhanced healing response associated with adjuvant IPC therapy will persist. The observations of equal patient-reported and functional outcome measures between the 2 groups at 3 and 12 months post-operatively demonstrated that the 2 weeks IPC intervention did not improve outcome measures from 3 months onwards. However, after the end of the IPC intervention at week 2, both treatment groups received immobilization in an orthosis until 6 weeks post-operatively when immobilization was ended. This suggested that the healing stimulatory effects of the IPC therapy did not persist after cessation of treatment when continued immobilization was applied. This conclusion needs additional studies where the IPC therapy should be applied during the whole time of post-operative lower limb immobilization. By applying IPC treatment during 6 weeks the therapy would impact both the proliferative as well as the regenerative healing phases during immobilization, which could conceivably affect also the patient-reported and functional outcome measures as well as lead to earlier return to activity. These researches stated that whether mechanical compression therapy should be administered as an out-patient treatment for leg-immobilized patients is, with the present and another published study in mind, a matter of both preventing the development of DVT as well as of counteracting the impaired healing associated with immobilization. As for yet, no cost-benefit analysis has been performed, yet the therapy is highly accepted by the patients. They stated that further investigation of the health economics of IPC intervention ought to be conducted to permit an informed decision on implementation at a population level.
Prophylaxis of Venous Thromboembolism in Neurosurgery
Chibbaro et al (2018) noted that the incidence of VT in neurosurgical practice is astonishingly high, representing a major cause of morbidity and mortality. Prophylaxis strategies include elastic stockings, low-molecular-weight heparin (LMWH), and IPC devices. These investigators evaluated the safety and efficacy of 2 different VT prophylaxis protocols implemented in a European neurosurgical center. All patients admitted for neurosurgical intervention between 2012 and 2016 were stratified as low-, moderate-, and high-risk of VT and received a combination of elastic stockings and LMWH. The protocol was modified in 2014 with the inclusion of peri-operative IPC devices for all patients and only in the high-risk group also post-operatively. At time of post-hoc analysis, data obtained from patients included in this study before 2014 (Protocol A, 3,169 patients) were compared with those obtained after the introduction of IPC (Protocol B, 3,818 patients). Among patients assigned to protocol A, 73 (2.3 %) developed DVT and 28 (0.9 %) developed PE, 9 of which were fatal (0.3 %). Among patients assigned to protocol B, 32 developed DVT (0.8 %) and 7 (0.18 %) developed PE, with 2 eventually resulting in the death of the patient. A post-hoc analysis confirmed that the use of pre-operative LMWH was not associated with a statistically significant greater risk of post-operative bleeding. The authors concluded that this study, despite its limitations of the non-randomized design, appeared to suggest that peri-operative IPC devices are a non-negligible support in the prophylaxis of clinically symptomatic DVT and PE.
Treatment of Upper Extremity Lymphedema Following Surgery
Moseley et al (2007) noted that secondary arm lymphedema is a chronic and distressing condition which affects a significant number of women who undergo breast cancer treatment. A number of health professional and patient instigated conservative therapies have been developed to help with this condition, but their comparative benefits are not clearly known. This systematic review undertook a broad investigation of commonly instigated conservative therapies for secondary arm lymphedema including; complex physical therapy, manual lymphatic drainage, pneumatic pumps, oral pharmaceuticals, low level laser therapy, compression bandaging and garments, limb exercises and limb elevation. It was found that the more intensive and health professional based therapies, such as complex physical therapy, manual lymphatic drainage, pneumatic pump and laser therapy generally yielded the greater volume reductions, while self-instigated therapies such as compression garment wear, exercises and limb elevation yielded smaller reductions. The authors concluded that all conservative therapies produced improvements in subjective arm symptoms and quality of life issues, where these were measured. Moreover, they stated that despite the identified benefits, there is still the need for large scale, high level clinical trials in this area.
The Canadian Agency for Drugs and Technologies in Health (CADTH)’s guidelines on “Intermittent pneumatic compression devices for the management of lymphedema” (Tran and Argaez, 2017) stated that “There is no cure for lymphedema. The complex decongestive therapy (CDT) is a multimodal therapy, which is recognized as a conservative management of lymphedema and consists of compression therapy (i.e., multilayer bandaging), manual lymphatic drainage (MLD), exercise and skin care. Intermittent pneumatic compression (IPC) can be used in the treatment of lymphedema as an adjunct to CDT, particularly in patients with compromised mobility or physical exercise. Although lymphedema reduces after application, the use of IPC remains controversial due to its adverse effects, including the recurrence of edema due to residual proteins remaining in the interstitial space, and potential lymphatic structure damage due to high pressure application”. The guideline also noted that the Japan Lymphedema Study Group “recommended” that “Currently, there is no evidence that IPC decreases the circumferential diameter of limbs with lymphedema (Recommendation grade: D)”.
Phillips and Gordon (2019) stated that pneumatic compression has been used for more than 40 years in the management of lymphedema (LE). Modes of application have evolved with little consensus regarding optimal treatment parameters or dosage. In a systematic review, these investigators evaluated the evidence for dosage of IPC for people with LE and, especially, that for upper versus lower limbs or child versus adult dosage. Medline, Embase, CINAHL, PubMed, and Scopus were searched with terms, including LE and IPC devices, with no restriction on time. Other materials searched included reference lists of included articles. Systematic review registration: PROSPERO ID: CRD42017054338. Studies were evaluated according to PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines and were excluded if they were not in English, not human, had physiological outcomes, or studied IPC in combination with other therapies. Quality appraisal, using the McMaster University Critical Review Tool, was undertaken by 2 researchers with differences resolved by a 3rd. A total of 122 full-text studies were screened for eligibility; 16 studies met inclusion criteria for final analysis. Of these, 4 were reported separately due to concurrent use of compression garments during the study period; 1 RCT met the requirements for a level II (National Health and Medical Research Council) rating; the remainder were level III-2 and below. Devices applying compression via multi-chamber sleeves were more commonly used in the past 20 years, with a trend toward lower pressures and shorter treatment times compared with earlier studies. Little evidence existed for application of specific dosage of IPC for children or a particular limb. New devices utilizing lower pressures support home use and self-management of LE. The authors concluded that low-level evidence of moderate quality showed significant outcomes achieved with dosage times of 45 to 60 mins, applying pressures between 30 and 60 mmHg in sequential IPC programs. These researchers noted that methodological limitations in most studies suggested caution in drawing conclusions.
Adjunctive Intermittent Pneumatic Compression for Individuals Receiving Pharmacologic Thromboprophylaxis
Arabi and colleagues (2019) examined if adjunctive intermittent pneumatic compression in critically ill patients receiving pharmacologic thromboprophylaxis would result in a lower incidence of DVT than pharmacologic thromboprophylaxis alone. These investigators randomly assigned patients who were considered adults according to the local standards at the participating sites (greater than or equal to 14, greater than or equal to 16, or greater than or equal to 18 years of age) within 48 hours after admission to an intensive care unit (ICU) to receive either IPC for at least 18 hours each day in addition to pharmacologic thromboprophylaxis with unfractionated or low-molecular-weight heparin (LMWH) (pneumatic compression group) or pharmacologic thromboprophylaxis alone (control group). The primary outcome was incident (i.e., new) proximal lower-limb DVT, as detected on twice-weekly lower-limb US following the 3rd calendar day since randomization until ICU discharge, death, attainment of full mobility, or trial day 28, whichever occurred first. A total of 2,003 patients underwent randomization -- 991 were assigned to the IPC group and 1,012 to the control group; IPC was applied for a median of 22 hours (IQR, 21 to 23) daily for a median of 7 days (IQR, 4 to 13). The primary outcome occurred in 37 of 957 patients (3.9 %) in the IPC group and in 41 of 985 patients (4.2 %) in the control group (relative risk [RR], 0.93; 95 % CI: 0.60 to 1.44; p = 0.74). Venous thromboembolism (PE or any lower-limb DVT) occurred in 103 of 991 patients (10.4 %) in the IPC group and in 95 of 1012 patients (9.4 %) in the control group (RR, 1.11; 95 % CI: 0.85 to 1.44), and death from any cause at 90 days occurred in 258 of 990 patients (26.1 %) and 270 of 1011 patients (26.7 %), respectively (RR, 0.98; 95 % CI: 0.84 to 1.13). The authors concluded that among critically ill patients who were receiving pharmacologic thromboprophylaxis, no benefit of adjunctive IPC in the prevention of incident proximal lower-limb DVT was observed.
Intra-Operative Intermittent Pneumatic Compression Devices in Venous Thromboembolism Prophylaxis in Total Hip and Total Knee Arthroplasty
Tyagi and colleagues (2018) noted that VTE is a common complication after total hip arthroplasty (THA) and total knee arthroplasty (TKA), occurring in up to 85 % of patients who are not treated with prophylaxis. The initiation of VTE development may occur intra-operatively. These investigators examined if this gap in VTE prophylaxis can be addressed by the use of intra-operative IPC devices (IPCDs) and if intra-operative IPCDs have a meaningful benefit in preventing symptomatic VTE. These researchers defined symptomatic VTE as DVT in either lower extremity or a PE. The authors evaluated the medical records of 3,379 patients who underwent THA or TKA at their institution in 2014 and 2015. Effects of various factors, including age, sex, body mass index (BMI), and smoking status, were compared between these 2 cohorts. Patients who experienced a symptomatic VTE were also matched by age, sex, and procedure type with randomly selected controls. In the patient sample, 47 patients (1.4 %) developed VTE; 40 (1.2 %) of these patients underwent TKA, whereas 7 (0.2 %) underwent THA; VTE occurred less frequently in patients who received intra-operative IPCDs (0.8 %) than in patients who did not receive them (1.5 %); however, this difference did not reach statistical significance. Total knee arthroplasty was associated with increased odds of VTE compared with THA, as was female sex. Moreover, these findings did not show a statistically significant benefit to the intra-operative use of IPCDs. The authors concluded that pneumatic compression remains a fast, easy, low-cost, low-risk, intuitive intervention that could supplement the post-operative multi-modal approach and is worthy of further study.
Treatment of End-Stage Renal Disease
Torres and colleagues (2019) stated that patients with end-stage renal disease (ESRD) experience frequent hemodialysis (HD) complications. Intra-dialytic hypotension (IDH) is a common complication presenting in approximately between 20 % and 50 % of HD sessions. Available interventions such as volume replacement or vasoactive medications are associated with significant side effects. Intermittent pneumatic compression has been proposed as a feasible intervention for the prevention of IDH, treatment of peripheral arterial disease and venous ulcers. These devices apply intermittent pressure to the legs improving arterial blood flow, mobilization of pooled blood with an increase in venous return increasing the effective circulatory volume. In a systematic review, these researchers reviewed the published clinical evidence on whether IPC has a circulatory benefit and was it well-tolerated among patients receiving HD. They identified studies examining the safety and efficacy of IPC in patients with ESRD. The primary outcome was IDH; secondary outcomes such as HD comfort, ultra-filtration volume, and physical activity were collected. No restrictions where used and these investigators included all observational and interventional studies; 2 reviewers performed screening and study quality assessment. These researchers included 7 studies -- 5 addressed IDH, and the rest were included for secondary outcomes such as physical capacity and HD comfort. In 1 randomized, cross-over study comparing exercise against IPC, 21 patients were randomized to 3 different arms (no intervention, cycling, and IPC) a decrease in the rates of IDH with IPC was described (43 %, 38 %, and 24 %, respectively; p = 0.014). The smaller studies corroborated these results; and all studies where at high risk of bias. The authors concluded that IPC might offer significant benefits for patients undergoing HD not limited to prevention of IDH, but also improvement of hemodialysis comfort and physical capacity. Moreover, these researchers stated that these findings should be interpreted in the context of its drawbacks.
Furthermore, UpToDate reviews on “Overview of the management of chronic kidney disease in adults” (Rosenberg, 2020), “Conservative care of end-stage renal disease” (Schell and Arnold, 2020), and “Pulmonary hypertension in patients with end-stage renal disease” (Hopkins et al, 2020) do not mention intermittent pneumatic compression as a management / therapeutic option.
Treatment of Post-Thrombotic Syndrome
Azirar and colleagues (2019) noted that post-thrombotic syndrome (PTS) is a long-term complication of DVT characterized by chronic complaints such as edema and skin changes including; venous ectasia, varicose veins, redness, eczema, hyper-pigmentation, and in severe cases fibrosis of the subcutaneous adipose in the affected limb. These chronic complaints are the effects of venous outflow restriction that can cause symptoms such as heaviness, itching, pain, cramps, and paresthesia; 20 % to 50 % of people with DVT develop post-thrombotic complications. Several non-pharmaceutical measures are used for prevention of PTS during the acute phase of DVT. These include elevation of the legs and compression therapy. There have been limited studies regarding the effectiveness of compression therapy for prevention or treatment of PTS. As a result, clinicians and guidelines differ in their assessment of compression therapy during treatment of DVT and in the treatment of PTS. This is an update of a review first published in 2003. These researchers examined the effectiveness of compression therapy for treatment of PTS, including elastic compression stockings and mechanical devices compared with no intervention, placebo and with each other. For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialized Register, CENTRAL, Medline, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries on July 2, 2018. They included trials that evaluated compression therapy for the treatment of PTS. The primary outcomes were severity of PTS and AEs. There were no restrictions on date or language; 2 review authors independently examined if potentially relevant studies met the inclusion criteria. One review author extracted and summarized data and the other review author verified them. They resolved disagreements by discussion. These researchers assessed methodological study quality with the Cochrane “Risk of bias” tool. They used GRADE to assess the overall certainty of the evidence supporting the outcomes assessed in this review. These investigators identified 4 trials, with 116 subjects, examining the effectiveness of compression therapy for treatment of PTS. The methodology used by each trial was too heterogeneous to perform a meta-analysis, so they reported their findings narratively. Two trials studied the effect of graduated elastic compression stockings (GECS) on improvement of PTS symptoms. One study reported beneficial hemodynamic effects, while the other found no benefits on PTS severity compared to placebo (very low-certainty evidence). There was very limited evidence available for AEs and quality of life (QOL). The 2 studies did not report on compliance rates during the study period. Two trials studied the effects of intermittent mechanical compression devices. Both reported improvement in PTS severity (low-certainty evidence). Improvement of the severity of PTS was defined by treatment “success” or “failure”. Only 1 study comparing compression devices evaluated AEs and QOL. Although 9 % of the subjects experienced adverse effects such as leg swelling, irritation, superficial bleeding, and skin itching (moderate-certainty evidence), QOL was improved (moderate-certainty evidence). Studies did not assess compliance using intermittent mechanical compression devices. None of the studies evaluated patient satisfaction. The authors concluded that there was very low-certainty evidence regarding the use of GECS for treatment of PTS as assessed by 2 small studies of short duration. One study reported beneficial hemodynamic effects, while 1 found no benefits on PTS severity compared to control/placebo stockings. There was very limited evidence for adverse effects, patient satisfaction, QOL, and compliance rates. There was low-certainty evidence favoring use of IPC devices compared to a control device for the treatment of severity owing to different measurements used by the studies reporting on this outcome and small studies of short duration. There was moderate-certainty evidence of improved QOL but possible increased adverse effects related to compression device use owing to small studies of short duration. These researchers stated that high-certainty evidence to support the use of compression therapy in prevention of PTS is lacking and any conclusions drawn from current evidence should be interpreted with care. These investigators stated that further research is needed to examine if compression could result in long-term reduction and relief of the symptoms caused by PTS, or prevent deterioration and leg ulceration.
An UpToDate review on “Post-thrombotic (postphlebitic) syndrome” (Kahn and Mathes, 2020) states that “Intermittent pneumatic compression or lymphedema therapy may offer symptomatic relief for patients with moderate-to-severe post-thrombotic syndrome. In a small clinical trial conducted in patients with severe post-thrombotic syndrome, intermittent pneumatic compression reduced intractable edema. In a later trial, a novel lower limb venous-return assist device improved the clinical manifestations of severe post-thrombotic syndrome alone and in combination with compression stockings”. However, intermittent pneumatic compression is not listed in the “Summary and Recommendations” section of this review.
Prophylaxis of Venous Thromboembolism in Individuals Undergoing Major Amputation of the Lower Extremity
Herlihy and colleagues (2020) noted that individuals undergoing major amputation of the lower limb are at increased risk of VTE. Risk factors for VTE in amputees include advanced age, sedentary lifestyle, longstanding arterial disease and an identifiable hyper-coagulable condition. Evidence suggested that pharmacological prophylaxis (e.g., heparin, factor Xa inhibitors, vitamin K antagonists, direct thrombin inhibitors, anti-platelets) is effective in preventing DVT, but is associated with an increased risk of bleeding. Mechanical prophylaxis (e.g., anti-embolism stockings, IPC and foot impulse devices), on the other hand, is non-invasive and has minimal side effects. However, mechanical prophylaxis is not always appropriate for individuals with contraindications such as peripheral arterial disease (PAD), arteriosclerosis or bilateral lower limb amputations. It is important to determine the most effective thromboprophylaxis for individuals undergoing major amputation and whether this is one treatment alone or in combination with another. This was an update of the review first published in 2013. These investigators examined the effectiveness of thrombo-prophylaxis in preventing VTE in people undergoing major amputation of the lower extremity. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialized Register, Cochrane Central Register of Controlled Trials, Medline, Embase and Cumulative Index to Nursing and Allied Health Literature databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to November 5, 2019. These researchers planned to undertake reference checking of identified trials to identify additional studies; they did not apply any language restrictions. These researchers included RCTs and quasi-RCTs, which allocated individuals undergoing a major unilateral or bilateral amputation (e.g., hip disarticulation, trans-femoral, knee disarticulation and trans-tibial) of the lower extremity to different types or regimens of thrombo-prophylaxis (including pharmacological or mechanical prophylaxis) or placebo. Two reviewers independently selected studies; and extracted data and assessed risk of bias. They resolved any disagreements by discussion. Outcomes of interest were VTE (DVT and pulmonary embolism (PE)), mortality, AEs and bleeding. They employed GRADE criteria to evaluate the certainty of the evidence. The 2 included studies compared different treatments; thus, these investigators could not pool the data in a meta-analysis.
These researchers did not identify any eligible new studies for this update; 2 studies with a combined total of 288 subjects met the inclusion criteria for this review. One study compared unfractionated heparin with LMWH and found no evidence of a difference between the treatments in the prevention of DVT (OR 1.23, 95 % CI: 0.28 to 5.35; 75 subjects; very low-certainty evidence). No bleeding events occurred in either group; deaths as well as AEs were not reported. This study was open-label and therefore at a high risk of performance bias. Furthermore, the study did not report the method of randomization, so the risk of selection bias was unclear. In the 2nd study, there was no evidence of a benefit from heparin use in preventing PE when compared to placebo (OR 0.84, 95 % CI: 0.35 to 2.01; 134 subjects; low-certainty evidence). Similarly, no evidence of improvement was detected when the level of amputation was considered, with a similar incidence of PE between the 2 therapeutic groups: above knee amputation (OR 0.79, 95 % CI: 0.31 to 1.97; 94 subjects; low-certainty evidence); and below knee amputation (OR 1.53, 95 % CI: 0.09 to 26.43; 40 subjects; low-certainty evidence). A total of 10 subjects died during the study; 5 underwent a post-mortem and 3 were found to have had a recent PE, all of whom had been on placebo (low-certainty evidence). Bleeding events were reported in less than 10 % of subjects in both treatment groups, but the study did not present specific data (low-certainty evidence). There were no reports of other AEs. This study did not report the methods used to conceal allocation of treatment, so it was unclear if selection bias occurred. However, this study appeared to be free from all other sources of bias. No study looked at mechanical prophylaxis. The authors did not identify any eligible new studies for this update. As these researchers only included 2 studies in this review, each comparing different interventions, there was insufficient evidence to make any conclusions regarding the most effective thrombo-prophylaxis regimen in individuals undergoing lower limb amputation. These researchers stated that further large-scale studies of good quality are needed.
Treatment of Intermittent Claudication
In a RCT, Hoel and colleagues (2021) examined the effects of lower extremity intermittent negative pressure (INP) treatment for 1 hour twice-daily for 12 weeks on the walking distance of patients with intermittent claudication (IC). Patients with IC were randomized to treatment with -40 mm Hg INP (treatment group) or -10 mm Hg INP (sham control group). Pain-free walking distance (PWD) and maximal walking distance (MWD) on a treadmill, resting and post-exercise ankle-brachial index (ABI), resting and post-ischemic blood flow (plethysmography), and QOL (EQ-5D-5L and Vascuqol-6) were measured at baseline and after 12 weeks of treatment. A total of 72 patients were randomized (treatment group, n = 38; sham control group, n= 34), and 63 had data available for the intention-to-treat (ITT) analyses. The between-group comparisons showed a significant change in the PWD, favoring the treatment group over the sham control group (estimated treatment effect, 50 m; 95 % CI: 11 to 89; p = 0.014). The PWD had increased by 68 m (p < 0.001) in the treatment group and 18 m (p = 0.064) in the sham control group. No significant difference was found in the change in the MWD between the 2 groups (estimated treatment effect, 42 m; 95 % CI: -14 to 97; p = 0.139). The MWD had increased by 62 m (p = 0.006) in the treatment group and 20 m (p = 0.265) in the sham control group. For patients with a baseline PWD of less than 200 m (n = 56), significant changes had occurred in both PWD and MWD between the 2 groups, favoring the treatment group (estimated treatment effect, 42 m; 95 % CI: 2 to 83; p = 0.042; and estimated treatment effect, 62 m; 95 % CI: 5 to 118; p = 0.032; respectively). Both overall and for the group of patients with a PWD of less than 200 m, no significant differences were found in the changes in the resting and post-exercise ABI, resting and post-ischemic blood flow, or QOL parameters between the 2 groups. The authors concluded that treatment with -40 mm Hg INP increased the PWD compared with sham treatment in patients with IC. For the patients with a baseline PWD of less than 200 m, an increase was found in both PWD and MWD compared with sham treatment. This was a relatively small study (n = 38 in the treatment group; and not sure how many of the 9 lost to follow-up were in this group) and a short-term follow-up (12 weeks). These preliminary findings need to be validated by well-designed studies.
The authors stated that this study had several drawbacks. These researchers used −10 mm Hg INP in the sham device to make it appear identical to the active device without affecting the arterial blood flow. The similarity in compliance between the groups and the low withdrawal rate in the sham control group indicated that the patients really were unaware of their treatment allocation; however, a small effect might have resulted from the repetitive exposure to −10 mm Hg INP, leading to an under-estimation of the treatment effect. More patients were lost to follow-up in the treatment group than in the sham control group because of user- or device-related problems. The use of the device requires some technical, cognitive, and motor capacity. Furthermore, some patients with a very small circumference of the lower leg might experience difficulty in achieving airtightness of the pressure chamber. Thus, the difference in those lost to follow-up between the 2 groups might have been random. Measurements of PWD is based on a subjective report of the onset of pain by the patient during the treadmill test. Therefore, the results might have been affected by the fact that individuals might perform differently when they were being observed. However, in a double-blind RCT, the risk of bias from this phenomenon appeared low. The patients were recruited from the vascular surgery departments at 3 hospitals in Norway. Thus, one should be careful about generalizing the results to other patient populations or settings. However, whether the results from the present study are also applicable to patients with more severe stages of PAD should be the subject of further research.
Treatment of Lower Limb Lymphedema in Patients with Type 2 Diabetes Mellitus
de Sire and colleagues (2021) stated that type 2 diabetes mellitus (T2DM) is a chronic disease associated with fluid accumulation in the interstitial tissue. Similar to IPC, manual lymphatic drainage (MLD) plays a role in reducing lymphoedema. In a single-center, pilot study, these researchers examined the effectiveness of a synergistic treatment with MLD and IPC in reducing lower limb lymphedema in T2DM patients. Adults with a clinical diagnosis of T2DM and lower limb lymphedema (stage II to IV) were recruited from July to December 2020. Subjects were randomized into 2 groups: experimental group, undergoing a 1-month rehabilitative program consisting of MLD and IPC (with a compression of 60 to 80 mmHg); control group, undergoing MLD and a sham IPC (with compression of less than 30 mmHg). The primary outcome was the lower limb lymphedema reduction, assessed by the circumferential method (CM). Secondary outcomes included passive range of motion (pROM) of hip, knee, and ankle; QOL; laboratory examinations such as fasting plasma glucose and HbA1c. At baseline (T0) and at the end of the 1-month rehabilitative treatment (T1), all the outcome measures were examined, except for the Hb1Ac assessed after 3 months. Out of 66 T2DM patients recruited, only 30 respected the eligibility criteria and were randomly allocated into 2 groups: experimental group (n = 15; mean age of 54.2 ± 4.9 years) and control group (n = 15; mean age of 54.0 ± 5.5 years). At the intra-group analysis, the experimental group showed a statistically significant improvement of all outcome measures (p < 0.05). The between-group analysis showed a statistically significant improvement in pROM of the hip, knee, ankle, EQ-VAS, and EQ5D3L index at T1. The authors concluded that a multi-modal approach consisting of IPC and MLD showed to play a role in reducing lower limb lymphedema, with an increase of pROM and HRQoL. Moreover, these researchers stated that since these were preliminary data, further studies are needed.
The authors stated that this study had several drawbacks. First, the small sample size (n = 15 in the experimental group), even though it was a single-center study. Second, the scarce literature on this topic did not allow the definition of specific outcomes for evaluating any intervention on lymphedema in T2DM. Third, the lack of data on glycosylated albumin that could be useful as an indicator of glycemic control.
Combined Intermittent Pneumatic Compression and Pharmacologic Prophylaxis for Thromboprophylaxis
Kakkos et al (2022) noted that it is generally assumed by practitioners and guideline authors that combined modalities (methods of treatment) are more effective than single modalities in preventing VTE, defined as DVT or PE, or both. This was the 2nd update of a Cochrane review 1st published in 2008. These investigators examined the effectiveness of combined IPC and pharmacological prophylaxis compared to single modalities in preventing VTE. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialized Register, CENTRAL, Medline, Embase, CINAHL, and AMED databases, and World Health Organization (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to January 18, 2021. These investigators searched the reference lists of relevant articles for additional studies. They included RCTs or controlled clinical trials (CCTs) of combined IPC and pharmacological interventions used to prevent VTE compared to either intervention individually. These researchers selected studies, applied Cochrane's risk of bias tool, extracted data, and resolved disagreements by discussion. They carried out fixed-effect model meta-analyses with ORs and 95 % CIs; and employed a random-effects model when there was heterogeneity. They evaluated the certainty of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The outcomes of interest were PE, DVT, bleeding and major bleeding.
A total of 34 studies entailing 14,931 participants, mainly undergoing surgery or admitted with trauma were included in this analysis; 25 studies were RCTs (12,672 participants) and 9 were CCTs (2,259 participants). Overall, the risk of bias was mostly unclear or high. These researchers used the GRADE approach to examine the certainty of the evidence; and this was downgraded due to the risk of bias, imprecision or indirectness. The addition of pharmacological prophylaxis to IPC compared with IPC alone reduced the incidence of symptomatic PE from 1.34 % (34/2,530) in the IPC group to 0.65 % (19/2,932) in the combined group (OR 0.51, 95 % CI: 0.29 to 0.91; 19 studies, 5,462 participants, low-certainty evidence). The incidence of DVT was 3.81 % in the IPC group and 2.03 % in the combined group showing a reduced incidence of DVT in favor of the combined group (OR 0.51, 95 % CI: 0.36 to 0.72; 18 studies, 5,394 participants, low-certainty evidence). The addition of pharmacological prophylaxis to IPC, however, increased the risk of any bleeding compared to IPC alone: 0.95 % (22/2,304) in the IPC group and 5.88 % (137/2,330) in the combined group (OR 6.02, 95 % CI: 3.88 to 9.35; 13 studies, 4,634 participants, very low-certainty evidence). Major bleeding followed a similar pattern: 0.34 % (7/2,054) in the IPC group compared to 2.21 % (46/2,079) in the combined group (OR 5.77, 95 % CI: 2.81 to 11.83; 12 studies, 4,133 participants, very low-certainty evidence). Tests for subgroup differences between orthopedic and non-orthopedic surgery participants were not possible for PE incidence as no PE events were reported in the orthopedic subgroup. No difference was detected between orthopedic and non-orthopedic surgery participants for DVT incidence (test for subgroup difference p = 0.19). The use of combined IPC and pharmacological prophylaxis modalities compared with pharmacological prophylaxis alone reduced the incidence of PE from 1.84 % (61/3,318) in the pharmacological prophylaxis group to 0.91 % (31/3,419) in the combined group (OR 0.46, 95 % CI: 0.30 to 0.71; 15 studies, 6,737 participants, low-certainty evidence). The incidence of DVT was 9.28 % (288/3,105) in the pharmacological prophylaxis group and 5.48 % (167/3,046) in the combined group (OR 0.38, 95 % CI: 0.21 to 0.70; 17 studies; 6,151 participants, high-certainty evidence). Increased bleeding side effects were not observed for IPC when it was added to anti-coagulation (any bleeding: OR 0.87, 95 % CI: 0.56 to 1.35, 6 studies, 1,314 participants, very low-certainty evidence; major bleeding: OR 1.21, 95 % CI: 0.35 to 4.18, 5 studies, 908 participants, very low-certainty evidence). No difference was detected between the orthopedic and non-orthopedic surgery participants for PE incidence (test for subgroup difference p = 0.82) or for DVT incidence (test for subgroup difference p = 0.69).
The authors concluded that evidence suggested that combining IPC with pharmacological prophylaxis, compared to IPC alone reduced the incidence of both PE and DVT (low-certainty evidence). Combining IPC with pharmacological prophylaxis, compared to pharmacological prophylaxis alone, reduced the incidence of both PE (low-certainty evidence) and DVT (high-certainty evidence). These researchers downgraded due to risk of bias in study methodology and imprecision. Very low-certainty evidence suggested that the addition of pharmacological prophylaxis to IPC increased the risk of bleeding compared to IPC alone, a side effect not observed when IPC was added to pharmacological prophylaxis (very low-certainty evidence), as expected for a physical method of thromboprophylaxis. The certainty of the evidence for bleeding was downgraded to very-low due to risk of bias in study methodology, imprecision and indirectness. The results of this update agreed with current guideline recommendations, which support the use of combined modalities in hospitalized people (limited to those with trauma or undergoing surgery) at risk of developing VTE. Moreover, these researchers stated that further investigations on the role of combined modalities in VTE prevention are needed to provide evidence for specific patient groups and to increase the certainty in the evidence.
Duval et al (2022) stated that Venous thromboembolic events (VTE) are frequent complications in hospitalized patients and a leading cause of preventable death in hospital. Pharmacologic prophylaxis is a standard of care (SOC) for prevention of VTE in at risk patients; however, the additional value of IPC is unclear. In a systematic review and meta-analysis, these investigators examined the effectiveness of adding IPC to pharmacologic prophylaxis for the prevention of VTE in hospitalized adults. They searched the Cochrane Central Register of Controlled Trials, Embase, Medline, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and the International Clinical Trials Registry Platform from inception to July 2022. These researchers included RCTs comparing the use of IPC in addition to pharmacological thromboprophylaxis to pharmacological thromboprophylaxis alone in hospitalized adults. Meta-analyses were carried out to calculate RR of VTE, DVT, and PE. These investigators examined the risk of bias using the Cochrane Risk of Bias Tool for Randomized Trials, Version 2 and the quality of evidence using the GRADE approach. They included 17 studies enrolling 8,796 participants. The IPC was mostly applied up to the thigh and pharmacological thromboprophylaxis was primarily LMWH. Adjunctive IPC was associated with a decreased risk of VTE (15 studies, RR = 0.53; 95 % CI: 0.35 to 0.81) and DVT (14 studies, RR = 0.52; 95 % CI: 0.33 to 0.81) but not PE (7 studies, RR = 0.73; 95 % CI: 0.32 to 1.68). The quality of evidence was graded low, downgraded by risk of bias and inconsistency. Moderate and very low-quality evidence, respectively, suggested that adjunctive IPC was unlikely to change the risk of all-cause mortality or adverse events. Subgroup analyses indicated a more evident apparent benefit in industry-funded studies. The authors concluded that the findings of this systematic review/meta-analysis indicated low-quality evidence under-pinning the additional use of IPC to pharmacological thromboprophylaxis for prevention of VTE and DVT. These researchers stated that further large, high-quality, randomized studies are needed to support its use and to identify patient subgroups for whom it could be beneficial. They noted that cost-effectiveness data are needed to justify healthcare resources used for IPC treatment; and future trials should also strive to examine patient-centered AEs related to IPC use, such as delirium or sleep disorders, which were not evaluated in any of the included trials.
The authors stated that this study had several drawbacks. First, VTE events were rare, generating wide CIs for some results. Second, the unusual shape of funnel plots precluded the exclusion of publication bias, which could have resulted in an over-estimation of the effect. Third, the results of some registered trials have not yet been published, such as those from the Efficacy of the Association Mechanical Prophylaxis + Anticoagulant Prophylaxis on Venous Thromboembolism Incidence in Intensive Care Unit (ICU) study, whereas others have only been presented in conference abstracts and could not be included in this review.
Venowave VW5
The Venowave is an Food and Drug Administration (FDA)-approved circulation booster designed to improve circulation in the lower extremities. The Venowave is a medical compression pump that is compact, light-weight, and battery-operated; it is designed for the treatment and alleviation of symptoms associated with poor circulation. When worn firmly on the calf, the Venowave produces a wave form motion forcing blood from the feet and legs back to the heart. This increase in blood flow draws oxygen to wound and ulcer sites, prevents blood pooling and clotting, and alleviates symptoms of PTS and other CVIs. The product is unique because it is light-weight (250 g or less than 0.5 lb), discreet (can be worn under pants or skirts easily), and allows patients to remain completely mobile. There are no wires or tubes. The Venowave compresses the calf 4 to 5 times/min to pump blood out of the leg; it can be used alone or in conjunction with other therapies (e.g., graduated compression stockings) for a synergistic effect.
Ginsberg et al (1999) noted that although uncommon, severe post-phlebitic syndrome may be associated with persistent, intractable pain and swelling that interfere with work and leisure activities. In a randomized, cross-over study, these researchers examined intermittent compression therapy with an extremity pump would benefit patients with this condition and, if so, whether the benefit was sustained. Between 1990 to 1996, all patients in the clinical thrombo-embolism program of an Ontario teaching hospital who had a history of DVT and intractable symptoms of post-phlebitic syndrome were recruited into the study. The study involved using an extremity pump twice-daily for a total of 2 months (20 mins/session). Subjects were randomly assigned to use either a therapeutic pressure (50 mm Hg) or a placebo pressure (15 mm Hg) for the 1st month. For the 2nd month, subjects used the other pressure. A questionnaire evaluating symptoms and functional status served as the primary outcome measure and was administered at the end of each 1-month period. A symptom score was derived by summing the scores for individual questions. At the end of the 2-month study, subjects were asked to indicate their treatment preference and to rate the importance of the difference between the 2 pressures. Treatment was considered successful if the patient preferred the therapeutic pressure and stated that he or she would continue using the extremity pump and that the difference between the therapeutic and placebo pressures was of at least slight importance. All other combinations of responses were considered to represent treatment failure. Subjects whose treatment was classified as successful were offered the opportunity to keep the pump and to alter pressure, frequency and duration of pump use to optimize symptom management. In July 1996, the authors contacted all study participants whose treatment had been classified as successful to examine if they were still using the pump and, if so, whether they were still deriving benefit. A total of 15 consecutive patients (12 women and 3 men) were enrolled in this trial. The symptom scores were significantly better with the therapeutic pressure (mean of 16.5) than with the placebo pressure (mean of 14.4) (paired t-test, p = 0.007). The treatment for 12 of the patients (80 %, 95 % CI: 52 % to 96 %) was considered successful. Of these, 9 patients continued to use the pump beyond the cross-over study and to derive benefit. The authors concluded that a trial of pump therapy was worthwhile for patients with severe post-phlebitic syndrome and that a sustained beneficial response could be expected in most patients.
O'Donnell et al (2008) stated that severe PTS is responsible for considerable disability, reduced QOL and increased healthcare costs. Current therapies are limited and often ineffective. These researchers carried out a randomized, cross-over, 2-center, controlled study to examine Venowave, a novel lower-limb venous-return assist device, for the treatment of severe PTS. Eligible subjects were allocated to receive, in randomized order, Venowave for 8 weeks and a control device for 8 weeks. The 8-week treatment periods were separated by a 4-week period when no device was used (i.e., wash-out period). The primary outcome measure was a “clinical success” defined as: reported benefit from the device; and moderate or greater improvement in symptoms of PTS; and willingness to continue using the device. Secondary outcome measures included QOL as measured by VEINES-QOL questionnaire (higher scores indicate better QOL), and PTS severity as measured by the Villalta PTS scale (higher scores indicate more severe PTS). A total of 32 patients were enrolled. Of these, 26 (80 %) were also using graduated compression stockings; 26 participants completed both trial periods. Clinical success occurred in 10 (31 %) participants receiving Venowave and 4 (13 %) participants receiving the control device, with 2 (6 %) participants reporting a clinical success with both devices (p = 0.11). Mean VEINES-QOL score at the end of study period was significantly greater (p = 0.004) for Venowave (52.5; SD 5.8) compared to control (50.2; SD 6.2). Mean Villalta scale score at the end of study period was significantly decreased (p = 0.004) for Venowave (12.2; SD 6.3) compared to control (15.0; SD 6.1). The authors concluded that Venowave appeared to be a very promising new therapy for patients with severe PTS, which may be used alone or in combination with graduated compression stockings.
Sobieraj-Teague et al (2012) noted that patients undergoing neurosurgical procedures are at risk of VTE, but often have contra-indications for anti-coagulant prophylaxis. In an open RCT, these investigators examined the effectiveness and tolerability of a new, light-weight, portable, battery-powered, intermittent calf compression device, Venowave, for the prevention of VTE in neurosurgical in-patients. They compared Venowave with control for the prevention of VTE in patients undergoing neurosurgery. The primary outcome was the composite of asymptomatic DVT detected by screening venography or compression ultrasound (US) performed on day 9 (± 2 days) and symptomatic VTE. These researchers randomized 75 patients to receive Venowave devices and 75 to the control group. All subjects were prescribed graduated compression stockings and physiotherapy. VTE occurred in 3 patients randomized to Venowave and in 14 patients randomized to control (4.0 % versus 18.7 %, RR 0.21; 95 % CI: 0.05 to 0.75, p = 0.008). Similar reductions were observed for proximal DVT (2.7 % versus 8.0 %) and symptomatic VTE (0 % versus 2.7 %), and the results were consistent in all subgroups examined. The authors concluded that Venowave devices were effective in preventing VTE in high-risk neurosurgical patients.
Makedonov et al (2020) stated that PTS is a form of CVI secondary to prior DVT affecting up to 50 % of patients following proximal DVT. There is no effective treatment of established PTS and its management lies in its prevention after DVT. Optimal anti-coagulation is key for PTS prevention. Among anti-coagulants, LMWHs have anti-inflammatory properties, and have a particularly attractive profile. Elastic compression stockings (ECS) may be helpful for treating acute DVT symptoms but their benefits for PTS prevention are debated. Catheter-directed techniques reduce acute DVT symptoms and might reduce the risk of moderate-severe PTS in the long-term in patients with ilio-femoral DVT at low-risk of bleeding. Statins may decrease the risk of PTS, but current evidence is lacking. Treatment of PTS is based on the use of ECS and lifestyle measures such as leg elevation, weight loss and exercise. Veno-active medications may be helpful and research is ongoing. Interventional techniques for the treatment of PTS should be reserved for highly selected patients with chronic iliac obstruction or greater saphenous vein reflux, but have not yet been assessed by robust clinical trials. These investigators stated that venous-return assist devices such as the Venowave can be tried for patients with moderate-to-severe PTS symptoms that are unresponsive to ECS. The evidence behind this was of low-certainty, as only 2 small, placebo-controlled, cross-over studies have been conducted (Azirar et al, 2019). O’Donnell et al (2008) enrolled 32 patients and did not find a difference in the primary endpoint (composite of reported benefit from the device, at least moderate improvement in symptoms and willingness to continue using the device). However, they found an improvement in the secondary endpoints of Villalta scale score (12.2 versus 15 for the device and placebo treatments, p = 0.004) and QOL (venous disease-specific quality of life scores of 52.5 versus 50.2 for the device and placebo treatments, p = 0.004). Ginsberg et al (1999) enrolled 15 patients with intractable PTS and examined an extremity pump that applied 50 mmHg of pressure. These researchers found significant improvement of a custom symptom score (p = 0.007). More importantly, 80 % of patients (12/15) were considered to have successful treatment.
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The above policy is based on the following references:
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