Horses are prone to lymphatic drainage disorders due to minimal distal limb musculature as well as their propensity to incur distal limb trauma. Peripheral lymphedema in the horse can be the manifestation of a variety of primary disease processes, including lymphangitis, cellulitis, vasculitis or venous congestion, hypoalbuminemia, and congestive heart failure,1 or a result of breed predilection, such as chronic progressive lymphedema (CPL) in draught breeds.2–5 Many of these can be devastating life-long disorders in which inadequate lymphatic drainage or excessive lymph fluid accumulation of the distal limbs leads to tissue damage and severe pain. Treatment strategies for distal lymphedema in the horse focus on local therapy with limb bandaging/wrapping, cold hydrotherapy, or dry cold compression, along with stimulation of lymphatic return with exercise.4 Additionally, for cases such as CPL, skin and feather care to control local skin infections can also be supportive.4 However, while bandaging of limbs, cold therapy, and exercise can improve limb swelling, these treatments are often inefficient and only have transient effects.4 Therefore, more efficient and cost-effective techniques to improve lymphatic return and equine distal lymphedema in a sustained manner are needed.
Combined decongestive therapy is the most effective therapeutic strategy in humans for the treatment of lymphedema.6 This consists of directional manual lymph drainage followed by compression bandaging combined with skin care and exercise, all of which are essential to improve circulation.6 Because of the labor-intensive nature of directional manual lymph drainage, therapy must be performed in a clinical setting. Therefore, at-home alternatives for the treatment of lymphedema were actively investigated and pneumatic compression therapy devices were created for both in-hospital and at-home use. Pneumatic compression therapy devices consist of specialized garments with air chambers that inflate and deflate in a sequential pattern based on pump-driven pressures and sensors to enhance lymphatic transport. In human medicine, pneumatic compression therapy devices are commonly used for the treatment of lymphedema as they have been scientifically proven to increase lymphatic clearance and improve patient quality of life in a cost-effective manner.6–8 Therefore, an equine-specific device that provides pneumatic compression therapy could dramatically improve therapy for equine limb lymphedema.
The objective of this study was to determine if pneumatic compression therapy using a novel equine-specific device could improve lymphatic flow in healthy horses. Our hypothesis was that pneumatic compression therapy with the EQ Press would improve lymphatic flow in equine forelimbs compared to untreated control limbs as determined by lymphoscintigraphy.
Materials and Methods
The use of animals in this study was approved by the North Carolina State University Institutional Animal Care and Use Committee (protocol No. 22-209). An equine-specific pneumatic compression device (EQ Press; Vetletics Inc) applied to the front limbs was used to provide pneumatic compression therapy. Like the human devices manufactured by the same company (Mego Afek AC Ltd), the EQ Press consists of patented smart technology air chambers within its garments but is specifically tailored to the horse’s limbs in a patent-pending design that extends from the hoof to the elbow (for forelimbs) or stifle (for hindlimbs) and with pumps that are extremely quiet for the horse. All garments are securely connected to the EQ Press saddle pad by buckles and the pumps are securely held on the saddle pad by Velcro (1 pump per side), making the entire device self-contained on the horse (https://vetletics.com; Supplementary Figure S1). Additional Velcro fasteners on the saddle pad keep any excess tubing from the pumps to the garments in place to accommodate different height horses. The battery-powered pumps can be set at a variety of pressures from 20 to 80 mm Hg and can be used for 8 hours before requiring recharging. The 4 air chambers per limb garment undergo repeated inflation and deflation cycles in which they inflate in a distal to proximal direction using sensors to reach the desired pressure as set on the pump with a short hold at maximum inflation of all chambers, thereby ensuring that lymphatic fluid is propelled proximally up the limb along a pressure gradient and without backflow. All horses were acclimated to the EQ Press once prior to the start of the study by applying the garments and operating the pumps for 5 minutes. Horses then underwent lymphoscintigraphy with the EQ Press (EQP) or as nontreatment control (CON) in a randomized crossover design. Treatment was randomized by an online random number generator with each horse undergoing bilateral forelimb lymphoscintigraphy twice with at least 2 weeks between studies.
Horses were sedated with intravenous detomidine hydrochloride, and the lateral pastern region of both forelimbs was aseptically prepared. Subcutaneous injection of Tc-99m sulfur colloid (0.6 millicuries [mCi] in 0.6 ml total volume) was performed at 2 locations (0.3 ml, 0.3 mCi per injection) at the pastern of each forelimb by a single author (DWK). The lateral pastern was identified 90 degrees from the dorsal midline as the starting location for injection. From here, 2 injections were performed 1 cm dorsal and 1 cm palmar to this “lateral midline” and approximately 1 cm proximal to the coronary band. Immediately following injection, treatment horses were fitted with the EQP, and treatment was initiated with pumps set at a pressure of 60 mm Hg. Control horses did not wear the EQP during lymphoscintigraphy. Five minutes following injection, successive static lateral images (60-second acquisition) were obtained by a single author (JR) distal to the carpus at 5, 10, 15, 30, 45, and 60 minutes and proximal to the carpus at 30, 45, and 60 minutes using a standard large field of view gamma camera (Equine Scanner H.R.; MiE America Inc) coupled with a dedicated processing computer. For all horses, the left forelimb was injected first. Following the 15-minute time point of the left forelimb, the right forelimb was injected, and images were acquired in an identical manner that allowed image acquisition of alternating limbs and time points until the completion of the study.
Lymphoscintigraphy images were evaluated by a single author (CRB) blinded to the treatment group. Lymphatic flow was scored by assigning a number to the time point at which scintigraphic uptake of Tc-99m sulfur colloid was first visualized at a predetermined anatomic location at a standardized image window and level. The accessory carpal bone (ACB) in the distal limb or the cubital lymph node (CLN) in the proximal limb was selected as the predetermined location. For the distal limb, a score was assigned 1 to 7 with 1 to 6 being time points 5, 10, 15, 30, 45, and 60 minutes, respectively, and with 7 being no visualization at the level of the ACB during the entirety of the study. For the proximal limb, a score was assigned 1 to 4 with 1 to 3 being time points 30, 45, and 60 minutes, respectively, and with 4 being no visualization at the level of the CLN during the entirety of the study. A lower score therefore correlated to a reduced time to reach the predetermined anatomic location.
A power analysis was not performed as no data exist to base a calculation. Continuous data were examined for normality using the Shapiro-Wilk test with parametric data (sedation) analyzed by a 2-tailed paired t test and nonparametric data (lymphoscintigraphy scoring) by Mann-Whitney U test. The Grubbs method (alpha 0.05) for single outlier exclusion was implemented for lymphoscintigraphy scoring. Statistical significance was considered P < .05. All analyses were performed in GraphPad Prism version 9.4.1 (GraphPad Software Inc).
Results
Six Thoroughbred horses (mares, n = 3; geldings, 3) underwent lymphoscintigraphy with or without EQP therapy. Horses had a median age of 13 years (range, 9 to 20 years) and a median weight of 540 kg (range, 402 to 582 kg). All horses acclimated easily and quickly to the EQP and tolerated sedation, lymphoscintigraphy, and EQP therapy. No significant difference in the amount of sedation was measured between CON and EQP horses during lymphoscintigraphic studies (P = .22). Representative images from a horse with and without EQP are presented for the distal and proximal limbs (Figure 1). Scores assigned to lymphoscintigraphy images for the distal and proximal limbs of all horses are presented in Supplementary Table S1. Compared to CON, pneumatic compression therapy with the EQP significantly reduced the time required (lower score) for Tc-99m sulfur colloid to reach the level of the ACB (P = .002) as assigned for the distal limb score and the CLN (P = .001) as assigned for the proximal limb score (Figure 2). A single horse during CON (2 of 12 limbs) had scintigraphic evidence of CLN uptake; however, no other CON horses had identifiable proximal uptake able to reach the lymph node.
Representative left front limb lymphoscintigraphy images of a single horse as no treatment control (CON) and with EQ Press (EQP) therapy following subcutaneous injection of Tc-99m sulfur colloid. Lateral static images indicate that proximal lymphatic flow of Tc-99m in the limb occurs faster with EQP treatment as determined by the time point to reach the accessory carpal bone (ACB; arrowhead) in the distal limb (A to C) and the cubital lymph node (CLN; asterisk) in the proximal limb (D and E). Images are oriented with dorsal/cranial to the left and proximal toward the top.
Citation: American Journal of Veterinary Research 84, 4; 10.2460/ajvr.22.12.0214
Pneumatic compression therapy using the EQ Press (EQP) significantly reduced the time for Tc-99m sulfur colloid to reach the accessory carpal bone (ACB) from the distal limb (P = .002) (A) and the cubital lymph node (CLN) from the proximal limb (P = .001) (B) compared to untreated control (CON) limbs as determined by lymphoscintigraphy. Data were analyzed by the Mann-Whitney U test with significance at P < .05.
Citation: American Journal of Veterinary Research 84, 4; 10.2460/ajvr.22.12.0214
Discussion
Uncontrolled lymphedema can result in chronic inflammation that progresses to skin fibrosis and adipose tissue accumulation that exacerbates fluid accumulation leading to disability and skin infections like cellulitis.2–4 Complete decongestive therapy is prescribed for people with lymphedema to improve lymphatic uptake and reduce swelling and typically utilizes compression bandaging and massage but is labor intensive and requires trained personnel to deliver.6,9 Recent insight has determined that pneumatic compression therapy provides enhanced benefits as it can significantly reduce edema, improve lymphatic propulsion rate, maintain improvement following clinic discharge, and also reduce the incidence of edema-associated cellulitis.6,7,10–13 Because our equine patients are also affected by lymphedema that has similar histopathologic dysfunction as in humans, we became interested in determining whether pneumatic compression therapy could similarly be effective at improving lymphatic flow.4 While horses presented within this study were healthy and unaffected by lymphedema, the EQP system did reduce the time needed for Tc-99m sulfur colloid to reach the ACB in the distal limb and the CLN in the proximal limb, which supported our hypothesis. Additionally, over 60 minutes, 10 of 12 control limbs in the study did not have scintigraphic uptake within the CLN. Therefore, these data support further clinical study of the EQ Press device as a strategy to improve the rate of lymphatic return in horses affected with lymphatic drainage disorders.
Lymphoscintigraphy in horses was first reported in 2006 by de Cock and colleagues14 in an effort to determine its utility in early diagnosis of CPL in draught horses. The authors developed a 4-point scale to quantify lymphatic flow and ascertained that clinically affected horses had increased lymphatic scores in the distal limbs compared to healthy horses, which correlated with static proximal movement of Tc-99m sulfur colloid. This was further supported by a case study of a 12-year-old Clydesdale diagnosed with CPL with skin lesions of a 9-year duration that had reduced lymphatic flow on lymphosctinigraphy.15 Additionally, de Cock and colleagues14 reported scintigraphic distribution of Tc-99m sulfur colloid was mostly confined to the distal limbs in normal horses with minimal uptake in the proximal limbs throughout the 120-minute lymphoscintigraphy study. This was similar to nontreated control limbs reported herein. However, following EQP therapy, the limbs of healthy horses were noted to have accelerated lymphatic flow from the pastern to the CLN at the elbow within 60 minutes. Therefore, it is plausible to believe that earlier uptake in more proximal locations following EQP therapy could improve lymphatic flow and associated clinical signs in horses affected by lymphedema.
In both limbs of a single horse in the study herein, there was scintigraphic uptake noted in the CLN of both proximal limbs without EQP therapy. This is suspected to be due to individual variation. However, following EQP treatment, the same horse had reduced time for scintigraphic uptake at the CLN following treatment. Of the other 5 horses without treatment, none had evidence of CLN uptake at any point in their studies; however, 9 of 10 limbs did subsequently have uptake in the CLN following EQP therapy. The reason 1 limb of a single horse never had identifiable CLN uptake despite EQP therapy is suspected to be due to a user and pump error as the pump of the left front was noted to alarm on 3 different instances and was reset each time throughout the scan. Despite external appearances indicating the air chambers maintained inflation at the time of the alarm, the device does not contain an external pressure gauge that can confirm the pressure achieved within the system. For this reason, the authors suspect 60 mm Hg was not achieved in the left front limb of this single horse, which led to a subsequent reduction in scintigraphic movement of Tc-99m sulfur colloid in that limb. Additionally, at the end of the lymphoscintigraphy study for this single horse, it was discovered that the most proximal chamber connection tubing device was not properly attached and sealed. In conjunction with the inability to determine that the pressure the chambers provided was truly 60 mm Hg, it appears likely that inadequate pressure contributed to the lack of CLN uptake in this single limb following EQP treatment. Using a statistical method for outlier exclusion, these two data points from the EQP treatment of the left front limb were identified as outliers and, therefore, removed from data analysis. Of note, the addition or exclusion of these data did not change the results of the statistical analysis.
Treatment with the EQ Press was instituted at 60 mm Hg for 60 minutes based on pneumatic compression therapy in human medicine as well as case data provided by Vetletics Inc.6,7 These data have indicated that therapy is beneficial in horses affected by lymphedema when set at a pressure of 60 mm Hg or higher and that horses not only tolerate EQ Press therapy but become relaxed during treatment. Additionally, the authors see the benefit of pneumatic compression therapy as provided by the EQ Press as one component of multimodal therapy for equine lymphedema and possibly athletic recovery. At this time, however, no scientific studies have been performed to determine how often treatment should be employed or its duration of effect. Further work is needed to determine how to most effectively implement EQ Press therapy into clinical practice.
Because this study included healthy equine forelimbs as a method to assess the effect of the EQ Press, the authors cannot make conclusions regarding its benefit in horses with lymphedema. This is the main limitation of the study. A controlled, randomized study evaluating the EQ Press for the treatment of equine limb lymphedema in clinically affected horses is warranted.
Our data support that an equine-specific pneumatic compression device, the EQ Press, enhances the lymphatic flow of Tc-99m sulfur colloid in healthy equine forelimbs as determined by lymphoscintigraphy. At two predetermined anatomical locations, scintigraphic uptake occurred significantly earlier in both the distal and proximal limb in horses undergoing EQ Press treatment compared to no treatment control. This warrants further study of the therapeutic benefit of the EQ Press in horses clinically affected by lymphedema and lymphatic drainage disorders as this system could enhance lymphatic return and improve therapy for such conditions in the horse.
Acknowledgments
Funding for this study was provided by a generous gift from Ross Annable. Stipend support for DWK was provided by NIH T32OD011130.
LVS is a cofounder and Chief Medical Officer of Vetletics Inc, which supplied the EQ Press for this study.
The authors would like to thank the technical staff of the North Carolina State University Diagnostic Imaging service for their assistance in the completion of this study.
Supplementary Materials
Supplementary materials are posted online at the journal website: avmajournals.avma.org.
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