Introduction

The use of medicinal leeching (Hirudotherapy) dates back over 3,000 years and is one of the oldest medical practices still performed today.¹ In the late 19th century, the discovery of hirudin, an anticoagulant found in the saliva of leeches, paved the way for evidence-based use of these invertebrates. Since that time, medicinal leeching has been studied and used extensively in human medicine, and many of the biologically active compounds in leech saliva have been shown to function therapeutically through numerous distinct, yet synergistic, avenues. At present, the main indication for medicinal leeching in both human and veterinary medicine is microvascular and reconstructive surgery, particularly the salvage of skin or myocutaneous flaps whose viability is threatened by venous congestion after implantation.^1–6

Currently, Hirudo medicinalis and Hirudo verbena are the most frequently used leech species for hirudotherapy. There are more than 100 bioactive materials found in leech saliva that work synergistically, including anti-inflammatory, bacteriostatic, analgesic, anesthetic, and anticoagulant compounds,² the most common of which is hirudin.¹ Once they pierce the skin, the leeches inject these bioactive materials and draw ∼5–15 mL of blood.⁷ Because of a histamine-like substance that acts as a local anesthetic found in the saliva of leeches, the process is pain free.³ Often, during the postattachment period, additional oozing of blood may be noted.

Although the use of medicinal leeches has been well studied in human medicine, there are still few reported uses of medicinal leeching in veterinary medicine. To date, there are only two reported clinical cases in veterinary medicine describing its use. One case documented a favorable outcome with medicinal leeching in a 3 yr old female spayed domestic shorthair for treatment of polycythemia vera.⁸ Another case showed success in treating venous stasis secondary to a constrictive wound in a 1 yr old male castrated domestic shorthair.³ Both patients significantly improved with medicinal leeching and the cats tolerated the procedures well, without evidence of pain or discomfort. There were no reported complications or adverse effects reported in either case. A recent review described the pathophysiology involved in leeching in dogs, cats, and horses for hip and elbow dysplasia; acute and chronic arthritis; diseases associated with inflammation of tendons, ligaments, and fascia; diseases of the vertebrae; and the treatment of scars.⁷

There are limited clinical data on medicinal leech therapy (MLT) in animals, but the vast spectrum of its applications and the favorable outcomes shown with its use in human medicine make it a promising treatment modality worthy of further study and exploration in veterinary medicine. Our objectives were to describe the indications, outcomes, complications, and utility of MLT in dogs and cats and to propose data to be collected for future medicinal leech therapy studies in veterinary medicine. We hypothesized that MLT is a valuable and efficacious tool to achieve complete healing of venous congestion and necrosis in compromised skin flaps and wounds.

Materials and Methods

A retrospective review of medical records for patients who underwent their first MLT treatments from January 7, 2012, to October 13, 2016, at one institution was performed. Data for all patients who received axial pattern flaps and all patients treated with MLT were identified through the Surgery Department and Financial Department databases. MLT patient data collected included age at first MLT, species, breed, sex, reason for original surgery or bandage, type of axial pattern flap or bandage, intraoperative complications, postoperative complications and time to postoperative complications, histopathology and culture results, pre-MLT mucous membrane capillary refill time (CRT), pre-MLT pack cell volume (PCV) or hematocrit (HCT), pre-MLT antibiotics, appearance and temperature of tissue before MLT, time to MLT after original surgery, number of leeching sessions, number of leeches used, length of leeching time, and number of days between leechings. Outcomes, including patient tolerance, post-MLT mucous membrane CRT, post-MLT CRT or HCT, post-MLT antibiotics, post-MLT appearance and temperature of tissue, complications with MLT, need for blood transfusion, use of bandage after MLT, need for revision surgery after MLT, and time to complete healing from last MLT, were recorded. Leeches of the H medicinalis species were used for MLT in all patients, and all leeches used in this study were purchased from Leeches U.S.A. LTD.

Before leeching, the affected skin/limb was prepared using chlorhexidine scrub followed by saline. After all soap residue was adequately removed, the areas surrounding the lesions were covered with 4 × 4 inch gauze or clear occlusive dressings to prevent leech migration. The number of leeches used was determined by the size of the lesion (one leech per 2 cm² area)⁴ and varied among patients. The leeches were placed over the attachment sites using nonpenetrating forceps and encouraged to latch by pricking the skin with a needle or applying a small amount of D5W over the affected area, if reluctant to feed.⁹ Leeching was carefully monitored to ensure that leech migration to healthy tissues or open wounds did not occur. Spontaneous detachment of leeches occurred after becoming fully engorged. Leeches were immersed in a cup of 70% ethanol (secured with a lid) for elimination after detachment and were never reused. Soft-padded bandages were applied in some cases because of continued passive bleeding. MLT frequency was determined by the primary clinician. Each MLT session was continued until there was visual improvement of venous congestion (skin color and swelling). Following MLT, PCV and total protein were recorded for some patients. All patients were treated with prophylactic antibiotics during and after MLT, as indicated for all patients undergoing MLT.^3,9,10 Antibiotic medications included amoxicillin-clavulanic acid, marbofloxacin, ampicillin-sulbactam, cefazolin, cefpodoxime, cephalexin, metronidazole, and ofloxacin ophthalmic solution.

Results

During the study period, 12 total patients were treated with MLT for venous congestion. Eight of the 12 MLT patients (67%) had venous congestion secondary to skin flaps, and 4 of the 12 MLT patients (33%) had venous congestion caused by constrictive bandages. Twenty-one hospital patients during that time period underwent reconstructive surgery with skin flaps, of whom 38% (n = 8) were treated with MLT.

Patient population consisted of nine dogs (75%) and three cats (25%). Six dogs (67%) were spayed females, two dogs (22%) were castrated males, and one dog (11%) was an intact female. Two cats (67%) were castrated males and one cat (33%) was a spayed female. Age at first MLT for all patients ranged from 1 to 9 yr with a mean of 6.7 yr. Age at first MLT for dogs ranged from 2 to 9 yr with a mean of 7 yr. Age at first MLT for cats ranged from 1 to 9 yr with a mean of 3.9 yr. Each patient’s breed was unique, with dog breeds including terrier mix, shepherd mix, bullmastiff, Boston terrier, smooth-coated Chihuahua, German shepherd, Pembroke Welsh corgi, Chihuahua mix, and boxer terrier and cat breeds including domestic shorthair, domestic longhair, and Maine coon.

The eight anatomic regions reconstructed with skin flaps included lateral elbow (n = 1), distal humerus (n = 1), crus (n =1), scrotum and inguinal area (n = 1), inferior eyelid (n = 1), mammary gland (n = 1), shoulder (n = 1), and entire eye (n = 1). Types of skin flaps used included thoracodorsal axial pattern (n = 2), axillary fold rotational (n = 1), caudal superficial epigastric axial pattern (n = 2), temporal axial pattern (n = 1), inguinal rotational (n = 1), and caudal auricular axial pattern (n = 1). Flaps were used for mast cell tumors (n =2), squamous cell carcinoma (n =1), soft tissue sarcomas (n =3), scar revision (n =1), and eyelid mass (n =1).

Four MLT patients had venous congestion caused by constrictive bandages. Anatomic regions bandaged were antebrachium (n = 1), distal pelvic limb (n = 1), crus (n = 1), and tarsus (n = 1). Bandages were initially placed for fractures (n = 2) and necrotic wounds (n = 2). Types of bandages used were wet to dry modified Robert-Jones (n = 1), debridement bandage using sodium chloride dressing and Manuka honey (n = 1), modified Robert-Jones (n = 1), and lateral splint (n = 1).

Intraoperative complications with skin flaps were reported in none of the patients. Time to postoperative complications for dogs was reported in six patients and ranged from 0 to 17 days with a mean of 3.3 days. Postoperative complications with flaps were venous congestion, edema, and necrosis of the flap. Complications with bandages included full-or partial-thickness constrictive lacerations with necrosis and edema. One patient already had a necrotic wound on initial presentation resulting from a bandage placed previously at another hospital.

Histopathology results were available for six patients and included mast cell tumor (n = 2), nerve sheath sarcoma (n = 1), other soft tissue sarcoma (n = 1), histiocytic proliferation suggestive of a reactive (systemic) histiocytosis (n = 1), and squamous cell carcinoma (n = 1). Culture results of wounds formed secondary to constrictive bandages were available for two patients and revealed multiple organisms in each patient, including Proteus mirabilis (n = 1), Staphylococcus pseudintermedius (n = 1), beta-hemolytic Streptococci (n = 2), and Staphylococcus aureus (n = 1). Ten patients (83%), including seven dogs (78%) and three cats (100%), were being treated with antibiotic medications before MLT. Seven patients (58%) were treated with one antibiotic medication before MLT, and three patients (25%) were treated with a combination of two antibiotic medications before MLT. The most common antibiotic used was amoxicillin-clavulanic acid (n = 5). Other antibiotic medications included marbofloxacin (n = 2), ampicillin-sulbactam (n = 1), cefazolin (n = 1), cefpodoxime (n = 1), cephalexin (n = 1), metronidazole (n = 1), and ofloxacin ophthalmic solution (n = 1). There was a significant indirect relationship between the time elapsed from the original surgery or bandage placement to the first MLT session in dogs and incidence of administration of antibiotic medications before MLT (P = .0404), indicating that patients who were being treated with antibiotics were likely to have their first MLT sessions sooner than patients who were not being treated with antibiotics. The average time from the original surgery/bandage to first MLT for dogs treated with antibiotic medications was 4 days, compared with 8.5 days for dogs who did not receive antibiotic treatment before MLT.

Before MLT, PCV or HCT was reported in six patients and ranged from 28 to 50% with a mean of 43%. Mucous membrane CRT before MLT was available in nine patients (75%) and was equal to 1 second in all patients. Affected tissue (congested or necrotic) before MLT appeared swollen, purple, black, or white in all patients. Affected tissue of one patient (8%) was reported to feel warm on palpation, and affected tissue of one patient (8%) was reported to feel cold on palpation. Pre-MLT tissue temperature was not reported in 10 patients (83%).

Number of MLT sessions in dogs ranged from one session to five sessions with a median of two sessions. Number of MLT sessions in cats ranged from two sessions to four sessions with a median of two sessions. Time to first MLT session from the original surgery or bandage in all patients ranged from 1 day to 29 days with a median of 1 day. Two days elapsed between the first and second MLT sessions of one patient. For all other patients treated with multiple MLT sessions, leechings were performed 1 day apart. The number of leeches used for MLT in dogs was recorded for 12 MLT sessions in six patients and ranged from one leech to four leeches with a mean of 2.6 leeches. The average number of leeches used for MLT in cats was recorded for seven MLT sessions in three patients and ranged from one leech to two leeches with an overall mean of 1.33 leeches. Total time of leeching was reported for three MLT sessions and ranged from 1.5 hr to 3 hr with a mean of 2.2 hr. Four patients (33%) were noted to tolerate MLT well and without resistance. Patient tolerance was not recorded for eight patients (67%), but there were no records of sedation medications administered to these patients during hospitalization.

There were no complications associated with MLT in 10 patients (83%). One patient (8%) was noted to have alopecia and hyperpigmentation 1 day after the first MLT session and an eschar of the distal 1/3 of the original skin flap 1 day after the fourth MLT session, which detached naturally (was not debrided) and developed healthy granulation tissue 16 days later. One patient (8%) developed an eschar of the original lesion, which was debrided and subsequently healed without complication. Blood transfusions were not required by any patients.

Affected tissue of one patient (8%) was noted to feel warm after the first MLT and the distal 20% of the flap felt cool on palpation after the third and fourth MLT. Affected tissue of one patient (8%), which was noted to feel cold on palpation before MLT, continued to feel cold on palpation after MLT. Post-MLT tissue temperature was not recorded in the remaining 10 patients (83%).

Following MLT sessions, nine patients (75%), including six dogs (67%) and three cats (100%), visibly showed clear improvement of the affected tissue (improvement in skin color from dusky purple to normal flesh color and resolution of swelling or deformation of the skin) and healed completely. Improvement or appearance of tissue following MLT was not recorded in two patients (17%). The patient (8%) whose affected tissue was noted to feel cold on palpation before MLT did not improve with MLT treatment.

The PCV of four patients (33%) was recorded 1 day after MLT and ranged from 23 to 44% with a mean of 35%. These PCV were all lower than they had measured before MLT. Difference in PCV from before MLT to after MLT ranged from 3 to 16% with a mean of 7.5%. Mucous membrane CRT in all 12 patients (100%) was 1 second following MLT. Bandages were placed in three patients (25%) after MLT because of residual oozing.

Twelve patients (100%) were treated with prophylactic antibiotic medications, which were continued during and following MLT as recommended for all patients undergoing MLT. Six patients (50%) were treated with one antibiotic medication following MLT, and six patients (50%) were treated with a combination of two antibiotic medications following MLT. The most common antibiotic used was amoxicillin-clavulanic acid (n = 5). Other antibiotic medications included enrofloxacin (n = 3), marbofloxacin (n = 3), ampicillin (n = 1), ampicillin-sulbactam (n = 1), cefpodoxime (n = 1), metronidazole (n = 1), pradofloxacin (n = 1), topical neomycin-polymyxin-bacitracin (n = 1), and ofloxacin ophthalmic solution (n = 1). Three patients (25%), including two dogs (22%) and one cat (33%), required revision surgeries (wound closure, wound debridement with VAC placement, and wound debridement). All three patients were being treated with MLT for venous congestion secondary to constrictive bandages. One dog who required revision surgery did not achieve complete healing, whereas all dogs who did not require revision surgery achieved complete healing. However, the cat who required revision surgery and the two cats who did not require revision surgery all achieved complete healing. Furthermore, there was a significant relationship between sex and the need for revision surgery in dogs (P = .0472), with intact female dogs having an increased occurrence of revision surgery. None of the patients in the present study developed obvious clinical signs associated with infection after MLT.

Time to complete healing was recorded for nine patients (75%) and ranged from 14 days to 120 days with a mean of 41 days. Time to complete healing in dogs ranged from 14 days to 42 days with a mean of 26.8 days. Time to complete healing in cats ranged from 36 days to 120 days with a mean of 69.7 days. One dog with a necrotic wound (8%) did not show improvement with MLT and was euthanized before complete healing owing to pulmonary parenchymal disease. Two dogs (17%) did not return to the hospital for final recheck evaluations. A significant direct relationship between the number of MLT sessions and time to complete healing was found in dogs (P = .0388), indicating that as the number of MLT sessions increased, there was increased time to complete healing.

Discussion

The high rate of complications associated with microvascular and reconstructive surgery has been well documented in both the human and veterinary medical fields.^11–14 Although the utility of MLT in treating questionably viable skin flaps and reimplantations has also been well documented in human medicine,^5,6,13–15 the MLT literature in veterinary medicine is lacking. This is the first retrospective study of MLT in veterinary medicine to the authors’ knowledge. Our results indicate that MLT may be a useful and effective treatment modality for venous congestion and necrosis in compromised skin flaps and wounds with success in resolving 75% of the lesions in this study. Our study is suggestive of the value of MLT not only in dogs and cats who have undergone skin flaps but also for treatment of wounds in which the skin perfusion has been compromised for other reasons.

Although arterial blood supply is crucial in providing nutrients to meet the metabolic demands of tissues, appropriate venous return is equally pivotal to tissue survival. With a mismatch between arterial inflow and venous outflow, venous congestion results in venous occlusion and failure of small veins due to their thin walls and low capacitance. This obstruction causes hypoxia, acidosis, microcirculatory thrombosis, platelet trapping, stasis, and ultimately flap necrosis, which may occur in as little as 3 hr.¹⁶ One study found flap necrosis in 15% of cats and 46% of dogs treated with axial pattern skin flaps, which required surgical debridement and chronic wet to dry dressings for further debridement and healing by second intention.¹ In a study of 10 dogs treated with axial pattern flaps, partial flap necrosis occurred in 7 dogs, of whom 6 required additional surgical management.¹⁷ In this cohort, long-term follow-up was available for six patients at an average of 49.7 mo postoperatively, at which time two dogs had complete flap survival and four dogs had distal flap necrosis.¹⁷ By removing venous blood, medicinal leeches establish temporary venous outflow and allow for passive decongestion, reducing capillary filling pressure. This gives damaged veins time to recover and capillary beds to reperfuse, resulting in neovascularization and ultimately shorter times to complete healing.

Studies in human medicine have shown high rates of success in salvaging flaps using MLT. In a review of 277 clinical cases a 77.98% success rate was reported following leech therapy and 22.02% of tissues were deemed unsalvageable, requiring excision.⁵ In another retrospective study, which evaluated the records of 39 patients treated with MLT, the total salvage rate was 90.9% and partial salvage rate was 9.1% for native skin and local flaps.⁶ A total salvage rate of 33.3%, partial salvage rate of 33.3%, and total loss rate of 33.3% was reported for regional and free flaps.⁶ Other retrospective reviews reported 100,¹³ 62.5,¹⁵ and 60.5%¹⁴ total salvage rates after MLT. Our study showed definitive improvement in 75% of patients and failure in 8%; however, 17% of patient records were lacking efficacy data of MLT.

As expected, we found a significant direct relationship between the average number of MLT sessions and time to complete healing. This finding is not surprising, as dogs with more severely compromised skin flaps and more necrotic wounds required increased numbers of MLT sessions to improve microcirculation and achieve complete healing. Thus, the need for additional leeching sessions lengthened the time required for the skin flaps and wounds to heal.

All dogs who did not require a revision surgery successfully achieved complete healing, whereas one dog with a more severely necrotic wound who required a revision surgery did not have successful healing of the wound. Due to the decreased vascular supply to the compromised wound, the association between revision surgery and complete healing is logical. However, all cats, including the cat who required revision surgery, achieved complete healing. Although the numbers in cats are too low to make definitive recommendations, this is a promising observation.

Our study found that dogs who were treated with antibiotic medications for their lesions before MLT experienced significantly decreased times from the original surgery or bandage to the first MLT session. The average time for dogs treated with antibiotic medications before MLT was 4 days, compared with 8.5 days for dogs who did not receive antibiotic treatment before MLT. Evidence of infection, increased risk for development of infection, and other indications for treatment of wounds with antibiotic medications before MLT may have compromised healing in those patients, thus increasing the risk for necrosis and venous congestion and, consequently, the need for MLT.

Female intact dogs had a significantly higher rate of revision surgeries in this study. Although interesting, the association between sex and indication for revision surgery is difficult to evaluate owing to the small sample size of the population. Contrary to our results, one veterinary study recently reported improved healing of wounds in intact female beagles compared with intact male beagles.¹⁸ A strong correlation between sex and healing ability has not been previously studied and the pathophysiology behind it has not been elucidated in veterinary medicine, but it may be due to the effects of circulating hormones on the healing process. Studies in humans have implicated estrogen as a major contributor to the regulation of age-associated delay in wound healing.¹⁹ Contrary to the results of our study, estrogen has been found to improve healing in older people, whereas androgens have been found to impair wound healing.²⁰

Despite large numbers of human patients—49.75% in one study⁵—requiring blood transfusions following MLT, none of the patients in the current study required blood transfusions. Furthermore, although all four patients whose PCV was recorded following MLT had decreased PCVs after MLT relative to before MLT, none of these patients were clinically affected and none of these patients show clinical signs of anemia (pale mucous membranes, tachycardia, or hypotension).

The primary limitations of this study are due to its retrospective nature and small sample size. Incomplete case data essential to retrospective review contributed to difficulty in making accurate comparisons. A number of records did not document the CRT of affected tissue before and after MLT, appearance and temperature of affected tissue before and after each MLT session, PCV or HCT before or after MLT, flap or wound size, number of leeches used, leeching time, success or failure with leech attachment, and patient tolerance. Furthermore, the need to rely on subjective analysis for outcomes of MLT treatment may have resulted in inconsistencies. Nevertheless, this study provides a solid foundation upon which future prospective studies may build to further evaluate the use of MLT in veterinary medicine.

In addition to PCV or HCT, coagulation panel results, and appearance of the tissue, data often collected with MLT treatment in people include CRT, glucose levels, and lactate levels of the affected tissue. Willingness or failure of leeches to feed, body position, room temperature, and puncture of the tissue with a needle are also recorded. Failure of leeches to feed has been shown to be a poor prognostic indicator for flap survival in people.²¹ Temperature of the tissue below 30°C has been shown to indicate complications with arterial or venous circulation.⁹ Therefore, the authors propose that veterinarians record similar data when performing medicinal leech therapy to use for future MLT studies. Additional application of this information includes aggregation of the data to determine prognostic indicators for salvage of flaps and wounds with MLT treatment. The authors have created a data collection form (Supplementary Appendix) to be used by veterinary clinicians with the goal of obtaining standardized, objective MLT data to use for future studies. Although the results of this study are exciting and hold promise for the future of MLT as a treatment modality in dogs and cats, prospective MLT studies using the proposed information are needed to obtain more complete and accurate data and to perform more precise assessments of indications, outcomes, complications, and prognoses with MLT use in veterinary medicine.

Conclusion

Medicinal leeching may be an effective and viable treatment for venous congestion and necrosis in compromised skin flaps and wounds and incurs minimal risk when appropriate protocols are followed. Medicinal leeches may be purchased easily online or via telephone at low costs from specialized leech breeding farms and can be shipped overnight for immediate use. Moreover, leeches may be stored in the hospital for extended periods of time, depending on storage conditions, with life spans of up to 10 yr. When stored in the hospital, leeches should be kept in cool, distilled water within lidded containers in the dark, and Hirudosalt should be added during daily water changes. The successes of MLT in the treatment of compromised skin flaps and wounds has been well documented in the human medical field for thousands of years, and this study is suggestive of the value of MLT when more conventional treatment methods fail in dogs and cats.