Administration safety of medical-grade honey (MGH) in septic synovial structures in horses: 3 cases

Abstract

The objective of this study was to investigate the postoperative use of intrasynovial honey as an antimicrobial after treatment for synovial sepsis in horses. One colt and 2 mares were presented with acute lameness, with or without an associated wound. All 3 cases were initially managed with surgical endoscopic or tenoscopic debridement and lavage for treatment of different synovial structures. Collection of synovial fluid was consistent with synovial sepsis and this was diagnosed in each case. All horses subsequently underwent arthroscopic lavage under general anesthetic and intraarticular or intrathecal medical-grade honey (MGH) was then instilled. All 3 cases recovered well and were free from lameness at all gaits. Although there is extensive research about the antimicrobial properties of honey and growing interest in the biocompatibility of honey in joints with the use of honey hydrogels in human medicine, the research in veterinary medicine is lacking. There are studies describing the antimicrobial properties of honey in healing wounds in horses, but there are no published studies describing the use of honey within a synovial structure. Further research is necessary to assess the biocompatibility of honey in equine articular cartilage. In the cases described in this article, the use of honey demonstrated a safe adjunctive therapy after conventional surgical treatment for septic arthritis.

Introduction

Honey has been widely used for medicinal purposes throughout history. Its documented use began with the ancient Egyptians who used honey to treat wounds and diseases of the intestine, as well as for embalming the dead (1). Since the emergence of antibiotics, the use of honey has decreased in veterinary medicine. With the emergence of antibiotic resistance, however, interest in the antimicrobial properties of honey has redeveloped (2).

As well as having antimicrobial properties, honey has also been shown to influence inflammation, local immunity, wound debridement, stimulation of tissue growth, and antioxidant activity (2). The main mechanisms by which honey acts as a broad-spectrum antimicrobial agent is through the release of hydrogen peroxide and its high osmolarity, which causes bacterial desiccation (3).

One particular area of research into the non-antibiotic properties of honey has shown potentially beneficial chondroprotective activity (4). Studies have also shown that honey has a high cytocompatibility in human joints (5). These properties are the focus of current studies to determine the possible role of honey in treating a range of cartilage injuries and arthritis. A few studies investigating the potential applications of manuka honey in veterinary medicine have largely focused on secondary intention healing of equine distal limb wounds (6–8). Another study by Mandel et al (9) recorded no adverse effects of the use of honey in wounds and showed that lacerations treated with honey were more likely to completely heal, as well as displaying less evidence of wound infection. Gustaffson et al (10) applied honey to the linea alba after exploratory laparotomy as a prophylactic measure and showed that it may significantly decrease the incidence of surgical site infections after colic surgery.

With this series of case reports, we documented the immediate postoperative introduction of intrasynovial honey following treatment for synovial sepsis. Clinical cases described include joints and tendon sheaths of varying duration. No associated adverse effects were reported, and all horses recovered from their injuries and survived long-term.

Case descriptions

Case 1

An 11-year-old palomino Welsh pony show mare (section B) was referred after progressively becoming non-weight bearing lame on the right hind leg over 48 h, with effusion of the digital flexor tendon sheath (DFTS). Serohemorrhagic synovial fluid was aspirated aseptically, with a total protein (TP) of 48 g/L and a white blood cell (WBC) count of 9.1 × 10⁹/L.

After premedication with procaine penicillin (Depocillin; Intervet, Milton Keynes, UK), 15 mg/kg body weight (BW) IM; gentamicin (Genta-Equine; Dechra, Lostock Gralam, Northwich, UK), 6.6 mg/kg BW, IV; and flunixin meglumine (Meflosyl; Zoetis, Parsippany, New Jersey, USA), 1.1 mg/kg BW, IV and sedation with acepromazine (Calmivet; Vétoquinol, Towcester, UK), 0.05 mg/kg BW, IV, and romifidine (Sedivet; Boehringer Ingelheim, Bracknell, UK), 0.120 mg/kg BW, IV. The pony was induced with a combination of ketamine (Ketavet; Zoetis), 2.2 mg/kg BW, IV and Diazepam Injection (Hameln, Gloucester, UK), 0.02 mg/kg BW, IV and positioned in left lateral recumbency.

General anesthesia was maintained with isofluorane (Isofluorane-Vet; Merial, Bracknell, UK) in oxygen and air in a semi-closed ventilating system. The right hind limb from the coronary band to proximal metatarsus was prepared aseptically with chlorhexidine (Hibiscrub; GlucoRx, Guildford, Surrey, UK). An Esmarch tourniquet was applied proximally to the metatarsus. Tenoscopy was carried out on the right hind digital flexor tendon sheath, as per Wilderjans et al (11). Routine diagnostic examination of the sheath showed inflammation and fibrin to be present. A sample of the fibrin was taken for culture and sensitivity and as much of this as possible was grossly removed using Ferris Smith rongeurs, a synovial shaver, and a curette. A total of 15 L of sterile saline was used.

All the incisions were closed with Novafil 2m (Polybutester monofilament, uncoated), leaving 1 portal with the egress cannula still in place. Manuka honey (C-vet; Covetrus, Dumfries, Scotland), 10 mL and 200 mg of amikacin (Amikin; Bristol-Myers Squibb, Denham, Uxbridge, UK) was placed in the sheath via the egress cannula before removing the cannula and suturing the portal. A double-layer halflimb bandage was applied for recovery. Anesthesia time was 100 min and surgical time was 65 min. The mare recovered uneventfully from anesthesia.

As the culture of samples taken before and during surgery yielded no bacterial growth, a sensitivity profile was not obtained. The mare was maintained on procaine penicillin (Depocillin; Intervet), 15 mg/kg BW, IM, q24h and gentamicin (Genta-Equine; Dechra), 6.6 mg/kg BW, IV, q12h for 5 d. She received phenylbutazone (Chanazone; Chanelle, Galway, Ireland), 2 g PO, q24h for 48 h.

Her bandage was changed on days 2 and 5. She remained sound at the walk throughout her 5 d of hospitalization prior to discharge. She had further bandage changes at home and the sutures were removed 10 d later. The mare was comfortable at all gaits and was fully back at work 9 mo later, when she qualified for the Welsh National Championships.

Case 2

A 6-month-old Thoroughbred colt sustained a puncture wound of less than 24 h duration on the dorsolateral aspect of the right carpus over the radiocarpal joint. Radiographs of the carpus showed no obvious osseous abnormalities. Premedication, sedation, induction, and maintenance of general anesthesia were the same as in Case 1.

The foal was placed in dorsal recumbency, with the right front limb supported at 120° in carpal flexion. The radiocarpal joint was tapped dorsally between the common digital extensor (CDE) and extensor carpi radialis (ECR) tendons: turbid yellow synovial fluid was obtained, with a total protein of 58 g/L, indicative of synovial sepsis.

Samples were submitted for culture and sensitivity testing. The joint was distended and fluid came out from the main wound. A routine dorsal arthroscopic approach to the radiocarpal joint was used for diagnostic assessment, debridement, and lavage (12). The interior of the radiocarpal joint was lavaged and modest quantities of fibrin removed, as in Case 1. The CDE and ECR tendon sheaths were also lavaged using a blunt cannula introduced through the wound.

After wound and endoscopy portal stitch closure of the wound and endoscopy as in Case 1, 10 mL of Manuka honey (C-vet; Covetrus) and 200 mg of amikacin (Amikin; Bristol-Myers Squibb) were instilled into the radiocarpal joint via the egress cannula, before removing the cannula and suturing the portal. A single-layer fulllimb bandage was applied before recovery. Anesthesia time was 100 min and surgical time was 55 min.

The postoperative antibiotic regime was the same as in Case 1. No bacterial growth developed from the culture plates. The bandage was changed on days 2 and 5 and the colt was discharged after 5 d. At follow-up 18 mo after surgery, the colt was reported to be free of lameness at all gaits.

Case 3

An 11-year-old Warmblood mare was referred for a 7-cm laceration wound on the distal lateral aspect of the right tarsus sustained 4 h earlier, overlying the tarsometatarsal (TMT) joint. A second smaller wound was present on the medial aspect close to the chestnut. The mare was grade 3/5 walking lame [American Association of Equine Practioners (AAEP)] on arrival. Four standard-orthogonal weight-bearing radiographs were obtained, revealing an open and displaced comminuted articular fracture of the head of the fourth metatarsal bone (Figure 1). These bone fragements were palpable digitally during cleaning.

Figure 1.

Clinical image of a dorsolateral plantaromedial oblique view of the right tarsus, with an open and displaced, comminuted articular fracture of the head of the fourth metatarsal bone.

Premedication, sedation, induction, and maintenance were as described in Case 1. The mare was placed in dorsal recumbency; the right hind limb was supported in 10° flexion and aseptically prepared from mid-tibia to mid-metatarsus. The lateral wound was extended a further 4 cm plantar and proximal, allowing the fragmented head of the fourth metatarsal bone to be removed. A swab of the deep tissues in this area was obtained for bacterial sensitivity testing.

The wound was cleaned and debrided with a combination of sharp dissection and curettage, while the visible TMT joint was lavaged using a 14G needle with sterile saline. The medial wound was also explored and found to communicate with the tarsal sheath. Two portals were created into the tarsal sheath, proximally and distally, as described by McIlwraith et al (12), allowing lavage with egress via the wound. A total of 15 L of sterile saline solution was used to lavage both synovial structures; 5 L for the TMT/lateral wound and 10 L for the tarsal sheath. Both wounds were sutured and the synovial structures (TMT and tarsal sheath) were medicated with 5 mL of sterile Manuka honey via the egress cannula. A full limb, double-layer bandage was applied for recovery. Anesthesia time was 85 min and surgical time was 55 min.

The postoperative antibiotics regime was the same as in Case 1, except that only a 3-day course was completed due to economic concerns and sensitivity test results. Bacterial culture yielded a profuse growth of a mixed group of bacteria with variable resistance to all the common antibiotics, with the exception of enrofloxacin. The mare was consequently switched to a 5-day course of oral enrofloxacin (Enrotron; Livisto) at 10 mg/kg BW once per day to go home. Comfort remained excellent postoperatively and the mare returned to normal use and work and remained sound at follow-up 2 y later.

Discussion

Bacterial contamination of a synovial structure quickly leads to synovial bacterial colonization and septic synovitis, which can be life-threatening to horses (13). Medicating a synovial structure with medical-grade honey intraoperatively sometimes necessitated gently warming the honey to dissolve the sugar crystals before injecting. Otherwise, it was an easy and rapid procedure that did not appear to have any adverse effects in the 3 horses described.

Antibiotic resistance, which is a major issue in the 21st century, is responsible for increased morbidity, treatment costs, and mortality rates in human medicine (14). Similarly, antibiotic resistance is a growing problem in the equine industry and the use of alternative antimicrobial substances, such as honey, as an adjunctive treatment may help to reduce the rate of acquired resistance.

Cooper et al (15) exposed 4 clinical isolates (Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and S. epidermis) to sub-lethal concentrations of Manuka honey for up to 28 d. No honey-resistant mutants developed. These types of bacteria are commonly identified on horse’s skin. For example, in a study at a UK veterinary referral hospital, a single culture of Gram-positive bacteria was the most frequent isolate (75%) from synovial sepsis, predominantly secondary to a wound, led by hemolytic Staphylococcus spp. (16). As well as extensive research into the antimicrobial properties of honey, an increasing interest has developed in the human literature in evaluating the chondroprotective effects and cytocompatibility of honey in the joint environment. It was confirmed that chrysin, a natural flavonoid extracted from honey, attenuates NLRP3 inflammasome signalling, reducing synovitis and the release of interleukin 1 beta (IL-1β), IL-18, substance p, and calcitonin gene-related peptide in a monosodium iodoacetate (MIA)-induced knee osteoarthritis model in rats (5).

Hu et al (4) demonstrated that quercetin suppresses inflammation by modulating polarization of synovial macrophages and inducing the expression of growth factors such as transforming growth factor beta (TGF-β) and insulin-like growth factor (IGF), which promote chondrogenesis. The chondroprotective effect was also observed in vivo, using intraarticular administration of quercetin.

Bonifacio et al (17) prepared a composite scaffold based on gellan gum, antibacterial Manuka honey, and an inorganic clay and highlighted their positive impact, which included significantly improving the scaffold’s cytocompatibility, mechanical performances, and morphological features. This composite scaffold was further investigated in co-culture, where it preserved cell proliferation over bacterial growth within the joint model.

In veterinary medicine, Bischofberger et al (8) investigated the effect of Manuka honey on the concentrations of TGF-β-1 and TGF-β-3 and reported that honey did not make a significant difference on the TGF concentrations.

This series of 3 case reports shows that sterile manuka honey applied inside inflamed synovial cavities was safe and had no adverse effects in these 3 individual horses. Further research is warranted to determine the effectiveness of honey compared to other local/systemic antibiotic therapy, as well as conducting studies into the biocompatibility of honey and equine articular cartilage.