Efficacy of shellac,a natural product,for the prevention of wet gangrene

Introduction

The pathophysiology of gangrene in the diabetic foot is particularly complex and is influenced by interactions between arterial insufficiency, neuropathy, ulceration and infection.^1,2 Gangrene usually represents a late manifestation of peripheral limb ischaemia in patients with diabetes mellitus,^3,4 often requires amputation^4–6 and may result in death.^3,7 Gangrene caused by peripheral arterial disease (PAD) is commonly aseptic or noninfected and has a ‘dry’ appearance, whereas gangrene caused by bacterial infections or sepsis has a ‘wet’ appearance.^1,2 Dry gangrene is usually less severe than wet gangrene and may result in autoamputation (i.e. spontaneous detachment from the body and elimination of a gangrenous part), whereas wet gangrene may lead to cellulitis, loss of the extremity, septicaemia and death.^1,3

Diabetic ischaemic peripheral gangrene most commonly affects the toes/digits, feet and in some cases the entire leg. ² PAD in patients with diabetes involves macro- and microangiopathy components,^3,8 the management of which generally focuses on the major causative component. ¹ PAD in patients with diabetes usually affects the medium and small arteries throughout the lower limb, particularly those in the leg and foot, whereas diabetic microangiopathy affects arterioles in the skin. ³ Many patients with diabetes develop gangrene caused by occlusive PAD, which is not amenable to revascularization procedures.^9,10

In most cases, aseptic dry gangrenous tissue is left for full demarcation and subsequent autoamputation. ¹⁰ Surgical debridement and amputation are usually reserved for infected or septic wet gangrene. ¹ Wet gangrene can develop from dry gangrene, however, often as a result of primary infection in immunocompromised patients with diabetes. ³ Thus, every effort must be made to prevent the infection of dry gangrenous tissue and its resulting transformation to wet gangrene.

For many patients with peripheral gangrene caused by long occlusive infrapopliteal atherosclerotic lesions, which are not amenable to standard vascular/endovascular reconstructive procedures, physicians often take a conservative approach and allow autoamputation. ¹⁰ Geriatric, bed-ridden patients with several comorbidities and patients with a short life expectancy, particularly those on mechanical ventilation in intensive care units, may also require conservative management, with nonsurgical interventions.^5–7 Moreover, patients in certain cultures, particularly in Saudi Arabia, refuse amputations for religious or cultural reasons. ³ Other patients are temporarily contraindicated for any surgical intervention, including major amputations. ¹ In such cases, the attending physicians must endeavour to prevent the transformation of dry to wet gangrene, while awaiting improvements in the patient’s condition. ¹⁰

Shellac is natural polymer of animal origin derived from the hardened secretion of the lac insect, Laccifer (Tachardia) lacca (order Homoptera, family Coccidea). These are scaly insects that grow on specific trees in China, India, Burma, Thailand, Laos, Cambodia and Vietnam. The resin is secreted to cover the insect larvae.^11,12 Shellac is made up of aliphatic, aleuritic, shelloic, and jalaric alicyclic hydroxy acids and their polyesters. It is not water soluble, but is soluble in alcohol and alkaline solutions. ¹¹ Shellac is widely used in the food industry for sealing and glossing as it forms a natural superficial layer that coats and protects foods. It is also used in the pharmaceutical industry where it is often used, as an alternative to synthetic polymers, as an enteric coating for phytopharmaceuticals and food additives.^13,14 Shellac is commonly used at the authors’ institution to preserve and embalm dead animals and cadavers for teaching gross anatomy. The early results of using shellac as a nontoxic preservative for human embalming were promising. ¹¹

The present clinical study investigated, for the first time, the topical application of shellac, compared with standard treatment with povidone-iodine (PVP-I), for preventing the progression of dry gangrene to wet gangrene and extension of gangrene to adjacent healthy tissues, in selected patients with diabetes mellitus who were offered the nonsurgical option of waiting for autoamputation. It was assumed that topically applied shellac would work as a natural polymer film that would protect the superficial tissues, embalm dead tissues and prevent tissue infection in patients undergoing conservative treatment while awaiting autoamputation. It was hypothesized that this approach would reduce the amputation rate in patients with unreconstructable PAD, in those who refused amputation for cultural reasons, in those who were unsuitable for immediate amputation and/or were waiting for improvements in their condition to undergo revascularization, and in elderly bed-ridden patients with a short life expectancy, contraindicated for surgery.

Patients and methods

Results

A total of 26 patients were enrolled and randomized into the study; 13 received shellac and 13 received PVP-I (conventional) treatment. Three patients allocated to conventional treatment withdrew 3 weeks after enrolment. The remaining patients fulfilled one of the stated endpoints. An example of application of shellac in an 82-year-old diabetic male with end-stage renal disease and unreconstructable PAD, who refused surgical amputation, is shown in Figure 1.

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Figure 1.

Plantar (a) and lateral (b) views of the foot of an 82 year-old male with type 2 diabetes who refused surgical amputation. The patient had end-stage renal disease, unreconstructable PAD and had undergone coronary artery bypass grafting 7 years previously. The patient died 8 months after starting shellac use without undergoing major amputation (written consent was obtained from the patient and his son for photography of his lesions to be included).

The characteristics of patients in both groups are summarized in Table 1. All patients had type 2 diabetes (duration > 5 years), presented with dry gangrene of the foot and had evidence of neuropathy. The prevalence of ischaemia was similar in both groups, whereas prior infection was more common in the shellac group and trauma was common in the conventional treatment group. These differences were not statistically significant, indicating that the two groups were relatively comparable. The main indications for waiting for autoamputation were the presence of unreconstructable distal PAD in 16 patients (69.5%), refusal to undergo surgical amputation and/or poor general condition of the patient.

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Table 1.

Baseline characteristics and study outcomes at 12 months in diabetic patients with unreconstructable peripheral vascular disease (n = 23), randomized to receive treatment with topical shellac or antiseptic application of povidone-iodine solution (conventional treatment) on gangrenous areas of the foot.

Characteristic	All patients n = 23	Shellac group n = 13	Conventional treatment group n = 10
Baseline characteristics
Males/females	16/7	10/3	6/4
Age	65.9 ± 12.9	67.2 ± 12.8	64.8 ± 13.6
Evidence of prior infection	10 (43.5)	7 (53.8)	3 (30.0)
Evidence of ischaemia	16 (69.6)	9 (69.2)	7 (70.0)
Evidence of trauma	8 (34.8)	4 (30.8)	4 (40.0)
Study outcomes at 12 months
Died during the trial	4 (17.4)	3 (23.1)	1 (10.0)
Amputated	12 (52.2)	6 (46.2)	6 (60.0)
Toe(s)	6 (26.1)	3 (23.1)	3 (30.0)
Major	6 (26.1)	3 (23.1)	3 (30.0)
Alive without amputation at 1 year	10 (43.5)	4 (30.8)	3 (30.0)

The overall rate of amputation was 52.2%: six patients in each group lost parts of their extremities. All of those who underwent surgical amputation had evidence of spreading infection. The ratio of major to minor amputation was 1 : 1 and included: six digit autoamputations that did not require surgical excision and were considered positive outcomes; six major amputations with three above-knee amputations in the conventional group, and two above-knee and one below-knee amputations in the shellac group. The overall rate of surgical amputations was higher in the conventional treatment group than in the shellac group (60.0% versus 46.2%, respectively), although this difference was not statistically significant.

In the shellac group, three patients died during the study, compared with one patient death in the conventional treatment group. All patients died due to comorbidities that led to cardiorespiratory failure; none of these deaths were directly related to the patients’ lower extremity clinical condition. At the time of death, each patient had preserved extremities without undergoing surgical amputation. The remaining 19 patients (82.6%) were still alive at the 12-month follow-up visit and, of these, only six underwent major amputation (31.6%) (Table 1). None of the patients treated with shellac developed an allergic reaction.

Discussion

Patients with diabetes are at high risk of developing foot complications, which may lead to tissue loss or gangrene. In the authors’ clinical practice, a large proportion of patients present late with overt gangrene.^3,15 In these advanced cases, little can be done other than to provide the best available medical treatment, which includes antibiotic therapy ⁹ and treatment of any underlying macrovascular disease. The final option in these patients with diabetic foot disease is usually planned surgical amputation.^1,5,6,8,15 In patients with sterile dry gangrene, however, a nonsurgical option is to wait for autoamputation. ¹⁰ This approach is often welcomed by patients in certain cultures where amputation is not acceptable for cultural or religious reasons. Other patients may also be offered this relatively conservative approach – particularly those with gangrene caused by severe unreconstructable PAD involving the foot and digital arteries, including patients with diabetes on haemodialysis for end-stage renal disease.^5,7,9 Another group of patients who wait for autoamputation includes elderly bed-ridden patients with comorbidities that contraindicate open surgical vascular bypass or percutaneous endovascular procedures. ⁸ In some of these patients, immediate surgical amputation may substantially increase mortality, with perioperative mortality rates ranging from 7–17%.^3,7,15 It is also of concern that gangrene may persist in some patients with diabetes, critical limb ischaemia and end-stage renal disease, despite successful grafting of a patent vascular bypass.^5,7 Thus, preserving the gangrenous tissue and preventing infection represent transient and/or permanent objectives in managing these groups of patients. Conservative treatment in these cases usually involves topical application of antiseptic solutions, such as PVP-I, as used in the present study.

The present prospective, randomized,controlled, pilot study tested a natural complementary and alternative medicine, shellac, compared with a routinely used chemical antiseptic (PVP-I). This approach was based on the reported preferences of patients with diabetes for using complementary and alternative medicines in Saudi Arabia and in other countries.^16,17 Shellac is already patented for such indications in Turkey and is used as superficial protective film in the food and pharmaceutical industry.^12–14 Shellac is also used as an ingredient in edible fruit coatings to limit water loss and prevent desiccation and weight loss, and to prevent pathogen entry. Shellac forms a barrier that is fairly impermeable to oxygen and water, and reduces gas exchange. The reduction in oxygen levels reduces the respiration rate of fruits and vegetables and prolongs their shelf-life by delaying oxidative breakdown of tissue.^12,18 Although, the whole mechanism of the preservation process is not yet known, the authors believe that shellac provides distinct and substantial chemical properties for embalming in clinical situations, similar to the effects observed in the preservation of foods. Shellac is also used for embalming dead animals, and was used by the current research group as a nontoxic preservative for human embalming. ¹¹ Das and Jacob reported a heightened prevalence of allergic contact dermatitis in areas where cosmetics that included shellac were applied. ¹⁹ Such side-effects were not observed in the present study. The antibacterial effects of shellac were also suggested in a report discussing on the nonclinical application of shellac. ²⁰

Shellac was applied as a natural barrier in the present study to protect the underlying sterile gangrenous tissue in order to prevent desiccation and microbial infection. Unlike antiseptics commonly used in the management of gangrene, shellac exerts no antibacterial activity against bacteria commonly isolated from diabetic foot disorders. The results were encouraging, as shellac showed superiority over PVP-I solution in terms of a lower rate of surgical amputation, although this difference was not statistically significant.

There were some limitations to this preliminary study, including the small numbers of patients treated in both groups and the short duration of follow-up. These limitations indicate that a larger study, which follows patients for longer time periods, is required. Another limitation was that, unlike in cadaver embalming, shellac was used as a topical protective barrier and does not penetrate the deeper tissue. ¹¹ The authors are currently developing a pressure chamber to enable shellac to penetrate deeper tissue under air pressure.

In conclusion, shellac is a natural polymer solution that may be used to embalm gangrenous tissue in selected patients with diabetes who refuse amputation or who are offered a nonsurgical option to wait for autoamputation. It may also be used to embalm gangrenous tissue in patients with a limited life expectancy, as well as bed-ridden patients and patients contraindicated for surgical procedures. Shellac may reduce rates of surgical amputation compared with antiseptic preparations. Additional larger studies are needed, to determine the long-term outcomes and safety of shellac.