Topics / Surgery / Vascular

Summary This is a short summary of Diabetic Foot Sepsis. It describes the main mechanisms that are responsible for the development of the disease. These mechanisms include peripheral neuropathy, vascular disease, and infection. We also discuss the importance of the Polyol Metabolic Pathway and how it is responsible for causing cellular damage. Diabetic Foot Sepsis is classified using the Meggit-Wagner classification and this will further help with management of the patient.

Definition

Diabetic foot sepsis can be defined as an infected foot that has been affected by peripheral neuropathy and/or peripheral arterial disease of the lower limb in a patient with diabetes. The severity of the infection may vary from cellulitis to gangrene.

Basics

The main mechanisms involved in the development of diabetic foot sepsis include:

Peripheral Neuropathy
- Autonomic Neuropathy: There is a lower level of perfusion because of a lack of adequate capillary recruitment and there is also increased shunting of blood around the capillary bed. The sweat and oil glands are also affected and this results in dry skin that is prone to “cracking”.
- Sensory Neuropathy: Loss of peripheral sensation prevents the patient from responding adequately to a nociceptive stimulus. This means that minor injuries usually go unnoticed by the patient until they are severe.
- Motor Neuropathy: There is associated muscle weakness and foot deformity that affects the joints and pressure points. Glycosylation of tendons causes stiffening and shortening of several tendons which result in various deformities (claw toes, hammer toes). These deformities also cause changes in pressure points.
Vascular disease
- Macrovascular disease: Diabetic patients have accelerated atherosclerosis resulting in poor circulation and decreased wound healing.
- Microvascular disease: There are mainly two hypotheses: The “hemodynamic hypothesis” and the “capillary steal syndrome”. The hemodynamic hypothesis suggests that blood flow dysregulation results in structural alterations such as thickening of the basement membrane and microvascular sclerosis. In the capillary steal syndrome, as explained above, autonomic neuropathy affects the sympathetic innervation to the microvasculature and results in the shunting of blood away from the capillaries.
Infection
- Usually, start as an infection caused by Staphylococcus or Streptococcus but as the infection progresses it quickly becomes a polymicrobial infection. In the last two stages, there is a significant increase in gram-negative and anaerobic microorganisms. Diabetes impairs the immune system to fight any infection. It causes a decrease in leukocyte migration (polymorph), decreases in phagocytosis, decreases in intracellular killing, and a decrease in chemotaxis. Treating an infected diabetic foot with antibiotics is very difficult. This is because in many cases, the vascular supply to the area has been affected and it reduces the ability of the antibiotic to read the target site.

The Polyol Metabolic Pathway

The Polyol Metabolic Pathway Chances are that one day you will be asked how Diabetes causes all these health issues. If you mention that it is caused by the "Polyol Metabolic Pathway" that person will be very impressed with you. Sometimes, this pathway is referred to as the "Sorbitol" pathway. This pathway is responsible for most of the diabetic microvascular damage in the retina, kidneys, and nerves.

In Diabetes, there is an excess amount of glucose. This means that although some of the glucose is converted into energy, the excess will be shunted into the polyol pathway. In this pathway, glucose is reduced by aldose reductase into sorbitol (which may be further converted into Fructose). These reactions (Glucose -> Sorbitol) cause a depletion of NADPH and oxidized NAD+. NADPH is needed for the formation of myo-inositol which is required for the normal function of the nerves. NAPDH is also needed for the formation of nitric oxide which is a vasodilator and it is also needed to prevent the formation of Reactive Oxygen Species (ROS) and cellular damage. The accumulation of Sorbitol increases the formation of Advanced Glycation End-Products (AGEs). The increased amount of sorbitol that accumulates inside the cells also causes an osmotic influx of water.

Risk Factors

The following is a list of factors that increases the overall risk that the patient will develop Diabetic Foot Sepsis.

Charcot joint/Charcot arthropathy
Peripheral vascular disease
Microvascular Complications: Peripheral Neuropathy, Retinopathy or Nephropathy
Macrovascular Complications: History of cerebral vascular disease, Coronary Heart Disease
Diabetes Mellitus > 10 years
The use of insulin (means the diabetes is more severe or advanced), Poor glycemic control
Age > 45, Male Gender
Smoking, Hypertension, Overweight, Obesity

Charcot arthropathy It is characterized by progressive destruction of bone and soft tissues at weight-bearing joints. There are two theories: neurotraumatic and neurovascular. The autonomic neuropathy (leading to abnormal blood flow) results in an abnormal bone formation, and the sensory neuropathy results in a "numbed" joint that is susceptible to various forms of trauma.

Presentation

The patient may present with symptoms and sign suggestive of having neuropathy, vascular disease, infection (local or systemic), tissue loss, or a deformity. The patients may also present as an emergency in the form of sepsis or septic shock or from complications of Diabetes Mellitus such as DKA/HHS. Having performed the necessary questions and assessment, you should be able to grade the patient using Wagner’s Classification. Always remember that Diabetes is a disease that affects many organs and a thorough history and examination is required. Read how to approach an ulcer in order to learn more about what questions to ask and how to examine this patient.

Classification

Meggitt–Wagner’s Classification
Ulcer Grading	Description
Grade 0	No ulcer. Intact skin. But the foot is at high risk. Not infected. Any post-ulcerative lesion that has been completely epithelialized.
Grade 1	Superficial, full thickness ulcer which is limited to the dermis, not extending to the subcutaneous tissue. Not infected.
Grade 2	Deep ulcer, extending through the subcutaneous tissue with exposed tendons, ligaments, joint capsules, deep fascia or bone but no osteomyelitis or abscess formation. Cellulitis is included here.
Grade 3	Abscess, joint sepsis or bone involvement (osteomyelitis)
Grade 4	Localized gangrene of the toes or forefoot
Grade 5	Extensive Gangrene involving the whole foot

Investigations

Blood
- Formal Blood: Full Blood Count, Septic Screen, Urea and Electrolytes with Creatinine, HbA1C (assess glycaemic control over the last 3 months)
- Blood Gas: Metabolic acidosis, high sugar level, high lactate
Cultures
- Take a deep tissue culture as superficial colonization of the wound may not be representative. Send this wound swab or tissue biopsy for microscopy, culture, and sensitivity.
ECG
Imaging
- X-Rays of the affected limb: This is to rule out osteomyelitis, but one should remember that x-ray changes for osteomyelitis take around 4-6 weeks to develop.
- Dopper/Duplex Ultrasound to assess for flow.
- Angiography
- CT Scan of the affected limb: May assist with the identification of deep space abscesses or collections.
- MRI Scan of the affected limb: This may assist in the detection of osteomyelitis earlier if there is any suspicion.
Other:
- Transcutaneous Oxygen Measurement (TCOM): This is sometimes also known as “Transcutaneous Partial Pressure of Oxygen”. It is a non-invasive way of measuring the quantity of skin oxygenation. This is a measurement of the oxygen tension from around 1 to 2mm deep in the local skin capillaries. We place the probe next to an ulcer and this will help us predict wound healing and the patient’s possible response to hyperbaric oxygen therapy. For instance, the normal oxygen tension ranges from 50-70mmHg. An oxygen tension < 40mmHg will cause impairment of wound healing. Oxygen tension < 30mmHg classifies the patient as having Critical Limb Ischemia.

Management

All diabetic patients should have a specialized diabetic foot examination and ideally should also be seen by a podiatrist. These patients should be managed together with a multidisciplinary team. The surgical management of Diabetic Foot Sepsis depends on the Wagner Classification. It should be noted that many patients develop Diabetic Foot Sepsis on the contra-lateral limb within 20 months of amputation. This means that these patients should be extensively managed by the multidisciplinary team even after an amputation to prevent this from happening.

Grade 0:
- This foot requires treatment with prevention and prophylaxis
- Educate the patient
- Counsel on footwear
- Regular diabetic foot examination
Grade 1:
- Antibiotics
- Control of co-morbidities (eg glycaemic control)
- Pressure Relief: Accommodative footwear, total contact cast/splint, walking brace, crutches, wheelchairs
Grade 2:
- Surgical Debridement
- Wound dressing
- Antibiotics
- Control of co-morbidities (eg glycaemic control)
- Pressure Relief: once the wound heals to Grade 1
Grade 3:
- Surgical Debridement with some form of amputation may be required in some cases.
- Wound dressing
- Antibiotics
- Control of co-morbidities (eg glycaemic control)
- Pressure Relief: once the wound heals to Grade 1
Grade 4:
- Extensive debridement and amputation (two-stage amputation). The patient may benefit from revascularization procedures.
- Wound dressing
- Antibiotics
- Control of co-morbidities (eg glycaemic control)
Grade 5:
- Below knee amputation
- Wound dressing
- Antibiotics
- Control of co-morbidities (eg glycaemic control)

Prevention

All patients should be educated about good lifestyle modifications guided by the Diabetes Management Guidelines. This includes but is not limited to the cessation of smoking, cessation of ethanol use, encouraging weight loss, exercise, dietary modification, diabetic foot examination, protective foot wear, and diabetic foot care.