Diabetes is a global health crises, which has major economic
consequences for patients, their families, and society.
Over the past few decades there has been an alarming rise in the
prevalence of diabetes. The International Diabetes Federation (IDF)
Atlas reported that the number of people with diabetes was
approximately 366 million in 2011, and by the year 2030 this number
will rise to 552 million people. It also estimated that
approximately 80% of people with diabetes live in low and middle
income countries, which are designated as the developing economics
in the world.
The prevalence of diabetes in India is particularly noticeable,
since the number of people with diabetes in India is exceedingly
high compared to any other country in the world. Per the latest IDF
Atlas, there were more than 65 million people with diabetes in
India.
Among the complications from diabetes, foot complications are a
major cause of hospital admission for diabetic persons. The presence
of foot complications increases health care costs and poses a heavy
socioeconomic burden, both on patients and the nation. A majority of
diabetic patients develop foot ulcer, gangrene, and abscess during
the course of their illness, which may require long-term
hospitalization and amputation.
Diabetic foot problems can be caused by the following:
The foot is the most vulnerable part of body, susceptible to injury,
infections, and patient neglect.
The foot is the site of neuropathy and ischemia.
Foot infections are polymicrobial in nature, and to avoid
complications they must be appropriately diagnosed and treated.
Diabetic foot ulcer management is multifactorial and is based on a
comprehensive clinical examination and an understanding of the
underlying etiology.4,5 Common treatment options in patients with
diabetic foot ulcers include mechanical and surgical debridement,
pressure relief/off-loading, and the use of various dressings and
topical agents designed to facilitate wound closure and promote re-epithelialization.
Advanced care modalities for the treatment of diabetic foot ulcers
include the use of growth factors, bio-engineered tissues,
electrical stimulation, ultrasound therapy, negative pressure wound
therapy, and hyperbaric oxygen therapy.
Hyperbaric oxygen therapy (HBOT) is defined as breathing 100% oxygen
at pressures higher than normal atmospheric pressure at sea level in
a hyperbaric chamber. (1 ATM is 14.7 pounds per square inch (PSI), 1
kg per square centimeter, or 760 mm Hg.) Since oxygen has an
important role in the physiology of wound healing, HBOT is a useful
adjunct in the treatment of diabetic foot ulcers6,7 because it helps
increase tissue oxygen tensions to levels that promote wound
healing, limit edema, and destroy certain anaerobic bacteria.
The aim of the study was to assess the benefits of HBOT for treating
non-healing chronic diabetic ulcers.
The objectives were to assess the effect of:
HBOT on healing of diabetic foot ulcers
Total number of amputations
Total operative procedures
Curing of infection
Hospital length of stay
Materials And Methods
This was a prospective randomized control study that compared the
effect of chronic wound healing when treated with and without HBOT.
From July 2013 to October 2015, 100 diabetic subjects, consecutively
hospitalized in our diabetology unit for foot ulcer, underwent our
diagnostic and therapeutic protocol and evaluated for potential
inclusion in the investigation. In addition to receiving standard
medical assessment, each patient was evaluated to determine whether
HBOT was contraindicated. Diabetic patients were considered eligible
if they were at least 18 years old and if they had a foot wound that
was present for at least three months despite appropriate local
systemic wound care. All patients were assessed by a vascular
surgeon at the time of inclusion, and only patients with adequate
distal perfusion or non-reconstructable peripheral vascular disease
were included in the study.
All the patients were further evaluated to determine whether or not
they would be suitable candidates to undergo HBOT. After confirming
eligibility, the patients were randomly assigned to the standard
treatment group or the standard treatment plus HBOT group. We
assigned patients using a random number table and allocated them to
the treatment groups according to a predetermined sequence where
consecutively enrolled patients corresponding to an even random
number received standard treatment and those corresponding to an odd
random number received standard treatment plus HBOT. We continued
this process until we had 50 participants in each treatment group.
All patients gave their informed consent. One subject randomized for
HBOT refused the treatment, and one subject expired four days after
admission due to acute stroke.
One subject, randomized for the non-HBOT, died of myocardial
infarction three days after admission. All three subjects were
excluded from the analysis of the results. Of the subjects, 48
underwent HBOT and 49 did not.
Diagnostic and Therapeutic Protocol
Upon hospital admission the patient’s lesions were classified
according to the Wagner Classification. In our clinical practice,
diabetic subjects with full-thickness gangrene (Wagner grade 4) or
abscess (Wagner grade 3) were admitted to the hospital. Subjects
with less-deep ulcers (Wagner grade 2) were also admitted if the
ulcer was large and infected and showed a defective healing in three
months.
All patients were examined for diabetic retinopathy (fundus oculi by
ophthalmologist), albumin excretion rate (mg/24 h, the average of
three 24-h collections), renal impairment (creatinine >1.3 mg/dL),
arterial hypertension (systolic blood pressure >160 mmHg and/or
diastolic blood pressure >95 mmHg or antihypertensive therapy),
coronary artery disease (CAD) (CAD-resting electrocardiogram and
Bmode echocardiography), obesity (BMI >24 kg/m2 for women, >25 kg/m2
for men), dyslipidemia (triglyceride 180mg/dL or higher), and
cholesterol (200mg/dL or higher and low-density lipoprotein 160mg/dL
or higher or on hypolipidemic therapy). On admission and at
discharge, glycosylated hemoglobin levels (HbAlc high-pressure
liquid chromatography, normal values 4.4-6%) were measured. Smokers
were defined as current, active smokers or those who quit within two
months of presentation. Specimens of the foot lesion, after
decontamination and debridement followed by curettage, were
collected for aerobic and anaerobic culture, and for antimicrobial
susceptibility testing to antibiotics. Susceptibility testing to
topical antimicrobial agents was also performed according to a
standardized protocol set up in our microbiology laboratory. X-rays
were taken of both feet and legs to discover medial arterial
calcifications and bone abnormalities.
The ankle-brachial blood pressure ratio (ankle-brachial index [ABI])
was measured by Doppler continuous wave technique. Initially,
aggressive debridement was performed, and the wound was dressed.
Dressings were changed at required intervals. After the collection
of swabs from the wound, patients were given empirical antibiotic
treatment. This was modified if necessary according to the
sensitivity tests. Blood glucose levels were optimized with insulin.
The feet were protected from uncontrolled mechanical stresses and
subjected to off-loading.
Patients then underwent HBOT. The antibiotic therapy was continued
during the hospital stay until the culture exam was negative. After
discontinuation of the antibiotic therapy, re-culturing to assess
the cure was performed every two days, for a total of three times.
An optimized metabolic control was pursued either with subcutaneous
insulin administrations or oral hypoglycemic agents. The decision to
carry out a major amputation was taken by the consultant surgeon who
was unaware of whether the HBOT was administered or not. Follow-up
visits were fixed at six months and one year following discharge.
The study ended when the patient was healed, the foot was amputated,
or there was no change. Statistical significance was defined at 5%
(p value <0.05).
Hyperbaric Oxygen Therapy
In the group randomized for HBOT, the patients breathed pure oxygen
in a mono place hyperbaric chamber, pressurized with air, with a
soft helmet. The chosen pressure in our study was 2.5 absolute
atmosphere (ATA) for a period of 90 minutes for each session for
five out of seven days in a week, with an off at the weekend.
Patients included in the study were those who:
Were 18 years or older and who were suffering from Type 1 or 2
diabetes mellitus
Had chronic non-healing ulcers (ie, more than six weeks and
non-healing for more than three months)
Had ulcers of a Wagner’s grade of 2, 3, or 4
Patients excluded from the study were those who:
Were on chemotherapy or suffering from malignancy
Had a high grade fever, coronary obstructive pulmonary disease, or
an upper respiratory tract infection
Had untreated pneumothorax
Had a seizure disorder
Were pregnant
Required vascular intervention, or who have had vascular surgery in
the lower limbs in the last two months
Had suspected poor compliance.
