Diabetic Ulcers

Hyperbaric Oxygen Therapy for Diabetic Ulcers

Associate Professor (ret’d) F Michael Davis, formerly Medical Director, Hyperbaric Medicine Unit, Christchurch Hospital

Summary

  • Hyperbaric oxygen therapy (HBOT) improved healing in six prospective randomised trials (RCT) of diabetic ulcers and reduced the rate of major amputation in two.1–6  In an additional RCT of mixed aetiology leg ulcers, including diabetic ulcers, healing was improved with HBOT.7
  • HBOT has been shown to be cost-effective even though it is a moderately expensive therapy.4
  • After HBOT, healing is maintained in the medium to long term because vascular neogenesis is promoted.1,5,8
  • Complication rates of HBOT are low and treatment is well tolerated by the majority of patients.
  • HBOT must be used in conjunction with good multidisciplinary wound care.

 

What is hyperbaric oxygen therapy

Hyperbaric oxygen therapy (HBOT) is the intermittent administration of 100% oxygen at pressures greater than normal ambient pressure. There are several ways to provide this, all of which require a pressure vessel in which the patient(s) sit or lie for 2–3 hours daily for several weeks.

 

The clinical evidence for HBOT 

Six small, prospective randomised trials of HBOT for diabetic ulcers have been published.1–6  All show improved healing and, in two, a reduction in major amputation rate was reported (Table 1). Follow-up studies suggest these benefits are maintained in the medium to long term (3–5 years).8  However, a recent Cochrane review concluded there was a need for further large randomised studies because the trials (Table 1) had various flaws in design and/or reporting not meeting Cochrane criteria.9

HBOT is a moderately expensive treatment. In Christchurch, the estimated cost of a 30-treatment HBOT course is approximately $12,000 per patient. However, the cost-benefit studies from the UK and USA show an overall saving by combining HBOT with standard modalities of care in the management of diabetic ulcers, as well as improved outcomes.4,8  The UK study reported an overall saving of approximately NZ$8,000 per patient treated compared to non-HBOT care.4

Locally, we have too small a database yet to have a good idea of how well we are doing. However, of the first 50 lower limb ulcers of mixed aetiology (approx. half DM ulcers) referred to HMU, 18 (36%) were healed and 7 (14%) substantially improved on medium-term (approx. 3 month) follow-up (NNT for improvement = 2). There has been no major morbidity from HBOT in these patients. An on-going prospective cohort Australasian study of HBOT for problem wounds, both diabetic and non-diabetic, with over 400 cases shows a similar early post-HBOT healing rate, increasing to over 75% at one year, irrespective of the aetiology. Despite the Cochrane conclusions, we are firmly of the view, from our local clinical experience that HBOT, combined with multidisciplinary wound care improves healing in selected patients.

 

How HBOT works

There are diverse actions of HBOT, including support of oxygen-dependent healing processes and, more importantly, cell-signalling effects that accelerate these processes for many hours beyond the HBOT exposure. The intermittent restoration of steep oxygen diffusion gradients in the peri-wound area stimulates fibroblast function in a dose-dependent manner.10,11  The cyclical pattern of hyperoxygenation/hypoxia leads to the release of local humoral mechanisms promoting wound healing. Recent work suggests a positive effect on nitric oxide metabolism in the diabetic wound. These changes result in an advancing field of neovasculogenesis. At the same time, oedema is reduced improving perfusion, and macrophage function is enhanced, particularly the ‘oxygen burst’ phase, in the hypoxic diabetic wound. HBOT is known to work synergistically with several antibiotics. Daily HBOT also corrects deficient neutrophil adhesion in Type II diabetes.

 

Whom to refer to HBOT

Any diabetic patient in whom a wound is not healing after a reasonable period of multidisciplinary wound care should be considered for HBOT. The international consensus is that an ulcer failing to respond after six weeks (or earlier, if the ulcer is limb-threatening) and for which no correctable large vessel disease is present should be referred for assessment for HBOT. Renal failure and concomitant major arterial disease carry a poorer prognosis for healing with HBOT just as they do with other interventions. Anecdotally, HBOT has been reported to be particularly useful in the neuropathic and Charcot foot.

The evidence in non-diabetic ulcers is more limited than for diabetic ulcers, but the same broad principles apply and HBOT has been shown to enhance healing in one small, prospective, randomised study.7

Problem wounds secondary to accidental trauma or medical misadventure in both diabetic and non-diabetic patients may be referred for assessment for HBOT under a prior approval ACC contract that has been in place nationally since March 2002. Many potential referrers are still unaware of this ACC-funded service.

Referrals to the Hyperbaric Medicine Unit at Christchurch Hospital may be made directly from primary care.

 

HBOT facilities in New Zealand

There are clinical HBOT facilities in Christchurch and Auckland, at the RNZN Medical Centre and at Quay Park Medical Centre. The only hyperbaric facility in New Zealand based in a civilian, tertiary-referral hospital is at Christchurch Hospital.

 

Table 1. Summary of randomised studies of hyperbaric oxygen therapy in diabetic and non-diabetic ulcers

Study

Patients ​Outcome Measure Results​ ​​Statistics​Comments
Kalani et al1​38​Healed ulcer Amputation

​13/17

2/17

10/21

7/21​

​<0.05

<0.05

​follow up 3yr
Faglia et al2​68​Amputation​3/35​11/33

​<0.02

Doctor et al3​30​Amputation​2/15​7/15​<0.05​weekly HBOT only
Abidia et al4​18

​Healed ulcer at 1yr

Wound area decrease

5/8

 

100%​

​1/8

 

52%

​0.026

 

0.027

​saving approx $8000per patient
Hammarlund & Sundberg7​16​Wound area decrease at 6 weeks ​35.7%​2.7%​0.001​Diabetic and non-diabetic ulcers
Lee et al5 (abstract only)​​32

​Wound healing time

Minor amptation

Mortality

​not

 

4/20

 

not

​stated

 

4/12

 

stated

0.03

 

0.005

 

0.03​

HBOT group had severer wounds; 2yr follow up​
Londahl et al 6​94​Healed ulcer at 1yr ​30/49​12/45​0.009​double blind
Amputation: BKA or AKA ​ ​

 

References

  1. Kalani M, Naderi N, Lind F, Brismar K.  Hyperbaric oxygen therapy for wound healing and limb salvage in diabetic foot lesions: Three year follow-up.  Undersea Hyperb Med 2000; 27(Suppl): 44-45
  2. Faglia E, Favales F, Ealdeghia et al.  Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischaemic diabetic foot ulcer.  Diabetes Care 1996; 19: 1338-1343
  3. Doctor N, Pandya S, Supe A.  Hyperbaric oxygen therapy in diabetic feet.  J Post Grad Med 1992; 38: 112-114
  4. Abidia A, Laden G, Kuhan G et al. The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: A double-blind randomized-controlled trial.  Eur J Endovasc Surg 2003; 25: 513-518
  5. Lee C-T, Ramiah R, Choong SK, Seng KC, Rajoo V. Adjunctive hyperbaric oxygen in diabetic foot ulcers: a randomized, prospective, double-blind study. Proceedings of the Undersea and Hyperbaric Medical Society Annual Scientific Meeting, Sydney, 2004.
  6. Londahl M, Katzman P, Nilsson A, Hammerlund C. Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes. Diabetes Care. 2010;33:998-1003.
  7. Hammarlund C, Sundberg T. Hyperbaric oxygen reduced size of chronic leg ulcers: a randomized double-blind study. Plast Reconstr Surg 1994; 93: 829-834
  8. Cianci P, Hunt TK.  Long term results of aggressive management of diabetic foot ulcers suggest significant cost effectiveness.  Wound Rep Reg 1997; 5: 141-146
  9. Oriani G, Faglia E, Favales F, Quarantiello A, Calia P, Michael M. Hyperbaric oxygen (HBO) in the treatment of diabetic gangrene. Proceedings of XXIst Annual Meeting of EUBS on Diving and Hyperbaric Medicine, Helsinki, Eds. Sipinen SA, Leinio M 1995: 120
  10. Kranke P, Bennett M, Martyn-St James M, Schnabel A, Debus SE. Hyperbaric oxygen therapy for treating chronic wounds. Cochrane Database of Systematic Reviews 2012, Issue 4. Art. No.: CD004123. DOI: 10.1002/14651858.CD004123.pub3
  11. Hunt TK, Pai MP. The effect of varying ambient oxygen tensions on wound metabolism and collagen synthesis. Surg Gynecol Obstet 1972; 135: 561-567
  12. Hehenberger K, Brismar K, Lind F, Kratz G. Dose-dependent hyperbaric oxygen stimulation of human fibroblast proliferation. Wound Rep Reg 1997; 5: 147-150

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