ECHM - ETRS
Joint Conference on

Oxygen and Tissue Repair
organized by

European Committee for Hyperbaric Medicine
andEuropean Tissue Repair Society
Ravenna, 27 – 28 October, 2006

Recommendations by the International Jury

Members of the Jury:J. Niinikoski, Finland (Chairman)
ECHM

ETRS

D. Bakker, The Netherlands,
F. Cronjé, South Africa
F. Lind, Sweden
D. Mathieu, France
J. Schmutz, Switzerland

T. Hunt, USA
R. Mani, United Kingdom
M. Romanelli, Italy
L. Téot, France
T. Wild, Austria

A. Marroni, Italy (Secretary)

Questions to be answered by the Jury
1. What are the incidence and the costs of wounds with delayed healing?
2. What tissue changes induced by hypoxia lead to delayed wound healing?
3. What methods are available in clinical practice to evaluate tissue hypoxia as a factor
responsible for delayed wound healing?
4. What is the rationale to add HBO to the conventional treatment of delayed woundhealing?
5. Which patients are most likely to benefit from adjunctive HBO?
6. Is HBO cost-effective in the management of patients with delayed wound healing?
7. What actions and studies have to be conducted in the near future to solve theremaining controversies?

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Recommendations
After having listened the expert reports and with the assistance of the literature
reviewers, the jury met to discuss all the presented evidence and came torecommendations for clinical practice.
To assess the quality of the existing evidence, the jury used the following scale:••••

Level 1: strong evidence,
Level 2: convincing evidence,
Level 3: existing but weak evidence,
Level 4: anecdotal evidence.

In order to indicate its evaluation of the strength of evidence supporting eachstatement, the jury graded its recommendations using the following scale:• Type I: Strongly recommended. Recommendations orStandards are supported by level 1 evidence.
• Type II: Recommended. Recommendations or guidelines aresupported by level 2 evidence.
• Type III: Optional. Statements are supported only by level 3
evidence.

1. What are the incidence and the cost of wounds with delayed
healing?
1. Diabetic foot ulcer:
Diabetic foot ulcers affect 6.8% of the diabetic population per year (USA). The
total cost over a three year period amounts to $26,700 per case with ischaemia;$16,100 without ischaemia; $43,100 with minor amputation; and $63,000 withamputation (Sweden).
2. Venous stasis ulcer:
The incidence increases with age approaching, 3-5 % above 65 and 12 % above
70 years (Sweden). The national costs implications are assessed to be in the orderof 5 Billion Euros (Germany).
3. Arterial insufficiency-related ulcer:
Approximately 4.5% of the population over 40 years has peripheral vasculardisease / chronic limb ischemia (CLI) affecting the lower extremity (USA). The
prevalence of CLI approaches 0.1-0.24% inhabitants in Western countries(Germany, Norway). The projected costs are $17,000 per CLI case (hospital costsonly); at 5 years (with prior reconstruction): $111,000 per case with major
amputation; $77,600 per case without amputation; $213,000 per case withimmediate major amputation.
4. Pressure ulcers:
These ulcers are a function of hospitalization, immobility and institutionalization.
The incidence is projected at 16.8 % of in-patients per year (Japan). The national
cost implications amount to 1.4 to 2.1 Billion Pounds (UK).
5. Radionecrosis:
The incidence for bone and soft tissue radionecrosis is in the order of 5%. The
projected costs, although unspecified, are surely high.

ECHM ETRS Ravenna 2006 Jury recommendations

Page 2 of 52. What tissue changes induced by hypoxia lead to delayed woundhealing?
1. Oxygen is an important factor in wound healing.
2. Hypoxia interferes with many components of wound healing. Many of these can bemodelled or expressed numerically.
3. There is in vitro, in vivo and clinical evidence of a relationship between theavailable amount of oxygen in the wound to healing processes. Oxygen is speciallyneeded in the inflammatory phase (level 1).
4. The presence of oxygen reduces wound oedema (level 1).
5. Bacterial killing is oxygen dependent. It is maximal at several hundred mm Hg
pO2, and goes almost to zero in hypoxic patients. There is evidence for therelationship between hypoxia to wound infection at the cellular, animal, andhuman level (level 1). Questions remain on the type of bacteria most sensitive tohypoxia and which clinical parameters are involved (CRP, fibrin, procollagen,leukocytes, neutrophils).
6. Angiogenesis, although previously thought to be induced by hypoxia, seems to be
directly sensitive to oxygen as a function of local lactate delivery. Angiogenesis is
reduced to zero at tissue tensions of 10 mm Hg. In clinically oxygen deficientsituations, the granulation tissue is not formed. There is evidence for an effect ofoxygen on angiogenesis in basic studies (level 1) and for animals and humans(level 2).
7. Collagen production is maximal at 250 mm Hg and falls to almost zero in severeclinical hypoxia (Km= 25 mm Hg pO2). Cell motility falls with loss of cell energy
production that occurs at or below 10 mm Hg pO2. There is evidence for the needof oxygen in collagen synthesis and strength in basic, animal and human wounds(level 1).
8. No data exists on oxygen and apoptosis of myofibroblasts in the remodellingphase.

3. What methods are available in clinical practice to evaluate
tissue hypoxia as a factor responsible for delayed woundhealing?
1. Currently there is a lack of technology to assess tissue hypoxia and cell
metabolism in clinical practice. The Near Infra Red Reflectance Spectrophotometry(NIRO) has the potential to measure both tissue pO2 and cellular cytochrome a-a3
redox state. However validation of the hypoxic state of cells using NIRO is yet tobe reported.
2. Several techniques are available for research rather than for clinical application:a.- Imaging techniques including PET scans, and MRI derived techniques.
b.- Direct measurements of tissue pO2 using e.g., subcutaneouspolarographic needle electrodes. These are invasive and therefore
unappealing in clinical practice.
3. Clinical techniques that assess altered perfusion state thereby permittingcomments on tissue hypoxia include:a.- Clinical assessment including ankle and toe pressure measurements
using portable Doppler are part of routine evaluation of patients.
b- Imaging techniques including Duplex ultrasonography, arteriography,
MRI techniques. These techniques are recommended part of the workup forrevascularisation.
c.- Techniques that assess local perfusion include:
1.
Clearance methods.
2.
Thermal clearance including thermography.

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3.
Laser Doppler flowmetry and imaging.
4.
Transcutaneous measurements of pO2 and pCO2.
The techniques permit interpretation of altered perfusion states. Eachtechnique offers subtly different information of microvascular function. All
the techniques require strict protocol to derive reliable data. Evidence forthe use of PtcO2 to assess viability of diabetic foot is at least level 3,
possibly level 2.

4. What is the rationale to add HBO to the conventional treatmentof delayed wound healing?
1. HBO is not required in situations where normal wound healing is anticipated. Its
primary role is restricted to certain situations of impaired or delayed woundhealing.
2. Delayed wound healing implies an acute wound not healing in the normal timeframe (4-6 weeks) under conditions of standard care or conventional treatment in
an uncompromised patient.
3. Among the factors that can cause delayed wound healing there are many both
systemic and local factors which impair oxygen delivery to the wound.
4. A key factor to achieve normal wound healing is to optimize the oxygen
concentration in or around the wound.
5. HBO can be used when standard care fails to achieve oxygen levels necessary fornormal wound healing.
6. The rationale for the use of HBO is because it has the potential, not only to correct
hypoxia, but also to improve tissue perfusion, to stimulate tissue repair and toprevent and treat infection.
Level of evidence:
Basic studies: level 1.
Animal studies with control group: level 2 to 1.
Human studies: level 3 to 2.
Recommendation for adding HBO to conventional treatment in delayed wound healing
is a type II recommendation.

5. Which patients are most likely to benefit from adjunctive HBO?
1. Prior to considering a patient for HBO, there shall be a complete clinical evaluation
with correction of systemic and local factors responsible for the delayed healing.
These include cessation of smoking, pressure measures, glycaemic control and soon. (type I recommendation).
2. The possibilities of revascularisation must be considered and either performed or
the possibility excluded (type I recommendation).
3. The two main conditions that prompt the possibility of using adjunctive HBO areinfection (i.e., periwound cellulitis, bone and joint infection) and ischaemia. When
HBO is planned to correct wound ischaemia (hypoxia), wound hypoxia and its
correction under hyperbaric condition should be measured using objectivemethods.(type I recommendation).
4. Presently there is reliable evidence that HBO is effective in reducing major
amputations in patients with diabetic foot ulcers (level 2). In cases of patientswith lower extremity wounds of other aetiologies, there is a paucity of reliable
evidence of the value of HBO treatment.

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6. Is HBO cost-effective in the management of patients withdelayed wound healing?
1. In determining the cost-effectiveness of HBO in the management of delayed
wound healing, certain assumptions have had to be made to simplify calculations.
Prospective research is recommended, but for the time being, the jury has
confidence that these approaches rival the economic basis for decisions made inother fields of healthcare.
2. Based on projections using Persels formula applied to the currently available data,a significant saving can be achieved using HBO as a standard adjunct in treating
necrotising infections, diabetic ulcers, and radiation necrosis as currently
recommended by the ECHM and UHMS. The number of HBO treatments has asignificant impact on cost-effectiveness ratios. Clinical guidelines arerecommended to assure optimal cost effectiveness (type I recommendation).
3. Based on this data, HBO for the problem wounds listed in the analysis, not onlyappears to be clinically effective, but also likely to reduce the general costs of anation’s healthcare, reduce the social impact of related illnesses and offer better
quality of life.

7. What actions and studies are required in the near future tosolve the remaining controversies?
1. Measure oxygen concentration in the wound and in the normal tissues (type Irecommendation);
2. Colleagues working in HBO interested in wound healing would be properly trainedin wound healing and use tools already developed in order to quantify clinicalresults (type I recommendation).
3. Hyperbaric personnel should be associated into multi-disciplinary teams withspecialist in other fields and basic scientists (type I recommendation).
4. Medical staff involved in Wound Care and Hyperbaric Medicine should receive
training in basic and clinical research methods on a continuously regular base(e.g. CME). (type I recommendation).
5. The relationship between the European Committee for Hyperbaric Medicine andthe European Society of Tissue Repair should continue with the 2 following
objectives:
1. - establishing a network of centres and teams involved in clinicaland basic research related to oxygen and wound healing.
2. - organizing seminars and workshops dedicated to clinical and basic
research training.
(type I recommendation).
6. Information and personnel exchange policies should be implemented between
hyperbaric and wound care facilities (type I recommendation).

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