, Volume 54, Issue 1, pp 65–68 | Cite as

Relationship between ulcer healing after hyperbaric oxygen therapy and transcutaneous oximetry, toe blood pressure and ankle–brachial index in patients with diabetes and chronic foot ulcers

  • M. LöndahlEmail author
  • P. Katzman
  • C. Hammarlund
  • A. Nilsson
  • M. Landin-Olsson
Short Communication



The randomised, double-blind, placebo-controlled Hyperbaric Oxygen Therapy (HBOT) in Diabetic Patients with Chronic Foot Ulcers (HODFU) study showed beneficial effect of HBOT. As this treatment is expensive and time-consuming, being able to select patients for therapy would be very useful. The aim of this study was to evaluate whether circulatory variables could help in predicting outcome of HBOT.


All HODFU study participants who completed therapy, predefined as receiving at least 36 out of 40 scheduled HBOT/placebo sessions, were included in this study (n = 75). Baseline transcutaneous oximetry (TcPO2), toe blood pressure (TBP) and ankle–brachial index (ABI) were measured. Ulcer healing rate was registered at the 9-month follow-up visit. An ulcer was considered healed when it was completely epithelialised and remained so at the 12-month follow-up.


In the HBOT group TcPO2 were significantly lower for patients whose ulcer did not heal as compared with those whose ulcers healed. A significantly increased healing frequency was seen with increasing TcPO2 levels in the HBOT group (TcPO2/healing rate: <25 mmHg/0%; 26–50 mmHg/50%; 51–75 mmHg/73%; and >75 mmHg/100%). No statistically significant relation between the level of TBP or ABI and healing frequency was seen.


Our results indicate that TcPO2 in contrast to ABI and TBP correlates to ulcer healing following HBOT. We suggest HBOT as a feasible adjunctive treatment modality in diabetic patients with chronic non-healing foot ulcers when basal TcPO2 at the dorsum of the foot is above 25 mmHg.

Trial registration



Mrs Thelma Zoegas Foundation and Faculty of Medicine, Lund University.


ABI Chronic hyperbaric oxygen therapy Diabetes Foot ulcer TcPO2 Toe blood pressure 



Ankle–brachial index


Systemic hyperbaric oxygen therapy


Hyperbaric oxygen treatment in diabetic patients with chronic foot ulcers


Toe blood pressure


Transcutaneous oximetry


Systemic hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for diabetic foot ulcers [1, 2, 3]. This treatment modality is expensive and time consuming, so being able to predict which patients will benefit from therapy would be very useful [4].

In the randomised, double-blind, placebo-controlled Hyperbaric Oxygen Treatment in Diabetic Patients with Chronic Foot Ulcers (HODFU) study, the effect of HBOT in diabetic patients with chronic foot ulcers Wagner grade 2, 3 and 4 was compared with the effect of hyperbaric air therapy (placebo) [5]. This study showed a beneficial effect of HBOT [6]. Therefore, we evaluated whether baseline arterial toe blood pressure (TBP), ankle–brachial index (ABI) or transcutaneous oximetry (TcPO2) could help in predicting the effect of HBOT.


Design and rationale of the HODFU study and results of ulcer healing outcome have been reported in detail previously [5, 6]. All HODFU study participants who completed therapy, predefined as receiving at least 36 out of 40 scheduled HBOT/placebo sessions, were included in this study (n = 75 out of 94). Baseline characteristics are given in Electronic supplementary material (ESM) Table 1.

The protocol was approved by the Ethics Committee at Lund University, Sweden. All participants provided written informed consent.

TcPO2 measurements

TcPO2 measurements were obtained with a Radiometer TCM2 (Radiometer, Copenhagen, Denmark) device. Calibration was performed before each measurement. All measurements were performed at 1 ATA and in supine position after 20 min of rest. Room temperature was kept between 21°C and 24°C. Patients were asked to avoid smoking or drinking coffee for at least 2 h before investigations.

According to our protocol, TcPO2 was measured on the dorsum of the foot, 2 cm proximal to the base of the third toe, or as close to this location as possible. Areas directly overlying bone or superficial veins were avoided. The measuring site was carefully cleaned and the electrochemical transducer was then applied to the skin using adhesive rings and contact liquid supplied by the manufacturer. To increase skin oxygen permeability the transducer was heated to 42°C. After baseline equilibration, TcPO2 values were recorded once every minute while the patient was breathing room air for 6 min, followed by 100% oxygen for another 6 min. The highest TcPO2 values while breathing air or oxygen were chosen as the basal and stimulated TcPO2, respectively.

Methods for measuring TBP and ABI have been described previously [6].


Comparisons were tested with Mann–Whitney U test. Correlations were tested with Pearson’s test of correlations. Differences in frequencies were analysed with Fisher’s exact test. A binary logistic regression was used to evaluate factors influence on outcome, with healing as the dependent variable.

A two-sided p value below 0.05 was considered statistically significant. Statistical analysis was performed using Statistica software, version 9.0 (Statsoft Inc, Tulsa, OK, USA).


In total, 75 patients were included in the study: 38 randomised to HBOT, 37 to placebo treatment. Patients’ baseline characteristics did not differ between HBOT and placebo [6]. Median ulcer duration at inclusion was 11.8 and 10.3 months (HBOT vs placebo, NS). TBP, ABI and basal/stimulated TcPO2 at 1 ATA did not significantly differ between the HBOT and placebo groups.

There was a statistically significant correlation between TBP and ABI (r 2 = 0.42, p = 0.0003, n = 68), and between basal and stimulated TcPO2 (r 2 = 0.53, p < 0.000001, n = 75). By contrast, no significant correlation was seen between TBP or ABI and TcPO2.

In the HBOT group, basal and stimulated TcPO2 were significantly lower for patients whose ulcer did not heal (non-healers) compared with those whose ulcers healed (healers) (Fig. 1). A statistically significant increased healing frequency was seen at higher TcPO2 levels (Fig. 2). These findings are also valid for the HBOT group in the intention-to-treat population of the HODFU study. No statistically significant relation between the level of TBP or ABI and healing frequency was seen. In the placebo group, basal and stimulated TcPO2 values were similar for healers compared with non-healers. In a binary regression analysis healers were compared with non-healers, including basal and stimulated TcPO2, TBP, ABI, age, diabetes duration and ulcer depth according to the Wagner classification scale. In the HBOT group basal TcPO2 was significantly related to ulcer healing (data not shown).
Fig. 1

Median basal TcPO2, stimulated TcPO2, TBP and ABI in patients with healed foot ulcers compared with patients with unhealed foot ulcers at 9-month follow-up after HBOT (ad) or placebo (eh), respectively. Data given as median, 25–75% and non-outlier min–max. **p < 0.01

Fig. 2

Ulcer healing frequency at the 9-month follow-up according to basal TcPO2, stimulated TcPO2, TBP and ABI in patients who received HBOT (n = 38). *p < 0.05, **p < 0.01


Vascular complications in diabetes might be considered secondary to impaired macro- and/or microvascular disease. Both ABI and TBP are used in the evaluation of macrovascular circulation. TcPO2, being a composite measure of several factors such as arterial pressure, arterial oxygen content, local tissue perfusion pressures, neurovascular function and local oxygen consumption, may be a more relevant measure, as it seems to reflect micro- as well as macrocirculation. TcPO2 has previously been shown to be related to outcome in diabetic foot ulcers [7]. Case series indicate that TcPO2 might be a predictor for healing after HBOT, but large comparative studies are still lacking. In our diabetic patients no correlation between foot ulcer healing and ABI was seen. Similarly, ABI was not reported as a factor influencing outcome of lower-extremity diabetic ulcers in a retrospective study including 1,006 patients from five hyperbaric facilities in the USA [8]. However, an absolute ABI value reduction of 0.1 was associated with a 1.7 times increased risk of major amputation in a randomised study by Faglia et al. [1]. Most studies evaluating the effect of HBOT on diabetic foot ulcers do not report TBP. In our study TBP could not be used as a predictor for ulcer healing, which is in agreement with the study by Kalani et al., in which major amputation was performed in nine (of 38) patients, with TBP normal in four, moderately decreased in three and severely decreased in two [3]. In our study, basal TcPO2 was significantly correlated with ulcer healing. Healing rates following HBOT decreased with decreasing basal TcPO2. No ulcer healed when basal TcPO2 was <25 mm and all ulcers healed when TcPO2 was >75 mmHg. In patients with TcPO2 26–50 and 51–75 mmHg, healing rates were 50% and 73%, respectively. Similar results have been reported by others. In a study by Fife et al., 629 patients with basal TcPO2 below 25 mmHg were less likely to benefit from HBOT than those with higher TcPO2 values [9]. Wattel et al. reported a mean basal TcPO2 of 32 mmHg in healers (n = 15), compared with 12 mmHg in non-healers in a case-series of 20 patients (11 with diabetes and nine arterial insufficiency without diabetes) given adjunctive treatment with HBOT [10]. In a retrospective study of 35 patients who received 16–20 sessions of HBOT after partial foot amputation, healing was achieved in all patients with a TcPO2 above 29 mmHg [11]. Oubre et al. performed a retrospective analysis of 73 HBOT-treated patients (37 with diabetes) with 85 chronic lower extremity ulcers [12]. Robust healing was achieved in 33 ulcers, minimal healing in 33 and no healing in 21. Basal mean TcPO2 in each of those groups were 57 mmHg, 44 mmHg and 38 mmHg, respectively. In the present study, stimulated TcPO2 was significantly higher in healers compared with non-healers. However, in a regression analysis, stimulated TcPO2 was not superior to basal TcPO2 in predicting ulcer healing. In the placebo group—mirroring routine clinical care—TcPO2 was of no prognostic value, possibly owing to a lower healing rate.

Although TcPO2 appears to be more useful as a prognostic factor for HBOT outcome than TBP and ABI, the method has several limitations. Measurements might be hampered by individual factors, such as electrode localisation, skin thickness and skin oxygen consumption, as well as ointments. Variation in patients’ respiratory or cardiac condition may influence TcPO2, and the presence of oedema could be an important confounding factor. In our study 7% of TcPO2 measurements were postponed for oedema reduction including transient soft tissue infection. Skin heating reduces the barrier to transcutaneous diffusion of oxygen, and even small changes in temperature might have an impact on TcPO2. A heating element keeps a constant electrode temperature, usually between 42°C and 45°C. At our hyperbaric unit, skin blistering and ulcer development have been seen as adverse reactions to TcPO2 measurement at 44°C. As a consequence, we use a transmitter temperature of 42°C, which might give 2–6% lower TcPO2 values compared with those taken at 44°C. Arguments have been raised in favour of TcPO2 measurement at hyperbaric conditions as a better way to predict benefit from HBOT in diabetic patients with chronic foot ulcers. We did not use this method in our study, because it is not practical in a diabetic foot clinic.

In conclusion, these results indicate that basal and stimulated TcPO2 in contrast to ABI and TBP, correlate to ulcer healing following HBOT. Further, we suggest hyperbaric oxygen therapy as a feasible adjunctive treatment modality in selected diabetic patients with chronic non-healing foot ulcers when basal TcPO2 at the dorsum of the foot is above 25 mmHg.



The authors are grateful to J. Jeffery for scientific advice and help with the English text; to registered nurse C. Johansson and assistant nurses G. Torildsson and M. Andersson at the Hyperbaric Unit for collaboration and invaluable help. This study was supported by unrestricted grants from Zoégas Foundation, Region Skåne Foundation and the Medical Faculty of Lund University.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2010_1946_MOESM1_ESM.pdf (24 kb)
ESM Table 1 Baseline characteristics (PDF 24.2 kb)


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • M. Löndahl
    • 1
    • 2
    Email author
  • P. Katzman
    • 1
  • C. Hammarlund
    • 3
  • A. Nilsson
    • 4
  • M. Landin-Olsson
    • 1
  1. 1.Institution for Clinical Sciences in LundLund UniversityLundSweden
  2. 2.Department of EndocrinologySkane University HospitalLundSweden
  3. 3.Department of AnesthesiologyHelsingborg HospitalHelsingborgSweden
  4. 4.Department of Internal MedicineÄngelholm HospitalÄngelholmSweden

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