INTRODUCTION
Preceding published researches of health-related quality of life (QOL) have shown distinct low quality of life in patients suffering from diabetic foot problems (Kinmond et al. 2003; Ribu & Wahl 2004). These patients experience relentless constraint on daily life basis due to the ulcer. These patients are often rendered helpless haunted by concern for the future, greater frustration with their lives, higher levels of depression and poorer psychosocial adjustment to illness (Kinmond et al. 2003; Ribu & Wahl 2004). Fejfarová et al. (2014) noted that 219patients with diabetic foot problems, in particularly those with previous major amputation history, have worse quality of life in the environment domain such as financial, quality and standard of living with worse stress readaptation ability. It is believed that late complications often affect patients by hindering social interactions hence, isolation, unemployment as a results of reduce mobility and ultimately results in financial problems (Herber et al. 2007; Goodridge et al. 2005).
Cellular processes in stages of wound healing such as cell metabolism, proliferation, and revascularization crucially requires oxygen. Systemic hyperbaric oxygen therapy (HBOT) was suggested to improve long term healing in chronic diabetic ulcers that have not improved with pertinent therapy (Lipsky & Berendt 2010). Oxygen therapy has demonstrated a vital role in increased antimicrobial activity, synthesis of collagen that enhances wound tensile strength and growth factor signal transduction (Eggleton et al. 2015). Furthermore, not only that it enhances neutrophil killing ability, hyperbaric oxygen also reduces local inflammation during revascularization of wound tissue by hindering inflammatory cell (neutrophil)–endothelial cell interaction (Eggleton et al. 2015; Kendall et al. 2013).
HBOT augments the apoptosis of phagocytes which interrupts the build-up of potentially necrotic cell debris (Almzaiel et al. 2013).
Apart from that, it also encourages angiogenesis and augment fibroblast activity (Kranke et al. 2004; Barnes 2006). Theoretically, HBOT appears to enhance the healing of ischemic foot ulcers in diabetic patients.
Londahl et al. (2010) conducted a randomized controlled trial of a total of 94 patients with Wagner grade 2, 3 or 4 ulcer were recruited. A total of 57% of these patients receiving HBOT had healed ulcer at 1-year follow up, while in the placebo group, only 29% had achieve healing. Hyperbaric sessions were conducted for 8 to 10 weeks (40 sessions in total, each session was 90 minutes at 2.5 ATA). The main aim was healed ulcer with complete epithelial regeneration. Patients divided randomly into two treatment groups were similar at initial study. More than half had undergone vascular surgery for lower limb affected.
Generally, there was no study that correlated the effects of hyperbaric oxygen therapy with patients’ quality of life. The present study aimed to assess the effects of HBOT in chronic DFU in terms of inflammatory markers, wound size reduction and quality of life.
MATERIALS & METHODS
Present study was prospective, randomised control and was conducted in a tertiary hospital. Patients were selected from June 2013 to December 2014. The selected patients were the ones who were admitted due to diabetic foot problems.
Inclusion criteria for this study were patients diagnosed with Diabetes Mellitus type 1 or 2, and had an ulcer at the foot or ankle for at least four weeks of duration. Ulcers were classified using Wagner classifications system, and only type 1, 2 or 3 were included. Patients with active infections were also included. Exclusion criteria were patients who were contraindicated for HBOT (e.g. chronic obstructive airway disease, middle ear infection etc.), patients diagnosed with critical limb ischaemia and patients who were pregnant or below 18 years of age. Patients who had severe medical illnesses that could influence the quality of life and had underwent lower limbs major amputation (level Syme’s and above) were also excluded from this study.
Both informed and written consent were obtained from patients who fitted the criteria and agreed to be included in the study. Monofilament and ankle brachial pressure index was done to gauge the severity of peripheral neuropathy and peripheral arterial disease. The size of ulcers and level of inflammatory markers were documented at initial presentation and at two and four weeks’ review. All patients were required to fill-out the SF-36 questionnaires after four weeks of treatment. SF-36, a self-reported questionnaire, was used in two languages, English and Malay. Both language version of SF-36 used in this study was translated and validated in the Malaysian population. This questionnaire covers eight domains/subscales of quality of life, comprising of physical facet (physical health components) and psychosocial facet (mental health components) of quality of life. The physical health consisted of Physical Functioning, Physical Role, Bodily Pain and General Health perception, while the mental health components are Role Emotional, Vitality, Mental Health and Social Functioning.
Patients were assigned randomly to two separate groups using a sealed envelope with treatment allocation inside; HBOT group and control group. Treatment in both groups included mechanical/chemical debridement, antibiotics, wound dressing and off-loading footwear. Only the HBOT group were subjected for hyperbaric oxygen therapy. Each session was conducted five days a week inmono-place hyperbaric chamber. (20-30 treatment sessions). A session consisted of a duration of compression in air for 5 mins, subsequently at 2.5 atmosphere absolute (ATA) treatment period for 85 mins, and then a 5 mins decompression period.
DATA ANALYSIS
SPSS version 22.0 software was used to analysed the data collected. Descriptive and analytical statistical functions of the software was used to analysed the demographic and clinical characteristics of the study sample. Independent t-test using a two-tailed test was used to compare mean values of continuous data and χ2 test was used to compare categorical data in order to evaluate inter-group differences. Mann Whitney-U test was used to compare the median score for each SF-36 domain and the summary scores between the two groups as the data was not normally distributed.
RESULTSDEMOGRAPHIC DATA
A total of 60 patients were recruited and analysed in present study and they were randomly divided into two groups. These patients were aged between 39 to 77 years in which 31 were males (51.2%) and 29 (48.3%) were females. A total of 14 (23.3%) of them were active smokers while another 46 (76.7%) were non-smokers, or had quit smoking more than 20 years. A total of 25 (41.7%) had chronic medical problem (chronic kidney disease, retinopathy, ischaemic heart disease). Mean duration of the chronic diabetic foot ulcer was 5.2 months, with 9 (16.7%) were type 1, 26 (43.3%) were type 2 and 25 (41.7%) were type 3 ulcers based on Wagner classification system (Table 1).
ANALYSING TOTAL WHITE CELL COUNT (TWCC) CHANGES IN HBOT AND CONTROL GROUP
During initial presentation, the total white cell count (TWCC) was high in both groups, but there was no significant different statistically at the initial presentation (p=0.087). The reduction of WCC was seen in both groups. However, the trend was more steady in the HBOT group until the end of treatment at day-30, and mostly had normalise. The reduction was significant in HBOT group (p=0.046) (Figure 1).
ANALYSING C-REACTIVE PROTEIN (CRP) CHANGES IN HBOT AND CONTROL GROUP
Similar to the TWCC changes, both groups have high C-reactive protein (CRP) at the initial presentation. Reduction of CRP protein was observed throughout the treatment in HBOT and the control group. The reduction trend was significant statistically in HBOT group which was more constant and steady compared to the control group (p=0.039) (Figure 2).
ANALYZING ULCER REDUCTION IN HBOT AND CONTROL GROUP
During the initial presentation, the ulcer size was statistically not significant in both groups (p=0.06). With the treatment, reduction in size of the ulcer was observed in both groups, and it was significant (p<0.001) in HBOT group (Figure 3). Using Pairwise comparison, wound reduction in every ten days of measurement was significant (p<0.001) in HBOT group compared to the control group (Table 2, Figure 4). ANALYSING THE QUALITY OF LIFE USING SF-36
There was statistically significant difference in both group of each domain. Patients treated with HBOT have better physical and mental health. Table 3 shows eight domain median scores and the SF-36 two summary scales. Mostly, diabetic foot ulcer treated without HBOT had lower median scores in all of SF-36 domains significantly. Hence, diabetic foot ulcer treated with HBOT had better quality of life. The summary scores showed a significantly poor Physical Component Summary in patients underwent HBOT than those treated with conventional treatment alone. This was also seen in Mental Component Summary with p value equal to 0.001.
DISCUSSION
The present study supports the management approach that use HBOT as an adjunct to the usual DFU treatment for selected diabetic patients as it enhances the healing of ulcers. HBOT had accelerated ulcer healing patients suffering from long-standing chronic ulcers compared to the control group treated with conventional treatment alone. All sixty patients (thirty in each group) in present study were compliant to each follow up and assessments. We found no significant difference in patients who were smoking (p = 0.06) or who had chronic medical illnesses such as chronic kidney disease, ischaemic heart disease, diabetic retinopathy etc. (p = 0.087), in both groups of HBOT and control group.
Patients having chronic diabetic foot ulcers were susceptible to develop recurrent infections, particularly when the wound failed to heal. In previous study, these patients needed multiple surgical debridement, antibiotic courses and prolong hospital stay. To monitor infections in our study, we used reliable infective markers such as white cell count and C-reactive protein level (Lipsky et al. 2012). The reduction of the infective markers (WCC and CRP) were seen in both group, which were statistically significant (p=0.046 and 0.039, respectively). We noticed that patients in both group developed not only recurrent infections due to the foot ulcers, but also from other sources (e.g. respiratory, urinary tract infections) thus exacerbating and influences the level of infective markers. Patients who developed infection in this study, with evidence of clinical and biochemical findings were treated accordingly.
This explains the steady reduction trend of white cell count and C-reactive protein in the HBOT group, as the elevation of oxygen tension enhances the neutrophil oxidative killing of bacteria in addition to oxygen being directly toxic to anaerobic organisms.
Previous studies supports the use of HBOT in the treatment of chronic diabetic foot ulcers which significantly improve wound healing (Barnes 2006; Londahl et al. 2010; Lipsky & Berendt 2010). We noticed similar outcome in this study and it is remarkably significant where the wound reduction seen in every phases of assessment which was conducted in every ten days of the treatment. Using pairwise comparison, the p value in each phase was less than 0.001 compared to the control group treated with conventional therapy alone. At six months follow up, 26 patients (86.7%) in HBOT group achieve complete ulcer healing as compared to 18 patients (60%) in the control group.
Diabetic complications may greatly interfere with the quality of life of diabetic patients (Wandell & Tovi 2000). The effect of foot problems to the QOL is the most popularly studied using self-reported SF-36 questionnaire. There were significantly different scores of all domains and the two summary scales in the SF-36 two groups. The Physical Functioning domain governs all physical tasks such as bending, stretching, walking and climbing stairs without limitation while the Role Physical domain tests on predicaments of tasks or other daily activities resulting from the physical health. The control group scored significantly, indicating severe and relentless restrictions with mobility. This is probably due to inability to mobilize secondary to non-weight-bearing regimen from foot ulcer. Mental health was not as severely impaired as some of the components in physical health. Our findings are in agreement of several studies that also focus on quality of living among patients struggling Diabetic Foot Ulcer. Such studies are by Valensi et al. (2005) and Ribu et al. (2006), of which both studies use the SF-36 Questionnaires and these two studies were both cross-sectional and observational design, only that Ribu et al. (2006) compared the scores of patients with DFU ulcer score to the general population without Diabetes where as Valensi et al. (2005) compared the QOL among Diabetic patients with and without DFU. These studies however, did not measure HBOT influence on ulcer healing and quality of living. Another study with results consistent to present study was done by Mazlina et al. (2011) and it compared the health-related quality of life in patients with DFU to diabetic patients without DFU, using the SF-36 questionnaires, it was observed that the two domains of physical health such as physical functioning and role physical domain were affected negatively great in patients with DFU. They also observed that mental health was affected but not as severely as the physical component.
Mental health measures the level of happiness, general well-being and constraints that emotional issue drawback on the degree of task one is able to carry out. The probable cause for patients in the control group having significantly low mental health score was attributed to having doubts as to when or whether the foot problems will heal. They may experience poorer psychosocial adjustments and experience living constraints.
Admittedly, the sample size for the present study was small due to this is pilot study in the country. It aims to study the effects of DFU towards quality of life but also the outcome of HBOT. Therefore, a bigger sample size is recommended for future study. We also had limitation to control each single dressing to be used in both HBOT and control groups.
CONCLUSION
In conclusion, it must be emphasised that HBOT is an adjunctive therapy to many other components essential in accelerating wound healing and in achieving better quality of life in chronic non-healing diabetic foot ulcer. The results of present and precedent should provide impetus and basis for larger multicentre prospective, randomized, double-blinded controlled studies in assessing the outcome of HBOT in healing of diabetic foot ulcers.
ACKNOWLEDGEMENT
The authors would like to thank Professor Dr Srijit Das for his technical help in publishing this manuscript. The authors would also like to thank Mr Mohd Amir Azmi for his help in ensuring high quality pictures.