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practice

A diabetic foot ulcer treated with


hydrogel and hyperbaric oxygen therapy:
a case study

Abstract: This study reports on the case of an elderly patient, with oxygen therapy (HBOT). After 60 sessions of the therapy, almost
diabetes, and a bullous wound on the left big toe that led to an complete closure of the wound was observed. There were no reports of
amputation of the first and second left toes. The amputation was discomfort or infection during the treatment. After seven months of
because of deep injury as it was not able to heal with a conventional treatment almost complete healing was observed with no infection.
treatment. After completing the normal treatment and the removal of a This treatment appears to be effective and should be recommended for
bacterial infection in the lesion, the patient underwent a treatment that the treatment of DFUs.
was based on a hydrogel gel (0.9% saline solution) and hyperbaric Declaration of interest: Nothing to declare.

diabetic foot ulcer  ● hydrogel ●  hyperbaric oxygen therapy  ●  HBOT

D
iabetic foot ulcer (DFU) is a serious to absorb wound exudate, the amount varying
complication of diabetes and the main between different brands.5 Hydrogels promote wound
reason for amputations involving the lower debridement by the rehydration of the non-viable
limbs.1 Risk factors for a DFU include diabetes tissue facilitating the process of natural autolysis.5
for >10 years, male, peripheral neuropathy, This study was approved by the Ethics of the Santa
abnormal structure of the foot, peripheral arterial disease Casa de Misericordia of Rio Grande Committee, RS,
(PAD), smoking, a history of previous ulcers or Brazil, under Protocol No 021/2014.
amputations, and poor glycaemic control.2 This study demonstrates the efficacy of topical
There are a huge amount of options for the treatment hydrogel in conjunction with HBOT on the healing
of DFUs, such as hyperbaric oxygen therapy (HBOT). process of a diabetic foot wound improving recovery
Treatment with HBOT involves an intermittent and quality of life (QoL).
administration of 100% oxygen, at pressures greater
than sea level, usually in daily sessions. This presents Case report
itself to be a promising treatment for severe cases of A 71-year-old male with type 2 diabetes for 10 years
DFU, as well as for some difficult healing of wounds (treated with metformin 850mg) presented with a
that are resistant to other therapies.3 myocardial infarction requiring angioplasty six months
Difficult healing wounds can be treated with saline before observing the wound. In December 2014, the
solutions as it has been shown to promote autolysis patient presented with a bullous wound on the left big
and the formation of granulation tissue.4 Hydrogel, toe that deteriorated, until March, when amputation of
prepared from 0.9% saline with 1% carbomer has both the first and second left toes was required. The
been successfully used for maintaining the wound angiotomography of the lower limbs showed a marked
bed and for promoting granulation tissue4 Hydrogels atheromatous disease of the arterial vessels, with a
consist of a matrix of insoluble polymers, with up to moderate stenosis (50–75%) in the middle third of the
96% water content, enabling them to donate water left superficial femoral artery. The postoperative wound
molecules to the wound’s surface and to maintain a was deep, significantly painful, had foul-smelling
moist environment at the wound bed. As the polymers serosanguinous drainage, and a necrotic area with
are only partially hydrated, hydrogels have the ability exposed muscle and tendon. The wound was topically
treated with sunflower oil, vitamins A and E, silicone,
Brazilian nut oil, and medium chain triglycerides, as
© 2017 MA Healthcare ltd

P. Aguiar,1 PhD; C. Amaral,2 MD; A. Rodrigues,1 Pharmacy Technician; *A.H. de Souza,3 well as oral therapy with 500mg of ciprofloxacin twice
PhD, Lecturer a day and 30mg codeine/500mg paracetamol when
*Corresponding author email: alessandrahubnersouza@gmail.com
there was local pain.
1  Federal University Hospital of Rio Grande, Rio Grande do Sul Brazil. 2 Hyperbaric Oxygen
Therapy Clinic of Rio Grande 3 Universidade Luterana do Brasil, Rio Grande, Rio Grande do Since the wound did not show any sign of
Sul, Brazil. improvement and the patient suffered a risk of further

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Table 1. Patient measurements over the 60 days of treatment


Session BP HR RR TC BG mg/dl Session BP HR RR TC BG mg/dl

1 130/80 120 22 36 158 31 80/50 100 20 36 116


2 110/70 105 20 36 150 32 80/60 102 20 35 145
3 150/80 108 20 36 178 33 100/60 102 25 35 138
4 120/80 96 20 36 135 34 90/60 100 16 35 134
5 140/80 88 18 35 135 35 80/50 92 18 36 90
6 110/80 100 16 35 131 36 80/50 102 22 35 126
7 120/70 104 21 35 129 37 110/80 65 16 36 102
8 140/80 96 18 35 159 38 100/70 88 18 36 145
9 130/70 100 20 36 125 39 110/70 88 18 36 119
10 130/70 104 16 36 133 40 70/45 88 16 35 147
11 110/60 96 20 36 187 41 90/60 90 20 36 146
12 120/80 92 16 36 123 42 120/80 100 20 35 96
13 120/80 100 20 36 143 43 90/60 88 20 36 149
14 120/80 84 16 36 154 44 80/60 80 20 36 146
15 90/60 104 20 36 98 45 80/60 88 20 36 177
16 100/70 84 20 36 127 46 90/60 84 18 35 108
17 110/60 76 16 35 79 47 100/60 85 20 36 116
18 100/60 76 20 36 124 48 120/80 100 21 35 132
19 80/50 76 20 36 155 49 100/70 82 20 35 108
20 100/60 96 18 35 92 50 70/40 84 18 36 118
21 150/80 84 18 35 165 51 80/60 98 20 35 160
22 100/60 104 20 35 103 52 90/60 98 18 36 152
23 110/70 107 20 35 104 53 80/50 100 18 35 134
24 80/60 89 16 35 102 54 100/70 102 18 36 141
25 100/60 104 20 36 131 55 80/50 88 20 35 141
26 120/70 97 20 36 153 56 70/50 82 18 36 118
27 120/80 82 20 36 94 57 100/60 96 16 36 171
28 90/60 87 16 36 123 58 110/70 100 18 36 112
29 120/80 100 20 35 93 59 110/80 79 16 36 108
30 90/60 80 20 36 132 60 80/60 98 20 36 108

BP—blood pressure; HR—heart rate; RR—respiratory rate; T—temperature; BG—blood glucose; days 1 to 60 of treatment in a hyperbaric oxygen therapy chamber

amputation, he sought the help of the Hyperbaric After seven days of treatment, there was reduction in
Medical Center of Rio Grande, RS, in March 2015. oedema, with a small amount of fibrinous material and
Tests were performed confirming hyperglycaemia granulation tissue in the wound base. At session 19
and wound cultures revealed the presence of Klebsiella (Fig  1b), intense granulation was observed. In addition,
oxytoca. The patient received 400mg sulfamethoxazole we noted some wound contraction and epithelialisation
and 80mg trimethoprim every 12 hours for seven days. with continued decrease in wound bed.
After completing the antibiotic course, he was then At session 26 there was well-vascularised granulation
treated with HBOT and topical hydrogel. tissue, a lower amount of fibrinous material, less
In April 2015, the HBOT treatment began (five times surrounding oedema and an improved appearance with
per week for 90 minutes), along with hydrogel daily regular wound edges and decreased wound size. The
dressing changes. The wound was cleansed with 0.9% hydrogel kept the moisture level in the wound stable
saline, then the hydrogel layer was applied and it was without causing cutaneous maceration.
© 2017 MA Healthcare ltd

covered with a gauze dressing. In addition, the patient At session 46, the granulation tissue formation
was instructed to protect the injury from trauma and to remained, as well as the presence of fibrinous material
rest. Diet guidelines were made in order to control the and decreasing wound depth, with continued decrease
patient’s blood glucose level (Table  1) and favour in open area. New epithelium was covering almost the
healing (Fig 1a, day 0). entire surface and the edges of the wound and its crust

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were covered with a yellowish colour. It was found


Fig 1. A 71-year-old male with diabetes. At presentation
that this did not interfere with the healing process. At (a); day 19 of treatment (b); day 58 of treatment (c)
session 58 (Fig  1c), there was further decrease in the
size of the open wound. The patient underwent a
a
total of 60 sessions without complications.
Data collected included clinical history and a
physical examination of the patient once a week. In
addition, there were the photographic records of the
injury. The dressings were changed daily so that the
wound was kept moist because of the regularly applied
hydrogel. There was no discomfort or complication
from the use of hydrogel, demonstrating
its tolerability.

Discussion
Open wounds heal by contraction of the edges and
migration of cells to the centre of the wound. The
wound bed is filled through fibroblast migration and b
the formation of new vessels that originate from
capillaries around the wound.6,7 Wound contraction
depends on the capacity of fibroblasts to migrate
through the extracellular matrix (ECM) and this
capacity is negatively influenced by many factors,
such as the use of steroids, a diagnosis of diabetes,
infection and vitamin deficiency.8 Our research has
found similar results from another group for a study
where hydrogel was used as control with a group of
153 patients. The healing rate, of the control group,
in that study was 32% after 16 weeks and complete
wound closure within 78 days. 11 This result
demonstrates hydrogel’s healing capacity,9 consistent
with the American Society of Plastic Surgeons’ c
recommendation that wound healing is promoted by
the maintenance of a moist environment.10
Hydrogels have been produced for use in tissue
engineering both in the pharmaceutical and
biomedical fields, due to their high capacity for water
absorption and biocompatibility.11 We chose to
combine hydrogel with HBOT, since HBOT accelerates
the tissue regeneration process of the wound and it is
a safe and effective therapy with few adverse events.12
Adverse events when they do occur include: pulmonary
toxicity, neurological toxicity, auditory discomfort
and barotraumas, facial sinus discomfort and transient
visual changes.13 HBOT accelerates the healing process
by increasing the capillary oxygenation, and thus,
promoting angiogenesis.14 Exposure to increased
barometric pressure inside a hyperbaric chamber Conclusion
increases the oxygen dissolved in the plasma. This DFUs are a major health problem and are an important
dissolved oxygen is the metabolically active fraction cause of morbidity, mortality and financial burden.19
that penetrates compromised tissues. 15 Treatment of comorbidites aids wound healing, as can
Neoangiogenesis and vasculogenesis occur due to the be seen in our study, where the blood glucose levels
stimulation of bone marrow-derived progenitor remain controlled.20
cells.16 Treatment with HBOT has antimicrobial effects The results of our case suggest that healing of DFUs
© 2017 MA Healthcare ltd

and increases intracellular leukocyte killing by the may be facilitated by a combination of topical hydrogel
oxygen-dependent peroxidase system.17 Wounds that and a higher oxygen supply as provided by using a
fail to progress through the normal phases of healing hyperbaric oxygen chamber. In this patient, the use of
demonstrate significant tissue hypoxia due to a poor hydrogel in conjunction with HBOT promoted healing
local perfusion.18,19 of a DFU.  JWC

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practice

References Practice Guideline: Chronic Wounds of the Lower Extremity. 2007; 1–21
1 Brem H, Sheehan P, Rosenberg HJ et al. Evidence-based protocol for 11 Benamer S, Mahlous M, Boukrif A et al. Synthesis and characterisation
diabetic foot ulcers. Plast Reconstr Surg 2006:193S–209S. https://doi. of hydrogels based on poly(vinyl pyrrolidone). Nucl Instrum Methods Phys
org/10.1097/01.prs.0000225459.93750.29 Res B 2006; 248(2):284–290. https://doi.org/10.1016/j.nimb.2006.04.072
2 Centers for Disease Control and Prevention. National diabetes fact 12 Löndahl M, Katzman P, Nilsson A, Hammarlund C. Hyperbaric oxygen
sheet: national estimates and general information on diabetes and therapy facilitates healing of chronic foot ulcers in patients with diabetes.
prediabetes in the United States, 2011. U.S. Department of Health and Diabetes Care 2010; 33(5):998–1003. https://doi.org/10.2337/dc09-1754
Human Services, Centers for Disease Control and Prevention, 2011. 13 Junior MR, Marra AR. Quando indicar a Oxigenoterapia Hiperbárica?
https://tinyurl.com/ycrabakl (accessed September 7 2017). [When to Indicate Hyperbaric Oxygen Therapy?] [In Portuguese] Rev
3 Oliveira N, Rosa P, Borges L et al. Treatment of diabetic foot AssocMed. Bras 2004; 50:3
complications with hyperbaric oxygen therapy: A retrospective 14 Vieira WA, Barbosa LR, Martin LM. Hyperbaric oxygen therapy as an
experience. Foot Ankle Surg 2014; 20(2):140–143. https://doi. adjuvant treatment for pyoderma gangrenosum. An Bras Dermatol 2011;
org/10.1016/j.fas.2014.02.004 86(6):1193–1196. https://doi.org/10.1590/S0365-05962011000600022
4 Jorge SA, Dantas RP. Abordagem Multiprofissional doTratamento de 15 Thom SR, Bhopale VM, Velazquez OC et al. Stem cell mobilization by
Feridas,[Multiprofessional approach to the Wounds] [In Portuguese] Ed. hyperbaric oxygen. AJP: Heart and Circulatory Physiology 2005;
Atheneu, 2003 290(4):H1378–H1386. https://doi.org/10.1152/ajpheart.00888.2005
5 Jones V, Grey JE, Harding KG. Wound dressings. BMJ 2006; 16 Almzaiel AJ, Billington R, Smerdon G, Moody AJ. Effects of hyperbaric
332(7544):777–780. https://doi.org/10.1136/bmj.332.7544.777 oxygen treatment on antimicrobial function and apoptosis of differentiated
6 Herndon DN, Hayward PG, Rutan RL, Barrow RE. Growth hormones HL-60 (neutrophil-like) cells. Life Sci 2013; 93(2-3):125–131. https://doi.
and factors in surgical patients. Adv Surg 1992;25:65–97 org/10.1016/j.lfs.2013.06.003
7 Gromack DT, Reyes BP, Mustoe TA. Current concepts in wound healing: 17 Hunt TK, Twomey P, Zederfeldt B, Dunphy JE. Respiratory gas
growth factor and macrophage interaction. J Trauma Inj Infect Crit Care tensions and pH in healing wounds. Am J Surg 1967; 114(2):302–307.
1990; 30(12 Suppl):129–133. https://doi. https://doi.org/10.1016/0002-9610(67)90388-1
org/10.1097/00005373-199012001-00026 18 Niinikoski JH. Clinical hyperbaric oxygen therapy, wound perfusion,
8 Skalli O, Gabbiani G. 1988. The biology of the myofibroblast relationship and transcutaneous oximetry. World J Surg 2004; 28(3):307–311. https://
to wound contraction and fibrocontractive diseases. In; Clark RAF, doi.org/10.1007/s00268-003-7401-1
Henson PM. The molecular and cellular biology of wound repair; New 19 Shobhana R, Rao PR, Lavanya A et al. Cost burden to diabetic
York: Plenum, Chap. 17, 373-402. patients with foot complicationsa study from southern India. J Assoc
9 Driver VR, Lavery LA, Reyzelman AM et al. A clinical trial of Integra Physicians India 2000; 48(12):1147–1150.
Template for diabetic foot ulcer treatment. Wound Repair Regen 2015; 20 Ruocco E, Sangiuliano S, Gravina AG et al. Pyoderma gangrenosum:
23(6):891–900. https://doi.org/10.1111/wrr.12357 an updated review. J Eur Acad Dermatol Venereol 2009; 23(9):1008–1017.
10. American Society of Plastic Surgeons. Evidence-based Clinical https://doi.org/10.1111/j.1468-3083.2009.03199.x

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