The Effect of Hyperbaric Oxygen Therapy on Psychological State and Wound Healing: A Case Report

The physiological control of wound healing depends on the correct balance between the different mechanisms of healing.¹ This complex process involves the interrelated and overlapping mechanisms of cell migration and proliferation, extracellular matrix synthesis, growth factors, and cytokines that coordinate the healing process.² Several factors influence the healing process, including wound-related factors such as size, depth, degree of contamination, and tissue necrosis. Systemic factors such as aging, nutritional status, stress, genetics, chronic diseases, and associated drug therapies also play a role in the healing process.^3,4

Long-term or extreme emotional stress can cause and perpetuate physical symptoms. The term psychosomatic, which was coined in 1818, is defined as physical symptoms resulting from a psychological condition.⁵ It is known that there are bidirectional pathways between the mind/brain and the immune system,⁶ and there is considerable evidence that inflammatory processes and social behavior are powerful regulators of each other.⁷ Furthermore, there are sufficient data to conclude that immune modulation by stressors or psychosocial interventions can lead to real changes in health, with the strongest direct evidence to date in wound healing.^8,9

Stress has been shown to have a statistically significant negative effect on wound healing.¹⁰ However, few studies have examined the effect of treatment to attenuate stress-induced delays in wound healing.

Hyperbaric oxygen therapy (HBOT) is an approved treatment for several diagnoses, including chronic nonhealing wounds and radiation necrosis.¹¹ As stated by Klakeel and Kowalske,¹¹ this technique “uses high pressures to saturate hemoglobin and dissolve oxygen into blood plasma to create a hyperoxemic environment to nourish and reverse local tissue damage caused by ischemia and hypoxemia.” It has also been hypothesized that HBOT may be beneficial in the management of certain mental health disorders, such as posttraumatic stress disorder; however, the value of HBOT in the management of mental illness is not well established.¹²

The management of difficult-to-heal chronic wounds and of anxiety and depression is associated with a high cost for both public health and the patient.^13,14 To promote well-being in individuals with a significant injury and emotional stress, it is a clinical necessity to investigate new non-pharmacological approaches with a bidirectional view of psychosomatic factors and wound healing. The scant available literature presents HBOT as a promising treatment in these cases. The goal of the present case study was to evaluate the effects of HBOT on skin healing and associated psychological factors in order to provide new data to reinforce and increase the body of evidence regarding the influence of psychosomatic factors on wound healing.

The present study was approved by the ethics committee of the Faculdade de Ciências Médicas de Minas Gerais, Belo Horizonte, Brazil (protocol No. 5.793.937). The patient provided written informed consent for the use of photographs and all health information relevant to this case.

A 62-year-old female patient presented with an infected sacrococcygeal (gluteal cleft) wound, with no signs of healing for 9 years. She reported several prior ineffective treatments and referrals from many dermatologists who could not define the wound etiology or provide the care necessary to improve the healing process.

The atypical wound (ie, wound of unknown etiology) started with intense itching (that could be reported like psychogenic itch influenced by psychological factors¹⁵), which caused recurrent bleeding. The wound evolved, with formations of vesicles that ruptured and never healed. The patient reported having previously used a variety of topical ointments: Dersani (Laboratório Daudt Oliveira Ltda [capric and caprylic acid triglycerides plus vitamins A and E]), collagenase chloramphenicol, rifampicin, Quadriderm RF cream (Mantecorp Farmasa Ltda [betamethasone, gentamicin, tolnaftate and clioquinol]), and ozonated sunflower oil.

At the time of the most recent presentation, the patient had a long-standing diagnosis of depression and no history of previous comorbidities (eg, diabetes, autoimmune disease, arterial hypertension, renal failure) that could influence the healing process. She was taking venlafaxine, oxcarbazepine, and levothyroxine. After several attempts to heal the wound during the past 9 years, the patient began HBOT, receiving 20 once-daily sessions (except on Saturdays and Sundays) for 120 minutes per session at 2.4 ATA (atmosphere absolute pressure). SilverCel (3M) nonadherent dressing—which is composed of a combination of silver, alginate, and carboxymethyl cellulose—was freshly applied after each treatment.

In the initial HBOT session, physical assessment showed the patient to be hydrated and to have the following vital signals: axillary temperature of 36.1ºC; heart rate of 80 beats per minute; normal rhythm, with no murmurs, gallops, or rubs on auscultation; blood pressure of 130/70 mm Hg; respiration rate of 27 breaths per minute; and blood glucose level of 119 mg/dL. These vital signals remained stable throughout treatment.

The patient presented with a sacrococcygeal wound between the buttocks, with some pink epithelial tissue at the margins and red granulation tissue visible at the medial wound bed, moist and irregular wound edges, a slightly foul odor characteristic of bacterial colonization, and a significant amount of light yellowish drainage (Figure, panel A). Itching was present from wound onset and during treatment, but absent at the end of HBOT treatment and for 12 months after that. After the 20th HBOT session, the patient was reassessed clinically. On physical examination, the wound was closed, with epithelial tissue free from signs of hyperemia or infection, and with no drainage or moisture (Figure, panel B).

In addition to undergoing a physical evaluation, the patient was assessed pretreatment and at 1-year follow-up after the end of HBOT using the Hospital Anxiety and Depression Scale (HADS)¹⁶ and the 36-Item Short Form Health Survey (SF-36)¹⁷ to assess correlation between wound healing and psychosomatic aspects. The HADS scoring for the probability of anxiety and depression is as follows: greater than or equal to 11, probable; 8 to 10, suggestive of; and less than 8, unlikely.¹⁸ The SF-36 measures 8 scales: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health.¹⁹ The questionnaire results in a score between 0 and 100 points, with higher scores indicating better health status and an average score of 50 deemed a normative value.

In the present study, the patient had a pretreatment HADS score in the range of probable anxiety and depression, and she scored low in all domains of the SF-36. However, most scores in both assessment tools were substantially improved after treatment (Table). Except for the general health aspect, which remained below normal after HBOT, all other aspects showed a surprising improvement.

The present case study confirms the healing effects of HBOT, along with improvement in quality of life and parameters of depression and anxiety. To the authors’ knowledge, this is the first study to describe the effects of HBOT on an atypical, difficult-to-heal wound in a patient with depression and anxiety.

Distress-related immune dysregulation may be a central mechanism behind a diverse array of health risks.^8,20 It has been well described that stress leads to negative emotions, which can result in the development of depression and anxiety,²¹ although current views also incorporate an understanding of the many physical symptoms related to psychological factors.²² As noted by Heruti et al,²³ “physical injuries are common occurrences that can have substantial implications for mental health and well-being.” A person with a physical injury may not report an increased perception of stress, and this lack of awareness can contribute to a further reduction in quality of life. Psychosomatic medicine studies that assess both immune activity near the site of wound healing and objective stressors demonstrate immunological alterations and pro-inflammatory activation associated with stress,⁶ mainly in processes such as depression and anxiety.²⁴ Different psychosomatic approaches such as qigong,²⁵ mindfulness-based stress reduction,²⁶ mindfulness awareness practices,²⁷ acupuncture,²⁸ relaxation and visualization therapy,²⁹ psychoneuroendocrinoimmunology-based meditation,³⁰ and enhanced psychological well-being have also resulted in reduced anxiety levels and depression as well as improvements in mood and sleep. In addition, HBOT has been linked to reduced anxiety and depression in several conditions, including incomplete spinal cord injury,³¹ posttraumatic stress disorder,³² and traumatic brain injury postconcussion.³³

In the present study, the patient’s HADS score was indicative of probable anxiety, and she was diagnosed with depression. Both anxiety and depression are stress factors that can result in difficulty healing. Difficulty healing, in turn, contributes negatively to mental health, thus perpetuating a negative cycle. Even with an unknown etiology, the hypothesis that a psychogenic itch probably was the initial factor to the wound development fits in the itch-scratch cycle. The authors of the present study state that because, almost 15 months after the HBOT treatment, the patient reported exacerbations of local symptoms such as pruritus and bleeding when she experienced depressed feelings. Psychological factors are known to influence itch.¹⁵ In the present case study, anxiety and depression may have contributed to maintaining the stress state, thus triggering impaired healing. In this regard, the present study highlights a new area of investigation, that is, whether HBOT may be a useful option in the management of psychogenic itch.

Over the years, several studies have been carried out to determine the right approach and the best therapies for wound healing. A general approach is required to facilitate the development of further studies.⁴ As such, HBOT has already become potentially selected as a feasible treatment in several areas. In the setting of traumatic brain injury, the proposed mechanism of action of HBOT is that increasing blood and tissue oxygenation to supraphysiological levels results in improved neuronal function by reactivating metabolic or electrical pathways.¹² Stem cell mobilization to injury sites, immune modulation, and effect on neurotransmitters have also been hypothesized as possible mechanisms of action.

Published research in this field remains scarce. However, the data presented here contribute to the clinical management of situations similar to those presented in this paper. Despite these positive results, more studies are needed to evaluate the long-term outcomes of HBOT on psychological state and wound healing.

The results in this single patient may not be generalizable. A limitation is that this study did not include biomarkers, which could aid in evaluating the influence of HBOT on such conditions. Although only a single case is presented, the data are of great value due the paucity of options to treat wound healing and psychogenic factors associated with atypical wounds, as stress and depressed feeling negatively influence the quality of life. Additional studies with more participants are necessary.

In the present case, although there was a marked improvement in the patient’s quality of life, depression, and anxiety, it is not possible to conclude definitively that the improvement was owing to both healing and its effect on daily activities or body image perception, or to the direct benefit of HBOT in neurological processes, or both. The healing effects due to HBOT treatment could be better addressed by assessing immune response factors or neurotransmitter levels, which could generate clues about how the treatment influenced psychosomatic and healing conditions. Further studies could then focus on systematically evaluating of the intrinsic mechanisms through which HBOT acts to improve psychological factors.

The use of HBOT in wound healing has proved to be effective, mainly in terms of improved quality of life. The present case study reinforces this fact and demonstrates that the wound healing is intrinsically connected with psychological mechanisms, which both could be substantially influenced by HBOT treatment.

Affiliations: ¹University of Calgary, Calgary, Alberta, Canada; ²Faculdade Ciências Médicas de Minas Gerais, Belo Horizonte - MG, Brazil.

Acknowledgments: The authors thank Nurse Paula Emmanoela Angelico dos Passos for providing the caretaking at the CLINOX (Clínica de Oxigenoterapia Hiperbárica).
 

Disclosure: The authors declare no conflict of interest.

Address all correspondence to: Alessandra Hubner de Souza, PhD; Alameda Ezequiel Dias, 275 - Centro, Belo Horizonte - MG, 30130-110, Brasil +55 31 3248-7100, alessandra.souza@cienciasmedicasmg.edu.br.

Funding: Fundação Educacional Lucas Machado (FELUMA), Faculdade Ciências Médicas de Minas Gerais (FCM-MG), Programa de Bolsas de Iniciação Cientifica (PROBIC-FCM-MG).

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