The role of hyperbaric oxygen therapy in peripheral vascular disease
(Portuguese PDF version)

Ricardo Costa Val1, Roberto Carlos de Oliveira e Silva2, Tarcizo Afonso Nunes3, Tatiana Karina De Puy e Souza4

1. Specialist in Angiology/Vascular Surgery, Brazilian Society of Angiology and Vascular Surgery (SBACV). Assistant Professor, Universidade Federal de Minas Gerais.
2. PhD, Universidade Federal de Minas Gerais.
3. PhD. Associate Professor, Universidade Federal de Minas Gerais.
4. Medical Student, School of Medicine of Barbacena, state of Minas Gerais.

Correspondence:
Ricardo Costa Val
Rua Aimorés, 612/1103
CEP 30140-070 - Belo Horizonte - MG
Tel.: +55 (31) 9972.6066/3224.2974
E-mail: costaval@mkm.com.br

ABSTRACT

Objective: In the last few years, hyperbaric oxygen therapy has been used more judiciously for medical purposes. Countless experimental and clinical studies have provided clarifying information on the physiological effects and mechanisms of such therapy. Nevertheless, many aspects regarding its mechanism, side effects and contraindications still remain unclear. Due to the increasing interest in this kind of treatment, its clinical applications will probably be widely disseminated in the future, mainly within the areas of angiology and vascular surgery. The objective of this article is to discuss and encourage debate on this subject through the description of three different cases of patients with vascular lesions who were submitted to hyperbaric oxygen therapy associated with other therapeutic procedures.

Methods: All three patients were submitted to 20 daily and consecutive sessions of hyperbaric oxygen therapy. Each session lasted for 120 minutes, at 2.5 ATM and with supplementary O2 at 100%. Surgical debridement was also performed. In addition, daily simple dressings with collagenase ointment and antimicrobial medication were applied.

Results: Some of the significant results observed after the hyperbaric oxygen therapy sessions were complete healing of the lesion, absence of pain, wound granulation, and reduction of the edema. However, one of the cases did not present any improvement regarding walking distance and reduction of the use of analgesic medication.

Conclusion: Hyperbaric oxygen therapy is a powerful therapeutic tool and has unique properties, which can be useful in the management of peripheral vascular diseases. It is of utmost importance that the professionals in charge of hyperbaric oxygen therapy be well trained. This therapy should not be considered a magic tool.

Key-words: oxygen inhalation therapy, peripheral vascular diseases, alternative therapies.
Palavras-chave: oxigenoterapia, doenças vasculares periféricas, terapias alternativas.

J Vasc Br 2003;2(3):176-81

Hyperbaric oxygen therapy (HBO) consists of intermittent oxygen inhalation at 100% in a closed chamber pressurized above 1 ATA. The high partial pressure of oxygen in inspired air determines an increase in the levels of O2 dissolved in blood plasma, which is the basis of this therapy. This state of hyperoxia is obtained from multiplace (for several patients) and monoplace (for one patient only) chambers. Monoplace chambers are pressurized with pure oxygen, whereas in multiplace chambers, the patient breathes through masks that provide oxygen at 100%, in a compressed air environment. In both cases, oxygen pressure is increased to the desired levels.1-3 Hyperbaric oxygen therapy is pioneered by Henshaw, a British physician who is credited with having developed the first hyperbaric chamber, in 1662, which he called Domicilium.4

In physiological terms, HBO consists of intermittent oxygen inhalation in a chamber pressurized above 1 ATA. The increase in oxygen pressure is often expressed in multiple values of absolute atmospheric pressure (ATA), in which 1 ATA is equal to 1 kg/cm2 or 735.5 mmHg/760 mmHg. According to currently accepted protocols, most oxygen therapies are performed with a pressure between 2 and 3 ATA, except for the treatment of arterial gas embolism and of decompression sickness, in which a higher pressure is crucial for the desirable effect. Under these circumstances, an air pressure of up to 6 ATA is used.5

Inhalation of air with high partial pressure of oxygen allows for a remarkable increase in the levels of O2 dissolved in blood plasma; however, it should be underscored that oxygen under normobaric pressure is not able to produce the reactions observed under hyperbaric conditions. Therefore, the compression chamber is essential for the production of such reactions.5

PATIENTS AND METHODS

First case

Forty-six-year-old housewife suffering from melanoderma, and critical ischemia (Fontaine class IV) of the right lower extremity secondary to thromboangiitis obliterans. She had been submitted to three unsuccessful arterial revascularizations during three years, due to arterial thrombosis (first surgery) or to early occlusion of the vein graft (last two surgeries). On admission, we observed distal trophic injury to the hallux with purulent secretion, absence of greater and palpable pulses in all sources starting from the femoral pulse, and poor distal runoff at arteriography. On physical examination with continuous wave Doppler, no arterial murmur was heard on distal arteries, close to the malleoli.

The patient was submitted to 20 daily and consecutive HBO sessions for 120 minutes at 2.5 ATM and with supplemental O2 at 100%. In addition, one week after the last session, she underwent surgical debridement of the necrotic tissues in the hallux, and received daily simple dressings with collagenase ointment, and antimicrobial medication.

Forty days after the last HBO session, we noted total healing of the trophic injury, which remained so for six months. However, during this period, we did not observe any improvement in walking distance and any reduction in painkiller prescription. Approximately one year after the surgery, the patient was readmitted with critical ischemia, and had to have the limb amputated at the thigh level.

Second case

Fifty-two-year-old male patient, agriculture worker, chronic smoker, suffering from leukoderma. On admission, the patient had history of painful injury at the medial base of the left hallux with an ischemic aspect, with around 90 days since development, secondary to local trauma. The patient had been receiving daily dressings with antiseptic solution and iodine at a health center in the countryside of Minas Gerais, but no improvement was observed. The initial investigation revealed occlusion of the distal superficial femoral artery with runoff from genicular branches to the popliteal artery, with good leg runoff, but with diffuse atheromatosis and occlusion of the anterior tibial artery. Two-phase murmur was detected in the posterior tibial artery on continuous wave Doppler, in addition to an ankle brachial pressure index of 0.47.

We opted for clinical treatment. The patient was submitted to 20 daily and consecutive HBO sessions for 120 minutes each, at 2.5 ATM and with supplemental O2 at 100%. In addition, the patient received daily collagenase dressings and local antimicrobial medication. At the beginning of the treatment, surgical debridement of necrotic tissues was also performed.

After the 20 sessions, we observed no pain at the site of injury and clear wound granulation (Figures 1 and 2). The patient was followed up at the outpatient clinic; the wound healed completely three months after the last HBO session. Currently, he has been doing regular walks and using platelet antiaggregant and hemorrheological drugs.

click hereFigure 1 - Trophic injury at the base of the right hallux. Beginning of treatment.

click hereFigure 2 -Aspect of the trophic injury after 20 HBO sessions and daily dressings. Evident tissue granulation.

Third case

Twenty-four-year-old male patient, student, suffering from leukoderma, victim of total rupture of the left popliteal artery secondary to a run-over. After 16 hours of ischemia, he underwent arterial revascularization of the extremity with contralateral reverse greater saphenous vein and large fasciotomy of the leg. He developed reperfusion syndrome of great clinical severity, which required intensive unit care, correction of hydroelectrolytic disorders, of hemostasis and urine alkalinization.

The patient was submitted to 20 daily and consecutive HBO sessions for 120 minutes each, at 2.5 ATM and with supplemental O2 at 100%. The treatment was initiated on the third postoperative day. In addition, the patient received daily dressings with collagenase ointment and local antimicrobial medication. Surgical debridements of necrotic tissues were also carried out during the treatment.

We observed remarkable and quick reduction of the edema on the entire left lower extremity, in addition to clear granulation of soft tissues, with later healing of the area submitted to fasciotomy during plastic surgery (Figures 3 and 4).

click hereFigure 3 - Wide view of the left lower extremity (LLE) on the 8th postoperative day and after six HBO sessions and dressings. Remarkable diffuse edema, area of fasciotomy and wound dehiscence in the inguinal region.

click hereFigure 4 - Same view of LLE at the end of 20 HBO sessions, including dressings and surgical debridement. The reduction of the edema is clearly observed, in addition to rich granulation of bloody areas.

DISCUSSION

Collagen synthesis, angiogenesis and epithelization are extremely reliant on oxygen tensions. In environments with low oxygen availability, both cellular and humoral activities are impaired, making healing physiology unsustainable. Oxygen is essential for the activity of polymorphonuclear cells, for fibroblast activation and for the hydroxylation of lysine and proline, a crucial stage of this synthesis. Hypoxia is the basic stimulus to angiogenesis. HBO elevates the pressure of oxygen between healthy and injured tissues, thus potentiating the stimulus for its development.3,6 In epithelial wounds, HBO enhanced the angiogenic response, as shown by histological analyses. An increase in vascularization was also clearly observed in cases of patients with malignant neoplasms who had their head and neck cancers resected or irradiated.7 These peculiarities favor the healing of ischemic wounds by the concomitant use of hyperbaric oxygen therapy and widely known measures, such as surgical removal of necrotic tissues, drainage of liquid and/or purulent collections, administration of antibiotics and correct dressing application.

In the three cases reported herein, we always used hyperbaric oxygen therapy judiciously, never in isolation. We noted, however, that tissue granulation and tissue response to surgical debridements yield better results when therapies are combined.

It is commonly known that at a pressure of 3 ATA, blood plasma contains 6.8 vol% of oxygen, which is the mean oxygen concentration required by the tissues. For that reason, hyperbaric oxygen therapy is used in cases of acute anemia or in situations in which individuals may not receive blood and its derivatives for medical and, especially, religious reasons.5,8 In our clinical practice, we have observed that patients who suffer from large blood loss feel better during HBO sessions, even when anemia is readily corrected.

In tissues submitted to acute ischemic events, such as compartmental syndrome or limb reimplantations, common situations in vascular trauma, there is a decrease in oxygen supply, which deviates energy production to anaerobic glycolysis. As oxygen supply is reduced and time is prolonged, the cellular metabolism slows down, resulting in injury to the cell membrane and in progressive increase of endothelial permeability, in a chain reaction. As soon as circulation is reestablished, the pressure of the distal vascular wall rises, causing physiological arteriovenous shunts to open and remarkable clinical edema to develop. Once again, there will be a self-sustainable response, producing a new deregulation of reflex cellular mechanisms, giving rise to paradoxical ischemia.9

Experimental studies showed that hyperbaric oxygen therapy was efficient in reducing edema after ischemic events. This is possible due to the transient vasoconstriction secondary to the high tissue pressure of oxygen. A reduction of approximately 20% in blood flow after the administration of O2 at the pressure of 2 ATA was observed in healthy human forearms of volunteer individuals.9 Such principles are of utmost importance in situations in which large reperfusion events are present.

In clinical practice, we often observe reperfusion events after traumatic situations. The reperfusion syndrome observed in the third case is extremely common and easily predicted. When we indicated hyperbaric oxygen therapy for situations that are similar to that case, this indication was based on the properties and knowledge described.

Some species of aerobic bacteria can produce enzymes (superoxyreductase and catalase) that break down free radicals, which are essential for bacterial destruction. On the other hand, anaerobic and microaerophilic bacteria cannot produce such enzymes, and are therefore susceptible to free radicals originated from oxygen supply. Given the increase in the supply of supplemental O2 by hyperbaric oxygen therapy, there is a direct effect on anaerobic and microaerophilic bacteria. Conversely, although it has no direct effect on aerobic bacteria, this therapy potentiates the activity of polymorphonuclear neutrophils,10 by acting synergistically with antimicrobial substances in cases of infections.

Clinical experience with hyperbaric oxygen therapy is extensive, including studies that confirm the reduction in amputation rates in patients who had severe ischemic foot ulcers (Wagner III and IV) by the combination of HBO with multidisciplinary therapies.11-15 Shorter hospital stays, reduced need of surgical procedures, lower costs of the therapy and the time necessary to treat these patients are statistically significant factors.

Based on the described angiogenic properties and on the improved healing of tissues, we have recommended HBO for patients with trophic injuries of the extremities, both as initial treatment and one that precedes a probable surgical procedure (first case) or as major clinical measure, in situations in which, despite the wound, we have a tissue with a reasonable blood supply (second case). In the first case, however, hyperbaric oxygen therapy was also used as a desperate healing attempt, in a surgically intractable and extremely unfavorable situation. In spite of the initial improvement, major amputation was inevitable, showing once again the severity of ischemic events secondary to vascular diseases.

Among the reported complications, secondary to hyperbaric oxygen therapy, we have situations related to secondary effects on organs and tissues that are susceptible to intracavitary pressure discrepancies, such as pneumothorax, otitis media, arterial gas embolism, ocular fibroplasia and transient compromise of expiratory capacity. The exposure to high pressures of O2 can also reduce the central nervous system threshold, which can result in seizures. The reported side effects are directly related to exposure time and to the absolute pressure of this therapy. The ideal patterns of O2 exposure are the following: pressure of 2.5 ATM, in intermittent sessions and length of approximately 90 to 120 minutes.3,5,16

With regard to the use of HBO during pregnancy, studies report that, in experimental animals, the exposure did not cause problems to their offspring. Russian studies show that HBO in pregnant women did not cause complications to the fetus.17

Currently, the main therapeutic indications of hyperbaric oxygen therapy are as follows:

1) Acute and extremely chronic conditions: decompression sickness (usually in divers); arterial gas embolism and severe intoxications caused by carbon monoxide; clostridial infections, such as myonecrosis and tetanus; necrotizing fasciitis; acute traumatic ischemia; severe epithelial disorders and diseases, such as epidermolysis bullosa and extensive burns.

2) Chronic conditions: actinic lesions; osteoradionecrosis; refractory osteomyelitis; healing disorders.

We can therefore say that there is scientific evidence for the indication of hyperbaric oxygen therapy in situations involving reperfusion, ischemic and infectious events.

CONCLUSIONS

Vascular diseases are severe clinical entities, especially peripheral disorders of ischemic etiology. Such diseases justify the constant search, based on ethical studies, for therapies that serve as an adjunct to conventional treatments.

Altogether, hyperbaric oxygen therapy is certainly one more therapeutic tool to be used and explored by modern angiology and vascular surgery.

REFERENCES

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14. Faglia E, Favales F, Aldeghi A, et al. Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. Diabetes Care 1996;19:1338-43.

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J Vasc Br - Official Publication of the Brazilian Society of Angiology and Vascular Surgery