STUDIES ON HYPERBARIC OXYGEN THERAPY
RELATIVE TO :
COMPLEX REGIONAL PAIN SYNDROME
(REFLEX SYMPATHIC DYSTROPHY)
(SUDECK'S SYNDROME)

The Journal of International Medical Research
2004; 32: 258 - 262

Effectiveness of Hyperbaric Oxygen Therapy in the Treatment of Complex Regional Pain Syndrome Department of Physical Therapy and Rehabilitation and Department of Underwater and Hyperbaric Medicine Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey.

In this double-blind, randomized, placebo-controlled study we aimed to assess the effectiveness of hyperbaric oxygen (HBO) therapy for treating patients with complex regional pain syndrome (CRPS). Of the 71 patients, 37 were allocated to the HBO group and 34 to the control (normal air) group. Both groups received 15 therapy sessions in a hyperbaric chamber. Pain, edema and range of motion (ROM) of the wrist were evaluated before treatment, after the 15th treatment session and on day 45. In the HBO group there was a sign significant decrease in pain and edema and a significant increase in the ROM of the wrist. When we compared the two groups, the HBO group had significantly better results with the exception of wrist extension. In conclusion, HBO is an effective and well-tolerated method for decreasing pain and edema and increasing the ROM in patients with CRPS. Introduction.

Severe local pains in the extremities, skin color changes, hypo- or hyperhydrosis and localized osteoporosis characterize complex regional pain syndrome (CRPS). Since its original description by Mitchell in 1864, CRPS, previously known as reflex sympathetic dystrophy, has been a poorly understood and frequently overlooked condition! And its etiology remains unclear. Trauma, which is often mild, is the main etiological factor but not the only one.2 Moreover, there is no relationship between the severity of trauma and the severity of the syndrome.3 the pathogenetic universally accepted mechanism proposed by Leriche is sympathetic-reflex imbalance.4 a factor contributing to many chronic pain syndromes is over activity of the sympathetic nervous system. The patient's pain is usually diffuse and does not correspond to a dermatome or peripheral nerve distribution. The clinical symptoms of CRPS arise from the sensory, motor and sympathetic nervous systems. Early diagnosis influences the response to treatment and the evolution of the disease. There are three stages in the development of CRPS: acute (stage I), dystrophic (stage II) and atrophic (stage II!).
-------------------------------------------------------------------------------------------------------- MZ Kiralp, ~ Yildiz, D Vural et al.
HBO therapy for complex regional Pain syndrome

The atrophic stage is irreversible and is characterized by stiffness and flexion contractures of the hand. The patient complains of vasomotor pain and the trophic changes in the skin, muscles and skeleton are permanent and progressively worsen until there is ankylosis and complete loss of function. There are usually no characteristic biochemical abnormalities. The typical radiographic signs of CRPS appear only after several weeks or months and constitute an important, but non-specific, finding in favor of a positive diagnosis of the disease. The radiographic examination can not be used to classify the stage of the syndrome. Treatment of CRPS is more difficult than the diagnosis and classification of the disease. There are a variety of treatments, but the treatment window is too short to obtain positive results and the disease progresses quickly to the next stage. Hyperbaric oxygen (HBO) therapy has been used worldwide to treat many diseases and involves breathing 100% oxygen via an endotracheal tube, mask or hood in a pressure chamber, under pressures higher than 1 atmosphere absolute (ATA). Dissolved oxygen in the blood can increase from 0.3% to 6.8% in proportion to the applied environmental pressure with HBO therapy. Both the increased concentration and the partial pressure of oxygen increase oxygenation of the whole body. The increased tissue oxygen enhances the growth of fibroblasts, formation of collagen, angiogenesis and the phagocytic capabilities of the hypoxic leucocytes.7.8 the aim of the present study was to examine the efficacy of HBO for treating CRPS.

Patients and Methods

PATIENTS

Patients who were diagnosed with posttraumatic CRPS at the Gulhane Military Medical Academy Haydarpasa Training Hospital Department of Physical Medicine and Rehabilitation between 2002 and 2003 participated in the study. All patients had stage I and II of the disease. Patients were allocated alternately to receive HBO therapy (HBO group) or normal air (control group). After randomization, a physician blinded to the group allocation evaluated the patients for contraindication to HBO therapy. Patients with contraindications for HBO therapy were excluded from the study, irrespective of their allocated group. Only the physician administering treatment knew whether the patients were receiving 100% oxygen or air. This was necessary for safety reasons. The time period between the diagnosis and the occurrence of the trauma was approximately 1.5 months. The patients had not received any treatment for CRPS and were given information pertaining to CRPS and HBO treatment. All patients gave informed consent. GATA Military Medical Faculty Ethical Committee approved the study.

TREATMENT

Both patient groups received 15 90-min therapy sessions with either HBO or normal air at 2.4 ATA on 5 days of the week (1 session per day). In addition, 500 mg paracetamol was given three times daily. No physical therapy was given to ensure standardization among the patients and to detect the efficacy of HBO therapy. Patients were evaluated before treatment, after completion of the 15 sessions, and after 45 days.

CLINICAL EVALUATION

Pain was evaluated using a visual analogue scale (VAS) where 0 was no pain and 10 was unbearable pain. Range of motion (ROM) evaluation included goniometric assessment of wrist extension and wrist flexion. Edema was evaluated by measuring the wrist circumference.
---------------------------------------------------------------------------------------------------------- MZ Kiralp, ~ Yildiz, D Vural et aL
HBO therapy for Cmplex Regional Pain Syndrome

Results

Of the 71 patients who participated in the trial (49 men, 22 women), 37 were in the HBO group (mean age 29.4 :t 10.2 years) and 34 in the control group (mean age 31.4 :f: 9.15 years). The VAS scores, wrist flexion, extension and circumference measurements before and after treatment are given in Table 1. In the VAS evaluation, it was seen that pain started to decrease from the first day and had decreased further after session 15 and day 45. This was statistically significant in the HBO group (P < 0.(01). A statistically significant increase in wrist flexion was also observed in the HBO group after 15 therapy sessions compared with before treatment, and on day 45 compared with after session 15 (P < 0.(01). A statistically significant decrease in the wrist circumference (due to decreased edema) was observed between groups, between the end of treatment (after session 15) and day 45 values (P < 0.(01). There was a statistically significant difference between the HBO and control groups for all variables (P < 0.001) except wrist extension.

Discussion

Complex regional pain syndrome is a chronic condition characterized by severe burning pain, extreme sensitivity to touch, swelling, excessive sweating and changes in bone and skin tissues. In previous studies, non-steroidal anti-inflammatory drugs (NSAIDs), narcotic analgesics and vasodilators were used as treatments for CRPS, but complete resolution of the signs and symptoms could not be achieved. In CRPS, hypoxia and acidosis reduced the pain threshold and tolerance. During HBO treatment hyperoxia causes vasoconstriction, decreases edema, and increases the partial pressure of oxygen in the tissues. In addition, it stimulates the activity of depressed osteoblasts and decreases the formation of fibrosis tissue. Thus it breaks up the physiopathological mechanism that is the basis of CRPS. These features of HBO therapy led us to evaluate its efficacy for treating CRPS. Tuter ET al.9 conducted a study on 35 subjects, 20 of whom received HBO treatment and 15 received combined analgesic medication. A significant decrease in the severity of pain was detected in the patients receiving HBO treatment. Moreover, allodynia and edema decreased, the ROM of extremities affected by CRPS increased and skin color returned to normal.

In his case report, PeachlO noted a patient with CRPS who had an allergy to steroids, NSAIDs and narcotic analgesics, and did not respond to vasodilators. His pains disappeared after a session of HBO, however, and his cyanosis decreased significantly.

In our study patients with post-traumatic CRPS of the upper extremity received 15 sessions of HBO therapy or normal air. In the HBO group there was a significant difference between the VAS scores and wrist flexion before and after treatment, and in wrist circumference between the 15th therapy session and day 45. A comparison of the HBO and control group results also revealed significant differences after the 15th therapy Session and day 45.

MZ Kiralpl ~ Yildiz~ 0 Vural et al
----------------------------------------------------------------------------------------------------------- HBO therapy for Complex Regional Pain syndrome

We consider this significant healing to be a result of the increased oxygenation of the tissues. None of the patients progressed to the third stage of the disease. In conclusion. HBO is an effective and well tolerated method of decreasing pain and edema and increasing the range of motion in CRPS

Our preliminary experience indicates that HBO therapy may be a valuable alternative to other methods for treating CRPS. ·

Received for publication 26 November 2003 Accepted subject to revision 2 December 2003 o Revised accepted 21 January 2004 Copyright If 2004 Cambridge Medical Publications
----------------------------------------------------------------------------------------------------------- Reflex Sympathetic Dystrophy

HYPERBARIC OXYGEN THERAPY IN THE TREATMENT OF
SUDECK'S SYNDROME (RSD, Complex Pain Syndrome)
G. Lovisetti, L. Lovisetti, AFavelli Istituto di Terapia Iperbarica via Oltrecolle 62, 22100 Como, Italy

SUMMARY:

The decrease in tissue hypoxia obtained with Hyperbaric Oxygenation (HB02) counteracts the effects of reflex vasomotor disturbances caused by an injury in post-traumatic Sudeck's syndrome. In reflex sympathetic dystrophy, after an initial vasospasm, a loss of vascular tone with persistent vasodilatation. Causes increased osseous vascularity and rapid bone resorption. Chronic edema results from venous overload and passive capillary repletion:; local lack of oxygen and acidosis cause demineralization and bone protein, atabolism. The hypoxic static induces undifferentiated mesenchymal cells and younger fibroblast to a rapid maturation, with abnormal production of fibrous tissue, retraction, and adhesions and joint stiffness.

In our experience HB02 proved to be very effective even after a few treatments resolve local swelling and to relieve pain 'in 13 of 15 patients affected by Sudeck's Syndrome who had not positively reacted to other therapies. In 14 patients the sympathetic dystrophy affected the lower limb. Strict diagnostics criteria based on history, physical examination and radiological pictures have been respected. Technetium scintigraphy was performed and confirmed diagnosis in 7 cases. A second Te scintigraphy carried out after 20 sessions of HB02 2.5ATA was available in 5 patients and demonstrated normalization of the vascular phase in 4 patients, and amelioration of the late (bone) phase in 3.

Post-traumatic Sudeck's Syndrome is a reflex sympathetic dystrophy which consists of pain and tenderness, usually in a distal extremity, associated with vasomotor instability. swelling and trophic skin changes arising after trauma. The severity of the syndrome is frequently unrelated to the severity of the injury and the dystrophy of often appears after minor trauma. The classic radiographic picture shows acute, patchy bone demineralization. Technetium scintigraphy displays augmented periarticular radionuclide activity. In its early manifestation as Sudeck's Syndrome is unrecognized or misdiagnosed and mistreated in many cases so the patient may have a prolonged and severe disability. No treatment, hitherto has proved to be very successful, once the disease has become established: various forms of physiotherapy, systemic administration of drugs ( anti-inflammatory agents, vasodilators, steroids, calcitonin ), peripheral chemical sympathectomy, infiltration of painful areas with local anesthetics, sympathectomy and sympathetic blocks, section of the sensory nerves or of the dorsal roots of the spinothalamic tract ( in intractable cases) have been reported in the literature. Despite any or all of these measures, many patients improve little or not at all, so that their symptoms persist for months or years. Some patients have attempted suicide because of all the psychological and economical problems related to the disease. The etiopathology of the condition is uncertain. The present pathogenic hypothesis is that after an injury to the limb there is an initial vasomotor reflex spasm and, in a second phase, a loss of vascular tone with persistent vasodilatation and rapid bone resorption.

The increased osseous vascularity appears on the radiogram as a mottled rarefaction caused by increased porosity and decrease in size, thickness and number of trabeculae. Chronic irritation of peripheral sensory nerve secondary to trauma and soft tissue damage determines increased afferent input, abnormal activity of internucial neuronal pool and continuous stimulation of sympathetic motor efferent fibers.

Accordingly to the "gate control theory", predominant small fibers input could result in the unchecked transmission of pain through an "open gate" and create the potential for summation, suppressing the influence of the substantia gelatinosa.Capillary bed repletion, venous overload, opening of the arterovenous shunts provoke tissue hypoxia, catabolite formation, chronic edema and acidosis. Acidosis, inactivity and vascular stasis determine bone resorption of the cortical haversian system. Hypoxia and acidosis lead undifferentiated mesenchymal cells and younger fibroblast to proliferation and quicker maturation ( a state which requires lower oxygen consumption) with abnormal fibrous tissue production, edema organization and joint stiffness. Reflex vasomotor disturbances, resulting in hypoxia, catabolite production and acidosis stimulate sensory nerve termination and close a vicious self sustaining cycle.

The use of HB02 in the treatment of post-traumatic Sudeck's Syndrome is rational. In fact hyperbaric oxygenation induces vasoconstriction and reduce edema: this counteracts vascular stasis and venous repletion, increases depresses osteoblast activity and mineralization, reduces fibrous tissue formation. HB02 therapy seems to break the vicious self sustaining cycle of reflex sympathetic dystrophy, because normalization of local tissue oxygen tension, pH and water interstitial content stops abnormal sensory nerve stimulation and efferent vasomotor phenomenon's.

MATERIAL AND METHOD:

Fifteen patients, (11 men and 4 women) suffering for reflex post - traumatic dystrophy have been treated with HB02 therapy. In 14 of the 15 cases the trauma affected the lower Limbs. The average age was 44.4 years. Initial injury was in 4 cases a calcaneus fracture In 3 cases a malleolus fracture; in the remaining patients Sudeck's Syndrome followed tibial shaft fracture (2 cases), supracondylar femur fracture, multiple metatarsal bone fractures, multiple metacarpal bone fractures and in 3 cases only an history of minor trauma was collected. The disease involved foot I and ankle in 13 cases, the knee in one case and the- hand and the wrist in no case. 10 patients had immobilization ion in cast as the treatment of choice in 3 cases ( supracondylar femur fracture, multiple metacarpal bone fractures, malleolus fracture) the patient underwent surgical treatment. Time elapsed between trauma and diagnosis was 2- 8 months.

Strict diagnostic criteria for inclusion in the study hen been based on history of injury to an extremity, basic examination and radiological picture. Technetium scintigraphy was performed in 7 cases to confirm diagnosis and in 6 cases assessed the evolution of the disease. Clinical diagnosis was based on the presence of pain, tenderness, swelling, vasomotor instability and joint stiffness long lasting after a trauma. Radiographic criteria included patchy. bone demineralization, osteoporosis and cortical cavitation. All the patients were in the acute phase of the syndrome. No case of treatment of the initial or of the atrophic stage has been included in the present study. HB02 protocol consisted in 20 sessions at 2.5 ATA ((5 sessions A week). A further series of 10 sessions was performed in patients (3 cases) present partial clinical recurrence during the week ensuing the termination of the 20 session protocol. A previous calcitonin regimen, although of very limited efficacy, was maintained during HB02 therapy in 5 subjects. No patient used analgesic drugs during HB02 treatment.

Avoidance from weight bearing, functional limb rest and use of an elastic stocking were strongly counseled in patients with lower limb involvement. Te scintigraphy was performed at the end of the 20 HB02 sessions in 6 cases. Radiographic controls were scheduled at 2 and 4 months.

ILLUSTRATIVE CASE REPORTS

1. A 50 year old bricklayer sustained a sprain to his left ankle which remained untreated. After two months ankle pain. quite slight at the beginning, get increasing with paroxysmal exacerbations ,extending to the forefoot and forcing the patient to suspend his work. The radiogram showed the classical picture of reflex sympathetic dystrophy. Pharmacological agents and physiotherapy remained for months ineffective. Presenting to our observation,6 months after the injury, the patient was unable to walk without crutches, suffered of intense and unduly pain and was severely depressed, lacking of confidence in any form of treatment Clinical examination revealed minimal swelling of the ankle, cutaneous hypersensitvity and a 50% decrease in movement of the subtalar and tibiotalar. After the first week of HB02 therapy the patient referred significant decrease in pain which after the second week almost disappeared. A progressive and complete recovery of the movements of the joints involved was recorded. After 20 sessions of HB02 patient was free of any symptom and walked normally. Te scintigraphy demonstrate normalization of the vascular phase and clear reduction of hypercapration in the late phase. Resolution of radiographic picture was slow.

2. 58 year old man. pensioner after an untreated left fore foot distortion the patient complained persistent refractory pain swelling, limitation of motion in the extremity and marked disability to walk. On the basis of clinical radiologic and To scintigraphic findings diagnosis of reflex algodystrophy was formulated 5 months after trauma. After only four HB02 treatments pain and swelling disappeared at the completion of the schedule the patient walked correctly without.crutches and was very satisfied. T e scintigraphy at the end of the therapy demonstrated significant reduction in the hypercaptation of the forefoot. At the 2 month control discrete amelioration in the radiologic pattern was observed.

RESULTS:

After the first week of HB02 a marked reduction of pain and tenderness in the extremity was observed in 9 patients: discrete clinical improvement has been recorded in 3 cases. Reduction of swelling and restoring of movements in the affected extremity has been progressive during the course of HB02 therapy. At the completion of the first HB02 cyde complete recovery ( no pain complete restoration of movements in the affected joints, no swelling) has been observed in 4 cases. Marked clinical improvement (occasional light pain minimal swelling atthe evening, almost normal movements in the affected joints) was present in 5 cases. Moderate clinical improvement (reduction of pain and swelling partial restoration of movements) has been present in 4 cases. In 2 patients despite some reduction of swelling significant pain persisted, in one of these patients, however, pain was present only during weight bearing on the affected extremity and in part could be referred to progressive subtalar degenerative changes after a calcaneus fracture. In 4 cases partial relapse of the symptoms in the weeks ensuing the completion of the first 20 HB02 sessions lead to a second 10 session HB02 cyde with complete recovery. In the 6 cases controlled at the Te scintigraphy after the 20 HB02 sessions normalization of the vascular phase was observed in 4 patients, and reduction in the hypercaptation in the late (bony) scintigram was present in 3 cases. No case of worsening of the scintigraphic picture has been recorded. Resolution ofthe classic radiologic pattern has been generally slow: In a few patients significant improvement at the 2 month control has been observed.

REFERENCES

1. Atkins RM. Duckworth. Kanis JA Features of algodystrophy after Colles' fracture. J Bone Joint Surg 72B:105-10,1990.
2. Benning R. Steinert. Diagnostic criteria of Sudeck Syndrome. Rontgenblatter 41: 239 45,1988
3. Katz MM. Hungerford OS. Reflex sympathetic dystrophy affecting the knee. J Bone Joint Surg 69B:797-803,1987.
4. Kozin F. Ryan LM,Carrera GF, Soin JS. Am J Med 70:23-30,1981.
5. Melzack R. Wall PO Pain mechanisms: a new theory. Sience 150:971-9.1965.
6. Oriani G. Malerba. Ossigenoterapia iperbarica.applicazoni diniche : sindromi neuro algodistrofiche. Ed. 510,1989.
7. Paleari CL. Brondolo W. La sindrome di Sudeck Post-traumatica.Ed. Minerva Mediva, 1960.
8. Poplawski ZJ' VViley AM, Murray JF. Post-traumatic dystrophy of the extre-mities. J Bone Joint Surg 65A:642-55.1983.
9. Schurawitzki H. VVickenhauser J. Fozouldis I. Sadil V, Flalka V. Sudeck syndrome a combined dinico-roentgenologic-nuclear medicine study. Unfall urgie 14:238-46 1988.
10. Schutzer SF, Gossling HR. The treatment of reflex sympathetic dystrophy syndrome. J Bone Joint Surg 66A: 625-29,1984
11. Von Rothkirch T Blauth W. Helbig S. Sudeck syndrome of the hand. Historical review, treatment concept and results. Handchir-Mikrochir Plast-Chir 21:115-26,1989.
-----------------------------------------------------------------------------------------------------------A 44-yr~0Id woman was suffering from acute smoke inhalation. The patient had an extensive medical history, including reflex sympathetic dystrophy syndrome (RSDS) of the left foot and ankle. A physical examination revealed a mottled and cyanotic foot and ankle. The entire foot and ankle were tender and cool to palpation; range of motion was severely reduced for both plantar and dorsiflexion. The patient's test results indicated a carboxyhemoglobin of 6.9%. She was unable to perform the psychometric test due to a severe headache.

Because of the symptom (headache) she was given hyperbaric oxygen (HBO) tolerated the treatment well. Fifteen minutes into the treatment she reported relief of pain in the foot, and the foot was less cyanotic and warmer to the touch. The patient stated that her foot was "pinker than it"s been in years" and that she was completely free of pain. She was asked to keep track of the duration of "pinkness" and pain relief: the foot stayed warm and pink for 8 h after treatment and painless for 18 h. She was next offered treatment at 2 ATA during the next scheduled 90-min. session to take place the following day. Her foot was warm and pink for 1 h after this treatment ~ painless for 2 h. She was treated the following week at 2.3 for 30 min., and after this session the patient reported that "her foot remained warm, pink, and painless for 30 h.

DISCUSSION

Reflex sympathetic dystrophy syndrome is a chronic condition of severe burning pain, extreme sensitivity to touch, swelling, excessive sweating, and changes in bone and skin tissue. Researchers (1) now believe that the symptoms occur because an injured nerve or nerves send mixed signals to the brain. In effect, these inappropriate signals short-circuit and interfere with normal blood flow and sensory signals, thus generating the symptoms of RSDS. The unremitting pain has caused many patients much physical and emotional misery.

This particular patient had few options for relief of the chronic pain associated with RSDS. She is allergic to steroids, non-steroidal anti-inflammation agents, and all narcotics; vasodilators were also ineffective. It is significant that her pain was relieved after initiation of HBO therapy.

Manuscript received May 1995: accepted June 1995.

REFERENCE

I. Lankford R. Thompson J. RSDS upper and lower extremity: diagnosis and management: operative hand surgery, vol 26. St. Louis, MO: Mosby, t 977:163-178.