Special Feature

Hyperbaric Oxygen Therapy

By Jun Takezawa, MD

Hyperbaric oxygen therapy (hbot) has long been accepted as a primary treatment for decompression sickness with and without air embolism, and the indications for its use have been expanding to various other diseases and pathological states. However, its effectiveness has not been thoroughly validated in terms of a risk-adjusted outcome.

There are 259 hyperbaric oxygen facilities with 344 monoplace chambers in the United States, and 4000-5000 patients are annually treated with HBOT. In Japan, there are 857 hyperbaric oxygen chambers with 799 mono-place chambers, and approximately 200,000 patients receive HBOT. It is surprising when realizing the differences between these countries.

The first systematic critical appraisal of published papers describing the effectiveness of HBOT was attempted by Genevieve Gabb, a medical student at Stanford University and Eugene D. Robin, in 1987.1 In this paper, they reviewed 61 papers and found that HBOT was claimed to be indicated in 132 diseases and pathologic states. However, when they re-evaluated the scientific basis for its indication, no randomized, controlled clinical trials (RCTs) were found to validate it, and most papers were case consecutive study and those without controls. They concluded that history of HBOT was characterized by unscientific and uncritical pragmatism, and HBOT was looking for diseases that might benefit from it. Furthermore, the risks of adverse effects of HBOT were rarely questioned.

Since the original criticism of HBOT by Gabb and Robin, significant effort has been placed to conduct RCTs for re-evaluating the effectiveness of HBOT. In the following summary, the effectiveness of HBOT as indicated in various diseases is re-evaluated based on the published results of RCTs.

Decompression Sickness

Approximately 500 recreational divers suffer from decompression sickness per year in the United States. HBOT reduces bubble size and corrects hypoxemia with improving hemostasis, endothelial damage, and neutrophil activation. HBOT at 2.5-3.0 atmospheres absolute (ATA) for 2-4 hours is indicated within six hours after the onset of symptoms. However, no RCT with normobaric oxygen as a control has been carried out. Nevertheless, HBOT is indicated to decompression sickness without supportive evidence made by RCT because of strong physiological basis and extensive experiences.

Multiple Sclerosis

Three double-blind RCTs were reported. Wood et al randomized 41 patients with multiple sclerosis into two groups;2 21 patients who received HBO and 20 patients receiving placebo gas mixture. A full 100% O2 was given at two ATA for 20 sessions of 90 minutes for one month. No benefits in terms of functional and claimed improvement were confirmed in the HBO group. Confavreux et al carried out another RCT on multiple sclerosis.3 Seventeen patients received HBOT 100% O2 at 1.5 ATA for 90 minutes, five days a week, for one month. The patients were followed-up for one year. There was no better improvement in patients of the HBOT group in terms of Kurtzke disability status score. Barnes et al reported the results of an RCT, which enrolled 120 patients.4 The patients with HBOT received 100% O2 at two ATA for 90 minutes daily for 20 sessions. HBOT did not alter disease progression as measured by the Kurtzke disability status score. Reversible retinal damage was significantly higher in the HBOT group. (See Table 1.)

Table 1-The RCTs for Multiple Sclerosis
Investigator Year Intervention Outcome
Barnes '87 2 ATA O2
1 ATA NA
NS
Haper '86 1.75 ATA O2
1.75 ATA 12.5% O2
NS
Wiles '86 2 ATA O2
1.1 ATA NA
+
Confavreux '86 1.5 ATA O2
1.1 ATA NA
NS
Wood '85 2 ATA O2
2 ATA 10% O2
NS


Gas Gangrene and Clostridial Infection

An alpha-toxin produced by clostridium causes myonecrosis and shock, resulting in extreme pain and tissue gas. Treatment includes surgical decompression/excision and penicillin administration. Although HBOT has been used as an adjunctive therapy, there has been no RCT where 100% O2 at one ATA was used as a control.

Diabetic Foot Ulcer

Four RCTs on diabetic foot ulcer were reported. Leslie et al conducted RCT on diabetic foot ulcer using topical HBOT.5 They enrolled 28 patients; 12 for topical HBOT group and 16 for the control group. Ulcer size did not significantly change between the groups on days 7 and 14. The topical HBOT was not effective in treating diabetic foot ulcer. Faglia et al enrolled 70 diabetic patients with foot ulcer;6 35 patients received systemic HBOT and 33 did not. The risk reduction for amputation in the treatment group was 0.26 (95% CI 0.08-0.84), markedly decreased the risk of amputation. Other trials with small patients’ numbers revealed no beneficial effect of HBOT. However, a further RCT with a larger observational number of patients is definitely required. (See Table 2.)

Table 2-The RCTs for Diabetic Foot Ulcer
Investigator Year Points Intervention Outcome
Leslie '88 12
16
1 ATA O2
1 ATA NA
NS
Faglia '96 35
33
2.5 ATA O2
1 ATA NA
Fewer Amputations
Hummarlund '94 8
8
2.5 ATA O2
2.5 ATA NA
NS
Zamboni '97 5
5
2.0 ATA O2
1 ATA NA
NS


Closed Head Trauma

Rockswold et al randomized 168 patients with closed head trauma (GCS < 9) into two groups;7 84 patients who received 100% O2 at 1.5 ATA every eight hours for one hour, for two weeks, and 82 control patients. Although the mortality rate tended to be smaller in the treated group (17% in HBOT vs 32% in control), the number of favorable outcomes in the treatment group did not increase significantly.

Crush Injury

Bouchour et al randomized 36 patients with crush injuries into two groups within 24 hours after surgery.8 Eighteen patients received HBOT (100% O2 at 2.5 ATA for 90 minutes, twice daily over 6 days), and 18 patients for placebo group. No significant differences in LOS, number of wound dressings complete healing, and additional surgery were observed between the groups. Subgroup analysis suggested that HBOT might provide patients younger than 40 years old receive severe (grade III) crush injury with less additional surgery and less improvement in wound healing.

Burn

Brannen et al conducted RCT on patients with burn who were referred to a burn center.9 The 125 burn patients admitted within 24 hours of injury. HBOT was provided at two ATA for 90 minutes, twice daily, greater than 10 treatments. No significant differences were observed in mortality, number of operations, and LOS for the survivors.

AMI (HBOT MI Study)

Stavistsky et al randomized a total of 112 patients with AMI to receive r-TPA or STK with HBOT, and r-TPA or STK alone.10 Although there was a trend in improving EF and time to relief chest pain in the HBOT group, other outcomes showed no difference between the groups. HBOT is not indicated in a patient with AMI.

Stroke

Nighoghossian enrolled 27 patients with MCA occlusion within 24 hours, and randomized them into two groups;11 100% O2 1.5 ATA (14) vs. NA 1.5 ATA (13). Although Orgogozo scale at one year was better in HBO, no difference in Rankin score at six months and one year was observed between the groups.

Acute Carbon Monoxide (CO) Poisoning

Several RCTs were conducted from 1989 to 1996. However, all failed to prove any beneficial effect of HBOT in patients with CO poisoning. (See Table 3.)

Table 3 -RCTs for Carbon Monoxide Poisoning
Author Year Pts Control Outcome
Raphael '89 343 100% O2 1 ATA NS
Thorn '95 65 100% O2 1 ATA NS
Duchess '95 26 100% O2 1 ATA ?
Weaver '95 50 100% O2 1 ATA NS
Mathieu '96 575 100% O2 1 ATA NS (1 yr.)


Recently, Scheinkestel et al randomized 191 patients with various severity of CO poising into two groups;12 patients who received HBOT with 100% O2at 2.8 ATA for 60 minutes for three days and the patients who received normobaric O2. More patients in the HBOT group received additional treatments, and HBOT patients had worse outcomes in the learning tests. There were no benefits in patients who received HBOT.

Summary

In summary, as shown in Table 4, there are a few indications of HBOT; decompression sickness and diabetic food ulcer. However, at present, so many patients with different diseases are treated with HBOT. The RCTs on these disease entities are urgently required to prove its effectiveness.

Table 4 - Current Indications of HBOT
Decompression Sickness

Embolism

Gangrene

Multiple Sclerosis

Diabetic Food Ulcer

Head Injury

RCT

-

-

+

+

+

+

Indication

+

?

-

-

+

-

Crush Injury

Burn

Acute MI

Stroke

CO Poisoning

RCT

+

+

+

+

+

Indication

-

-

-

-

-



References

1. Gabb G, Robin ED. Hyperbaric oxygen-A therapy in search of diseases. Chest 1987;92:1974-1982.

2. Wood J, et al. A double-blind trial of hyperbaric oxygen in the treatment of multiple sclerosis. Med J Aust 1985;6:238-240.

3. Confavreux C, et al. Ineffectiveness of hyperbaric oxygen therapy in multiple sclerosis. A randomized placebo-controlled double blind study. Presse Med 1986; 15:1319-1322.

4. Barnes M P, et al. Hyperbaric oxygen and multiple sclerosis: Final results of a placebo-controlled, double blind trial. J Neurol Neurosurg Psychiatry 1987;50: 1402-1406.

5. Leslie CA, et al. Randomized controlled trial of topical hyperbaric oxygen for treatment of diabetic foot ulcers. Diabetes Care 1988;11:111-115.

6. Faglia E, et al. Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. A randomized study. Diabetes Care 1996;19:1338-1343.

7. Rockswold GL, et al. Results of a prospective randomized trial for treatment of severely brain-injured patients with hyperbaric oxygen. J Neurosurg 1992;76:929-934.

8. Bouachour G, et al. Hyperbaric oxygen therapy in the management of crush injuries: A randomized double-blind placebo-controlled clinical trial. J Trauma 1996;41:333-339.

9. Brannen AL, et al. A randomized prospective trial of hyperbaric oxygen in a referral burn center population. Am Surg 1997;63:205-208.

10. Stavitsky Y, et al. Hyperbaric oxygen and thrombolysis in myocardial infarction: The HOT MI’ randomized multicenter study. Cardiology 1998;90:131-136.

11. Nighoghoissan N, et al. Hyperbaric oxygen in the treatmet of acute ischemic stroke. Stroke 1995;26: 1369-1372.

12. Scheinkestel CD, et al. Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: A randomized controlled clinical trial. Med J Aust 1999;170:
203-210.