Researchers Call for Larger Studies at Lower Oxygen Doses
By Sandra Basu
WASHINGTON – The use of hyperbaric oxygen to improve mild traumatic brain injury (mTBI) resulted in no symptom relief at the exposure pressure tested, according to a new report, which calls for larger studies at lower total oxygen doses.1
“Given that HBO2, in this controlled study, demonstrates no therapeutic value, requires long treatment series, is expensive, exposes patients to potential side effects, and has limited availability, clinical usage is not warranted for the management of symptoms of chronic mTBI at this treatment pressure,” wrote the authors.
Study authors noted that both the test and control groups improved more than expected six months after developing mTBI but said it could have been the result of the placebo or other unrelated effects. The test group received doses of hyperbaric oxygen at 2.4 ATA but did not show “significant symptomatic improvement” in their post-concussion syndrome symptoms over a group receiving a sham therapy.
In the sham therapy, study participants breathed room air in the chamber at 1.3 ATA.
Hyperbaric oxygen is an approved therapy for medical conditions such as dive-related injuries, soft-tissue healing and carbon monoxide poisoning but is not an FDA-approved treatment for TBI symptoms. Citing anecdotal evidence that the treatment is beneficial for TBI sufferers, members of Congress members and advocacy groups have pressed DoD to explore its use.
The current study, published recently in the Journal of Neurotrauma, is one of three planned in the collaborative initiative for HBO2 research developed by DoD and VA. Researchers in this study were from the USAF School of Aerospace Medicine, at Lackland AFB, TX; the Uniformed Services University of the Health Sciences in Bethesda, MD; Virginia Commonwealth University and the Richmond Defense and Veterans Brain Injury Center, both in Richmond and VA’s national Physical Medicine and Rehabilitation Program office.
“These trials utilize varying HBO2 doses and clinically relevant, consistent measures of outcome addressing physical, cognitive, and behavioral functioning,” the study authors acknowledge. “Given the large numbers of individuals experiencing these injuries and the paucity of proven treatments, the current study and its companion studies take on added clinical significance and military relevance.”
For the pilot study, researchers at the U.S. Air Force School of Aerospace Medicine recruited 50 active duty servicemembers with post-concussion syndrome from various bases who were still symptomatic three to 71 months after their TBI injury. Post-concussion syndrome is defined as persistence of mTBI symptoms for more than three months after injury.
The researchers administered 100% oxygen at 2.4 ATA for 90 minutes to the intervention group, while the sham-control group breathed air (21% O2) for 90 minutes at 1.3 ATA (about the pressure at 11 feet of sea water) with a slow drift to 1.2 ATA. Exposures were done on weekdays only for a total of 30 exposures over an eight-week period.
The Agency for Healthcare and Research Quality recommended in 2003 that future research involving HBO2 use for TBI look at hyperbaric oxygen from a dose response perspective. As a result, the study “bracketed the pressure of 1.5 ATA seen in most anecdotal chronic mTBI case reports and series by using 1.3 ATA air and 2.4 ATA 100% oxygen,” according to the authors.
Overall improvement could have been due to placebo effect, the natural resolution of symptoms over time, “or possibly an effect from exposure to sham-control partial pressures of oxygen or nitrogen,” the researchers note, adding that the change in living environment and routine to become part of the study may also have had a positive influence.
Lead author George Wolf, MD, a staff physician at Wilford Hall Ambulatory Surgical Center and an associate faculty member at U.S. Air Force School of Aerospace Medicine, told U.S. Medicine that the study results do not necessarily mean that HBO2 is ineffective for TBI patients but that study results suggest “2.4 ATA is not your optimal treatment pressure.”
Wolf and his colleagues note in their report that “future studies with lower dose HBO2 are needed to assess this and are planned as part of the DoD-VA cooperative group. Other proposed treatment pressures (oxygen doses), individual treatment duration and number of treatments may or may not have similar results.”
Both Col. Leonardo Profenna, MD, chief of hyperbaric medicine at the Air Force School of Aerospace Medicine, and Wolf said the hyperbaric oxygen research is important in light of the need to help find new therapies for troops struggling with TBI.
“With TBI there are so few biological treatments that can actually improve the performance of the injured brain. That is why it is so important for us to look into hyperbaric oxygen … to try to find an optimal dose where it is helpful,” Profenna told U.S. Medicine.
John T. Povlishock, PhD, editor-in-chief of the Journal of Neurotrauma and neuroscience professor at the Medical College of Virginia in Richmond, called the article “a particularly important communication that addresses a continued area of controversy, particularly as it relates to the treatment of our military personnel sustaining mild traumatic brain injury.”
“While the authors stress that, based upon their findings, larger multicenter, randomized, controlled, double-blinded clinical trials should be conducted,” Povlishock said, “the compelling data in this communication does not support any therapeutic value for hyperbaric oxygen treatment, striking a cautionary note for those involved in the care and management of this patient population.”
The study was primarily funded by the U.S. Air Force Medical Support Agency Medical Modernization Directorate and the 711th Human Performance Wing, with additional support of the U.S. Navy Bureau of Medicine and Surgery and the USAMRMC, according to U.S. Army Medical Materiel Development Activity.
1. Wolf EG, Cifu D, Baugh L, Carne W, Profenna L. The Effect of Hyperbaric Oxygen on Symptoms Following Mild Traumatic Brain Injury. J Neurotrauma. 2012 Oct 2. [Epub ahead of print] PubMed PMID: 23031217.