The report is a product of the VA/HSR Evidence Synthesis Program.

Evidence Brief: Hyperbaric Oxygen Therapy for Traumatic Brain Injury and/or PTSD

Following certain types of injuries, our bodies may demand more oxygen than is available in the normal air we breathe to supply our cells with the fuel necessary for healing processes (i.e., metabolism, cellular growth and repair). Hyperbaric oxygen therapy (HBOT) is designed to increase the supply of oxygen to our blood and tissues. In normal air, the oxygen level is only around 21%; HBOT delivers 100% medical grade oxygen inside a chamber where the air pressure is raised at least 1.4 times greater than normal. The FDA has cleared HBOT for several types of injuries, including wound healing, necrotizing infections, burns, radiation injury, and carbon monoxide poisoning. Given the microscopic and macroscopic wounds to the white matter of the brain that have been attributed to traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD), HBOT also has been explored as a therapy for these conditions. However, the available evidence from randomized controlled trials on using HBOT for TBI and/or PTSD has been controversial, widely debated, and potentially confusing. For example, a 2015 US Government Accountability Office report and an independent systematic review (Crawford et al., June 2017) have concluded that HBOT is no better than sham. Despite these findings, HBOT continues to be promoted for the treatment of TBI and/or PTSD, largely based on case series and anecdotal testimonials.

Given this controversy, the ESP Coordinating Center responded to a request from VA's Center for Compassionate Care Innovation for an evidence brief on the use of hyperbaric oxygen therapy for the treatment of TBI, PTSD, or their co-occurrence. Findings will be used to inform considerations of the clinical use of HBOT in Veterans with TBI and/or PTSD. Investigators with VA's Evidence-based Synthesis Coordinating Center in Portland, OR reviewed the literature including: MEDLINE®, Cochrane Central Register of Controlled Trials, CINAHL, PILOTS, the Database of Randomized Controlled Trials in Diving and Hyperbaric Medicine, as well as scientific information requests to 20 manufacturers from 1/1/2012 to 9/20/2017. After reviewing 314 articles, 26 (including 16 randomized controlled trials) were used for this evidence brief.

Summary of Review
Reviewers found that the large treatment benefits demonstrated for HBOT in uncontrolled case series have not been easily replicated in well-controlled randomized controlled trials (RCTs). Possible explanations raised for this include:

• The potential benefits are subtle and demonstration requires larger RCTs;
• HBOT is, in fact, ineffective;
• The sham design has been problematic; and/or
• Bias against HBOT (and other emerging treatments) in VA/DoD investigators that conducted RCTs (and the medical field in general) has led to flaws in the design and interpretation of HBOT research.

Reviewers found no indication that investigator bias caused flaws in the design or interpretation of VA/DoD RCTs and are unconvinced that the current evidence clearly points to one explanation over another for HBOT's lack of consistent benefits. The uncertain evidence that HBOT is effective does not support broad usage of HBOT as initial treatment. For patients who have not responded to or tolerated trials of other treatment options however, the conflicting evidence and positive response in case series may be seen as justification to try HBOT. Some sites in VA are offering such treatment to a limited number of Veterans. Veterans and their physicians should carefully weigh the possibility of individual benefit against the substantial costs of HBOT (which must be paid for in the community), the possible risks (e.g., barotrauma, pulmonary complications) and the lack of strong evidence for lasting benefit.

Future Research
A small-scale clinical demonstration may provide the opportunity to improve data collection on comorbidities, clinically relevant patient outcomes, patient expectations, and documentation of the types and durations of previous and ongoing treatments. Clinical evaluation should be done in tandem with neuroimaging and an assessment of the role of potentially exaggerated patient expectations that may result due to publicized reports of HBOT as a "miracle cure." In addition, to improve our knowledge about HBOT's potential to improve clinically meaningful outcomes, investigators suggest the establishment of a set of validated outcome measures that include minimally important symptom difference thresholds. To control for potential natural waxing and waning of symptoms and evaluate durability, they suggest outcome assessment at multiple time points during and 6 to 12 months following the treatment period. Also, in order to potentially improve consistency in the interpretation of future HBOT RCT results, the investigators suggest that future HBOT researchers consult with and document endorsement from HBOT proponents on the design of a randomized controlled trial.

Reference
Peterson K, Bourne D, Anderson J, Boundy E, Helfand M. Evidence Brief: Hyperbaric Oxygen Therapy (HBOT) for Traumatic Brain Injury and/or Post-traumatic Stress Disorder. VA ESP Project #09-199; 2018.

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This Management e-Brief is provided to inform you about recent HSR&D findings that may be of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. If you have any questions or comments about this Brief, please email CIDER. The Center for Information Dissemination and Education Resources (CIDER) is a VA HSR&D Resource Center charged with disseminating important HSR&D findings and information to policy makers, managers, clinicians, and researchers working to improve the health and care of Veterans.

This report is a product of VA/HSR&D's Quality Enhancement Research Initiative's (QUERI) Evidence-Based Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers –; and to disseminate these reports throughout VA.

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