Systematic Review and Dosage Analysis: Hyperbaric Oxygen Therapy Efficacy in Mild Traumatic Brain Injury Persistent Postconcussion Syndrome

Abstract

BackgroundMild traumatic brain injury results in over 15% of patients progressing to Persistent Postconcussion Syndrome, a condition with significant consequences and limited treatment options. Hyperbaric oxygen therapy has been applied to Persistent Postconcussion Syndrome with conflicting results based on its historical understanding/definition as a disease-specific therapy. This is a systematic review of the evidence for hyperbaric oxygen therapy (HBOT) in Persistent Postconcussion Syndrome using a dose-analysis that is based on the scientific definition of hyperbaric oxygen therapy as a dual-component drug composed of increased barometric pressure and hyperoxia.MethodsIn this review, PubMed, CINAHL, and the Cochrane Systematic Review Database were searched from August 8–22, 2021 for all adult clinical studies published in English on hyperbaric oxygen therapy in mild traumatic brain injury Persistent Postconcussion Syndrome (symptoms present at least 3 months). Randomized trials and studies with symptomatic and/or cognitive outcomes were selected for final analysis. Randomized trials included those with no-treatment control groups or control groups defined by either the historical or scientific definition. Studies were analyzed according to the dose of oxygen and barometric pressure and classified as Levels 1–5 based on significant immediate post-treatment symptoms or cognitive outcomes compared to control groups. Levels of evidence classifications were made according to the Centre for Evidence-Based Medicine and a practice recommendation according to the American Society of Plastic Surgeons. Methodologic quality and bias were assessed according to the PEDro Scale.ResultsEleven studies were included: six randomized trials, one case-controlled study, one case series, and three case reports. Whether analyzed by oxygen, pressure, or composite oxygen and pressure dose of hyperbaric therapy statistically significant symptomatic and cognitive improvements or cognitive improvements alone were achieved for patients treated with 40 HBOTS at 1.5 atmospheres absolute (ATA) (four randomized trials). Symptoms were also improved with 30 treatments at 1.3 ATA air (one study), positive and negative results were obtained at 1.2 ATA air (one positive and one negative study), and negative results in one study at 2.4 ATA oxygen. All studies involved <75 subjects/study. Minimal bias was present in four randomized trials and greater bias in 2.ConclusionIn multiple randomized and randomized controlled studies HBOT at 1.5 ATA oxygen demonstrated statistically significant symptomatic and cognitive or cognitive improvements alone in patients with mild traumatic brain injury Persistent Postconcussion Syndrome. Positive and negative results occurred at lower and higher doses of oxygen and pressure. Increased pressure within a narrow range appears to be the more important effect than increased oxygen which is effective over a broad range. Improvements were greater when patients had comorbid Post Traumatic Stress Disorder. Despite small sample sizes, the 1.5 ATA HBOT studies meet the Centre for Evidence-Based Medicine Level 1 criteria and an American Society of Plastic Surgeons Class A Recommendation for HBOT treatment of mild traumatic brain injury persistent postconcussion syndrome.

The effect of hyperbaric oxygen therapy on cognition, performance, proteomics, and telomere length—The difference between zero and one: A case report

“…HBO2 therapy is a well-established treatment modality for non-healing wounds, radiation injuries as well as different hypoxic or ischemic events (such as carbon monoxide toxicity, infections, among others). In the past decade, evidence has accumulated on the benefits of HBO2 therapy in different types of brain injuries including stroke and traumatic brain injury (TBI) (3)(4)(5)(6)(7). Recently, by using a novel protocol, it has been evaluated for enhancement of both cognitive and physical capabilities in healthy adults (11).…”

“…Hyperbaric oxygen (HBO2) therapy is one idea that has been FDA approved and is efficacious in the treatment of 13 different medical conditions including decompression sickness, nonhealing wounds, severe anemia, carbon monoxide poisoning, among others (2). It also has been used off label for closed head injuries, post-stroke, post-traumatic stress syndrome (PTSD) and post-concussion syndrome (PCS) (3)(4)(5)(6)(7). Numerous HBO2 therapy mechanisms have been shown in both preclinical and clinical models including anti-inflammatory effects, stem cells recruitment, angiogenesis, neurogenesis, increased cerebral blood flow, mitochondrial function restoration, and cellular metabolism.…”

Oxygen Straight to the Brain: An Overview of Hyperbaric Oxygen Therapy for a Variety of Brain Morbidities

“…Testing the hypothesis that HBOT can be used in the treatment of TBI has taken many different forms with a variety of treatment tables and durations with the most advantageous results coming from treatment pressures taking place at 1.3 to 1.5 ATA for 60 min daily for 2 to 4 wk (4,6). On the other hand, the least effective pressure is found to be 2.4 ATA, with pressures greater than 2.0 ATA proving to be much less efficacious at the treatment of mild TBI postconcussion syndrome symptoms to the point that the cost and risk greatly outweighs the benefit.…”

New scientific definitions

“…3 The inadequacy of the modern definition has become even more apparent with the inability to reconcile the seemingly conflicting conclusions and confusion in the multiple U.S. Department of Defense mild traumatic brain injury/persistent postconcussion syndrome studies. 5 ]…”

“…Given the aforementioned flaws, the cumulative knowledge of the bioactivity of increased barometric or hydrostatic pressure, 4 5 the inescapable acknowledgment that HBO 2 includes increased pressure in addition to increased pressure of oxygen, 5 and the U.S. Food and Drug Administration’s identification of this dual component nature of HBO 2 , 5 it is incumbent upon the hyperbaric medicine field to change the definition of HBO 2 to embrace and account for the science underpinning it. Therefore, this is a proposal that HBO 2 should be redefined as a type of hyperbaric therapy.…”