When I meet with friends, relatives and work colleagues, I get asked about what I do. When I explain my job, I always get asked, “Does hyperbaric oxygen therapy really work for traumatic brain injury?”
I know many of those who are reading this blog have the same question in mind. It’s a pretty important question for a person that has a TBI.
So – does it work or not?
In my opinion, yes.
But opinions are like belly-buttons, everyone has one. What you really need are facts and studies that support your opinion (if you are impatient to find them, jump HERE). Now, me saying that HBOT can help treat a TBI will probably raise a few eyebrows. Let’s face it, neurologists, psychiatrists and researchers have been going after this problem for decades. Me saying that a pressurized gas can heal the ravages of a traumatic brain injury may sound far-fetched. But you don’t know what I know… and neither do a lot of highly-trained doctors.
You see, doctors are the problem. And the solution to getting HBOT as a therapy approved.
After finishing a 4-year baccalaureate program in college, medical school takes another 4 years to complete. In school you sample different specialties (family medicine, emergency medicine, etc.) and it then takes another 3 – 7 years of residency/fellowship to complete a specialty. On average, doctors are exposed to 3 – 4 days of education of hyperbaric medicine in their general training. This training does not include the current research, only the well-established treatments. In all, not much exposure or education is given to doctors-in-training for hyperbaric medicine.
After graduation, a doctor needs to maximize the number of patients and billable procedures’ he or she can accomplish. Med school started getting really expensive in the 1980’s. This means that doctors are busy people and specialized in the area of medicine that they practice and keeps them employed.
Doctors keep current in their specialty by joining general medical societies (The American Medical Association) and societies that cater to their specialties (American Academy of Neurology, for example). The amount of information out in the medical research journals is humongous, even within specialties.
And it just keeps growing.
The graph on the right shows the growth rate for the past 30 years for medical and scientific papers. And it is not going to slow down any time soon. Separating the metaphorical chaff from wheat isn’t easy, either.
Finding the time to read, let alone keep up, is a daunting and time consuming task. So doctors, like most of us, rely on experts and opinion leaders to keep them informed. Usually they gather at conferences to discuss the burning issues and emerging problems that affect their specialty.
Doctors and patients are also relying on comments and opinions from trusted sources. Comments on research, such as the one below, are normally provided by trained medical providers, who are non-experts in the field of hyperbaric medicine and have a passing knowledge of the research literature:
I’m sure that Dr. Silver is an excellent Psychiatrist (the New England Journal of Medicine has a reputation for selecting excellent doctors), but his specialty or training is not hyperbaric medicine (although he does do research on TBI and pharmaceuticals). The details and nuances of hyperbaric oxygen play a big part in understanding technical information and getting the right conclusions out of data. This will become very relevant when we discuss the Department of Defense sponsored studies.
More importantly, the impact that a specialty has depends on the size of the membership and what illness it treats. So, let’s see what the different populations of doctors in each specialty are in the US. The chart below is the number of active physicians (MD’s and DO’s) as of 2012 in each of the specialties below (the data was compiled from the Henry J. Kaiser Family website and the American Academy of Neurology website). The largest single group is Psychiatry, which coincidentally is the specialty that handles the majority of TBI management. At the extreme end is Hyperbaric Medicine, with about 2,000 active specialists in the US.
Hyperbaric medicine is a very small specialty compared to any of the other specialties. It mostly focuses on wound treatment, skin burns and difficult to treat infections. They have no lobbying arm in Congress and the average NIH budget for HBOT research is less than $2 million/year. Alzheimer’s disease averages $450 million and TBI research average $90 million (information was from the NIH website).
So, why don’t you hear about HBOT in a positive light? Those who have the membership (and money) have bigger bullhorns and access to funding institutions. Hyperbaric medicine is tiny and underfunded.
What A Little Digging around Shows
The biggest complaint that is tossed around by many physicians is the lack of data showing the effectiveness of HBOT for traumatic brain injury. Point granted…but only if you ignore the literature.
There are several papers (some are case reports, other are observational studies) that show the effect that HBOT has on diagnosed traumatic brain injury. All are uniformly positive, many with long-term maintenance of recovery and with mild to no side effects from the treatments on humans. These reports are listed below:
- Shi XY, Tang ZQ, Sun D, He XJ. Evaluation of hyperbaric oxygen treatment of neuropsychiatric disorders following traumatic brain injury. Chin Med J (Engl). 2006;119(23):1978-82.
- Hardy P, Johnston KM, De Beaumont L, Montgomery DL, Lecomte JM, Soucy JP, et al. Pilot case study of the therapeutic potential of hyperbaric oxygen therapy on chronic brain injury. J Neurol Sci. 2007;253(1-2):94-105.
- Lin JW, Tsai JT, Lee LM, Lin CM, Hung CC, Hung KS, et al. Effect of hyperbaric oxygen on patients with traumatic brain injury. Acta Neurochir Suppl. 2008;101:145-9.
- Wright JK, Zant E, Groom K, Schlegel RE, Gilliland K. Case report: Treatment of mild traumatic brain injury with hyperbaric oxygen. Undersea Hyperb Med. 2009; 36(6):391-9.
- Harch PG, Fogarty EF, Staab PK, Van Meter K. Low pressure hyperbaric oxygen therapy and SPECT brain imaging in the treatment of blast-induced chronic traumatic brain injury (post-concussion syndrome) and post traumatic stress disorder: a case report. Cases J. 2009;2:6538.
- Sahni T, Jain M, Prasad R, Sogani SK, Singh VP. Use of hyperbaric oxygen in traumatic brain injury: Retrospective analysis of data of 20 patients treated at a tertiary care centre. Br J Neurosurg. 2011.
- Stoller KP. Hyperbaric oxygen therapy (1.5 ATA) in treating sports related TBI/CTE: two case reports. Med Gas Res. 2011;1(1):17. PMCID: 3231948.
- Paul G. Harch, Susan R. Andrews, Edward F. Fogarty, Daniel Amen, John C. Pezzullo, Juliette Lucarini, Claire Aubrey, Derek V. Taylor, Paul K. Staab, and Keith W. Van Meter. A phase I study of low-pressure hyperbaric oxygen therapy for blast-induced post-concussion syndrome and post-traumatic stress disorder. J Neurotrauma. 2012 Jan 1;29(1):168-85.
From these eight reports, a total of 396 human subjects were enrolled. Some studies did only 2 treatments of HBOT. Other did over 100 treatments. All used 1.5 atmospheres in pure Oxygen. The studies are designed around two types of testing systems: 1) split study subjects into groups that received standard treatments for TBI or standard treatments for TBI plus HBOT; 2) Measure performance before HBOT and then after HBOT in study participant with long-standing TBIs (greater than 2 years). All saw improvements that were statistically significant.
At this point, the usual chorus of “but these are not randomized, placebo or sham controlled clinical trials (RCTs)” comes up (if you need a definition for a randomized, controlled trial, click here). All true, except that other drugs or treatments have been accepted into the medical mainstream without placebo/sham RCTs. Penicillin is just one example. In any event, randomized placebo controlled clinical trials are not the end-all, be-all in medical research. Plenty of clinically relevant data can be gotten with a cross-over RCT, such as the one below.
- Boussi-Gross R, Golan H, Fishlev G, Bechor Y, Volkov O, Bergan J, et al. Hyperbaric Oxygen Therapy Can Improve Post Concussion Syndrome Years after Mild Traumatic Brain Injury – Randomized Prospective Trial. PLoS One. 2013;8(11):e79995. (CIVILIAN) )(ISRAEL)
The study by Boussi-Gross (depicted above) showed a statistically significant difference before and after treatment for the HBOT group after forty, 1.5 ATA treatments. A total of 32 study participants were in the HBOT treatment group, while 24 study participants were assigned to the wait group. In total, 56 study subjecst were treated with HBOT. The wait group showed no statistically sigificant changes in their test results during the 2 months that the HBOT group was treated. After thewait group was treated with HBOT (or crossed-over to the treatment), the wait group improved as much as the HBOT treatment group.
Pretty clear cut. HBOT works for the treatment of mTBI at 1.5 ATA.
The Other Results
But what about all those Department of Defense (DoD) funded studies!? I mean, these are big budget, well controlled and thoroughly vetted studies done by the Armed Forces medical and research division of the United States of America. Those are REAL studies, sham RCTs! And they showed that HBOT does not help with TBI.
Or did they?
- Wolf G, Cifu D, Baugh L, Carne W, Profenna L. The effect of hyperbaric oxygen on symptoms after mild traumatic brain injury. J Neurotrauma. 2012;29(17):2606-12. (DoD) (USA)
The study by Wolf et al. is one of the few studies to use a sham treatment in HBOT. Also, for the first time a higher pressure regime was used (2.4 ATA) than the traditional 1.5 ATA used for mTBI. Now, a sham is suppose to be a treatment or procedure that does not produce an improvement…it should be flat…unless there is a placebo effect. The only way you can establish a placebo effect is to absolutely rule out that your treatment (or drug) produces a biological activity. That’s a hard thing to do with oxygen, since it is always biologically active. Explaining why oxygen cannot be used as a placebo is a separate blog post (stay tuned for the next post…I promise to make it fun…really…about oxygen).
In any case, both exposures produced changes (improvements) in symptoms measured in the PCL-M (Post-Traumatic Disorder Check List-Military) for these service members.
Which one produced the best outcomes: the 1.3 ATA or the 2.4 ATA?
Out of the 22 symptoms that were measured, 9 significantly improved under air treatment at 1.3 ATA. The 2.4 ATA treatment produced one significant improvement in a symptom. If this was a placebo effect (a psychological effect), the number of improvements and the magnitude of the improvements should have been equal across the board for both pressures. Only the sham treatment had such a lopsided improvement for the study participants.
Why would a “sham” produce a better outcome?
The sham increased oxygen concentration anywhere from 28-43% above normal (pressure in the sham were in the range of 1.3ATA to 1.2 ATA). Any increase in dissolved oxygen in the body can produce (under pressure) a measurable biological response (I’m saving the explanation for the next blog post…honest). Dosages of oxygen are as real as dosages of pills. Too much of a drug can harm you, too little will do nothing…just right will treat what is ailing you. Oxygen under pressure is no different than a pill.
And the conclusions by Wolf et al. is the following:
“The current study in participants with postconcussive syndrome from chronic mTBI demonstrates no efficacy in symptom relief with HBO2 at an exposure pressure of 2.4 ATA for 90 min given once daily for 30 treatments; however, both groups improved more than would be expected greater than 6 months after mTBI. It is recommended that larger, multicenter, randomized, controlled (both sham-control and wait-list), double-blinded clinical trials be conducted at lower total oxygen doses as recommended by AHRQ.”
Dr. Wolf is an experienced MD, trained in the field of hyperbaric medicine. He is an Air Force officer (Colonel) and a careful clinician. He is being a scientist when ascerting the facts of the study. In this case he has drawn conclusion from his two test parameters (1.3 ATA, Air; 2.4 ATA 100% Oxygen)…they were not sufficiently different from one another to reach statistical significance. The improvements seen in both groups were not statistically siginificant when 1.3 ATA was compared to 2.4 ATA. Let that sink in for a minute…both groups improved sufficiently to be statistically significant from their starting (baseline) values, but not different enough between both groups to register as significant.
That was all Dr. Wolf and his colleagues could conclude.
And he acknowledge that the improvements were greater than expected with chronic mTBI study participants. More studies are needed, with better controls in order to reach a solid conclusion.
So, did this study conclude that HBOT is ineffective for mTBI?
Pressurized air (at 1.3 ATA) appears to alleviate more symptoms of a chronic TBI better than pure oxygen (at 2.4 ATA). The statistics from before treatment and after treatment bear it out.
And it showed that HBOT is safe for individuals with a TBI…even at pressures as high as 2.4 ATA.
OK. But What About the Other Studies?
The other DoD studies, which were going in parallel or right after the Wolf study, came to a different conclusion for their results. The analysis of these three published articles will take quite a while to explain, so I will go into detail on my next blog post (oh yeah…along with how oxygen works you will get a detailed analysis of these three studies…two-for-one…lucky you). But at least these three studies concluded the same thing as the Wolf et al. studies…HBOT is safe for individuals with a TBI.
- Cifu DX, Hart BB, West SL, Walker W, Carne W. The Effect of Hyperbaric Oxygen on Persistent Postconcussion Symptoms. J Head Trauma Rehabil. 2013. (DoD) (USA)
- Walker WC, Franke LM, Cifu DX, Hart BB. Randomized, Sham-Controlled, Feasibility Trial of Hyperbaric Oxygen for Service Members With Postconcussion Syndrome: Cognitive and Psychomotor Outcomes 1 Week Postintervention. Neurorehabil Neural Repair. 2013. (DoD) (USA)
- Cifu DX, Walker WC, West SL, Hart BB, Franke LM, Sima A, et al. Hyperbaric oxygen for blast-related postconcussion syndrome: Three-month outcomes. Ann Neurol. 2014;75(2):277-86. (DoD) (USA)
Oh… and the DoD funded studies are the few studies that fail to show any improvement of TBI symptoms with HBOT. The majority of civilian studies (from four countries and seven independent civilians clinical groups) have shown positive outcomes.
Parting Thought for Those Affected
I have worked with physicians trained in HBOT, run clinical research with HBOT and seen first-hand the effects of HBOT on people suffering from the long-term effects of traumatic brain injury (TBI). The majority of folks that undergo HBOT improved to a surprising degree. A small minority does not improve…and we don’t know why. We would love to find out.
Now, my opinion on HBOT is that it works to treat neurological injuries based on clinical research I have performed, review of the literature and my training as a Ph.D. (Neurobiology/Toxicology). I have no financial interest in HBOT; it's actually costing me money, time and career advancement to be a proponent, let alone a researcher in this field.
So, why do I do it? Well, to put it simply, it works. And there are many people that are living better lives because they have undergone treatment with HBOT for a TBI. When there is a treatment that can work for TBI, training TBI victims to cope with a “new normal” as a standard of care is getting very close to malpractice. Unfortunately, there is a lot of information out there that can trip up a well-trained physician but the reliance on authority or experts as a guide to treatment is a poor substitute for firsthand experience.
Fortunately there are a growing number of physicians (MD’s, DO’s, NP’s and clinical PhD’s) that are recognizing the limitations of pharmaceutical, psychological and psychiatric methods for rehabilitation. They are looking for alternatives to help their patients. They are finding positive results with HBOT.
You see, I was not a proponent of HBOT when I first jumped into this field in 2010. Like many medical practitioners and researchers, I thought that HBOT might be useful for only a few things in medicine (decompression sickness, wound treatment and the like) but treating neurological conditions? It’s only a gas under pressure. How could it work?
Glad you asked. We’ll see how in the next blog post, too.
“While we applaud good science, there comes a point […] of stagnation as the standard of evidence required for the blessing of organized medicine exceeds reality (where most of us live).”
– George Mychaskiw II, DO, FAAP, FACOP,
UHM 2012, Vol. 39, No. 4 – How many deaths will it take? AN EDITORIAL PERSPECTIVE
Placebo: (Science: pharmacology) Any dummy medical treatment, originally, a medicinal preparation having no specific pharmacological activity against the patients illness or complaint given solely for the psychophysiological effects of the treatment, more recently, a dummy treatment administered to the control group in a controlled clinical trial in order that the specific and non-specific effects of the experimental treatment can be distinguished i.e., the experimental treatment must produce better results than the placebo in order to be considered effective. An innocuous or inert medication; given as a pacifier or to the control group in experiments on the efficacy of a drug. An inactive substance given to a patient to satisfy an apparent psychological need. (http://www.biology-online.org/dictionary/Placebo),
Sham: Being a treatment or procedure that is performed as a control and that is similar to but omits a key therapeutic element of the treatment or procedure under investigation. (http://www.merriam-webster.com/medical/sham).
RCT: A randomized controlled trial (or randomized control trial; RCT) is a specific type of scientific experiment, in which study subjects, after assessment of eligibility and recruitment, but before the intervention to be studied begins, are randomly allocated to receive one or other of the alternative treatments under study (http://en.wikipedia.org/wiki/Randomized_controlled_trial).
Cross-over RCT: Randomized, controlled crossover experiments are especially important in health care. In a randomized clinical trial, the subjects are randomly assigned to different arms of the study which receive different treatments. When the randomized clinical trial is a repeated measures design, the same measures are collected multiple times for each subject. A crossover clinical trial is a repeated measures design in which each patient is randomly assigned to a sequence of treatments, including at least two treatments (of which one "treatment" may be a standard treatment or a placebo) (http://en.wikipedia.org/wiki/Crossover_study).