Investigational hyperbaric oxygen therapy (HBOT) indications: inflammatory bowel disease
Read on to find out what the scientific literature says regarding HBOT for inflammatory bowel disease.
The recent HBOT experience
HBOT for ulcerative colitis
Until this point, all of the papers have concerned advanced CD, and none have combined UC cases in the mix. Pagoldh et al. designed a prospective, randomized, open-label clinical trial for HBOT intervention and UC, published in 2013.
The primary objective of the study was to assess effects of HBOT on Mayo Score, laboratory tests, and fecal weight. The short version of the results show … ummmm … no improvement vs the control group in any of the categories. It appears that UC responds quite differently to HBOT than CD. Correction, HBOT appears to have no place in UC based on this study, even though the two disease states share similar TNF activity and several papers showing severe UC exacerbations are ameliorated with HBOT.
Speaking for myself, Pagoldh’s conclusion doesn’t make sense. The mechanism of action for HBOT should be the same for either UC or CD. How would HBOT work in one disease and not the other? I’m not attributing value to the following statement, just stating fact: The Pagoldh study is the only “negative” HBOT study in the IBD literature.
There are problems with the Pagoldh study. In fact, I would be reticent to accept the conclusions of this study as it has been performed. First, the power of the study is a problem. They set n=10 for each group. Only eight patients were enrolled in the ‘control’ arm of the study, and five completed while three did not. On the intervention side, there were 10 HBOT patients, of which only four completed the HBOT trial and six withdrew. In my mind, there is a significant amount of statistical bias, and one might easily interpret the data to rule out a process that is actually good (a Type II error).
In addition, while the study was randomized, it was not blinded, nor was there a sham control arm. This raises some potential methodological errors that may have tilted the conclusions of the study. Overall, I wish that the study contained more patients in both arms and was free of potential bias by using a sham control arm.
Stay with me now … more to come. There is yet another systematic review of HBOT in IBD. Coming up shortly.
Patients with refractory inflammatory bowel disease ‘heal’ after pelvic exenteration and adjunct HBOT
Many of the patients with IBD have proctocolectomy procedures. You would logically think that the disease is within the colon, and that when you remove the affected bowel, the disease severity ceases. Not so simple. Patients with persistent perineal draining sinus cavities fail to heal from the proctocolectomy. Up to 33% of these patients can have continued draining sinuses for a year or more following muscle free flap procedures to close the perineal cavity left by the surgery. (I remember taking care of these patients when I was on surgery rotations in medical school. Definitely a difficult management!)
Chan and colleagues (2013) studied four patients who had medically refractory IBD and were undergoing a pelvic exenteration procedure and either a vertical or transverse rectus flap for closure. These four patients (2 with CD and 2 with UC) had HBOT (25 – 30 treatments preoperatively) consisting of 2.4 ATA for 90 minutes of oxygen breathing. When logistically possible, 10 treatments postoperatively were delivered. All four patients were declared ‘healed’ by 3 months postoperatively. None of the four patients had recurring sinus formation for 35 months follow up period.
Reviews conclude that adjunct HBOT is potentially efficacious for refractory inflammatory bowel disease
Dulai and colleagues from the Inflammatory Bowel Disease Center at Dartmouth-Hitchkock performed a systematic review of hyperbaric oxygen and inflammatory bowel disease in 2014. Their review of the literature was much more thorough than we’ve gone through to this point. They found 17 studies, involving more than 600 patients (286 with CD and 327 with UC). Overall response rate was 86% (the same whether UC or CD). With CD perineal sinus, 18/40 completely healed and 17/40 partially healed.
They conclude that HBOT is relatively safe with minor complications and potentially efficacious for IBD patients who are refractory to medical management (worst of the worst). Still, there have been no blinded, randomized, sham controlled studies. Ahhh, but Dulai and colleagues will come back with exactly that study in 2017 published in the American Journal of Gastroenterology.
A retrospective review of 32 consecutive patients with refractory UC were reviewed. (Remember the Pagoldh study? This one refutes its findings.) Over the period from 1994-2011, these patients had the standard care as well as 40 HBOT treatments. This research group reported a number of clinical and laboratory parameters (worth the read, if you are interested). Pre-HBOT stool frequency was 7, whereas post-HBOT was 1. Bloody stools went from 10 to 0. Endoscopy severity score decreased significantly. Biopsies with analysis for CD44 stem cells were greatly improved post-HBOT.
A randomized controlled study shows that HBOT is effective for ulcerative colitis
Dulai returns with a phase 2A pilot multi-center, randomized, double-blind, sham-controlled study in 2017. This still does NOT answer the questions, nor is it definitive. It is a pilot study and proof of concept. This study looked at patients who were hospitalized due to a UC moderate-severe flare. Even with low recruitment, we see the following trends. Clinical remission at day 5 and day 10 were 50% for the HBOT group to 0% for the sham-control.
HBOT patients did not require progression to secondary medications (10% vs 63% in the sham group). HBOT patients did not require urgent colectomy (0% vs 38% in the sham group). While this study needs to be done again with a much larger number of patients, the design looks very good. Sham is provided by taking patients to 1.34 ATA and breathing air the entire time. As an aside, Dr. Lin Weaver and staff from Salt Lake City have shown that patients compressed to 1.2 and 1.3 ATM are required to clear ears, feel heat of compression, and have no idea what final pressure they have been exposed to. Hence, an excellent sham design.
And there you have it … from 1989 to 2019!
So, what is the conclusion on adjunctive HBOT for inflammatory bowel disease?
Of all the papers reviewed, only 1 (Pagoldh) was a negative trial. There are statistical reasons that we should be reticent about accepting that study. In fact, there were a number of case studies and case series with UC that were positive, including the Dulai pilot study. Dulai suffers the same statistical lack of power as Pagoldh. Based on the above, I would discount the Pagoldh paper, because Dulai follows the general trend of all the UC case series papers. Yes, I guess I’m biased, but we all are to some extent. So:
For severe IBD, medically refractory, I would recommend using adjunctive HBOT off-label for these patients. For the HBOT regimen, I would start with 40 treatments and allow patient response/or non-response to guide further treatments.
Find the full article by Eugene R. Worth, MD, M.Ed., FABA, ABPM/UHM here.