Letter to the editor on:
Side effects of Hyperbaric Treatment in children with Cerebral Palsy
As the senior clinicians involved in the largest randomized trial of Hyperbaric Oxygen Therapy (HBOT) for children with cerebral palsy (CP) (1) as well as in the McGill pilot study on the same subject (2), we would like to comment on the article by Muller-Bolla et al (3) recently published in your journal about our randomized trial. We question the intent of such an article but we will keep our focus on more important issues. We want to state that none of the authors of this paper were involved with the provision of the treatments or the evaluations of the children. The title of the article was actually not correct; it should have been "Side effects of hyperbaric treatment etc" because children in both groups experienced ear problems.
First, the article and even the abstract are misleading the readers about the type of study this was and the results of our randomized trial. The term placebo-controlled was not allowed to be used in the paper that was published in the Lancet. Furthermore, it is untrue that this study proved that there were no benefits from hyperbaric treatment for this patient population. The fact is that both groups of children treated with two very different hyperbaric treatment dosages (1.75 ATA-100% O2 and 1.3 ATA with air) improved significantly. The motor improvements that were seen and measured with the G.M.F.M. (4) were greater, more generalized and were obtained in a shorter period of time than most of the changes found in any other studies of recognized conventional therapies in the treatment of children with cerebral palsy 5-8. The children in both groups improved an average of ten times more during the two months of hyperbaric treatment (whilst all other therapies and medication were stopped) than during the three months follow-up (when medication and all the ancillary treatments were restarted). This impressive change in the rate of improvements clearly indicates the probable effectiveness of hyperbaric treatment. The Lancet commentary (9) and even a report from American Health Agency concluded that the hypothesis of both treatments being equally effective should be retained, possibly as the main hypothesis. The very low pressure protocol (1.3 ATA) had never been tried on children with CP prior to the trial, so we did not expect that this supposedly sham treatment would produce changes of the similar magnitude as those observed with the 1.75 ATA HBOT group. It was an intriguing surprise for everyone and was interpreted in The Lancet commentary as a remarkable finding.
Since that study, reports have been made on the possible efficacy of a low pressure hyperbaric treatment in humans and in animal studies10 and all trials conducted in many countries with HBOT in C.P. have demonstrated positive results.
The second important issue we would like to address is the frequency and severity of the side effects during the course of our study. We were in charge of the center in which the majority (65 out of 111) of the children were treated during the trial. We are convinced that the most probable explanation for the high incidence of middle ear barotrauma (MEBT) reported in Muller-Bolla article compared to other studies is due to the simple fact that children were systematically evaluated, even in the absence of any symptoms, by physicians inexperienced in the evaluation of MEBT. They were instructed to report any ear drum redness, which was then considered as MEBT. Most children were allowed to be pressurised the next day after a positive ear examination. Only one child had to withdraw from the study because of MEBT. It is not surprising that there were 46 MEBT observed compared to only 20 complaints of ear pain! In fact, there were not many more cases of ear pain reported in the higher pressure group than in the mild treatment group (11 compared to 9). It makes us wonder what the percentage of reported MEBT would be if a study was conducted with such instructions, by inexperienced physicians, on divers getting out of the water or even on passengers disembarking from a commercial flight.
Since that study, most protocols of HBOT in C.P. are now recommending a pressurization of 1.5 ATA or less which certainly reduces the risks of potential side effects.
We were responsible, during the course of the studies, for more than 4,500 pressurizations and are aware of more than 40,000 other HBO treatments given to children with CP that we follow regularly. Only a few have been referred for myringotomy because of a MEBT. We did not see a single significant complication or permanent injury. The reality is that in the vast majority of cases children with C.P. can undertake HBO treatment without significant complications and in most cases it will improve their quality of life and that of their families.
We also want to point out that in the two last pages of Muller-Bolla's article there is an exact word for word repetition of a 20 lines paragraph restating a misinformation. We are the co-authors of the Montgommery et al. article published in this journal and it is false that in this pilot study we ever saw or mentioned respiratory distress or acute respiratory failure. All 25 children included in this study were treated for one hour at 1.75 ATA. and there were no serious complications or side effects.
Finally, the last paragraph of this article actually contradicts most of what have been written before, even in the abstract. It states that: "This study shows that exposure to low hyperbaric pressure is associated with minor signs of barotrauma compared to very low exposure. All other side effects were rare and similar in both groups." Both groups actually experienced minor barotrauma but there was a slight increase in the group treated at 1.75 ATA. It is wrong to state that "all other side effects were rare" ; they cannot be rare if they did not occur. It should be stated that they were absent.
HBOT for CP is a very promising, and safe treatment now scientifically supported by the positive results of several open trials. We certainly recommend ensuring adequate supervision and recognise the need for further research. Considering that there are few effective treatments for children with cerebral palsy we are convinced that research in HBO therapy for treatment of CP must be pursued. We need to confirm the underlying mechanisms behind the impressive changes that have been observed in thousands of children and to better define the indications and dosages appropriate to individual patients in neurological condition. The side effects reported by Muller-Bolla et al were simply those due to a change in pressure and did not relate to the dosage of oxygen being used.
Pierre Marois, MD., FRCPC, Physiatrist
Michel Vanasse, MD., FRCPC, Neurologist
CHU Sainte-Justine, Montréal, Canada
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