Feeling the pressure

I’ve been quite techie in my posts recently so maybe its time for something more clinical. I received a request from a journalist with the popular science magazine “New Scientist” to comment on an article (Mukherjee et al, 2014) reporting on research purporting to provide evidence of the efficacy of hyperbaric oxygen therapy for children with cerebral palsy.

Such articles “discovering” new treatments for cerebral palsy appear every so often. The last time hyperbaric oxygen was discovered was just over a decade ago. At the time a number of centres throughout the UK, Europe and Australia started offering the treatment and many parents sought these out. The fact that this interest appears to have largely died away I think speaks for itself.

Despite its claims the article is published in Undersea and Hyperbaric Medicine Journal. This suggests to me that it has either been rejected from mainstream journals in the cerebral palsy field or that the authors have chosen not to submit it for the rigorous peer review that this would entail. Assuming that it has been reviewed and assessed as lacking credibility I looked at the article myself.

The article is actually well written with the authors being particularly honest in highlighting several limitations. The most obvious is that this is not a randomised trial. The control group were those children with parents who did not want hyperbaric treatment for some reason.  This group is much smaller than the other groups and contains a higher proportion of more severely involved children (quadriplegia) than two of the other groups. The authors also accept that there was no blinding of clinicians, families or assessors.

The other obvious issue is that all children were also undergoing an intense rehabilitation programme over a six month period of the study whereas the hyperbaric oxygen was only offered over the first two months. The similarity between the three treatment groups is remarkable despite marked differences in the hyperbaric oxygen regime. The lowest dose of hyperbaric oxygen is actually one of hyperbaric air. The other doses are of pure oxygen (5 x more oxygen) at considerably higher pressures. I’m no expert in hyperbaric medicine but if the hyperbaric regime is the important factor here I’m surprised that such marked differences between regimes make so little difference to the results (summarised in Figure 1).

Mukherjee Fig 1

The improvement appears to continue throughout the treatment period and not just over the early period when hyperbaric oxygen was being used.  Given that the differences between control and hyperbaric oxygen might be attributed to some inherent bias in selecting the controls, the most direct explanation of the data would appear to me to be that the common rehabilitation programme is responsible for change rather than the different hyperbaric oxygen regimes.

Mukherjee Fig 2

The improvements in GMFM appear large particularly as plotted against the GMFM “growth curves” in Figure 2. There are, however, also issues here. Comparison of the age range and means of all treatment groups suggests a highly skewed distribution with a large number of very young children and a small number of adolescents. The mean value is almost certainly a poor indicator of central tendency and the median should have been used which will almost certainly be considerably lower. You can see that if the age at which the lines in Figure 2 are plotted where reduced by just one year then the improvements over six months would be much closer to those expected on the basis of the growth curves. The early years of childhood are a time of rapid development of motor function in all children, including those with cerebral palsy, and particular care is needed to take this into account while quantifying the effect of specific interventions at this age.

The other issue here is that the growth curves are based on data from Canadian children attending established ambulatory rehabilitation programmes on an on-going basis. If the children in the hyperbaric oxygen study had been less well managed before being recruited then the rapid gains on starting such a comprehensive rehabilitation programme for the first time may not be that surprising.

The acknowledgements list also makes interesting reading in that it is suggests that there are a considerable number of stakeholders in this project. I could imagine that providing evidence for the efficacy of this treatment could be extremely important for its future. In the light of this I’m not convinced by the final statement that “the authors report that no conflict of interest exists with this submission”. (Of course this merely highlights implicit conflicts of interest in almost everything that is published in the scientific literature and it may be a little unfair to make this criticism of this study and not of others).

In summary it appears quite clear to me why mainstream journals might have been reluctant to publish such a study and I’d think it extremely unlikely that this is the break through that it might appear at first site.

If the paper has been declined by the mainstream CP journals then it is interesting to reflect on whether this has been “successful” or not. The paper is well written and appears to report results of an observational study that has been conducted at least as rigorously as many others that are routinely accepted by such journals. The authors have been particularly honest in reporting the limitations of the study. The explanations as to why the results may not be as sensational as first appears are quite subtle and I’m not particularly surprised that they have been over-looked by authors who (like most of us when we publish) want to place a particular spin on their results.

If the article had been accepted then the journal editors could have asked the authors to revise their manuscript to draw more balanced conclusions or could have included an editorial emphasizing an alternative point of view. I think it unlikely that the popular scientific press would have raised an eyebrow.  Instead the article has appeared in a journal dedicated to hyperbaric medicine with an editorial written by protagonists for this “new” therapy who conclude that it “could be the coveted neurotherapeutic method for children suffering from neurological dysfunctions due to CP”. I’m not convinced that this is a good result for the CP community who I think have enough to contend without the publicity that occasional reports of such “wonder cures” gives rise to.


Mukherjee A, Raison M, Sahni T, Arya A, Lambert J, Marois P, James PB, Parent A, Ballaz L (2014). Intensive rehabilitation combined with HBO2 therapy in children with cerebral palsy: a controlled longitudinal study. Undersea and Hyperbaric Medicine Journal 41(2):77-85.



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