Rapid Responses to:
|
|
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
Keep to the basics
- Carl J Heneghan (19 August 2006)
-
Comparison with hyperbaric oxygenation for necrotizing fasciitis.
- Richard G Fiddian-Green (22 August 2006)
-
No double standards in research, please
- Peter C Gotzsche (26 August 2006)
-
Hyperbaria, Hyperoxia or Hypothermia - what is the real X-factor?
- Roy K Philip (5 September 2006)
-
Hyperbaric Oxygen Treatment for Neonatal Hypoxic-ischemic Encephalopathy
- Philip B James (7 September 2006)
|
|
|||
|
Carl J Heneghan, Clinical research fellow & deputy director CEBM Centre for Evidence-Based Medicine, Dept of Primary Health Care, University of Oxford
Send response to journal:
|
In the review by Liu et al of treatment of hyperbaric oxygen there are a number of methodological issues that need to be addressed For instance, alternate allocation to treatment group, or methods based on patient characteristics such as date of birth, order of entry into the clinic or day of clinic attendance, are not reliably random. Such allocation sequences are predictable, and reduce the guarantee that no potential subjects have been excluded by foreknowledge of the intervention. [1] These trials should be removed in a sensitivity analysis as well as the trials not reporting ‘random’ in the methods section. Authors should be contacted for clarification if inadequate reporting is felt to be the problem. Using simple randomization methods often leads to the sample size being similar in the two groups and inadequate reporting of the baseline characteristics [2]. Attempts should be made to compare the baseline characteristics of trials where allocation concealment is unclear or not used. Trials not reporting baseline characteristics should be removed in the sensitivity analysis. In trials that report adequately concealed allocation, compared to inadequate or unclear yield larger estimates of treatment effects (P < .001). Odds ratios were can be exaggerated by 41% for inadequately concealed trials and by 30% for unclearly concealed trials (adjusted for other aspects of quality) [3]. If the Chinese medical literature is to be a rich source of evidence then reporting of the basic principals of critical appraisal and analyzing high versus low quality data remains important. Remove the rubbish and concentrate on the studies that are judged to be valid. [1] Beller EM, Gebski V, Keech AC. Randomisation in clinical trials. Med J Aust. 2002 Nov 18;177(10):565-7. [2] Altman DG, Dore CJ. Randomisation and baseline comparisons in clinical trials. Lancet. 1990 Jan 20;335(8682):149-53. PMID: 1967441 [PubMed - indexed for MEDLINE] [3] Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995; 273: 408-412. <PubMed> Competing interests: None declared |
|||
|
|
|||
|
Richard G Fiddian-Green, FRCS, FACS None
Send response to journal:
|
Like many others I have used hyperbaric oxygenation to treat necrotizing fasciitis [at Groote Schuur where it was a common problem] and have been impressed with the results but there is no evidence-base to support the conclusion that it was the hyperbaric oxygenation per se rather than the associated treatments that had the beneficial effect (1). The same applies to its use in the management of flaps and grafts (2). Why then should the brain be any different? If there is indeed a benefical effect of hyperbaric oxygenation in the brain, as anecdotal reports (3,4) suggest, can we be sure that it is the hyperbaric oxygen per se that had had the beneficial effect or might the benefical effect have been due to an improvement in nutrient uptake and/or utilization? 1. Jallali N, Withey S, Butler PE. Hyperbaric oxygen as adjuvant therapy in the management of necrotizing fasciitis. Am J Surg. 2005 Apr;189(4):462-6. 2. Friedman HI, Fitzmaurice M, Lefaivre JF, Vecchiolla T, Clarke D. An evidence-based appraisal of the use of hyperbaric oxygen on flaps and grafts. Plast Reconstr Surg. 2006 Jun;117(7 Suppl):175S-190S; discussion 191S- 192S. 3. Fiddian-Green RG. Oxygen administration can reverse neurological deficit following carotid cross-clamping. Br J Anaesth. 2005 Aug;95(2):274-5. 4. www.redflagsdaily.com/forum/brain_repair Competing interests: None declared |
|||
|
|
|||
|
Peter C Gotzsche, Director Nordic Cochrane Centre, Rigshospitalet, DK-2100 Copenhagen O, Denmark
Send response to journal:
|
In their abstract (1), the authors describe the Cochrane controlled trials register and other global databases as ”Western”, in contrast to Chinese databases. They also note that the reporting of the trials they identified was poor by ”Western (CONSORT) standards”. Finally, they note that the Chinese medical literature may be a rich source of evidence but provide no evidence for this statement. All randomised trials, and also trials that have possibly been randomised, are eligible for inclusion in the Cochrane controlled trials register. The Chinese Cochrane Centre has handsearched a large number of Chinese journals for such trials and they have been included in the register. There is therefore nothing ”Western” about the database. Equally puzzling is the authors’ idea that CONSORT should in some way be ”Western”. The CONSORT recommendations for improving the reporting of randomised trials are evidence-based, and should therefore be useful for all trial authors. Finally, it has been shown that Chinese trials are far more positive, on average, than trials performed in other countries. For example, a systematic review found that all 36 included Chinese trials of acupuncture were positive (2), versus only 25 of the 47 included US trials, and another review found substantial sample size bias in Chinese trials of acupunture (3). It therefore seems that not only the conclusions can be overly positive, but also the results. This does not lend support to the authors’ statement about a rich source of evidence in the Chinese medical literature, unless they operate with a particular type of ”Chinese” evidence that they have not described in their paper. Chinese trials can and should, of course, contribute importantly to systematic reviews and evidence-based medicine, but the unwarranted polarisation in this paper is not helpful. Disclaimer: The views expressed in this letter represent those of the author and are not necessarily the views or the official policy of The Cochrane Collaboration. References 1. Liu Z, Xiong T, Meads C. Clinical effectiveness of treatment with hyperbaric oxygen for neonatal hypoxic-ischaemic encephalopathy: systematic review of Chinese literature BMJ 2006;333:374. 2. Vickers A, Goyal N, Harland R, Rees R. Do Certain Countries Produce Only Positive Results? A Systematic Review of Controlled Trials. Controlled Clin Trials 1998;19:159-66. 3. Tang JL, Zhan SY, Ernst E. Review of randomised controlled trials of traditional Chinese medicine. BMJ 1999;319:160-1. Competing interests: I work in a Cochrane centre. |
|||
|
|
|||
|
Roy K Philip, Consultant Paediatrician Neonatal Intensive Care Unit, Regional Maternity Hospital, Limerick, Ireland
Send response to journal:
|
In their review Liu et al suggest that hyperbaric oxygen (HBO) is frequently applied in China for hypoxic-ischaemic encephalopathy (HIE) of term neonates and would warrant further studies to prove efficacy prior to convincing the west. Perhaps the authors overlooked a series of articles in Lancet 1, 2 and other western journals 3 looking at this ‘new and novel’ approach in the early 60’s. Fair play by the authors, they were not randomised trials. However, at least alluding to their work would have given the reader a suggestion that the neonatal application of HBO for resuscitation and HIE was attempted more than four decades ago in the west. What is the true ‘healing touch’ when using HBO for neonatal HIE? Hyperbaria, hyperoxia and perhaps hypothermia are all operating at variable proportions in the apparently single intervention of HBO. Authors have acknowledged that different megapascals of hyperbaria were used in the various trials qualifying for inclusion. That too applied three times daily for a varying length of time. Readers have the option to guess the wide variations in oxygen tensions (21% to 100%) these infants were exposed in the hyperbaria group and the ‘usual care’ group of the eligible studies. Would there be unexpected repercussions, including retinopathy, when hyperbaria is combined with 100% oxygen that too when the blood-brain barrier is compromised in HIE? May I remind that evidence supporting resuscitation of newborn with room air (not 100% oxygen) is mounting in the recent western 4 and eastern 5 literature. Lastly, the liquefied oxygen in the cylinder is a potential hypothermic agent, unless warmed and humidified, prior to delivery to the infant. Possibly among the studies qualified for systematic review were infants managed at room temperature / lower. If the body temperature fell to 33 0C to 35 0C among some infants in the hyperbaric arm of the trial, we may be seeing the indirect benefits of brain cooling6 in the Chinese literature! It is perhaps more prudent to look at one defined component of hyperbaric oxygen controlling for the other potential variables prior to hailing a cocktail treatment. 1. Hutchison JH, Kerr MM, Williams KG, Hopkinson WI. Hyperbaric oxygen in the resuscitation of newborn. Lancet 1963; 13: 1019-22. 2. Goodlin RC, Perry D. Hyperbaric oxygen in resuscitation of asphyxiated newborn rabbits. Lancet 1964; 13: 1124 3. Hutchison JH, Kerr MM. The use of hyperbaric oxygen in asphyxia neonatorum and the respiratory distress syndrome. Acta Anaesthesiol Scand 1966; 25: 397-8. 4. Tan A, Schulze A, O’Donnell CP et al. Air versus oxygen for the resuscitation of infants at birth. Cochrane Database Syst Rev 2005; (3): CD002273 5. Ramji S, Rasaily R, Mishra PK, et al. Resuscitation of asphyxiated newborns with room air or 100% oxygen at birth: a multicentric clinical trial. Indian Pediatr 2003Jun; 40: 510-7 6. Jacobs S, Hunt R, Tarnow-Mordi W, et al. Cooling for newborns with hypoxic-ischaemic encephalopathy. Cochrane Database Syst Rev 2003; 4: CD003311. Competing interests: None declared |
|||
|
|
|||
|
Philip B James, Professor of Hyperbaric Medicine University of Dundee, Ninewells Hospital, Dundee DD1 9SY
Send response to journal:
|
In their review of Chinese experience of hyperbaric treatment in neonates Liu et al1 do not discuss the scientific basis for using high levels of oxygen in the presence of neonatal hypoxia. It is often forgotten that barometric pressure determines oxygen delivery; hyperbaric conditions are simply needed to increase the dosage of oxygen in much the same way as an elevation of hydrostatic pressure is used to administer intravenous fluids. Most of the interventions currently being investigated in neonatal hypoxia, such as sedation and hypothermia, simply aim to reduce oxygen demand by reducing metabolism. Magnetic Resonance Spectroscopy (MRS) has shown that grossly subnormal ATP levels indicating the energy failure due to hypoxia may be present for 35 days despite normal haemoglobin oxygen saturation.2 MRS has also shown that high lactic acid levels, another indicator of hypoxia, correlate with an increased risk of death, persistent vegetative coma and severe disability in infants.3 However, the rationale in using oxygen in hypoxia extends beyond providing the energy derived from ATP, as oxygen regulates vascular tone through a mechanism involving nitric oxide and the formation of nitrosohaemoglobin. High levels of oxygen reduce blood-brain barrier permeability and have been also been demonstrated to control cerebral oedema by lower intracranial pressure.4 However oxygen also regulates the level of the protein Hypoxia- Inducible 1 alpha (H.I.F. 1 alpha) responsible for damaging inflammation. Hypoxia produced by an abrupt reduction of oxygen levels in incubators was responsible for retinopathy of the newborn, not oxygen toxicity.5 Hyperbaric oxygen treatment is well-established in China because it is regarded as a proven treatment and it is generally seen as unethical to conduct controlled studies of what is essentially an increase in oxygen dosage in the presence of hypoxia. References 1. Liu Z, Xiong T, Meads C. Clinical effectiveness of treatment with hyperbaric oxygen for neonatal hypoxic-ischaemic encephalopathy: systematic review of Chinese literature. Br Med J 2006;333:374-384. 2. Ashwal S, Holshouser BA, Tomasi LG, Shu S, et al. 1H-magnetic resonance spectroscopy-determined cerebral lactate and poor neurological outcomes in children with central nervous system disease Ann Neurol 1997;41:470-481. 3. Martin E, Buchli R, Ritter S, et al. Diagnostic and prognostic value of cerebral magnetic resonance spectroscopy in neonates with perinatal asphyxia. Pediatric Res 1996;40:749-758 4. Sukoff MH, Ragatz RE. Hyperbaric oxygenation for the treatment of acute cerebral edema. Neurosurgery 1982;10:29-38. 5. James PB. Retinopathy of the newborn is due to hypoxia not oxygen toxicity. In; Evrard P, Richelme C, Tardieu M. eds. Proc 3rd Congress of the European Paediatric Neurology Society. Monduzi Editore, Bologna 1999;41-44. Competing interests: None declared |
|||