PEDIATRICS Vol. 110 No. 3 September 2002, pp. 615-616
COMMENTARY |
Oxygen Therapy: 50 Years of Uncertainty
Oxygen must have been given to more infants than any other medicinal product in the last 60 years. Despite that, we still know very little about how much infants actually need, or how much it is wise to give. Given that we have also known for nearly 50 years that it is easy to damage the eyes of preterm infants by giving too much oxygen, especially in the first few weeks of life,1,2 the depth of our ignorance is really quite embarrassing.It was the use of a randomized, controlled trial to inform clinical practice that first made clinicians aware that although oxygen was a "good thing," it was quite possible to have "too much of a good thing." Despite that, with one honorable exception,3 no other clinical trial has ever been conducted since then to clarify how much oxygen infants really need.4 The preterm infant grows without any difficulty in utero with arterial blood that is only 70% to 80% saturated.5 Why, then, do we persist in trying to keep the oxygen saturation of this same infant above 90% after birth?6
The only large attempt to build on the insight provided by the first clinical trials, finally published in 1977, used a descriptive, observational approach, but this failed to provide any worthwhile additional information.7 Additional trials were clearly going to be needed,8 but they were never conducted. One attempt was made, when it first became possible to monitor arterial oxygen tension noninvasively, to see whether this technology would reduce the risk of excessive oxygen exposure. There was no evidence that it did,9 although the trial did produce indirect evidence that serious retinopathy became more common when arterial partial pressure exceeded 80 mm Hg (10.7 kPa).10 No comparable attempt has yet been made to show whether saturation monitoring is any more effective in this regard.
Two well-designed clinical trials have now finally been performed to discover how best to optimize oxygen use in preterm infants >1 month old. The STOP-ROP trial failed to find convincing evidence that giving additional oxygen significantly reduced the rate at which retinal damage progressed once this was well underway,11 and the article by McGregor et al12 in this issue of Pediatrics describes, elegantly, the findings in those infants who could not be included in the main trial because oxygen saturation was already >94% without supplementation.
Now comes news of another trial, recently completed in Australia (the BOOST Trial), the objective of which was to discover whether oxygen supplementation improves growth or the later developmental progress of infants <30 weeks’ gestation. Those infants who were still deemed to need supplemental oxygen once they reached 32 weeks’ postmenstrual age were randomly allocated oximeters adjusted so that staff could aim to keep functional saturation at 91% to 94% or 95% to 98% until supplementation no longer seemed necessary without anyone knowing which infants were in which group. There was no evidence that more generous supplementation improved outcome.13 It is not clear whether those given more oxygen experienced more pulmonary problems, as they tended to do in the STOP-ROP trial.11 More (64% vs 46%) were certainly still in oxygen at 36 weeks’ postmenstrual age.
Having failed to find any evidence that mild desaturation is damaging to preterm infants >1 month old, we now need to readdress the issue of how much oxygen these infants really need in the first month of life. Manipulating the amount of oxygen given may do little for the speed with which retinopathy progresses once it has developed, but we still do not know whether we could stop it from developing in the first place if we treated the preterm infant more like a fetus in the first few weeks of life without increasing early mortality or long-term disability.4 Fifty years of observational study have gotten us nowhere.14,15 We need a large collaborative controlled trial to address this issue. At least 2 skeptical (but anonymous) commentators argued for this (in this journal) back in 1977.8 Their arguments remain just as cogent today as they were 25 years ago.
James Cook University Hospital
Middlesbrough, TS4 3BW, United Kingdom
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FOOTNOTES
Received for publication May 30, 2002; Accepted May 30, 2002.
Reprint requests to (W.T.) James Cook University Hospital, Middlesbrough, United Kingdom. E-mail: win.tin{at}stees.nhs.uk
REFERENCES
- Patz A, Hoeck LE, de la Cruz E. Studies on the effect of high oxygen administration in retrolental fibroplasia, I. Nursery observations. Am J Ophthalmol.1952; 35 :1248 –1253[Web of Science][Medline]
- Kinsey VE, Jacobus JT, Hemphill F. Retrolental fibroplasia: cooperative study of retrolental fibroplasia and the use of oxygen. Arch Ophthalmol.1956; 56 :481 –543
- Usher RH. Treatment of respiratory distress syndrome. In: Winters RW, ed. The Body Fluids in Pediatrics. Boston, MA: Little Brown; 1973:303–337
- Askie LM, Henderson-Smart DJ. Restricted versus liberal oxygen exposure for preventing morbidity and mortality in preterm or low birth weight infants. Cochrane Library, Issue 4. Oxford, United Kingdom: Update Software; 2001
- Nicolini U, Nicolaidis P, Fisk N, et al. Limited role of fetal blood sampling in prediction of outcome in intrauterine growth retardation. Lancet.1990; 336 :768 –772[CrossRef][Web of Science][Medline]
- Vijayakumar E, Ward GJ, Bullock CE, et al. Pulse oximetry in infants <1500 gm at birth on supplementary oxygen: a national survey. J Perinatol.1997; 17 :341 –345[Medline]
- Kinsey VE, Arnold HJ, Kalina RE, et al. PaO2 levels and retrolental fibroplasia: report of the Cooperative Study.
Pediatrics.1977; 60
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[Abstract/Free Full Text] - Les Chermignonards Désenchantés. Oxygen and retrolental fibroplasia.
Pediatrics.1977; 60
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–754 (see also Pediatrics. 1978;62:439–440)
[Abstract/Free Full Text] - Flynn JT, Bancalari E, Bawol R, et al. Retinopathy of prematurity. A randomized prospective trial of transcutaneous oxygen monitoring. Ophthalmology1987; 94 :630 –638[Web of Science][Medline]
- Flynn JT, Bancalari E, Snyder ES, et al. A cohort study of transcutaneous oxygen tension and the incidence and severity of retinopathy of prematurity. N Engl J Med.1992; 326 :1050 –1054[Abstract]
- The STOP-ROP Multicenter Study Group. Supplemental therapeutic oxygen for prethreshold retinopathy of prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes.
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[Abstract/Free Full Text] - McGregor ML, Bremer DL, Cole C, et al. Retinopathy of prematurity outcome in infants with prethreshold retinopathy of prematurity and oxygen saturation >94% in room air: the High Oxygen Percentage in Retinopathy of Prematurity Study.
Pediatrics.2002; 110
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[Abstract/Free Full Text] - Askie L, Henderson-Smart D, Irwig L, et al. The effect of differing oxygen saturation targeting ranges on long term growth and development of extremely preterm, oxygen dependent infants: The BOOST Trial [abstract.]. Pediatr Res.2002; 51 :378
- Silverman WA. Retrolental fibroplasia: a modern parable. Monographs in Neonatology. New York, NY: Grune & Stratton; 1964:64
- Tin W, Milligan DWA, Pennefather P, et al. Pulse oximetry, severe retinopathy, and outcome at one year in babies of less than 28 weeks gestation. Arch Dis Child.2001; 84 :F106 –F110[CrossRef]
PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics
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eLetters:
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- Oxygen Therapy: 50 years of Ignorance
- Kenneth Stoller, MD, FAAP
- Pediatrics Online, 8 Sep 2002 [Full text]
- Oxygen Therapy: 50 years of Ignorance
- Win Tin
- Pediatrics Online, 13 Sep 2002 [Full text]
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