Published online February 29, 2008
PEDIATRICS Vol. 121 No. 3 March 2008, pp. 654-655 (doi:10.1542/peds.2007-3798)

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LETTER TO THE EDITOR

Hypotension and Brain Injury in Premature Infants: In Reply

Adré J. du Plessis, MBChB, MPH
Department of Neurology
Children's Hospital Boston and Harvard Medical School
Boston, MA 02115

We appreciate the interest of Hall and Kaiser in our recent article.¹ We agree that the role of systemic hemodynamics in prematurity-related brain injury is an extremely complex issue, and that currently "conclusions regarding cause and effect are problematic." Two fundamental obstacles impede development of rational, brain-oriented management strategies of systemic hemodynamics in premature infants. First, we do not understand the critical features of systemic hemodynamic changes (eg, magnitude, duration, repetition, timing, and dynamic nature) that constitute a cerebrovascular insult in the premature infant. Second, we remain unable to reliably diagnose the onset of brain injury in critically ill infants. Clinical signs are subtle or absent, and the repeated bedside imaging required to address cause and effect during high-risk periods remains confined to cranial ultrasound with its limited sensitivity to most parenchymal, especially nonhemorrhagic, injury. Dependence on routine clinical ultrasound is an acknowledged limitation of our study, leaving us unable to address the possibility that early and aggressive antihypotensive measures "may have prevented (or even caused) brain injury."

Our goal was to use comprehensive measurements of mean arterial pressure (MAP) in different time domains (ie, very short term using the SD of MAP at 2-Hz recording; short term using a 5-minute mean MAP; and longer term, using the hypotensive index) to examine the association between widely used definitions of systemic hypotension and cranial ultrasound abnormalities. Despite periods when MAP was not available (delayed arterial line placement; unavailability of research staff and equipment), our approach was more systematic and comprehensive than those used in previous studies, wherein hemodynamic measures have ranged from a 24-hour average blood pressure (BP)² to the single lowest BP over periods as long as 3 days.³ We used all grades of germinal matrix-intraventricular hemorrhage (GM-IVH) as a single outcome on the basis of the assumption that they occur on a mechanistic continuum. Grouping grade III GM-IVH and parenchymal echodensities may be useful for prediction of neurodevelopmental outcome, but this was not a goal of our study.

On the basis of accumulating evidence from our studies,^1,4 our opinion is that isolated, static measures of physiologic signals are merely snapshots in time and are unable to do justice to the enormous complexity of the transitional circulation. Justifiable concerns exist regarding the efficacy of currently used pressor inotropes. However, data for brain injury caused by these agents are hardly compelling, and equipoise is not clear. Before placebo-controlled clinical trials of pressor inotropes begin, we need to redefine and validate management guidelines by using dynamic monitoring techniques of brain perfusion, rather than the static BP thresholds currently in use.

REFERENCES

1. Limperopoulos C, Bassan H, Kalish LA, et al. Current definitions of hypotension do not predict abnormal cranial ultrasound findings in preterm infants. Pediatrics.2007; 120 (5):966 –977[Abstract/Free Full Text]
2. Cunningham S, Symon AG, Elton RA, Zhu C, McIntosh N. Intra-arterial blood pressure reference ranges, death and morbidity in very low birthweight infants during the first seven days of life. Early Hum Dev.1999; 56 (2–3):151 –165[CrossRef][Web of Science][Medline]
3. Dammann O, Allred EN, Kuban KC, et al. Systemic hypotension and white-matter damage in preterm infants. Dev Med Child Neurol.2002; 44 (2):82 –90[CrossRef][Web of Science][Medline]
4. Soul JS, Hammer PE, Tsuji M, et al. Fluctuating pressure-passivity is common in the cerebral circulation of sick premature infants. Pediatr Res.2007; 61 (4):467 –473[CrossRef][Web of Science][Medline]

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PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics

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This Article Extract Full Text (PDF) Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in Web of Science Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by du Plessis, A. J. Search for Related Content PubMed Articles by du Plessis, A. J. Related Collections Heart & Blood Vessels Social Bookmarking                         What's this?