A new study from the NICHD neonatal network Batton B, Li L, Newman NS, Das A, Watterberg KL, Yoder BA, et al. Use of Antihypotensive Therapies in Extremely Preterm Infants. Pediatrics. 2013 May 6.,This prospective cohort study was specifically designed to look at hypotension treatments, in infants less than 27 weeks gestation during the first 24 hours of life. Of a cohort of 367 babies, the authors found that 55% received at least one therapy for low BP; and, just like the ELGAN study, they found great variation in treatment of hypotension between centres.There was a variety of catecholamines used for treatment, some received hydrocortisone, and one baby received vasopressin.
The authors examined several different definitions of hypotension; despite this they were unable to show much association between hypotension and short term outcomes. In fact infants who were treated for hypotension had worse outcomes than those not treated, in particular intracranial hemorrhage, both overall and the more severe grades, as well as more retinopathy and lower survival. The lower survival was due to different mortality rates after the first week of life. All of the different outcomes disappeared after statistical adjustment.
Beau Batton and his colleagues end with the following statement ”Until there are data to suggest otherwise, antihypotensive therapy should be used cautiously for these infants because treatment of low BP is associated with similar or worse infant outcomes without evidence of benefit. Large, high-quality studies are needed to support evidence based recommendations for BP management in this population”
Gene Dempsey and I and our collaborators agree! See the HIP trial link on this blog page.
Speaking of which, some of the HIP collaborators have just published this article: Sirc J, Dempsey EM, Miletin J: Cerebral tissue oxygenation index, cardiac output and superior vena cava flow in infants with birth weight less than 1250 grams in the first 48 hours of life. Early Hum Dev 2013, 89(7):449-452. It gives some very interesting normal values (if you can call anything a normal value in a baby who weighs less than 1250g) for cerebral oxygenation and systemic flows over the first couple of days of life. Interestingly even this group, who have a history of interest in ”permissive hypotension ©” treated 20% of the cohort with interventions to raise the blood pressure. Just showing yet again how important it is that we gather some reliable data about how to treat these infants, with what, and at what thresholds of clinical indicators.
Neonatal Research 
Hi Keith – the authors did not seem to consider the possibility that infants treated for hypotension do worse because firstly such infants are more likely to in fact be hypotensive (which is probable) and secondly because hypotension is harmful (certainly possible), and thirdly because treatment does not fully mitigate that harm (likely!). One could conduct a similar study showing that infants treated for meningitis have worse outcomes than infants not treated for meningitis.
Not to dispute that we need much better data on the effectiveness or otherwise of our treatments.
Hi
I am not sure I would guess that they didn’t consider those possibilities, they are just impossible to exclude in an observational study, even a well done prospective cohort like this one.
I assume from their data and all the rest that we’ve reviewed, that low blood pressure is not a good marker of poor tissue oxygen delivery. Some infants with low BP are in shock, and have poor outcomes, some are fine with low SVR and do well without any intervention. Can we identify which are in which group? Are there some in the second group that might still benefit from having the BP pushed up? Are there some that have harm from having their BP pushed up?
The HIP trial will use primarily clinical signs to try and make those discriminations, and then try and confirm with ancillary tests (ECHO, NIRS, EEG).