A prolonged break, which occurred for various reasons, is at an end. I have a few posts lined up for the next few days, but will start with news about a new publication, an editorial I wrote with one of our fellows, Marie Janaillac (Barrington KJ, Janaillac M. Treating hypotension in extremely preterm infants. The pressure is mounting. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2016). The editorial was written to accompany another article about the outcomes of very preterm infants with low blood pressures. That article appeared on-line in the Archives in November, (Batton B, et al. Early blood pressure, antihypotensive therapy and outcomes at 18–22 months’ corrected age in extremely preterm infants. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2015).
We summarized the paper like this :
… the authors examined survival without neurological injury or developmental delay at 18–22 months in their cohort of infants less than 27 weeks gestation. They divided infants into 4 groups: those who received or did not receive antihypotensive therapy, and within each of those groups, those who had a slower than average rise in their blood pressure, and those with a faster increase. The primary outcome was not associated with a slower rise in blood pressure among untreated infants, but was strongly associated with hypotension treatment. Babies who received antihypotensive treatment, those with a good, and those with a poor response, were more likely to die, to have motor dysfunction, or to have developmental delay (in cognitive and language domains) than untreated infants. A potential mechanistic explanation is that the treated patients had a much higher incidence of brain injury on ultrasound (severe IVH or periventricular leukomalacia). These associations remained after adjusting for severity of illness measures.
You can never, of course, be sure that there is a causative relationship between the use of an intervention and an adverse outcome based on observational data alone. But the data are worrying, they follow on the heels of data from the German Neonatal Network (Faust K, et al. Short-term outcome of very-low-birthweight infants with arterial hypotension in the first 24 h of life. Archives of disease in childhood Fetal and neonatal edition. 2015;100(5):F388-92), that defined hypotension differently, but also showed that treatment of hypotension was associated with an increase in severe intraventricular hemorrhage and bronchopulmonary dysplasia. In the German study there was also an association with lower blood pressure and more complications also among infants who were not treated, but the associations with treatment were much stronger than the associations with lower BP. Odds Ratios for treatment effects were between 1.5 and 2.4, but for low blood pressure they were 0.94 to 0.97 (all significant at <0.01).
Where does this leave us? With the necessity to perform prospective trials. As we put it in the editorial
For hypotension treatment, there are many who will say that they do not have ‘equipoise’; those who are convinced that not treating, in the face of poor autoregulation, risks cerebral ischaemia, and others who are convinced that treating the numbers is irrational and risks drug toxicity. But we should all be able to agree that, if reasonable people hold differing opinions, there is real uncertainty. Even if we have strong hunches or preferences for one treatment approach over another, the lack of certainty should enable us, indeed force us, to perform the research we need to reduce that uncertainty and improve care for our babies.
We end the editorial with a plea to perform trials like HIP, and others that are needed to be able to provide an evidence base for future care.