A new prospective multi-center evaluation, of cardiac function and the causes of hypotension after PDA ligation, has just published data about adrenal function.
The babies all had a serum cortisol measured before the surgery, and had a 1 microg/kg ACTH stimulation test. They had cortisol measured post-op also, at between 10 and 12 hours postop, which is the average time of peak use of inotropes, and the time when El-Khuffash, Jain, and McNamara have demonstrated the worst left ventricular dysfunction. (that link is to a very nice, fairly brief, review article about the important issues). The new study found no difference in the cortisol levels or the ACTH response between normotensive and hypotensive infants (about half were in each group). They did, however, show that the worst infants, who needed at least 15 mics of dopamine or dobutamine total dose per kg per min, had substantially lower post-operative cortisol concentrations. Although there was some overlap with the less sick infants.
This is somewhat different to a previous study (El-Khuffash A, McNamara PJ, Lapointe A, Jain A. Adrenal function in preterm infants undergoing patent ductus arteriosus ligation. Neonatology. 2013;104(1):28-33) published last year from the Sick Kids group, (including Anie Lapointe who is now my colleague at Sainte Justine). That previous study also did ACTH stimulation tests before PDA ligation, and showed that infants who had lower responses (<750 nmol 1 h after 35 microg/kg ACTH) were more likely to have postoperative hypotension, and more likely to have post-operative deterioration of their respiratory function as well. Interestingly in that study, the left ventricular output (LVO) was not associated with the pre-op cortisol responses. So perhaps less cortisol reserve s associated with an inability to maintain SVR, leading to hypotension rather than low cardiac output. Patrick McNamara’s group at Sick Kids uses a lot of milrinone in the babies with lower LVO, which might also be implicated in these responses.
I am not sure why the differences between these 2 studies, they are of course both observational, the differences may just be random variations. The much lower dose for the ACTH test in the new study might be one reason. (By the way to convert from the ‘american’ units of ng/ml to nmol/ml multiply by 2.8 (or to be precise by 2.759) I just had to look that up). But what test is preferable, and how to define relative adrenal insufficiency is still a mystery to me.
One other interesting aspect of the new study is that they measured other cortisol precursors and metabolites, and they were all low in the severe hypotension babies. Which implies that the problem is not with the adrenal gland but with the responsiveness of the entire hypothalamo-pituitary-adrenal axis.