I have only ever prescribed a vasopressin infusion once for a baby. An infant was dying of septic shock and I done everything that I thought might help, without any evident benefit. So I decided to try vasopressin, based on case reports and series in older children and adults, and a few cases in newborns; the baby became immediately anuric, rather than oliguric, and although the blood pressure increased slightly everything else got worse (acidosis, oxygenation etc.)

Vasopressin, as the name implies, has vasoconstrictor effects, it might be helpful therefore if the major pathophysiology is vasodilatation; but when there is cardiac dysfunction it is unlikely to be helpful.

Now I didn’t write a case report of my experience, but another group who saw a positive response did so: (Radicioni M, Troiani S, Camerini PG. Effects of terlipressin on pulmonary artery pressure in a septic cooled infant: an echocardiographic assessment. J Perinatol. 2012;32(11):893-5.) That is of course a major problem with case reports of therapy; people tend to report when things go well, but not when they don’t! I think if everyone who had tried vasopressin (or terlipressin, a long acting analogue) with a poor response wrote up their experience we might have a much more representative literature, but good luck getting them published.

Pellicer A, Riera J, Lopez-Ortego P, Bravo MC, Madero R, Perez-Rodriguez J, et al. Phase 1 study of two inodilators in neonates undergoing cardiovascular surgery. Pediatr Res. 2012.This on the other hand is a much better way to introduce new agents into clinical use. Start with a small RCT with very careful evaluation of PK and PD. This was an RCT in 20 newborn infants who had cardiac surgery at 1 to 4 weeks of age. Many such babies get hemodynamic support after surgery, in this study they were randomized before surgery to either milrinone or levosimendan, which was started during the surgery, and continued for 48 hours, after that the study was no longer masked, as the milrinone continued, but the levosimendan stopped. It would probably be better to compare each to placebo (it was a masked trial) but that would raise its own ethical issues. The authors show very little difference between the agents, which means that either they are equally effective, or equally ineffective (which is the problem with not having a placebo group). One worrying thing the authors showed was the progressive accumulation of active metabolites of levosimendan, that didn’t appear to be cleared very well, and were still detectable 14 days later! There were some minor other differences between the groups, or uncertain significance.

I’m sure there will be another new agent along in a minute, it would be great if the initial reports of use were not case reports, which are completely unreliable and nearly always positive, but small careful RCTs evaluating safety, kinetics, and hemodynamic responses, like Adelina Pellicer’s group have done. Then moving on to adequately powered placebo controlled studies, like the excellent milrinone trial of Mary Paradisis and her co-workers.