Premies with Sepsis, what is happening to the circulation?

This is  a study of the hemodynamic profile of preterm infants who have septic shock, compared to matched controls. And an analysis of changes after institution of therapy.

Saini SS, Kumar P, Kumar RM: Hemodynamic changes in preterm neonates with septic shock: a prospective observational study. Pediatric critical care medicine: 2014, 15(5):443-450.

This is, I think, almost unique data. There is a previous study of the hemodynamic profile of infants who were thought to have sepsis (from Koert de Waal and Nick Evans) but not, like this study, restricted to that group of babies that are most problematic and high-risk, those in shock.

We really need data like these in order to be able to decide which kinds of therapy to test. I was, based on guesswork rather than data, of the opinion that septic shock in the newborn was often different to the kind of urosepsis that is a common cause of (usually gram negative) septicemia and warm shock in the adult. That was largely based on animal data, particularly data based on animal modelf of GBS sepsis .

This study using mostly echocardiography, along with clincial assessment, studied 52 preterm infants with a diagnosis of septic shock, half of whom had positive cultures. There were 52 infants matched for gestational and postnatal age who served as controls.

One thing these authors did not do was to divide the cases by cause of sepsis, I think it is likely, or at least possible, that gram negative organisms and their endtoxins lead to a differnet hemodynamic profile than gram positive organisms. Certainly in the studies I mentioned in newborn animals with GBS sepsis, they usually have a low cardiac output, and cold shock, which is a bit different to what these authors show, in their preterms. Of the 26 babies with positive cultures, 18 had gram negative organisms. I guess with only 8 ‘others’ (6 gram positives, 2 fungi) an analysis by type of organism would be problematic, but on the other hand it would have helped people to have preliminary data to see if enterococcal or staphylococcal sepsis might be different.

There are some findings, though, which are difficult to understand, for example, the study reports a substantially higher left ventricular output, LVO, in the septic babies than the controls, suggesting vasodilatation as an important cause of the shock, which is understandable, but at the same time, RVO was higher than LVO in both groups, and was essentially the same in the 2 groups, meaning that in the controls RVO was very much higher than LVO, while in the septic shock babies it was only slightly higher.

To have a right ventricular output so much higher than left is quite surprising. Usually, of course, with an open PDA and a left to right shunt, the LVO is higher than the RVO. If there are no shunts at all, the 2 are obviously equivalent. If the RVO is that much higher than the LVO, then maybe the control babies had large left-to-right inter-atrial shunts, which woud be strange, or large right to left PDA shunts, which also wouldn’t make a lot of sense.

Other published data are consistent with what I am saying here, for example, this study (Sirc J, Dempsey EM, Miletin J: Diastolic ventricular function improves during the first 48-hours-of-life in infants weighting <1250 g. Acta Paediatr 2015, 104(1):e1-6.) shows LVO consistently greater than RVO and increasing over the first 48 hours of life.

Which suggests to me that maybe there is a systematic error in the measurements by this group, inflating RVO. So we should treat these data with caution, and note that they suggest that vasodilatation is common in preterm babies with gram negative sepsis, or with negative cultures and similar clinical findings. But they can’t be considered definitive.

Further studies of the hemodynamics of septic shock are need to confirm these findings in the systemic circulation and clarify what is happening in the relative outputs of the 2 ventricles, and the circulatory shunts.

When we look at the effects of therapy, the authors were able to have before and after data from 41 septic babies who receive either dopamine or dobutamine. They didn’t show much in teh way of changes, apart from some increases in heart rate, particularly with dopamine.

More data about infants with septic shock would definitely help to determine which therapies are the most appropriate to study.

About Keith Barrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
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