Patent ductus arteriosus: time to grasp the nettle?

The management of patent ductus arteriosus is controversial, and there are diverse approaches to treatment, ranging from very conservative management through to early and aggressive securing of ductus closure, either pharmacologically or surgically. This lack of consensus on best management reflects a paucity of high quality randomised controlled trials, with many published studies focusing on establishing points of treatment, rather than looking for benefits of intervention over more conservative management. Despite this lack of good evidence views on ductus management can be entrenched, with accompanying loss of equipoise. This review looks at our current situation with regard to ductus arteriosus management and the need for good quality trials especially in the light of other published studies, concerning postnatal steroids, caffeine and oxygen which have demonstrated unexpected benefits - or sometimes unexpected harm - from long-familiar drugs.

Peripheral blood flow and oxygen extraction in the sick, newborn very low birth weight infant shortly after birth.

This study examined the relationship between blood pressure, peripheral blood flow (PBF), and peripheral fractional oxygen extraction (FOE). Variables that may influence PBF and peripheral FOE were also measured. Measurements of PBF by near infrared spectroscopy and fractional shortening by echocardiography were made within 12 h of birth in 24 infants less than 32 wk gestation. Blood gases, Hb, temperature, and blood pressure were also measured. PBF was significantly correlated with fractional shortening (r = 0.56, p = 0.005), Po2 (r = -0.5, p = 0.01), and peripheral temperature (r = 0.52, p = 0.01). Peripheral FOE was significantly correlated with fractional shortening (r = -0.48, p = 0.02), Po2 (r = 0.52, p = 0.02), and Pco2 (r = -0.53, p = 0.008), but not with peripheral temperature. There was no significant correlation between blood pressure and either PBF or peripheral FOE. These results indicate the importance of several physiologic variables, but not blood pressure, in determining peripheral tissue oxygen delivery in sick preterm infants receiving intensive care. It adds weight to the idea that blood pressure should not be considered a surrogate for peripheral blood flow and oxygen delivery.

CSF cytokine levels in preterm infants may reflect systemic inflammation and are independent of gestation.

BACKGROUND: Among preterm infants, high concentrations of inflammatory mediators in cerebrospinal fluid (CSF) are associated with poor outcome. Previous studies have not indicated whether CSF concentrations of inflammatory mediators are associated with important confounders such as gestational age. AIMS: To examine associations between CSF concentrations of inflammatory mediators and gestational age, maternal features suggestive of inflammation, characteristics of the CSF sample or the presence of a systemic inflammatory response. STUDY DESIGN AND SUBJECTS: Aliquots of CSF obtained during routine investigation of potential sepsis among infants born before 35 weeks gestation were assayed for 17 mediators of inflammation using a fluorescent multi-bead analyser. Other information was collected from routine clinical records. RESULTS: 39 infants were assessed. CSF levels of mediators of inflammation were not correlated with gestational age. CSF red blood cell counts were correlated with CSF concentrations of IL-6, GM-CSF and IL-17 (each p<0.003). CSF lactate was correlated with CSF concentrations of IL-1beta, IL-6, GM-CSF, G-CSF, IFN-gamma and MIP-1beta. CSF concentrations of IL-1beta, IL-6, G-CSF, TNF-alpha and IFN-gamma were higher in infants with a raised CRP within 24 h of delivery (each p<0.003). CONCLUSIONS: CSF concentrations of inflammatory mediators most probably reflect inflammatory pathologies and are not influenced by gestational age. They may also, however, reflect contamination with blood or systemic inflammation. CSF concentrations of inflammatory mediators may not provide a specific indicator of CNS inflammation.

Cerebral fractional oxygen extraction is inversely correlated with oxygen delivery in the sick, newborn, preterm infant.

Cerebral blood flow (CBF) is known to be low in newborn infants, but this has not been shown to be damaging. The purpose of this study was to investigate the relationships between cerebral haemoglobin flow, blood flow, oxygen delivery, oxygen consumption, venous saturation, and fractional oxygen extraction (OEF) in newborn, preterm infants. Measurements were made by near-infrared spectroscopy in 13 very preterm, extremely low birth weight infants (median gestation 25 weeks) during the first 3 days after birth. There was a negative correlation between cerebral oxygen delivery and OEF (n=13, r=-0.5, P=0.03), which implies that when there is a reduction in cerebral oxygen delivery in sick preterm infants, increased cerebral oxygen extraction may be responsible for maintaining oxygen availability to the brain. During the first 3 days after birth CBF (n=13, r=0.7, P=0.01), oxygen delivery (n=13, r=0.5, P=0.03), and oxygen consumption (n=13, r=0.7, P=0.004) all increased. This increase in oxygen consumption indicates increased cerebral metabolic activity after birth, which is likely to be a normal adaptation to extrauterine life. The increases in blood flow and oxygen delivery may also be normal adaptations that facilitate this increase in metabolic activity. There was a decrease (P=0.04) in mean (+/-s.d.) cerebral OEF between day 1 (0.37+/-0.10) and day 2 (0.29+/-0.09), with no change between day 2 and day 3. Taking into account the negative correlation between OEF and oxygen delivery, this decrease in OEF may be because of increased oxygen delivery during this time.

Postnatal changes in cerebral oxygen extraction in the preterm infant are associated with intraventricular hemorrhage and hemorrhagic parenchymal infarction but not periventricular leukomalacia.

Fluctuations in cerebral hemodynamics have been implicated in the pathogenesis of acquired brain damage in babies born prematurely. This study examined the changes in cerebral fractional oxygen extraction (FOE) over the first 3 d after birth in 25 very-low-birth-weight preterm infants. Twelve infants had no major cerebral injury and 13 had acquired brain injury; cystic periventricular leukomalacia (PVL) was present in 4 and intraventricular hemorrhage (IVH) in 9, of whom 2 also had hemorrhagic parenchymal infarction (HPI). Normal values (median, 5(th)-95(th) centiles) for cerebral FOE in very-low-birth-weight infants with no cerebral injury were 0.38 (0.23-0.53) on d 1, 0.31 (0.18-0.45) on d 2, and 0.28 (0.17-0.38) on d 3. Infants who developed cystic PVL had no significant change in cerebral FOE during the first 3 d after birth. By contrast, cerebral FOE fluctuated in infants with IVH over the 3 d of measurement, decreasing from d 1 to d 2 (p = 0.03) and increasing from d 2 to d 3 (p = 0.02). The highest cerebral FOE values were seen in the two infants with HPI. The different patterns of change in cerebral FOE with HPI and cystic PVL provide additional evidence that the pathogenesis of these two conditions is different. Because high cerebral FOE is likely to be a consequence of low cerebral oxygen delivery, probably because of low cerebral blood flow, our results indicate that fluctuations in cerebral blood flow may occur when there is IVH or HPI.

Cerebral fractional oxygen extraction in very low birth weight infants is high when there is low left ventricular output and hypocarbia but is unaffected by hypotension.

This study examined the relationships between cerebral fractional oxygen extraction (FOE), mean arterial blood pressure (MABP), left ventricular output (LVO), blood gases, and other physiologic variables in 36 very-low-birth-weight preterm infants during the first 3 d after birth. There was a decrease in cerebral FOE (p = 0.008), and rises in LVO (p < 0.0001) and MABP (p = 0.02) during the 3 d. Between d 1 and 2, cerebral FOE decreased (p = 0.007) and LVO increased (p < 0.0001). There was no relationship between MABP and cerebral FOE. LVO correlated negatively with cerebral FOE on d 1 (p = 0.01), but not on d 2 (p = 0.07). On d 1, median pressure of arterial CO(2) was lower in infants with low LVO (<5(th) centile) and high cerebral FOE (>95(th) centile) than in infants with low LVO (<5(th) centile) but normal cerebral FOE (5(th)-95(th) centile) (p = 0.03). These findings suggest that cerebral FOE was increased only when LVO was low and there was hypocarbia. MABP had no demonstrable effect. It is likely that increased cerebral FOE is a normal physiologic response to maintain an adequate oxygen supply to the cerebral tissues when LVO is low and hypocarbia has caused vasoconstriction. It is possible that the cerebral hemispheres are low-priority vascular beds in the preterm infant, and that the high cerebral FOE is a result of reduced hemispheric blood flow to maintain MABP in the presence of low LVO.