Background of HIP

As with many clinical practices in medicine, the rationale for certain procedures /interventions in the preterm newborn have been supported by a belief that the procedure/intervention was beneficial using suboptimal studies that could not produce good quality data. Moreover, many of these interventions have been derived from the adult literature and have not been validated in the newborn.

Hypotension remains a significant problem in the preterm infant and is statistically associated with adverse short-term and long-term outcomes. Currently no uniform criteria exist to define hypotension and the evidence to support our current management strategies is limited.

Shock is a pathological state characterised by inadequate tissue oxygen delivery to meet demand. There is little or no correlation between systemic blood flow and blood pressure in the preterm infant and very low systemic perfusion (shock) can occur with normal, low or high blood pressure. Despite this, the mainstay of management has been to maintain blood pressure above certain parameters, the principal concern being that hypotension results in low end organ blood flow, resulting in impaired cerebral blood flow, cerebral ischaemia and brain injury.

On the other hand preterm infants with blood pressure lower than average often have no biochemical or clinical signs of shock, they often have normal systemic blood flow and they presumably have low systemic vascular resistance and adequate tissue oxygen delivery and probably do not require treatment. Careful observation of such infants without intervention, an approach previously coined permissive hypotension, may well be appropriate.

When systemic oxygen delivery falls, there are a number of initial compensatory responses which occur that maintain perfusion and oxygen delivery to the most vital organs which include peripheral vasoconstriction to maintain blood pressure, i.e. shock without hypotension. Progression to the uncompensated phase is characterised by signs of poor perfusion accompanied with low blood pressure, i.e. shock with hypotension, ultimately leading to the irreversible stage if appropriate therapy is not instituted. In contrast to the permissive hypotension approach mentioned above, intervention to improve perfusion may be warranted in infants with shock despite normal blood pressure. Excessive intervention in preterm infants may be unnecessary, more importantly it may be harmful. Analysis of a large neonatal database (CNN) has demonstrated that treatment of hypotension was associated with an increase in serious brain injury. This held true even after the blood pressure was included in the regression mode, suggesting that it is treatment of hypotension, rather than the presence of hypotension which is harmful. The common interventions, fluid boluses followed by dopamine, could as well be harmful. Observational data has shown an association of fluid boluses with intracranial bleeding and in animal models intraventricular haemorrhage after hypotension can be induced by rapid volume infusion. Fluctuations in blood pressure when inotropes are introduced are well known and could also trigger haemorrhage. Furthermore, dopamine, the most commonly used inotrope, has effects on many physiologic functions including pituitary effects which lead to secondary hypothyroidism, a known risk factor for poor long-term outcome in the preterm infant. Current standard approaches to evaluation and treatment of transitional circulatory problems in the preterm infant may be harmful. It is essential that these approaches are adequately investigated.