Haemodynamic insufficiency occurs when there is a state of poor organ blood flow resulting in cellular energy failure due to an inability of tissue oxygen delivery to satisfy tissue oxygen demand. Haemodynamic insufficiency in the 48 hours after birth reflects a different disease process from older children and adults by acting on anatomy which is different from that seen in older age groups.
The 48 hours after birth differ markedly from all other periods in human life and are characterised by a unique and dynamic anatomy. This is accompanied by striking changes in function as the circulatory system of the healthy newborn infant adapts rapidly to life outside the womb. Immediately after birth the foramen ovale and ductus arteriosus are patent and functional. These foetal channels usually close within the first day of life. If these processes are impaired, as is often the case in preterm infants, consequences to health can be severe, life-threatening and even fatal.
In current clinical practice, diagnostic and therapeutic approaches are different when managing neonates born at less than 32 weeks gestation. Haemodynamic insufficiency in the first 48 hours after birth at less than 32 weeks´gestation is associated with increased risk of death and neurodisability.
There are anatomic features of the cardiovascular system that render neonates born at less than 32 weeks’ gestation unique. These relate to:
The myocardium (myocytes are less well-developed before 32 weeks of gestation);
Neuronal control (the autonomic nervous system is considerably less active before 32 weeks of gestation).
The specific physiological features of the adaptation to birth at extreme prematurity are:
the ductus arteriosus (this is more likely to be patent with left-to-right or bidirectional shunt among extremely preterm neonates than in other neonates);
the extent of ventricular distensibility (affecting preload) which is less following birth before 32 weeks than following birth after 32 weeks gestation;
the reduced reserve for ventricular contractility that is seen during foetal life.
Failure to adapt to circulatory changes results in early haemodynamic insufficiency in the newborn less than 32 week´s gestation. About 80% of the infantswho initially develop low systemic blood flow will subsequently develop systemic hypotension. A significant proportion of babies born at less than 32 weeks’ gestation require cardiovascular support in the hours after birth.
Dobutamine is widely used as an inotrope. Its unique effects make it suitable for the treatment of cardiogenic shock in adults and children more than 48 hours old. These effects are likely to be particularly relevant to the treatment of haemodynamic insufficiency during the transition to extrauterine life.
Proveca are developing intravenous dobutamine for the treatment of haemodynamic insufficiency during the transition to extrauterine life as part of a Framework 7 European (FP7) consortium. The Paediatric Committee (PDCO) of the European Medicines Agency (EMA) adopted a positive opinion of for a PIP for dobutamine in December 2012. EMA Link