Comprehensive, real-time hemodynamic monitoring and data acquisition: An essential component of the development of individualized neonatal intensive care

Introduction

Recent advances in biomedical research and technology have allowed clinicians to obtain more clinically relevant physiologic, biochemical, and genetic information that could be useful in the diagnosis and management of various conditions. Neonatology has become one of the rapidly evolving subspecialties at the frontier of this progress. However, the field of neonatal hemodynamics, while being extensively investigated in basic/animal laboratory and clinical research settings, remains inadequately understood. Accordingly, we continue to have difficulties in establishing reliable criteria for the diagnosis of the most common deviations from physiology, such as neonatal hypotension, especially during the period of immediate postnatal transition. This, in turn, leads to a paucity of established, evidence-based guidelines on when and how to intervene in a neonate presenting with these conditions. Thus we must recognize the significant limitations of our current understanding of a number of clinically relevant aspects of neonatal cardiovascular physiology and pathophysiology and acknowledge the existing vast differences in opinions on diagnostic criteria and treatment approaches in neonatal intensive care and neonatal cardiovascular pathophysiology in particular.

The next logical step in identifying individual patients with early signs of hemodynamic compromise is to develop and implement comprehensive objective hemodynamic monitoring systems that enable continuous and real-time monitoring and acquisition of multiple hemodynamic parameters of systemic and regional blood flow and oxygen demand-delivery coupling. The information obtained can then be used to design and execute clinical trials in subpopulations of neonates exhibiting common hemodynamic features and targeted by a given intervention. This approach will enable timely identification of the individual patient in the future in whom a trial-tested, individualized management plan can be utilized and the response to the pathophysiology- and evidence-based interventions monitored.

Limitations of conventional monitoring

Multiple studies have shown an association between severe cardiovascular compromise and increased morbidity and mortality in affected patients. Although there is some evidence for improved outcome in hypotensive preterm infants responding to vasopressor-inotropes with increases in blood pressure and cerebral blood flow, ^, essentially none of the suggested interventions or medications used (dopamine, epinephrine, dobutamine, milrinone or vasopressin) has been properly studied to determine the actual impact of the treatment on clinically relevant medium- and long-term outcomes.

The failure to identify effective interventions for the treatment of neonatal hemodynamic compromise stems from several unresolved challenges. The cardiovascular system of the newborn undergoes rapid changes during transition to extrauterine life, and these changes are greatly affected by multiple intrinsic and extrinsic factors. Such factors include, but are not limited to, individual variations in the degree of immaturity based on gestational and postnatal age, coexisting comorbidities including the need for positive pressure ventilation, the complex interactions between systemic and regional blood flow, and underlying genetic heterogeneity.

Another fundamental challenge is the lack of pathophysiology- and evidence-based definition of neonatal hypotension (see Chapters 1 and 3 ). Measurements of blood pressure with or without the use of indirect clinical indicators of perfusion remain the major criterion in the assessment of the hemodynamic status and the need for interventions. Normative blood pressure values in preterm and term infants have been reported in population-based studies, and mean arterial blood pressure increases with increasing gestational and postnatal age ( Chapter 3 ). ^, However, blood pressure within the normal range for a given gestational and postnatal age does not necessarily reflect normal organ blood flow. And, similarly, abnormally low blood pressure values do not automatically translate into compromised organ blood flow (see Chapters 1 and 3 ). So, for patients of the same gestational age and degree of maturity, the same blood pressure values can be associated with either adequate or compromised systemic and organ perfusion. More so, even for the same patient under different conditions and points in time, the same blood pressure values may represent adequate or compromised systemic and/or organ perfusion. The reason for such limitations of using the blood pressure alone as an indicator of hemodynamic compromise lies in the fact that blood pressure is determined by the interaction between systemic blood flow (represented by effective cardiac output) and systemic vascular resistance. Thus the same values of blood pressure, the dependent variable, can result from different combinations of the other two, independent, variables. In the early, compensated phase of shock, blood pressure remains within the normal range while non-vital organ perfusion has, by definition, decreased. As many pathophysiologic mechanisms may lead to inadequate organ blood flow, whether they affect effective cardiac output, systemic vascular resistance, or both, failure to recognize these changes potentially leads to delay in initiation of treatment, exhaustion of limited compensatory mechanisms, and a resultant progression to the uncompensated phase of shock, with obvious signs of decreased organ perfusion and oxygen delivery. On the other hand, unnecessary treatment might also be started if the condition is thought to have reached the treatment threshold when, in reality, systemic and/or regional blood flow is maintained. In addition, identification of the primary pathophysiologic mechanism that could prompt appropriately targeted intervention becomes more challenging when reliable information on the status of the macro-circulation and/or tissue oxygen delivery is not readily available.

Other conventional hemodynamic parameters (heart rate and arterial oxygen saturation), even if continuously monitored along with blood pressure, as well as capillary refill time, urine output, and serum lactate levels, have significant limitations for timely and accurate assessment of both the cardiovascular status and the response to interventions aimed to treat the hemodynamic compromise. Therefore inclusion of targeted assessment of systemic blood flow and regional organ perfusion becomes paramount to overcome these limitations and identify at-risk patients in a timely manner and intervene appropriately.