Hemodynamic Changes During Rewarming Phase of Whole-Body Hypothermia Therapy in Neonates with Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: To delineate the systemic and cerebral hemodynamic response to incremental increases in core temperature during the rewarming phase of therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Continuous hemodynamic data, including heart rate (HR), mean arterial blood pressure (MBP), cardiac output by electrical velocimetry (COEV), arterial oxygen saturation, and renal (RrSO2) and cerebral (CrSO2) regional tissue oxygen saturation, were collected from 4 hours before the start of rewarming to 1 hour after the completion of rewarming. Serial echocardiography and transcranial Doppler were performed at 3 hours and 1 hour before the start of rewarming (T-3 and T-1; "baseline") and at 2, 4, and 7 hours after the start of rewarming (T+2, T+4, and T+7; "rewarming") to determine Cardiac output by echocardiography (COecho), stroke volume, fractional shortening, and middle cerebral artery (MCA) flow velocity indices. Repeated-measures analysis of variance was used for statistical analysis. RESULTS: Twenty infants with HIE were enrolled (mean gestational age, 38.8 ± 2 weeks; mean birth weight, 3346 ± 695 g). During rewarming, HR, COecho, and COEV increased from baseline to T+7, and MBP decreased. Despite an increase in fractional shortening, stroke volume remained unchanged. RrSO2 increased, and renal fractional oxygen extraction (FOE) decreased. MCA peak systolic flow velocity increased. There were no changes in CrSO2 or cerebral FOE. CONCLUSIONS: In neonates with HIE, CO significantly increases throughout rewarming. This is due to an increase in HR rather than stroke volume and is associated with an increase in renal blood flow. The lack of change in cerebral tissue oxygen saturation and extraction, in conjunction with an increase in MCA peak systolic velocity, suggests that cerebral flow metabolism coupling remained intact during rewarming.

Prediction of Hemodynamic Response to Epinephrine via Model-Based System Identification.

In this study, we present a system identification approach to the mathematical modeling of hemodynamic responses to vasopressor-inotrope agents. We developed a hybrid model called the latency-dose-response-cardiovascular (LDC) model that incorporated 1) a low-order lumped latency model to reproduce the delay associated with the transport of vasopressor-inotrope agent and the onset of physiological effect, 2) phenomenological dose-response models to dictate the steady-state inotropic, chronotropic, and vasoactive responses as a function of vasopressor-inotrope dose, and 3) a physiological cardiovascular model to translate the agent's actions into the ultimate response of blood pressure. We assessed the validity of the LDC model to fit vasopressor-inotrope dose-response data using data collected from five piglet subjects during variable epinephrine infusion rates. The results suggested that the LDC model was viable in modeling the subjects' dynamic responses: After tuning the model to each subject, the r (2) values for measured versus model-predicted mean arterial pressure were consistently higher than 0.73. The results also suggested that intersubject variability in the dose-response models, rather than the latency models, had significantly more impact on the model's predictive capability: Fixing the latency model to population-averaged parameter values resulted in r(2) values higher than 0.57 between measured versus model-predicted mean arterial pressure, while fixing the dose-response model to population-averaged parameter values yielded nonphysiological predictions of mean arterial pressure. We conclude that the dose-response relationship must be individualized, whereas a population-averaged latency-model may be acceptable with minimal loss of model fidelity.

Hemodynamic monitoring of the critically ill neonate: An eye on the future.

By continuous assessment of dynamic changes in systemic and regional perfusion during transition to extrauterine life and beyond, comprehensive neonatal hemodynamic monitoring creates numerous opportunities for both clinical and research applications. In particular, it has the potential of providing additional details about physiologic interactions among the key hemodynamic factors regulating systemic blood flow and blood flow distribution along with the subtle changes that are frequently transient in nature and would not be detected without such systems in place. The data can then be applied for predictive mathematical modeling and validation of physiologically realistic computer models aiming to identify patient subgroups at higher risk for adverse outcomes and/or predicting the response to a particular perturbation or therapeutic intervention. Another emerging application that opens an entirely new era in hemodynamic research is the use of the physiometric data obtained by the monitoring and data acquisition systems in conjunction with genomic information.

Modeling of neonatal hemodynamics during PDA closure.

The transition of the fetus at birth to extrauterine life is an extremely complex process. As part of the hemodynamic transition, the closure of ductus arteriosus, a fetal shunt, is among the key steps to achieve normal postnatal cardiovascular function. However, significant gaps remain in our knowledge pertaining to the hemodynamics of normal ductal closure, and in case of failure of closure, to the hemodynamic consequences and treatment of the patent ductus arteriosus (PDA) in preterm infants. This paper presents a mathematical model of a newborn's cardiovascular system with five peripheral organ systems, the ductus arteriosus, and the baroreceptor reflex. We present the hemodynamic findings during simulation of sudden ductal closure, an event seen in real life when the PDA is closed surgically. The results of our model match the clinical data.

Effect of carbon dioxide on cerebral blood flow velocity in preterm infants during postnatal transition.

AIM: High arterial carbon dioxide (PaCO2 ) and cerebral reperfusion are associated with peri/intraventricular haemorrhage. Our aim was to study the relationship between PaCO2 and cerebral blood flow (CBF) in preterm infants during postnatal transition. METHODS: We prospectively studied ≤30 weeks' gestation haemodynamically stable preterm infants during the first three postnatal days (n = 21; gestational age 25.8 ± 1.4 weeks). We measured middle cerebral artery mean flow velocity (MCA-MV) as a surrogate for CBF at the time of blood gas analysis. RESULTS: We obtained 78 PaCO2 -MCA-MV data pairs. The expected positive linear relationship between PaCO2 and MCA-MV was absent on the first postnatal day, equivocal on the second and present on the third. Using piecewise bilinear regression models, we identified PaCO2 breakpoints at 52.7 and 51.0 mmHg for postnatal days two and three, respectively. CONCLUSION: In haemodynamically stable preterm neonates, the expected positive linear relationship between PaCO2 and CBF may be absent on postnatal day one. On postnatal day three, and possibly day two, a PaCO2 threshold exists for this relationship, above which CBF becomes reactive to PaCO2 . We speculate that the enhanced CBF response to PaCO2 above the threshold contributes to the reperfusion injury and partly explains the association between hypercapnia and peri/intraventricular haemorrhage.

Transitional cardiovascular physiology and comprehensive hemodynamic monitoring in the neonate: relevance to research and clinical care.

A thorough understanding of developmental cardiovascular physiology is essential for early recognition of cardiovascular compromise, selective screening of at-risk groups of neonates, and individualized management using pathophysiology-targeted interventions. Although we have gained a better understanding of the physiology and pathophysiology of postnatal cardiovascular transition over the past decade with the use of sophisticated methods to study neonatal hemodynamics, most aspects of neonatal hemodynamics remain incompletely understood. In addition, targeted therapeutic interventions of neonatal hemodynamic compromise have not been shown to improve mortality and clinically relevant outcomes. However, the recent development of comprehensive hemodynamic monitoring systems capable of non-invasive, continuous and simultaneous bedside assessment of cardiac output, organ blood flow, microcirculation, and tissue oxygen delivery has made sophisticated analysis of the obtained physiologic data possible and has created new research opportunities with the potential of direct implications to patient care.

Neonatal hemodynamics: monitoring, data acquisition and analysis.

Monitoring of cardiovascular function is critical to both clinical care and research as the use of sophisticated monitoring systems enable us to obtain accurate, reliable and real-time information on developmental hemodynamics in health and disease. Novel approaches to comprehensive hemodynamic monitoring and data acquisition will undoubtedly aid in developing a better understanding of developmental cardiovascular physiology in neonates. In addition, development and use of state-of-the-art, comprehensive hemodynamic monitoring systems enable the recognition of signs of cardiovascular compromise in its early stages, and provide information on the hemodynamic response to treatment in critically ill patients.

Continuous non-invasive cardiac output measurements in the neonate by electrical velocimetry: a comparison with echocardiography.

OBJECTIVE: Electrical velocimetry (EV) is a non-invasive method of continuous left cardiac output monitoring based on measurement of thoracic electrical bioimpedance. The objective was to validate EV by investigating the agreement in cardiac output measurements performed by EV and echocardiography. DESIGN: In this prospective observational study, left ventricular output (LVO) was simultaneously measured by EV (LVO(ev)) using Aesculon and by echocardiography (LVO(echo)) in healthy term neonates during the first 2 postnatal days. To determine the agreement between the two methods, we calculated the bias (mean difference) and precision (1.96×SD of the difference). As LVO(echo) has its own limitations, the authors also calculated the 'true precision' of EV adjusted for echocardiography as the reference method. RESULTS: The authors performed 115 paired measurements in 20 neonates. LVO(ev) and LVO(echo) were similar (534±105 vs 538±105 ml/min, p=0.7). The bias and precision of EV were -4 and 234 ml/min, respectively. The authors found the true precision of EV to be similar to the precision of echocardiography (31.6% vs 30%, respectively). There was no difference in bias and precision between the measurements obtained in patients with or without a haemodynamically significant patent ductus arteriosus. CONCLUSIONS: EV is as accurate in measuring LVO as echocardiography and the variation in the agreement between EV and echocardiography among the individual subjects reflects the limitations of both techniques.

Dose-dependent hemodynamic and metabolic effects of vasoactive medications in normotensive, anesthetized neonatal piglets.

The developmentally regulated hemodynamic effects of vasoactive medications have not been well characterized. We used traditional and near-infrared spectroscopy monitoring technologies and investigated the changes in heart rate, blood pressure, common carotid artery (CCA) blood flow (BF), cerebral, renal, intestinal, and muscle regional tissue O2 saturation, and acid-base and electrolyte status in response to escalating doses of vasoactive medications in normotensive anesthetized neonatal piglets. We used regional tissue O2 saturation and CCA BF as surrogates of organ and systemic BF, respectively, and controlled minute ventilation and oxygenation. Low to medium doses of dopamine, epinephrine, dobutamine, and norepinephrine increased blood pressure and systemic and regional BF in a drug-specific manner, whereas milrinone exerted minimal effects. At higher doses, dopamine, epinephrine, and norepinephrine but not dobutamine decreased systemic, renal, intestinal, and muscle BF, while cerebral BF remained unchanged. Epinephrine induced significant increases in muscle BF and serum glucose and lactate concentrations. The findings reveal novel drug- and dose-specific differences in the hemodynamic response to escalating doses of vasoactive medications in the neonatal cardiovascular system and provide information for future clinical studies investigating the use of vasoactive medications for the treatment of neonatal cardiovascular compromise.