Dose-Dependent Hemodynamic and Metabolic Effects of Vasoactive Medications in Normotensive, Anesthetized Neonatal Piglets

Abstract

ABSTRACT: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 O 2 saturation, and acid-base and electrolyte status in response to escalating doses of vasoactive medications in normotensive anesthetized neonatal piglets. We used regional tissue O 2 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. (Pediatr Res 70: 473-479, 2011) C ardiovascular compromise is a frequently encountered condition in the critically ill preterm and term infant (1) resulting in inadequate tissue O 2 delivery, impaired cerebral blood flow (CBF) autoregulation, and, potentially, end-organ injury and death (1-3). Our limited ability to accurately monitor changes in neonatal hemodynamics curtails timely recognition, and thus treatment, of neonatal shock.Although vasopressor-inotropes, inotropes, and lusitropes have been used to manage neonatal cardiovascular compromise with an attempt to tailor the treatment to the suspected primary etiology (1), there is only limited information available on the safety and effectiveness of these medications (1,4) and little is known about their developmentally regulated dose-dependent hemodynamic actions (4,5). Recent advances in bedside hemodynamic monitoring techniques using, among others, near-infrared spectroscopy (NIRS) have made continuous, noninvasive monitoring of tissue O 2 delivery (6) possible. Accordingly, data on tissue O 2 delivery and utilization (7) and regional O 2 saturation in critically ill adults, children, and, more recently, neonates have become available (2,3,8 -10).To gain insight into the specific, drug-related changes in neonatal hemodynamics, we used traditional and NIRS hemodynamic monitoring technologies and investigated the changes in heart rate, blood pressure (BP), common carotid artery (CCA) blood flow (BF), cerebral regional tissue O 2 saturation (CrSO 2 ), renal (kidney) regional tissue O 2 saturation (KrSO 2 ), intestina...

Randomized, Placebo-Controlled Trial of Dobutamine for Low Superior Vena Cava Flow in Infants

“…Although this was a setback, the rate of low SVC flow reported in this study is in accordance with recent publications. 18 These preliminary results support a significant effect of DB on HR, as has been shown in mature newborn animals 19 and small observational studies in neonates. 20 DB administration did not raise any safety issues in this context, because no dose-limiting effects were observed during the study.…”

Abdominal Near-Infrared Spectroscopy Detects Low Mesenteric Perfusion Early in Preterm Infants with Hemodynamic Significant Ductus Arteriosus

“…Another possible limitation of the present study has been the exclusion of patients on vasoactive drugs. In experimental and clinical studies, it has been shown that these drugs, depending on the dosage, can cause relevant alterations in the register of the mean regional tissue perfusion measured by NIRS [29,30]. This situation was especially common in patients with lower GA in whom it was extremely difficult/impossible to place the abdominal sensor.…”

Dobutamine in Paediatric Population: A Systematic Review in Juvenile Animal Models

“…Similarly, some of the studies showed an increase in heart rate in a dose-dependent manner [5], [9], [11]–[13], [16], [18], [23], [26], [28]. An increase in stroke volume was mainly observed in studies using prolonged infusion (from 2 to 6 h) at doses higher than 10 µg/kg/min [6], [8], [9], [17].…”

“…In general, although studies were conducted in different animal species, more than 62% of them were performed in pigs [5]–[19].…”

“…Similarly, 42% of the studies used a control group [5]–[8], [12], [13], [15], [17], [21], [22]. Some studies assessed the effects of dobutamine by comparison with baseline data and/or the effect of other drugs.…”