Cardiovascular Supportive Therapies for Neonates With Asphyxia — A Literature Review of Pre-clinical and Clinical Studies

Asphyxiated neonates often have hypotension, shock, and poor tissue perfusion. Various “inotropic” medications are used to provide cardiovascular support to improve the blood pressure and to treat shock. However, there is incomplete literature on the examination of hemodynamic effects of these medications in asphyxiated neonates, especially in the realm of clinical studies (mostly in late preterm or term populations). Although the extrapolation of findings from animal studies and other clinical populations such as children and adults require caution, it seems appropriate that findings from carefully conducted pre-clinical studies are important in answering some of the fundamental knowledge gaps. Based on a literature search, this review discusses the current available information, from both clinical studies and animal models of neonatal asphyxia, on common medications used to provide hemodynamic support including dopamine, dobutamine, epinephrine, milrinone, norepinephrine, vasopressin, levosimendan, and hydrocortisone

Treating Hypotension in Preterm Neonates With Vasoactive Medications

Preterm neonates often have hypotension which may be due to various etiologies. While it is controversial to define hypotension in preterm neonates, various vasoactive medications are commonly used to provide the cardiovascular support to improve the blood pressure, cardiac output, or to treat shock. However, the literature on the systemic and regional hemodynamic effects of these antihypotensive medications in neonates is deficient and incomplete, and cautious translation of findings from other clinical populations and animal studies is required. Based on a literature search on published reports, meta-analytic reviews, and selected abstracts, this review discusses the current available information on pharmacologic actions, clinical effects, and side effects of commonly used antihypotensive medications including dopamine, dobutamine, epinephrine, norepinephrine, vasopressin, and milrinone in preterm neonates

The Effect Of Milrinone On Splanchnic And Cerebral Perfusion In Infants With Congenital Heart Disease Prior To Surgery: An Observational Study.

Despite the advancement in the postoperative care of neonates with congenital heart disease (CHD), there is little information on preoperative management of systemic and regional hemodynamics, which may be related to outcomes. We aimed to determine the preoperative effect of milrinone, a phosphodiesterase III inhibitor, on cardiac output and splanchnic and cerebral perfusion in neonates with CHD. Neonates with CHD requiring cardiac surgery were enrolled in a prospective, single-blinded study once a clinical decision of starting milrinone (0.75 μg/kg per minute intravenously) using institutional criteria was made. Demographic and clinical variables and outcomes were recorded. Combined cardiac output and measures of splanchnic (superior mesenteric and celiac arteries) and cerebral (anterior and middle cerebral arteries) perfusion were determined by Doppler studies at 0, 6, 24, and 48 h after milrinone infusion. Investigators were unaware of intervention time points and patients in analyzing blood flow measurements. Seventeen term (39.2 ± 1.3 weeks) neonates were included with hypoplastic left-sided heart syndrome (78.5%) as the most common diagnosis. Combined cardiac output increased by 28% within 48 h (613 ± 154 vs. 479 ± 147 mL/kg per minute at baseline, P < 0.05). Superior mesenteric artery mean velocity increased at 6 h and throughout 48 h of milrinone infusion (P < 0.05). Peak and mean velocities at cerebral arteries increased with milrinone infusion (P < 0.05~0.08), and the corresponding changes at celiac artery were modest. There were no significant changes in splanchnic and cerebral resistive and pulsatility indices during milrinone infusion. Milrinone increases cardiac output with concurrent effects on splanchnic and cerebral blood flows during the short-term preoperative use in neonates with CHD.44115-12

The effect of milrinone on splanchnic and cerebral perfusion in infants with congenital heart disease prior to surgery

Despite the advancement in the postoperative care of neonates with congenital heart disease (CHD), there is little information on preoperative management of systemic and regional hemodynamics, which may be related to outcomes. We aimed to determine the preoperative effect of milrinone, a phosphodiesterase III inhibitor, on cardiac output and splanchnic and cerebral perfusion in neonates with CHD. Neonates with CHD requiring cardiac surgery were enrolled in a prospective, single-blinded study once a clinical decision of starting milrinone (0.75 μg/kg per minute intravenously) using institutional criteria was made. Demographic and clinical variables and outcomes were recorded. Combined cardiac output and measures of splanchnic (superior mesenteric and celiac arteries) and cerebral (anterior and middle cerebral arteries) perfusion were determined by Doppler studies at 0, 6, 24, and 48 h after milrinone infusion. Investigators were unaware of intervention time points and patients in analyzing blood flow measurements. Seventeen term (39.2 ± 1.3 weeks) neonates were included with hypoplastic left-sided heart syndrome (78.5%) as the most common diagnosis. Combined cardiac output increased by 28% within 48 h (613 ± 154 vs. 479 ± 147 mL/kg per minute at baseline, P < 0.05). Superior mesenteric artery mean velocity increased at 6 h and throughout 48 h of milrinone infusion (P < 0.05). Peak and mean velocities at cerebral arteries increased with milrinone infusion (P < 0.05∼0.08), and the corresponding changes at celiac artery were modest. There were no significant changes in splanchnic and cerebral resistive and pulsatility indices during milrinone infusion. Milrinone increases cardiac output with concurrent effects on splanchnic and cerebral blood flows during the short-term preoperative use in neonates with CHD.44211512

Hemodynamic effects of high frequency oscillatory ventilation with volume guarantee in a piglet model of respiratory distress syndrome.

Respiratory failure is a common condition faced by critically ill neonates with respiratory distress syndrome (RDS). High frequency oscillatory ventilation (HFOV) is often used for neonates with refractory respiratory failure related to RDS. Volume guarantee (VG) mode has been added to some HFOV ventilators for providing consistent tidal volume. We sought to examine the impact of adding the VG mode during HFOV on systemic and cerebral hemodynamics, which has not been studied to date. A neonatal piglet model of moderate to severe RDS was induced by saline lavage. Piglets (full term, age 1-3 days, weight 1.5-2.4 kg) were randomized to have RDS induced and receive either HFOV or HFOV+VG (n = 8/group) or sham-operation (n = 6) without RDS. Cardiac function measured by a Millar® catheter placed in the left ventricle as well as systemic and carotid hemodynamic and oxygen tissue saturation parameters were collected over 240 min of ventilation. Mean airway pressure, alveolar-arterial oxygen difference and left ventricular cardiac index of piglets on HFOV vs. HFOV+VG were not significantly different during the experimental period. Right common carotid artery flow index by in-situ ultrasonic flow measurement and cerebral tissue oxygen saturation (near-infrared spectroscopy) significantly decreased in HFOV+VG at 240 min compared to HFOV (14 vs. 31 ml/kg/min, and 30% vs. 43%, respectively; p<0.05). There were no significant differences in lung, brain and heart tissue markers of oxidative stress, ischemia and inflammation. HFOV+VG compared to HFOV was associated with similar left ventricular function, however HFOV+VG had a negative effect on cerebral blood flow and oxygenation

Infants Born to Mothers Who Were SARS-CoV-2 Positive during Pregnancy and Admitted to Neonatal Intensive Care Unit

INTRODUCTION: Our objective was to compare neonatal outcomes and resource use of neonates born to mothers with SARS-CoV-2 positivity during pregnancy with neonates born to mothers without SARS-CoV-2 positivity. METHODS: We conducted a two-country cohort study of neonates admitted between January 1, 2020, and September 15, 2021, to tertiary neonatal intensive care unit (NICU) in Canada and Sweden. Neonates from mothers who were SARS-CoV-2 positive during pregnancy were compared with three randomly selected NICU neonates of mothers who were not test-positive, matched on gestational age, sex, and birth weight (±0.25 SD). Subgroup analyses were conducted for neonates born &lt;33 weeks' gestation and mothers who were SARS-CoV-2 positive ≤10 days prior to birth. Primary outcome was duration of respiratory support. Secondary outcomes were in-hospital mortality, neonatal morbidity, late-onset sepsis, receipt of breast milk at discharge, and length of stay. RESULTS: There were 163 exposed and 468 matched neonates in Canada, and 303 exposed and 903 matched neonates in Sweden. There was no statistically significant difference in invasive or noninvasive respiratory support durations, mortality, respiratory and other neonatal morbidities, or resource utilizations between two groups in both countries in entire cohort and in subgroup analyses. Receipt of breast milk at discharge was lower in the Canadian neonates of mothers who were SARS-CoV-2 positive ≤10 days before birth (risk ratio 0.68, 95% CI: 0.57-0.82). CONCLUSION: Maternal SARS-CoV-2 positivity was not associated with increased durations of respiratory support, morbidities, mortality, or length of hospital stay in Canada and Sweden among neonates admitted to tertiary NICU

Two-year neurodevelopmental outcomes of infants undergoing neonatal cardiac surgery for interrupted aortic arch: A descriptive analysis

ObjectiveThis study determined neurodevelopmental outcomes of survivors of neonatal cardiac surgery for interrupted aortic arch through an interprovincial program and explored preoperative, intraoperative, and postoperative outcome predictors.MethodsChildren who underwent neonatal cardiac surgery for interrupted aortic arch at 6 weeks old or younger between 1996 and 2006 had a multidisciplinary neurodevelopmental assessment at 18 to 24 months old (mental and psychomotor developmental indices as mean ± SD and delay [score <70]). Survivor outcomes were compared by univariate and multivariate analyses and compared between children with and without chromosomal abnormality.ResultsOutcomes were available for all 26 survivors (mortality, 3.7%). Mental and psychomotor developmental indices were 75.8 ± 17.1 and 72.3 ± 16.9, respectively, with significantly lower scores for children with chromosomal abnormalities, which accounted for 29% of the variance in developmental indices. For the remaining 17 children without chromosomal abnormalities, mental and psychomotor developmental indices were 82.7 ± 14.5 and 79.1 ± 14.3, respectively, with deep hypothermic circulatory arrest time and Apgar score at 5 minutes contributing 46% of the variance in mental developmental index.ConclusionsThe neurodevelopmental indices of children who have undergone neonatal cardiac surgery for interrupted aortic arch are below normative values; those of children with chromosomal abnormalities are even lower. For children without a chromosomal abnormality, longer deep hypothermic circulatory arrest times and low Apgar scores predict lower mental developmental indices at 18 to 24 months of age