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Critically ill neonates admitted to neonatal intensive care units require specialized pharmacological treatment due to various medical conditions. However, despite the decades of clinical use of some pharmacological agents, there are still significant knowledge gaps surrounding their everyday use. The wide variability of drugs used in neonates, and how they are used in different settings worldwide, precisely reflects this fact. A major factor contributing to this variability is the lack of adequate studies regarding the effectiveness and safety of medications administered to neonates, especially in those born preterm. This is mainly due to inherent difficulties in performing pharmacokinetic, pharmacodynamic, and clinical studies in this age group. In this review, we discuss the existing data on medications most commonly used in the respiratory and cardiovascular care of the sick neonate. Knowledge gaps and future perspectives are highlighted, as well.

Anti-hypotensive treatment, which includes dopamine, dobutamine, epinephrine, norepinephrine, milrinone, vasopressin, terlipressin, levosimendan, and glucocorticoids, is a long-established intervention in neonates with arterial hypotension (AH). However, there are still gaps in knowledge and issues that need clarification. The main questions and challenges that neonatologists face relate to the reference ranges of arterial blood pressure in presumably healthy neonates in relation to gestational and postnatal age; the arterial blood pressure level that potentially affects perfusion of critical organs; the incorporation of targeted echocardiography and near-infrared spectroscopy for assessing heart function and cerebral perfusion in clinical practice; the indication, timing, and choice of medication for each individual patient; the limited randomized clinical trials in neonates with sometimes conflicting results; and the sparse data regarding the potential effect of early hypotension or anti-hypotensive medications on long-term neurodevelopment. In this review, after a short review of AH definitions used in neonates and existing data on pathophysiology of AH, we discuss currently available data on pharmacokinetic and hemodynamic effects, as well as the effectiveness and safety of anti-hypotensive medications in neonates. In addition, data on the comparisons between anti-hypotensive medications and current suggestions for the main indications of each medication are discussed. [ABSTRACT FROM AUTHOR]

Anti-hypotensive treatment, which includes dopamine, dobutamine, epinephrine, norepinephrine, milrinone, vasopressin, terlipressin, levosimendan, and glucocorticoids, is a long-established intervention in neonates with arterial hypotension (AH). However, there are still gaps in knowledge and issues that need clarification. The main questions and challenges that neonatologists face relate to the reference ranges of arterial blood pressure in presumably healthy neonates in relation to gestational and postnatal age; the arterial blood pressure level that potentially affects perfusion of critical organs; the incorporation of targeted echocardiography and near-infrared spectroscopy for assessing heart function and cerebral perfusion in clinical practice; the indication, timing, and choice of medication for each individual patient; the limited randomized clinical trials in neonates with sometimes conflicting results; and the sparse data regarding the potential effect of early hypotension or anti-hypotensive medications on long-term neurodevelopment. In this review, after a short review of AH definitions used in neonates and existing data on pathophysiology of AH, we discuss currently available data on pharmacokinetic and hemodynamic effects, as well as the effectiveness and safety of anti-hypotensive medications in neonates. In addition, data on the comparisons between anti-hypotensive medications and current suggestions for the main indications of each medication are discussed.

Background: BP monitoring is mandatory in all newborns to find out the cardiac as well as renal diseases. Premature infants have a limited ability to auto regulate cerebral blood flow when compared to full-term infants and hypotension is a major concern in them. Measures should be taken to detect neonatal hypotension and hypertension as earlier as possible and thereby they can be managed well. Aim: To determine the normative distribution of blood pressure in healthy newborns in the tertiary care setting in 1st 48 hours of life. To find out the factors affecting blood pressure in healthy newborn and to find out relationship between blood pressure distribution and anthropometric measurements of neonates. Materials and Methods Study design: This is a descriptive cross sectional study was conducted in the post-natal ward of DR.SMCSI Medical College Hospital, Karakonam, Kerala, India. Study population: Newborns in the postnatal ward after physical examination including modified Ballard assessment and APGAR score at 1 and 5 minutes were selected for the study. Study size: Study consisted of 400 Newborn. Study tools and Data collection procedure: Blood pressure measurements were taken at age 0–24 hours and 25-48 hours, three times at five minutes interval to get average values. BP measurement was performed with the neonate in the supine position, either awake or quiet or during sleep. The newborn was left for 10-15 min after the application of appropriate size cuff to the right arm to ensure quietness [12] . The automatic cuff inflation and deflation by the instrument rendered display of the BP values (systolic, diastolic and MAP) on the screen. Values are disregarded if any movement occurred during the measurement. The entire procedure was repeated twice as a standardization procedure for deriving on a single valid measurement. Weights of infants were measured by placing the baby naked on an infant’s weighing scale and length of the newborn was measured using an Infantometer. Results: The mean SBP, DBP and MAP for term babies in the first 24 hours of life were 70.7±14 mmHg, 39.1±11 mmHg and 49.6±11 mmHg respectively. For preterm, the corresponding values were 70.1±21 mmHg, 36.5±12 mmHg and 47.7±13.8 mmHg respectively. A significant positive correlation (p value<0.05) was observed between heart rate and blood pressure values of newborns both at 0-24 and 25- 48 hours of life. Conclusion: The normative distribution of mean arterial pressure in the term neonates in the first 48 hours of life was 49±9 mmHg. The normative distribution of mean arterial pressure in the preterm neonates in the first 48 hours of life was 47±13 mmHg. All three parameters (SBP, DBP, and MAP) were lower in preterm neonates compared to term neonates. DBP and MAP values significantly rose with increase in the birth weight of neonates at 0- 24 hours. Blood pressure values of neonates are also influenced by gestational diabetes mellitus and use of antenatal steroid. Maternal age and maternal BMI were found to have a significant influence in the blood pressure values of their babies. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of low dose vasopressin on the hemodynamics of neonates with persistent pulmonary hypertension and catecholamine refractory shock. Methods: This retrospective study was conducted in a level III NICU of a tertiary care teaching hospital, south India. Eighteen neonates with hypoxemic respiratory failure due to persistent pulmonary hypertension of newborn with catecholamine refractory shock were studied. Neonates were managed for hypotension with conventional inotropic support with the additional use of low dose vasopressin (LDV). Effect of vasopressin on oxygenation index (OI), blood pressure, duration of inotropic usage and survival was evaluated. Results: Mean OI was 38.2 ± 4.9, and mean blood pressure was 30.7 ± 5.3 mmHg before the start of vasopressin. Initiation of LDV (0.0003 ± 0.0001 IU/kg/min) for a median duration 36.4 ± 17.9 h was followed by a reduction in OI (p < 0.001), control of hypotension (p < 0.001), reduction in lactic acidosis (p < 0.001) and decline in inotropic support. Conclusions: In resource-restricted settings, LDV may be useful as a rescue therapy for persistent pulmonary hypertension of newborn with catecholamine refractory shock. [ABSTRACT FROM AUTHOR]

Objectives: Some monochorionic twin pregnancies need intensive cardiac management even in the absence of twin-to-twin transfusion syndrome after birth. The purpose of this study was to investigate risk factors related to persistent hypotension requiring cardiotonic agent use among monochorionic twin pregnancies without twin-to-twin transfusion syndrome.Study Design: This was a retrospective study of 316 monochorionic twin pregnancies without twin-to-twin transfusion syndrome (632 babies). All cases were treated in the neonatal intensive care unit. Hypotension was defined as mean arterial blood pressure below the norm for gestational age. Decreased left ventricular ejection fraction was defined as a value <60%. Dopamine, dobutamine and phosphodiesterase III inhibitor were used as cardiotonic agents for hypotension persisting even after adequate infusion.Results: Among the 632 cases, 33 (5.2%) needed cardiotonic agents for persistent hypotension. The frequency of persistent hypotension with decreased left ventricular ejection fraction was significantly higher among larger twins (4.4%) than among smaller twins (0.6%, p = 0.0038). In larger twins, multivariate analysis showed that Z-score for cardiothoracic area ratio (odds ratio, 2.31; p < 0.001), tricuspid regurgitation (odds ratio, 6.34; p = 0.015) and gestational age at delivery (odds ratio, 0.66; p < 0.001) correlated with persistent hypotension. In smaller twins, univariate analysis showed gestational age at delivery, birth weight, Z-score for birth weight and Z-score for cardiothoracic area ratio of the larger twin were related to persistent hypotension. Concentration of brain natriuretic peptide in the umbilical vein in larger and smaller twins were significantly correlated (coefficient of correlation = 0.792, p < 0.001).Conclusions: In monochorionic twin pregnancies, attention needs to be given to cardiac size along with amniotic fluid and fetal growth. Both larger and smaller twins carry risks of persistent hypotension after birth. Close observation is needed, especially in cases where the larger twin displays cardiomegaly despite absence of twin-to-twin transfusion syndrome. [ABSTRACT FROM AUTHOR]

Early postnatal hypotension in premature infants is treated with escalating doses of vasopressor-inotropes (VI), followed by hydrocortisone if VI therapy fails. The adverse effects of this standard clinical practice have not been well reported. In a retrospective case-control study, we compared the complications associated with VI and hydrocortisone (HCVI) treatments in extremely low-birth-weight infants (≤1000 g) with contemporaneous normotensive medication-naïve controls via standard univariate and multivariate analyses. Birth weight, gestational age, and receipt of antenatal steroids did not differ between VI (n = 74) and control (n = 124) groups, while the occurrence of gestational diabetes mellitus and risks for patent ductus arteriosus, intraventricular-periventricular hemorrhage, spontaneous intestinal perforation, ventriculomegaly, and bronchopulmonary dsyplasia were higher in VI. Infants in the HCVI group (n = 69) had lower birth weight, gestational age, and receipt of antenatal steroids and higher risks for intraventricular-periventricular hemorrhage, bronchopulmonary dysplasia, air leaks, and patent ductus arteriosus than controls. Whereas the occurrences of spontaneous intestinal perforation, ventriculomegaly, and maternal diabetes mellitus did not differ, that of maternal hypertension trended to be lower in HCVI recipients (P = 0.06). In conclusion, hypotensive extremely low-birth-weight infants treated with VI or with HCVI are susceptible to intraventricular-periventricular hemorrhage, bronchopulmonary dysplasia, and patent ductus arteriosus. Furthermore, those who receive inotropes are at risk for spontaneous intestinal perforation and ventriculomegaly. Maternal diabetes mellitus increases the occurrence of hypotension, which responds to VI. Maternal hypertension does not contribute to VI responsive and tends to decrease the occurrence of VI-refractory hypotension. [ABSTRACT FROM AUTHOR]

Abstract Renal tubular dysgenesis (RTD) is a developmental abnormality of the nephron characterized by fetal anuria, oligohydramnios, and severe postnatal hypotension. Genetic forms have an autosomal recessive inheritance and are caused by mutations in genes encoding key components of the renin-angiotensin pathway. We report three patients from two unrelated families with RTD due to pathogenic variants of the angiotensin-converting enzyme (ACE) gene, in whom RTD was associated with microcolon. We also detail key variations of the renin-angiotensin system in one of these infants. The severe intestinal developmental abnormality culminating in microcolon and early terminal ileum perforation/necrotizing enterocolitis is a novel finding not previously associated with RTD, which points to a role of the renin-angiotensin system in gut development. [ABSTRACT FROM AUTHOR]

Each newborn enters this world facing tremendous respiratory, hemodynamic and neuroendocrine challenges while going through drastic physiological changes during the process of adaption from fetal to postnatal life. Even though the vast majority of term infants transition smoothly without apparent consequences, this task becomes increasingly arduous for the extremely preterm infant. Methods & results: This article reviews the physiology and pathophysiology of cardiovascular adaptation of the very preterm neonate. In particular it describes the physiology of fetal circulation, summarizes the hemodynamic changes occurring during preterm births and discusses the impact of the most frequently seen clinical scenarios that place additional burden on the premature infant during immediate transition. Finally an emphasis is placed on discussing common clinical dilemmas and practical aspects of developmental hemodynamics such as neonatal hypotension and patent ductus arteriosus; clinical presentations the neonatologist encounters on a daily basis. Conclusion: The review provides a physiology-based view on the hemodynamics of the immediate postnatal transitional period.

Background Each newborn enters this world facing tremendous respiratory, hemodynamic and neuroendocrine challenges while going through drastic physiological changes during the process of adaption from fetal to postnatal life. Even though the vast majority of term infants transition smoothly without apparent consequences, this task becomes increasingly arduous for the extremely preterm infant. Methods & results This article reviews the physiology and pathophysiology of cardiovascular adaptation of the very preterm neonate. In particular it describes the physiology of fetal circulation, summarizes the hemodynamic changes occurring during preterm births and discusses the impact of the most frequently seen clinical scenarios that place additional burden on the premature infant during immediate transition. Finally an emphasis is placed on discussing common clinical dilemmas and practical aspects of developmental hemodynamics such as neonatal hypotension and patent ductus arteriosus; clinical presentations the neonatologist encounters on a daily basis. Conclusion The review provides a physiology-based view on the hemodynamics of the immediate postnatal transitional period. [ABSTRACT FROM AUTHOR]

The article provides an understanding of the management of hypotension in very low-birth-weight (VLBW) infant during the Golden Hour of infant resuscitation. Importance is given on the need for a clinician to determine the causes of neonatal hypotension, including hypovolemia, infection, maternal anesthesia and pneumothorax. Also a clinical manifestation of hypotension is shock, either it be compensated, uncompensated, or irreversible. Treatment options include fluid resuscitation, use of vasopressors, respiratory support and temperature stabilization.

This article is about a national survey looking at the policies for management of neonatal hypotension across the neonatal units in the UK. The survey shows a wide variation across the country in the management practice for neonatal hypotension and highlights the need for national guidelines. [ABSTRACT FROM AUTHOR]

Early postnatal hypotension in premature infants is treated with escalating doses of vasopressor-inotropes (VI), followed by hydrocortisone if VI therapy fails. The adverse effects of this standard clinical practice have not been well reported. In a retrospective case-control study, we compared the complications associated with VI and hydrocortisone (HCVI) treatments in extremely low-birth-weight infants (≤1000 g) with contemporaneous normotensive medication-naïve controls via standard univariate and multivariate analyses. Birth weight, gestational age, and receipt of antenatal steroids did not differ between VI ( n  = 74) and control ( n  = 124) groups, while the occurrence of gestational diabetes mellitus and risks for patent ductus arteriosus, intraventricular-periventricular hemorrhage, spontaneous intestinal perforation, ventriculomegaly, and bronchopulmonary dsyplasia were higher in VI. Infants in the HCVI group ( n  = 69) had lower birth weight, gestational age, and receipt of antenatal steroids and higher risks for intraventricular-periventricular hemorrhage, bronchopulmonary dysplasia, air leaks, and patent ductus arteriosus than controls. Whereas the occurrences of spontaneous intestinal perforation, ventriculomegaly, and maternal diabetes mellitus did not differ, that of maternal hypertension trended to be lower in HCVI recipients ( P  = 0.06). In conclusion, hypotensive extremely low-birth-weight infants treated with VI or with HCVI are susceptible to intraventricular-periventricular hemorrhage, bronchopulmonary dysplasia, and patent ductus arteriosus. Furthermore, those who receive inotropes are at risk for spontaneous intestinal perforation and ventriculomegaly. Maternal diabetes mellitus increases the occurrence of hypotension, which responds to VI. Maternal hypertension does not contribute to VI responsive and tends to decrease the occurrence of VI-refractory hypotension.