The measurement of blood pressure in the very low birth weight newborn infant is not simple and may be erroneous because of numerous factors. Assessment of cardiovascular insufficiency in this population should be based on multiple parameters and not only on numeric blood pressure readings. The decision to treat cardiovascular insufficiency should be made after considering the potential complications of such treatment. There are numerous potential strategies to avoid or mitigate hypoperfusion states in the very low birth weight infant.

The original guideline, “The Management of Hypotension in the Very-Low-Birth-Weight Infant: Guideline for Practice,” was published in 2011 by the National Association of Neonatal Nurses (NANN) with the objective, “To provide an evidence-based clinical guideline for the management of systemic hypotension in very low birth weight infants during the first 3 days of postnatal life.” At the time of revision, it was determined that a collaborative effort between NANN and the Committee on Fetus and Newborn of the American Academy of Pediatrics would best function to create the foundation for an updated, relevant clinical report that would serve all neonatal providers. There are similarities throughout this report to the original NANN publication. However, this clinical report addresses recent updates in research and evidence-based practice in relation to caring for the neonate with hypotension.

Identification and management of clinically significant systemic hypoperfusion in the infant born weighing less than 1500 g (ie, very low birth weight [VLBW] infant) during the first week of postnatal life is challenging. The objectives are to recognize cardiovascular insufficiency (ie, insufficient cardiac output to meet metabolic needs and provide adequate end-organ tissue perfusion), which can clinically present as hypotension, delayed capillary refill, oliguria, and/or metabolic acidosis, to determine when to intervene, and to decide which appropriate evidence-based strategy to use.1,2  There is no consensus that a specific blood pressure (BP) threshold in VLBW infants predicts pathology. In addition, the threshold values that potentially warrant intervention are probably different for newborn infants of the same gestational age and weight and will also change for the same neonate during successive postnatal days. Moreover, the literature is conflicting regarding the range of BP values that may influence outcomes such as morbidity, mortality, and neurodevelopmental outcomes in this population.1,3,4  Frequently used numeric thresholds, such as a BP measurement that is below a mean arterial pressure (MAP) of 30 mm Hg, or a MAP value that is less than the infant’s gestational age in weeks, are arbitrary and not supported by high-level evidence. Moreover, there are many difficulties in obtaining valid BP values, either by invasive intraarterial measurements or by noninvasive cuff technology, in this population.5  Published arbitrary values that reflect population “norms” will vary by gestational age, postnatal age, and weight and do not necessarily correlate with inherent physiologic responses or cardiovascular insufficiency in the patient. However, deleterious consequences of hypoperfusion include a reduction in the delivery of oxygen and other nutrients to the cells, anaerobic metabolism, lactic acidosis, and cell death.1,5,6  The management of hypotension in the VLBW infant should include an understanding of the infant’s presenting diagnosis; the physiologic consequences of the conversion from fetal to neonatal circulation; the significance of shunting through the foramen ovale and ductus arteriosus; recent pH, carbon dioxide, oxygen tensions, and base deficit and how they may alter cerebral hemodynamics; and systemic vasodilation, vasoconstriction, and cardiac function. Additionally, an understanding of how cerebral hemodynamics are influenced by systemic hemodynamics is necessary when making decisions on how to manage hypotension; systemic hypoperfusion depends on the complex interaction among these various factors, especially cardiac output, systemic vascular resistance, and MAP.4 

This clinical report reviews transitional physiology of the VLBW infant, current and emerging methods for assessing BP and end-organ perfusion, and current treatment practices aimed at minimizing morbidity and mortality in VLBW infants with cardiovascular insufficiency.6,7 

The immaturity of the fetal cardiovascular and pulmonary systems in VLBW infants affects the transitional physiology from fetal to neonatal life. When transition is abnormal, perfusion may be compromised because of factors associated with hypovolemia, immature myocardium and the structural persistence of fetal channels (ie, patent ductus arteriosus), adrenal insufficiency and immaturity of the sympathetic and parasympathetic responses, and peripheral baroreceptors and chemoreceptors. Hypovolemia may result from intrapartum fetal blood loss or a decrease in placental transfusion secondary to apnea at birth. Additional risk factors for low blood volume may include emergency cesarean delivery, low Apgar scores, the need for mechanical ventilation, and multiple births.8  Decreased preload attributable to absolute hypovolemia or vasodilatory shock attributable to an abnormally elevated blood vessel capacitance will result in decreased cardiac output and hypoperfusion. Although there is no evidence that correlates the presence of hypotension in preterm newborn infants with hypovolemia, a meta-analysis comparing delayed versus immediate umbilical cord clamping in preterm infants demonstrated improved hemodynamics, higher hematocrits, less need for transfusion, and lower hospital mortality rate in infants in the delayed cord clamping cohort.9 

The VLBW newborn infant has more difficulty than the term neonate adapting to the changes that occur at birth, including the rapid increase in systemic vascular resistance (SVR).10  This difficulty adapting to the increase in SVR may lead to decreased cardiac output resulting from an increase in left ventricular afterload.11  The VLBW infant is at increased risk for hemodynamic instability because of immature cardiac myocytes. The autonomic nervous system is less responsive to stimuli, resulting in reduced ventricular contractility, making the heart less able to distend and, therefore, decreasing preload. Increased vascular resistance is a compensatory mechanism to maintain normal BP; however, poor cardiac contractility reduces cardiac output that manifests as hypotension. The premature myocardium has decreased energy stores, fewer mitochondria and contractile elements, higher water content, and underdeveloped smooth muscle. Contractility is highly dependent on extracellular calcium, an important vulnerability because VLBW infants are at risk for hypocalcemia. These disadvantages, which may affect cardiac output and systemic blood flow, are exacerbated by hypoxia and acidosis.10  Usual changes in pulmonary vascular resistance and SVR at birth, which result in alteration of the fetal shunts (foramen ovale and ductus arteriosus), may not occur in the VLBW neonate, thus allowing those shunts to remain patent. Perinatal asphyxia and sepsis may also contribute to myocardial dysfunction in the VLBW infant. Moreover, the characteristics of the immature myocardium make it relatively unresponsive to inotropic treatment.11 

The immature endocrine responses of the VLBW infant also contribute to a higher risk of hypoperfusion. Acute hypoxemia in the term newborn infant is associated with increases in vasopressin, glucocorticoids, epinephrine, norepinephrine, and adrenocorticotropic hormone and results in redistribution of blood flow to vital organs. These responses are blunted in the VLBW infant. Immaturity of the adrenal glands may limit the VLBW infant’s ability to maintain cortisol production in the event of a sustained stress. Because of immaturity of the sympathetic and parasympathetic systems and the presence of chemoreceptors and baroreceptors in the aortic arch and carotid sinus, the compromised VLBW infant may have difficulty maintaining adequate perfusion pressure. In addition, the dysfunction of the autoregulatory system puts the compromised VLBW neonate at increased risk of developing reperfusion injury.12 

When deciding to treat hypotension in VLBW infants, the objective is to maintain adequate systemic blood flow, thereby ensuring perfusion and oxygen delivery to all organs and tissues. Specifically, special emphasis is focused on sustaining cerebral blood flow and oxygen delivery.12  Some research has been able to associate hypotension, however defined, with low systemic blood flow (LSBF) or decreased effective circulating blood volume, which reduces the volume of blood reaching organs and tissues. LSBF results in reduced oxygen transport to the organs and can lead to shock, diminished cerebral blood flow, and increased risk for unfavorable neurodevelopmental outcomes.8,1216  Numeric hypotension in the first several days of life in a VLBW infant raises concerns for adequate brain perfusion.7,8,12,13,1722  Significant numeric hypotension with associated clinical manifestations during the first 24 hours of life has been associated with adverse outcomes in VLBW infants <29 weeks’ gestation, including intraventricular hemorrhage (IVH), periventricular leukomalacia, bronchopulmonary dysplasia, the potential for intestinal injury, and death.3,8 

St Peter et al22  reported that the incidence of death and severe IVH were significantly higher in 24- to 28-weeks’ gestational age neonates born with hypotension, which was classified as a MAP <30 mm Hg or less than the corresponding gestational age. In addition, they found a threefold increased incidence of severe IVH (grade 3 or 4) and a significantly increased incidence of retinopathy of prematurity in infants with MAP <30 mm Hg versus ≥30 mm Hg. No differences in outcomes of necrotizing enterocolitis and bronchopulmonary dysplasia were noted by this numeric definition of hypotension. Infants who received vasopressors had higher rates of death and severe IVH in this study.22  Some studies suggest that the neuroprotective mechanism of cerebral autoregulation is compromised below a MAP of 30 mm Hg.23,24  The reduction in blood flow to white matter in the preterm infant brain raises the concern that a mean BP threshold of 30 mm Hg may be clinically important, resulting in an increased incidence of periventricular/intraventricular hemorrhage when this value is not maintained.25  Conversely, other studies have shown no relationship between MAP and cerebral blood flow.26  Specifically, a large observational study of newborn infants of extremely low gestational age (born before 28 weeks’ gestation) found that hypotension defined by traditional measurements in this population was not associated with an increased incidence of brain injury.27  These contradictory findings suggest a mechanism for regulating cerebral blood flow in these neonates at levels below generally accepted norms of BP. However, many factors other than BP can determine clinically meaningful outcomes.12,20,26  In addition, there is some evidence that autoregulatory mechanisms that protect circulation to the vascular bed of the forebrain in VLBW infants may be immature so that stress at delivery may result in vasoconstriction of forebrain vessels. Thus, VLBW infants may have decreased total cerebral blood flow despite measured “normal” BP values.12,28  Other evidence suggests that perfusion to the brain is significantly increased from the date of birth to the day after birth regardless of gestational age in preterm neonates born at less than 34 weeks’ gestation.29 

Evidence substantiating the assessment of organ perfusion in relation to systemic blood flow is complex and adequate perfusion cannot be achieved simply by the maintenance of a “normal” BP. The relationship among BP, systemic blood flow, SVR, and blood flow regulation of various organs during the transition to extrauterine life in the extremely preterm neonate is multifactorial. Evaluating the hemodynamics that affect organ perfusion in the VLBW infant is dependent on knowledge of blood flow in the superior vena cava (SVC), blood flow in the pulmonary bed, resistance in peripheral and pulmonary circulations, blood flow in the ductus arteriosus, output from the right ventricle, adequacy of myocardial function from existing pathology or congenital abnormalities, tissue oxygenation, and hypo- or hypercapnia, among others.6,28,30  Unfortunately, many of these factors are not easily monitored in a noninvasive manner. Studies have not demonstrated convincing evidence that intervening at a specific threshold BP in extremely preterm infants results in less mortality or adverse neurodevelopmental outcomes.31  Furthermore, at least 2 studies imply that treatment with inotropic agents and/or volume administration may be associated with an increase in morbidities such as intraventricular hemorrhage.32,33  Studies by Eriksen et al that attempted to demonstrate that treatment of numeric hypotension with dopamine resulted in decreased cerebral autoregulation have shown mixed results in newborn piglets.34  Other retrospective studies have reported that treatment of hypotension in this population was associated with an increase in adverse outcomes compared with matched infants who were not treated.3,19,35  However, one should view these findings with caution, because treatment in these retrospective studies may indicate more severe clinical hypotension. Limitations include the possibility that intervention for hypotension could be related to a more vulnerable patient population or that ineffective or late initiation of treatment was not identified as part of the findings. In either case, hypotension in these studied populations could lead to critical cerebral hypoperfusion resulting in long-term neurodevelopmental disability. The discrepant findings demonstrate the need for additional randomized control trials to evaluate “permissive hypotension” (ie, allowing blood pressures to fall a certain percentage below accepted norms) and associated outcomes in an extremely preterm animal model. Noori et al have suggested several levels of hypoperfusion, including a functional BP threshold (a value several mm Hg less than the numeric threshold at which cerebral function may become compromised) and an ischemic BP threshold (a value approximating 50% of normal cerebral blood flow, which compromises the structural integrity of the brain).12 

Effective monitoring of LSBF is a critical assessment component for the clinician to be able to effectively manage hypoperfusion in the extremely preterm infant.6,12  However, this assessment is confounded by the ability of current technologies to effectively measure LSBF on extremely small infants. Given the limitations of our current understanding of measuring neonatal BP, the hemodynamic status of the VLBW newborn infant should be assessed by an evaluation of all systems involved in maintaining organ perfusion, which includes assessment of cardiac function, respiratory function, renal and hepatic function, oxygenation, hemoglobin level, presence of adrenal sufficiency, and autoregulation of blood flow.5  The goal should not be to avoid numeric hypotension but to prevent the consequences of shock.4  Although several parameters are used to define and treat hypoperfusion in VLBW infants, these standards are subjective and not based on strong evidence. Additional assessment findings representing decreased organ perfusion (eg, oliguria) can serve to inform the provider when determining whether there is a need for intervention in the presence of numeric hypotension. Other clinical indications include abnormal physical examination, tachycardia, metabolic and lactic acidosis, and prolonged capillary refill time. However, some of these signs (particularly decreased urine output) may occur late in the course of the hypoperfusion.31 

Preterm infants’ heart rates are variable, with a “normal range” of 120 to 160 beats per minute.36  Cardiac output is the product of stroke volume and heart rate. Clinicians often interpret tachycardia as a response to low cardiac output and unstable hemodynamic status. However, other factors, such as gestational age, central nervous system function, degree of illness, pain, and temperature can affect an infant’s heart rate, making it difficult to use this parameter in isolation when determining perfusion status. However, sustained tachycardia that is not explained by fever or pain is suggestive of hypovolemia.

Commonly, oxygen saturation is continuously monitored by pulse oximetry in unstable VLBW infants, and, although a late sign of hypoperfusion, oxygen saturation can inform clinicians about the fractional saturation of oxygen in preductal or postductal arterial hemoglobin being transported to tissues and vital organs.33,37,38 

Using typical oxygen saturation probes and monitors, perfusion index (PI) can be calculated.38  PI is derived from the percent difference of infrared signal ratio between pulsatile (ie, arterial blood flow) and nonpulsatile (ie, tissue, bone, organ) absorbers and correlates with peripheral perfusion, SVC blood flow, cardiac output, and stroke volume in newborn infants.38  An observational study of more than 300 preterm infants with gestational ages less than 32 weeks found that PI varied with certain clinical factors (ie, lower PI readings were found during dopamine infusion and mechanical ventilation, and higher PI readings were correlated with female sex, increasing gestational age, and wide pulse pressure). Good correlation between PI and regional cerebral oxygenation (rSco2) was also demonstrated between 24 and 72 hours of life.39  It has been suggested that a combination of PI, functional echocardiography, amplitude-integrated electroencephalography (aEEG), and near-infrared spectroscopy (NIRS) may provide a method for noninvasive, continuous monitoring of the hemodynamics and perfusion in neonates during transition, but more research is needed.12 

Capillary refill time (CRT) is a common clinical tool used to assess the hemodynamic status in preterm infants, with the chest as the site used most often.41  Normal CRT in newborn infants is reported as less than 4 seconds but varies widely and has inconsistent correlation with SVC flow.41  CRT values greater than 4 seconds may be a sign of poor perfusion.41 

Urinary output (UO) has been used to assess organ perfusion status but is confounded in newborn infants because of transitional physiology and the resultant prediuretic phase followed by a diuretic phase.32  Moreover, UO is calculated and expressed as milliliters per killigram per hour (mL/kg/hour) and may not fall into an abnormal range until hours after a hypoperfusion episode. Because fluid intakes in the first 24 hours vary greatly, comparison of UO to total fluid intake may be more meaningful to assessing kidney perfusion in an individual patient. After the first day of age, UO should stabilize and reflect the infant’s fluid balance.32  UO of less than 1.5 mL/kg/hour accompanied by other signs of hypoperfusion after 24 hours of age should be investigated.42  Accurate UO can be challenging to measure in neonates without indwelling urinary catheters, although the use of such catheters carries inherent risks.

Serum lactate is frequently used in the evaluation of hypoperfusion in VLBW infants, although few studies in this population have correlated high serum lactate concentrations with adverse outcomes43,44  or have correlated serum lactate concentrations with end-organ perfusion or blood flow.32  In addition, in the circumstance of poor perfusion, lactate can accumulate but not circulate until perfusion has improved. Use of serum lactate concentration as a measurement of anaerobic metabolism attributable to hypoperfusion can be confounded by the presence of liver abnormalities, inborn errors of metabolism, or medications.32 

The most common definitions of hypoperfusion in the neonate, during the transition, are (1) a BP measurement that falls below a MAP of 30 mm Hg, or (2) a MAP that is less than the gestational age (in weeks) of the infant.45  The Management of Hypotension in the Preterm Extremely Low Gestational Age Newborn (HIP) Trial defined hypotension as a MAP “1 mm Hg below a MAP value equivalent to gestational age that persisted over a 15-minute period.”2  Because 90% or more of extremely preterm infants born between 23 and 26 weeks’ gestation will maintain a MAP of 30 mm Hg or greater after 3 postnatal days,46  many investigators, including the HIP Trial group, used this definition to specify hypotension in the first 72 hours of life.2  After the transitional period, shunting from the patent ductus arteriosus and foramen ovale is less likely to be the etiology of symptomatic hypotension,46  which may need to be considered along with other clinical and laboratory findings for the management of hypotension beyond the third day of life. However, these simplistic and mostly nonevidence-based definitions of hypotension in the first 72 hours of life are largely based on principles of developmental cardiovascular physiology and interpretation of factors that constitute hypoperfusion, which can result in clinically relevant negative consequences to the VLBW neonate.

The standard measurement of MAP is through the use of an arterial catheter, either peripherally inserted through the radial artery or centrally inserted through the umbilical artery.47  This method provides direct measurement but is subject to numerous problems. Because of the small size of the catheters, miniscule bubbles can lead to inaccurate BP readings.48  The absence or distortion of the dichrotic notch should suggest dampening of the waveform and erroneous readings. In addition, risks such as painful insertion (with a peripheral arterial line), infection, the introduction of emboli, and formation of thrombus are considerations when using these lines.

The accuracy of noninvasive cuff BP readings can be confounded by the size and fit of the cuff on the infant’s limb, the infant’s position (prone or supine), and the infant’s state of arousal.49  Moreover, cuff BP readings are not continuous.

Point-of-care ultrasonography is a broad term that refers to the use of portable ultrasonography technology and offers clinicians the opportunity to assess the neonate at the bedside with minimal disruption.50  Functional echocardiography, also known as targeted neonatal echocardiography (TNE), is the use of point-of-care ultrasonography technology to perform focused evaluation of the neonate’s cardiovascular function, providing information about ventricular systolic function, direction and severity of atrial and ductus arteriosus shunting, and estimations of right ventricular and pulmonary arterial pressures.2  The goal for TNE is to monitor the hemodynamic status with associated pathophysiology and the response to treatment, preferably after structural anomalies and arrhythmias have been ruled out.51  Clinical scenarios in which TNE may be useful in this context in the VLBW neonate during the first 72 hours of life include suspected patent ductus arteriosus, evaluation of cardiac function with potential perinatal asphyxia, and abnormal cardiovascular adaptation presenting with numeric hypotension, lactic acidosis, oliguria, or other signs of low systemic blood flow states.51  The use of TNE as an assessment tool for hypoperfusion in VLBW infants is not considered a standard of care at this time for many reasons, including a relative lack of expertise in the use of the technology by noncardiologists in the NICU, timely access to the equipment, lack of evidence-based clinical practice guidelines related to the management of hypoperfusion in VLBW infants,51  support from radiology colleagues, and legal concerns.52 

Transcutaneous Doppler ultrasonography is a continuous-wave device that is less expensive than typical ultrasonography equipment. Using this technique, blood flow velocity across pulmonary and/or aortic valves is measured and cardiac output can be calculated.53  Although this technique provides useful information via a relatively easy technique, there is high interuser variability.53  When evaluating the superior vena cava, systemic blood flow is low in many extremely preterm infants during the first 6 to 12 hours of life, often without a corresponding low BP value.7  The immature myocardium of the VLBW infant exhibits decreased ability to direct blood flow against the increased SVR that results after separation from the low-resistance placental circuit and may result in decreased systemic blood flow.7  As the transition progresses over the first 36 hours of postnatal life, LSBF usually improves and the systemic blood flow (ie, SVC flow) normalizes.7,54  However, using SVC blood flow as a surrogate for systemic blood flow in VLBW infants has limitations, as does the measurement of left ventricular output by evaluating the velocity of blood flow distal to the aortic valve using Doppler ultrasonography.55  As described in the 2011 NANN guideline “The Management of Hypotension in the Very-Low-Birth-Weight Infant: Guideline for Practice,” left-to-right ductal shunting during the first few postnatal days limits the efficacy of this technique. Right ventricular output, as measured by echocardiography, during the first 24 hours of life is believed to be a relatively more accurate measure of systemic blood flow at this time. Low right ventricular output measured before 48 hours of life in VLBW infants has been correlated with low aEEG activity in these infants, and low mean BP has been correlated with excessive discontinuity of electroencephalography (EEG).56  Low cerebral blood flow (CBF) in very preterm infants has been associated with abnormal electroencephalography and increased risk of poor long-term outcome.56 

Current investigations to assess organ blood flow in VLBW neonates are being conducted by using NIRS.12  By measuring certain oxygen-dependent compounds that selectively absorb near-infrared light during passage through blood vessels, this technique may help evaluate blood flow to vital organs including the brain. Oxygenation indices can be calculated from the measurement of the oxygen-dependent compounds.12  Using the Fick principle and assuming certain constants, CBF can also be measured.39  Using NIRS, the rSco2, a measure of cerebral hemodynamics, can be calculated and monitored, utilizing rSco2 and cerebral fractional tissue oxygen extraction reference curves.57  NIRS monitoring holds promise, but several problems prevent its widespread clinical use at this time, including a lack of validation studies and nonstandardization of mathematical models between different NIRS programs.57 

The inability to effectively monitor hemodynamic changes at the tissue level and blood flow to specific organs hampers the understanding of what constitutes hypotension in VLBW infants. Although BP can be measured both invasively and noninvasively and treated to achieve currently accepted “normal” ranges, it has become evident that BP is only one of many components that determine overall tissue perfusion and, thus, oxygen delivery to specific organs in VLBW infants.12  Several reviews suggest that evaluation of hemodynamics should be accomplished by using an integrated approach that considers all systems involved in maintaining organ perfusion and integrates the assessment of cardiac function, respiratory function, oxygenation, hemoglobin, presence of adrenal insufficiency, and autoregulation of blood flow.1,4,5,12,20,30,35  This approach could provide for more individualized assessment and management of hypoperfusion in this vulnerable population.

Currently, other methods to assess perfusion in VLBW infants are being evaluated. Measures of cerebral function, such as EEG and aEEG, may be useful adjuncts in assessing the functional impact of perfusion changes in the brain. aEEG, which can be readily applied at the bedside by trained nurses, can provide basic level bedside evaluation of cerebral electrical activity. More commonly used to assess brain function and diagnose seizures in association with hypoxic ischemic encephalopathy in term and near-term infants, aEEG studies in VLBW neonates have examined the relationship between bedside readings, cardiovascular hemodynamics during the postnatal transition period, and neurodevelopmental outcomes.12,58,59  Impedance electrical cardiometry, also referred to as thoracic electrical bioimpedance, noninvasively assesses beat-to-beat cardiac output using echocardiographic measurements of cardiac output and may be useful as a trending tool.12,53  However, results may not be accurate in infants with high cardiac output or who are on high-frequency ventilation,60  and more studies are needed. Other emerging technologies and methods to measure cardiac output in preterm infants include visible light technology, indicator dilution techniques, and arterial pulse contour analysis.12,53 

As has been discussed previously, the management of hypotension in the VLBW infant is complex, depending on the assessment of many clinical and laboratory factors. This issue will require continued scrutiny and well-developed research in the future. The definitions of hypotension used by different clinicians vary widely and thus will affect treatment strategies until evidence provides clear parameters for this diagnosis. Several interventions are used to treat low BP in this vulnerable population. Treatments currently used include volume expansion, vasopressor-inotropes, lusitropes, and corticosteroids.

The provision of adequate circulating blood volume begins at birth. Recent editions of The Textbook of Neonatal Resuscitation (seventh and eighth editions) recommend delayed cord clamping for 30 to 60 seconds in the vigorous preterm newborn infant with intact placental circulation.45  Hypovolemia or ineffective circulating blood volume is not a common cause of numeric hypotension in the VLBW infant in the first 72 hours of life unless there is evidence of intrapartum asphyxia, tight nuchal cord or fetal blood loss attributable to fetal-maternal hemorrhage, antepartum hemorrhage, twin-to-twin transfusion syndrome, vasa previa, or cord accidents.61,62  Antenatal steroids, delayed cord clamping, and not requiring mechanical ventilation are associated with a higher postnatal BP.63 

Substrates used for volume expansion to treat low BP include normal saline, lactated Ringer solution, type O Rh-negative blood, and albumin. Since 2005, the Neonatal Resuscitation Program has recommended isotonic saline or packed red blood cells in preference to albumin when volume expansion is indicated. A trend toward increased mortality when albumin was used compared with normal saline for volume expansion was demonstrated by Oca et al.64  However, this finding has not been supported by randomized controlled trials.65,66  The primary rationale for the preferential use of normal saline rather than albumin as a volume expander is that crystalloid is as effective, less expensive, and readily available.67 

Inotropes have the primary pharmacologic action of increasing myocardial contractility, lusitropes increase the rate of myocardial relaxation, vasopressors increase vascular tone, and corticosteroids act by up-regulating cardiovascular adrenergic receptor expression.68,69  Consideration should be given to the neonate’s underlying cause of hypotension and the pharmacologic actions of the drug being prescribed.

Although dopamine may increase renal perfusion at low doses, higher-dose dopamine therapy may result in decreased end-organ perfusion, possibly because dopamine decreases left ventricular output. Thus, despite improved BP measurements, high-dose dopamine therapy may lead to strain on the myocardium and decreased oxygen delivery. Dopamine can also lead to dangerously elevated levels of CBF through previously ischemic tissue, resulting in reperfusion injury and IVH.12,22,6971  Other potential risks of dopamine therapy include cardiac arrhythmias; extravasation injury; increased pulmonary arterial pressure, which, in turn, may worsen pulmonary hypertension if present; inhibition of thyrotropin leading to transient hypopituitarism; and inhibition of growth hormone and gonadotropins.7276 

Low- to moderate-dose epinephrine has been used as an alternative to dopamine for the treatment of hypotension in VLBW infants, but there are knowledge gaps concerning epinephrine’s effect on systemic blood flow in this population. Low-dose epinephrine has active β-adrenergic effects, but its α-adrenergic effects are weaker. Despite producing some vasodilation, administration usually results in increased cardiac output and BP.63  However, higher doses of epinephrine result in increased vascular resistance and decreased cardiac output secondary to increased peripheral vascular resistance, increasing the risk of decreased end-organ perfusion. Short-term adverse effects of epinephrine include significant increases in heart rate, higher lactate concentrations, lower bicarbonate concentrations, and hyperglycemia, which may require insulin.77  Careful small increases in epinephrine dosage in hypotensive VLBW infants have not been reported to result in abnormal neurologic events, or long-term adverse outcomes such as death, cerebral palsy, or profound neurodevelopmental delay.63,77 

Dobutamine produces predominantly β-adrenergic effects yielding increased myocardial contractility and decreased pulmonary and systemic vascular resistance.78  At moderate to high doses (5 mcg/kg per minute to 20 μg/kg per minute), dobutamine will increase cardiac output and BP.69,79  When compared with dopamine, dobutamine increases SVC flow and right and left ventricular output more effectively, which may result in improved end-organ perfusion.12,79 

Hydrocortisone is as effective as inotropes such as dopamine for improving hypotension in VLBW infants. However, the data on the long-term safety of corticosteroids used for this purpose is limited.80  Studies have shown that hydrocortisone increases BP, increases tissue perfusion, and prevents ischemic tissue injury as a standalone therapy or in conjunction with volume and inotropic therapies.81  The studies on the use of hydrocortisone for the treatment or prevention of bronchopulmonary dysplasia are controversial, but infants with serum cortisol concentrations below the median who were treated with hydrocortisone had increased survival without bronchopulmonary dysplasia when compared with those who did not receive this therapy.81  Although the neurodevelopmental effects are unclear, in a 2-year follow-up study of extremely preterm infants randomly assigned to receive early hydrocortisone to prevent bronchopulmonary dysplasia, the group receiving hydrocortisone had a statistically significant improvement in developmental outcome in neonates born at 24 to 25 weeks’ gestation but not those born at 26 to 27 weeks’ gestation.82  Moreover, in a study of vasopressor-resistant preterm infants with borderline hypotension, a low-dose regimen of hydrocortisone had no effect on CBF.83 

Milrinone is a selective phosphodiesterase III inhibitor used to improve cardiac output by improving ventricular contractility, enhancing diastolic relaxation, and decreasing peripheral vascular resistance. A study of the effectiveness of milrinone versus placebo in hypotensive VLBW infants in a double-blind randomized controlled trial demonstrated that milrinone did not prevent LSBF in these infants. No adverse effects of milrinone were demonstrated in this study.84  Currently, there is no strong evidence to support the use of milrinone for the treatment of hypotension in VLBW infants.

All treatments of hypotension in the VLBW population have potential adverse effects and should be carefully considered. It is recommended that each therapy or drug used have careful titration with cautious stepwise increases in dosage to reach the desired effect. Moreover, the provider may increase inotropic drug dosage approximately every 3 to 5 minutes to achieve the desired result, if the drug is being delivered with correct line priming and the infusion pump has been properly set up and calibrated.63,68,69,71 

Continued research efforts should be encouraged to ensure the most recent evidence-based treatment options are used to manage BP in VLBW neonates and to clearly define what constitutes hypotension in this population. All parameters of effective circulating blood volume should be considered before deciding on specific interventions for treatment. This report suggests a cautious and conservative approach that is based on known physiology in this population. However, the knowledge gaps on transitional cardiovascular physiology and pathophysiology in VLBW infants makes it difficult to establish any specific guidelines on the treatment of hypotension in this population. At the current time, clinical trials addressing this question have been unable to provide the appropriate information and lacked the power to give specific guidance on the management of neonatal hypotension in clinical practice.63  One recently concluded study, The Hypotension in Preterm Infants (HIP) randomized trial in newborn infants born before 28 weeks’ gestation with mean BP less than gestational age in the first 72 hours of life, was terminated early due to problems with enrollment. Although the study lacked power, it failed to demonstrate significant differences in clinical outcomes at 36 weeks postmenstrual age between the treatment group (saline bolus/dopamine) and restrictive management group (5% dextrose infusion only).85  Future trials that use clinically relevant outcome measures to define hypotension in VLBW infants are needed to establish reasonable BP values and treatment modes in this population. Ongoing large randomized controlled trials such as the NEO-CIRC project (http://www.neocirculation.eu) may provide some additional evidenced-based recommendations. At the present time, the following recommendations can be made:

  • The diagnosis of cardiac insufficiency in the VLBW infant should not be based on a threshold BP value alone. The measurement of BP in this population is not simple and may be erroneous.

  • Assessment of BP should be based on multiple parameters including gestational age, weight, and postnatal age using standardized tables that recognize values >2 standard deviations below the mean. The diagnosis of cardiac insufficiency that warrants treatment should consider other factors including physical findings, such as hypotonia, tachycardia, and poor capillary refill, clinical findings, such as poor urine output, laboratory studies, such as metabolic acidosis and increased lactate concentrations, and bedside evaluation using technology such as functional echocardiography (when available).

  • The treatment of cardiac insufficiency is not without hazard, and the decision to treat should consider the potential complications of such treatment.

  • Delayed cord clamping, decreased blood sampling, appropriate ventilatory management (ie, avoiding excessive mean airway pressure and hypocarbia), and other attempts to avoid hypovolemia, anemia, and decreased cardiac output may have an important role in avoiding or mitigating hypoperfusion states in the VLBW infant.

  • Jay P. Goldsmith, MD, FAAP

  • Erin Keels, DNP, APRN-CNP, NNP-BC

  • Roxanne Stahl, MSN

  • Lee Shirland, MS, APRN, NNP-BC

  • Lisa Grisham, NNP-BC

  • James Cummings, MD, Chairperson

  • Ivan Hand, MD

  • Ira Adams-Chapman, MD, MD

  • Susan W. Aucott, MD

  • Karen M. Puopolo, MD

  • Jay P. Goldsmith, MD

  • David Kaufman, MD

  • Camilia Martin, MD

  • Meredith Mobitz, MD

  • Brenda Poindexter, MD

  • Dan L. Stewart, MD

  • Timothy Jancelewicz, MD – AAP Section on Surgery

  • Michael Nervy, MD – Canadian Paediatric Society

  • Russell Miller, MD – American College of Obstetricians and Gynecologists

  • RADM Wanda Barfield, MD, MPH – Centers for Disease Control and Prevention

  • Lisa Grisham, APRN, NNP-BC – National Association of Neonatal Nurses

  • Jim Couto, MA

This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication.

Clinical reports from the American Academy of Pediatrics benefit from expertise and resources of liaisons and internal (AAP) and external reviewers. However, clinical reports from the American Academy of Pediatrics may not reflect the views of the liaisons or the organizations or government agencies that they represent.

The guidance in this report does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate.

All clinical reports from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time.

     
  • aEEG

    amplitude-integrated electroencephalography

  •  
  • BP

    blood pressure

  •  
  • CBF

    cerebral blood flow

  •  
  • CRT

    capillary refill time

  •  
  • IVH

    intraventricular hemorrhage

  •  
  • LSBF

    low systemic blood flow

  •  
  • MAP

    mean arterial pressure

  •  
  • NANN

    National Association of Neonatal Nurses

  •  
  • NIRS

    near-infrared spectroscopy

  •  
  • PI

    perfusion index

  •  
  • rSco2

    regional cerebral oxygenation

  •  
  • SVC

    superior vena cava

  •  
  • SVR

    systemic vascular resistance

  •  
  • TNE

    targeted neonatal echocardiography

  •  
  • UO

    urinary output

  •  
  • VLBW

    very low birth weight

1
McClean
CW
,
Noori
S
,
Cayabyab
RG
,
Seri
I
.
Cerebral circulation and hypotension in the premature infant: diagnosis and treatment
. In
Perlman
JM
,
Cilio
MR
,
Poplin
RA
, eds.
Neonatology Questions and Controversies: Neurology
, 2nd ed.
Philadelphia, PA
:
Saunders/Elsevier
;
2012
:
3
25
2
Dempsey
EM
,
Barrington
KJ
,
Marlow
N
, et al.
HIP Consortium
.
Management of hypotension in preterm infants (The HIP Trial): a randomised controlled trial of hypotension management in extremely low gestational age newborns
.
Neonatology
.
2014
;
105
(
4
):
275
281
3
Batton
B
,
Li
L
,
Newman
NS
, et al.
Eunice Kennedy Shriver National Institute of Child Health & Human Development Neonatal Research Network
.
Early blood pressure, antihypotensive therapy and outcomes at 18-22 months’ corrected age in extremely preterm infants
.
Arch Dis Child Fetal Neonatal Ed
.
2016
;
101
(
3
):
F201
F206
4
Alderliesten
T
,
Lemmers
PM
,
van Haastert
IC
, et al
.
Hypotension in preterm neonates: low blood pressure alone does not affect neurodevelopmental outcome
.
J Pediatr
.
2014
;
164
(
5
):
986
991
5
Jones
JG
,
Smith
SL
.
Shock in the critically ill neonate
.
J Perinat Neonatal Nurs
.
2009
;
23
(
4
):
346
354
,
quiz 355–356
6
Watterberg
KL
.
Hydrocortisone dosing for hypotension in newborn infants: less is more
.
J Pediatr
.
2016
;
174
:
23
26.e1
7
Batton
B
,
Li
L
,
Newman
NS
, et al.
Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
.
Evolving blood pressure dynamics for extremely preterm infants
.
J Perinatol
.
2014
;
34
(
4
):
301
305
8
Faust
K
,
Härtel
C
,
Preuß
M
, et al.
Neocirculation Project and the German Neonatal Network (GNN)
.
Short-term outcome of very-low-birthweight infants with arterial hypotension in the first 24 h of life
.
Arch Dis Child Fetal Neonatal Ed
.
2015
;
100
(
5
):
F388
F392
9
Fogarty
M
,
Osborn
DA
,
Askie
L
, et al
.
Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis
.
Am J Obstet Gynecol
.
2018
;
218
(
1
):
1
18
10
Kluckow
M
.
Low systemic blood flow and pathophysiology of the preterm transitional circulation
.
Early Hum Dev
.
2005
;
81
(
5
):
429
437
11
Osborn
DA
,
Paradisis
M
,
Evans
N
.
The effect of inotropes on morbidity and mortality in preterm infants with low systemic or organ blood flow
.
Cochrane Database Syst Rev
.
2007
; (
1
):
CD005090
12
Noori
S
,
McClean
CW
,
Seri
I
.
Cerebral circulation and hypotension in the premature infant: diagnosis and treatment
. In:
Perlman
JM
,
Cilio
MR
,
Polin
RA
, eds.
Neonatology Questions and Controversies: Neurology
, 3rd ed.
Philadelphia, PA
:
Saunders/Elsevier
;
2019
:
1
26
13
Miall-Allen
VM
,
de Vries
LS
,
Whitelaw
AG
.
Mean arterial blood pressure and neonatal cerebral lesions
.
Arch Dis Child
.
1987
;
62
(
10
):
1068
1069
14
Goldstein
RF
,
Thompson
RJ
Jr
,
Oehler
JM
,
Brazy
JE
.
Influence of acidosis, hypoxemia, and hypotension on neurodevelopmental outcome in very low birth weight infants
.
Pediatrics
.
1995
;
95
(
2
):
238
243
15
Osborn
DA
,
Evans
N
,
Kluckow
M
.
Hemodynamic and antecedent risk factors of early and late periventricular/intraventricular hemorrhage in premature infants
.
Pediatrics
.
2003
;
112
(
1 Pt 1
):
33
39
16
Hunt
RW
,
Evans
N
,
Rieger
I
,
Kluckow
M
.
Low superior vena cava flow and neurodevelopment at 3 years in very preterm infants
.
J Pediatr
.
2004
;
145
(
5
):
588
592
17
Kluckow
M
,
Seri
I
.
Cardiovascular compromise in the preterm infant during the first postnatal day
. In
Seri
I
,
Kluckow
M
, eds.
Neonatology Questions and Controversies: Hemodynamics and Cardiology
, 3rd ed.
Philadelphia, PA
:
Elsevier
;
2019
:
471
488
18
Watkins
AM
,
West
CR
,
Cooke
RW
.
Blood pressure and cerebral haemorrhage and ischaemia in very low birthweight infants
.
Early Hum Dev
.
1989
;
19
(
2
):
103
110
19
Fanaroff
AA
,
Fanaroff
JM
.
Short- and long-term consequences of hypotension in ELBW infants
.
Semin Perinatol
.
2006
;
30
(
3
):
151
155
20
Tyszczuk
L
,
Meek
J
,
Elwell
C
,
Wyatt
JS
.
Cerebral blood flow is independent of mean arterial blood pressure in preterm infants undergoing intensive care
.
Pediatrics
.
1998
;
102
(
2 Pt 1
):
337
341
21
Martens
SE
,
Rijken
M
,
Stoelhorst
GM
, et al.
Leiden Follow-Up Project on Prematurity, The Netherlands
.
Is hypotension a major risk factor for neurological morbidity at term age in very preterm infants?
Early Hum Dev
.
2003
;
75
(
1–2
):
79
89
22
St Peter
D
,
Gandy
C
,
Hoffman
SB
.
Hypotension and adverse outcomes in prematurity: comparing definitions
.
Neonatology
.
2017
;
111
(
3
):
228
233
23
Greisen
G
.
Autoregulation of cerebral blood flow in newborn babies
.
Early Hum Dev
.
2005
;
81
(
5
):
423
428
24
Milligan
DW
.
Failure of autoregulation and intraventricular haemorrhage in preterm infants
.
Lancet
.
1980
;
1
(
8174
):
896
898
25
O’Leary
H
,
Gregas
MC
,
Limperopoulos
C
, et al
.
Elevated cerebral pressure passivity is associated with prematurity-related intracranial hemorrhage
.
Pediatrics
.
2009
;
124
(
1
):
302
309
26
Logan
JW
,
O’Shea
TM
,
Allred
EN
, et al.
ELGAN Study Investigators
.
Early postnatal hypotension is not associated with indicators of white matter damage or cerebral palsy in extremely low gestational age newborns
.
J Perinatol
.
2011
;
31
(
8
):
524
534
27
O’Shea
TM
,
Allred
EN
,
Dammann
O
, et al.
ELGAN study Investigators
.
The ELGAN study of the brain and related disorders in extremely low gestational age newborns
.
Early Hum Dev
.
2009
;
85
(
11
):
719
725
28
Noori
S
,
Stavroudis
TA
,
Seri
I
.
Systemic and cerebral hemodynamics during the transitional period after premature birth
.
Clin Perinatol
.
2009
;
36
(
4
):
723
736
,
v
29
Kehrer
M
,
Blumenstock
G
,
Ehehalt
S
,
Goelz
R
,
Poets
C
,
Schöning
M
.
Development of cerebral blood flow volume in preterm neonates during the first two weeks of life
.
Pediatr Res
.
2005
;
58
(
5
):
927
930
30
Seri
I
,
Evans
J
.
Controversies in the diagnosis and management of hypotension in the newborn infant
.
Curr Opin Pediatr
.
2001
;
13
(
2
):
116
123
31
Osborn
DA
,
Evans
N
.
Early volume expansion for prevention of morbidity and mortality in very preterm infants
.
Cochrane Database Syst Rev
.
2004
;
2004
(
2
):
CD002055
32
de Boode
WP
.
Clinical monitoring of systemic hemodynamics in critically ill newborns
.
Early Hum Dev
.
2010
;
86
(
3
):
137
141
33
Askie
LM
,
Darlow
BA
,
Finer
N
, et al.
Neonatal Oxygenation Prospective Meta-analysis (NeOProM) Collaboration
.
Association between oxygen saturation targeting and death or disability in extremely preterm infants in the neonatal oxygenation prospective meta-analysis collaboration
.
JAMA
.
2018
;
319
(
21
):
2190
2201
34
Eriksen
VR
.
Rational use of dopamine in hypotensive newborns: improving our understanding of the effect on cerebral autoregulation
.
Dan Med J
.
2017
;
64
(
7
):
B5388
35
Dempsey
EM
,
Al Hazzani
F
,
Barrington
KJ
.
Permissive hypotension in the extremely low birthweight infant with signs of good perfusion
.
Arch Dis Child Fetal Neonatal Ed
.
2009
;
94
(
4
):
F241
F244
36
Gomella
TL
.
Neonatology. Management, Procedures, On-Call Problems, Diseases, and Drugs
, 7th ed.
New York, NY
:
McGraw Hill
;
2013
37
Tin
W
,
Lal
M
.
Principles of pulse oximetry and its clinical application in neonatal medicine
.
Semin Fetal Neonatal Med
.
2015
;
20
(
3
):
192
197
38
Lima
AP
,
Beelen
P
,
Bakker
J
.
Use of a peripheral perfusion index derived from the pulse oximetry signal as a noninvasive indicator of perfusion
.
Crit Care Med
.
2002
;
30
(
6
):
1210
1213
39
Alderliesten
T
,
Lemmers
PM
,
Baerts
W
,
Groenendaal
F
,
van Bel
F
.
Perfusion index in preterm infants during the first 3 days of life: reference values and relation with clinical variables
.
Neonatology
.
2015
;
107
(
4
):
258
265
40
Stranak
Z
,
Semberova
J
,
Barrington
K
, et al.
HIP Consortium
.
International survey on diagnosis and management of hypotension in extremely preterm babies
.
Eur J Pediatr
.
2014
;
173
(
6
):
793
798
41
Gale
C
.
Question 2. Is capillary refill time a useful marker of haemodynamic status in neonates?
Arch Dis Child
.
2010
;
95
(
5
):
395
397
42
Escourrou
G
,
Renesme
L
,
Zana
E
, et al
.
How to assess hemodynamic status in very preterm newborns in the first week of life?
J Perinatol
.
2017
;
37
(
9
):
987
993
43
Deshpande
SA
,
Platt
MP
.
Association between blood lactate and acid-base status and mortality in ventilated babies
.
Arch Dis Child Fetal Neonatal Ed
.
1997
;
76
(
1
):
F15
F20
44
Groenendaal
F
,
Lindemans
C
,
Uiterwaal
CS
,
de Vries
LS
.
Early arterial lactate and prediction of outcome in preterm neonates admitted to a neonatal intensive care unit
.
Biol Neonate
.
2003
;
83
(
3
):
171
176
45
American Academy of Pediatrics, American Heart Association
.
Textbook of Neonatal Resuscitation
, 7th ed.
Elk Grove Village, IL
:
American Academy of Pediatrics
;
2016
46
Nuntnarumit
P
,
Yang
W
,
Bada-Ellzey
HS
.
Blood pressure measurements in the newborn
.
Clin Perinatol
.
1999
;
26
(
4
):
981
996
,
x
47
Shahid
S
,
Dutta
S
,
Symington
A
,
Shivananda
S
;
McMaster University NICU
.
Standardizing umbilical catheter usage in preterm infants
.
Pediatrics
.
2014
;
133
(
6
):
e1742
e1752
48
Weindling
AM
.
Blood pressure monitoring in the newborn
.
Arch Dis Child
.
1989
;
64
(
4 Spec No
):
444
447
49
Darnall
R
.
Blood pressure monitoring
. In
Brans
WH
, ed.
Physiologic Monitoring and Instrumental Diagnosis in Perinatal and Neonatal Medicine
.
Cambridge, United Kingdom
:
Cambridge University Press
;
1995
:
246
266
50
Burdjalov
V
,
Srinivasan
P
,
Baumgart
S
,
Spitzer
AR
.
Handheld, portable ultrasound in the neonatal intensive care nursery: a new, inexpensive tool for the rapid diagnosis of common neonatal problems
.
J Perinatol
.
2002
;
22
(
6
):
478
483
51
Mertens
L
,
Seri
I
,
Marek
J
, et al.
Writing Group of the American Society of Echocardiography
;
European Association of Echocardiography
;
Association for European Pediatric Cardiologists
.
Targeted neonatal echocardiography in the neonatal intensive care unit: practice guidelines and recommendations for training. Writing group of the American Society of Echocardiography (ASE) in collaboration with the European Association of Echocardiography (EAE) and the Association for European Pediatric Cardiologists (AEPC)
.
J Am Soc Echocardiogr
.
2011
;
24
(
10
):
1057
1078
52
Mirza
HS
,
Logsdon
G
,
Pulickal
A
,
Stephens
M
,
Wadhawan
R
.
A national survey of neonatologists: barriers and prerequisites to introduce point-of-care ultrasound in neonatal ICUs
.
Ultrasound Q
.
2017
;
33
(
4
):
265
271
53
Vrancken
SL
,
van Heijst
AF
,
de Boode
WP
.
Neonatal hemodynamics: from developmental physiology to comprehensive monitoring
.
Front Pediatr
.
2018
;
6
:
87
54
Batton
B
,
Zhu
X
,
Fanaroff
J
, et al
.
Blood pressure, anti-hypotensive therapy, and neurodevelopment in extremely preterm infants
.
J Pediatr
.
2009
;
154
(
3
):
351
357
,
357.e1
55
Bouissou
A
,
Rakza
T
,
Klosowski
S
,
Tourneux
P
,
Vanderborght
M
,
Storme
L
.
Hypotension in preterm infants with significant patent ductus arteriosus: effects of dopamine
.
J Pediatr
.
2008
;
153
(
6
):
790
794
56
Cayabyab
R
,
McLean
CW
,
Seri
I
.
Definition of hypotension and assessment of hemodynamics in the preterm neonate
.
J Perinatol
.
2009
;
29
(
Suppl 2
):
S58
S62
57
Alderliesten
T
,
Dix
L
,
Baerts
W
, et al
.
Reference values of regional cerebral oxygen saturation during the first 3 days of life in preterm neonates
.
Pediatr Res
.
2016
;
79
(
1-1
):
55
64
58
Shibasaki
J
,
Toyoshima
K
,
Kishigami
M
.
Blood pressure and aEEG in the 96 h after birth and correlations with neurodevelopmental outcome in extremely preterm infants
.
Early Hum Dev
.
2016
;
101
:
79
84
59
West
CR
,
Groves
AM
,
Williams
CE
, et al
.
Early low cardiac output is associated with compromised electroencephalographic activity in very preterm infants
.
Pediatr Res
.
2006
;
59
(
4 Pt 1
):
610
615
60
Hsu
KH
,
Wu
TW
,
Wu
IH
, et al
.
Electrical cardiometry to monitor cardiac output in preterm infants with patent ductus arteriosus: a comparison with echocardiography
.
Neonatology
.
2017
;
112
(
3
):
231
237
61
Kluckow
M
.
The pathophysiology of low systemic blood flow in the preterm infant
.
Front Pediatr
.
2018
;
6
:
29
62
Bhat
BV
,
Plakkal
N
.
Management of shock in neonates
.
Indian J Pediatr
.
2015
;
82
(
10
):
923
929
63
Dempsey
EM
.
What should we do about low blood pressure in preterm infants
Neonatology
.
2017
;
111
(
4
):
402
407
64
Oca
MJ
,
Nelson
M
,
Donn
SM
.
Randomized trial of normal saline versus 5% albumin for the treatment of neonatal hypotension
.
J Perinatol
.
2003
;
23
(
6
):
473
476
65
Lynch
SK
,
Mullett
MD
,
Graeber
JE
,
Polak
MJ
.
A comparison of albumin-bolus therapy versus normal saline-bolus therapy for hypotension in neonates
.
J Perinatol
.
2008
;
28
(
1
):
29
33
66
So
KW
,
Fok
TF
,
Ng
PC
,
Wong
WW
,
Cheung
KL
.
Randomised controlled trial of colloid or crystalloid in hypotensive preterm infants
.
Arch Dis Child Fetal Neonatal Ed
.
1997
;
76
(
1
):
F43
F46
67
Shalish
W
,
Olivier
F
,
Aly
H
,
Sant’Anna
G
.
Uses and misuses of albumin during resuscitation and in the neonatal intensive care unit
.
Semin Fetal Neonatal Med
.
2017
;
22
(
5
):
328
335
68
Rabe
H
,
Rojas-Anaya
H
.
Inotropes for preterm babies during the transition period after birth: friend or foe?
Arch Dis Child Fetal Neonatal Ed
.
2017
;
102
(
6
):
F547
F550
69
Noori
S
,
Seri
I
.
Neonatal blood pressure support: the use of inotropes, lusitropes, and other vasopressor agents
.
Clin Perinatol
.
2012
;
39
(
1
):
221
238
70
Barrington
KJ
,
Finer
NN
,
Chan
WK
.
A blind, randomized comparison of the circulatory effects of dopamine and epinephrine infusions in the newborn piglet during normoxia and hypoxia
.
Crit Care Med
.
1995
;
23
(
4
):
740
748
71
Barrington
KJ
.
Hypotension and shock in the preterm infant
.
Semin Fetal Neonatal Med
.
2008
;
13
(
1
):
16
23
72
Van den Berghe
G
,
de Zegher
F
,
Lauwers
P
.
Dopamine suppresses pituitary function in infants and children
.
Crit Care Med
.
1994
;
22
(
11
):
1747
1753
73
Seri
I
,
Rudas
G
,
Bors
Z
,
Kanyicska
B
,
Tulassay
T
.
Effects of low-dose dopamine infusion on cardiovascular and renal functions, cerebral blood flow, and plasma catecholamine levels in sick preterm neonates
.
Pediatr Res
.
1993
;
34
(
6
):
742
749
74
Seri
I
.
Cardiovascular, renal, and endocrine actions of dopamine in neonates and children
.
J Pediatr
.
1995
;
126
(
3
):
333
344
75
Dong
BJ
.
How medications affect thyroid function
.
West J Med
.
2000
;
172
(
2
):
102
106
76
Rios
DR
,
Moffett
BS
,
Kaiser
JR
.
Trends in pharmacotherapy for neonatal hypotension
.
J Pediatr
.
2014
;
165
(
4
):
697
701.e1
77
Valverde
E
,
Pellicer
A
,
Madero
R
,
Elorza
D
,
Quero
J
,
Cabañas
F
.
Dopamine versus epinephrine for cardiovascular support in low birth weight infants: analysis of systemic effects and neonatal clinical outcomes
.
Pediatrics
.
2006
;
117
(
6
):
e1213
e1222
78
Subhedar
NV
,
Shaw
NJ
.
Dopamine versus dobutamine for hypotensive preterm infants
.
Cochrane Database Syst Rev
.
2003
; (
3
):
CD001242
79
Noori
S
,
Friedlich
P
,
Seri
I
.
Cardiovascular and renal effects of dobutamine in the neonate
.
NeoReviews
.
2004
;
5
(
11
):
E22
E26
80
Evans
M
.
Hemodynamically based pharmacologic management of circulatory compromise in the newborn
. In
Seri
I
,
Kluckow
M
, eds.
Neonatology Questions and Controversies: Hemodynamics and Cardiology
, 3rd ed.
Philadelphia, PA
:
Elsevier
;
2018
:
521
534
81
Gaissmaier
RE
,
Pohlandt
F
.
Single-dose dexamethasone treatment of hypotension in preterm infants
.
J Pediatr
.
1999
;
134
(
6
):
701
705
82
Baud
O
,
Trousson
C
,
Biran
V
,
Leroy
E
,
Mohamed
D
,
Alberti
C
;
PREMILOC Trial Group
.
Two-year neurodevelopmental outcomes of extremely preterm infants treated with early hydrocortisone: treatment effect according to gestational age at birth
.
Arch Dis Child Fetal Neonatal Ed
.
2019
;
104
(
1
):
F30
F35
83
Noori
S
,
Friedlich
P
,
Wong
P
,
Ebrahimi
M
,
Siassi
B
,
Seri
I
.
Hemodynamic changes after low-dosage hydrocortisone administration in vasopressor-treated preterm and term neonates
.
Pediatrics
.
2006
;
118
(
4
):
1456
1466
84
Paradisis
M
,
Evans
N
,
Kluckow
M
,
Osborn
D
.
Randomized trial of milrinone versus placebo for prevention of low systemic blood flow in very preterm infants
.
J Pediatr
.
2009
;
154
(
2
):
189
195
85
Dempsey
EM
,
Barrington
KJ
,
Marlow
N
, et al.
HIP Consortium
.
Hypotension in preterm infants (HIP) randomised trial
.
Arch Dis Child Fetal Neonatal Ed
.
2021
;
106
(
4
):
398
403