1. Nist, Marliese Dion BSN, RNC-NIC
  2. Backes, Carl H. MD
  3. Moorehead, Pamela BS
  4. Wispe, Jonathan MD


The immature cardiovascular system of very preterm infants predisposes them to low systemic blood flow during the first week of life, a state that may be damaging to multiple organ systems. There are many treatment strategies for the maintenance of cardiovascular equilibrium in these infants, each with its own advantages and risks. Caregivers are responsible for assessing the circulatory status of each patient and evaluating the effectiveness of interventions aimed at maintaining adequate systemic blood flow. Therefore, it is important to have an understanding of the mechanics of transitional circulation, the relationship between blood pressure and systemic blood flow, and the therapies used to treat infants with compromised organ perfusion.


Article Content

The maintenance and support of cardiovascular health in the preterm infant are paramount. The approaches used to support blood pressure and organ perfusion in these infants vary greatly. At present, there is no consensus in the medical literature on the definition of neonatal hypotension, and there is no evidence supporting one treatment modality over another. Despite up to 98% of infants receiving treatment for low blood pressure in some neonatal intensive care units (NICUs) throughout the country, there is a lack of evidence showing that current treatment strategies consistently improve clinical outcomes.1


Nursing staff and other caregivers must be able to assess and report the circulatory status of preterm infants and to evaluate the effects of interventions intended to maintain cardiovascular equilibrium. Recognizing that nurses are in the best position to perform repeated, practical, comprehensive assessments of their patients, the present review is intended to provide the nurse with knowledge of cardiovascular equilibrium in the preterm infant and interventions used for preterm infants who display cardiovascular compromise. This review has the following objectives: (1) to discuss the unique vulnerability of the preterm infant to cardiovascular compromise; (2) to evaluate the relationship between blood pressure and blood flow in the preterm infant; (3) to examine commonly used medications intended to restore blood pressure in the preterm neonate; (4) to assess the potential role of nursing staff in treatment algorithms related to neonatal hemodynamics; and (5) to provide an evidence-based "best practice" algorithm to assist in bedside support of cardiovascular health.


Preterm Infant: Immaturity of the Cardiovascular System and Clinical Consequences

Preterm infants in the first week of life commonly experience blood pressure values that traditionally have been seen as lower than normal. The causes of low blood pressure in the very preterm infant can include transitional dysfunction of the heart muscle, patent ductus arteriosus (PDA), ventilation with high mean airway pressures, and immature vasoregulation.2,3 When the low resistance circuit of the placenta is removed following birth, the left ventricle of the heart must begin pumping against an increased peripheral vascular resistance.4,5 Unlike the term infant, the immature heart muscle of the preterm infant may not be able to pump effectively against the increased peripheral vascular resistance, resulting in decreased organ perfusion.6 Second, a PDA can impact systemic blood flow. One study found an inverse relationship between PDA diameter and superior vena cava blood flow.2 Left to right shunting occurring through the PDA during the transitional period resulted in infants with large PDAs, having lower systemic blood volume. Third, ventilation with high mean airway pressures decreases left ventricular output and systemic blood flow.2 Finally, relative adrenal insufficiency in the preterm infant affects the infant's ability to respond appropriately to endogenous catecholamines, resulting in improper vasodilation.3


The high clinical concern for low blood pressure is the presumed resulting inadequate systemic blood flow and organ perfusion. Inadequate systemic blood flow can negatively affect all organ systems, including the brain, gastrointestinal tract, renal system, and liver.3 An increased incidence of intraventricular hemorrhage (IVH), periventricular leukomalacia, necrotizing enterocolitis, and hepatic and renal injury have been reported in preterm infants with hypotension in the first days of life.4 Long-term neurodevelopmental sequelae have also been reported.


Relationship Between Blood Pressure and Systemic Blood Flow

The primary goal of the medical team in the setting of hemodynamic compromise is to maintain tissue perfusion-that is, avoidance of shock. At present, there are no practical, reliable, and reproducible measures of tissue perfusion in the preterm neonate. As a surrogate marker of perfusion, the medical team relies on blood pressure to guide clinical decision making. However, recent evidence suggests that there may be a poor relationship between blood pressure and blood flow in the preterm infant, particularly in the setting of a highly variable systemic vascular resistance.6-8 One study, in particular, found a weak, time-sensitive relationship between superior vena cava blood flow and blood pressure in their study of preterm infants born before 30 weeks' gestational age.2


Because there is no reliable, practical method for assessing organ perfusion, it is difficult to find a consensus on the target blood pressure necessary to avoid complications in the preterm infant.5 Previous studies have arbitrarily used the infant's gestational age in weeks as the goal mean blood pressure.8 Some authors have, however, suggested that mean blood pressure should be greater than 30 mmHg at all times. Not surprisingly, there is no evidence showing that maintenance of blood pressure at a predetermined "target" number improves clinical outcomes. In fact, there is some evidence that outcomes are worse in treated infants, perhaps because of the side effects of therapeutic interventions.7,8


More recent evidence argues that the decision to treat cardiovascular compromise in the preterm infant should not be based solely on blood pressure alone, but also must incorporate clinical signs of poor perfusion, including delayed capillary refill, color, heart rate, and urinary output.7 For instance, a survey of 93 Canadian neonatologists found that the majority of physicians rely on blood pressure and clinical evidence of hypoperfusion when making decisions to treat patients for low systemic blood flow.9 Evidence suggests that hypotensive preterm infants with signs of adequate peripheral perfusion and their normotensive counterparts experience similar rates of necrotizing enterocolitis, periventricular leukomalacia, grades 3-4 IVH, and mortality.7 The importance of clinical assessment of the preterm infant in management decisions underscores the value of the bedside nurse in providing minute-to-minute changes in cardiovascular status of the preterm infant. Therefore, the utility of the bedside nurse in contributing to decisions regarding the treatment of hemodynamic compromise in the preterm infant is gaining widespread acceptance. To that end, nurses must be knowledgeable about the interventions used to treat low blood pressure and their potential complications to contribute fully to ongoing discussions on the optimal management strategies.


Treatment Strategies in Neonatal Hypotension

Treatment of neonatal hypotension first depends on determining and treating the underlying cause. In addition to this, the therapeutic regimens used to treat low blood pressure vary greatly and include the use of vasopressors/inotropes, steroids, and normal saline (NS). A discussion of the pharmacoreceptors targeted by each modality is helpful in better understanding the mechanism of each therapy.


Review of Pharmacoreceptors

The adrenergic receptors are most often targeted when pharmacological support is required in hypotensive neonates. There are 2 classes of adrenergic receptors: [alpha]-adrenergic receptors and the [beta]-adrenergic receptors. The [alpha]-adrenergic and [beta]-adrenergic receptors located in the cardiovascular system are targeted for their effects on cardiac contractility and vasoregulation. In addition, some of the observed clinical effects of pharmacotherapy result from stimulation of dopaminergic receptors in the heart and renal vasculature. See Table 1 for a review of these receptors, their locations, and the effects of stimulation.

Table 1 - Click to enlarge in new windowTABLE 1. Receptor Targets of Pharmacotherapy

Vasopressors and Inotropes Commonly Used for Blood Pressure Support in Neonates

Dopamine, dobutamine, and epinephrine are the most commonly used drugs for blood pressure support in very preterm infants. These drugs activate different cell receptors of the cardiovascular system in a dose-dependent manner (see Table 2). The majority of what is known about these medications is the result of studies in adults.10 Therefore, the effects of these medications in neonates are presumed similar to those in adults. The effects of these drugs are based on the receptors that they activate and their affinity for those receptors. For example, dobutamine has a greater affinity for [beta]1-adrenergic receptors than for [beta]2-adrenergic receptors and, therefore, results in improved contractility at lower doses. At higher doses, however, the effects of [beta]2-adrenergic stimulation (ie, peripheral vasodilation) are prominent, often resulting in decreasing blood pressure.

Table 2 - Click to enlarge in new windowTABLE 2. Most Frequently Used Vasopressors/Inotropes

Studies of dopamine, dobutamine, and epinephrine provide fairly consistent results, but the clinical utility of these findings is unclear.3,11,12 Dopamine reliably increases blood pressure in preterm infants, but this effect is mostly due to its vasoconstrictive properties. These vasoconstrictive properties can adversely affect systemic blood flow. Because of the increase in afterload caused by dopamine, studies have also shown that dopamine can decrease left ventricular output. Dobutamine increases left ventricular output by increasing cardiac contractility but has minimal effects on blood pressure. Because dobutamine causes peripheral vasodilation, dobutamine does not reliably increase blood pressure and appears to be most useful in cases of myocardial dysfunction. Epinephrine increases cardiac contractility and blood pressure, while improving left ventricular output. At high doses, epinephrine can cause significant vasoconstriction, similar to dopamine.


Recent evidence-based practice guidelines published by the National Association of Neonatal Nurses support the administration of vasopressors to hypotensive infants with clinical signs of decreased systemic blood flow.13 These guidelines suggest that dopamine be used as a first-line treatment for infants with hypotension related to sepsis or hypotension of unknown etiology; however, while evidence supports the use of dopamine in this population, some authors argue that epinephrine may be better as a first-line treatment, as it preserves left ventricular output at low doses.11 Most importantly, the guidelines highlight the importance of determining, if possible, the underlying cause of hypotension (ie, hypovolemia, sepsis, myocardial dysfunction), as hypotension is usually a symptom of underlying pathology.


The goal of any pharmacological intervention is to balance the need to maintain an adequate perfusion pressure with the need to prevent such extreme vasoconstriction that systemic blood flow is compromised. Large-scale, randomized, controlled trials are needed to evaluate long-term clinical outcomes and the clinical usefulness of these pharmacological agents. To date, there have been few randomized, controlled trials investigating the use of the vasopressor agents in the treatment of neonatal hypotension, with a paucity of evidence to guide clinical decision making on the best drug for a given patient.


Vasopressor-Resistant Hypotension

Some preterm infants experience vasopressor-resistant hypotension, a state in which previously therapeutic doses of vasopressors become ineffective with continued therapy. This condition is related to the downregulation of adrenergic receptors in the cardiovascular system with prolonged exposure to exogenous catecholamines and the relative adrenal insufficiency of preterm infants.3 Term infants are better able to upregulate adrenergic receptor expression in response to cortisol release. The adrenal insufficiency of preterm infants prevents this cortisol surge and the subsequent upregulation of adrenergic receptors. Steroids are often used in preterm infants with vasopressor-resistant hypotension to stimulate adrenergic receptor expression.10



Glucocorticoids such as hydrocortisone and dexamethasone affect blood pressure by inducing the expression of adrenergic receptors within the cardiovascular system, inhibiting catecholamine metabolism, and increasing intracellular calcium, which increases vascular smooth muscle and cardiac responsiveness to vasopressors.3 Glucocorticoids elevate blood pressure in very preterm infants for whom vasopressors have lost maximal effectiveness and, in most cases, allow the dose of vasopressor to be weaned.3,10 It may be useful to measure baseline cortisol levels in infants for whom glucocorticoids are being considered, as this will enable the medical team to better determine which infants are most likely to benefit from this treatment.13 There are many documented side effects associated with glucocorticoids in the preterm infant including hyperglycemia, intestinal perforation (especially with concomitant administration of indomethacin), and fungal sepsis.3,14 The effect on neurological development as well as long-term clinical outcomes is unclear.


Volume Expansion

In preterm infants with systemic hypotension, NS is often used as a first-line intervention.10,15 Although administration of volume occasionally results in improvements in blood pressure, a systematic review by Osborn and Evans15 found no significant difference in important clinical outcomes for infants who received NS versus those who did not. Because of the risks for IVH, bronchopulmonary dysplasia, and gastrointestinal sequalae associated with fluid overload, the routine administration of volume expanders to treat hypotension is not recommended in preterm infants in the first days of life, unless there are specific reasons to suggest that hypovolemia is present.3,10,13,14 Volume expansion via fluid boluses should be reserved for infants with evidence for hypovolemia, such as placental abruption or acute hemorrhage. Should the medical team determine that volume expansion is necessary, it is important to administer the fluid bolus slowly, typically over 30 to 60 minutes, as more rapid administration is associated with an increased risk for IVH.16


Clinical Assessment of Neonatal Hemodynamics

Given the evidence supporting treatment strategies that initiate the therapy partly based on clinical evidence of decreased end organ perfusion (decreased urine output [UOP], prolonged capillary refill, increased heart rate), regular clinical assessments by caregivers are essential in optimizing cardiovascular management in the preterm infant. Nurses can provide accurate, real-time assessment to other members of the medical team on the infant's current hemodynamic status. Those responsible for ongoing care of the infant are best positioned to identify any changes in cardiovascular performance from a temporal perspective. Nurses evaluate the patient's status before initiating the therapy and frequently reassess for the intended effects and complications of all interventions.


An evidence-based best practice treatment algorithm can assist the nurse in understanding treatment strategies for preterm infants who display cardiovascular compromise (see Figure). This algorithm underscores the importance of the nurse's frequent, thorough assessments of the patient's cardiovascular status.

Figure. No caption a... - Click to enlarge in new windowFigure. No caption available.


Despite the lack of evidence regarding the pathophysiology of hypotension and the benefits of one therapeutic intervention over another, the proportion of infants receiving treatment for low blood pressure is very high-as many as 98% of infants with a birth weight less than 1500 g in some NICUs throughout the country.1 A rigorous assessment of clinical status including perfusion, heart rate, and UOP should be undertaken before initiating the therapy. For instance, if the patient is well perfused and has good UOP, even with a mean arterial pressure < 25 mmHg, it may be prudent not to intervene and continue to closely monitor hemodynamic status. Alternatively, if the patient is poorly perfused and has poor UOP, even in the setting of a higher mean arterial blood pressure, it may be more efficacious to intervene. In any case, the underlying cause of the infant's hypotension must be determined so that targeted interventions may improve systemic blood flow and reduce the need to treat hypotension.8 Although nurses have a unique and vital role in all patient care decisions, the importance of nursing input may be particularly critical in the assessment of neonatal hemodynamics and cardiovascular compromise because the patient's status can change so rapidly. While awaiting additional trials investigating the utility of measuring and treating markers of poor tissue perfusion (near-infrared spectroscopy, bedside ultrasound), we believe that algorithms that clearly define the role and expectations of the bedside nurse in obtaining clinical data on important cardiovascular parameters will likely improve clinical outcomes.




1. Barrington KJ. Hypotension and shock in the preterm infant. Semin Fetal Neonatal Med. 2008;13(1):16-23. [Context Link]


2. Kucklow M, Evans N. Low superior vena cava flow and intraventricular haemorrhage in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2000;82(3):F188-F194. [Context Link]


3. Seri I. Circulatory support of the sick preterm infant. Semin Neonatol. 2001;6(1):85-95. [Context Link]


4. Noori S, Stavroudis TA, Seri I. Systemic and cerebral hemodynamics during the transitional period after premature birth. Clin Perinatol. 2009;36(4):723-736. [Context Link]


5. Seri I. Management of hypotension and low systemic blood flow in the very low birth weight neonate during the first postnatal week. J Perinatol. 2006;26(suppl 1):S8-S13. [Context Link]


6. Evans N. Assessment and support of the preterm circulation. Early Hum Dev. 2006;82(12):803-810. [Context Link]


7. 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. [Context Link]


8. Conway-Orgel M. Management of hypotension in the very low-birth-weight infant during the golden hour. Adv Neonatal Care. 2010;10(5):241-245. [Context Link]


9. Dempsey EM, Barrington KJ. Diagnostic criteria and therapeutic interventions for the hypotensive very low birth weight infant. J Perinatol. 2006;26:677-681. [Context Link]


10. Schmaltz C. Hypotension and shock in the preterm neonate. Adv Neonatal Care. 2009;9(4):156-162. [Context Link]


11. Dempsey EM, Barrington KJ. Treating hypotension in the preterm infant: when and with what: a critical and systematic review. J Perinatol. 2007;27:469-478. [Context Link]


12. Osborn DA. Diagnosis and treatment of preterm transitional circulatory compromise. Early Hum Dev. 2005;81(5):413-422. [Context Link]


13. Vargo L, Seri I. The management of hypotension in the very-low-birth-weight infant: guideline for practice, 2011. Accessed June 18, 2011. [Context Link]


14. Dempsey EM, Barrington KJ. Evaluation and treatment of hypotension in the preterm infant. Clin Perinatol. 2009;36(1):75-85. [Context Link]


15. Osborn DA, Evans NJ. Early volume expansion for prevention of morbidity and mortality in very preterm infants. Cochrane Database Syst Rev. 2001;(4): CD002055. [Context Link]


16. Goldberg RN, Chung D, Goldman SL, Bancalari E. The association of rapid volume expansion and intraventricular hemorrhage in the preterm infant. J Pediatr. 1980;96(6):1060-1063. [Context Link]


For more than 58 additional continuing education articles related to neonatal, go to


dobutamine; dopamine; epinephrine; hypotension; preterm infant; steroid; systemic blood flow; volume expansion