Medication Summary
In premature infants younger than 30 weeks' gestation, poor cardiac contractility is common; patients benefit from early institution of dobutamine. Other agents often used to manage hypotension in preterm infants include dopamine, epinephrine, norepinephrine, vasopressin, and milrinone; clinicians should closely monitor these infants for side effects of these medications. [19]
Patients with septic shock benefit from dopamine as first-line management; it has been found to be more effective than dobutamine and albumin in correcting blood pressure for short-term treatment in these situations; however, the effect of these drugs on long-term outcome is unknown.
Although adrenaline is used for cardiovascular compromise, its effect on mortality and morbidity has not yet been evaluated.
No evidence suggests that milrinone is beneficial in prevention of low systemic blood flow in ill, very-preterm neonates during the first postnatal day.
Evidence for using various inotropes or vasopressors is mainly derived from the adult or child population as not many trials have been published in neonatal population. It is thus generally advisable to manage newborns with shock using a physiologic-based approach with support of functional echocardiography. The first-line management in many scenarios is administration of normal saline boluses, but evidence does not support that it always increases blood pressure [22] or superior vena cava (SVC) flow. [23] Moreover, the majority of hypotensive preterm infants are not hypovolemic; hence, overzealous fluid administration is to be avoided. [24] However, when there is definitive evidence of volume loss in hypovolemic shock and also in redistributive shock, then volume expansion with saline or colloids can be considered.
Over the last couple of decades, practices in managing shock and hypotension in the newborn have changed but without significant change in mortality. The use of dopamine and dobutamine has shown a decreasing trend, along with a concomitant increase in use of epinephrine and hydrocortisone. [25] Additionally, trials that had been planned in the last decade regarding the use of inotropes, such as the Hypotension in Preterm Infants (HIP) trial (dopamine), Dobutamine for NEOnatal CIRCulatory failure (NeoCirc) trial (dobutamine guided by SVC flow), and Treatment of Hypotension of Prematurity (TOHOP) trial (intervention guided by compromised tissue perfusion), were not completed; thus, there are no substantive data to guide the use of inotrope/vasopressor agents in this population.
There are multiple challenges in performing trials in neonates on the use of various inotropes. These trials are difficult to initiate, and multi-site studies require interaction with multiple agencies. Additionally, enrollment can be challenging, with timely informed consent being a major factor. Also, lack of clinician equipoise and the unwillingness to enroll patients have been identified as key obstacles.
Thus, the choice of inotropes or vasopressors for medical management of shock is physiology based rather than evidence based, and it is increasingly guided by functional echocardiographic findings.
Cardiovascular drugs and their effects
The image below demonstrates presumed effects of cardiovascular drugs commonly used in neonatology. [17] The right side denotes more vasodilatory effects, whereas the left side shows more vasoconstrictory effects. On the Y-axis (inotropic properties), higher positions indicate more inotropic characteristics. The larger the size of the (semi-)circle, the more chronotropic effects.
Shock and Hypotension in the Newborn. Presumed effects of commonly used cardiovascular drugs in neonatal intensive care. X-axis (effect on vascular tone): The more to the right, the more vasodilatory effects; the more to the left, the more vasoconstrictory effects. Y-axis (inotropic properties): The higher on the Y-axis, the more inotropic characteristics. The larger the size of the (semi-)circle, the more chronotropic effects. It should be noted that the effect on vascular tone depends on the used dosage that determines which adrenergic receptors are activated (e.g., dopamine and epinephrine). Courtesy of Springer Nature [de Boode WP et al. The role of neonatologist performed echocardiography in the assessment and management of neonatal shock. Pediatr Res. 2018 Jul;84(suppl 1):57-67. Online at: https://www.nature.com/articles/s41390-018-0081-1. PMID: 30072807.].
Alpha/Beta Adrenergic Agonists
Class Summary
Cardiovascular performance deteriorates and cardiac output falls if effective therapy is not administered. Adrenergic antagonists improve the patient’s hemodynamic status by increasing myocardial contractility and heart rate, resulting in increased cardiac output. They also increase peripheral resistance by causing vasoconstriction. Increased cardiac output and increased peripheral resistance lead to increased blood pressure.
Dopamine
Dopamine stimulates adrenergic and dopaminergic receptors. Its hemodynamic effect is dependent on the dose. Lower doses predominantly stimulate dopaminergic receptors that, in turn, produce renal and mesenteric vasodilation. Cardiac stimulation and peripheral vasoconstriction is produced by higher doses.
Dobutamine
Dobutamine produces vasodilation and increases the inotropic state. At higher dosages, it may cause increased heart rate, exacerbating myocardial ischemia.
Epinephrine (Adrenalin)
Epinephrine elicits alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. The drug's beta-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.
Isoproterenol (Isuprel)
Isoproterenol possesses beta1- and beta2-adrenergic receptor activity. It binds to beta receptors of the heart, smooth muscle of the bronchi, skeletal muscle, vasculature, and alimentary tract. Isoproterenol elicits positive inotropic and chronotropic actions.
Norepinephrine (Levophed)
Norepinephrine is used to treat protracted hypotension following adequate fluid-volume replacement. It stimulates beta1- and alpha-adrenergic receptors, increasing cardiac muscle contractility and heart rate, as well as vasoconstriction; this results in systemic blood pressure and coronary blood flow increases. After obtaining a response, the rate of flow should be adjusted and maintained at a low-normal blood pressure, such as 80-100 mmHg systolic, sufficient to perfuse vital organs.
Vasodilators
Class Summary
Preload reduction with vasodilators is thought to be helpful in acute decompensated heart failure by reducing congestion and minimizing cardiac oxygen demand. Afterload reduction is also thought to be helpful in some patients with acute decompensated heart failure by decreasing myocardial oxygen demand and improving forward flow.
Hydralazine
Hydralazine decreases systemic resistance through direct vasodilation of arterioles.
Nitroprusside (Nitropress)
Nitroprusside produces vasodilation and increases inotropic activity of the heart. At higher dosages, it may exacerbate myocardial ischemia by increasing heart rate.
Inotropic agents
Class Summary
Inotropic agents increase cardiac contractility and may reduce vascular tone by vasodilatation.
Phentolamine (Oraverse)
Phentolamine has positive inotropic and chronotropic effects on the heart. Phentolamine is an alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine and norepinephrine action, reducing hypertension resulting from catecholamine effects on alpha receptors.
Milrinone
Milrinone is a bi-pyridine positive inotrope and vasodilator with little chronotropic activity. Its mode of actions differs from that of digitalis glycosides and catecholamines. Milrinone selectively inhibits phosphodiesterase type III (PDE III) in cardiac and smooth vascular muscle, resulting in reduced afterload and preload and increased inotropy.
Volume Expanders
Class Summary
The use of crystalloid or colloid solutions is appropriate, unless the source of hypovolemia is hemorrhage, in which case whole or reconstituted blood is more appropriate.
Sodium chloride hypertonic, ophthalmic
Isotonic sodium chloride solution is a low-cost alternative that is readily available.
Albumin (Albuminar, Buminate)
Albumin is useful for plasma volume expansion and the maintenance of cardiac output.
Lactated Ringer solution with isotonic sodium chloride
Each fluid is essentially isotonic and has equivalent volume restorative properties. Although some differences between metabolic changes are observed with the administration of large quantities of either fluid, for practical purposes and in most situations, the differences are clinically irrelevant. Importantly, there is no demonstrable difference in hemodynamic effect, morbidity, or mortality with resuscitation.
Antibiotics, Other
Class Summary
In early onset neonatal sepsis, ampicillin and either gentamicin or cefotaxime are the antimicrobials of choice until a specific infectious agent is identified.
Ampicillin
Ampicillin has bactericidal activity against susceptible organisms.
Cefotaxime (Claforan)
Cefotaxime is a third-generation cephalosporin that possesses antimicrobial effects on a predominantly gram-negative spectrum. Its efficacy against gram-positive organisms is lower.
Gentamicin
Gentamicin is an aminoglycoside antibiotic for gram-negative coverage. It is used in combination with an agent against gram-positive organisms and one that covers anaerobes. Dosing regimens are numerous; adjust the dose based on creatinine clearance (CrCl) and changes in the volume of distribution. The drug may be administered intravenously or intramuscularly.
Follow each regimen by at least a trough level drawn on the third dose (0.5 h before dosing). Peak levels may be drawn 0.5 hour after a 30-minute infusion. If the trough level is greater than 2 mg/L, increase the dosing interval.
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Shock and Hypotension in the Newborn. Determinants of cardiac function and oxygen delivery to tissues. Adapted from Strange GR. APLS: The Pediatric Emergency Medicine Course. 3rd ed. Elk Grove Village, Ill: American Academy of Pediatrics; 1998:34.
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Shock and Hypotension in the Newborn. Assisted ventilation newborn – intubation and meconium aspiration. Video courtesy of Therese Canares, MD, and Jonathan Valente, MD, Rhode Island Hospital, Brown University.
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Shock and Hypotension in the Newborn. Presumed effects of commonly used cardiovascular drugs in neonatal intensive care. X-axis (effect on vascular tone): The more to the right, the more vasodilatory effects; the more to the left, the more vasoconstrictory effects. Y-axis (inotropic properties): The higher on the Y-axis, the more inotropic characteristics. The larger the size of the (semi-)circle, the more chronotropic effects. It should be noted that the effect on vascular tone depends on the used dosage that determines which adrenergic receptors are activated (e.g., dopamine and epinephrine). Courtesy of Springer Nature [de Boode WP et al. The role of neonatologist performed echocardiography in the assessment and management of neonatal shock. Pediatr Res. 2018 Jul;84(suppl 1):57-67. Online at: https://www.nature.com/articles/s41390-018-0081-1. PMID: 30072807.].
Tables
Agent Type |
Agent |
Initial Dosage |
Additional Factors |
Volume expanders |
Isotonic sodium chloride solution |
10-20 mL/kg intravenous (IV) |
Inexpensive, available |
Albumin (5%) |
10-20 mL/kg IV |
Expensive |
|
Plasma |
10-20 mL/kg IV |
Expensive |
|
Lactated Ringer solution |
10-20 mL/kg IV |
Inexpensive, available |
|
Isotonic glucose |
10-20 mL/kg IV |
Inexpensive, available |
|
Whole blood products |
10-20 mL/kg IV |
Limited availability |
|
Reconstituted blood products |
10-20 mL/kg IV |
Use type O negative |
|
Vasoactive drugs |
Dopamine |
5-20 mcg/kg/min IV |
Never administer intra-arterially |
Dobutamine |
5-20 mcg/kg/min IV |
Never administer intra-arterially |
|
Epinephrine |
0.05-1 mcg/kg/min IV |
Never administer intra-arterially |
|
Hydralazine |
0.1-0.5 mg/kg IV every 3-6 h |
Afterload reducer |
|
Isoproterenol |
0.05-0.5 mcg/kg/min IV |
Never administer intra-arterially |
|
Nitroprusside |
0.5-8 mcg/kg/min IV |
Afterload reducer |
|
Norepinephrine |
0.05-1 mcg/kg/min IV |
Never administer intra-arterially |
|
Phentolamine |
1-20 mcg/kg/min IV |
Afterload reducer |
|
Milrinone |
22.5-45 mcg/kg/h continuous IV infusion (ie, 0.375-0.75 mcg/kg/min) |
Afterload reducer in cardiac dysfunction; reduce the dose in the setting of renal impairment |
