The use of vasoactive medications in the management of critically ill pediatric patients is common, with formal recommendations for their use in pediatric advanced life support algorithms first published over 30 years ago. Vasoactives are utilized throughout all pediatric age ranges and disease processes and continue to serve an important therapeutic role in the resuscitation of critically ill children. An understanding of the physiologic and pharmacologic underpinnings of each vasoactive class and subtype is absolutely necessary for the pediatric acute care provider. The provision of timely and effective therapy in the critical care or emergency room setting also requires an understanding of the wide variety of etiologies that contribute to hemodynamic instability in children: septic, cardiogenic, distributive, and hypovolemic shock states, in addition to cardiogenic shock related to acute heart failure or decompensated chronic heart failure. This chapter will describe the various medical therapies that modulate cardiovascular physiology, often termed vasoactives, while comparing and contrasting their pharmacologic properties, indications, and current practice in the pediatric population.
Medications that primarily target receptors on peripheral arterial vasculature with resulting vasoconstriction and increased systemic arterial blood pressure are classified as vasopressors. Myocardial and peripheral adrenergic receptors present on cell surfaces play vital roles in the mechanistic action of vasopressors. In particular, α-adrenergic receptors function as excitatory triggers for vasoconstriction with multiple subtypes (eg, α1A, α1B, α1C, α2) identified with unique properties in their respective tissue distributions. These receptors belong to the G protein–coupled superfamily of receptors, which utilize intracellular signals to regulate the release of calcium in peripheral smooth muscle cells. An alternative mechanism for vasoconstriction can be found in the activation of dopaminergic receptors. The DA1 receptor, a postsynaptic receptor located in the renal, splanchnic, coronary, and cerebral vascular beds, produces smooth muscle relaxation on stimulation.
Phenylephrine is a pure α1 agonist resulting in peripheral arterial vasoconstriction with no inotropic effect. It is metabolized by oxidative deamination and glucuronidation and is renally eliminated as inactive metabolites. The intravenous onset of action is rapid and half-life is short (15–20 minutes). It has been used in patients with tetralogy of Fallot with hypercyanotic spells to increase pulmonary blood flow during acute episodes of desaturation. It can be administered as a bolus in acute situations or as a continuous infusion. Afterload, with associated increases in myocardial oxygen consumption, is often increased due to the profound vasoconstriction that occurs with use, and therefore should be avoided in patients with heart failure.
Vasopressin is also known as antidiuretic hormone. When given intravenously, the half-life is short (~10 minutes) and it is hepatically metabolized. The effect desired of vasopressin therapy is dependent on clinical indication and dose. Dosing of vasopressin can vary widely, with low doses used for treatment of diabetes insipidus, mid-range doses used ...