Author: Melissa Colizza, MD - CHU Sainte-Justine Montreal, Quebec
A 7-year-old girl with suprasystemic idiopathic pulmonary hypertension is undergoing cardiac catheterization. During the procedure, the blood pressure decreases to 65/35. Which of the following medications is MOST appropriate to treat the systemic hypotension?
Pulmonary hypertension (PH) is one of the most important causes of perioperative mortality and morbidity in the pediatric population. The three most common causes of pulmonary hypertension in the pediatric population are bronchopulmonary dysplasia, congenital heart disease or left-sided heart disease, and idiopathic PH. Patients with PH often come to the cardiac catheterization lab for diagnostic or therapeutic procedures. The risk of significant cardiovascular events in patients with PH is related to the severity of the PH. Patients with suprasystemic pulmonary arterial pressure (PAP) are at high risk for morbidity and mortality. While it is important to maintain hemodynamics as close to baseline as possible for diagnostic procedures, vasopressors or inotropic agents are sometimes required to preserve appropriate coronary perfusion and myocardial function.
Phenylephrine has a long history of successful use by anesthesiologists. Its main advantage is it increases the systemic vascular resistance (SVR) more than it does pulmonary vascular resistance (PVR), and thus helps minimize leftward shift of the ventricular septum, improving coronary perfusion and ventricular performance overall. Siehr et al. published a pilot study in 15 pediatric patients with severe pulmonary hypertension undergoing cardiac catheterization, comparing phenylephrine, epinephrine, and vasopressin. Phenylephrine did decrease the PVR:SVR ratio to slightly below 1.0 in some patients but had a more variable effect on PVR than norepinephrine or vasopressin, especially in patients with suprasystemic PH.
Norepinephrine has been a first-line agent in both pediatric and adult PH. It is a powerful systemic vasoconstrictor, a mild inotrope and overall improves right ventricle to pulmonary artery coupling as well as coronary perfusion pressure. Studies in the early 2000’s involving neonatal lambs with high-dose norepinephrine (0.5 mcg/kg/min) demonstrated both increased PAP and pulmonary blood flow, which supports the hypothesis of a pulmonary vasodilatory effects. Similar studies in human neonates have also suggested norepinephrine might decrease PVR because of a finding of improved oxygenation. However, these studies may have been confounded by the presence of a left-to-right shunt. Moreover, norepinephrine has been shown to increase PVR at high doses in both in vitro and in vivo studies. While it improves the PVR:SVR ratio, this may well be the result of increased SVR and cardiac output.
Arginine vasopressin has become increasingly popular over the last ten years for the treatment of systemic hypotension in the context of elevated PVR. As a non-catecholamine agent, it is effective in acidotic patients such as those in profound shock. While earlier human studies reported conflicting results on the effect of vasopressin on the pulmonary vasculature, more recent publications describe its successful use in PH patients. The aforementioned study by Siehr showed a consistent decrease in the PVR:SVR ratio as well as pulmonary arterial pressure to systemic arterial pressure (PAP:SAP) ratio with the use of vasopressin in the cardiac catheterization lab. An in-vitro study using human radial and pulmonary arteries compared the vasoconstrictor response of phenylephrine, norepinephrine, vasopressin and metaraminol and demonstrated that vasopressin had the weakest pulmonary vasoconstrictive response of these agents. Some animal and human studies have also hypothesized that vasopressin could induce pulmonary vasodilation via stimulation of the V1 receptor induced release of endothelial-derived nitric oxide but this finding remains inconsistent to date.
The evaluation and management of PH in the setting of noncardiac surgery has been comprehensively reviewed in a recent scientific statement from the American Heart Association (Rajagopal et al). Vasopressin is the preferred vasoconstrictor for low systemic blood pressure due to its minimal effects on PVR. However, high doses (0.08-0.1 U/min) should be avoided due to the possibility of coronary vasoconstriction and right ventricular ischemia. Norepinephrine is a suitable alternative to vasopressin. Phenylephrine should be avoided due to its effect on increasing PVR, SVR and causing reflex bradycardia. Although epinephrine may also be considered, it can produce undesirable tachycardia, induce arrhythmias and increased myocardial oxygen consumption.
Siehr SL, Feinstein JA, Yang W, Peng LF, Ogawa MT, Ramamoorthy C. Hemodynamic Effects of Phenylephrine, Vasopressin, and Epinephrine in Children With Pulmonary Hypertension: A Pilot Study. Pediatr Crit Care Med . 2016;17(5):428-437. doi: 10.1097/PCC.0000000000000716
Currigan DA, Hughes RJ, Wright CE, Angus JA, Soeding PF. Vasoconstrictor responses to vasopressor agents in human pulmonary and radial arteries: an in vitro study. Anesthesiology. 2014;121(5):930-936. doi: 10.1097/ALN.0000000000000430
Tourneux P, Rakza T, Bouissou A, Krim G, Storme L. Pulmonary circulatory effects of norepinephrine in newborn infants with persistent pulmonary hypertension. J Pediatr. 2008;153(3):345-349. doi: 10.1016/j.jpeds.2008.03.007
Coleman RD, Chartan CA, Mourani PM. Intensive care management of right ventricular failure and pulmonary hypertension crises. Pediatr Pulmonol. 2021;56(3):636-648. doi: 10.1002/ppul.24776
Rajagopal S, Ruetzler K, Ghadimi K et al. Evaluation and management of pulmonary hypertensionin noncardiac surgery: A scientific statement from the American Heart Association. Circulation. 2023; 147:1317-1343. https://doi.org/10.1161/CIR.0000000000001136