Authors: Kaitlin M. Flannery, MD, MPH - Stanford University AND Amy Babb MD - Monroe Carell Jr. Children’s Hospital, Vanderbilt
An eight-month-old boy with a history of Williams syndrome underwent repair of supravalvar aortic stenosis 24 hours ago. The blood pressure is noted to be 124/84 despite administration of additional analgesic and sedative medications. The last lactate was increased from 2.4 to 5.8, and the urine output is 0.6 cc/kg/hr. Liver transaminases have doubled over the last 24 hours. Which of the following antihypertensive medications is MOST appropriate to treat this patient?
EXPLANATION
Anti-hypertensive medications are frequently utilized in pediatric patients who undergo cardiac surgery. Causes of perioperative hypertension include activation of the sympathetic nervous system from excessive catecholamines, peripheral vasoconstriction, volume overload, and decreased baroreceptor sensitivity. Nitroglycerin, sodium nitroprusside, nicardipine, and clevidipine represent various vasodilator therapies used in pediatric patients after cardiac surgery. Nitroglycerin is a venodilator that is rarely effective as a monotherapy for elevated systemic vascular resistance. Sodium nitroprusside causes both arterial and venous dilatation. Due to its rapid onset of action, it is more likely to be associated with undesired hypotension during drug titration. In addition, there is a risk of cyanide toxicity with resultant hepatic dysfunction and thiocyanate toxicity with potential renal dysfunction.
Clevidipine is a dihydropyridine L-type calcium channel blocker that is used as an intravenous infusion to decrease systemic vascular resistance by direct arterial vasodilation. The mechanism of action is identical to nicardipine but with differing pharmacokinetics, which are detailed in the table below.
Clevidipine is rapidly metabolized by hydrolysis of ester linkages and occurs within the blood compartment and extravascular tissues. Therefore, drug metabolism is not affected by hepatic and/or renal function.
Clevidipine is available in a lipid emulsion that appears similar to propofol. Due to its high lipid content, administration of clevidipine and propofol infusions over prolonged periods may warrant monitoring of triglyceride levels. In addition, lipid enteral infusions for nutrition may require dose adjusting with concomitant clevidipine use to avoid hypertriglyceridemia. It should also be noted that the clevidipine preparation contains soybean oil and egg yolk phospholipid, posing a question about food allergy cross-reactivity.
The correct answer is B. Clevidipine is the correct answer because its metabolism is not affected by renal or hepatic dysfunction, which are present in this patient. Nicardipine is metabolized by the liver and thus its action may be prolonged in the setting of rising lactate and hepatic dysfunction. Sodium nitroprusside should be avoided in this patient as it is associated with a risk of cyanide and thiocyanate toxicity, which can further worsen liver and renal dysfunction, respectively.
REFERENCES
Ma M, Martin E, Algaze C, et al. Williams syndrome: supravalvar aortic, aortic arch, coronary, and pulmonary arteries: is comprehensive repair advisable and achievable? Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2023;26:2-8.
Wu M, Ryan KR, Roesenthal DN, Jahadi O, Moss J, Kwiatkowski DM. The use of clevidipine for hypertension in pediatric patients receiving mechanical circulatory support. Pediatr Crit Care Med. 2020;21(12):e1134-1139.
Aronson S, Dyke CM, Stierer KA, et al. The ECLIPSE trials: comparative studies of clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. Anesth Analg. 2008;107(4):1110-1121.
