Study: Inhaled Levosimendan Non-Inferior to IV Administration in Pediatric Surgery

Jared Kaltwasser

In a first-of-its kind study, young children undergoing heart surgery had similar results regardless of whether they received levosimendan intravenously or via inhalation.

Pediatric patients who underwent on-cardiopulmonary bypass cardiac surgery appeared to respond equally well to inhaled levosimendan (LS) compared with intravenous administration of the drug, according to new research.

Children born with left-to-right intracardiac shunts often suffer from pulmonary arterial hypertension (PAH), a condition that can affect the outcome of cardiac surgery in such patients.

PAH is defined as having pulmonary arterial pressure (PAP) greater than 20 mmHg as measured during right-sided heart catheterization. Writing in the Journal of Clinical Anesthesia, corresponding author Ibrahim Abdelbaser, MD, of Mansoura University in Egypt, and colleagues explained that the use of cardiopulmonary bypass in children with PAH can lead to aggravation of PAP, potentially causing a pulmonary hypertensive crisis and acute right ventricular dysfunction.

LS, a calcium sensitizing inodilator, has been shown to reduce PAP and offset some of the risk associated with the procedure when given intravenously during surgery. In inhaled form, the drug has been shown to decrease PAP and improve right ventricular function. In the new non-inferiority study, the authors wanted to know whether inhaled LS might perform equally well at reducing PAP in pediatric patients undergoing surgical repair of congenital heart disease.

The investigators recruited 50 patients, all between the ages of 1 and 5, who were scheduled to undergo surgical repair of left-to-right intracardiac shunts complicated by pulmonary hypertension. The 44 patients who were randomized were split into 2 equal groups. The first received an intravenous infusion of LS at a rate of 0.1 μg/kg/min beginning after anesthesia induction and continuing for 24 hours. The second group received LS through a simple jet nebulizer connected to an oxygen source flowing at a rate of 10/L/min. The nebulizer was attached to the inspiratory limb of the anesthesia ventilator close to the endotracheal tube.

Following surgery, patients were administered the drug using a face mask attached to a nebulizer. In these patients, the LS dose was divided into 4 doses over 24 hours of 36 μg/kg every 6 hours and dissolved in 3 mL saline 0.9%.

The investigators found that the inhaled version of LS was not inferior to intravenous LS when it came to reducing PAP. The authors collected data at 5 time points following induction of anesthesia and found the intravenous administration group had a significantly higher mean heart rate at 3 of the time points and significantly lower arterial blood pressure at 3 of the time points, compared with the inhalation group.

Additionally, they found patients who were administered inhaled LS had less tachycardia and hypotension, which are the most common adverse effects of intravenous LS. Patients with inhaled LS were also less likely to need vasoactive drugs.

“To the best of our knowledge, our study is the first clinical trial in children that used inhaled LS for controlling pulmonary hypertension,” the authors said, noting that earlier research in adults undergoing mitral valve replacement similarly found inhaled LS was non-inferior.

“In summary, we have found that inhalation of LS is non-inferior to intravenous LS in reducing the high PAP in children [who] underwent on-pump cardiac surgery, as both routes similarly reduce PAP,” the authors concluded.

Reference:

Abdelbaser I, Mageed NA, Elfayoumy SI, Elgamal MF, Elmorsy MM, and Taman HI. The direct comparison of inhaled versus intravenous levosimendan in children with pulmonary hypertension undergoing on-cardiopulmonary bypass cardiac surgery: a randomized, controlled, non-inferiority study. J Clin Anesth. Published online March 16, 2021. doi:10.1016/j.jclinane.2021.110231