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Safety of enteral sildenafil in hemodynamically unstable children

Published online by Cambridge University Press:  03 May 2019

Alexandra M. Bednarz ,
Emily N. Israel ,
Elizabeth J. Beckman ,
Michael Johansen  and
Christopher A. Thomas
Alexandra M. Bednarz
Affiliation:
Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafayette, IN, USA
Emily N. Israel
Affiliation:
Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafayette, IN, USA Department of Pharmacy, Riley Hospital for Children at Indiana University Health, Indianapolis, IN, USA
Elizabeth J. Beckman
Affiliation:
Department of Pharmacy, University of Kentucky HealthCare, Lexington, KY, USA
Michael Johansen
Affiliation:
Section of Pediatric Cardiology, Riley Hospital for Children at Indiana University Health, Indianapolis, IN, USA
Christopher A. Thomas*
Affiliation:
Department of Pharmacy Services, Phoenix Children’s Hospital, Phoenix, AZ, USA
*
Author for correspondence: C. A. Thomas, Department of Pharmacy Services, Phoenix Children’s Hospital, 1919 E. Thomas Rd., Inpatient Pharmacy, Phoenix, AZ 85016, USA. Tel: 1-602-933-4028; Fax: 602-933-1876; E-mail: [email protected]
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Abstract

Background:

Enteral sildenafil may be used in the intensive care unit for treatment of pulmonary arterial hypertension. We aimed to determine if initial enteral sildenafil dosing is safe in children receiving concurrent vasoactive infusions.

Methods:

We performed a single-centre retrospective chart review that included patients less than 2 years of age in paediatric and cardiovascular intensive care units at an academic medical centre from 1 January, 2010 to 30 November, 2016. Included patients received concomitant enteral sildenafil and a continuously infused vasoactive agent. Exclusion criteria consisted of mechanical circulatory support, any form of dialysis, or a suspicion of septic shock at the time of sildenafil initiation. We sought to identify patients who developed worsening hemodynamic instability after initiation of enteral sildenafil defined as one or more of the following observations within 24 hours of sildenafil initiation: sildenafil discontinuation, total fluid bolus receipt >10 ml/kg, increased vasoactive support, epinephrine intravenous push administration, and/or the initiation of mechanical circulatory support.

Results:

Worsening hemodynamic instability was identified in 35% of the 130-patient cohort. Patients younger than 4 months were at increased risk of further hemodynamic instability compared with older patients (56% versus 44%, p = 0.0003) despite receiving lower median doses (1.28 mg/kg/day versus 1.78 mg/kg/day, p = 0.01).

Conclusions:

Critically ill children receiving vasoactive infusions may be at increased risk for further hemodynamic instability after initiation of enteral sildenafil, particularly in younger patients. This population may benefit from lower starting enteral sildenafil doses of 0.25 mg/kg/dose or less every 8 hours to avoid further hemodynamic compromise.

Keywords

Sildenafilpulmonary hypertensionhemodynamicscritical illnessinfantschildren
Type
Original Article
Information
Cardiology in the Young , Volume 29 , Issue 5 , May 2019 , pp. 589 - 593
Copyright
© Cambridge University Press 2019 

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References

De’Alto, M, Mahadevan, VS. Pulmonary arterial hypertension associated with congenital heart disease. Eur Respir Rev 2012; 21(126): 328–337.CrossRefGoogle Scholar
Abman, SH, Hansmann, G, Archer, SL, et al. Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society. Circulation 2015; 132: 2037–2099.CrossRefGoogle ScholarPubMed
Dhariwal, AK, Bavdekar, SB. Sildenafil in pediatric pulmonary arterial hypertension. J Postgrad Med 2015; 61(3): 181–192.CrossRefGoogle ScholarPubMed
Siehr, SL, McCarthy, EK, Ogawa, MT, Feinstein, JA. Reported sildenafil side effects in pediatric pulmonary hypertension patients. Front Pediatr 2015; 3: 12.CrossRefGoogle ScholarPubMed
Gaies, MG, Jeffries, HE, Niebler, RA, et al. Vasoactive-Inotropic Score (VIS) is associated with outcome after infant cardiac surgery: an analysis from the Pediatric Cardiac Critical Care Consortium (PC4) and virtual PICU system registries. Pediatr Crit Care Med 2014; 15(6): 529–537.CrossRefGoogle Scholar
Barst, RJ, Beghetti, M, Pulido, T, et al. STARTS-2: long-term survival with oral sildenafil monotherapy in treatment-naïve pediatric pulmonary arterial hypertension. Circulation 2014; 129(19): 1914–1923.CrossRefGoogle ScholarPubMed
Barst, RJ, Ivy, DD, Gaitan, G, et al. A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naïve children with pulmonary arterial hypertension. Circulation 2012; 125: 324–334.CrossRefGoogle ScholarPubMed
Humpl, T, Reyes, JT, Erickson, S, et al. Sildenafil therapy for neonatal and childhood pulmonary hypertensive vascular disease. Cardiol Young 2011; 21(2): 187–93.CrossRefGoogle ScholarPubMed
Kaestner, M, Schranz, D, Warnecke, G, et al. Pulmonary hypertension in the intensive care unit. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart 2016; 102: ii57–ii66.CrossRefGoogle ScholarPubMed
Zamanian, RT, Haddad, F, Doyle, RL, Weinacker, AB. Management strategies for patients with pulmonary hypertension in the intensive care unit. Crit Care Med 2007; 35(9): 2037–2050.CrossRefGoogle ScholarPubMed
Simonca, L, Tulloh, R. Sildenafil in infants and children. Children (Basel) 2017; 4(7): 60.Google ScholarPubMed
Kearns, GL, Abdel-Rahman, SM, Alander, SW, et al. Developmental pharmacology – drug disposition, action, and therapy in infants and children. New Engl J Med 2003; 349: 1157–1167.CrossRefGoogle ScholarPubMed
Hill, KD, Tunks, RD, Barker, PCA, et al. Sildenafil exposure and hemodynamic effect after stage II single-ventricle surgery. Pediatr Crit Care Med 2013; 14(6): 593–600.CrossRefGoogle ScholarPubMed
Hill, KD, Sampson, MR, Li, JS, et al. Pharmacokinetics of intravenous sildenafil in children with palliated single ventricle heart defects: effect of elevated hepatic pressures. Cardiol Young 2016; 26(2): 354–362.CrossRefGoogle ScholarPubMed
Bentlin, MR, Saito, A, De Luca, AK, et al. Sildenafil for pulmonary hypertension after cardiac surgery. J Pediatr (Rio J) 2005; 81(2): 175–178.CrossRefGoogle ScholarPubMed
Raja, SG, Danton, MD, MacArthur, KJ, Pollock, JC. Effects of escalating doses of sildenafil on hemodynamics and gas exchange in children with pulmonary hypertension and congenital cardiac defects. J Cardiothorac Vasc Anesth 2007; 21(2): 203–207.CrossRefGoogle ScholarPubMed
Freeman, SB, Taft, LF, Dooley, KJ, et al. Population-based study of congenital heart defects in Down syndrome. Am J Med Genet 1998; 80: 2013–2017.3.0.CO;2-8>CrossRefGoogle ScholarPubMed
Beghetti, M, Rudzinski, A, Zhang, M. Efficacy and safety of oral sildenafil in children with Down syndrome and pulmonary hypertension. BMC Cardiovasc Disord 2017; 17(1): 177.CrossRefGoogle ScholarPubMed
Palma, G, Giordano, R, Russolillo, V, et al. Sildenafil therapy for pulmonary hypertension before and after pediatric congenital heart surgery. Tex Heart Inst J 2011; 38(3):238–242.Google ScholarPubMed
El Midany, AAH, Mostafa, EA, Azab, S, et al. Perioperative sildenafil therapy for pulmonary hypertension in infants undergoing congenital cardiac defect closure. Int Cardiovasc Thorac Surg 2013; 17(6): 963–968.CrossRefGoogle ScholarPubMed