Title: Effect of preoperative oral sildenafil on intraoperative hemodynamics in patients with severe pulmonary artery hypertension undergoing mitral valve replacement

Authors: Vijay Shewale, Manish Jadhao, Vaibhav Shah, Chaitanya Raut, Prashant Mishra, Jayant Khandekar

 DOI: https://dx.doi.org/10.18535/jmscr/v8i4.51

Abstract

   

Aim: Long standing severe mitral stenosis or mitral regurgitation is usually associated with pulmonary hypertension. Severe pulmonary hypertension is a risk factor for right ventricular dysfunction and is associated with morbidity and mortality in patients undergoing mitral valve surgery. Sildenafil is selective phosphodiesterase type 5 inhibitor which is increasingly used for pulmonary hypertension. But there is lack of evidence of its usefulness in pulmonary hypertension due to mitral valve disease. The study aims to assess the effectiveness of preoperative oral sildenafil on severe pulmonary hypertension and incidence of RV failure in patients undergoing mitral valve replacement surgery.

Materials & Methods: A total of 50 patients scheduled for mitral valve replacement with severe pulmonary hypertension (pulmonary artery pressure greater than 30 mm of hg) on preoperative transthoracic echo  who got operated during January 2019 to march 2019 , were randomly treated with oral sildenafil 25 mg (N = 25) or placebo (N = 25) eight hourly for 48 hours before surgery. Hemodynamic  variables were measured 5 minutes after induction of anaesthesia (T1-baseline), 30 minutes at weaning from cardiopulmonary bypass (CPB) (T2) and after 1,2, and 6 hours (T3, T4, T5, respectively) during the postoperative period.

Result: Patient characteristics and baseline hemodynamics were similar between groups. Systolic and mean pulmonary arterial pressures and pulmonary vascular resistance were significantly lower in the sildenafifil group at all times without any changes in mean systemic arterial pressure and systemic vascular resistance. Ventilation time and postoperative recovery room stay were significantly lower in sildenafil group.

Conclusion: Sildenafil has significant vasodilatory effect on pulmonary vessels as compared with placebo in mitral valve replacement patients with severe pulmonary hypertension. It also reduces ventilation time and intensive care unit (ICU) stay time as compared with placebo. It is concluded that sildenafil is effective in reducing pulmonary hypertension when administered preoperatively in patients with severe pulmonary hypertension undergoing mitral valve replacement surgery.

Keywords: Sildenafil, Pulmonary Hypertension, Mitral Valve Replacement, Pulmonary Hemodynamics.

References

  1. Simonneau G, Galie N, Rubin LJ, Langleben D, Seeger W, Domenighetti G, et al. Clinical classification of pulmonary hypertension. J Am] Coll Cardiol. 2004;43(12 Suppl S):5S-12S.
  2. Christman BW, McPherson CD, Newman JH, King GA, Bernard GR, Groves BM, et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med. 1992;327:70-5.
  3. Stewart DJ, Levy RD, Cernacek P, Langleben D. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann Intern Med. 1991;114:464-9.
  4. Ghofrani HA, Pepke-Zaba J, Barbera JA, Channick R, Keogh AM, Gomez-Sanchez MA, et al. Nitric oxide pathway and phosphodiesterase inhibitors in pulmonary arterial hypertension. J Am Coll Cardiol. 2004;43(12 Suppl S):68S-72S.
  5. Raja SG, Nayak SH. Sildenafil: emerging cardiovascular indications. Ann Thorac Surg. 2004;78:1496-506.
  6. Matsumoto T, Kobayashi T, Kamata K. Phosphodiesterase in the vascular system. J Smooth Muscle Res. 2003;39:67-86.
  7. Corbin JD, Francis SH. Pharmacology of phosphodiesterase-5 inhibitors. Int J Clin Pract. 2002;56:453-9.
  8. Trachte AL, Labato EB, Urdaneta F, Hess PJ, Klodell CT, Martin TD, et al. Oral sildenafil reduces pulmonary hypertension after cardiac surgery. Ann Thorac Surg. 2005;79:194-7.
  9. Ward C, Hancock BW. Extreme pulmonary hypertension caused by mitral valve disease: Natural history and results of surgery. Br Heart J 1975;37:74‑8.
  10. Malouf JF, Enriquez‑Sarano M, Pellikka PA, Oh JK, Bailey KR, Chandrasekaran K, et al. Severe pulmonary hypertension in patients with severe aortic valve stenosis: Clinical profile and prognostic implications. J Am Coll Cardiol 2002;40:789-795.
  11. Mangano DT. Biventricular function after myocardial revascularization in humans: deterioration and recovery patterns during the first 24 hours. Anesthesiology 1985;62:571-7.
  12. Calvin JE Jr. Acute right heart failure: Pathophysiology, recognition, and pharmacological management. J Cardiothorac Vasc Anesth 1991;5:507-13.
  13. Rabe KF, Tenor H, Dent G, Schudt C, Nakashima M, Magnussen H. Identification of PDE isozymes in human pulmonary artery and effect of selective PDE inhibitors. Am J Physiol 1994;266:536-43
  14. Giad A, Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 1995; 333:214-21.
  15. Boolell M, Allen MJ, Ballard SA, Gepi Attee S, Muirhead GJ, Naylor AM, et al. Sildenafil: An orally active type 5 cyclic GMP‑specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 1996;8:47-52.
  16. Kloner RA, Zusman RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol 1999;84:11N-7.
  17. Sastry BK, Narasimhan C, Reddy NK, Raju BS. Clinical efficacy of sildenafil in primary pulmonary hypertension: A randomized, placebo‑controlled, double‑blind, crossover study. J Am Coll Cardiol 2004;43:1149-53.
  18. Wilkens H, Guth A, König J, Forestier N, Cremers B, Hennen B, et al. Effects of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation 2001;104:1218‑22.
  19. Cubillos‑Garzón LA, Casas JP, Morillo CA. Sildenafil in secondary pulmonary hypertension. Int J Cardiol 2003;89:101‑2.
  20. Ghofrani HA, Wiedemann R, Rose F, Schermuly RT, Olschewski H, Weissmann N, et al. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: A randomized controlled trial. Lancet 2002;360:895‑900.
  21. Schermuly RT, Kreisselmeier KP, Ghofrani HA, Yilmaz H, Butrous G, Ermert L, et al. Chronic sildenafil treatment inhibits monocrotaline‑induced pulmonary hypertension in rats. Am J Respir Crit Care Med 2004;169:39‑45.

Corresponding Author

Vijay Shewale

Department of Cardiovascular and Thoracic Surgery, Lokmanya Tilak Municipal Medical College, Sion, Mumbai, India