Correspondence  |   December 2004
Treatment of Rebound Pulmonary Hypertension: Why Not Sildenafil?
Author Notes
  • Alder Hey Hospital, Liverpool, United Kingdom.
Article Information
Correspondence   |   December 2004
Treatment of Rebound Pulmonary Hypertension: Why Not Sildenafil?
Anesthesiology 12 2004, Vol.101, 1480. doi:
Anesthesiology 12 2004, Vol.101, 1480. doi:
To the Editor:—
I read with great interest the case report by Augoustides et al.  1 published in the April issue of Anesthesiology. They highlight the important issue of rebound pulmonary hypertension after withdrawal of inhaled prostacyclin and make a case for the use of inhaled iloprost. They propose that inhaled iloprost may allow gradual controlled withdrawal of perioperative inhaled selective pulmonary vasodilation, probably as a result of its favorable pharmacokinetics. Hence, in their opinion it has great promise in the management of perioperative pulmonary hypertension after cardiac surgery. However, I think that if the authors had highlighted the advantages of using sildenafil, instead of iloprost, in this scenario their case report would have made a more lasting and useful contribution to the existing literature on the topic of management of rebound pulmonary hypertension.
Pulmonary hypertension remains a major complication after surgical correction of congenital and long-standing valvular heart disease. Inhaled nitric oxide has been shown to reduce, but not eliminate, potentially life-threatening episodic pulmonary hypertensive crises.2 Nitric oxide increases intracellular cyclic guanosine monophosphate, resulting in smooth muscle vasodilation. Phosphodiesterase type 5 is responsible for cyclic guanosine monophosphate breakdown in lung tissue. Abrupt discontinuation of nitric oxide may be complicated by life-threatening events, and phosphodiesterase activity may play a role in this phenomenon.3 Sildenafil (Viagra; Pfizer Laboratories, New York, NY), a selective and potent inhibitor of phosphodiesterase type 5, augments pulmonary vasodilation with nitric oxide and reduces the risk of pulmonary hypertensive crises in an at-risk postoperative patient.4 Furthermore, it ameliorates the rebound pulmonary hypertension caused by withdrawal of inhaled pulmonary vasodilators.5 
Compared with the standard treatment, inhaled nitric oxide, sildenafil is superior in decreasing the mean pulmonary artery pressure and equally effective and selective in reducing pulmonary vascular resistance.6 It also causes a significant increase in the cardiac index.6 Its availability in oral, inhaled and intravenous forms, longer half-life of 4 h,4 and proven efficacy in randomized controlled trials7–9 are some of the distinguishing features which make sildenafil first-choice agent for managing rebound pulmonary hypertension.
Thus, my question for Augoustides et al.  is “Why inhaled iloprost and not sildenafil?”
Alder Hey Hospital, Liverpool, United Kingdom.
Augoustides JG, Culp K, Smith S: Rebound pulmonary hypertension and cardiogenic shock after withdrawal of inhaled prostacyclin. Anesthesiology 2004; 100:1023–5Augoustides, JG Culp, K Smith, S
Miller OI, Tang SF, Keech A, Pigott NB, Beller E, Celermajer DS: Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: A randomized double-blind study. Lancet 2000; 356:1464–9Miller, OI Tang, SF Keech, A Pigott, NB Beller, E Celermajer, DS
Ivy DD, Kinsella JP, Ziegler JW, Abman SH: Dipyridamole attenuates rebound pulmonary hypertension after inhaled nitric oxide withdrawal in postoperative congenital heart disease. J Thorac Cardiovasc Surg 1998; 115:875–82Ivy, DD Kinsella, JP Ziegler, JW Abman, SH
Atz AM, Lefler AK, Fairbrother DL, Uber WE, Bradley SM: Sildenafil augments the effect of inhaled nitric oxide for postoperative pulmonary hypertensive crises. J Thorac Cardiovasc Surg 2002; 124:628–9Atz, AM Lefler, AK Fairbrother, DL Uber, WE Bradley, SM
Atz AM, Wessel DL: Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology 1999; 91:307–10Atz, AM Wessel, DL
Michelakis E, Tymchak W, Lien D, Webster L, Hashimoto K, Archer S: Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide. Circulation 2002; 105:2398–403Michelakis, E Tymchak, W Lien, D Webster, L Hashimoto, K Archer, S
Stocker C, Penny DJ, Brizard CP, Cochrane AD, Soto R, Shekerdemian LS: Intravenous sildenafil and inhaled nitric oxide: A randomised trial in infants after cardiac surgery. Intensive Care Med 2003; 29:1996–2003Stocker, C Penny, DJ Brizard, CP Cochrane, AD Soto, R Shekerdemian, LS
Bharani A, Mathew V, Sahu A, Lunia B: The efficacy and tolerability of sildenafil in patients with moderate-to-severe pulmonary hypertension. Indian Heart J 2003; 55:55–9Bharani, A Mathew, V Sahu, A Lunia, B
Ghofrani HA, Wiedemann R, Rose F, Schermuly RT, Olschewski H, Weissmann N, Gunther A, Walmrath D, Seeger W, Grimminger F: Sildenafil for treatment of lung fibrosis and pulmonary hypertension: A randomised controlled trial. Lancet 2002; 360:895–900Ghofrani, HA Wiedemann, R Rose, F Schermuly, RT Olschewski, H Weissmann, N Gunther, A Walmrath, D Seeger, W Grimminger, F