Eur J Cardiothorac Surg 2003;24:837-839
© 2003 Elsevier Science NL
Successful weaning from inhaled nitric oxide using dipyridamole
Yoshikatsu Saiki*,
Yoshio Nitta,
Yusuke Tsuru,
Koichi Tabayashi
Department of Cardiovascular Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
Received 13 May 2003;
received in revised form 14 July 2003;
accepted 15 July 2003.
* Corresponding author. Tel.: +22-717-7222; fax: +22-717-7227
e-mail: ysaiki{at}mail.cc.tohoku.ac.jp
 |
Abstract
|
|---|
A 33-year-old woman with an atrial septal defect associated with severe pulmonary hypertension underwent suture closure of the defect after assessment of operability by lung biopsy. Postoperative course was complicated by suprasystemic refractory pulmonary hypertension, and she became dependent upon treatment with inhaled nitric oxide. After multiple attempts to withdraw nitric oxide, dipyridamole was administered and blunted the rebound pulmonary hypertension after subsequent nitric oxide withdrawal.
Key Words: Nitric oxide • Pulmonary hypertension • Dipyridamole
|
1. Introduction
|
|---|
Inhaled nitric oxide (NO) is an established treatment for postoperative pulmonary hypertension, but, rebound pulmonary hypertension after its discontinuation is occasionally encountered and causes a significant set back in patient recovery.
We report a case in whom refractory postoperative pulmonary hypertension was sustained and multiple attempts to withdraw NO were unsuccessful. Dipyridamole, a cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE) 5 inhibitor, at least in part, contributed to successful discontinuation of NO.
|
2. Case report
|
|---|
A 33-year-old woman presented to a local hospital with recent onset of dyspnea and decreased exercise tolerance. A chest X-ray showed a prominent pulmonary artery silhouette with a cardiothoracic ratio of 47%. An echocardiogram revealed a secundum atrial septal defect (ASD) of 18.5 mm in length. Cardiac catheterization confirmed the ASD with an oxygen saturation step up at midatrium level. A left to right shunt was calculated as 33% without a right to left component. Pulmonary artery pressure was 83/27 mmHg, while the systemic pressure was 97/60 mmHg. The patient was referred to our hospital and slated for an open lung biopsy to determine suitability for surgical closure of the ASD. An open lung biopsy from the left lingual and lower lobes showed a mixed type of musculoelastosis and plexogenic arteriopathy. The histology was carefully evaluated by a cardiovascular pathology specialist, and surgical repair of the ASD was recommended. She underwent a suture closure of the secundum ASD via a partial sternotomy incision using cardiopulmonary bypass. There was no residual ASD after the closure. After transfer to an intensive care unit, her pulmonary artery pressure rose to suprasystemic levels, and her hemodynamics gradually deteriorated with manifestations of low cardiac output. NO inhalation was started and was increased to as much as 10 ppm, and effectively lowered the ratio of systolic pulmonary artery pressure to systemic artery pressure (Pp/Ps) and also improved oxygenation with increased urine output. However, attempts to withdraw NO during the next 5 postoperative days were unsuccessful due to a decrease in cardiac output and a rapid increase in Pp/Ps (Fig. 1)
. Additional pharmacological therapies, including prostacyclin, were tried, but failed to eliminate the systemic hypotension associated with NO withdrawal. After 11 days of mechanical ventilation and multiple attempts to discontinue NO, it was felt that surgical creation of a small ASD was necessary to enable weaning from NO and mechanical ventilation. On the 12th postoperative day, she underwent fenestration of the interatrial septum. After an 8-mm circumference ASD was created using a fenestrated patch, her pulmonary artery pressure fell to 80% of systemic pressure. Tapering of NO was then cautiously attempted, however, she failed to wean off NO again developing a low cardiac output (Fig. 1). The hemodynamic instability was also associated with systemic desaturation. Despite the fact that Pp/Ps decreased significantly after surgical creation of the small ASD, it seemed that her pulmonary vascular reactivity remained NO-dependent. NO therapy was reinstituted at 10 ppm. On the 15th day, dipyridamole (0.6 mg/kg per day) was started in an attempt to prevent the rebound phenomenon. Within the same day of dipyridamole introduction, her hemodynamics markedly improved as demonstrated by increased cardiac output and urine output along with improved oxygenation. NO was finally discontinued 5 days after start of dipyridamole without rebound pulmonary hypertension. She was eventually extubated and discharged home in a stable condition on oral prostacyclin as recommended by Barst [1].
View larger version (30K):
[in this window]
[in a new window]
|
Fig. 1. Course in the intensive care unit. Alterations in nitric oxide concentration, changes in cardiac index and ratio of systolic pulmonary artery pressure to systemic artery pressure are depicted. A Swan–Ganz catheter was removed on day 10 and re-introduced on day 12. Note the gradual increase in cardiac index without a rise in Pp/Ps after administration of dipyridamole. NO, nitric oxide; Pp/Ps, ratio of systolic pulmonary artery pressure to systemic artery pressure; C.I., cardiac index; PGI2, prostacyclin.
|
|
|
3. Discussion
|
|---|
Adverse hemodynamic effects following NO withdrawal occur in a subset of patients with severe pulmonary hypertension and may cause life-threatening events or may be transient and resolve over time [2,3]. Inhaled NO induced down-regulation of endogenous NO synthase, decreased NO sensitivity, and an imbalance of vasodilator and vacoconstrictor stimuli are suggested mechanisms responsible for rebound pulmonary hypertension [4]. Recent reports suggest that dipyridamole, a cGMP-specific PDE5 inhibitor, is a promising agent to attenuate rebound pulmonary hypertension after discontinuation of NO and acts by inhibiting hydrolysis of cGMP in vascular smooth muscle [5,6].
There are an increasing number of reports which state that dipyridamole is a promising substance for the treatment of pulmonary hypertension among pediatric patients as well as in experimental animal models [5–8]. However, there are only two publications that deal with dipyridamole treatment of pulmonary hypertension in adults [9,10]. Fullerton et al. demonstrated an effective reduction in pulmonary vascular resistance with combination therapy of inhaled nitric oxide plus dipyridamole in the patients undergoing valve replacement [9]. Jiang et al. examined the effect of dipyridamole in a patient with cardiac failure who underwent hemicolectomy [10]. The patient we describe was an adult with a congenital ASD associated with severe pulmonary hypertension. A lung biopsy prior to the corrective surgery revealed a mixed type of musculoelastosis and plexogenic arteriopathy with moderate thickening of the smooth muscle layers, and which differentiated the pathohistological changes from primary pulmonary hypertension. Collateral channels near the obstructive arteriopathy, which are a contraindication for definitive surgery, were not present in the specimens. Based on these findings surgical repair was advised. Unfortunately, refractory postoperative pulmonary hypertension exceeded our pre-operative estimates. Undoubtedly, fenestration of the ASD patch contributed to a decline in the Pp/Ps. However, even after the palliative procedure, the reactive component of severe pulmonary hypertension was unchanged as evidenced by a significant fall in cardiac output after discontinuing NO.
In our patient, dipyridamole seemed to be efficacious, causing a rise in cardiac output without rebound pulmonary hypertension and allowing the patient to be weaned from prolonged NO inhalation. Potential side effects of dipyridamole, such as bleeding tendency from inhibition of platelet aggregation, and systemic hypotension due to general vasodilatation, were carefully monitored, and were not encountered in the present case. Although pulmonary hypertensive patients associated with congenital heart defects represent a very heterogeneous group of patients and their responses to therapeutic interventions vary [1], the use of dipyridamole deserves consideration as a treatment in the setting of failed withdrawal from NO inhalation in patients with a long-standing pulmonary hypertension.
|
References
|
|---|
- Barst R. Reduction in recalcitrant pulmonary hypertension after operation for atrial septal defect [Invited commentary]. Ann Thorac Surg 2001;72:906-907.[Free Full Text]
- Miller O.I., Tang S.F., Keech A., Celermajer D.S. Rebound pulmonary hypertension on withdrawal from inhaled nitric oxide. Lancet 1995;346:51-52.[Medline]
- Lavoie A., Hall J.B., Olson D.M., Wylam M.E. Life-threatening effects of discontinuing inhaled nitric oxide in severe respiratory failure. Am J Respir Crit Care Med 1996;153:1985-1987.[Abstract]
- Giad A., Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 1995;333:214-221.[Abstract/Free Full Text]
- Ivy D.D., Kinsella J.P., Ziegler J.W., Abman S.H. Dipyridamole attenuates rebound pulmonary hypertension after inhaled nitric oxide withdrawal in postoperative congenital heart disease. J Thorac Cardiovasc Surg 1998;115:875-882.[Abstract/Free Full Text]
- Al-Alaiyan S., Al-Omran A., Dyer D. The use of phosphodiesterase inhibitor (dipyridamole) to wean from inhaled nitric oxide. Intensive Care Med 1996;22:1093-1095.[Medline]
- Schermuly R.T., Roehl A., Weissmann N., Ghofrani H.A., Leuchte H., Grimminger F., Seeger W., Walmrath D. Combination of nonspecific PDE inhibitors with inhaled prostacyclin in experimental pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2001;281:L1361-L1368.[Abstract/Free Full Text]
- Foubert L., De Wolf D., Mareels K., Van Belleghem Y., Reyntjens K., Mortier E., Van Nooten G. Intravenous dipyridamole enhances the effects of inhaled nitric oxide and prevents rebound pulmonary hypertension in piglets. Pediatr Res 2002;52:730-736.[Medline]
- Fullerton D.A., Jaggers J., Piedalue F., Grover F.L., McIntyre R.C., Jr Effective control of refractory pulmonary hypertension after cardiac operations. J Thorac Cardiovasc Surg 1997;113:363-370.[Abstract/Free Full Text]
- Jiang Z.Y., Costachescu T., Derouin M., Blaise G. Treatment of pulmonary hypertension during surgery with nitric oxide and vasodilators. Can J Anaesth 2000;47:552-555.[Medline]
This article has been cited by other articles:
|
|
|
|
 
J. Cai, Z. Su, Z. Shi, Y. Zhou, Z. Xu, Z. Xu, and Y. Yang
Nitric Oxide and Milrinone: Combined Effect on Pulmonary Circulation After Fontan-Type Procedure: A Prospective, Randomized Study
Ann. Thorac. Surg.,
September 1, 2008;
86(3):
882 - 888.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
1. Introduction
