Effects of intravenous treprostinil in high-risk patients after total cavo-pulmonary connection_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANG Xiaofeng , LU Zhongyuan , ZHU Zhiyuan ,  WANG Xu

Department of Pediatric Intensive Care Unit, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, P. R. China;

Corresponding author：

WANG Xu, Email: fwpicu@163.com

Keywords：

Treprostinil; total cavo-pulmonary connection; high-risk; hemodynamics

DOI：

10.7507/1007-4848.202202039

Video：

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Objective To explore the effects of intravenous treprostinil in different doses on the hemodynamics and postoperative outcomes after high-risk total cavo-pulmonary connection (TCPC). Methods From 2018 to 2021, among 189 patients who underwent TCPC in the Department of Pediatric Cardiac Surgery of Fuwai Hospital, 26 high-risk patients who received the intravenous treprostinil therapy were retrospectively analyzed. There were 12 males and 14 females, with an age of 4 (3, 6) years and a weight of 17.6±6.2 kg. The patients were divided into two groups: a high-dose group [15 patients, maintaining dose>10 ng/(kg·min)] and a low-dose group [11 patients, maintaining dose≤10 ng/(kg·min)]. The hemodynamics before treprostinil using and during the first 24 hours after reaching the maintaining dose of treprostinil, and postoperative outcomes of the two groups were investigated. Results The incidence of heterotaxia was higher in the high-dose group (66.7% vs. 18.2%, P=0.021). During the observation period, the mean pulmonary artery pressure decreased from 11.9±3.6 mm Hg to 11.0±3.3 mm Hg in the low-dose group (P=0.013), and from 12.9±4.7 mm Hg to 10.2±3.4 mm Hg in the high-dose group (P=0.001). The decreasing effect in the high-dose group was better than that in the low-dose group (P=0.010). There was no statistical difference in the postoperative outcomes between the two groups (P>0.05). In terms of side effects, patients needed temporarily increased dosage of vasoactive drugs to maintain stable blood pressure during 6-12 h after treprostinil therapy in the high-dose group. Conclusion In patients after high-risk TCPC, intravenous high-dose treprostinil has a better therapeutic effect on reducing pulmonary artery pressure. However, it should be noted that increased dosage of vasoactive agents may be required to maintain blood pressure stability in patients with high-dose treprostinil.

Citation： WANG Xiaofeng, LU Zhongyuan, ZHU Zhiyuan, WANG Xu. Effects of intravenous treprostinil in high-risk patients after total cavo-pulmonary connection. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(3): 422-427. doi: 10.7507/1007-4848.202202039 Copy

1.	Becker K, Uebing A, Hansen JH. Pulmonary vascular disease in Fontan circulation—Is there a rationale for pulmonary vasodilator therapies? Cardiovasc Diagn Ther, 2021, 11(4): 1111-1121.
2.	Al-Shawk M, Banjoko A, Axiaq A, et al. Perioperative and long-term management of Fontan patients. Cardiol Young, 2021, 31(5): 775-785.
3.	Kotani Y, Chetan D, Zhu J, et al. Fontan failure and death in contemporary Fontan circulation: Analysis from the last two decades. Ann Thorac Surg, 2018, 105(4): 1240-1247.
4.	Latus H, Lederle A, Khalil M, et al. Evaluation of pulmonary endothelial function in Fontan patients. J Thorac Cardiovasc Surg, 2019, 158(2): 523-531.
5.	Chugh R. The Fontan thromboprophylaxis dilemma: To give, or what not to give. J Am Coll Cardiol, 2019, 74(8): 1082-1085.
6.	Goldberg DJ, French B, McBride MG, et al. Impact of oral sildenafil on exercise performance in children and young adults after the Fontan operation: A randomized, double-blind, placebo-controlled, crossover trial. Circulation, 2011, 123(11): 1185-1193.
7.	Rhodes J, Ubeda-Tikkanen A, Clair M, et al. Effect of inhaled iloprost on the exercise function of Fontan patients: A demonstration of concept. Int J Cardiol, 2013, 168(3): 2435-2440.
8.	Hebert A, Mikkelsen UR, Thilen U, et al. Bosentan improves exercise capacity in adolescents and adults after Fontan operation: The TEMPO (treatment with endothelin receptor antagonist in Fontan patients, a randomized, placebo-controlled, double-blind study measuring peak oxygen consumption) study. Circulation, 2014, 130(23): 2021-2030.
9.	Giardini A, Balducci A, Specchia S, et al. Effect of sildenafil on haemodynamic response to exercise and exercise capacity in Fontan patients. Eur Heart J, 2008, 29(13): 1681-1687.
10.	伍琼, 贾镭, 荆志成, 等. 曲前列尼尔治疗肺动脉高压的研究进展. 中华心血管病杂志, 2017, 45(9): 810-813.
11.	Ablonczy L, Tordas D, Kis E, et al. Use of subcutaneous treprostinil in pediatric pulmonary arterial hypertension-bridge-to-transplant or long-term treatment? Pediatr Transplant, 2018, 22(2): 1-10.
12.	Constantine A, Dimopoulos K, Jenkins P, et al. Use of pulmonary arterial hypertension therapies in patients with a Fontan circulation: Current practice across the United Kingdom. J Am Heart Assoc, 2022, 11(1): e023035.
13.	Rychik J, Atz AM, Celermajer DS, et al. Evaluation and management of the child and adult with Fontan circulation: A scientific statement from the American Heart Association. Circulation, 2019. [Epub ahead of print].
14.	Vigano G, McMahon CJ, Walsh K, et al. High-risk Fontan completion patients achieve low perioperative risk and benefit from cavopulmonary connection 7 years out. Eur J Cardiothorac Surg, 2019, 56(4): 664-670.
15.	Ozawa H, Hoashi T, Ohuchi H, et al. Long-term outcomes after fenestration closure in high-risk Fontan candidates. Pediatr Cardiol, 2021, 42(6): 1356-1364.
16.	Bigelow AM, Ghanayem NS, Thompson NE, et al. Safety and efficacy of vasopressin after Fontan completion: A randomized pilot study. Ann Thorac Surg, 2019, 108(6): 1865-1874.
17.	农绍汉. 新生儿毛细血管渗漏综合征. 中国当代儿科杂志, 2020, 22(10): 1056-1060.

1. Becker K, Uebing A, Hansen JH. Pulmonary vascular disease in Fontan circulation—Is there a rationale for pulmonary vasodilator therapies? Cardiovasc Diagn Ther, 2021, 11(4): 1111-1121.
2. Al-Shawk M, Banjoko A, Axiaq A, et al. Perioperative and long-term management of Fontan patients. Cardiol Young, 2021, 31(5): 775-785.
3. Kotani Y, Chetan D, Zhu J, et al. Fontan failure and death in contemporary Fontan circulation: Analysis from the last two decades. Ann Thorac Surg, 2018, 105(4): 1240-1247.
4. Latus H, Lederle A, Khalil M, et al. Evaluation of pulmonary endothelial function in Fontan patients. J Thorac Cardiovasc Surg, 2019, 158(2): 523-531.
5. Chugh R. The Fontan thromboprophylaxis dilemma: To give, or what not to give. J Am Coll Cardiol, 2019, 74(8): 1082-1085.
6. Goldberg DJ, French B, McBride MG, et al. Impact of oral sildenafil on exercise performance in children and young adults after the Fontan operation: A randomized, double-blind, placebo-controlled, crossover trial. Circulation, 2011, 123(11): 1185-1193.
7. Rhodes J, Ubeda-Tikkanen A, Clair M, et al. Effect of inhaled iloprost on the exercise function of Fontan patients: A demonstration of concept. Int J Cardiol, 2013, 168(3): 2435-2440.
8. Hebert A, Mikkelsen UR, Thilen U, et al. Bosentan improves exercise capacity in adolescents and adults after Fontan operation: The TEMPO (treatment with endothelin receptor antagonist in Fontan patients, a randomized, placebo-controlled, double-blind study measuring peak oxygen consumption) study. Circulation, 2014, 130(23): 2021-2030.
9. Giardini A, Balducci A, Specchia S, et al. Effect of sildenafil on haemodynamic response to exercise and exercise capacity in Fontan patients. Eur Heart J, 2008, 29(13): 1681-1687.
10. 伍琼, 贾镭, 荆志成, 等. 曲前列尼尔治疗肺动脉高压的研究进展. 中华心血管病杂志, 2017, 45(9): 810-813.
11. Ablonczy L, Tordas D, Kis E, et al. Use of subcutaneous treprostinil in pediatric pulmonary arterial hypertension-bridge-to-transplant or long-term treatment? Pediatr Transplant, 2018, 22(2): 1-10.
12. Constantine A, Dimopoulos K, Jenkins P, et al. Use of pulmonary arterial hypertension therapies in patients with a Fontan circulation: Current practice across the United Kingdom. J Am Heart Assoc, 2022, 11(1): e023035.
13. Rychik J, Atz AM, Celermajer DS, et al. Evaluation and management of the child and adult with Fontan circulation: A scientific statement from the American Heart Association. Circulation, 2019. [Epub ahead of print].
14. Vigano G, McMahon CJ, Walsh K, et al. High-risk Fontan completion patients achieve low perioperative risk and benefit from cavopulmonary connection 7 years out. Eur J Cardiothorac Surg, 2019, 56(4): 664-670.
15. Ozawa H, Hoashi T, Ohuchi H, et al. Long-term outcomes after fenestration closure in high-risk Fontan candidates. Pediatr Cardiol, 2021, 42(6): 1356-1364.
16. Bigelow AM, Ghanayem NS, Thompson NE, et al. Safety and efficacy of vasopressin after Fontan completion: A randomized pilot study. Ann Thorac Surg, 2019, 108(6): 1865-1874.
17. 农绍汉. 新生儿毛细血管渗漏综合征. 中国当代儿科杂志, 2020, 22(10): 1056-1060.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Effects of intravenous treprostinil in high-risk patients after total cavo-pulmonary connection

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