Efficacy of low-dose inhaled nitric oxide in the treatment of severe hypoxemia after Sun’soperation: A retrospective cohort study_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

MA Xiaozhong ¹ , ZHANG Shaopeng ¹ ,  BAI Yunpeng ¹ , WU Zhenhua ² , ZHAO Feng ¹ , CHEN Qingliang ¹ , JIANG Nan ¹

1. Department of Cardiac Surgery, Tianjin Chest Hospital, Tianjin, 300222, P. R. China;
2. Intensive Care Unit, Tianjin Chest Hospital, Tianjin, 300222, P. R. China;

Corresponding author：

BAI Yunpeng, Email: oliverwhite@126.com

Keywords：

Inhaled nitric oxide; low-dose; Sun’s operation; hypoxemia

DOI：

10.7507/1007-4848.202310042

Video：

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Objective To investigate the efficacy of low-dose inhaled nitric oxide (iNO) in the treatment of severe hypoxemia after Sun’s operation. Methods The clinical data of patients undergoing Sun’s operation for acute Type A aortic dissection in our hospital from January 2020 to June 2022 were retrospectively analyzed. Patients who received conventional treatment before November 2021 were enrolled as a control group. After November 2021, iNO was used in our hospital, and the patients who received iNO as an iNO group. The preoperative clinical baseline data, perioperative clinical data and oxygenation index were compared between the two groups. Results A total of 54 patients were included in the control group, including 45 males and 9 females, with an average age of 53.0±10.9 years. A total of 27 patients were included in the iNO group, including 21 males and 6 females, with an average age of 52.0±10.6 years. The preoperative body mass index of the two groups was greater than 25 kg/m², white blood cell count, C-reactive protein were significantly higher than normal level, but there was no statistical difference between the groups (P＞0.05). There were no statistical differences in intraoperative data between the two groups (P＞0.05). The iNO group had significantly shorter duration of mechanical ventilation, postoperative ICU stay, and postoperative hospital stay than the control group (P<0.001). After 12 h of iNO treatment, hypoxic condition improved obviously, oxygenation indices in 12 h, 24 h, 36 h,48 h, 60 h and 72 h in the iNO group were significantly higher than those in the control group (P<0.05). Conclusion The treatment of severe hypoxemia after Sun’s surgery with low-dose of iNO is safe and effective, can significantly improve oxygenation function, and has significant advantages in shortening ventilator use time, postoperative ICU stay and postoperative hospital stay, but it is not significant in changing postoperative mortality.

Citation： MA Xiaozhong, ZHANG Shaopeng, BAI Yunpeng, WU Zhenhua, ZHAO Feng, CHEN Qingliang, JIANG Nan. Efficacy of low-dose inhaled nitric oxide in the treatment of severe hypoxemia after Sun’soperation: A retrospective cohort study. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2024, 31(5): 762-767. doi: 10.7507/1007-4848.202310042 Copy

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2.	Sun L, Qi R, Zhu J, et al. Total arch replacement combined with stented elephant trunk implantation: A new "standard" therapy for type A dissection involving repair of the aortic arch? Circulation, 2011, 123(9): 971-978.
3.	Ma WG, Zhang W, Wang LF, et al. Type A aortic dissection with arch entry tear: Surgical experience in 104 patients over a 12-year period. J Thorac Cardiovasc Surg, 2016, 151(6): 1581-1592.
4.	Gong M, Wu Z, Xu S, et al. Increased risk for the development of postoperative severe hypoxemia in obese women with acute type A aortic dissection. J Cardiothorac Surg, 2019, 14(1): 81.
5.	Song XC, Nie S, Xiao JL, et al. Risk factors and long-term prognosis for postoperative hypoxemia in patients with acute type A aortic dissection: A retrospective observational study. Medicine (Baltimore), 2022, 101(50): e32337.
6.	Stephens RS, Shah AS, Whitman GJ. Lung injury and acute respiratory distress syndrome after cardiac surgery. Ann Thorac Surg, 2013, 95(3): 1122-1129.
7.	Lai MY, Chu SM, Lakshminrusimha S, et al. Beyond the inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Pediatr Neonatol, 2018, 59(1): 15-23.
8.	Nakane T, Esaki J, Ueda R, et al. Inhaled nitric oxide improves pulmonary hypertension and organ functions after adult heart valve surgeries. Gen Thorac Cardiovasc Surg, 2021, 69(12): 1519-1526.
9.	Duan XZ, Xu ZY, Lu FL, et al. Inflammation is related to preoperative hypoxemia in patients with acute Stanford type A aortic dissection. J Thorac Dis, 2018, 10(3): 1628-1634.
10.	Sheng W, Le S, Song Y, et al. Preoperative nomogram and risk calculator for postoperative hypoxemia and related clinical outcomes following Stanford type A acute aortic dissection surgery. Front Cardiovasc Med, 2022, 9: 851447.
11.	Wang Y, Xue S, Zhu H. Risk factors for postoperative hypoxemia in patients undergoing Stanford A aortic dissection surgery. J Cardiothorac Surg, 2013, 8: 118.
12.	Rossaint R, Falke KJ, López F, et al. Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med, 1993, 328(6): 399-405.
13.	Dellinger RP, Trzeciak SW, Criner GJ, et al. Association between inhaled nitric oxide treatment and long-term pulmonary function in survivors of acute respiratory distress syndrome. Crit Care, 2012, 16(2): R36.
14.	El Kebir D, Hubert B, Taha R, et al. Effects of inhaled nitric oxide on inflammation and apoptosis after cardiopulmonary bypass. Chest, 2005, 128(4): 2910-2917.
15.	Waldow T, Alexiou K, Witt W, et al. Attenuation of reperfusion-induced systemic inflammation by preconditioning with nitric oxide in an in situ porcine model of normothermic lung ischemia. Chest, 2004, 125(6): 2253-2259.
16.	Lang JD, Smith AB, Brandon A, et al. A randomized clinical trial testing the anti-inflammatory effects of preemptive inhaled nitric oxide in human liver transplantation. PLoS One, 2014, 9(2): e86053.
17.	Li Z, Zhang H, Baraghtha S, et al. Short- and mid-term survival prediction in patients with acute type A aortic dissection undergoing surgical repair: Based on the systemic immune-inflammation index. J Inflamm Res, 2022, 15: 5785-5799.
18.	Xu H, Wang H, Wu L, et al. Prognostic value of systemic inflammation response index in acute type A aortic dissection. World J Surg, 2023, 47(10): 2554-2561.
19.	Qin C, Zhang H, Gu J, et al. Dynamic monitoring of platelet activation and its role in post-dissection inflammation in a canine model of acute type A aortic dissection. J Cardiothorac Surg, 2016, 11(1): 86.
20.	Al Sulaiman K, Korayem GB, Altebainawi AF, et al. Evaluation of inhaled nitric oxide (iNO) treatment for moderate-to-severe ARDS in critically ill patients with COVID-19: A multicenter cohort study. Crit Care, 2022, 26(1): 304.
21.	Olsson C, Franco-Cereceda A. Impact of organ failure and major complications on outcome in acute type A aortic dissection. Scand Cardiovasc J, 2013, 47(6): 352-358.
22.	Gebistorf F, Karam O, Wetterslev J, et al. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults. Cochrane Database Syst Rev, 2016, 2016(6): CD002787.
23.	Ri HS, Son HJ, Oh HB, et al. Inhaled nitric oxide therapy was not associated with postoperative acute kidney injury in patients undergoing lung transplantation: A retrospective pilot study. Medicine (Baltimore), 2018, 97(22): e10915.
24.	Spina S, Lei C, Pinciroli R, et al. Hemolysis and kidney injury in cardiac surgery: The protective role of nitric oxide therapy. Semin Nephrol, 2019, 39(5): 484-495.
25.	Gerlach H, Keh D, Semmerow A, et al. Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: A prospective, randomized, controlled study. Am J Respir Crit Care Med, 2003, 167(7): 1008-1015.
26.	Yoshiyasu N, Sato M, Nakajima D, et al. Current status of inhaled nitric oxide therapy for lung transplantation in Japan: A nationwide survey. Gen Thorac Cardiovasc Surg, 2021, 69(10): 1421-1431.
27.	Laube M, Amann E, Uhlig U, et al. Inflammatory mediators in tracheal aspirates of preterm infants participating in a randomized trial of inhaled nitric oxide. PLoS One, 2017, 12(1): e0169352.
28.	Kamenshchikov NO, Duong N, Berra L. Nitric oxide in cardiac surgery: A review article. Biomedicines, 2023, 11(4): 1085.
29.	Campelo AE, Cutini PH, Massheimer VL. Testosterone modulates platelet aggregation and endothelial cell growth through nitric oxide pathway. J Endocrinol, 2012, 213(1): 77-87.
30.	Gries A, Bode C, Peter K, et al. Inhaled nitric oxide inhibits human platelet aggregation, P-selectin expression, and fibrinogen binding in vitro and in vivo. Circulation, 1998, 97(15): 1481-1487.

1. Gaggero G, Valle L, Ferro J, et al. Type A aortic dissection. Autops Case Rep, 2021, 12: e2021346.
2. Sun L, Qi R, Zhu J, et al. Total arch replacement combined with stented elephant trunk implantation: A new "standard" therapy for type A dissection involving repair of the aortic arch? Circulation, 2011, 123(9): 971-978.
3. Ma WG, Zhang W, Wang LF, et al. Type A aortic dissection with arch entry tear: Surgical experience in 104 patients over a 12-year period. J Thorac Cardiovasc Surg, 2016, 151(6): 1581-1592.
4. Gong M, Wu Z, Xu S, et al. Increased risk for the development of postoperative severe hypoxemia in obese women with acute type A aortic dissection. J Cardiothorac Surg, 2019, 14(1): 81.
5. Song XC, Nie S, Xiao JL, et al. Risk factors and long-term prognosis for postoperative hypoxemia in patients with acute type A aortic dissection: A retrospective observational study. Medicine (Baltimore), 2022, 101(50): e32337.
6. Stephens RS, Shah AS, Whitman GJ. Lung injury and acute respiratory distress syndrome after cardiac surgery. Ann Thorac Surg, 2013, 95(3): 1122-1129.
7. Lai MY, Chu SM, Lakshminrusimha S, et al. Beyond the inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Pediatr Neonatol, 2018, 59(1): 15-23.
8. Nakane T, Esaki J, Ueda R, et al. Inhaled nitric oxide improves pulmonary hypertension and organ functions after adult heart valve surgeries. Gen Thorac Cardiovasc Surg, 2021, 69(12): 1519-1526.
9. Duan XZ, Xu ZY, Lu FL, et al. Inflammation is related to preoperative hypoxemia in patients with acute Stanford type A aortic dissection. J Thorac Dis, 2018, 10(3): 1628-1634.
10. Sheng W, Le S, Song Y, et al. Preoperative nomogram and risk calculator for postoperative hypoxemia and related clinical outcomes following Stanford type A acute aortic dissection surgery. Front Cardiovasc Med, 2022, 9: 851447.
11. Wang Y, Xue S, Zhu H. Risk factors for postoperative hypoxemia in patients undergoing Stanford A aortic dissection surgery. J Cardiothorac Surg, 2013, 8: 118.
12. Rossaint R, Falke KJ, López F, et al. Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med, 1993, 328(6): 399-405.
13. Dellinger RP, Trzeciak SW, Criner GJ, et al. Association between inhaled nitric oxide treatment and long-term pulmonary function in survivors of acute respiratory distress syndrome. Crit Care, 2012, 16(2): R36.
14. El Kebir D, Hubert B, Taha R, et al. Effects of inhaled nitric oxide on inflammation and apoptosis after cardiopulmonary bypass. Chest, 2005, 128(4): 2910-2917.
15. Waldow T, Alexiou K, Witt W, et al. Attenuation of reperfusion-induced systemic inflammation by preconditioning with nitric oxide in an in situ porcine model of normothermic lung ischemia. Chest, 2004, 125(6): 2253-2259.
16. Lang JD, Smith AB, Brandon A, et al. A randomized clinical trial testing the anti-inflammatory effects of preemptive inhaled nitric oxide in human liver transplantation. PLoS One, 2014, 9(2): e86053.
17. Li Z, Zhang H, Baraghtha S, et al. Short- and mid-term survival prediction in patients with acute type A aortic dissection undergoing surgical repair: Based on the systemic immune-inflammation index. J Inflamm Res, 2022, 15: 5785-5799.
18. Xu H, Wang H, Wu L, et al. Prognostic value of systemic inflammation response index in acute type A aortic dissection. World J Surg, 2023, 47(10): 2554-2561.
19. Qin C, Zhang H, Gu J, et al. Dynamic monitoring of platelet activation and its role in post-dissection inflammation in a canine model of acute type A aortic dissection. J Cardiothorac Surg, 2016, 11(1): 86.
20. Al Sulaiman K, Korayem GB, Altebainawi AF, et al. Evaluation of inhaled nitric oxide (iNO) treatment for moderate-to-severe ARDS in critically ill patients with COVID-19: A multicenter cohort study. Crit Care, 2022, 26(1): 304.
21. Olsson C, Franco-Cereceda A. Impact of organ failure and major complications on outcome in acute type A aortic dissection. Scand Cardiovasc J, 2013, 47(6): 352-358.
22. Gebistorf F, Karam O, Wetterslev J, et al. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults. Cochrane Database Syst Rev, 2016, 2016(6): CD002787.
23. Ri HS, Son HJ, Oh HB, et al. Inhaled nitric oxide therapy was not associated with postoperative acute kidney injury in patients undergoing lung transplantation: A retrospective pilot study. Medicine (Baltimore), 2018, 97(22): e10915.
24. Spina S, Lei C, Pinciroli R, et al. Hemolysis and kidney injury in cardiac surgery: The protective role of nitric oxide therapy. Semin Nephrol, 2019, 39(5): 484-495.
25. Gerlach H, Keh D, Semmerow A, et al. Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: A prospective, randomized, controlled study. Am J Respir Crit Care Med, 2003, 167(7): 1008-1015.
26. Yoshiyasu N, Sato M, Nakajima D, et al. Current status of inhaled nitric oxide therapy for lung transplantation in Japan: A nationwide survey. Gen Thorac Cardiovasc Surg, 2021, 69(10): 1421-1431.
27. Laube M, Amann E, Uhlig U, et al. Inflammatory mediators in tracheal aspirates of preterm infants participating in a randomized trial of inhaled nitric oxide. PLoS One, 2017, 12(1): e0169352.
28. Kamenshchikov NO, Duong N, Berra L. Nitric oxide in cardiac surgery: A review article. Biomedicines, 2023, 11(4): 1085.
29. Campelo AE, Cutini PH, Massheimer VL. Testosterone modulates platelet aggregation and endothelial cell growth through nitric oxide pathway. J Endocrinol, 2012, 213(1): 77-87.
30. Gries A, Bode C, Peter K, et al. Inhaled nitric oxide inhibits human platelet aggregation, P-selectin expression, and fibrinogen binding in vitro and in vivo. Circulation, 1998, 97(15): 1481-1487.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Efficacy of low-dose inhaled nitric oxide in the treatment of severe hypoxemia after Sun’soperation: A retrospective cohort study

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