pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLCpulmo-2556Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESЭффективность и безопасность ингаляционного оксида азота при острой легочной гипертензии у больных с обострением ХОБЛEfficacy and safety of inhaled nitric oxide in patients with acute pulmonary hypertension due to exacerbation of chronic obstructive pulmonary disease (COPD)АвдеевC. H.AvdeevS. N.

Москва

ЦареваH. А.TsarevaN. A.

Москва

НеклюдоваГ. B.NekludovaG. V.

Москва

ЧучалинА. Г.ChuchalinA. G.

Москва

НИИ пульмонологии Минздрава РФRussian Federation200419082021028996Copyright © Авдеев C.H., Царева H.А., Неклюдова Г.B., Чучалин А.Г., 20212021Авдеев C.H., Царева H.А., Неклюдова Г.B., Чучалин А.Г.Avdeev S.N., Tsareva N.A., Nekludova G.V., Chuchalin A.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/2556

Задачи исследования — изучить эффекты ингаляционного оксида азота (iNO) на легочную гемодинамику и газообмен у больных с легочной гипертензией на фоне обострения ХОБЛ, выявить оптимальную дозу iNO, оценить факторы-предикторы ответа на iNO.

Пациенты — 15 больных с обострением ХОБЛ (3 женщины, 12 мужчин; средний возраст 58,0 ± 6,4 года; FEV1 0,88 ± 0,24 л; РаO2 52,6 ± 3,5 мм рт. ст.; РаСO2 49,4 ± 8,2 мм рт. ст.), не требующих респираторной поддержки.

Параметры гемодинамики и оксигенации оценивались до начала исследования (на фоне 0 2) и затем последовательно в конце сеансов iNO в концентрациях 10, 20 и 30 ppm (на фоне 0 2). Пациенты считались "ответчиками" при наличии снижения среднего давления в легочной артерии (Рра) или легочного сосудистого сопротивления (PVR) более чем на 20 % . Для постоянного контроля NO и NO2 был использован  электрохимический анализатор PrinterNOx.

На фоне терапии iNO наблюдалось улучшение легочной гемодинамики: Рра снизилось от 36 ± 6  до 28 ± 3 мм рт. ст. (р < 0,01), PVR снизилось от 371 ± 83 до 249 ± 49 дин с/см-5 (р < 0,01), сердечный индекс не изменился. При iNO 10 ppm наблюдалось достоверное улучшение оксигенации ( Р а 0 2 повысилось от 64 ± 6 до 6 8  ± 9 мм рт. ст., р < 0,01; Qs/Qt уменьшилось от 23 ± 5 до 20 ± 4 % , р < 0,05),  а С 0 2 не изменилось. 12 (80 % ) больных ответили на терапию ¡NO. Была выявлена корреляция между изменениями Рра и PVR и базальными уровнями Рра и PVR (все р < 0,01) и показателем pH артериальной крови (все р < 0,05).

Заключение. ¡NO достоверно улучшает показатели легочной гемодинамики и газообмена у больных с обострением ХОБЛ, оптимальная доза ¡N 0 для терапии легочной гипертензии и гипоксемии составляет 10 ppm. Ответ на ¡NO выше у больных с более высокими значениями Рра и PVR и респираторным ацидозом.

The study objective was to assess effects of inhaled nitric oxide (iNO) on pulmonary hemodynamics and gas exchange in patients with acute cor pulmonale due to acute exacerbation of COPD and to evaluate an optimal dose and factors predicting the response to iNO in these patients.

Fifteen patients (3 females, 12 males; mean age of 58.0 ± 6.4 yrs; FEV1 0.88 ± 0.24 L; PaO2 52.6 ± 3.5 mm Hg; PaCO2 49.4 ± 8.2 mm Hg) with acute exacerbation of COPD, not requiring respiratory support were involved to the study.

Oxygenation and haemodynamic variables were measured initially against the supplemental oxygen back­ ground and then 15 min after each sequential addition of 10, 20, and 30 ppm iNO to the gas mixture. The patients were considered as responders if the mean pulmonary artery pressure (Ppa) or the pulmonary vascular resistance (PVR) decreased by 20 % . An electrochemical gas sensor device PrinterNOx provided continuous analysis of nitric oxide and oxidative nitric oxide products.

There was an improvement in haemodynamic variables during the iNO inhalations: Poa decreased from 36 ± 6 to 28 ± 3 mm Hg, PVR decreased from 371 ± 83 to 249 ± 49 dyne sec/cm-5 (all p < 0.01), the cardiac index did not change. There was a mild but significant improvement in oxygenation at 10 ppm iNO ( P a 0 2 increased from 64 ± 6 to 6 8 ± 9 mm Hg, p < 0.01, and Qs/Qt reduced from 23 ± 5 to 20 ± 4 % , p < 0.05), Pa C 0 2 remained unchanged. Twelve patients (80 % ) responded to iNO. The ¡NO-induced decrease in Ppa and PVR correlated positively with the basal Ppa and PVR (all p< 0 .01 ) and negatively with the basal pH (all p < 0.05).

Conclusion. Our data show that iNO improves the pulmonary hemodynamics and oxygenation in patients with acute exacerbation of COPD and that the optimal iNO dose for the treatment of both pulmonary hyper tension and hypoxemia was 10 ppm. The response to iNO was greater in patients with more severe pulmonary hypertension and respiratory acidosis.

ReferencesMacNee W. State of the art: Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease (Parts 1). Am. J. Respir. Crit. Care Med. 1994; 150: 833-852.MacNee W. State of the art: Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease (Parts 1). Am. J. Respir. Crit. Care Med. 1994; 150: 833-852.Weitzenblum E., Hirth C., Roeslin N. et al. Les modification hemodynamiques pulmonaire au cours de l'insuffisance respiratoire aiguë des bronchopneumopathies chroniques. Respiration 1971;28:539-554.Weitzenblum E., Hirth C., Roeslin N. et al. Les modification hemodynamiques pulmonaire au cours de l'insuffisance respiratoire aiguë des bronchopneumopathies chroniques. Respiration 1971;28:539-554.Cremona G., Higenbottam T. Is there a place for vasodilators in stable COPD? In: Similowski T., Whitelaw W.A., Derenne J.-P., eds. Clinical management of stable COPD. New York: Marcel Dekker. Inc., 2002. 359-382.Cremona G., Higenbottam T. Is there a place for vasodilators in stable COPD? In: Similowski T., Whitelaw W.A., Derenne J.-P., eds. Clinical management of stable COPD. New York: Marcel Dekker. Inc., 2002. 359-382.Peinado V., Santos S., Ramirez J. et al. Response to hypoxia of pulmonary arteries in chronic obstructive pulmonary disease: an in vitro study. Eur. Respir. J. 2002; 20: 332-338.Peinado V., Santos S., Ramirez J. et al. Response to hypoxia of pulmonary arteries in chronic obstructive pulmonary disease: an in vitro study. Eur. Respir. J. 2002; 20: 332-338.Hart C.M. Nitric oxide in adult lung disease. Chest 1999; 115: 1407-1417.Hart C.M. Nitric oxide in adult lung disease. Chest 1999; 115: 1407-1417.Germann P., Ziesche R., Leitner C. et al. Addition of nitric oxide to oxygen improves cardiopulmonary function in patients with severe COPD. Chest 1998; 114: 29-35.Germann P., Ziesche R., Leitner C. et al. Addition of nitric oxide to oxygen improves cardiopulmonary function in patients with severe COPD. Chest 1998; 114: 29-35.Roger N., Barbera J.A., Roca J. et al. Nitric oxide inhalation during exercise in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 1997; 156: 800-806.Roger N., Barbera J.A., Roca J. et al. Nitric oxide inhalation during exercise in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 1997; 156: 800-806.Baigorri F., Joseph D., Artigas A., Blanch L. Inhaled nitric oxide does not improve cardiac or pulmonary function in patients with an exacerbation of chronic obstructive pulmonary disease. Crit. Care Med. 1999; 27: 2153-2158.Baigorri F., Joseph D., Artigas A., Blanch L. Inhaled nitric oxide does not improve cardiac or pulmonary function in patients with an exacerbation of chronic obstructive pulmonary disease. Crit. Care Med. 1999; 27: 2153-2158.Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. N H L B I/ W H O workshop report. Publication N 2701, April 2001. 1-100.Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. N H L B I/ W H O workshop report. Publication N 2701, April 2001. 1-100.Jardin F., Dubourg О., Bourdorias J.P. Echocardiographic paatern of acute cor pulmonale. Chest 1997; 111: 209-217.Jardin F., Dubourg О., Bourdorias J.P. Echocardiographic paatern of acute cor pulmonale. Chest 1997; 111: 209-217.Sitbon O., Humbert М., Jagot J.L. et al. Inhaled nitric oxide as a screening agent for sagely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension. Eur. Respir. J. 1998; 12: 265-270.Sitbon O., Humbert М., Jagot J.L. et al. Inhaled nitric oxide as a screening agent for sagely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension. Eur. Respir. J. 1998; 12: 265-270.Chemla D., Castelain V., Herue P. et al. Haemodynamic evaluation of pulmonary hypertension. Eur. Respir. J. 2002; 20: 1314-1331.Chemla D., Castelain V., Herue P. et al. Haemodynamic evaluation of pulmonary hypertension. Eur. Respir. J. 2002; 20: 1314-1331.Авдеев C.H., Царева H.А., Неклюдова Г.В. и др. Ингаляционный оксид азота при первичной легочной гипертензии: влияние на легочную гемодинамику, газообмен и транспорт кисло­ рода. Пульмонология 2001; 4: 34-39.Авдеев C.H., Царева H.А., Неклюдова Г.В. и др. Ингаляционный оксид азота при первичной легочной гипертензии: влияние на легочную гемодинамику, газообмен и транспорт кисло­ рода. Пульмонология 2001; 4: 34-39.Kitabatake A., ¡noue М., Asao М. et al. Noninvasive evaluation of pulmonary hypertension by a pulsed doppler technique. Circulation 1983; 68: 302-309.Kitabatake A., ¡noue М., Asao М. et al. Noninvasive evaluation of pulmonary hypertension by a pulsed doppler technique. Circulation 1983; 68: 302-309.Quanjer P.H., Tammeling G.J., Cotes J.E. et al. Lung volumes and forced ventilatory flows. Eur Respir J 1993; 6 (suppl. 16): 5-40.Quanjer P.H., Tammeling G.J., Cotes J.E. et al. Lung volumes and forced ventilatory flows. Eur Respir J 1993; 6 (suppl. 16): 5-40.Pepke-Zaba J., H igenbottam T.W ., Dinh-Xuan A.T. et al. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet 1991; 338: 1173-1174.Pepke-Zaba J., H igenbottam T.W ., Dinh-Xuan A.T. et al. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet 1991; 338: 1173-1174.Ignarro L.J. Biological actions and properties of endothelium- derived nitric oxide formed and released from artery and vein. Circ. Res. 1989; 65: 1-21.Ignarro L.J. Biological actions and properties of endothelium- derived nitric oxide formed and released from artery and vein. Circ. Res. 1989; 65: 1-21.M oinard J., M anier G., Pillet О. et al. Effect of inhaled nitric oxide on hemodynamics and V / Q inequalities in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 1994; 149: 1482-1487.M oinard J., M anier G., Pillet О. et al. Effect of inhaled nitric oxide on hemodynamics and V / Q inequalities in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 1994; 149: 1482-1487.Barbera J.A., Roger N., Roca J. et. al. Worsening of pulmonary gas exchange with nitric oxide inhalation in chronic obstructive pulmonary disease. Lancet 1996; 347: 436-440.Barbera J.A., Roger N., Roca J. et. al. Worsening of pulmonary gas exchange with nitric oxide inhalation in chronic obstructive pulmonary disease. Lancet 1996; 347: 436-440.Yoshida М., Taguchi O., Gabazza E.C. et al. Combined inhalation of nitric oxide and oxygen in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 1997; 155: 526-529.Yoshida М., Taguchi O., Gabazza E.C. et al. Combined inhalation of nitric oxide and oxygen in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 1997; 155: 526-529.Wagner P.D., D antzker D.R., Dueck R. et al. Ventilation-perfusion inequality in chronic obstructive pulmonary disease. J. Clin. Invest. 1977; 59: 203-216.Wagner P.D., D antzker D.R., Dueck R. et al. Ventilation-perfusion inequality in chronic obstructive pulmonary disease. J. Clin. Invest. 1977; 59: 203-216.Hopkins S.R., Johnson E.C., Richardson R.S. et al. Effects of inhaled nitric oxide on gas exchange in lungs with shunt or poorly ventilated areas. Am. J. Respir. Crit. Care Med. 1997; 156: 484-491.Hopkins S.R., Johnson E.C., Richardson R.S. et al. Effects of inhaled nitric oxide on gas exchange in lungs with shunt or poorly ventilated areas. Am. J. Respir. Crit. Care Med. 1997; 156: 484-491.Gerlach H., Rossaint R., Pappert D., Falke K. Time-course and dose-response of nitric oxide inhalation for systemic oxygenation and pulmonary hypertension in patients with adult respiratory distress syndrome. Eur. J. Clin. Invest. 1993; 23: 499-502.Gerlach H., Rossaint R., Pappert D., Falke K. Time-course and dose-response of nitric oxide inhalation for systemic oxygenation and pulmonary hypertension in patients with adult respiratory distress syndrome. Eur. J. Clin. Invest. 1993; 23: 499-502.Puybasset L., Stew art T., Rouby J.-J. et al. Inhaled nitric oxide reverses the increase in pulmonary vascular resistance induced by permissive hypercapnia in patients with acute respiratory distress syndrome. Anesthesiology 1994; 80: 1254-1267.Puybasset L., Stew art T., Rouby J.-J. et al. Inhaled nitric oxide reverses the increase in pulmonary vascular resistance induced by permissive hypercapnia in patients with acute respiratory distress syndrome. Anesthesiology 1994; 80: 1254-1267.Le Cras T.D., M cM urtry I.E. Nitric oxide production in the hypoxic lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 2001; 280: L575-L582.Le Cras T.D., M cM urtry I.E. Nitric oxide production in the hypoxic lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 2001; 280: L575-L582.Giaid A., Saleh D. Reduced expression of endothelial nitric oxide synthase in the lung of patients with pulmonary hyperten­ sion. N. Engl. J. Med. 1995; 333: 214-221.Giaid A., Saleh D. Reduced expression of endothelial nitric oxide synthase in the lung of patients with pulmonary hyperten­ sion. N. Engl. J. Med. 1995; 333: 214-221.Clini E., Cremona G., Сатрапа M. et al. Production of endogenous nitric oxide in chronic obstructive pulmonary disease and patients with cor pulmonale. Correlates with Echo-Doppler assessment. Am. J. Respir. Crit. Care Med. 2000; 162: 446-450.Clini E., Cremona G., Сатрапа M. et al. Production of endogenous nitric oxide in chronic obstructive pulmonary disease and patients with cor pulmonale. Correlates with Echo-Doppler assessment. Am. J. Respir. Crit. Care Med. 2000; 162: 446-450.Zieche R., Petkou V., Williams J. et al. Lipopolysaccharide and interleukin 1 augment the effects of hypoxia and inflammation in chronic obstructive pulmonary disease. Proc. Natl. Acad. Sci. USA 1996; 93: 12478-12483.Zieche R., Petkou V., Williams J. et al. Lipopolysaccharide and interleukin 1 augment the effects of hypoxia and inflammation in chronic obstructive pulmonary disease. Proc. Natl. Acad. Sci. USA 1996; 93: 12478-12483.Gibbons G.H. Endothelial function as a determinant of vascular function and structure: A new therapeutic target. Am. J. Cardiol. 1997; 79: 3-8.Gibbons G.H. Endothelial function as a determinant of vascular function and structure: A new therapeutic target. Am. J. Cardiol. 1997; 79: 3-8.

The authors declare that there are no conflicts of interest present.