Use of inhaled vasodilators in ARDS patients

Hamza Alhawamleh; Sadeen  Zein Eddin; Yara Almadani; Basel Naim Alrawashdeh; Mazen Al-Qadi

doi:10.58877/japaj.v2i1.131

Authors

Hamza Alhawamleh Jordan University of science and technology, School of medicine. Internal Medicine Department, Tafila Govermental Hospital, Al- Tafila, Jordan https://orcid.org/0009-0008-5340-1867
Sadeen Zein Eddin Mutah University, School of Medicine https://orcid.org/0000-0003-1388-3159
Yara Almadani University of Jordan , School of medicine
Basel Naim Alrawashdeh Jordanian Royal Medical Services, Amman, Jordan
Mazen Al-Qadi University of Pittsburgh , Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine

DOI:

https://doi.org/10.58877/japaj.v2i1.131

Keywords:

ARDS, management, inhaled vasodilators

Abstract

Abstract:

Acute Respiratory Distress Syndrome (ARDS) is a severe lung injury leading to bilateral lung opacities and severe hypoxemic respiratory failure. It results from acute inflammation, endothelial dysfunction, and disruption of the alveolar-capillary membrane. ARDS management encompasses lung-protective supportive care such as lung-protective ventilation strategies. Inhaled pulmonary vasodilators show potential as adjunctive therapies for refractory hypoxemia and hold promise in improving oxygenation and reducing pulmonary vascular resistance in severe ARDS. However, their impact on mortality remains uncertain and current evidence supports their role as rescue therapies. Prudent consideration and assessment of potential benefits and risks are crucial when integrating these agents into clinical practice.

References

References:

Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA [Internet]. 2016;315(8):788–800. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26903337?dopt=Abstract DOI: https://doi.org/10.1001/jama.2016.0291

Ware LB, Matthay MA. The Acute Respiratory Distress Syndrome. New England Journal of Medicine [Internet]. 2000 May 4;342(18):1334–49. Available from: https://www.nejm.org/doi/full/10.1056/NEJM200005043421806

Fan E, Brodie D, Slutsky AS. Acute Respiratory Distress Syndrome. JAMA. 2018 Feb 20;319(7):698. DOI: https://doi.org/10.1001/jama.2017.21907

SteinbergKP, HudsonLD, GoodmanRB, etal. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med. 2006;354(16):1671-1684. DOI: https://doi.org/10.1056/NEJMoa051693

Tongyoo S, Permpikul C, Mongkolpun W, et al. Hydrocortisone treatment in early sepsis-associated acute respiratory distresssyndrome: results of a randomized controlled trial. Crit Care. 2016;20(1):329. DOI: https://doi.org/10.1186/s13054-016-1511-2

Villar J, Ferrando C, Martínez D, et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre,randomised controlled trial. Lancet Respir Med. 2020;8(3):267-276. DOI: https://doi.org/10.1016/S2213-2600(19)30417-5

RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with Covid-19: preliminary report. N Engl J Med. 2020 Jul 17;NEJMoa2021436.

Afshari A, Brok J, Møller AM, Wetterslev J. Inhaled Nitric Oxide for Acute Respiratory Distress Syndrome and Acute Lung Injury in Adults and Children. Anesthesia & Analgesia. 2011 Jun;112(6):1411–21.

Raffin, T.A. ARDS: Mechanisms and Management. Hosp. Pract. 1987, 22, 65–80. [CrossRef] DOI: https://doi.org/10.1080/21548331.1987.11703362

Zaid Y., Guessous F., Puhm F., Elhamdani W., Chentoufi L., Morris A.C., Cheikh A., Jalali F., Boilard E., Flamand L. Platelet reactivity to thrombin differs between patients with COVID-19 and those with ARDS unrelated to COVID-19. Blood Adv. 2021;5:635–639. doi: 10.1182/bloodadvances.2020003513. [PMC free article] [PubMed] [CrossRef] [Google Scholar] [Ref list] DOI: https://doi.org/10.1182/bloodadvances.2020003513

Fuller B.M., Mohr N.M., Skrupky L., Fowler S., Kollef M.H., Carpenter C.R. The Use of Inhaled Prostaglandins in Patients With ARDS. Chest. 2015;147:1510–1522. doi: 10.1378/chest.14-3161. [PMC free article] [PubMed] [CrossRef] [Google Scholar] [Ref list]

Rossaint, R.; Falke, K.J.; Lopez, F.; Slama, K.; Pison, U.; Zapol, W.M. Inhaled Nitric Oxide for the Adult Respiratory Distress Syndrome. N. Engl. J. Med. 1993, 328, 399–405. [CrossRef]

Lisi, F.; Zelikin, A.N.; Chandrawati, R. Nitric Oxide to Fight Viral Infections. Adv. Sci. 2021, 8, 2003895. [CrossRef] [PubMed] DOI: https://doi.org/10.1002/advs.202003895

Yu, B.; Ichinose, F.; Bloch, D.B.; Zapol,W.M. Inhaled nitric oxide. Br. J. Pharmacol. 2019, 176, 246–255. [CrossRef] DOI: https://doi.org/10.1111/bph.14512

McIntyre RC, Jr., et al. Thirty years of clinical trials in acute respiratory distress syndrome. Crit Care Med. 2000;28(9):3314-31. DOI: https://doi.org/10.1097/00003246-200009000-00034

Shoemaker WC. Controversies in the pathophysiology and fluid management of postoperative adult respiratory distress syndrome. Surg Clin North Am 1985;65(4):931-63 DOI: https://doi.org/10.1016/S0039-6109(16)43688-1

Zimmerman JL, Hanania NA. Vasodilators in mechanical ventilation. Crit Care Clin 1998;14(4):611-27. DOI: https://doi.org/10.1016/S0749-0704(05)70023-3

Kadowitz PJ, et al. Pulmonary and systemic vasodilator effects of the newly discovered prostaglandin, PGI2. J Appl Physiol 1978;45(3):408-13. DOI: https://doi.org/10.1152/jappl.1978.45.3.408

GlaxoSmithKline. Flolan packageinsert. 2001.

van Heerden PV. Systemic levels of 6- keto-prostaglandin F1 alpha following administration of inhaled aerosolized prostacyclin. Anaesth Intensive Care 1997;25(6):701-3. DOI: https://doi.org/10.1177/0310057X9702500620

Taylor RW, Zimmerman JL, Dellinger RP, Straube RC, Criner GJ, Davis K, Kelly KM, Smith TC, Small RJ, Inhaled nitric oxide in ARDS study group low- dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial, JAMA 291 (2004) 1603–1609, 10.1001/jama.291.13.1603. [PubMed: 15069048] DOI: https://doi.org/10.1001/jama.291.13.1603

Rossaint R, Falke KJ, Lopez F, et al. Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med. 1993;328:399–405. DOI: https://doi.org/10.1056/NEJM199302113280605

Benzing A, Geiger K. Inhaled nitric oxide lowers pulmonary capillary pressure and changes longitudinal distribution of pulmonary vascular resistance in patients with acute lung injury. Acta Anaesthesiol Scand. 1994;38:640–645. DOI: https://doi.org/10.1111/j.1399-6576.1994.tb03970.x

Benzing A, Brautigam P, Geiger K, et al. Inhaled nitric oxide reduces pulmonary transvascular albumin flux in patients with acute lung injury. Anesthesiology. 1995;83:1153–1161. DOI: https://doi.org/10.1097/00000542-199512000-00004

Gibson, L.E.; Di Fenza, R.; Lang, M.; Capriles, M.I.; Li, M.D.; Kalpathy-Cramer, J.; Little, B.P.; Arora, P.; Mueller, A.L.; Ichinose, F.; et al. Right Ventricular Strain Is Common in Intubated COVID-19 Patients and Does Not Reflect Severity of Respiratory Illness. J. Intensive Care Med. 2021, 36, 900–909. [CrossRef] DOI: https://doi.org/10.1177/08850666211006335

Sato, R.; Dugar, S.; Cheungpasitporn, W.; Schleicher, M.; Collier, P.; Vallabhajosyula, S.; Duggal, A. The impact of right ventricular injury on the mortality in patients with acute respiratory distress syndrome: A systematic review and meta-analysis. Crit. Care 2021, 25, 172. [CrossRef] DOI: https://doi.org/10.1186/s13054-021-03591-9

19 Dessap, A.M.; Boissier, F.; Charron, C.; Bégot, E.; Repessé, X.; Legras, A.; Brun-Buisson, C.; Vignon, P.; Vieillard-Baron, A. Acute corpulmonale during protective ventilation for acute respiratory distress syndrome: Prevalence, predictors, and clinical impact. Intensive Care Med. 2015, 42, 862–870. [CrossRef] DOI: https://doi.org/10.1007/s00134-015-4141-2

Gebistorf F, Karam O, Wetterslev J, Afshari A, Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults, Cochrane Database Syst. Rev. (2016) CD002787, 10.1002/14651858.CD002787.pub3.

Adhikari NKJ, Burns KEA, Friedrich JO, Granton JT, Cook DJ, Meade MO, Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis, BMJ 334 (2007) 779, 10.1136/bmj.39139.716794.55. [PubMed: 17383982]

Afshari A, Brok J, Møller AM, Wetterslev J, Inhaled nitric oxide for acute respiratory distress syndrome and acute lung injury in adults and children: a systematic review with meta-analysis and trial sequential analysis, Anesth. Analg. 112 (2011) 1411–1421, 10.1213/ANE.0b013e31820bd185. DOI: https://doi.org/10.1213/ANE.0b013e31820bd185

Adhikari NK, Burns KE, Friedrich JO, Granton JT, Cook DJ, Meade MO. Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis. BMJ 2007;334(7597):779. [PUBMED:17383982] DOI: https://doi.org/10.1136/bmj.39139.716794.55

Valdivielso JM, Blantz RC. Acute renal failure: is nitric oxide the bad guy?. Antioxidants and Redox Signaling 2002; 4(6):925–34. [PUBMED: 12573141] DOI: https://doi.org/10.1089/152308602762197461

Clutton-Brock J. Two cases of poisoning by contamination of nitrous oxide with higher oxides of nitrogen during anaesthesia. Br J Anaesth 1967;39:388–92. DOI: https://doi.org/10.1093/bja/39.5.388

Greenbaum R, Bay J, Hargreaves MD, Kain ML, Kelman GR, Nunn JF, et al. Effects of higher oxides of nitrogen on the anesthetized dog. Br J Anaesth 1967;39:393–404. DOI: https://doi.org/10.1093/bja/39.5.393

Zwissler, B., Kemming, G., Habler, O., Kleen, M., Merkel, M., Haller, M. et al. (1996) Inhaled prostacyclin (PGI2) versus inhaled nitric oxide in adult respiratory distress syndrome. Am J Respir Crit Care Med 154: 1671–1677. DOI: https://doi.org/10.1164/ajrccm.154.6.8970353

Eisenhut, T., Sinha, B., Grottrup-Wolfers, E., Semmler, J., Siess, W. and Endres, S. (1993) Prostacyclin analogs suppress the synthesis of tumor necrosis factor-alpha in LPS-stimulated human peripheral blood mononuclear cells. Immunopharmacology 26: 259–264. DOI: https://doi.org/10.1016/0162-3109(93)90042-O

Wen, F., Watanabe, K. and Yoshida, M. (1996) Inhibitory effects of interleukin-6 on release of PGI2 by cultured human pulmonary artery smooth muscle cells. Prostaglandins 52: 93–102. DOI: https://doi.org/10.1016/0090-6980(96)00055-X

Ware, L. and Matthay, M. (2000) The acute respiratory distress syndrome. N Engl J Med 342: 1334–1349. DOI: https://doi.org/10.1056/NEJM200005043421806

GlaxoSmithKline (2011) Flolan (epoprostenol sodium) package insert. Research Triangle Park, NC: GlaxoSmithKline

Walmrath D, Schneider T, Schermuly R, Olschewski H, Grimminger F, Seeger W. Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome.AmJ Respir Crit Care Med 1996;153(3):991–996. DOI: https://doi.org/10.1164/ajrccm.153.3.8630585

Walmrath D, Schneider T, Pilch J, Grimminger F, Seeger W. Aerosolized prostacyclin in adult respiratory distress syndrome. Lancet 1993;342(8877):961–962. DOI: https://doi.org/10.1016/0140-6736(93)92004-D

Van Heerden PV, Webb SAR, Hee G, Corkeron M, Thompson WR. Inhaled aerosolized prostacyclin as a selective pulmonary vasodilator for the treatment of severe hypoxemia. Anaesth Intens Care 1996;24(1):87–90 DOI: https://doi.org/10.1177/0310057X9602400115

Pappert D, Busch T, Gerlach H, Lewandowski K, Radermacher P, Rossaint R. Aerosolized prostacyclin versus inhaled nitric oxide in children with severe acute respiratory distress syndrome. Anesthesiology 1995;82(6):1507–1511. DOI: https://doi.org/10.1097/00000542-199506000-00020

36 van Heerden PV, Barden A, Michalopoulos N, Bulsara MK, Roberts BL. Dose-response to inhaled aerosolized prostacyclin for hypoxemia due to ARDS. Chest 2000;117(3):819–827. DOI: https://doi.org/10.1378/chest.117.3.819

37 Bein T, Metz C, Keyl C, Sendtner E, Pfeifer M. Cardiovascular and pulmonary effects of aerosolized prostacyclin administration in severe respiratory failure using a ventilator nebulization system. J Cardiovasc Pharmacol 1996;27(4):583–586 DOI: https://doi.org/10.1097/00005344-199604000-00019

Domenighetti G, Stricker H, Waldispuehl B. Nebulized prostacyclin (PGI2) in acute respiratory distress syndrome: impact of primary (pulmonary injury) and secondary (extrapulmonary injury) disease on gas exchange response. Crit Care Med 2001; 29(1):57–62. DOI: https://doi.org/10.1097/00003246-200101000-00015

Walmrath D, Schneider T, Pilch J, Schermuly R, Grimminger F, Seeger W. Effects of aerosolized prostacyclin in severe pneumonia: impact of fibrosis. Am J Respir Crit Care Med 1995;151(3 Pt1):724–730. DOI: https://doi.org/10.1164/ajrccm/151.3_Pt_1.724

Dellinger RP, Zimmerman JL, Taylor RW, Straube RC, Hauser DL, Criner GJ, et al. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med 1998; 26(1):1523. DOI: https://doi.org/10.1097/00003246-199801000-00011

Burghuber OC, Silberbauer K, Haber P, Sinzinger H, Elliott M, Leithner C. Pulmonary and antiaggregatory effects of prostacyclin after inhalation and intravenous infusion. Respiration 1984;45(4): 450–454 DOI: https://doi.org/10.1159/000194653

Dahlem_P, van_Aalderen_WM, de_Neef_M, Dijkgraaf_MG, Bos_AP. Randomized controlled trial of aerosolized prostacyclin therapy in children with acute lung injury. Critical Care Medicine 2004;32(4):1055-60. [PUBMED: 15071401] DOI: https://doi.org/10.1097/01.CCM.0000120055.52377.BF

Siddiqui_S, Salahuddin_N, Zubair_S, Yousuf_M, Azam_I, Gilani_AH. Use of inhaled PGE1 to improve diastolic dysfunction, LVEDP, pulmonary hypertension and hypoxia in ARDS - a randomized clinical trial. Open Journal of Anesthesiology 2013;3(2):109-15. [DOI: 10.4236/ojanes.2013.32027] DOI: https://doi.org/10.4236/ojanes.2013.32027

Gebistorf F, Karam O, Wetterslev J, Afshari A. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults. Cochrane Database of Systematic Reviews. 2016 Jun 27; DOI: https://doi.org/10.1002/14651858.CD002787.pub3

Fuller BM, Mohr NM, Skrupky L, Fowler S, Kollef MH, Carpenter CR. The Use of Inhaled Prostaglandins in Patients With ARDS. Chest [Internet]. 2015 Jun;147(6):1510–22. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451707/ DOI: https://doi.org/10.1378/chest.14-3161

Simran Ganeriwal, Alves G, Schleicher M, Hockstein MA, Tonelli AR, Duggal A, et al. Right ventricle-specific therapies in acute respiratory distress syndrome: a scoping review. 2023 Mar 12;27(1). DOI: https://doi.org/10.1186/s13054-023-04395-9

Bijan Safaee Fakhr, Raffaele Di Fenza, Gianni S, Wiegand SB, Miyazaki Y, Morais A, et al. Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia. 2021 Nov 1;116:7–13. https://www.sciencedirect.com/science/article/pii/S1089860321000859?via%3Dihub DOI: https://doi.org/10.1016/j.niox.2021.08.003

Khokher W, Malhas SE, Beran A, Iftikhar S, Burmeister C, Mhanna M, et al. Inhaled Pulmonary Vasodilators in COVID-19 Infection: A Systematic Review and Meta-Analysis. Journal of Intensive Care Medicine. 2022 Aug 2;37(10):1370–82. https://doi.org/10.1177/08850666221118271 DOI: https://doi.org/10.1177/08850666221118271