Korean J Crit Care Med.  2017 May;32(2):154-163. 10.4266/kjccm.2016.00976.

Effect of Renin-Angiotensin System Blockage in Patients with Acute Respiratory Distress Syndrome: A Retrospective Case Control Study

Affiliations
  • 1Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
  • 2Seoul National University Hospital and Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. sangmin2@snu.ac.kr

Abstract

BACKGROUND
Acute respiratory distress syndrome (ARDS) remains a life-threatening disease. Many patients with ARDS do not recover fully, and progress to terminal lung fibrosis. Angiotensin-converting enzyme (ACE) inhibitor is known to modulate the neurohormonal system to reduce inflammation and to prevent tissue fibrosis. However, the role of ACE inhibitor in the lungs is not well understood. We therefore conducted this study to elucidate the effect of renin-angiotensin system (RAS) blockage on the prognosis of patients with ARDS.
METHODS
We analyzed medical records of patients who were admitted to the medical intensive care unit (ICU) at a tertiary care hospital from January 2005 to December 2010. ARDS was determined using the Berlin definition. The primary outcome was the mortality rate of ICU. Survival analysis was performed after adjustment using propensity score matching.
RESULTS
A total of 182 patients were included in the study. Thirty-seven patients (20.3%) took ACE inhibitor or angiotensin receptor blocker (ARB) during ICU admission, and 145 (79.7%) did not; both groups showed similar severity scores. In the ICU, mortality was 45.9% in the RAS inhibitor group and 58.6% in the non-RAS inhibitor group (P = 0.166). The RAS inhibitor group required a longer duration of mechanical ventilation (29.5 vs. 19.5, P = 0.013) and longer ICU stay (32.1 vs. 20.2 days, P < 0.001). In survival analysis, the RAS inhibitor group showed better survival rates than the non-RAS group (P < 0.001).
CONCLUSIONS
ACE inhibitor or ARB may have beneficial effect on ARDS patients.

Keyword

acute respiratory distress syndrome; angiotensin-converting enzyme inhibitors; angiotensin receptor antagonists; mortality; renin-angiotensin system

MeSH Terms

Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Angiotensins
Berlin
Case-Control Studies*
Fibrosis
Humans
Inflammation
Intensive Care Units
Lung
Medical Records
Mortality
Prognosis
Propensity Score
Renin-Angiotensin System*
Respiration, Artificial
Respiratory Distress Syndrome, Adult*
Retrospective Studies*
Survival Rate
Tertiary Healthcare
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Angiotensins

Figure

  • Figure 1. Enrollment and analysis of patients. ICU: intensive care unit; SNUH: Seoul National University Hospital; ARDS: acute respiratory distress syndrome.

  • Figure 2. Kaplan-Meier survival analysis. ACE: angiotensinconverting enzyme; ARB: angiotensin receptor blocker; ICU: intensive care unit.


Reference

References

1. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000; 342:1334–49.
Article
2. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994; 149(3 Pt 1):818–24.
Article
3. Krafft P, Fridrich P, Pernerstorfer T, Fitzgerald RD, Koc D, Schneider B, et al. The acute respiratory distress syndrome: definitions, severity and clinical outcome. An analysis of 101 clinical investigations. Intensive Care Med. 1996; 22:519–29.
Article
4. Phua J, Badia JR, Adhikari NK, Friedrich JO, Fowler RA, Singh JM, et al. Has mortality from acute respiratory distress syndrome decreased over time? A systematic review. Am J Respir Crit Care Med. 2009; 179:220–7.
5. Abel SJ, Finney SJ, Brett SJ, Keogh BF, Morgan CJ, Evans TW. Reduced mortality in association with the acute respiratory distress syndrome (ARDS). Thorax. 1998; 53:292–4.
Article
6. Erickson SE, Martin GS, Davis JL, Matthay MA, Eisner MD; NIH NHLBI ARDS Network. Recent trends in acute lung injury mortality: 1996-2005. Crit Care Med. 2009; 37:1574–9.
Article
7. Pugin J, Verghese G, Widmer MC, Matthay MA. The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome. Crit Care Med. 1999; 27:304–12.
Article
8. Marshall R, Bellingan G, Laurent G. The acute respiratory distress syndrome: fibrosis in the fast lane. Thorax. 1998; 53:815–7.
Article
9. McClintock D, Zhuo H, Wickersham N, Matthay MA, Ware LB. Biomarkers of inflammation, coagulation and fibrinolysis predict mortality in acute lung injury. Crit Care. 2008; 12:R41.
Article
10. Meduri GU, Headley S, Kohler G, Stentz F, Tolley E, Umberger R, et al. Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS: plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time. Chest. 1995; 107:1062–73.
11. Bhatia M, Moochhala S. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol. 2004; 202:145–56.
Article
12. Burnham EL, Janssen WJ, Riches DW, Moss M, Downey GP. The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance. Eur Respir J. 2014; 43:276–85.
Article
13. Quesnel C, Piednoir P, Gelly J, Nardelli L, Garnier M, Lecon V, et al. Alveolar fibrocyte percentage is an independent predictor of poor outcome in patients with acute lung injury. Crit Care Med. 2012; 40:21–8.
Article
14. Martin C, Papazian L, Payan MJ, Saux P, Gouin F. Pulmonary fibrosis correlates with outcome in adult respiratory distress syndrome: a study in mechanically ventilated patients. Chest. 1995; 107:196–200.
15. Kranzhofer R, Browatzki M, Schmidt J, Kubler W. Angiotensin II activates the proinflammatory transcription factor nuclear factor-kappaB in human monocytes. Biochem Biophys Res Commun. 1999; 257:826–8.
16. Hernandez-Presa M, Bustos C, Ortego M, Tunon J, Renedo G, Ruiz-Ortega M, et al. Angiotensin-converting enzyme inhibition prevents arterial nuclear factor-kappa B activation, monocyte chemoattractant protein-1 expression, and macrophage infiltration in a rabbit model of early accelerated atherosclerosis. Circulation. 1997; 95:1532–41.
17. Arndt PG, Young SK, Poch KR, Nick JA, Falk S, Schrier RW, et al. Systemic inhibition of the angiotensin-converting enzyme limits lipopolysaccharide induced lung neutrophil recruitment through both bradykinin and angiotensin II-regulated pathways. J Immunol. 2006; 177:7233–41.
18. He X, Han B, Mura M, Xia S, Wang S, Ma T, et al. Angiotensin-converting enzyme inhibitor captopril prevents oleic acid-induced severe acute lung injury in rats. Shock. 2007; 28:106–11.
Article
19. Wang R, Ibarra-Sunga O, Verlinski L, Pick R, Uhal BD. Abrogation of bleomycin-induced epithelial apoptosis and lung fibrosis by captopril or by a caspase inhibitor. Am J Physiol Lung Cell Mol Physiol. 2000; 279:L143–51.
Article
20. Cohen EP, Molteni A, Hill P, Fish BL, Ward WF, Moulder JE, et al. Captopril preserves function and ultrastructure in experimental radiation nephropathy. Lab Invest. 1996; 75:349–60.
21. Molteni A, Moulder JE, Cohen EF, Ward WF, Fish BL, Taylor JM, et al. Control of radiation-induced pneumopathy and lung fibrosis by angiotensin-converting enzyme inhibitors and an angiotensin II type 1 receptor blocker. Int J Radiat Biol. 2000; 76:523–32.
22. Brooks WW, Bing OH, Robinson KG, Slawsky MT, Chaletsky DM, Conrad CH. Effect of angiotensin-converting enzyme inhibition on myocardial fibrosis and function in hypertrophied and failing myocardium from the spontaneously hypertensive rat. Circulation. 1997; 96:4002–10.
Article
23. Ishidoya S, Morrissey J, McCracken R, Reyes A, Klahr S. Angiotensin II receptor antagonist ameliorates renal tubulointerstitial fibrosis caused by unilateral ureteral obstruction. Kidney Int. 1995; 47:1285–94.
Article
24. Schieffer B, Wirger A, Meybrunn M, Seitz S, Holtz J, Riede UN, et al. Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodeling after myocardial infarction in the rat. Circulation. 1994; 89:2273–82.
Article
25. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012; 307:2526–33.
26. Frank AJ, Thompson BT. Pharmacological treatments for acute respiratory distress syndrome. Curr Opin Crit Care. 2010; 16:62–8.
Article
27. National Heart, Lung, and Blood Institute ARDS Clinical Trials Network, Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, et al. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014; 370:2191–200.
Article
28. Kor DJ, Iscimen R, Yilmaz M, Brown MJ, Brown DR, Gajic O. Statin administration did not influence the progression of lung injury or associated organ failures in a cohort of patients with acute lung injury. Intensive Care Med. 2009; 35:1039–46.
Article
29. Jaimes F, De La Rosa G, Morales C, Fortich F, Arango C, Aguirre D, et al. Unfractioned heparin for treatment of sepsis: a randomized clinical trial (the HETRASE study). Crit Care Med. 2009; 37:1185–96.
Article
30. Kor DJ, Erlich J, Gong MN, Malinchoc M, Carter RE, Gajic O, et al. Association of prehospitalization aspirin therapy and acute lung injury: results of a multicenter international observational study of atrisk patients. Crit Care Med. 2011; 39:2393–400.
Article
31. Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005; 353:1685–93.
Article
32. Moss M, Gillespie MK, Ackerson L, Moore FA, Moore EE, Parsons PE. Endothelial cell activity varies in patients at risk for the adult respiratory distress syndrome. Crit Care Med. 1996; 24:1782–6.
Article
33. Conner ER, Ware LB, Modin G, Matthay MA. Elevated pulmonary edema fluid concentrations of soluble intercellular adhesion molecule-1 in patients with acute lung injury: biological and clinical significance. Chest. 1999; 116(1 Suppl):83S–4S.
34. Flori HR, Ware LB, Glidden D, Matthay MA. Early elevation of plasma soluble intercellular adhesion molecule-1 in pediatric acute lung injury identifies patients at increased risk of death and prolonged mechanical ventilation. Pediatr Crit Care Med. 2003; 4:315–21.
Article
35. Parsons PE, Eisner MD, Thompson BT, Matthay MA, Ancukiewicz M, Bernard GR, et al. Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med. 2005; 33:1–6.
Article
36. Seccia TM, Belloni AS, Guidolin D, Sticchi D, Nussdorfer GG, Pessina AC, et al. The renal antifibrotic effects of angiotensin-converting enzyme inhibition involve bradykinin B2 receptor activation in angiotensin II-dependent hypertension. J Hypertens. 2006; 24:1419–27.
Article
37. Yamamoto K, Mano T, Yoshida J, Sakata Y, Nishikawa N, Nishio M, et al. ACE inhibitor and angiotensin II type 1 receptor blocker differently regulate ventricular fibrosis in hypertensive diastolic heart failure. J Hypertens. 2005; 23:393–400.
Article
38. Karimian G, Mohammadi-Karakani A, Sotoudeh M, Ghazi-Khansari M, Ghobadi G, Shakiba B. Attenuation of hepatic fibrosis through captopril and enalapril in the livers of bile duct ligated rats. Biomed Pharmacother. 2008; 62:312–6.
Article
39. Jonsson JR, Clouston AD, Ando Y, Kelemen LI, Horn MJ, Adamson MD, et al. Angiotensin-converting enzyme inhibition attenuates the progression of rat hepatic fibrosis. Gastroenterology. 2001; 121:148–55.
Article
40. Needham DM, Colantuoni E, Mendez-Tellez PA, Dinglas VD, Sevransky JE, Dennison Himmelfarb CR, et al. Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study. BMJ. 2012; 344:e2124.
Article
41. Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003; 348:683–93.
Article
42. Angel MJ, Bril V, Shannon P, Herridge MS. Neuromuscular function in survivors of the acute respiratory distress syndrome. Can J Neurol Sci. 2007; 34:427–32.
Article
43. Villar J, Sulemanji D, Kacmarek RM. The acute respiratory distress syndrome: incidence and mortality, has it changed? Curr Opin Crit Care. 2014; 20:3–9.
44. MacCallum NS, Evans TW. Epidemiology of acute lung injury. Curr Opin Crit Care. 2005; 11:43–9.
Article
45. Soubani AO, Shehada E, Chen W, Smith D. The outcome of cancer patients with acute respiratory distress syndrome. J Crit Care. 2014; 29:183.e7–183.
Article
46. Matchar DB, McCrory DC, Orlando LA, Patel MR, Patel UD, Patwardhan MB, et al. Systematic review: comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension. Ann Intern Med. 2008; 148:16–29.
Article
47. Vega IL. ACE inhibitors vs ARBs for primary hypertension. Am Fam Physician. 2015; 91:522–3.
48. Laverman GD, Remuzzi G, Ruggenenti P. ACE inhibition versus angiotensin receptor blockade: which is better for renal and cardiovascular protection? J Am Soc Nephrol. 2004; 15 Suppl 1:S64–70.
Article
49. Wang CY, Calfee CS, Paul DW, Janz DR, May AK, Zhuo H, et al. One-year mortality and predictors of death among hospital survivors of acute respiratory distress syndrome. Intensive Care Med. 2014; 40:388–96.
Article
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