Role of Hypertonic Saline Nebulization Therapy in Patients with Early Acute Respiratory Distress Syndrome

ABSTRACT

Acute respiratory syndrome (ARDS) is a life threatening condition with high mortality rates. It is characterized by inflammation of the lung parenchyma leading to impaired gas exchange with concomitant systemic release of inflammatory mediators causing protracted inflammation, increased vascular permeability, increased permeability of alveolar epithelial cells, extravasation of plasma and leucocyte infiltration, and frequently resulting in multiple organ failure. Since inflammation is thought to contribute to the pathogenesis of ARDS, it is rational to explore modulating therapies for this inflammation, provided the adverse effect of such treatment is not excessive. Hypertonic saline nebulizer 3% NaCl is a potent anti-inflammatory agent, and immunomodulator, which exert inhibitory effects in several stages of the inflammatory cascade and would seem to be a logical choice for treatment of ARDS. This study included 60 patients according to sample size admitted to the Department of Critical Care Medicine at the Alexandria Main University Hospital meeting criteria of ARDS according to Berlin's definition. They were categorized into two groups group I (control group) included thirty patients, and group II (study group) included thirty patients who received 4ml of hypertonic saline nebulization once daily for 7 days. All cases were subjected to history taking, clinical examination, assessment of disease severity (APACHEII), laboratory investigations, ABG, and chest X-ray, with measurement of lung mechanics (compliance, airway resistance, peak and plateau pressures, PEEP), hypoxic index, lung injury score (LIS), and SOFA score. Hypoxic index, LIS and SOFA score were significantly improved in hypertonic saline group than control group. Also, intensive care unit (ICU) stay and mechanical ventilation days were reduced in the hypertonic saline group with statistically significant difference. Survival was significantly higher in the hypertonic saline group.  Initiation of hypertonic saline nebulization therapy for patients with early ARDS appears to be tolerable and may be beneficial with significant improving in oxygenation with trend to decrease mortality, ICU stay, and mechanical ventilation days and so may be added to protective lung strategy.

Keywords: Acute respiratory distress syndrome (ARDS), hypertonic saline, hypoxic index.

REFERENCES

1. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000;342(18):1301-8.
2. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet 1967; 2:319–23.
3. Wark PA, McDonald V. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev 2000(2):Cd001506.
4.  Reeves EP, Williamson M, O’Neill SJ, Greally P, McElvaney NG. Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis. Am J Respir Crit Care Med 2011; 183:1517–23.
5. Angle N, Hoyt DB, Coimbra R, Liu F, Herdon-Remelius C, Loomis W, et al. Hypertonic saline resuscitation diminishes lung injury by suppressing neutrophil activation after hemorrhagic shock. Shock 1998; 9:164–70.
6. Middleton PG, Pollard KA, Wheatley JR. Hypertonic saline alters ion transport across the human airway epithelium. Eur Respir J 2000; 17:195–9.
7. Khan TZ, Wagener JS, Bost T, Martinez J, Accurso FJ, Riches DW. Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med 1995; 151:1075–82.
8. Mandelberg A, Tal G, Witzling M, Someck E, Houri S, Balin A, et al. Nebulized 3% hypertonic saline solution treatment in hospitalized infants with viral bronchiolitis. Chest 2003;123(2):481-7.
9. Taube C, Holz O, Mucke M, Jorres RA, Magnussen H. Airway response to inhaled hypertonic saline in patients with moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;164(10 Pt 1):1810-5
10. Angle N, Hoyt DB, Coimbra R, Liu F, Herdon-Remelius C, Loomis W, et al. Hypertonic saline resuscitation diminishes lung injury by suppressing neutrophil activation after hemorrhagic shock. Shock 1998; 9:164–70.
11. Gonzalez RJ, Moore EE, Ciesla DJ, Neto JR, Biffl WL, Silliman CC. Hyperosmolality abrogates neutrophil cytotoxicity provoked by post-shock mesenteric lymph. Shock 2002; 18:29–32.
12. Powers KA, Woo J, Khadaroo RG, Papia G, Kapus A, Rotstein OD. Hypertonic resuscitation of hemorrhagic shock upregulates the anti-inflammatory response by alveolar macrophages. Surgery 2003; 134:312–8.
13. Kotz S, Balakrishnan N, Read CB, Vidakovic B. Encyclopedia of statistical sciences. 2nded. Hoboken, N.J.: Wiley-Interscience; 2006.
14. Kirkpatrick LA, Feeney BC. A simple guide to IBM SPSS statistics for version 20.0. Student ed. Belmont, Calif.: Wadsworth, Cengage Learning; 2013.
15. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000;342(18):1301-8.
16. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, et al. Effect of a protectiveventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338:347-54.
17. Dahroug AH, Abu Khabar AH, Atta EM, Elmorsi AA, El Bordiny MM. Effect of inhaled corticosteroids on levels of alveolar cytokines and outcome of patients with early acute respiratory distress syndrome. MD Thesis. Faculty of Medicine, Alexandria University, Egypt; 2012.
18.  Tomooka LT, Murphy C, Davidson TM. Clinical study and literature review of nasal irrigation. Laryngoscope 2000; 110:1189–1193
19. Inci I, Ampollini L, Arni S, Jungraithmayr W, Inci D, Hillinger S, et al. Ex vivo reconditioning of marginal donor lungs injured by acid aspiration. J Heart Lung Transplant 2008;27(11):1229–36.
20. Kellett F, Redfern J, Niven RM. Evaluation of nebulised hypertonic saline (7%) as an adjunct to physiotherapy in patients with stable bronchiectasis. Respir Med 2005;99(1):27-31.
21. Riedler J, Reade T, Button B, Robertson CF. Inhaled hypertonic saline increases sputum expectoration in cystic fibrosis. J Paediatr Child Health 1996;32:48–50.
22. Sateesh Pujari, & Estari Mamidala. (2015). Anti-diabetic activity of Physagulin-F isolated from Physalis angulata fruits. The American Journal of Science and Medical Research, 1(2), 53–60. https://doi.org/10.5281/zenodo.7352308
23. Murray TS. The effect of hypertonic saline on in vitro Pseudomonas aeruginosa colonization. Ped Pulmonol 2010;45: A367.
24. Gould NS, Gauthier S, Kariya CT, Min E, Huang J, Day BJ. Hypertonic saline increases lung epithelial lining fluid glutathione and thiocyanate: two protective  CFTR-dependent thiols against oxidative injury. Respir Res 2010;11:119.
25. Moore E, Denver Health and Hospital Authority. Clinical Trial of Nebulized Hypertonic Saline to Attenuate Post-Traumatic Acute Lung Injury [Unpublished results]. Clinical trial [Last Updated: 1 July, 2016]. available from; https://clinicaltrials.gov/ct2/show/study/NCT01667666.[Accessed On: 26 Aug, 2016].