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VOLUME 27 , ISSUE 8 ( August, 2023 ) > List of Articles

SYSTEMATIC REVIEW

Role of Nebulized Heparin in Clinical Outcome of COVID-19 Patients with Respiratory Symptoms: A Systematic Review

Bhavna Gupta, Pallavi Ahluwalia, Nidhi Gupta, Anish Gupta

Keywords : Acute respiratory distress syndrome, Coronavirus disease-2019, Nebulized heparin, Pandemic, Randomized study, Randomized controlled trial, Respiratory failure, SARS, SARS-CoV-2, Unfractionated heparin

Citation Information : Gupta B, Ahluwalia P, Gupta N, Gupta A. Role of Nebulized Heparin in Clinical Outcome of COVID-19 Patients with Respiratory Symptoms: A Systematic Review. Indian J Crit Care Med 2023; 27 (8):572-579.

DOI: 10.5005/jp-journals-10071-24511

License: CC BY-NC 4.0

Published Online: 31-07-2023

Copyright Statement:  Copyright © 2023; The Author(s).


Abstract

Coronavirus disease-2019 (COVID-19) is an extremely contagious illness caused by the SARS-CoV-2 virus and has been declared a pandemic by the World Health Organization (WHO). There are currently no particular treatments, however, nebulized heparin has been offered as a viable therapy. The purpose of this systematic review is to assess the efficacy of nebulized heparin in COVID-19 patients with respiratory symptoms. Methods: Relevant studies were identified through a systematic search of the PubMed, Medline, Embase, Cochrane Library and Web of Science, and Scopus databases. The search terms included “nebulized heparin,” “COVID-19,” and “SARS-CoV-2.” Studies that evaluated the use of nebulized heparin in COVID-19 patients with respiratory symptoms were included. The rest of the studies along with those that were not published in English were excluded. The systematic review was registered under PROSPERO-CRD42023413927. Observations: Five studies have been included in this systematic review. Case reports, case series, observational studies, and randomized controlled trial (RCT) comprised the studies. The patient sample sizes ranged from 2 to 98. The studies assessed the efficacy of nebulized heparin in COVID-19 patients with variable disease severity. The evaluated outcomes included mortality, hospital stay duration, oxygen requirements, and laboratory parameters. Conclusion: Based on the clinical studies included in this systematic review, nebulized heparin may be useful in the management of COVID-19. Oxygen saturation was greater, inflammatory indicators were lower, and hospital stays were shorter in these patients. However, the studies had limitations, including inconsistent sample sizes, varying dosages of nebulized heparin, and no control groups. Nebulized heparin in patients with COVID-19 needs to be studied further to determine its safety and effectiveness.


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  1. World Health Organization. COVID-19 clinical management: living guidance. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1. Accessed on: 20 April 2023.
  2. Al-Samkari H, Karp Leaf RS, Dzik WH, Carlson JCT, Fogerty AE, Waheed A, et al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood 2020;136(4):489–500. DOI: 10.1182/blood.2020006520.
  3. Abou-Ismail MY, Diamond A, Kapoor S, Arafah Y, Nayak L. The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management. Thromb Res 2020;194:101–115. DOI: 10.1016/j.thromres.2020.06.029.
  4. Avila J, Long B, Holladay D, Gottlieb M. Thrombotic complications of COVID-19. Am J Emerg Med 2021;39:213–218. DOI: 10.1016/j.ajem.2020.09.065.
  5. Bertanha M, Rodrigues LDS, Mellucci Filho PL, Moroz A, Pardini MIMC, Sobreira ML, etal. Nebulized enriched heparin to treat no critical patients with Sars-Cov-2: Triple-blind clinical trial. Medicine (Baltimore) 2021;100(51):e28288. DOI: 10.1097/MD.0000000000028288.
  6. Mulloy B, Hogwood J, Gray E, Lever R, Page CP. Pharmacology of heparin and related drugs, Pharmacol. Rev 2016;68(1):76–141. DOI: 10.1124/pr.115.011247.
  7. Young, E. The anti-inflammatory effects of heparin and related compounds. Thromb Res 2008;122(6):743–752. DOI: 10.1016/j.thromres.2006.10.026.
  8. Van Haren FMP, Page C, Laffey JG, Artigas A, Rimblas MC, Nunes Q, et al. Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence. Crit Care 2020;24(1):454. DOI: 10.1186/s13054-020-03148-2.
  9. Rentsch CT, Beckman JA, Tomlinson L, Gellad WF, Kidwai-Khan F, Skanderson M, et al. Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study. BMJ 2021;372:n311. DOI: 10.1136/bmj.n311.
  10. Umapathi T, Kor AC, Venketasubramanian N, Lim CC, Pang BC, Yeo TT, et al. Large artery ischaemic stroke in severe acute respiratory syndrome (SARS). J Neurol. 2004;251(10):1227–1231. DOI: 10.1007/s00415-004-0519-8.
  11. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020;18(5): 1094–1099. DOI: 10.1111/jth.14817.
  12. Tuinman PR, Dixon B, Levi M, Juffermans NP, Schultz MJ. Nebulized anticoagulants for acute lung injury – a systematic review of preclinical and clinical investigations. Crit Care 2012;12(16(2):R70. DOI: 10.1186/cc11325.
  13. van Haren FMP, van Loon LM, Steins A, Smoot TL, Sas C, Staas S, et al. Inhaled nebulised unfractionated heparin for the treatment of hospitalised patients with COVID-19: a multicentre case series of 98 patients. Br J Clin Pharmacol. 2022;88(6):2802–2813. DOI: 10.1111/bcp.15212.
  14. Erelel M, Kaskal M, Akbal-Dagistan O, Issever H, Dagistanli AS, Balkanci H, et al. Early effects of low molecular weight heparin therapy with soft-mist inhaler for COVID-19-induced hypoxemia: a phase IIb trial. Pharmaceutics 2021;13(11):1768. DOI: 10.3390/pharmaceutics13111768.
  15. DeNucci G, Wilkinson T, Sverdloff C, Babadopulos T, Woodcock A, Shute J, et al. Inhaled nebulised unfractionated heparin (UFH) for the treatment of hospitalised patients with COVID-19: a randomised controlled pilot study. Pulm Pharmacol Ther 2023;80:102212. DOI: 10.1016/j.pupt.2023.102212.
  16. Gupta B, Chandrakar S, Gupta N, Jain G. Nebulized heparin to reduce COVID-19-induced acute lung injury: a prospective observational study. Indian J Crit Care Med 2023;27(3):222–224. DOI: 10.5005/jp-journals-10071-24420.
  17. Douen A, Basit A, Panetti R, Farag P, Mbolu G, Popilevsky F, et al. Old medicine for new problems: potential role of a novel treatment using nebulized heparin in COVID-19 ARDS. Chest 2021;160(4):A943–A944. DOI: 10.1016/j.chest.2021.07.879.
  18. Phelps MK, Olson LM, Patel MAVB, Thompson MJ, Murphy CV. Nebulized heparin for adult patients with smoke inhalation injury: a review of the literature. J Pharm Technol 2020;36(4):130–140. DOI: 10.1177/8755122520925774.
  19. Serisier DJ, Shute JK, Hockey PM, Higgins B, Conway J, Carroll MP. Inhaled heparin in cystic fibrosis. Eur Respir J 2006;27(2):354–358. DOI: 10.1183/09031936.06.00069005.
  20. Miller AC, Elamin EM, Suffredini AF. Inhaled anticoagulation regimens for the treatment of smoke inhalation-associated acute lung injury: a systematic review. Crit Care Med 2014;42(2):413–419. DOI: 10.1097/CCM.0b013e3182a645e5.
  21. Xiaodong Lan, Zhiyong Huang, Ziming Tan, Zhenjia Huang, Dehuai Wang, Yuesheng Huang, Nebulized heparin for inhalation injury in burn patients: A systematic review and meta-analysis. Burns & Trauma 2020;8:tkaa015. DOI: 10.1093/burnst/tkaa015.
  22. Yildiz-Pekoz A, Ozsoy Y. Inhaled heparin: therapeutic efficacy and recent formulations. J Aerosol Med Pulm Drug Deliv. 2017;30:143–156. DOI: 10.1089/jamp.2015.1273.
  23. Bendstrup KE, Gram J, Jensen JI. Effect of inhaled heparin on lung function and coagulation in healthy volunteers. Eur Respir J 2002;19(4):606–610. DOI: 10.1183/09031936.02.00105202.
  24. Wang J, Hajizadeh N, Moore EE, McIntyre RC, Moore PK, Veress LA, et al. Tissue plasminogen activator (tPA) treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): a case series. J Thromb Haemost. 2020;18(7):1752–1755. DOI: 10.1111/jth.14828.
  25. Ball L, Schultz MJ, Pelosi P. Nebulised heparin for patients on ventilation: implications for COVID-19 pneumonia. The Lancet. Respir Med. 2021;9(4):321–322. DOI: 10.1016/S2213-2600(20)30513-0.
  26. Dixon B, Schultz MJ, Hofstra JJ, Campbell DJ, Santamaria JD. Nebulized heparin reduces levels of pulmonary coagulation activation in acute lung injury. Crit Care 2010:14(5):445. DOI: 10.1186/cc9269.
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