International Journal of Pediatrics

Current Issue

By Issue

By Author

By Subject

Author Index

Keyword Index

About Journal

Aims and Scope

Editorial Board

Publication Ethics

Indexing and Abstracting

Related Links

FAQ

Peer Review Process

News

The Effect of Pentoxifylline on the Prevention of Ards in Picu Patients: A Randomized Double-Blind Clinical Trial

Document Type : review article

Authors

1 Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Science, Mashhad, Iran

2 Department of Surgery, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

4 Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Clinical pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

10.22038/ijp.2024.72502.5274

Abstract

Background: Inflammation has a remarkable role in Acute Respiratory Distress Syndrome (ARDS) pathophysiology. Pentoxifylline is a phosphodiesterase IV inhibitor with anti-inflammatory and anti-thrombotic properties, which has had positive results in rodents with ARDS. Due to the lack of human studies, we designed this clinical trial to evaluate the pentoxifylline effect on ARDS prevention in high-risk pediatric patients.
Methods: We included thirty-four children from Akbar hospital’s pediatric intensive care unit (PICU). These patients were highly susceptible to ARDS progression. Using a randomized, double-blind method, 17 patients received pentoxifylline tablets three times a day for a week, while others received placebo tablets at the same interval for seven days. Lung Injury Prediction Score (LIPS), vital signs, pulse oximetry, PaO2, pH, and PaCO2 were measured at baseline and every day for a week period. CRP was assessed at baseline, then on the third and seventh days. Finally, we imported all the data to SPSS software to compare the treatment and placebo groups.
Results: Each placebo and treatment group had seventeen patients who had no statistically significant difference in baseline demographic information or lab data. The variations in LIPS score (P=0.475), CRP (P=0.053), pH (P=0.199), PO2 (P=0.077), PCO2 (P=0.528), Heart rate (P=0.086), Respiratory rate (P=0.512), Diastolic blood pressure (P=0.572), Systolic blood pressure (P=0.517), and SPO2 (P=0.260) were compared between the two groups; and no significant difference was observed.
Conclusion: The results of this clinical trial suggest that pentoxifylline had no prophylactic effect on pediatric ARDS, but for confirmation, further clinical trials with different designs and larger sample sizes are required.

Keywords

References
  1. Q. Li, X. Hu, R. Sun, Y. Tu, F. Gong, Y. Ni, Resolution acute respiratory distress syndrome through reversing the imbalance of Treg/Th17 by targeting the cAMP signaling pathway, Mol Med Rep 14(1) (2016) 343-8.
  2. D.G. Ashbaugh, D.B. Bigelow, T.L. Petty, B.E. Levine, Acute respiratory distress in adults, Lancet 2(7511) (1967) 319-23.
  3. C.Y. Yang, C.S. Chen, G.T. Yiang, Y.L. Cheng, S.B. Yong, M.Y. Wu, C.J. Li, New Insights into the Immune Molecular Regulation of the Pathogenesis of Acute Respiratory Distress Syndrome, Int J Mol Sci 19(2) (2018).
  4. V.M. Ranieri, G.D. Rubenfeld, B.T. Thompson, N.D. Ferguson, E. Caldwell, E. Fan, L. Camporota, A.S. Slutsky, Acute respiratory distress syndrome: the Berlin Definition, Jama 307(23) (2012) 2526-33.
  5. J.L. Mendez, R.D. Hubmayr, New insights into the pathology of acute respiratory failure, Curr Opin Crit Care 11(1) (2005) 29-36.
  6. S.M. Heidemann, A. Nair, Y. Bulut, A. Sapru, Pathophysiology and Management of Acute Respiratory Distress Syndrome in Children, Pediatr Clin North Am 64(5) (2017) 1017-1037.
  7. M. Cepkova, M.A. Matthay, Pharmacotherapy of acute lung injury and the acute respiratory distress syndrome, J Intensive Care Med 21(3) (2006) 119-43.
  8. S.I. Said, H.D. Foda, Pharmacologic modulation of lung injury, Am Rev Respir Dis 139(6) (1989) 1553-64.
  9. L.R. Schouten, F. Veltkamp, A.P. Bos, J.B. van Woensel, A. Serpa Neto, M.J. Schultz, R.M. Wösten-van Asperen, Incidence and Mortality of Acute Respiratory Distress Syndrome in Children: A Systematic Review and Meta-Analysis, Crit Care Med 44(4) (2016) 819-29.
  10. R.G. Khemani, L. Smith, Y.M. Lopez-Fernandez, J. Kwok, R. Morzov, M.J. Klein, N. Yehya, D. Willson, M.C.J. Kneyber, J. Lillie, A. Fernandez, C.J.L. Newth, P. Jouvet, N.J. Thomas, Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study, Lancet Respir Med 7(2) (2019) 115-128.
  11. S. Nye, R.J. Whitley, M. Kong, Viral Infection in the Development and Progression of Pediatric Acute Respiratory Distress Syndrome, Front Pediatr 4 (2016) 128.
  12. A.G. Randolph, Management of acute lung injury and acute respiratory distress syndrome in children, Crit Care Med 37(8) (2009) 2448-54.
  13. E. Fan, D. Brodie, A.S. Slutsky, Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment, Jama 319(7) (2018) 698-710.
  14. Pediatric acute respiratory distress syndrome: consensus recommendations from the Pediatric Acute Lung Injury Consensus Conference, Pediatr Crit Care Med 16(5) (2015) 428-39.
  15. S.R. Kahn, W. Lim, A.S. Dunn, M. Cushman, F. Dentali, E.A. Akl, D.J. Cook, A.A. Balekian, R.C. Klein, H. Le, S. Schulman, M.H. Murad, Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, Chest 141(2 Suppl) (2012) e195S-e226S.
  16. G.L. Drusano, What are the properties that make an antibiotic acceptable for therapy of community-acquired pneumonia?, J Antimicrob Chemother 66 Suppl 3 (2011) iii61-7.
  17. M.J.D. Griffiths, D.F. McAuley, G.D. Perkins, N. Barrett, B. Blackwood, A. Boyle, N. Chee, B. Connolly, P. Dark, S. Finney, A. Salam, J. Silversides, N. Tarmey, M.P. Wise, S.V. Baudouin, Guidelines on the management of acute respiratory distress syndrome, BMJ Open Respir Res 6(1) (2019) e000420.
  18. B.T. Thompson, R.C. Chambers, K.D. Liu, Acute Respiratory Distress Syndrome, N Engl J Med 377(6) (2017) 562-572.
  19. M. Ghasemnejad-Berenji, S. Pashapour, S. Sadeghpour, Pentoxifylline: A Drug with Antiviral and Anti-Inflammatory Effects to Be Considered in the Treatment of Coronavirus Disease 2019, Med Princ Pract 30(1) (2021) 98-100.
  20. C.P. Samlaska, E.A. Winfield, Pentoxifylline, J Am Acad Dermatol 30(4) (1994) 603-21.
  21. D. Brie, A. Sahebkar, P.E. Penson, M. Dinca, S. Ursoniu, M.C. Serban, A. Zanchetti, G. Howard, A. Ahmed, W.S. Aronow, P. Muntner, G.Y. Lip, N.D. Wong, J. Rysz, M. Banach, Effects of pentoxifylline on inflammatory markers and blood pressure: a systematic review and meta-analysis of randomized controlled trials, J Hypertens 34(12) (2016) 2318-2329.
  22. L.J. Marques, L. Zheng, N. Poulakis, J. Guzman, U. Costabel, Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages, Am J Respir Crit Care Med 159(2) (1999) 508-11.
  23. F. Seirafianpour, S. Mozafarpoor, N. Fattahi, A. Sadeghzadeh-Bazargan, M. Hanifiha, A. Goodarzi, Treatment of COVID-19 with pentoxifylline: Could it be a potential adjuvant therapy?, Dermatol Ther 33(4) (2020) e13733.
  24. M.C. Bachmann, C. Morais, G. Bugedo, A. Bruhn, A. Morales, J.B. Borges, E. Costa, J. Retamal, Electrical impedance tomography in acute respiratory distress syndrome, Crit Care 22(1) (2018) 263.
  25. J.A. Blumenthal, M.G. Duvall, Invasive and noninvasive ventilation strategies for acute respiratory failure in children with coronavirus disease 2019, Curr Opin Pediatr 33(3) (2021) 311-318.
  26. I.S. Oliveira-Júnior, C.C. Maganhin, A.A. Carbonel, C.M. Monteiro, S.S. Cavassani, R.M. Oliveira-Filho, Effects of pentoxifylline on TNF-alpha and lung histopathology in HCL-induced lung injury, Clinics (Sao Paulo) 63(1) (2008) 77-84.
  27. B.K. Kim, S. Kim, C.Y. Kim, Y.J. Kim, S.H. Lee, J.H. Cha, J.H. Kim, Predictive Role of Lung Injury Prediction Score in the Development of Acute Respiratory Distress Syndrome in Korea, Yonsei Med J 62(5) (2021) 417-423.
  28. W. Feret, M. Nalewajska, Ł. Wojczyński, W. Witkiewicz, P. Kłos, V. Dziedziejko, A. Pawlik, Pentoxifylline as a Potential Adjuvant Therapy for COVID-19: Impeding the Burden of the Cytokine Storm, J Clin Med 10(22) (2021).
  29. M. Giorgi, S. Cardarelli, F. Ragusa, M. Saliola, S. Biagioni, G. Poiana, F. Naro, M. Massimi, Phosphodiesterase Inhibitors: Could They Be Beneficial for the Treatment of COVID-19?, Int J Mol Sci 21(15) (2020).
  30. G.R. Milne, T.M. Palmer, Anti-inflammatory and immunosuppressive effects of the A2A adenosine receptor, ScientificWorldJournal 11 (2011) 320-39.
  31. D. Mokra, J. Mokry, Phosphodiesterase Inhibitors in Acute Lung Injury: What Are the Perspectives?, Int J Mol Sci 22(4) (2021).
  32. A. Guerrero, A2A Adenosine Receptor Agonists and their Potential Therapeutic Applications. An Update, Curr Med Chem 25(30) (2018) 3597-3612.
  33. J. Deree, J. Martins, T. de Campos, J.G. Putnam, W.H. Loomis, P. Wolf, R. Coimbra, Pentoxifylline attenuates lung injury and modulates transcription factor activity in hemorrhagic shock, J Surg Res 143(1) (2007) 99-108.
  34. J.A. Weigelt, J.F. Norcross, K.R. Borman, W.H. Snyder, 3rd, Early steroid therapy for respiratory failure, Arch Surg 120(5) (1985) 536-40.
  35. R.M. Schein, R. Bergman, E.H. Marcial, D. Schultz, R.C. Duncan, P.I. Arnold, C.L. Sprung, Complement activation and corticosteroid therapy in the development of the adult respiratory distress syndrome, Chest 91(6) (1987) 850-4.
  36. R.C. Bone, C.J. Fisher, Jr., T.P. Clemmer, G.J. Slotman, C.A. Metz, Early methylprednisolone treatment for septic syndrome and the adult respiratory distress syndrome, Chest 92(6) (1987) 1032-6.
  37. E.K. Bajwa, C.K. Malhotra, B.T. Thompson, D.C. Christiani, M.N. Gong, Statin therapy as prevention against development of acute respiratory distress syndrome: an observational study, Crit Care Med 40(5) (2012) 1470-7.
  38. H. Yadav, R.K. Lingineni, E.J. Slivinski, K.A. Stockler, A. Subramanian, G.S. Oderich, D.A. Wigle, R.E. Carter, D.J. Kor, Preoperative statin administration does not protect against early postoperative acute respiratory distress syndrome: a retrospective cohort study, Anesth Analg 119(4) (2014) 891-898.
  39. H.J. Ford, W.H. Anderson, B. Wendlandt, T. Bice, A. Ceppe, J. Lanier, S.S. Carson, Randomized, Placebo-controlled Trial of Inhaled Treprostinil for Patients at Risk for Acute Respiratory Distress Syndrome, Ann Am Thorac Soc 18(4) (2021) 641-647.
  40. E. Festic, G.E. Carr, R. Cartin-Ceba, R.F. Hinds, V. Banner-Goodspeed, V. Bansal, A.T. Asuni, D. Talmor, G. Rajagopalan, R.D. Frank, O. Gajic, M.A. Matthay, J.E. Levitt, Randomized Clinical Trial of a Combination of an Inhaled Corticosteroid and Beta Agonist in Patients at Risk of Developing the Acute Respiratory Distress Syndrome, Crit Care Med 45(5) (2017) 798-805.
  41. B. Dixon, R.J. Smith, D.J. Campbell, J.L. Moran, G.S. Doig, T. Rechnitzer, C.M. MacIsaac, N. Simpson, F.M. van Haren, A.N. Ghosh, Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial, The Lancet Respiratory Medicine 9(4) (2021) 360-372.
  42. D.J. Kor, R.E. Carter, P.K. Park, E. Festic, V.M. Banner-Goodspeed, R. Hinds, D. Talmor, O. Gajic, L.B. Ware, M.N. Gong, Effect of aspirin on development of ARDS in at-risk patients presenting to the emergency department: the LIPS-A randomized clinical trial, Jama 315(22) (2016) 2406-2414.
  43. B.S. Smith, D. Yogaratnam, K.E. Levasseur-Franklin, A. Forni, J. Fong, Introduction to drug pharmacokinetics in the critically ill patient, Chest 141(5) (2012) 1327-1336.
  44. S.I. Blot, F. Pea, J. Lipman, The effect of pathophysiology on pharmacokinetics in the critically ill patient--concepts appraised by the example of antimicrobial agents, Adv Drug Deliv Rev 77 (2014) 3-11.
  45. B.A. Boucher, G.C. Wood, J.M. Swanson, Pharmacokinetic changes in critical illness, Crit Care Clin 22(2) (2006) 255-71, vi.
International Journal of Pediatrics
Volume 12, Issue 1
January 2024
Pages 18517-18529
Files
Share
How to cite
Statistics