Anış ARIBOĞAN, Elif REYHAN, Egemen BİLGİN, Hasan AKMAN, Uğur ÖZBEK, Uğur ORAL

Künt göğüs travması olgularında pentoksifilin uygulamasının serum Tnf-alfa düzeyi ve akciğer hasarlanması üzerine etkileri

Çalışmamızda kunt göğüs yaralanması ve pulmoner kontüzyon mevcut olgularda erken dönemde pentoksifilin uygulamasının pulmoner disfonksiyon ve akut akciğer hasarlanması (Adult Respiratory Distress Syndrome=ARDS) gelişimi üzerine etkileri değerlendirildi. Kunt göğüs travması ve pulmoner kontüzyona bağlı akut solunum yetmezliği mevcut 21 erişkin hasta iki grupta ele alındı, 1.grupta (n=11) olguların yoğun bakım ünitesine kabullerinden itibaren 72 saat süresince pentoksifilin 1-1.5 mg/kg/saat dozda IV infüzyon olarak uygulanırken II. grup (n=10) kontrol kabul edildi. Tüm olgularda yoğun bakım ünitesine kabullerinden itibaren 72 saat süresince; 8 saatlik periyodlarla hemodinamik parametreler; (kardiyak indeks (CI), doku oksijen sunumu (DO2), sistemik vasküler rezistans indeks (SVRI) ve pulmoner vasküler rezistans indeks (PVRI); yerleştirilen pulmoner arter kateteri ile ölçüldü. Pik havayolu basıncı, ortalama havayolu basıncı, statik komplians ve ekspire edilen tidal volümler 8 saatlik periodlarla kaydedildi. Hastaların serum TNF-alfa düzeyleri (ELISA yöntemi ile), lökosit ve trombosit değerleri 24 saatlik aralıklarla belirlendi ve vücut ısıları kaydedildi. "Akciğer hasarlanma skorları" 24 saatlik periodlarda değerlendirildi. ARDS nedeniyle kaybedilen olgular kaydedildi. Verilerin istatistiksel değerlendirmesinde Student's-t ,Varyant analiz ve ki-kare testleri kullanıldı. p2 değerlerinde 8.saatten itibaren II.gruba göre istatistiksel olarak önemsiz bir artış saptandı (p>0.05). I. grup SVRI değerlerinin S.saat ölçümünde azaldığı ve önemli bir değişiklik göstermeden devam ettiği belirlendi (p>0.05). I. gruba ait PVRI değerleri ise 48., 56., 64. ve 72. saatlerde II. gruba göre önemli derecede azalma gösterdi (p0.05). TNF-α ve Akciğer hasarlanma skorunun I. grupta 24. saatten itibaren her aşamada II. gruba göre önemli derecede düşük olduğu saptandı (p0.05). Olguların prognozu değerlendirildiğinde I. grupta 2, II. grupta 3 hastanın ARDS ile kaybedildiği belirlendi (p>0.05). Sonuç olarak; kunt göğüs yaralanması ve pulmoner kontüzyon olgularında travmayı izleyen erken dönemde infüzyon şeklinde pentoksifilin uygulamasının hemodinamik parametreleri önemli derecede etkilemeden gelişebilecek inflamatuar yanıt ve akut akciğer hasarlanmasının kontrolünde alternatif bir yaklaşım olabileceği kanısına varıldı.

Effects of pentoxifylline on serum Tnf-alpha concentration and control of lung injury in blunt chest trauma patients

In this study effects of pentoxifylline on control of lung injury and ARDS development in patients with pulmonary contusion due to blunt chest trauma. Twenty-one adult blunt chest trauma patients presenting with acute respiratory failure due to pulmonary contusion were scheduled for this study Pentoxifylline was used in group I (n=11) with 1-1.5 mg/kg/hour infusion during the first 72 hours of the early phase intensive care therapy and group II (n=10) was considered. In both group pulmonary artery catheter derived hemodynamic parameters (Cardiac index, Oxygen delivery, pulmonary vascular resistance index and systemic vascular resistance index) and respiratory parameters (peak and mean airway pressure, static compliance and exhaled tidal volumes) were measured every 8 hours. Lung injury was scored with the 'Lung injury score" every 24 hours during a 72-hour period Serum concentration of TNF-α leucocyte and platelets counts and body temperature were determined every 24 hours during a 72-hour period The patients who died from ARDS were noted in both groups Student's-t test, chi-square and analysis of variance were used for statistical analysis p0 05). PVRI values were decreased significantly at the 48.,56 ,64 and 72 hour measurements compared with control group (p0.05). In conclusion in patients with blunt chest trauma and pulmonary contusion use of pentoxyfilline infusion during the early phase of treatment could be considered as an effective measure to prevent inflammatory response to control acute lung injury without changing hemodynamic parameters.

PDF

___

1. Bernard GR, Artigas A, Brigham KL,et al: Report of the American-European Consensus Conference on acute respiratory distress sydrome: Definition, mechanism, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 151:818-824.
2. Boldt J, Müller M, Heesen M,et al: Influence of different volume therapies and pentoxyfilline infusion on circulating soluble adhesion molecules in critically ill patients. Crit Care Med 1996; 24:385-391.
3. Coccia MT, Waxman K, Solimaan MH, et al: Pentoxyfilline improves survival following hemorragic shock. Crit Care Med 1989;17:36-38.
4. Chick TW, Scotto P, Icenogle MV, et al: Effects of pentoxyfilline on pulmonary hemodynamics during acute hypoxia in anesthetized dogs. Am Rev Resp dis 1988; 137:1099-1103.
5. Clark GC, Schecter WP, Trunkey DD: Variables affecting outcome in blunt chest trauma: Flail chest vs pulmonary contusion. J Trauma 1988; 28:298-304.
6. Demling RH, Pomfret EA: Blunt chest trauma. New Horizons 1993;1:402-421.
7. Doherty GM, Jensen JC, Alexander R,et al: Pentoxyfilline suppresion of tumor necrosis factor gene transcription.Surgery 1991;110:192-198.
8. Erickson D, Shinozaki T, Beekman E, et al: Relationship of arterial blood gases and pulmonary radiographs to degree of pulmonary damage in experimental pulmonary contusion. J Trauma 1991; 11:689-694.
9. Hammerschmidt DE, Kotasek D, McCarthy T,et al: Pentoxyfilline inhibits granulocyte and platelet function, including granulocyte priming by platelet activating factor. J Lab Clin Med 1988; 112: 254-263.
10. Ishizaka A, Wu Z, Stephens KE, et al: Attenuation of acute lung injury in septic guinea pigs by pentoxyfilline.Am Rev Respir Dis 1988; 138: 376-382.
11. Kaye DA, Ikhlass NI, Kadowitz P,et al: Analysis of responses to pentoxifylline in the pulmonary vascular bed of the cat. Crit Care Med 1996; 24:263-266.
12. Lechener AJ, Rouben LR, Potthoff LH,et aal: Effects of pentoxyfilline on tumor necrosis factor production and survival during lethal E.coli sepsis vs disseminated candidiasis with fungal septic shock. Circ Shock 1993;39:306-315.
13. Lilly CM, Sandhu JS, Ishizaka A,et al: Pentoxyfilinne prevents tumor necrosis factor –induced lung injury. Am Rev Resp Dis 1989; 139:1361-1368.
14. Meskini N, Nemoz G, Okyayuz-Baklouti I: Phosphodiesterase inhibitory profile of some related xanthine derivatives pharmacologically active on the peripheral microcirculation. Biochem Pharmacol 1994;47: 781-788.
15. Montravers P, Fagon J, Gibert C,et al: Pilot study of cardiopulmonary risk from pentoxyfilline in adult respiratory distress sydrome. Chest 1993; 103:1017-1022.
16. Murray JF, Matthay MA, Luce JM, et al: An expanded definition in the adult respiratory distress sydrome. Am Respir Dis 1988; 138:720-723.
17. Pasquier C, Franzini E, Abedinzaldelr Z, Hakim J: Protective effect of pentoxyfilline against hydroxyl radical-induced damage to proteins in pentoxyfilline and analogues: effects on leukocyte function. Hakim J,Mandel GL (eds). Basel:Karger,1988, 91-96.
18. Porter JM, Culter BS, Lee BY, et al: Pentoxyfilline efficacy in the treatment of intermittent claudication: Multi-center controlled double-blind trial with objective assessment of chronic occlusive arterial disease patients.Am Heart J 1982; 104: 66-72.
19. Powe J, Short A, Sidrald W, Driedger A: Pulmonary accumulation of polymorphonuclear leukocytes in the adult respiratory distress syndrome. Crit Care Med 1982; 10:712-718.
20. Schaed UF: Pentoxyfilline increases survival in murine endotoxin shock and decreases of formationof tumor necrosis factor. Circ Shock 1990; 31:171-181.
21. Schönharting M, Musikic P, Müller R, The hemorheological and antitrombotic potential of pentoxyfilline (Trental)- A review. Pharmatherapeutica 1988; 5:159-169.
22. Sigurdsson GH, Youssef H:Effects of pentoxyfilline on hemodynamics, gas exchange and multiple organ platelet sequestration in experimental endotoxic shock. Acta Anaesthesiol Scand 1993; 37:396-403.
23. Stephen KE, Ishizaka A, Larrick JW, Raffin TA: Tumor necrosis factor causes increased pulmonary permeability and edema: Comparison to septic acute lung injury. Am Rev Resp Dis 1988; 137:1364-1370.
24. Sullivan GW, Carper HT, Novick Jr, Mandell GL: Inhibition of inflamatory action of interleukin-1 and tumor necrosis factor (alpha) on neutrophil function by pentoxyfilline. Infect Immun 1988; 56:1722-1729.
25. Trunkey DD, Lewis FR: Chest trauma. Surg Clin North Am 1980; 60:1541-1549.
26. Wagner RB, Jamieson RM: Pulmonary contusion: Evaluation and classification by computed tomography. Surg Clin North Am 1989; 69:31-39.
27. Ward A, Clissod SP: Pentoxyfilline. A review of its pharmacodynamic and pharmacokinetic properties and its therapeutic efficacy. Drugs 1987; 34: 50-97.
28. Welsh CH, Lien D, Worthen GS, Weil JV: Pentoxyfilline decreases endotoxin-induced pulmonary neutrophil sequestration and extravascular protein accumulation in dog. Am Rev Resp Dis 1988; 138:1106-1114.
29. Zeni F, Pain P, Vindimian M, et al: Effects of pentoxyfilline on circulating cytokine concentrations and hemodynamics in patients with septic shock:Results from a double-blind,randomized placebo-controlled study.Crit Care Med 1996; 24:207-214