Burcu AKBAY, Banu AYHAN, Savaş YILBAŞ, Bayram KARATAŞ, Seda B. AKINCI, Fatma SARICAOĞLU, Ülkü AYPAR

Mekanik ventilasyon uygulanan tavşanlarda profopol infüzyonunun metabolik ve biyokimyasal etkilerinin değerlendirilmesi

Amaç: Uzun süreli propofol infüzyonuna bağlı olarak; laktik asidoz, lipidemik plazma, pankreatit ve kalp yetmezliği gibi durumlar gözlenebilir. Nadir görülen; ancak ölümcül olabilen bu klinik durum, Propofol Infüzyon Sendromu (PRIS) olarak tanımlanmıştır. Bu çalışmada; uzun süreli propofol infüzyonu ile sedasyonu sağlanan, mekanik ventilasyon uygulanan tavşanlarda, propofol infüzyonunun metabolik ve biyokimyasal parametrelere etkilerini incelemeyi amaçladık. Yöntem: Çalışmamızda 12 adet, 2500-3500 gr, 3-4 aylık, erkek, Yeni Zelanda cinsi tavşan kullanıldı. Ksilazine ve atropin premedikasyonundan sonra; ketaminle anestezi indüksiyonu sonrası trakeotomi açıldı ve ventilatöre bağlandı. Grup 1 (PI + Serum fizyolojik, n:6)'e dahil edilen tavşanlara; %2'likpropofol, 20 mg kg'1 saat'1, infüzyon şeklinde uygulandı. Grup 2 (Sevofluran + Serum fizyolojik, n:6)'ye dahil edilen tavşanlara; 4 it dkl %100 oksijen içersinde, %1,5'lik sevofluran ile inhalasyon anestezisi uygulandı. Sedasyon seviyeleri 30 dk.'da bir değerlendirildi; sedasyon seviyesi (BIS değeri 40-60 arasında), klinik veya vital bulgulara göre propofol infüzyon hızı ve sevofluranın %100 oksijen içindeki yüzdesi değiştirildi. Tüm vital bulguları (kalp hızı, invaziv arter basıncı, Sp02, vücut ısısı, BIS değerleri ve idrar çıkışı) 15 dk'da bir takip edildi. Arterial kan gazı analizi 2 saat arayla, diğer tüm serum biokimya testleri için ise 12 saat arayla kan örnekleri alındı. Her iki gruptaki deneklere uygulanan anestezi yöntemine, denekler ölene kadar veya 24 saat süresince devam edildi. Bulgular: Çalışmamızda iki grup karşılaştırıldığında; propofol grubunda, sevofluran grubuna göre; kolesterol, trigliserit ve VLDL değerlerinde, 12. ve 24. saatlerde anlamlı bir artış gözlenmiştir. Propofol grubunda, sevofluran grubu ile karşılaştırıldığında; CK-MB değerlerinde 24. saatte, myoglobülin ve amilaz değerlerinde ise 12. saatte, daha fazla artış olduğu saptanmıştır. Ayrıca; propofol grubundaki deneklerde sevofluran grubundakilere göre; sodyum değerlerinin düşük, potasyum ve fosfor değerlerinin ise yüksek olduğu gözlenmiştir. Sonuç: Sağlıklı hayvanlarda, ventilasyon uygulanarak-, yüksek doz propofol ile oluşturulmuş bu model; kritik hastalığı nedeni ile mekanik ventilatöre bağlanmış yoğun bakım hastalarını birebir yansıtmasa da; propofol infüzyonunun metabolik ve biyokimyasal etkilerinin mekanizmasının açığa çıkarılması ve oluşabilecek PRIS sendromuna benzer tabloların tedavisine yönelik ajanların denenmesi amacıyla model olarak kullanılabilir.

Evaluate of metabolic and biochemical effects of infusion of propofol in rabbits who undergoing mechanical ventilation

Objective: The clinical condition which is a result of long-term infusion of propofol defined as Propofol Infusion Sendrome (PRIS) is a rare syndrome which can lead to lactic acidosis, lipemic plasma, pancreatit and cardiac failure and is often fatal. In our study, we aimed to evaluate metabolic and biochemical effects of infusion of propofol for long term sedation of rabbits undergoing mechanical ventilation. Methods: 2500-3500 gr weight, 3-4 months, male, white 12 New Zealand rabbits were used in the study. After the rabbits were premedicated with xylazine and atropine, after induction with ketamine, rabbits were opened tracheostomy and were connected the ventilator. Group 1 (PI + Saline, n:6): In this group 2% injectable lipid solution of propofol infused to animals at a rate of 20 mg1 kg' hr. Group 2 (Sevoflurane + Saline, n:6): In this group inhalation anesthesia with 1.5% sevoflurane in 100% oxygen of 4 L' min was started. The sedation levels of all animals were evaluated for every 30 minutes; sedation level (BIS level is between 40-60), the propofol infusion rate and sevoflurane percentage in 100% 02 were changed according to clinical or vital signs. All their vital signs (heart rate, invazive arterial pressure, Sp02, body temperature, BIS values and urine output) were observed for every 15 minutes. Arterial blood gases analysis were obtained every 2 hours and other biochemical parameters were obtained every 12 hours. Anesthesia methods used in the animals in all groups were continued until the animals died or during 24 hours. Results: In this study we found that; when compared to two groups; in the propofol group; levels of cholesterol, trigliserid and VLDL were higher than in the sevoflurane group at 12"'and 24"' hours. Levels ofCK-MB at 24th hours, myoglobuline and amylase levels at 12"' hours in the propofol group were higher than in the sevoflurane group. We observed that rabbits who were in the propofol group had decreased sodium levels and increased potassium and phosphorus levels statistically. Conclusion: Although this model which was created with high doses propofol in healty animals who undergoing mechanical ventilation, is not a reflection of the intensive care patients who had mechanical ventilation for treatment of critical illness, it can be used to become known biochemical and metabolic mechanism of infusion of propofol. So that the mechanism can be used for investigate the treatment models for occur ability of like PRIS syndrome treatment.

PDF

___

1. Mistraletti G, Donatelli F, Carli F. Metabolic and endocrine effects of sedative agents. Curr Opin Crit Care 2005;11(4):312-317.
2. Vasile B, Rasulo F, Candiani A, Latronico N. The pathophysiology of propofol infusion syndrome: A simple name for a complex syndrome. Intensive Care Med 2003;29(9): 1417-1425.
3. Rona G. Catecholamine cardiotoxicity. J Mol Cell Cardiol 1985; 17(4):291-306.
4. Bray RJ. Propofol infusion syndrome in children. Paediatr Anaesth 1998;8(6):491-499.
5. Fudickar A, Bein B, Peter H, Tonner PH. Propofol infusion syndrome in anaesthesia and intensive care medicine. Curr Opin Anaesthesiol 2006; 19(4):404^10.
6. Karakitsos D, Poularas J, Kalogeromitros A, Karabinis A. The propofol infusion syndrome treated with haemofiltration. Is there a time for genetic screening? Acta Anaesthesiol Scand 2007; 51(5):644-645.
7. Fodale V, La Monaca E. Propofol infusion syndrome: an overview of a perplexing disease. Drug Saf 2008;31(4):293-303.
8. Uezono S, Hotta Y, Takakuwa Y, Ozaki M. Acquired carnitine deficiency: A clinical model for propofol infusion syndrome? Anesthesiology 2005; 103(4):909.
9. Ypsilantis P, Politou M, Mikroulis D, et al. Organ toxicity and mortality in propofol-sedated rabbits under prolonged mechanical ventilation. Anesth Analg 2007; 105(1): 155-166.
10. Ypsilantis P, Mikroulis D, Politou, et al. Tolerance to propofol's sedative effect in mechanically ventilated rabbits. Anesth Analg 2006; 103(2):359-365.
11. Martın-Cancho MF, Lima JR, Luis L, Crisostomo V, Carrasco-Jimenez MS, Uson-Gargallo J. Relationship of bispectral index values, haemodynamic changes and recovery times during sevoflurane or propofol anaesthesia in rabbits. Lab Anim 2006; 40(l):28-42
12. Kayaalp SO.: Genel Anestezinin Farmakolojik Yönü ve Genel Anestezikler. Tıbbi Farmakoloji. 9 Baskı, Ankara, Hacettepe TAŞ:2001;765-78.
13. Claeys MA, Gepts E, Camu F. Haemodynamics changes during anaesthesia induced and maintained with propofol. Br J Anaesth 1988;60(l):3-9
14. Brüssel T, Theissen JL, Vigfusson G, Lunkenheimer PP, Van Aken H, Lawin P. Haemodynamic and cardiodynamic effect of propofol and ethomidate: negative inotropic of properties of propofol. Anaesth Analg 1989;69(l):35-40.
15. Mulier JP, Wounters PF, Van Aken H, Vermaut G, Vandermeersch E. Cardiodynamics effects of propofol in comparison with thiopental: assessment with a transesophageal echocardiographic approach. Anaesth Analg 1991;72(l):28-35.
16. Ilkiw JE, Pascoe PJ, Haskins SC, Patz JD. Cardiovascular and respiratory effects of propofol administration in hypovolemic dogs. Am J Vet Res 1992;53(12):2323-2327.
17. Estafanous FG, Urzua J, Yared JP, Zurick AM, Loop FD, Tarazi RC. Pattern of haemodynamic alterations during coronary artery operations. J Thorac Cardiovasc Surg 1984;87(2):175-182.
18. Stelow EB, Johari VP, Smith SA, Crosson JT, Apple FS. Propofol-associated rhabdomyolysis with cardiac involvement in adults: chemical and anatomic findings. Clinical Chemistry 2000; 46(4):577-581.
19. Story DA, Poustie S, Liu G, McNicol PL. Changes in plasma creatinine concentration after cardiac anesthesia with isoflurane, propofol, or sevoflurane: a randomized clinical trial. Anesthesiology 2001 ;95(4): 842-848.
20. S Gülbin, D Yavuz, K Buket, A KA. Subanestezik Konsantrasyonlarda Solutulan Desfluran ve Sevofluranın Sıçanlarda; Karaciğer ve Böbrçjt Toksisitesi ile Davranışları Üzerine Etkileri. Türk Anest Rean Der Dergisi 2007;35(2):83-89.
21. Slater MS, Mullins RJ. Rhabdomyolysis and myoglobinuric renal failure in trauma and surgical patients: a review. J Am Coll Surg 1998;186(6):693-716.
22. Koch M, De Backer D, Vincent JL. Lactic acidosis: An early marker of propofol infusion syndrome? Intensive Care Medicine 2004; 30(3):522.
23. Kill C, Leonhardt A, Wulf H. Lactic acidosis after short-term infusion of propofol for anaesthesia in a child with osteogenesis imperfecta. Paediatric Anaesthesia 2003;13(9):823-826.
24. Haase R, Sauer H, Eichler G. Lactic acidosis following short-term propofol infusion may be an early warning of propofol infusion syndrome. J Neurosurg Anesthesiol 2005; 17(2): 122-123.
25. Machata AM, Gonano C, Birsan T, Zimpfer M, Spiss CK. Rare but dangerous adverse effects of propofol and thiopental in intensive care. J Trauma 2005;58(3):643-645.
26. Marinella MA. Lactic acidosis associated with propofol. Chest 1996;109(1):292.
27. Burow BK, Johnson ME, Packer DL. Metabolic acidosis associated with propofol in the absence of other causative factors. Anesthesiology 2004;101(1):239-241.
28. Salengros JC, Velghe-Lenelle CE, Bollens R, Engelman E, Barvais L. Lactic acidosis during propofol-remifentanil anesthesia in an adult. Anesthesiology 2004;101(l):241-243.
29. Liolios A, Guerit JM, Scholtes JL, Raftopoulos C, Hantson P. Propofol infusion syndrome associated with short-term large-dose infusion during surgical anesthesia in an adult. Anesth Analg 2005; 100(6): 1804-1806.
30. Betrosian AP, Papanikoleou M, Frantzeskaki F, Diakalis C, Georgiadis G. Myoglobinemia and propofol infusion. Acta Anaesthesiol Scand 2005;49(5):720.
31. Antognini JF, Wang XW, Carstens E. Isoflurane anesthetic depth in goats monitored using the bispectral index of the electroencephalogram. Vet Res Commun 2000:24(6):361-370.
32. Haga HA, Tevik A, Moerch H Bispectral index as an indicator of anesthetic depth during isoflurane anesthesia in the pig. Veterinary Anesthesia and Analgesia 1999;26(l):3-7.
33. Haga HA, Tevik A, Moerch H. Electroencephalographic and cardiovascular indicators of nociception during isoflurane anesthesia in pigs. Veterinary Anesthesia and Analgesia 2001; 28(3): 126-131.
34. Greene SA, Benson GJ, Tranquilli WJ, Grimm KA. Relationship of canine bispectral index to multiples of sevoflurane minimal alveolar concentration, using patch or subdermal electrodes. Comp Med 2002;52(5):424-428.
35. Khiabani KT, Kerrigan CL. A new protocol for prolonged general anesthesia in rabbits. Plast Reconstr Surg 1998; 102(5): 1787.
36. Türe H, Mercan A, Koner O, Aykac B, Türe U. The effects of propofol infusion on hepatic and pancreatic function and acid-base status in children undergoing craniotomy and receiving phenytoin. Anesth Analg 2009;109(2):366-371.
37. Gottschling S, Meyer S, Krenn T, et al. Effects of short-term propofol administration on pancreatic enzymes and triglyceride levels in children. Anaesthesia 2005;60(7):660-663.
38. Jawaid Q, Presti ME, Neuschwander-tetri BA, Burton FR. Acute pancreatitis after single-dose exposure to propofol: a case report and review of literature. Dig Dis Sci 2002;47(3):614-618.
39. Zhang YL, Guan CY, Hu SF, Zhou DC. Effect of long-term sevoflurane anesthesia on markers of myocardial damage. Zhonghua Yi Xue Za Zhi 2009;89(27):1916-1918.
40. Özlü O, Ozkara HA, Eris S, Ocal T. Propofol anaesthesia and metabolic acidosis in children. Paediatric Anaesthesia 2003; 13(l):53-57.