Publication: Effects of Propofol and Midazolam on the Inflammation of Lungs after Intravenous Endotoxin Administration in Rats
Abstract
Amaç: Sepsiste akciğer komplikasyonları önemli bir yer tutar (ARDS, diffüz pnömoni gibi). Akut respiratuar distres sendromu (ARDS) akciğerde alveollere aşırı nötrofil migrasyonu ile karakterizedir. Propofol ve midazolam yoğun bakımlarda hasta sedasyonu için çok yaygın olarak kullanılan ilaçlardır. Escherichia Coli endotoksini ile oluşturulan sepsis modelinde propofol ve midazolam anestezisi altında akciğerlere nötrofil göçünü ve hemodinamik parametreleri değerlendirmeyi amaçladık. Gereç ve Yöntem: 40 adet rat (Spraque-Dawley cinsi) rastgele dört gruba- ayrıldı. 1- Grup E (Endotoksemi grubu) 2- Grup K (Kontrol grubu) 3- Grup PE (Propofol-Endotoksemi grubu) 4- Grup ME (Mida- zolam-Endotoksemi grubu). Tüm deneklere intraperitoneal 30 mg/kg tiyopental sodyum verildi. Denekler trakestomi yoluyla ventile edildiler. Devamlı kan basıncının ölçülmesi ve kan örneklerinin alınabilmesi için femoral arter kanüle edildi. Grup Edeki deneklere E.Coliden elde edilmiş lipopolisakkarit derivesi intravenöz olarak 15 mg/kg uygulandı. Grup Kdaki deneklere %0,9 NaCL 1 mL/kg intravenöz uygulandıktan sonra 1 mL/kg/saat infüzyona devam edildi. Grup PEdeki deneklere E. Coli endotoksininden 15 mg/kg intravenöz uygulandıktan sonra 10 mg/kg Propofol intravenöz olarak uygulandı Daha sonra 10 mg/kg/ saat propofol infuzyonuna devam edildi. Grup MEdeki deneklere de E.Coli endotoksininden 15 mg/kg intravenöz uygulandıktan sonra 0,1 mg/kg Midazolam enjekte edildi. 0,1 mg/kg/saat midazolam infüzyo- nu uygulandı. Denekler 5. saat sonunda intravenöz potasyum klorid verilerek sakrifıye edildi. Akciğerleri çıkarıldı. %10 formalin içinde 3-5 gün fıkse edildi ve parafın bloklarına gömüldü. Akciğer kesitleri, nötro- fıl yoğunluğuna göre 0-3 arasında histopatolojik olarak skorlandı. Bulgular: Grup E deki deneklerin akciğer dokularında yoğun nötrofil göçü mevcuttu (grade 2, 3). Grup ME deki denek akciğerlerinde orta derecede nötrofil göçü mevcutken (grade 1, 2) Grup PE de sadece %30 denekte hafif nötrofil göçüne rastlandı (grade 1). Sonuç: Endotoksinle indüklenen sepsis modelinde propofol infüzyo- nunun midazolamla karşılaştırıldığında akciğerlere daha az nötrofil göçü ile ilişkili olduğu ve literatürün de ışığında serbest radikal aracılı lipit peroksidasyonunu ve hastaların sistemik inflamasyonu hafiflete- bileceği sonucuna vardık.
Objective: Pulmonary complications are important sepsis (such as ARDS, diffuse pneumonia). Acute respiratory distress syndrome (ARDS) is characterized by the extensive migration of neutrophils into alveoli of the lungs. Propofol and midazolam are the most widely used agents for sedation in intensive care units. Aimed to investigate the effects of anaesthesia with propofol and midazolam on measured hemodynamic variables and neutrophil migration induced by Esch- erichia Coli endotoxin (ECE) in pulmonary viscera. Materials and Methods: Forty Sprague Dawley male rats were ran- domly assigned to four groups: Thiopental Sodium 30 mg/kg was administered intraperitoneally to anesthetize the rats. They were ventilated via tracheotomy. Femoral artery was cannulated for the measurement of continuous blood pressure and gases. Group C was the control. After the administration of 1 mL/kg 0.9% NaCL, infusion began at 1 mL/kg/h rate. In Group E 15 mg/kg lipopolysaccharide de- rived from ECE was administered iv. In Group PE, after a bolus dose of 10 mg/kg propofol and 15 mg/kg ECE, 10 mg/kg/h infusion was applied. In Group ME, after 0.1 mg/kg midazolam bolus dose and 15 mg/kg ECE administration, 0.1 mg/kg/h infusion was administered iv. Rats were sacrified by iv potassium chloride. The lungs were then removed, fixed in 10% buffered formalin for 3 days and embedded in paraffin. They were graded on a scale of 0-3 according to the ag- gregation of neutrophils. Results: There was intense neutrophil migration in Group E (grade 2, 3). However, although mild neutrophil migration was obtained in 70% of the rat lungs in Group ME (grade 1, 2), it was recorded in only 30% of Group PE (grade 1). Conclusion: The sepsis model induced by ECE and compared with midazolam, propofol anaesthesia is associated with less neutrophil in- filtration. In the light of the literature, propofol attenuate the free-radi- cal-mediated lipid peroxidation and systemic inflammation in patients.
Objective: Pulmonary complications are important sepsis (such as ARDS, diffuse pneumonia). Acute respiratory distress syndrome (ARDS) is characterized by the extensive migration of neutrophils into alveoli of the lungs. Propofol and midazolam are the most widely used agents for sedation in intensive care units. Aimed to investigate the effects of anaesthesia with propofol and midazolam on measured hemodynamic variables and neutrophil migration induced by Esch- erichia Coli endotoxin (ECE) in pulmonary viscera. Materials and Methods: Forty Sprague Dawley male rats were ran- domly assigned to four groups: Thiopental Sodium 30 mg/kg was administered intraperitoneally to anesthetize the rats. They were ventilated via tracheotomy. Femoral artery was cannulated for the measurement of continuous blood pressure and gases. Group C was the control. After the administration of 1 mL/kg 0.9% NaCL, infusion began at 1 mL/kg/h rate. In Group E 15 mg/kg lipopolysaccharide de- rived from ECE was administered iv. In Group PE, after a bolus dose of 10 mg/kg propofol and 15 mg/kg ECE, 10 mg/kg/h infusion was applied. In Group ME, after 0.1 mg/kg midazolam bolus dose and 15 mg/kg ECE administration, 0.1 mg/kg/h infusion was administered iv. Rats were sacrified by iv potassium chloride. The lungs were then removed, fixed in 10% buffered formalin for 3 days and embedded in paraffin. They were graded on a scale of 0-3 according to the ag- gregation of neutrophils. Results: There was intense neutrophil migration in Group E (grade 2, 3). However, although mild neutrophil migration was obtained in 70% of the rat lungs in Group ME (grade 1, 2), it was recorded in only 30% of Group PE (grade 1). Conclusion: The sepsis model induced by ECE and compared with midazolam, propofol anaesthesia is associated with less neutrophil in- filtration. In the light of the literature, propofol attenuate the free-radi- cal-mediated lipid peroxidation and systemic inflammation in patients.