Sepsiste adrenal fonksiyonlar ve fizyolojik doz steroid tedavisi

Abstract

ÖZET Sepsis tedavisindeki yeni gelişmelere rağmen ölüm oranı halen yüksektir. Sepsisli hastalarda steroid tedavisi ile ilgili tartışmalar sürmektedir. Bu çalışmada fizyolojik dozda prednizolonun sepsis tedavisindeki yeri araştırılmıştır. Bu çalışmada 40 sepsisli hasta değerlendirilmeye alındı. Tüm hastalara bazal kortizol ölçümü ve ACTH stimülasyon testi yapıldı. Ardışık olarak bir gruba standart sepsis tedavisi diğer gruba standart tedavinin yanısıra fizyolojik doz prednizolon tedavisi verildi. Hastaların %77.5 (31/40)'inde toplumda gelişen infeksiyon, %22.5 (9/40)'inde hastane infeksiyonu vardı. Hastaların ortalama APACHE II skorları 16.6±6.9, steroid alan grupta 17.6±4.5 ug/dL ve standart tedavi grubunda 21.0±7.9 ug/dL idi. Çalışmamızda gram-negatif sepsis oranı 71%27.7 (11/40), gram-pozitif sepsis oranı %37.7 (15/40) saptanırken 13 hastada etken belirlenemedi. Steroid alan ve almayan gruplar karşılaştırıldığında, ölüm oranı steroid alan grupta %40 (8/20), standart tedavi grubunda %60 (12/20) bulundu (p>0.05). Hastane infeksiyonu olan hastalarda ölüm oranı steroid alan grupta %50 (2/4), standart tedavi grubunda %100 (5/5) bulundu (p>0.05). Ortalama bazal kortizol düzeyi tüm hastalarda 50.8+29.1 ug/dL, steroid alan grupta 49.3+28 ug/dL, standart tedavi grubunda 52.4+30.8 ug/dL iken steroid alan grupta ölen hastalarda 44.4+24.8 ug/dL, yaşayan hastalarda 52.5+30.5 ug/dL ve standart tedavi grubunda ölen hastalarda 60.5+34.7 ug/dL,yaşayan hastalarda 40.3+19.9 ug/dL bulundu. İyileşen hastalarda ondördüncü gün bazal kortizol düzeyi 17.2+8.6 ug/dL idi. Birinci ve ondördüncü gün bazal kortizol düzeyleri arasındaki fark istatistiksel açıdan anlamlı bulundu (p<0.001). Ortalama pik kortizol düzeyi tüm hastalarda 74.6+36.2 ug/dL, steroid alan grupta 76.8+33.3 ug/dL, standart tedavi grubunda 72.5+39.6 ug/dL iken steroid alan grupta ölen hastalarda 73.1+35.1 Mg/dL, yaşayan hastalarda 79.2+33.5 ug/dL ve standart tedavi grubunda ölen hastalarda 80.7+45.9 ug/dL, yaşayan hastalarda 60.1+25.7 ug/dL bulundu. Kortizol cevabı ortalaması tüm hastalarda 20.6+25.1 ug/dL, steroid alan grupta 24.2+28.5 ug/dL, standart tedavi grubunda 17.1+21.2 ug/dL iken steroid alan grupta ölen hastalarda 28.7+22.1 ug/dL, yaşayan hastalarda 21.2+32.7 u,g/dL ve standart tedavi grubunda ölen hastalarda 16.3±24.6 (ig/dL, yaşayan hastalarda 18.2+16.3 ug/dL bulundu. Bazal ve pik kortizol ile kortizol cevabı ortalamalarında gruplara ve mortaliteye göre anlamlı bir fark görülmedi. Tüm hastalarımızın bazal kortizol düzeyi 11 ug/dL'nin üstündeydi ve 14 hastanın kortizol cevabı 9 (ig/dL'nin altındaydı. Bu hastalardan steroid alan gruptaki beş hastanın ikisi 72(%40) ve standart tedavi grubundaki dokuz hastanın beşi (%55.6) hasta öldü. Kortizol cevabı 9 ug/dL'nin altında olan hastaların bazal kortizol düzeyi ortalaması 50.4±32.8 u,g/dL iken kortizol cevabı 9 ng/dL'nin üstünde olan hastaların bazal kortizol düzeyi ortalaması 5 1. 1±27.6 ug/dL idi. Her iki grup arasında anlamlı bir fark yoktu. Hastalarımızdan sadece birinde (%2.5) bazal ve pik kortizol düzeyleri 20 ug/dL'nin altındaydı ve bu hasta öldü. Bu durum adrenal yetmezlik olarak değerlendirildi. Sepsisten septik şoka ilerleyen süreçte adrenal yetmezliğin sanıldığı kadar yüksek olmadığı sonucuna vardık. Hastalarımızda hem bazal ve hem de ACTH stimülasyonu sonrası kortizol düzeyi ortalamaları normal değerlerin üzerindeydi. Buna rağmen steroid almayan grupta mortalite istatistiksel olarak anlamlı bulunmasa da yüksekti. Sonuç olarak, fizyojik doz steroid tedavisi mortaliteyi düşürdü, fakat iki grup arasındaki fark anlamlı değildi. Sepsiste fizyojik doz steroid tedavisi daha geniş hasta gruplarıyla değerlendirilmelidir. 73

SUMMARY The death rate is still high in sepsis in spite of development in treatment of sepsis. Steroid therapy in patients with sepsis is still controversial. In this study, we investigated the role of steroids in physiologic dosage in the treatment of sepsis. Forty patients with sepsis are enrolled in this study. Basal Cortisol measurement and ACTH stimulation tests were carried out in all patients. The patients were divided in to two groups consequtively; one group received only standard sepsis treatment and second group received standard sepsis treatment and prednisolon in physiologic dose. Community-acquired sepsis were determined in 77.5% (31 of 40) patients, nosocomial sepsis in remaining 22.5% (9 of 40) patients. Mean APACHE II scores was 21+7.9 ug/dL, in the group given standard 74treatment and 17.6+4.5 ug/dL in the steroid therapy groups. Gram-negative bacteria isolated in 27.7% (11 of 40) patients and gram-positive bacteria in 37.7% (15 of 40) patients. No pathogen was isolated in the remain 44.6% (13 of 40) patients.. The mortality rate was 40% (8 of 20) in the steroid therapy group and 60% (12 of 20) in the standard treatment group (p>0.05). In patients with nosocomial infections the mortality rate was 50% (2 of 4) in steroid therapy group and 100% (5 of 5) in standard treatment group (p>0.05). Mean basal Cortisol level were 50.8±29.1 ug/dL in all patients, 49.3+28 ug/dL in steroid therapy group and 52.4+30.8 ug/dL in standard treatment group. Basal Cortisol level were found to be 44.4+24.8 ug/dL in patients who died in steroid therapy group and 52.5+30.5 ug/dL in survivors. Basal Cortisol levels were 60.5+34.7 ug/dL in patients who died in standard treatment group and 40.3+19.9 ug/dL in survivors. Basal Cortisol level in the 14 day was 17.2+8.6 ug/dL in patients who get better. The difference between first and fourteenth day basal Cortisol levels were statistically significant (pO.0001). Mean peak Cortisol levels were 74.6+36.2 ug/dL in all patients, 76.8+33.3 ug/dL in steroid therapy group and 72.5+39.6 ug/dL in standard treatment group. Peak Cortisol levels were 73.1±35.1ug/dL in patients who died in steroid therapy group and 79.2+33.5 ug/dL in survivors. Peak Cortisol levels were found to be 80.7+45.9 ug/dL in the patients who died standard treatment group and 60.1+25.7 ug/dL in survivors. Mean Cortisol responses were 20.6+25.1 ug/dL in all patients, 24.2±28.5 ug/dL in steroid therapy group and 17.1±21.2 ug/dL in standard treatment group. Cortisol responses were 28.7 ±22.1 ug/dL in patients who died in steroid therapy group and 21.2+32.7 ug/dL in survivors. Cortisol responses were found to be 16.3+24.6 ug/dL in the patients who died standard treatment group and 18.2+16.3 ug/dL in survivors. For the consideration of groups and mortality, there was no significant difference between the levels of basal and peak Cortisol and Cortisol response. Basal Cortisol levels were higher than 11 ug/dL in all patients except for 14, whose Cortisol levels were lower than 9 ug/dL. Of these 14, 40% (2 of 5) of the patients in the steroid therapy group and 55.6 % (5 of 9) in standard treatment group were lost. Mean basal 75Cortisol level was 50.4+32.8 ug/dL in patients whose Cortisol responses were lower than 9 mg/dl, while it was 51.1+27.6 ug/dL for the patients who had Cortisol responces higher than 9 ug/dL. There was no statistically significant difference between two groups. Only one patient had basal and peak Cortisol level lower than 20 ug/dL and he was lost. This condition was evaluated as adrenal insufficiency. In advancing process from sepsis to septic shock, it was concluded that adrenal insufficiency was not frequent as supposed. In our patients both basal and Cortisol levels after ACTH stimulation were above normal values. However the mortality rate was higher in standard treatment group, although this was not statistically significant. In conclusion, physiologic dose prednisolon decreased the mortality but, the difference between two groups was not significant. Physiologic dose steroid in sepsis should be evaluated in a large group of patients. 76