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Abstrak :
Insidens insufisiensi adrenal pada pasien renjatan sepsis dilaporkan sekitar 40-65. Sitokin IL-1 dan IL-6 dapat menstimulasi sekresi kortisol sedangkan TNF-? serta MIF berperan dalam menghambat pembentukan kortisol. Penelitian ini bertujuan untuk mengetahui peran IL-1, IL-6, TNF-? dan MIF dalam terjadinya insufisiensi adrenal relatif pada renjatan sepsis.Penelitian eksperimental dilakukan di laboratorium FKH IPB berlangsung selama 6 bulan April-September 2015 . Model anak babi yang dipakai berumur 6-8 minggu dengan berat badan 5-10 kg. Pemilihan sampel dengan consecutive sampling dengan total n = 20. Anak babi diberikan infus endoktoksin dengan dosis 50 ug/kg BB. Sampel darah untuk analisis IL-1, IL-6, TNF-?, MIF, ACTH, kortisol, 17 OHP, DHEA, androstenedion diambil sebelum pemberian endotoksin dan tiap 15 menit hingga terjadi renjatan sepsis, kemudian dilakukan uji synacthen. Pemeriksaan imunohistokimia dilakukan pada kelenjar adrenal, hipofisis, dan hipotalamus.Dari 19 anak babi yang dianalisis mengalami renjatan sepsis dalam waktu 60 menit. Karakteristik sampel tidak berbeda bermakna antara kedua kelompok. Kadar IL-6 pada kelompok IAR dibandingkan dengan kelompok tanpa IAR berbeda bermakna pada menit ke-45 0,65 0,5-4,32 pg/dL vs. 0,54 0,51-0,61 pg/dL , p = 0,008 . Kadar IL-1 antara kelompok IAR dibandingkan kelompok tanpa IAR tidak berbeda bermakna. Kadar TNF-? pada kelompok IAR dibandingkan dengan kelompok tanpa IAR berbeda bermakna pada menit ke-15 1862,5 327,9-4511,14 pg/dL vs. 155,38 24,67-394,10 pg/dL , p = 0,002 dan menit ke-30 4295,76 246,9-5913,37 pg/dL vs. 422,90 101,05-4129,42 pg/dL , p = 0,007 . Kadar MIF kelompok IAR dibandingkan dengan kelompok tanpa IAR berbeda bermakna pada saat renjatan sepsis 25,28 18,45-30,64 ng/dL vs. 11,30 7,1-15,14 ng/dL p = 0,003 . Pemeriksaan imunohistokimia hanya pada hipotalamus yang menunjukkan pewarnaan terhadap IL-1, IL-6, TNF-? dan MIF pada kelompok dengan IAR. Pada renjatan sepsis dan insufisiensi adrenal relatif kadar TNF-? meningkat pada menit-menit awal, kemudian kadar IL-6 meningkat kemudian serta terakhir kadar MIF meningkat pada saat renjatan sepsis. Kadar IL-1 tidak terdapat perbedaan antara kedua kelompok. Kata kunci: IL-1, IL-6, insufisiensi adrenal relatif, MIF, renjatan sepsis, TNF-?

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Incidence of adrenal insufficiency in septic shock ranged between 40 ndash 65 . The mechanism of relative adrenal insufficiency in septic shock is caused by inflammatory mediators. This study aimed to identify the role of IL 6, IL 1 in stimulating ACTH and cortisol release, and the role of TNF and MIF in inhibiting the level of ACTH and cortisol in septic shock with relative adrenal insufficiency RAI in order to develop guidelines for relative adrenal insufficiency marker.Experimental study was conducted in Veterinary Faculty, Bogor Agricultural Institute for 6 months Apri ndash September 2015 . Piglet models Sus scrofa aged 6 ndash 8 weeks weighing 5 ndash 10 kg. Consecutive sampling was used with total 20 piglets. Piglet models were given 50 ug kg endotoxin infusion Escherichia coli O111 B4 Sigma chemical, St. Louis, MO, USA . Blood sample for analysis of IL 1, IL 6, TNF , MIF, ACTH, cortisol, 17 OHP, DHEA, androstenedione was collected before endotoxin administration and every 15 minutes until septic shock occurred. Piglet models were monitored using PiCCO monitor. Stimulation test was then performed using synthetic corticotropin Synacthen and blood sample was collected again along with immunohistochemistry examination of the adrenal, pituitary and hypothalamus glands.From 19 study subjects analized, all subject had septic shock in 60 minutes. Study subject characteristics in each group were similar. The level of IL 6 at 45 minutes had a significant different compared to the group without RAI 0.65 0.5 ndash 4.32 pg dL vs. 0.54 0.51 ndash 0.61 pg dL , p 0.008 . The level of IL 1 during septic shock were not significantly different between both groups. The level of TNF in RAI group had significant different compared to the group without RAI at 15 minutes 1862.5 327.9 ndash 4511.14 pg dL vs. 155.38 24.67 ndash 394.10 pg dL , p 0.002 and at 30 minutes 4295.76 246.9 ndash 5913.37 pg dL vs. 422.90 101.05 ndash 4129.42 pg dL , p 0.007 The level of MIF in group with RAI during septic shock had a significant different compared to the group without RAI t 25.28 18.45 ndash 30.64 ng dL vs. 11.30 7.1 ndash 15.14 ng dL , p 0.003 . Immunohisto chemistry staining of IL 1, IL 6, TNF , and MIF was observed only in the hypothalamus glands of the RAI group. In septic shock and relative adrenal insufficiency, TNF increased in earlier minutes, then IL 6 increased and later MIF increased in septic shock condition. IL 1 level had no difference increment for both group.Keywords IL 1, IL 6, MIF, relative adrenal insufficiency, septic shock, TNF

Abstrak :
ABSTRAK
Inflamasi sistemik pada renjatan sepsis dapat menyebabkan insufisiensi adrenal. Kadar asam lemak bebas ALB yang tinggi diketahui menyebabkan inflamasi steril dan menghambat adrenocorticothropic hormone dan sekresi kortisol. Pemberian hidrokortison pada renjatan sepsis diharapkan memperbaiki hemodinamik, menurunkan ketergantungan terhadap obat vasoaktif dan memperbaiki disfungsi organ.Penelitian bersifat studi eksperimental yang bertujuan menilai pengaruh ALB dan pemberian hidrokortison terhadap hemodinamik, kadar laktat, cedera paru dan kadar kortisol darah pada renjatan sepsis model anak babi. Penelitian dilaksanakan di Divisi Bedah dan Radiologi Departemen Klinik Reproduksi dan Patologi Fakultas Kedokteran Hewan Institut Pertanian Bogor FKH IPB pada April -September 2015 dan telah disetujui oleh Komisi Etik Hewan FKH IPB.Delapan model anak babi Sus scrofa berusia 6-8 minggu dengan berat 5-10 kg dibagi dalam 2 kelompok, yaitu kelompok lipid dan kelompok kontrol. Kelompok lipid diberi lipid 20 sebanyak 3 gram/kgbb intravena dan kelompok kontrol tanpa pemberian lipid sebelum induksi sepsis. Pengukuran parameter hemodinamik dengan Pulse Contour Cardiac Output PiCCO . Pengukuran kadar laktat dengan i-Stat. Cedera paru ditentukan dengan pengukuran extravascular lung water index EVLWI dan rontgen toraks. Tes synacthen dilakukan untuk mengetahui adanya insufisiensi adrenal relatif IAR .Pengaruh ALB terhadap hemodinamik dinilai dengan rerata cardiac index 60 menit setelah pemberian hidrokortison yang berbeda bermakna [2,14 0,06 l/menit/m2 vs. 2,75 0,04 l/menit/m2 p 0,002 ]. Jumlah cairan dan obat vasoaktif yang dibutuhkan kelompok lipid untuk mempertahankan mean arterial blood pressure > 65 mmHg lebih banyak dibandingkan kelompok kontrol. Kadar laktat meningkat sebelum induksi sepsis pada kelompok lipid [2,28 0,52 vs. 1,28 0,45 mmol/L p 0,001 ]. Bersihan laktat pada kelompok lipid lebih buruk dibandingkan kelompok kontrol. Extravascular lung water index kelompok lipid lebih tinggi bermakna dibanding kelompok kontrol setelah 60 menit resusitasi [21 4,04 mL/kg vs. 12,38 2,32 mL/kg p 0,004 ]. Gambaran radiologi efusi pleura dan edema pulmonal terjadi pada seluruh model anak babi kelompok lipid. Insufisiensi adrenal relatif terjadi pada 7 model anak babi di kelompok lipid dan 4 di kelompok kontrol.Kesimpulan penelitian ini adalah kadar ALB yang tinggi memperberat inflamasi dan merupakan faktor risiko terjadinya IAR. Kata kunci: Asam lemak bebas, cedera paru, hemodinamik, hidrokortison insufisiensi adrenal relatif, laktat, renjatan sepsis, sepsis.

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ABSTRACT
Cortisol deficiency is associated with increased morbidity and mortality during critical illness. Dysregulation of immune system in septic shock triggers adrenal insufficiency. Free fatty acid FFA is known to induced sterile inflammation and inhibit adrenocorticothropic hormone and cortisol secretion. Hydrocortisone administration is expected to improve hemodynamic, decrease dependency of vasoactive drugs and improve organ dysfunction in septic shock.The aim of this study is to find out the effect of FFA and hydrocortisone administration on hemodynamic parameters, lactate, lung injury and blood cortisol levels in septic shock piglet models, conducted in April September 2015 in the Division of Surgery and Radiology School of Veterinary Medicine, Institut Pertanian Bogor IPB and has been approved by the Animal Ethics Committee of School of Veterinary Medicine IPB. Sixteen piglet models Sus scrofa entered the study. The piglets were 6 8 weeks old, weighing 5 10 kg divided into two groups, lipids and control groups. Administration of 3 g kg BW of lipid 20 were performed intravenously before sepsis induction for lipid group. Hemodynamic measurement by Pulse Contour Cardiac Output PiCCO by Picco. Lactate measurement by i Stat. Lung injury was determined by Extravascular lung water index EVLWI and chest X ray. Synacthen test to determine relative adrenal insufficiency RAI .FFA influences was shown on cardiac index 60 min after adminstration of hydrocortisone in lipid group 2.14 0.06 L min m2 and control group 2.75 0.04 L min m2 p 0.002 . Lipid group require fluids and vasoactive drugs more than the control grup to maintain mean arterial blood pressure 65 mmHg. Lactate levels before induction of sepsis lipid group 2.28 0,52 mmol L and control group 1.28 0.45 mmol L p 0.001 . Lactate clearance in lipid group was worse than the control group. Extravascular lung water index at 60 minutes after resuscitation in lipid group 21 4.04 mL kg and control group 12.38 2.32 mL kg p 0.004 . Pleural effusion and pulmonary edema were found in all piglet models in lipid group. Relative adrenal insufficiency occured to 7 piglet model in lipid gorup and 4 in control group.Conclusion High level FFA aggravate inflammation in septic shock and is a risk factor for RAI. Hydrocortisone administration improve circulation and lactate levels. Keywords FFA, hemodynamic, hydrocortisone, lactate, lung injury, relative adrenal insufficiency, sepsis, septic shock