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"Latar belakang. Acute respiratory distress syndrome (ARDS) merupakan salah satu komplikasi fatal sepsis berat. Penggunaan cairan koloid sebagai cairan resusitasi dapat menurunkan kejadian ARDS lebih banyak karena memiliki berat molekul yang lebih tinggi dibandingkan cairan kristaloid. Peningkatan extravascular lung water (EVLW), kadar interleukin-8 (IL-8) dan vascular cell adhesion molecule-1 (VCAM-1) telah diteliti sebagai indikator penting yang berperan dalam patogenesis ARDS. Penelitian pada hewan coba diharapkan dapat memberikan penjelasan yang lebih baik mengenai patofisiologi ARDS yang kompleks dan sulit dimengerti. Tujuan. Mengungkap pengaruh cairan koloid atau kristaloid terhadap kejadian ARDS pada model hewan coba babi dengan sepsis berat, serta menganalisis pengaruh cairan kristaloid atau koloid terhadap peningkatan EVLW, IL-8, dan VCAM-1. Metode. Penelitian ini merupakan studi eksperimental acak tersamar ganda, dilakukan di Laboratorium Bedah Eksperimental, Fakultas Kedokteran Hewan, Institut Pertanian Bogor, dengan menggunakan babi (Sus scrofa) yang sehat berusia 2-3 bulan, berat badan 8-12 kg. Subjek dialokasikan secara acak menjadi dua kelompok, yaitu yang mendapatkan cairan resusitasi koloid atau kristaloid. Setelah pemberian endotoksin 50 μg/kg, tanda klinis ARDS, EVLW, IL-8, dan VCAM-1 dipantau saat sepsis, sepsis berat, 1 jam, dan 3 jam pasca-resusitasi cairan. Tiga jam pasca-resusitasi, dilakukan eutanasia pada babi, kemudian spesimen jaringan paru diambil untuk pemeriksaan histopatologi. Hasil Utama. ARDS kategori ringan lebih banyak terdapat pada kelompok koloid, sedangkan ARDS kategori sedang lebih banyak pada kelompok kristaloid. Rerata skor cedera paru pada kelompok koloid lebih rendah dibandingkan dengan kristaloid (0,4 vs. 0,7; p=0,001). Peningkatan EVLW lebih sedikit terjadi pada kelompok koloid dibandingkan dengan kristaloid pada 1 jam (1,0 vs. 3,0 mL/kgbb; p=0,030) dan 3 jam pasca-resusitasi (2,7 vs. 6,3 mL/kgbb; p=0,034). Pada kedua kelompok, kadar IL-8 meningkat secara bermakna setelah pemberian endotoksin (103,1 vs. 3854,5 pg/mL; p=0,012 pada kelompok koloid dan 125,0 vs. 4419,3 pg/mL; p=0,003 pada kelompok kristaloid). Nilai kadar IL-8 dan VCAM-1 tidak berbeda bermakna antara kedua kelompok. Simpulan. Penggunaan cairan koloid sebagai cairan resusitasi tidak menurunkan kemungkinan kejadian ARDS dibandingkan kristaloid. Cairan koloid berhubungan dengan peningkatan EVLW dan skor cedera paru yang lebih rendah dibandingkan dengan cairan kristaloid, tetapi tidak pada kadar IL-8 dan VCAM-1.

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Background. Acute respiratory distress syndrome (ARDS) is a fatal complication of severe sepsis. Due to its higher molecular weight, the use of colloids in fluid resuscitation may be associated with fewer cases of ARDS compared to crystalloids. Extravascular lung water (EVLW) elevation and levels of interleukin-8 (IL-8) and vascular cell adhesion molecule-1 (VCAM-1) have been studied as indicators playing a role in the pathogenesis of ARDS. The use of animal models may provide a better understanding of the complex and poorly understood pathophysiology of ARDS.

Objectives. To determine the effects of colloid or crystalloid fluid resuscitation on the incidence of ARDS, elevation of EVLW, and levels of IL-8 and VCAM-1, in swine models with severe sepsis.

Methods. This was a randomized trial conducted at the Laboratory of Experimental Surgery, School of Veterinary Medicine, Institut Pertanian Bogor, using healthy swine (Sus scrofa) models aged 2 to 3 months with a body weight of 8 to 12 kg. Subjects were randomly allocated to receive either colloid or crystalloid fluid resuscitation. After administration of 50 μg/kgbw of endotoxin, clinical signs of ARDS, EVLW, IL-8, and VCAM-1 were monitored during sepsis, severe sepsis, and one- and three hours after fluid resuscitation. Three hours after resuscitation, euthanasia was performed on the animal and the lung tissue specimen was taken for histopathological examination.

Results. Mild ARDS was more prevalent in the colloid group, while moderate ARDS was more frequent in the crystalloid group. Mean lung injury score was lower in colloid compared to crystalloid group (0.4 vs. 0.7; p=0.001). The increase in EVLW was lower in the colloid compared to the crystalloid group both at one hour (1.0 vs. 3.0 mL; p=0.030) and three hours post-resuscitation (2.7 vs. 6.3 mL/kg; p=0.034). In both groups, IL-8 levels were significantly higher after endotoxin administration (103.1 vs. 3854.5 pg/mL; p=0.012 in the colloid group and 125.0 vs. 4419.3 pg/mL; p=0.003 in the crystalloid group). There was no significant difference in IL-8 and VCAM-1 levels between the two groups.

Conclusion. The use of colloids in fluid resuscitation does not decrease the probability of ARDS events compared to crystalloids. Compared to crystalloids, colloids are associated with a lower increase in EVLWI and a lower mean lung injury score, but not with IL-8 or VCAM-1 levels."

"Renjatan merupakan kegawat-daruratan tersering pada anak. Laktat sering digunakan sebagai target keberhasilan resusitasi pada renjatan sepsis, namun sepertiga kasus renjatan pada anak tidak mengalami peningkatan kadar laktat alaktatemia . Penilaian laktat sebagai target keberhasilan resusitasi masih menjadi perdebatan. Penelitian sebelumnya menyimpulkan nilai bersihan laktat berkaitan dengan luaran pasien renjatan sepsis. Laktat dehidrogenase LDH -1, LDH-5 dan delivery oxygen DO2 berperan dalam metabolisme laktat dan menyebabkan kondisi alaktatemia dan hiperlaktatemia pada pasien renjatan anak.Penelitian ini bertujuan untuk mencari etiologi alaktatemia pada renjatan anak melalui pemeriksaan isoenzim LDH-1, LDH-5 dan DO2 selama proses resusitasi 6 jam. Penelitian ini adalah penelitian potong lintang pada 56 renjatan sepsis dan 44 hipovolemik berusia 1 bulan sampai 18 tahun di 4 rumah sakit umum. Pemeriksaan tekanan darah mean arterial pressure/ MAP, indeks jantung cardiac index, CI dan indeks tahanan vaskular sistemik systemic vascular resistance index, SVRI , DO2 dan pengambilan darah untuk pemeriksaan LDH-1 dan 5 dilakukan sebelum dan setelah resusitasi.Pada penelitian ini didapatkan usia terbanyak berada dalam rentang 1 ndash;59 bulan 56, dengan pasien yang datang dengan kondisi berat skor pediatric logistic organ dysfunction/PELOD-2 ge; 10 31, median kadar laktat jam ke-0 adalah 2,5 mmol/L. Angka kematian 20 . Proporsi hiperlaktatemia lebih tinggi secara bermakna p = 0,028 pada pasien renjatan dengan skor PELOD-2 ge; 10 71,9 . Tidak ada perbedaan bermakna isoenzim LDH-1, LDH-5 dan DO2 antara kelompok alaktatemia dan hiperlaktatemia. Tidak ada perbedaan bermakna MAP, CI, SVRI antar kelompok alaktatemia dan hiperlaktatemia. Tidak ada perbedaan bermakna luaran pasien berdasarkan nilai bersihan laktat.Simpulan: Pasien yang mengalami alaktatemia tidak terbukti aktivitas LDH-1 meningkat sedangkan pada hiperlaktatemia aktivitas LDH-5 meningkat. Kadar DO2 lebih tinggi pada kelompok alaktatemia dan lebih rendah pada hiperlaktatemia.

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Shock is the most common emergency condition in pediatric patients. Lactate levels have been used widely as resuscitation target in septic condition. Meanwhile, one third cases did not showed elevated lactate levels alactatemia . Lactate levels as a target for successful resuscitation is still being considered. Previous studies concluded lactate clearance has correlated with the septic shock patients outcome. Lactate dehydrogenase LDH 1, LDH 5 and delivery oxygen DO2 have an important role in lactate metabolism and causing alactatemia and hyperlactatemia in pediatric shock.

The objectives of this study were to determine the alactatemia etiology in pediatric shock using isoenzyme LDH 1, LDH 5 and DO2 examination during 6 hours resuscitation. This was a cross sectional study done in 56 patients with septic shock and 44 patients with hypovolemia, within aged 1 month until 18 years old in 4 general hospitals. Mean arterial pressure MAP , cardiac index CI , and systemic vascular resistance index SVRI , DO2, LDH 1 and LDH 5 were done before and after resuscitation.

This study found the most common age is in average 1 ndash 59 months 56 , proportion of patients who came with severe condition pediatric logistic organ dysfunction PELOD 2 score ge 10 was 31 , median of lactate levels in 0 hours was 2.5 mmol L. Death rate was 20 . Hyperlactatemia proportion was higher significantly p 0.028 in shock patients with PELOD 2 score ge 10 71.9. There was no differences in MAP, CI, SVRI values between alactatemia and hyperlactatemia groups. There was no differences in outcome based on lactate clearance.

Conclusion Patients with alactatemia do not prove that their LDH 1 activity is increased while in hyperlactatemia, the activity of LDH 5 is increased. DO2 levels were higher in the alactatemia group and lower in hyperlactatemia group."

"Panduan resusitasi anak umumnya menganjurkan pemberian cairan dalam jumlah besar. Beberapa penelitian memperlihatkan bahwa penggunaan cairan yang agresif meningkatkan mortalitas. Penelitian pada hewan menunjukkan tekanan vena sentral yang tinggi memicu pelepasan atrial natriuretic peptide ANP , sementara penelitian invitro memperlihatkan ANP meluruhkan glycocalyx endotel vaskular dan meningkatkan permeabilitas endotel. ANP juga memicu vasodilatasi. Hemodilusi berpotensi menurunkan pasokan oksigen tubuh DO2 . Penelitian bertujuan untuk melihat pengaruh resusitasi cairan terhadap kadar ANP serum, peluruhan glycocalyx endotel vaskular, extravascular lung water index ELWI , mean arterial pressure MAP , kadar hemoglobin dan pasokan oksigen. Hewan model renjatan adalah 11 ekor Sus scrofa jantan, usia 6-10 minggu. Renjatan dilakukan dengan metode fixed pressure hemorrhage. Resusitasi pertama dilakukan dengan jumlah cairan sesuai darah yang dikeluarkan resusitasi normovolemik , dilanjutkan dengan 40 mL/kg resusitasi hipervolemik . Pengukuran hemodinamik dilakukan dengan PICCO. Serum ANP dan Syndecan-1, petanda peluruhan glycocalyx, dilakukan dengan teknik ELISA. Hasil penelitian menunjukkan terjadinya peningkatan ANP pasca resusitasi normovolemik p = 0,043 , yang kemudian menurun kembali dalam 30 menit. Peluruhan glycocalyx tidak terjadi. Perbedaan ELWI pada 60 menit pasca resusitasi secara statistik bermakna, dengan perbedaan 0,93 mL/kg 95 IK:0,19 -3,62 . Terdapat korelasi kuat antara SVRI dan CI pasca resusitasi hipervolemik r = -0,587 . Tidak ada perbedaan MAP pasca resusitasi normovolemik dan hipervolemik. Kadar hemoglobin pasca resusitasi hipervolemik lebih rendah daripada pasca resusitasi normovolemik p = 0,009 . Pasokan oksigen tubuh pasca resusitasi hipervolemik lebih tinggi daripada pasca resusitasi normovolemik p = 0,012 . Simpulan: Resusitasi cairan pada renjatan akibat perdarahan tidak mengakibatkan peluruhan glycocalyx endotel vaskular. Peningkatan ELWI amat terbatas. SVRI berkorelasi terbalik dengan CI. Tidak ada perbedaan MAP antara resusitasi normovolemik dan hipervolemik. Resusitasi hipervolemik menyebabkan hemodilusi yang diimbangi dengan peningkatan curah jantung.

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Many pediatric guidelines recommend liberal fluid resuscitation, but recent studies showed that aggressive fluid resuscitation might increase mortality. Animal studies showed that high central venous pressure induced ANP secretion. Invitro studies showed convincing evidence that ANP induced glycocalyx shedding. ANP also induced vasodilatation through cGMP signal transduction pathways. Hemodilution due to a large amount of resuscitation fluid potentially decreasing oxygen delivery.The objectives of this study were investigating the effect of fluid resuscitation, in the animal model, with special concern on serum ANP, glycocalyx shedding indicate by serum Syndecan-1 , changes in extravascular lung water, systemic vascular resirtance and mean arterial pressure, hemoglobin level and oxygen delivery DO2 . The animal models were 11 male domestic pigs, 6 -10 weeks old. The shock was induced with fixed pressure hemorrhage method. Fluid resuscitation was done in 2 phases. On the first attempt, we replaced total numbers of blood that withdrawn normovolemic resuscitation . On the second attempt, we gave 40 mL/kg resuscitation fluids hypervolemic resuscitation . The hemodynamic measurements were done with PICCO. Serum ANP and Syndecan-1 were measure with ELISA method.We found that serum ANP increased after normovolemic resuscitation p = 0.043 and immediately back to base level in 30 minutes. Glycocalyx shedding did not occur. Extravascular lung water index minimally increased. There was a strong correlation between SVRI and CI at hypervolemic resuscitation r = -0.587 . There was no difference in mean arterial pressure between normovolemic and hypervolemic resuscitation. Hemoglobin level after hypervolemic resuscitation was lower than after normovolemic resuscitation p = 0.009 . Oxygen delivery was higher after hypervolemic resuscitation p = 0.012 .Conclusions: Hypervolemic resuscitation in this hemorrhagic shock model did not induce glycocalyx shedding, extravascular lung water index minimally increased. Systemic vascular resistance index negatively correlated to cardiac index. Fluid resuscitation may induce hemodilution, but oxygen delivery can be compensated by increasing cardiac output. "

"Akumulasi rantai globin-α berlebihan pada membran SDM thalassemia-β mayor menyebabkan hemolisis, eritropoiesis tidak efektif dan anemia kronik sehingga memerlukan transfusi sel darah merah (SDM) terus menerus. Transfusi rutin dan hemolisis mengakibatkan besi bebas sebagai radikal bebas dan membentuk radikal peroksil lipid di membran SDM sehingga memperberat hemolisis. Antioksidan α-tokoferol menghambat pembentukan radikal peroksil lipid tersebut.Penelitian ini bertujuan untuk menilai peran α-tokoferol terhadap hemolisis dan stres oksidatif. Penelitian ini merupakan uji klinis acak tersamar ganda pada thalassemia-β mayor usia 5–18 tahun yang mendapat transfusi dan kelasi besi rutin di Pusat Thalassemia RSUP dr.Ciptomangunkusumo Kiara. Intervensi plasebo dan α-tokoferol diberikan selama empat minggu. Suplementasi α-tokoferol berdasarkan rekomendasi Institute of Medicine (IOM), 4–8 tahun 200 mg/hari; 9–13 tahun 400 mg/hari; 14–18 tahun 600 mg/hari. Penilaian penanda hemolisis menggunakan haptogobin (Hp), hemopeksin (Hx) dan fragilitas osmotik SDM. Penanda stres oksidatif yaitu MDA, GSH, GSSG, rasio GSH/GSSG dan α-tokoferol. Pemeriksaan laboratorium dilakukan sebelum dan setelah diberikan plasebo/α-tokoferol, sesaat sebelum transfusi SDM. Analisis uji t-tidak berpasangan untuk melihat perbedaan antara kelompok studi dan uji korelasi untuk melihat hubungan antara variabel.Pada bulan Desember 2016 hingga Juli 2017, 40 subjek mampu menyelesaikan penelitian, 20 subjek kelompok plasebo dan 20 subjek kelompok α-tokoferol. Nilai rerata Hp lebih besar pada kelompok α-tokoferol (3,01 mg/dL) dibandingkan kelompok plasebo (1,08 mg/dL), secara statistik berbeda bermakna (p = 0,021). Nilai rerata kadar Hx dan persentase hemolisis SDM tidak berbeda bermakna pada kedua kelompok studi (p > 0,05). Tidak ada perbedaan bermakna pada kelompok α-tokoferol dan plasebo untuk kadar MDA (1,003 nmol/L dan 1,07 nmol/L), GSH (5,81 µM dan 6,15 µM), GSSG (1,77 µM dan 1,86 µM) dan rasio GSH/GSSG (1,29 dan 1,31), (P > 0,05).Antioksidan α-tokoferol dapat mengurangi hemolisis dan secara tidak langsung memperbaiki kadar Hp pada thalassemia-β mayor, akan tetapi tidak mampu memengaruhi stres oksidatif.

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The accumulation of excess unmatchedα-globin chains in the red blood cell membrane of β-thalassemia major leads to hemolysis, ineffective erythropoiesis and chronic anemia which needs multiple red blood cell transfusion. Routine transfusions may lead to iron overload as free radical in the red blood cell membrane, resulting clinically as severe hemolysis. Alpha-tocopherol as an antioxidant has been known as a potent scavenger of hydroxyl lipid radical.The aim of this study was to evaluate the effects of α-tocopherol in hemolysis and oxidative stress on the red cell membrane in β-thalassemia major. This randomized double-blind, placebo-controlled study was done in β-thalassemia major patients range aged 5–18 years old who regularly had transfusion and receiving iron chelating agents at Thalassemia centre, Kiara Ciptomangunkusumo Hospital. All subjects were randomized to receive either α-tocopherol or placebo orally for 4 weeks. Subjects in the experimental group received α-tocopherol, the doses based on the recommendation from Institute of Medicine (IOM) as follows: 200 mg/day for 4–8 years old; 400 mg/day for 9–13 years old; 600 mg/day for 14–18 years old. Laboratory analysis for hemolysis variables were haptoglobin, hemopexin, osmotic fragility test. Oxidative stress and antioxidant variables were MDA, GSH, GSSG, GSH/GSSG ratio, and α-tocopherol. All variable were evaluated before 4 weeks and after consuming α-tocopherol or placebo, just before they received a blood transfusion. The statistical analysis results using independent t-test and correlation test.During December 2016–July 2017, 40 subjects completed the study, they were 20 subjects in the placebo group and 20 subjects in the α-tocopherol group. There was significant enhancement of haptoglobin mean level in the α-tocopherol group (3.01 mg/dL) compared to placebo (1.08 mg/dL), (p = 0.021). The mean level of hemopexin and the percentage of RBC hemolysis did not significantly different in both groups, (p > 0.05). We also did not find any significantly different in mean level of MDA (1.003 nmol/L and 1.07 nmol/L), GSH (5.81 µM and 6.15 µM), GSSG (1.77 µM and 1.86 µM) and GSH/GSSG ratio (1.29 and 1.31), (p > 0.05) for the α-tocopherol and placebo groups.The effects of α-tocopherol may improve hemolysis and haptoglobin level indirectly in β-thalassemia major, but there was no significant role in oxidative stress."

"Kebocoran plasma sistemik pada sepsis dapat mengakibatkan berbagai komplikasi dari renjatan sampai kematian. Belum ada teknik andal untuk menilai kebocoran plasma sistemik pada anak. Degradasi glikokaliks, ditandai meningkatnya sindekan-1 dalam darah, menyebabkan perubahan permeabilitas vaskular sistemik. Pada glomerulus bermanifestasi sebagai albuminuria sehingga kenaikan rasio albumin-kreatinin (ACR) urin berpotensi menggambarkan kebocoran plasma sistemik. Sampai saat ini belum ada rujukan nilai sindekan-1 dan ACR urin sebagai penanda kebocoran plasma sistemik pada anak. Penelitian ini bertujuan untuk mengetahui peran ACR urin dan nilai rujukan ACR urin sebagai penanda kebocoran plasma sistemik pada anak sepsis dan mengkaji kaitannya dengan sindekan-1.Penelitian ini terdiri atas studi deskriptif pada anak sehat dan penelitian longitudinal prospektif dengan rancangan potong lintang berulang terhadap anak sepsis, dilakukan di RSUP Cipto Mangunkusumo Jakarta, RSUP H. Adam Malik Medan dan RSUP Kariadi Semarang dalam rentang waktu Maret–Desember 2015. Dilakukan pemeriksaan sindekan-1 dan ACR urin pada pasien sepsis yang dirawat di instalasi rawat intensif anak pada hari rawatan ke-1, 2, 3 dan 7, dan mencatat skor Pediatric Logistic Organ Dysfunction pada hari rawatan ke-1 dan 3.Tiga puluh subjek sehat dan 49 subjek sepsis diikutsertakan dalam penelitian. Pada kelompok sehat didapati median ACR urin 10,5 (3–88) mg/g dan rerata sindekan-1 sebesar 27,7 (SB 2,24) ng/mL. Sindekan-1 di atas persentil 90 (41,42 ng/mL) ditetapkan sebagai batasan kebocoran plasma sistemik. Didapati 40 orang (81,6%) subjek sepsis dengan sindekan-1 > 41,42 ng/mL dan 33 orang (67,3%) menunjukkan ACR urin > 300 mg/g pada hari rawatan 1. Didapati koefisien korelasi (r) 0,32 (P < 0,001) antara ACR urin dan sindekan-1. Area under the curve ACR urin terhadap kebocoran plasma sistemik diperoleh sebesar 65,7% (95% IK 54,5–77%; P = 0,012). ACR urin > 157,5 mg/g ditetapkan sebagai cut-off point kebocoran plasma sistemik dengan sensitivitas 77,4% dan spesifisitas 48%. ACR urin dapat digunakan sebagai penanda kebocoran plasma sistemik, peningkatan ACR urin akan mengikuti peningkatan sindekan-1.

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Systemic plasma leakage during sepsis can cause several complications from shock to death. There is no feasible measurement of systemic plasma leakage in children. Glycocalyx degradation, marked by increased serum syndecan-1, alters vascular permeability. In the glomerulus this can manifest as albuminuria, therefore elevated urinary albumin-creatinine ratio (ACR) potentially provides an index of systemic plasma leakage. Nowadays. there is no reference value of syndecan-1 and urinary ACR as a marker of systemic plasma leakage in pediatric population. This study aims to analyze the role of urinary ACR and to determine its reference value as a marker of systemic plasma leakage in pediatric sepsis, by analyzing its correlation with syndecan-1.

This study consisted of descriptive study on healthy children and longitudinal prospective study with repeated cross-sectional design on septic children, was conducted at Cipto Mangunkusumo Hospital Jakarta, Haji Adam Malik Hospital Medan and Kariadi Hospital Semarang from March to December 2015. We examined serum syndecan-1 and urinary ACR of septic patients in pediatric intensive care unit on day 1, 2, 3 and 7. Pediatric Logistic Organ Dysfunction (PELOD) score were recorded on day 1 and 3.

Thirty healthy subjects and 49 septic subjects were recruited. In the healthy group, median of urinary ACR was 10.5 (3–88) mg/g and mean of syndecan-1 was 27.7 + 2.24) ng/mL. Syndecan-1 more than 90th percentile (41.42 ng/mL) was determined as systemic plasma leakage. Forty (81.6%) septic subjects had syndecan-1 > 41.42 ng/mL and 33 (67.3%) subjects had urinary ACR > 300 mg/g on day 1. Correlation coefficient (r) between urinary ACR and syndecan-1 was 0.32 (P < 0.001). Area under the curve of urinary ACR and plasma leakage was 65.7% (95% CI 54.5–77%; p = 0.012). Urinary ACR > 157.5 mg/g was determined as cut-off point of systemic plasma leakage with sensitivity 77.4% and specificity 48%. Urinary ACR can be used as marker of systemic plasma leakage. Increased urinary ACR would indicate increased syndecan-1."

"Anak sakit kritis terutama sepsis mengalami degradasi protein yang tinggi, yang memperburuk luaran bila masukan nutrisi tidak adekuat. Kiraan jumlah kebutuhan protein yang ada saat ini ternyata dalam praktiknya kurang dari 90 memenuhi target kebutuhan. Di lain sisi, variasi genetik individu juga memengaruhi luaran. Polimorfisme gen TNF?-308 berhubungan dengan luaran yang buruk berbagai penyakit infeksi dan inflamasi, walaupun hasil yang diperoleh berbeda-beda.Penelitian ini bertujuan mengetahui hubungan nutrisi tinggi protein terhadap prognosis pasien sepsis skor PELOD , lama rawat dan lama pemakaian ventilator, serta menganalisis peran pelbagai faktor yang berperan terhadap skor PELOD, termasuk polimorfisme gen TNF?-308.Penelitian ini merupakan uji klinis randomisasi pada 80 anak sepsis di 4 rumah sakit. Intervensi diberikan asam amino parenteral, yaitu Aminosteril infant 6 untuk usia < 1 tahun dan Aminofusin pediatric 5 untuk usia ge; 1 tahun. Kelompok eksperimental diberikan asam amino 4 g/KgBB/hari, sedangkan kelompok kontrol menerima 2 g/KgBB/hari selama tiga hari, kemudian dilakukan pencatatan skor PELOD pada hari ke-1,2 dan 3, lama hari rawat dan lama pemakaian ventilator. Dilakukan pemeriksaan keseimbangan nitrogen selama tiga hari, pemeriksaan kadar prealbumin hari ke-1 dan ke-3, pemeriksaan kadar TNF-? dan IL-10. Pemeriksaan polimorfisme dengan metode PCR polymerase chain reaction ndash; RFLP restriction fragment length polymorphism . Pada kelompok kontrol, diperoleh rerata skor PELOD pada hari ke-1 20,5 10,6 , hari ke-2 19,8 13,8 dan hari ke-3 19,8 15,4 ; median lama rawat 7 hari 3 ndash;19 dan median lama pemakaian ventilator 5 hari 1 ndash;14 . Pada kelompok eksperimental, diperoleh rerata skor PELOD berturut-turut 22,4 10,8 ; 20,5 13,9 ; 18,8 14,5 ; median lama rawat 7 hari 4 ndash;27 dan median lama pemakaian ventilator 4 hari 1 ndash;27 . Tidak ditemukan perbedaan bermakna skor PELOD, lama rawat dan lama pemakaian ventilator antara 2 kelompok. Diperoleh perbedaan bermakna secara statistik pada keseimbangan nitrogen baik hari ke-1,2, dan 3 p = 0,003; p = 0,016; p = 0,046 . Dari 80 subjek, 6 subjek 7,5 dengan polimorfisme gen TNF?-308 G/A atau heterozigot dan tidak ditemukan homozigot.Tidak ditemukan peran usia, jenis kelamin, status gizi, pemberian nutrisi tinggi protein dan polimorfisme gen TNF?-308 terhadap skor PELOD. Kata kunci: polimorfisme gen TNF?-308, protein tinggi, sepsis

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Critically ill children, particularly with sepsis, have high protein degradation which worsens outcome if nutritional intake are inadequate. Currently, the estimated protein requirement is less than 90 target requirement. In addition, individual genetic variation also affects the outcome of these population. Tumor necrosis factor TNF 308 gene polymorphism is associated with poorer outcome of several infectious disease and inflammation, although the results are conflicting.This study aimed to determine the association between high protein nutrition intervention with prognosis of sepsis which is measured by PELOD score, length of stay, and duration of mechanical ventilation use. We also analyze the role of TNF 308 gene polymorphism which contribute to PELOD score.This was a randomized clinical trial in 80 children with sepsis in four hospitals. The interventions were parenteral amino acid, which includes Aminosteril infant 6 for subjects aged below one year and Aminofusin pediatric 5 for subjects aged above one year. Subjects in the experimental group were provided with amino acid 4 g KgBW day while those in the control group were provided with amino acid 2 g KgBW day for three consecutive days. PELOD scores in day 1, 2, 3, length of stay, and duration of mechanical ventilation use, were recorded. Nitrogen balance was measured for three days and prealbumin levels were measured in day 1 and 3. TNF and IL 10 levels were also measured. Polymorphism was measured using polymerase chain reaction PCR ndash restriction fragment length polymorphism RFLP .In the control group, the mean PELOD score on day 1, 2, 3 were 20.5 10.6 , 19.8 13.8 , and 19.8 15.4 , respectively. Median length of stay was 7 3 ndash 19 days and median duration of mechanical ventilation was 5 1 ndash 14 days. In the experimental group, obtained mean PELOD score was 22.4 10.8 20.5 13.9 18.8 14.5 consecutively median length of stay was 7 days 4 ndash 27 and median duration of ventilator use was 4 days 1 ndash 27 . There was no significant difference in PELOD score, length of stay, and duration of mechanical ventilation use between both groups. There was a significant difference in nitrogen balance on day 1, 2, and 3 p 0.003, p 0.016, and p 0.046, respectively . Of the 80 subjects, 6 7.5 subjects with TNF 308 G A gene polymorphism or heterozygotes, and no homozygote was found.Age, gender, nutritional status, provision of high protein nutrients, and TNF 308 gene polymorphism have no significant role in PELOD score. Keywords high protein, sepsis, TNF 308 gene polymorphism."