Disertasi

Efek Asam Amino Rantai Cabang Tinggi Leusin terhadap Ketebalan Otot, Interleukin-6, C-Reactive Protein, Skor Sequential Organ Failure Assessment pada Pasien Sakit Kritis: Uji Klinis Acak Tersamar Ganda = The Effect of Leucine-enriched Branched-chain Amino Acid on Muscle Thickness, Interleukin-6, C-Reactive Protein, Sequential Organ Failure Assessment Score in Critically-ill Patients: Doubleblind Randomized Clinical Trial.

Latar Belakang: Wasting otot umum dialami pasien sakit kritis di perawatan intensif (ICU) akibat peningkatan proteolisis dan penurunan sintesis protein otot, yang disebabkan oleh aktivasi sitokin proinflamasi. Wasting otot akan memperlambat pelepasan ventilator, meningkatkan mortalitas, disabilitas fisik pada penyintas sakit pasca perawatan ICU. Asam amino rantai cabang (AARC), terutama leusin, meningkatkan sintesis protein otot dan menurunkan inflamasi melalui aktivasi jalur mammalian target of rapamycin (mTOR). Studi menunjukkan efek positif AARC terhadap ketebalan otot, kadar interleukin-6 (IL-6), c-reactive protein (CRP) yang terbatas pada subjek sehat maupun non-kritis, namun perannya pada populasi sakit kritis, juga terhadap skor sequential organ failure assessment (SOFA) sebagai prediktor mortalitas, belum diketahui. Metode: Penelitian ini menggunakan desain uji klinis acak tersamar ganda pada 34 subjek pasien ICU dengan skor SOFA ≥4 yang direkrut sejak Desember 2023 hingga Mei 2024 dari RS Umum Pusat Nasional Dr. Cipto Mangunkusumo (RSUPNCM) dan RS Universitas Indonesia (RSUI). Subjek grup intervensi diberikan produk AARC tinggi leusin enteral (leusin 19 g dengan rasio l-isoleusin : l- leusin : l-valin = 1:2:1,2) sebesar 40 g per hari selama 10 hari. Kedua grup mendapatkan makanan cair tinggi protein komersial dengan target minimal 20 kkal/kg BB/hari dan maksimal rasio nitrogen : non-protein calorie = 1:70, dan neuromuscular electrical stimulation (NMES) 1 kali/hari (durasi 30 menit). Data karakteristik usia, jenis kelamin, indeks massa tubuh (IMT), penyakit dasar diukur saat baseline. Selama studi, diambil data asupan energi, protein, residu nasogastrik, sesi NMES, balans cairan harian, % overload cairan, penggunaan antibiotik. Pengukuran ketebalan otot quadriceps femoris dekstra dengan ultrasonografi, kadar CRP, IL-6 serum, penilaian skor SOFA, profil asam amino dilakukan saat baseline dan hari ke-10 studi. Hasil: Penurunan ketebalan otot quadriceps femoris signifikan lebih rendah pada grup intervensi dibandingkan kontrol [0 (-37–50)% versus -13 (-31 – -3)%; p < 0,001], penurunan IL-6 bermakna pada grup intervensi sebesar -67 (-99–29)% (p 0,001), penurunan CRP bermakna pada grup intervensi dibandingkan kontrol [-39,4 (-260,2– 88,2) versus 38,1 (-370–127,2) mg/L; p 0,04]. Tidak terdapat perbedaan bermakna pada penurunan skor SOFA antar kedua grup. Faktor asupan energi dan protein memengaruhi penurunan CRP. Simpulan: Suplementasi AARC tinggi leusin secara signifikan meminimalisir penurunan ketebalan otot quadriceps femoris, menurunkan IL-6 dan CRP pada subjek sakit kritis.
Kata kunci: asam amino rantai cabang tinggi leusin, tebal otot, interleukin-6, c-reactive protein, SOFA, sakit kritis.


Background: Muscle wasting is commonly experienced by critically ill patients in intensive care units (ICUs) due to increased proteolysis and decreased muscle protein synthesis, driven by the activation of proinflammatory cytokines. Muscle wasting slows ventilator weaning, increases mortality, and leads to physical disabilities in survivors following ICU care. Branched-chain amino acids (BCAAs), particularly leucine, enhance muscle protein synthesis and reduce inflammation through the activation of the mammalian target of rapamycin (mTOR) pathway. Studies have demonstrated the positive effects of BCAAs on muscle thickness, interleukin-6 (IL-6) levels, and Creactive protein (CRP) in healthy or non-critically ill subjects. However, their role in critically ill populations and their impact on the Sequential Organ Failure Assessment (SOFA) score, a predictor of mortality, remains unknown. Methods: This study employed a double-blind, randomized clinical trial design involving 34 ICU patients with SOFA scores ≥ 4, recruited between December 2023 and May 2024 from Dr. Cipto Mangunkusumo National General Hospital (RSUPNCM) and Universitas Indonesia Hospital (RSUI). The intervention group received leucineenriched BCAA supplementation (19 g leucine with a ratio of l-isoleucine:l-leucine:lvaline = 1:2:1.2) at 40 g per day via enteral for 10 days. Both groups were provided commercial high-protein liquid diets targeting a minimum of 20 kcal/kg body weight/day with a nitrogen-to-non-protein calorie ratio of 1:70 and underwent neuromuscular electrical stimulation (NMES) once daily (30-minute sessions). Baseline measurements included age, sex, body mass index (BMI), and underlying diseases. Data collected during the study included energy and protein intake, nasogastric tube residuals, NMES sessions, daily fluid balance, percentage of fluid overload, and antibiotic use. Quadriceps femoris muscle thickness (right leg) was measured using ultrasonography, while serum CRP and IL-6 levels, SOFA scores, and amino acid profiles were assessed at baseline and day 10 of the study. Results: This study showed a significantly lower reduction in quadriceps femoris muscle thickness in intervention group compared to the control [0 (-37–50)% versus -13 (-31 – -3)%; p < 0,001], a significant reduction in IL-6 levels in intervention group only - 67 (-99–29)% (p 0,001), and a significant reduction in CRP levels compared to the control [-39.4 (-260.2; 88.2) versus 38.1 (-370; 127.2) mg/L, p 0.04]. There was no significant difference in the reduction of SOFA scores between the two groups. Energy and protein intake were associated with reductions in CRP levels. Conclusion: Leucine-enriched BCAA supplementation can significantly minimize quadriceps femoris muscle thickness reduction and decrease IL-6 and CRP levels in critically ill patients.
Keywords: branched-chain amino acid, leucine, muscle thickness, interleukin-6, creactive protein, SOFA, critical illness.