Latar Belakang dan Tujuan: Pembedahan kraniotomi dapat meningkatkan respon inflamasi tubuh akibat memprovokasi respon stres neuroendokrin. Interleukin-6 adalah salah satu parameter inflamasi memiliki hubungan yang erat pada inflamasi pasca operasi kraniotomi. Kombinasi fentanil dengan midazolam dan deksmedetomidin sebagai obat analgesia memiliki peran menghambat regulasi inflamasi sehingga bisa mengurangi pelepasan mediator inflamasi termasuk Interleukin-6. Tujuan penelitian untuk memperoleh hasil perbandingan pemberian kombinasi fentanil dengan midazolam dan deksmedetomidin terhadap kadar interleukin-6 pada pasien pasca kraniotomi di ruang ICUSubjek dan Metode: Penelitian menggunakan uji klinis double-blind randomized controlled trial (RCT) dengan 32 subjek penelitian yang setelah memenuhi kriteria inklusi dibagi secara acak menjadi 2 kelompok. Kelompok A mendapat kombinasi fentanil dan midazolam kontinyu dan kelompok B mendapat deksmedetomidin kontinyuHasil: Terdapat penurunan nilai rata-rata kadar interleukin-6 pada kelompok pemberian kombinasi fentanil dengan midazolam dan kelompok pemberian deksmedetomidin, namun secara statistik tidak memberikan nilai yang signifikan antara kedua kelompokSimpulan: Pemberian kombinasi fentanil dengan midazolam dan deksmedetomidin memberikan efek sebanding dalam menurunkan kadar Interleukin-6. Comparison of Interleukin-6 Levels between Continuous Combination of Fentanil and Midazolam with Dexmedetomidine Continuity in Postoperating Patients Craniotomy in ICUAbstractBackground and Objective: Craniotomy surgery can increase the body's inflammatory response by provoking a neuroendocrine stress response. Interleukin-6 as one of the inflammatory parameters has a close relationship with inflammation after craniotomy surgery. Combination fentanyl with midazolam and dexmedetomidine as anelgesia drugs have the role of inhibiting inflammatory regulation to reduce the release of inflammatory mediators including Interleukin-6. The aim of this study to compare the results of Combination fentanyl with midazolam and dexmedetomidine administration on interleukin-6 levels in post-craniotomy patients in the ICU room.Subjects and Methods: This study is an experimental study with The Pretest-Posttest Control Group Design, with a double blind randomized controlled trial (RCT) clinical trial where in this study two groups were divided. After obtaining approval from the Ethics Committee of the Faculty of Medicine, University of Sumatera Utara Medan, 32 research samples were collected, which after meeting the inclusion criteria were randomly divided into 2 groups. Group A received a combination of fentanyl and midazolam and group B received dexmedetomidine. The data obtained were tested using SPSS.Results: There was a decrease in the mean value of interleukin-6 levels in combination fentanyl with midazolam administration group and the dexmedetomidine administration group, but statistically did not provide a significant value between the two groups.Conclusion: Combination fentanyl with midazolam and dexmedetomidine administration have comparable effects in reducing Interleukin-6 levels.