Efek Proteksi Otak Metamizol Intravena Sebagai Farmakologik Hipotermi Terhadap Suhu Inti Dan Kadar Interleukin-6 Pada Pasien Cedera Kepala Berat

Muhammad Erias, Ruli Herman Sitanggang, Tatang Bisri

Abstract


Latar Belakang dan Tujuan: Cedera kepala berat merupakan salah satu penyebab mortalitas dan morbiditas bagi pasien pasca trauma. Sirkulasi sitokin interleukin-6 (IL-6) pada cedera kepala berat dan proteksi otak dalam pengaturan suhu berhubungan dengan hasil luaran berupa morbiditas dan mortalitas. Tujuan dari penelitian ini mengkaji efek proteksi otak metamizol intravena sebagai farmakologik hipotermi terhadap suhu inti dan kadar interleukin pada cedera otak traumatik.
Subjek dan Metode: Penelitian merupakan penelitian tersamar acak ganda yang dilakukan pada 30 pasien dewasa dengan cedera kepala berat yang dikelompokkan menjadi dua kelompok yaitu kelompok kontrol dan kelompok metamizol (M). Kelompok M diberikan metamizol intravena 15 mg/kgbb setiap 8 jam selama 72 jam. Data yang dicatat adalah suhu membran timpani setiap 8 jam dan kadar IL-6 setiap 24 jam selama 72 jam. Penelitian dilakukan selama bulan Juli sampai Agustus 2016 dan hasil penelitian diuji statistik menggunakan uji t berpasangan, uji Mann-Whitney, Uji Chi-square dan uji Fisher's Exact.
Hasil: Penelitian menunjukkan bahwa nilai IL-6 pada kelompok M 244,20±93,07, lebih rendah dari kelompok K 375,20±152,62 dengan nilai p=0,006 pada jam ke-48 dan pada jam ke-72 dengan kadar IL-6 197,20±76,03 dan nilai p=0,008 sehingga bermakna secara statistik (p<0,05). Subjek pada kelompok M juga menunjukkan suhu tubuh yang lebih rendah secara keseluruhan dan bermakna secara statistik (p<0,01).
Simpulan: Metamizole mempunyai efek proteksi otak dan mempunyai kegunaan sebagai farmakologik hipotermi pada cedera kepala traumatik.

Effect Brain Protection Metamizol Intravenous as Pharmacalogic Hypothermia to Core Temperature and Interleukin-6 Level in Severe Traumatic Brain Injury

Background and Objective: Severe traumatic brain injury (TBI) is one of the major cause of morbidity and mortality in trauma. Circulating interleukin-6 (IL-6) and neuroprotection from temperature has a strong relation with improve outcome. The aim of this study is to evaluate the brain protection properties of intravenous metamizole as a hypothermic pharmacologic in reducting IL-6 and core temperature regulation on severe TBI. 

Subject and Method: This is a randomized controlled trial to 30 adult pasien with severe TBI which was distributed into two groups which was control group (K) and metamizole group(M). The M grup was given 15 mg/kgbw of intravenous metamizole every 8 hours for 72 hours. Core temperature from the tympnic membrane every 8 hours and IL-6 every 24 hours was noted for 72 hours. This studi was conducted from July to August 2016 and the data was then analyzed statistically using the paire t test, Mann-Whitney test, Chi-Square test and Fishers’s Exact test.
Result: Shows that IL-6 on the M group was 244.20±93.07 which was lower than the K group at 375.20±152.62 with p=0.006 on the 48th hour and on the 72nd hour with IL-6 at 197.20±76.03 with p=0.008 which is statistically significant (p<0.005) and also shows lower temperature at every recording with p<0.01.
Conclusion: Metamizole has brain protecting properties in reducing circulating IL-6 and has uses as a hypothermic agent in severe TBI.


Keywords


cedera kepala berat; hipotermi; interleukin-6; metamizol; hypothermia; interleukin-6; metamizole; severe head injury

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References


Sydenham E, Roberts I, Alderson P. Hypothermia for traumatic head injury. The Cochrane Library. John Wiley and Sons. 2009;2:1-49.

Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007;99:4–9.

Algattas H, Huang J. Traumatic brain injury pathophysiology and treatments: early, intermediate, and late phases post-injury. Int J Mol Sci. 2014;15:309–41.

Mrozek S, Vardon F, T Geeraerts. Brain temperature: physiology and pathophysiology after brain injury. Anesthesiology Research and Practice 2012;1:1–14.

Bell D, Adams J. The secondary management of traumatic brain injury. Dalam: McKinlay J, editor. Neurocritical Care. Edisi ke-1. London: Springer;2010. hlm 19–30.

Thompson H, Kirkness C, Mitchell P. Intensive care unit management of fever following traumatic brain injury. Journal of Intensive and Critical Care Nursing. 2007;23: 91–6.

Hashizume M, Mihara M. The role of interleukin 6 in the pathogenesis of rheumatoid arthritis. Hindawi Publishing Corporation Arthritis. 2011;1:1–8.

Shaikh Z. Cytokines and their physiologic and pharmacologic functions in inflamation. Int J of Pharm & Life Sciences. 2011;11: 1247–63.

Clifton G, Miller E, Choi S, Levin H, McCaule S, Smith K. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med..2001;8:556–63.

Malvar D, Soares D, Febricio A, Kanashiro A, Machado R, Figueiredo M. The antipyretic effect of dypyrone is unrelated to inhibition of PGE2 synthesis in the hypothalamus. British Journal of Pharmacology.2011;162:1401–09.

Cohen O, Zylber-Katz E, Caraco Y, Granit L, Levy M. Cerebrospinal fluid and plasma concentrations of dipyrone metabolites after a single oral dose of dipyrone. Eur J Clin Pharmacol.1998;7:549–53.

Gozzoli V, Treggiari M, Kleger G, Pasclae R. Fathi M, Picards C, dkk. Randomized trial of the effect of antipyresis by metamizol, propacetamol or external cooling on metabolism, hemodynamics and inflammatory response. Intensive Care Med.2004;30:401–7.

Woodcock T, Kossmann M. The role of markers of inflammation in traumatic brain Injury. Frontiers in Neurology.2013;4(18):1–18.

Gomes C. R., Karavitis J, Palmer J, Faincer D, Ramirez L, Nomellini V. Interleukin-6 contributes to age-related alteration of cytokine production by macrophage. Hindawi Publishing Corporation Mediators of Inflamation. 2010;10(7):1–8.

Polderman K, Herold I. Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods. Crit Care Med.2009;39(3):1101–20.

Saosa A, Raposo F, Fonseca S. Valente L, Duarte F, Goncalves M, dkk. Meansurement of cytokines and adhesion molecules in the first 72 hours after severe trauma: association with severity and outcome.2015;25:1–8.

Erta M, Quintana A, Hidalgo J. Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci.2012;8(9):1254–66.

Smith W. Neurocritical care written examinations and outlines. Neurocritical care society.2011. www.neurocriticalcareorg.

Nikolova I, Tencheva J, Voikinov J, Petkova V, Benasat N, Danchev N. Metamizole a review profile of well known forgotten drug part II pharmaceutical and non clinical profile. Biotechnology & Biotechnological Equipment. 2012;26:3329–37.

Antunes A, Sotomaior V, Sakamoto K, Martins C, Aguiar L. Interleukin-6 plasmatic levels in patients with head trauma and intracerebral hemorrhage. Asian Journal of Neurosurgery. 2010;5:68–77.




DOI: https://doi.org/10.24244/jni.vol6i2.42

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