EFFECTIVINESS OF AMANTADINE FOR SEVERE TRAVMATIC BRAIN INJURY: CASE SERIES AND LITERATURE REVIEW

Öz

Traumatic brain injury (TBI) is the most common cause of death among young population. Approximately 10-15% of these patients, are associated with many severe comorbid conditions, are discharged in vegetative state. Amantadine acts as both a NMDA receptor antagonist and an indirect dopamine agonist. But its exact mechanism of action is still unknown. It is frequently use to increase alertness in patients with TBI. In this presentation, we aimed to present the eight cases with TBI which were treated with Amantadine in İntensive Care Unit (ICU). The characteristics of the cases are given in Table 1. All of patients with traumatic brain injury were intubated and unconscious upon arrival. We used Thiopental sodium for sedation to all patients. Amantadine sulfate treatment was started in the first hour as 200 mg / day and treatment was continued for at least 10 days. Traumatic brain injury (TBI) are serious health problems with social and economic consequences. Although there are many methods for to increase neurological recovery, there is still no specific treatment. Amantadine is a reliable and frequently used drug for to improve the neurological recovery of the patients with TBI. In the literature, the studies on the use of amantadine in patients with TBI was compared with the control group and various parameters. These studies were shown that neurological recovery was better in the amantadine group. We used some variables such as Glasgow Coma Scale (GKS), Full Outline of Unresponsiveness (FOUR) scale and duration of stay at ıcu and hospital. FOUR scale are better reflects the neurological status in intubated patients. Although there are a limited number of articles indicating efficacy, new studies on amantadine use, dose, and duration are needed in patients with TBI.

Anahtar Kelimeler

• Amantadine
• Neurological Recovery
• Severe Travmatic Brain Injury

CİDDİ TRAVMATİK BEYİN HASARINDA AMANTADİN ETKİNLİĞİNİN DEĞERLENDİRİLMESİ: OLGU SERİSİ VE LİTERATÜR DERLEMESİ

Öz

Travmatik beyin hasarı (TBH) genç nüfus arasında sık görülen bir ölüm sebebidir. Bu hastaların yaklaşık % 10-15'nde ciddi komorbiditeler görülmektedir ve vejetatif bir hayat ile taburcu edilmektedirler. Amantadin, NMDA (N-metil-D-aspartat) reseptör antagonisti ve indirekt dopamin agonisti gibi davranmaktadır. Fakat etki mekanizması net değildir. TBH olan hastalarda uyanıklığı artırmak için hala kullanılmaktadır. Bu olgu serisinde, TBH ile yoğun bakımda takip edilen ve tedavilerinde amantadin kullanılan 8 hasta sunulmuştur. Olguların özellikleri Tablo 1'de verilmiştir. Travmatik beyin hasarı olan tüm hastalar geldiklerinde bilinçsizdi ve entübe edildiler. Tüm hastalara sedasyon için tiyopental sodyum 3 mg/kg yükleme sonrası 3-5 mg/ kg / saat infüzyon dozlarında kullanıldı. Amantadin sülfat tedavisine ilk saatte 200 mg / gün olarak başlandı ve tedaviye en az 10 gün devam edildi. Travmatik beyin hasarı (TBI), sosyal ve ekonomik sonuçları olan ciddi bir sağlık problemidir. Nörolojik iyileşmeyi artırmak için pek çok yöntem bulunmasına rağmen hala spesifik bir tedavisi yoktur. Amantadin, TBH'li hastaların nörolojik iyileşmesi için güvenilir ve sıklıkla kullanılan bir ilaçtır. Literatürde TBH'li hastalarda amantadin kullanımına ilişkin çalışmalar kontrol grubu ve çeşitli parametreler ile karşılaştırılmıştır. Bu çalışmalar, amantadin grubunda nörolojik iyileşmenin daha iyi olduğunu göstermiştir. Glasgow Koma Ölçeği (GKS), Full Outline of Unresponsiveness (FOUR) skalası ve yoğun bakım ve hastanede kalış süresi gibi bazı değişkenler kullandık. FOUR skalası entübe hastalarda nörolojik durumu daha iyi yansıtır. Etkinliği gösteren sınırlı sayıda makale olmasına rağmen TBH'li hastalarda amantadin kullanımı, dozu, süresi ile ilgili yeni çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

• Amantadin
• Nörolojik İyileşme
• Şiddetli Travmatik Beyin Hasarı

Kaynakça

1. 1. Daugherty J, Waltzman D, Sarmiento K, Xu L. Traumatic Brain Injury-Related Deaths by Race/Ethnicity, Sex, Intent, and Mechanism of Injury - United States, 2000-2017. MMWR. Morb Mortal Wkly Rep 2019; 68(46): 1050–6.
2. 2. Peterson AB, Xu L, Daugherty J, Breiding MJ. Surveillance report of traumatic brain injury-related emergency department visits, hospitalizations, and deaths, United States; Centers for Disease Control and Prevention National Center for Injury Prevention and Control; 2019.
3. 3. Ng Si Yun, Alan Yiu Wah Lee. Traumatic Brain Injuries: Pathophysiology and Potential Therapeutic Targets. Front Cell Neurosci 2019; 13: 528.
4. 4. Whyte J, Katz D, Long D, et al. Predictors of outcome in prolonged posttraumatic disorders of consciousness and assessment of medication effects: a multicenter study. Arch Phys Med Rehabil 2005; 86: 453-62.
5. 5. Wendel HA, Snyder MT, Pell S. Trial of amantadine in epidemic influenza. Clin Pharmacol Ther 1966; 7(1): 38‐43.
6. 6. Chandler MC, Barnhill JL, Gualtieri CT. Amantadine for the agitated head-injury patient. Brain inj 1988; 2(4): 309-11.
7. 7. Hughes S, Colantonio A, Santaguida PL, Paton T. Amantadine to enhance readiness for rehabilitation following severe traumatic brain injury. Brain Inj 2005; 19(14): 1197-206.
8. 8. Miller KS, Miller JM. Toxic effects of amantadine in patients with renal failure. Chest 1994; 105(5): 1630.

9. 9. Aksu NM, Şenlikçi H, Akkaş M, Özmen MÖ. The Neurological Improvement of a Patient After Amantadine Infusion. JAMCR 2013; 4: 161-3.
10. 10. Stelmaschuk S, Will MC, Meyers T. Amantadine to Treat Cognitive Dysfunction in Moderate to Severe Traumatic Brain Injury. J Trauma Nurs 2015; 22(4): 194-203.
11. 11. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012.
12. 12. Stelmaschuk S, Will MC, Meyers T. Amantadine to Treat Cognitive Dysfunction in Moderate to Severe Traumatic Brain Injury. J Trauma Nurs 2015; 22(4):194-203.
13. 13. Yang Y, Teja S, Baig K. Bilateral corneal edema associated with amantadine. CAMJ 2015; 20: 187(15):1155-8.
14. 14. Lin CC, Cheng CY, Hu PS,Lin CP, Hsu SL. Amantadine-related corneal edema and endothelial cell loss: Four case reports. Taiwan J Ophthalmol 2014;4: 137-40
15. 15. Hughes B, Feiz V, Flynn SB, Brodsky MC. Reversible amantadine-induced corneal edema in an adolescent. Cornea 2004; 23(8): 823-4.
16. 16. Deogaonkar M, Wilson K, Vitek J. Amantadine induced reversible corneal edema. J Clin Neurosci 2011; 18: 298-9.
17. 17. Maxwell CB, Jenkins AT. Drug-induced heart failure. Am J Health Syst Pharm 2011; 68: 1791-804.
18. 18. Schwartz M,Patel M, Kazzi Z, Morgan B. Cardiotoxicity after massive amantadine overdose. J Med Toxicol 2008; 4(3): 173-9.
19. 19. Giacino JT, Whyte J, Bagiella E, et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med 2012; 366(9): 819-26.
20. 20. Wheaton P, Mathias JL, Vink R. Impact of Early Pharmacological Treatment on Cognitive and Behavioral Outcome After Traumatic Brain Injury in Adult: a Meta-Analysis. Jclin Psychopharmacol 2009; 29: 468-77.
21. 21. Abbasivash R, Valizade Hasanloei MA, Kazempour A, Mahdkhah A, Shaaf Ghoreishi MM, Akhavan Masoumi G. The Effect of Oral Administration of Amantadine on Neurological Outcome of Patients With Diffuse Axonal Injury in ICU. J Exp Neurosci 2019; 27: 13.
22. 22. Saniova B, Drobny M, Kneslova L, Minarik M. The outcome of patients with severe head injuries treated with amantadine sulphate. J Neural Transm 2004; 111: 511-4.
23. 23. Hughes S, Colantonio A, Santaguida PL, Paton T. Amantadine to enhance readiness for rehabilitation following severe traumatic brain injury. Brain Inj 2005; 19: 1197-1206.
24. 24. Hammond FM, Bickett AK, Norton JH, Pershad M. Effectiveness of amantadine hydrochloride in reduction of chronic traumatic brain injury irritability and aggression. J Head Trauma Rehabil 2014; 29: 391-9.
25. 25. Şahin AS, Şahin M, Öztürk NK, Kızılateş E, Karslı B. Comparision Of GCS And FOUR Scores Used In The Evaluation Of Neurological Status In Intensive Care Units. J Contemp Med 2015; 5(3): 167-72.
26. 26. Wijdicks EF, Bamlet WR, Maramattom BV, Manno EM, McClelland RL. Validation of a new coma scale: The FOUR score. Annals of neurology 2005; 58(4): 585-93.