Kardiyak Arrest Sonrası Yoğun Bakım Hastalarında Amantadin Tedavisinin Nörolojik ve Laboratuvar Sonuçlar Üzerine Etkisi: Retrospektif Bir Analiz

Abstract

Amaç: Kardiyopulmoner arrest (KPA), yüksek mortalite ve ciddi nörolojik hasar riski nedeniyle önemli bir halk sağlığı sorunudur. Bu retrospektif çalışma, KPA sonrası spontan dolaşımın geri dönüşünü (ROSC) sağlayan ve yoğun bakım ünitesine (YBÜ) yatırılan hastalarda amantadin’in nörolojik iyileşme, mortalite ve inflamatuar biyomarkerlar üzerindeki etkisini araştırmıştır. Materyal ve metod: Bu retrospektif gözlemsel çalışma, 1 Ocak 2016 ile 31 Aralık 2020 tarihleri arasında ROSC sonra yoğun bakım ünitesine yatırılan ve en az altı gün kalan 18-85 yaş arası hastaları içermiştir. Hastalar iki gruba ayrılmıştır: amantadin grubu (Grup A, n=31) ve kontrol grubu (Grup C, n=47). Demografik bilgiler, GCS, CPC ve laboratuvar parametreleri (laktat, nötrofil, lenfosit, NLR) 1., 2., 4. ve 6. günlerde kaydedilmiştir. İstatistiksel analiz SPSS 22.0 kullanılarak yapılmıştır.

Bulgular: Gruplar arasında yaş, cinsiyet veya KPR süresi açısından anlamlı bir fark bulunmadı. Hedeflenen sıcaklık yönetimi A grubunda daha yaygındı. GKS, CPC ve inflamatuar belirteçler gruplar arasında anlamlı farklılık göstermezken, 6. günde laktat seviyeleri hayatta kalanlarda anlamlı derecede daha düşüktü. Hayatta kalamayanlarda ise 2. gün nötrofil seviyeleri ve 4. gün NLR anlamlı derecede daha düşüktü.

Sonuç: Amantadin nöroprotektif faydalar sağlayabilir, ancak istatistiksel anlamlılığa ulaşılamamıştır. Daha büyük prospektif çalışmalara ihtiyaç vardır. Laktat, nötrofil ve NLO, KPA sonrası hastalarda değerli prognostik göstergeler olabilir.

Keywords

• Amantadin
• Kardiyopulmoner resüsitasyon (CPR)
• Glasgow Koma Skalası (GKS)
• Nötrofil/lenfosit oranı (NLR)
• Serebral performans kategorisi (SPK)
• Nöroproteksiyon

Effect of Amantadine Therapy on Neurological and Laboratory Outcomes in Post-Cardiac Arrest Intensive Care Patients: A Retrospective Analysis

Abstract

Background: Cardiopulmonary arrest (CPA) is a major public health issue due to its high mortality and risk of severe neurological impairment. This retrospective study investigated the impact of amantadine on neurological recovery, mortality, and inflammatory biomarkers in patients who achieved return of spontaneous circulation (ROSC) after CPA and were admitted to the intensive care unit (ICU).

Materials and Methods: This retrospective observational study included patients aged 18-85 years who were admitted to the ICU after ROSC and stayed for at least six days between January 1, 2016, and December 31, 2020. Patients were divided into two groups: amantadine group (Group A, n=31) and control group (Group C, n=47). Demographics, GCS, CPC, and laboratory parameters (lactate, neutrophil, lymphocyte, NLR) were recorded on days 1, 2, 4, and 6. Statistical analysis was performed using SPSS 22.0.

Results: No significant differences were found between the groups in terms of age, sex, or CPR duration. Targeted temperature management was more common in Group A. While GCS, CPC, and inflammatory markers did not significantly differ between groups, lactate levels on day 6 were significantly lower in survivors. In non-survivors, day 2 neutrophil levels and day 4 NLR were significantly lower.

Conclusions: Amantadine may offer neuroprotective benefits, though statistical significance was not reached. Larger prospective studies are needed. Lactate, neutrophil, and NLR may be valuable prognostic indicators in post-CPA patients.

Keywords

• Amantadine
• Cardiopulmonary resuscitation (CPR)
• Glasgow Coma Scale (GCS)
• Neutrophil/lymphocyte ratio (NLR)
• Cerebral Performance Category (CPC)
• Neuroprotection

References

1. 1. Graham R, McCoy MA SA. Strategies to Improve Cardiac Arrest Survival; Committee on the Treatment of Cardiac Arrest: Current Status and Future Directions; Board on Health Sciences Policy; Institute of Medicine. 1st ed. Washington, D.C.: National Academies Press; 2015.
2. 2. Lynge TH, Risgaard B, Banner J, Nielsen JL, Jespersen T, Stampe NK, et al. Nationwide burden of sudden cardiac death: A study of 54,028 deaths in Denmark. Heart Rhythm 2021;18:1657-65.
3. 3. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation 2017;135.
4. 4. Meaney PA, Bobrow BJ, Mancini ME, Christenson J, de Caen AR, Bhanji F, et al. Cardiopulmonary Resuscitation Quality: Improving Cardiac Resuscitation Outcomes Both Inside and Outside the Hospital. Circulation 2013;128:417-35.
5. 5. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart Disease and Stroke Statistics—2015 Update. Circulation 2015;131.
6. 6. Love G, Haines C. Predicting Survival from In - Hospital CPR: An Update. Med Res Arch 2020;8. https://doi.org/10.18103/mra.v8i3.2038.
7. 7. Joundi RA, Rabinstein AA, Nikneshan D, Tu J V., Fang J, Holloway R, et al. Cardiac Arrest in Acute Ischemic Stroke: Incidence, Predisposing Factors, and Clinical Outcomes. Journal of Stroke and Cerebrovascular Diseases 2016;25:1644-52.
8. 8. Nolan JP, Sandroni C, Böttiger BW, Cariou A, Cronberg T, Friberg H, et al. European Resuscitation Council and European Society of Intensive Care Medicine guidelines 2021: post-resuscitation care. Intensive Care Med 2021;47:369-421.

9. 9. Sorini Dini C, Geraci G, Valente S, Tizzani E, Sacco A, Grimaldi M, et al. [Post-cardiac arrest syndrome: definition, pathophysiology, and management]. G Ital Cardiol (Rome) 2025;26:488-99.
10. 10. Hong DK, Park YS, Woo JS, Kim JH, Beom JH, Chung SP, et al. Transient Global Ischemia-Induced Brain Inflammatory Cascades Attenuated by Targeted Temperature Management. Int J Mol Sci 2021;22:5114.
11. 11. Michels G, Pöss J, Thiele H. ERC-Leitlinien 2021 zur kardiopulmonalen Reanimation. Herz 2022;47:4-11.
12. 12. Loggini A, Tangonan R, El Ammar F, Mansour A, Goldenberg FD, Kramer CL, et al. The role of amantadine in cognitive recovery early after traumatic brain injury: A systematic review. Clin Neurol Neurosurg 2020;194:105815.
13. 13. Ghalaenovi H, Fattahi A, Koohpayehzadeh J, Khodadost M, Fatahi N, Taheri M, et al. The effects of amantadine on traumatic brain injury outcome: a double-blind, randomized, controlled, clinical trial. Brain Inj 2018;32:1050-5.
14. 14. Heran M, Lindsay P, Gubitz G, Yu A, Ganesh A, Lund R, et al. Canadian Stroke Best Practice Recommendations: Acute Strke Management, 7th Edition Practice Guidelines Update, 2022. Can J Neurol Sci 2024;51:1-31.
15. 15. Öner Ö, Hanci V, Gürkok MÇ, Ergan B, Yaka E, Gökmen AN. The effect of amantadine treatment on neurological outcome and mortality in mechanically ventilated severe head trauma patients in intensive care unit. Medicine 2024;103:e38172.
16. 16. Zhao Q, Li H, Li H, Zhang J. Research progress on pleiotropic neuroprotective drugs for traumatic brain injury. Front Pharmacol 2023;14.
17. 17. Sahin F, Peksen S, Kocayigit H, Kaya B, Erdem AF. Effect of amantadine in comatose patients: Traumatic brain injury versus post-cardiac resuscitation syndrome. Neurol Asia 2025;30:603-8.
18. 18. Plaitano EG, Scharf RA, Aboutaleb PE, Glennon AL, Melkumova E, Green-LaRoche DM. Informing future randomized controlled trials of amantadine hydrochloride in neurocritical care and post-neurocritical care stroke patients through a retrospective study. BMC Neurol 2024;24:338. 19. Danysz W, Dekundy A, Scheschonka A, Riederer P. Amantadine: reappraisal of the timeless diamond—target updates and novel therapeutic potentials. J Neural Transm 2021;128:127-69.
19. 20. Reynolds JC, Rittenberger JC, Callaway CW. Methylphenidate and amantadine to stimulate reawakening in comatose patients resuscitated from cardiac arrest. Resuscitation 2013;84:818-24.
20. 21. Coppler PJ, Gagnon DJ, Flickinger KL, Elmer J, Callaway CW, Guyette FX, et al. A multicenter, randomized, doubleblind, placebo-controlled trial of amantadine to stimulate awakening in comatose patients resuscitated from cardiac arrest. Clin Exp Emerg Med 2024;11:205-12.
21. 22. McGuigan PJ, Pauley E, Eastwood G, Hays LMC, Jakobsen JC, Moseby-Knappe M, et al. Drug therapy versus placebo or usual care for comatose survivors of cardiac arrest; a systematic review with meta-analysis. Resuscitation 2024;205:110431.
22. 23. Węgrzyn D, Kutwin-Chojnacka A, Bilski J, Mroszczyk K, Węgrzyn K. Neurotrophic Factors in the Treatment of Acute Brain Hypoxia Secondary to Cardiac Arrest: a Case Report. J Med Life 2019;12:233-5.
23. 24. Dekundy A, Pichler G, El Badry R, Scheschonka A, Danysz W. Amantadine for Traumatic Brain Injury—Supporting Evidence and Mode of Action. Biomedicines 2024;12:1558.
24. 25. Grüdtner DOM, Rocha JP, Monteiro MD, Mazon J, Silveira GSB, Koerbel A. Efficacy and safety of amantadine for functional recovery in adults with traumatic brain injuries: A comprehensive systematic review and meta-analysis. Clin Neurol Neurosurg 2025;257:109084.
25. 26. Zhou B-C, Zhang Z, Zhu J-J, Liu L-J, Liu C-F. Blood Lactate or Lactate Clearance: Which Is Robust to Predict the Neurological Outcomes after Cardiac Arrest? A Systematic Review and Meta-Analysis. Biomed Res Int 2018;2018:1-11.
26. 27. Patel VH, Vendittelli P, Garg R, Szpunar S, LaLonde T, Lee J, et al. Neutrophil-lymphocyte ratio: A prognostic tool in patients with in-hospital cardiac arrest. World J Crit Care Med 2019;8:9-17.
27. 28. Altaş ÖF, Kızılkaya M. The Effects of Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio and Prognostic Markers in Determining the Mortality in Patients Diagnosed With Pneumonia in Intensive Care. Medeni Med J 2021.
28. 29. Forget P, Khalifa C, Defour J-P, Latinne D, Van Pel M-C, De Kock M. What is the normal value of the neutrophil-to-lymphocyte ratio? BMC Res Notes 2017;10:12.
29. 30. Weiser C, Schwameis M, Sterz F, Herkner H, Lang IM, Schwarzinger I, et al. Mortality in patients resuscitated from out-of-hospital cardiac arrest based on automated blood cell count and neutrophil lymphocyte ratio at admission. Resuscitation 2017;116:49-55.