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Citicoline in severe traumatic brain injury: indications for improved outcome

A retrospective matched pair analysis from 14 Austrian trauma centers

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Summary

Goal-oriented management of traumatic brain injury (TBI) can save the lives and/or improve the long-term outcome of millions of affected patients worldwide. Additionally, enhancing quality of life will save enormous socio-economic costs; however, promising TBI treatment strategies with neuroprotective agents, such as citicoline (CDP-choline), lacked evidence or produced contradictory results in clinical trials. During a prehospital TBI project to optimize early TBI care within 14 Austrian trauma centers, data on 778 TBI patients were prospectively collected. As preceding evaluations suggested a beneficial outcome in TBI patients treated at the Wiener Neustadt Hospital (WNH), we aimed to investigate the potential role of citicoline administration, solely applied in WNH, in those patients. In a retrospective subgroup analysis we compared 67 patients from WNH with citicoline administration and 67 matched patients from other Austrian centers without citicoline use. Patients with Glasgow Coma Scale score <13 on site and/or Abbreviated Injury Scale of the region “head” >2 were included. Our analysis revealed significantly reduced rates of intensive care unit (ICU) mortality (5% vs. 24%, p < 0.01), in-hospital mortality (9% vs. 24%, p = 0.035) and 6‑month mortality (13% vs. 28%, p = 0.031), as well as of unfavorable outcome (34% vs. 57%, p = 0.015) and observed vs. expected ratio for mortality (0.42 vs. 0.84) in the WNH (citicoline receivers) group. Despite the limitations of a retrospective subgroup analysis our findings suggest a possible correlation between early and consequent citicoline administration and beneficial outcomes. Therefore, we aim to set up an initiative for a prospective, multicenter randomized controlled trial with citicoline in sTBI (severe TBI) patients.

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Acknowledgements

The authors acknowledge the members of the International Neurotrauma Research Organization (INRO) and collaborative partners for their work and the collection of data used for analyses in this article. In particular, we want to express our special thanks and dedicate this publication to Walter Mauritz who provided the impetus for this investigation. Walter passed away in May 2015. He was Vice President of the INRO and Professor of Anesthesiology and Intensive Care Medicine at Trauma Hospital “Lorenz Boehler” 2 in Vienna. We thank Chiesi Pharmaceuticals for providing a research grant to facilitate data analysis and writing assistance. We thank Ulrike Posch for providing medical writing services on behalf of Chiesi Pharmaceuticals.

Funding

The INRO prehospital project was funded jointly by the Austrian Ministry of Health (Contract Oct. 15, 2008) and by the Austrian Worker’s Compensation Board (AUVA; FK 11/2008 and FK 11/2010). Data analysis was supported by a grant from AUVA (FK 09/13). INRO is supported by an annual grant from Mrs. Ala Auersperg-Isham and Mr. Ralph Isham through the Neurotrauma Foundation, and by small donations from various sources. Chiesi Pharmaceuticals provided a non-educational grant to facilitate initial data analysis at INRO and writing assistance.

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Authors and Affiliations

  1. Department of Anesthesiology, Emergency Medicine and Intensive Care and Karl Landsteiner Institute of Emergency Medicine, General Hospital Wiener Neustadt, Wiener Neustadt, Austria

    Helmut Trimmel, Andrea Wodak, Guenther Herzer & Daniel Csomor

  2. Department of Public Health, Faculty of Health Sciences and Social Work, Trnava University, Trnava, Slovakia

    Marek Majdan

  3. International Neurotrauma Research Organization (INRO), Vienna, Austria

    Alexandra Brazinova

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  1. Helmut Trimmel
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  2. Marek Majdan
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  3. Andrea Wodak
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  6. Alexandra Brazinova
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Correspondence to Helmut Trimmel.

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Conflict of interest

H. Trimmel reports non-financial support from Chiesi Pharmaceuticals during the conduct of the study. M. Majdan, A. Wodak, G. Herzer, D. Csomor and A. Brazinova declare that they have no competing interests.

Additional information

Author contributions H. Trimmel concepted, initiated and designed the study, collected, analyzed and interpreted data, drafted and critically revised the manuscript. M. Majdan performed the statistical analysis, contributed to data interpretation and helped to draft and revise the manuscript. A. Wodak, G. Herzer and D. Csomor contributed to data acquisition and data analysis, and helped to revise the manuscript. A. Brazinova conceived the INRO prehospital TBI project, participated in its design, coordination and data analysis, and critically revised the manuscript. All authors read and approved the final manuscript.

Caption Electronic Supplementary Material

508_2017_1240_MOESM1_ESM.tif

S1 Fig. Flow diagram of participating Austrian centers and patients from the INRO prehospital database. (*lost to follow up due to incomplete dataset. AIS abbreviated injury scale, GCS Glasgow coma scale, INRO International Neurotrauma Research Organization, WNH Wiener Neustadt Hospital)

508_2017_1240_MOESM2_ESM.tif

S2 Fig. Pressure parameters and heart rate of survivors and non-survivors under citicoline therapy. (CPP cerebral perfusion pressure, HR heart rate, ICP intracranial pressure, MAP mean arterial pressure)

S3 Fig. Mean S100B levels of survivors and non-survivors under citicoline therapy by day of treatment. S100B µg

S1 Table. Patterns of citicoline use at WNH

S2 Table. Laboratory parameters of citicoline patients by clinical outcome

S3 Table. Medication parameters of citicoline patients at WNH

S4 Table. Preliminary RCT study design for continuous and early citicoline in sTBI in Austria

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Trimmel, H., Majdan, M., Wodak, A. et al. Citicoline in severe traumatic brain injury: indications for improved outcome. Wien Klin Wochenschr 130, 37–44 (2018). https://doi.org/10.1007/s00508-017-1240-9

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