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Severe Traumatic Brain Injury - therapeutic interventions and outcome evaluation

Réen, Linus LU (2025) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
A substantial external force transmitted to the brain may cause a severe traumatic brain injury (sTBI) , resulting in structural brain damage and/or functional impairment. Despite progress in management, traumatic brain injury remains a major cause of severe disability and death. This thesis evaluates treatment strategies and novel interventions in children and adults with sTBI and comprises the following components: Lund Concept (LC) treatment in children and adults; changes in zero-reference points for Intracranial pressure (ICP) and mean arterial pressure (MAP); a randomized trial protocol on Salovum®’s effect on ICP and inflammatory markers; and initial results from the trial described in Paper IV. Papers I–III are retrospective... (More)
A substantial external force transmitted to the brain may cause a severe traumatic brain injury (sTBI) , resulting in structural brain damage and/or functional impairment. Despite progress in management, traumatic brain injury remains a major cause of severe disability and death. This thesis evaluates treatment strategies and novel interventions in children and adults with sTBI and comprises the following components: Lund Concept (LC) treatment in children and adults; changes in zero-reference points for Intracranial pressure (ICP) and mean arterial pressure (MAP); a randomized trial protocol on Salovum®’s effect on ICP and inflammatory markers; and initial results from the trial described in Paper IV. Papers I–III are retrospective cohorts, while Paper V is based on prospectively collected data.
Paper I. The cohort consisted of 135 sTBI children. Overall mortality was 43%, and 10% among patients receiving neurointensive care. Outcomes were good in 60%, moderate in 25%, and unfavorable in 15% of patients. Cerebral perfusion pressure (CPP) <40 mmHg or >60 mmHg, and ICP >15 mmHg, were associated with poor outcome.
Paper II. Adult sTBI patients (n=135) were included. The 30-day and 6-month mortality rates were 16% and 20%, respectively. A favorable outcome was achieved in 48% of patients.
Paper III. Fourty-nine sTBI patients between 2013-2016 and 53 patients between 2018-2022 were included. ICP increased after changing the reference point to the external acoustic meatus (EAM) (p < 0.0001). Use of metoprolol (50% vs. 13%; p = 0.0002) decreased, while norepinephrine use increased (42% vs. 98%; p <0.0001).
Paper IV. Twenty sTBI patients are randomized to receive treatment with Salovum® or placebo. The primary endpoints are ICP and inflammatory markers measured in plasma and microdialysate.
Paper V. Ten initial patients from the study described in Paper IV were included. Mean ICP did not differ between the groups (11±6 mmHg vs. 11±4 mmHg; p = 0.6). Comprehensive cytokine analyses in microdialysate and plasma revealed no convincing differences between patients treated with Salovum® and those who received placebo.
In conclusion, treatment of sTBI according to the Lund Concept (LC) resulted in low mortality and unfavorable outcome in children and was well tolerated in adults. Changing zero-reference points for ICP and MAP significantly altered medical management. Initial findings do not support the hypothesis that Salovum® affects ICP or the inflammatory response in sTBI.
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Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Associate professor Raj, Rahul, Division of Neurosurgery, Helsinki University Hospital
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Severe TBI, Trauma, Neurointensive Care, ICP, CPP
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2025:132
pages
128 pages
publisher
Lund University, Faculty of Medicine
defense location
Belfragesalen, BMC D15, Klinikgatan 32 i Lund
defense date
2025-11-28 13:30:00
ISSN
1652-8220
ISBN
978-91-8021-785-9
language
English
LU publication?
yes
id
21dc0ea5-bb27-473d-9c89-b21dc625c590
date added to LUP
2025-10-22 09:35:56
date last changed
2025-11-06 11:58:46
@phdthesis{21dc0ea5-bb27-473d-9c89-b21dc625c590,
  abstract     = {{A substantial external force transmitted to the brain may cause a severe traumatic brain injury (sTBI) , resulting in structural brain damage and/or functional impairment. Despite progress in management, traumatic brain injury remains a major cause of severe disability and death. This thesis evaluates treatment strategies and novel interventions in children and adults with sTBI and comprises the following components: Lund Concept (LC) treatment in children and adults; changes in zero-reference points for Intracranial pressure (ICP) and mean arterial pressure (MAP); a randomized trial protocol on Salovum®’s effect on ICP and inflammatory markers; and initial results from the trial described in Paper IV. Papers I–III are retrospective cohorts, while Paper V is based on prospectively collected data.<br/>Paper I. The cohort consisted of 135 sTBI children. Overall mortality was 43%, and 10% among patients receiving neurointensive care. Outcomes were good in 60%, moderate in 25%, and unfavorable in 15% of patients. Cerebral perfusion pressure (CPP) &lt;40 mmHg or &gt;60 mmHg, and ICP &gt;15 mmHg, were associated with poor outcome.<br/>Paper II. Adult sTBI patients (n=135) were included. The 30-day and 6-month mortality rates were 16% and 20%, respectively. A favorable outcome was achieved in 48% of patients.<br/>Paper III. Fourty-nine sTBI patients between 2013-2016 and 53 patients between 2018-2022 were included. ICP increased after changing the reference point to the external acoustic meatus (EAM) (p &lt; 0.0001). Use of metoprolol (50% vs. 13%; p = 0.0002) decreased, while norepinephrine use increased (42% vs. 98%; p &lt;0.0001).<br/>Paper IV. Twenty sTBI patients are randomized to receive treatment with Salovum® or placebo. The primary endpoints are ICP and inflammatory markers measured in plasma and microdialysate.<br/>Paper V. Ten initial patients from the study described in Paper IV were included. Mean ICP did not differ between the groups (11±6 mmHg vs. 11±4 mmHg; p = 0.6).  Comprehensive cytokine analyses in microdialysate and plasma revealed no convincing differences between patients treated with Salovum® and those who received placebo.<br/>In conclusion, treatment of sTBI according to the Lund Concept (LC) resulted in low mortality and unfavorable outcome in children and was well tolerated in adults. Changing zero-reference points for ICP and MAP significantly altered medical management. Initial findings do not support the hypothesis that Salovum® affects ICP or the inflammatory response in sTBI.<br/>}},
  author       = {{Réen, Linus}},
  isbn         = {{978-91-8021-785-9}},
  issn         = {{1652-8220}},
  keywords     = {{Severe TBI, Trauma, Neurointensive Care, ICP, CPP}},
  language     = {{eng}},
  number       = {{2025:132}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Severe Traumatic Brain Injury - therapeutic interventions and outcome evaluation}},
  url          = {{https://lup.lub.lu.se/search/files/232046420/Linus_R_en_-_WEB.pdf}},
  year         = {{2025}},
}