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On severe traumatic brain injury: aspects of an intra cranial pressure-targeted therapy based on the Lund concept
Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience.
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Severe Traumatic Brain Injury (sTBI) is a major cause of mortality and morbidity. At the Department of Neurosurgery Umeå University Hospital subjects with sTBI are treated with an intracranial pressure (ICP) guided therapy based on physiological principles, aiming to optimise the microcirculation of the brain so avoiding secondary brain injuries. The investigations in this thesis are unique in the sense that all patients with sTBI were treated according to the guidelines of an ICP targeted therapy based on the “Lund concept”.

As the treatment is based on normalisation of the ICP, the accuracy and reliability of the measuring device is of outmost importance. Therefore the accuracy, drift, and complications related to the measuring device was prospectively studied (n=128). The drift was 0,9 ± 0,2 mmHg during a mean of 7,2 ± 0,4 days and the accuracy high. No clinical significant complications were noted.

In 1997 uni- or bilateral decompressive hemi-craniectomy (DC) was introduced into the treatment guidelines. The effect of DC on the ICP and outcome was retrospectively analysed for subjects with sTBI treated 1998-2001. In the subjects who underwent DC the ICP was 36,4 mmHg immediately before and 12,6 mmHg immediately after the DC. The ICP then levelled out at just above 20 mmHg. The ICP was significant lower during the 72 hours following DC. The outcome did not differ between subjects who had undergone DC or not.

Subclinical electroencephalographic seizures and status epilepticus have been reported to be common in subjects treated for traumatic brain injury (TBI). This can negatively influence the outcome giving rise to secondary brain injuries. The occurrence of seizures in subjects treated for TBI using continuous EEG monitoring was therefore prospectively studied. During 7334 hours of EEG recording in 47 patients no electroencephalographic seizures were observed.

Theoretically, and based on animal studies, prostacyclin (PGI2) can improve the microcirculation of the brain, decreasing the risk for secondary ischaemic brain injury. PGI2 was introduced to the treatment in a prospective randomised double blinded study (epoprostenol 0,5 ng/kg/min). The effect of PGI1 pkt was analysed using the lactate/pyruvate ratio (L/P) measured by cerebral microdialysis in order to study the energy metabolism in the brain. The outcome was measured as Glasgow Outcome Scale (GOS) at 3 months follow-up. Forty-eight subjects were included. The L/P was pathological high during the first day, thereafter decreasing. There was no significant difference in L/P or outcome between the treated and non-treated group. At 3 months the mortality was 12,5% (95,8% was discharged alive from the ICU), and favourable outcome (GOS 4-5) was 52%.

In the same study the brain injury biomarkers S-100B and NSE were followed twice a day for five days to evaluate brain injury and investigate the possible use of these biomarkers for outcome prediction. Initially the biomarkers were elevated to pathological levels which decreased over time. The biomarkers were significant elevated in subjects with Glasgow Coma Scale 3 (GCS) and GOS 1 compared with subjects with GCS 4-8 and GOS 2–5, respectively. A correlation to outcome was found but this correlation could not be used to predict clinical outcome.

It is concluded that the ICP measurements are valid and the treatment protocol is a safe and solid protocol, yielding among the best reported results in the world, in regard to favourable outcome as well as in regard to mortality. Epoprostenol in the given dose was not shown to have any effects on the microdialysis parameters nor the clinical outcome. In sTBI L/P and brain injury biomarkers can not be used to predict the final outcome.

Place, publisher, year, edition, pages
Umeå: Farmakologi och klinisk neurovetenskap , 2008. , 75 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1225
Keyword [en]
severe traumatic brain injury, ICP targeted therapy, ICP, hemicraniectomy, seizures, prostacyclin, microdialysis, outcome, S100B, NSE
National Category
Surgery
Identifiers
URN: urn:nbn:se:umu:diva-1908ISBN: 978-91-7264-680-3 (print)OAI: oai:DiVA.org:umu-1908DiVA: diva2:142381
Public defence
2008-11-21, Betula, 6M, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2008-11-07 Created: 2008-11-07 Last updated: 2010-01-18Bibliographically approved
List of papers
1. Clinical experience with the intraparenchymal intracranial pressure monitoring Codman MicroSensor system.
Open this publication in new window or tab >>Clinical experience with the intraparenchymal intracranial pressure monitoring Codman MicroSensor system.
2005 (English)In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 56, no 4, 693-698 p.Article in journal (Refereed) Published
Keyword
Brain/radiography, Humans, Intracranial Hypertension/*diagnosis/radiography, Intracranial Pressure, Monitoring; Physiologic/*instrumentation/methods, Reproducibility of Results, Tomography; X-Ray Computed
Identifiers
urn:nbn:se:umu:diva-5819 (URN)15792507 (PubMedID)
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2017-12-14Bibliographically approved
2. Effective ICP reduction by decompressive craniectomy in patients with severe traumatic brain injury treated by an ICP-targeted therapy
Open this publication in new window or tab >>Effective ICP reduction by decompressive craniectomy in patients with severe traumatic brain injury treated by an ICP-targeted therapy
2007 (English)In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 24, no 6, 927-935 p.Article in journal (Refereed) Published
Abstract [en]

Severe traumatic brain injury (TBI) is one of the major causes of death in younger age groups. In Umea, Sweden, an intracranial pressure (ICP) targeted therapy protocol, the Lund concept, has been used in treatment of severe TBI since 1994. Decompressive craniectomy is used as a protocol-guided treatment step. The primary aim of the investigation was to study the effect of craniectomy on ICP changes over time in patients with severe TBI treated by an ICP-targeted protocol. In this retrospective study, all patients treated for severe TBI during 1998-2001 who fulfilled the following inclusion criteria were studied: GCS <or= 8 at intubation and sedation, first recorded cerebral perfusion pressure (CPP) of >10 mm Hg, arrival within 24 h of trauma, and need of intensive care for >72 h. Craniectomy was performed when the ICP could not be controlled by evacuation of hematomas, sedation, ventriculostomy, or low-dose pentothal infusion. Ninety-three patients met the inclusion criteria. Mean age was 37.6 years. Twenty-one patients underwent craniectomy as a treatment step. We found a significant reduction of the ICP directly after craniectomy, from 36.4 mm Hg (range, 18-80 mm Hg) to 12.6 mm Hg (range, 2-51 mm Hg). During the following 72 h, we observed an increase in ICP during the first 8-12 h after craniectomy, reaching approximately 20 mm Hg, and later levelling out at approximately 25 mm Hg. The reduction of ICP was statistically significant during the 72 h. The outcome as measured by Glasgow Outcome Scale (GOS) did not significantly differ between the craniectomized group (DC) and the non-craniectomized group (NDC). The outcome was favorable (GOS 5-4) in 71% in the craniectomized group, and in 61% in the non-craniectomized group. Craniectomy is a useful tool in achieving a significant reduction of ICP overtime in TBI patients with progressive intracranial hypertension refractory to medical therapy. The procedure seems to have a satisfactory effect on the outcome, as demonstrated by a high rate of favorable outcome and low mortality in the craniectomized group, which did not significantly differ compared with the non-craniectomized group.

Keyword
Adolescent, Adult, Aged, Brain Injuries/complications/*physiopathology/*surgery, Clinical Protocols/standards, Craniotomy/*methods/standards, Emergency Medical Services/methods/standards, Female, Humans, Intracranial Hypertension/etiology/*physiopathology/*surgery, Male, Middle Aged, Patient Selection, Postoperative Complications/prevention & control, Skull/*surgery, Time Factors, Treatment Outcome
Identifiers
urn:nbn:se:umu:diva-7153 (URN)10.1089/neu.2005.356E (DOI)17600510 (PubMedID)
Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2017-12-14Bibliographically approved
3. Absence of electroencephalographic seizure activity in patients treated for head injury with an ICP targeted therapy
Open this publication in new window or tab >>Absence of electroencephalographic seizure activity in patients treated for head injury with an ICP targeted therapy
Show others...
2009 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 110, no 2, 300-305 p.Article in journal (Refereed) Published
Abstract [en]

OBJECT: The authors prospectively studied the occurrence of clinical and nonclinical electroencephalographically verified seizures during treatment with an intracranial pressure (ICP)-targeted protocol in patients with traumatic brain injury (TBI). METHODS: All patients treated for TBI at the Department of Neurosurgery, University Hospital Umea, Sweden, were eligible for the study. The inclusion was consecutive and based on the availability of the electroencephalographic (EEG) monitoring equipment. Patients were included irrespective of pupil size, pupil reaction, or level of consciousness as long as their first measured cerebral perfusion pressure was > 10 mm Hg. The patients were treated in a protocol-guided manner with an ICP-targeted treatment based on the Lund concept. The patients were continuously sedated with midazolam, fentanyl, propofol, or thiopental, or combinations thereof. Five-lead continuous EEG monitoring was performed with the electrodes at F3, F4, P3, P4, and a midline reference. Sensitivity was set at 100 muV per cm and filter settings 0.5-70 Hz. Amplitude-integrated EEG recording and relative band power trends were displayed. The trends were analyzed offline by trained clinical neurophysiologists. RESULTS: Forty-seven patients (mean age 40 years) were studied. Their median Glasgow Coma Scale score at the time of sedation and intubation was 6 (range 3-15). In 8.5% of the patients clinical seizures were observed before sedation and intubation. Continuous EEG monitoring was performed for a total of 7334 hours. During this time neither EEG nor clinical seizures were observed. CONCLUSIONS: Our protocol-guided ICP targeted treatment seems to protect patients with severe TBI from clinical and subclinical seizures and thus reduces the risk of secondary brain injury.

National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-3599 (URN)10.3171/2008.4.17538 (DOI)
Available from: 2008-11-07 Created: 2008-11-07 Last updated: 2017-12-14Bibliographically approved
4. Prostacyclin treatment in severe traumatic brain injury: a microdialysis and outcome study
Open this publication in new window or tab >>Prostacyclin treatment in severe traumatic brain injury: a microdialysis and outcome study
2009 (English)In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 26, no 8, 1251-1262 p.Article in journal (Refereed) Published
Abstract [en]

Prostacyclin (PGI2) is a potent vasodilator, inhibitor of leukocyte adhesion, and platelet aggregation. In trauma the balance between PGI2 and thromboxane A2 (TXA2) is shifted towards TXA2. External provided PGI2 would, from a theoretical and experimental point of view, improve the microcirculation in injured brain tissue. This study is a prospective consecutive double blinded randomised study on the effect of PGI2 versus placebo in severe traumatic brain injury (sTBI). All patients with sTBI were eligible. Inclusion criteria: verified sTBI, Glasgow Coma Score (GCS) at intubation and sedation ≤8, age 15 - 70 years, a first recorded cerebral perfusion pressure (CPP) of ≥ 10mmHg, and arrival within 24h of trauma. All subjects received an intra-cranial pressure (ICP) measuring device, bilateral intracerebral microdialysis catheters, and a microdialysis catheter in the abdominal subcutaneous adipose tissue. Subjects were treated according to an ICP targeted therapy based on the Lund concept. 48 patients, mean age of 35.5 years, and a median GCS 6 (3-8) were included. We found no significant effect of epoprostenol on either the lactate pyruvate ratio (L/P) at 24 hours or the brain glucose levels. There was no significant difference in clinical outcome between the two groups. The median Glasgow Outcome Score (GOS) at 3 months was 4, and mortality was 12.5%. The favourable outcome (GOS 4-5) was 52%. The initial L/P did not prognosticate for outcome. Thus our results indicate that there is no effect of PGI2 at a dose of 0.5 ng/kg/min on brain L/P, brain glucose levels or outcome at 3 months. The treatment seemed to yield a high number of favourable outcome and low mortality

Identifiers
urn:nbn:se:umu:diva-3600 (URN)10.1089/neu.2008.0605 (DOI)19226191 (PubMedID)
Available from: 2008-11-07 Created: 2008-11-07 Last updated: 2017-12-14Bibliographically approved
5. S-100B and NSE are poor outcome predictors in severe traumatic brain injury treated by an ICP targeted therapy
Open this publication in new window or tab >>S-100B and NSE are poor outcome predictors in severe traumatic brain injury treated by an ICP targeted therapy
(English)Manuscript (Other academic)
Identifiers
urn:nbn:se:umu:diva-3601 (URN)
Available from: 2008-11-07 Created: 2008-11-07 Last updated: 2010-03-03Bibliographically approved

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