Coma, Traumatic Brain Injury
Conditions
Keywords
traumatic brain injury, glutamine, microdialysis, metabolism
Brief summary
Severe traumatic brain injury is associated with life-threatening and incapacitating secondary injury. Contemporary therapeutic interventions are aimed at preventing and treating secondary damage. In this context, improved cerebral metabolism is an important target in modern neurointensive care. The main hypothesis is that continuous intravenous infusion of glutamyl-alanyl dipeptide restores disturbed brain metabolism following severe traumatic brain injury.
Detailed description
Patients suffering from severe traumatic brain injury and requiring multimodal neuromonitoring during pharmacological coma will receive alanyl-glutamine dipeptide (Dipeptiven) as part of standard clinical nutrition. In two groups of patients the influence of different duration of infusion (group 1: 24 hours; group 2: 5 days) will be investigated. For this, pharmacokinetic and pharmacodynamic parameters in plasma and brain are determined. Increased plasma glutamine and alanine in arterial and jugular venous plasma and in cerebral microdialysates are to reflect efficacy of Dipeptiven infusion. Plasma glutamate levels as well as changes in cerebral glutamate, lactate, lactate/pyruvate ratio, intracranial pressure, bispectral index electroencephalography will be measured to exclude potential adverse effects
Interventions
DRUGDipeptiven
two groups: group 1: continuous infusion for 24 hours group 2: continuous infusion for 5 days
Sponsors
Swiss National Science Foundation
Fresenius Kabi
University Hospital, Zürich
University of Zurich
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* severe traumatic brain injury * prolonged pharmacologic coma * multimodal neuromonitoring (microdialysis, ptiO2) * enteral nutrition
Exclusion criteria
* patients anticipated to decease within 48 hours * abdominal injury * mass transfusion * renal impairment * hepatic impairment * barbiturate coma * parenteral nutrition * weight below 50 kg * weight above 100 kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| plasma glutamine levels | 2 to 7 days | changes in plasma glutamine levels during and after infusion of alanyl-glutamine compared to baseline and intra-infusion values expressed in absolute (micromole/ liter) or relative (%) values |
| cerebral glutamine | 2 to 7 days | changes in cerebral glutamine levels during and after infusion of alanyl-glutamine compared to baseline and intra-infusion values expressed in absolute (micromole/ liter) or relative (%) values |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| cerebral glutamate | 2 to 7 days | changes in cerebral glutamate reflecting cerebral energetic deficit during and after infusion of alanyl-glutamine compared to baseline and intra-infusion values expressed in absolute (micromole/ liter) or relative (%) values |
| cerebral lactate | 2 to 7 days | changes in cerebral lactate and lactate/pyruvate ratio reflecting cerebral energetic deficit during and after infusion of alanyl-glutamine compared to baseline and intra-infusion values expressed in absolute (millimole/ liter) or relative (%) values |
| bispectral index electroencephalography | 2 to 7 days | changes in bispectral index EEG reflecting neuronal activation during and after infusion of alanyl-glutamine compared to baseline and intra-infusion values expressed in absolute or relative (%) values |
| intracranial pressure | 2 to 7 days | changes in intracranial pressure reflecting brain edema during and after infusion of alanyl-glutamine compared to baseline and intra-infusion values expressed in absolute (mm Hg) or relative (%) values |
| cerebral lactate to pyruvate ratio | 2 to 7 days | changes in lactate/pyruvate ratio reflecting cerebral energetic deficit during and after infusion of alanyl-glutamine compared to baseline and intra-infusion values expressed in absolute (millimole/ liter) or relative (%) values |
Countries
Switzerland
Outcome results
None listed