Optimized Therapy in Severe Traumatic Brain Injured Patients

Phase 4

Completed

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

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Dipeptiven	Dipeptiven	0.75 g/ kg/ d Dipeptiven ( L- alanine- L- glutamine; 82 mg/ ml L- alanine, 134.6 mg/ ml L- glutamine; Fresenius Kabi, Switzerland) continuous intravenous infusion

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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
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
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
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