Lactate Therapy After Traumatic Brain Injury
Condition: Traumatic Brain Injury; Subarachnoid Hemorrhage
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Subarachnoid Hemorrhage; Hemorrhage; Wounds and Injuries
Study type: Interventional

Summary: 
      Background: Although glucose is essential to cerebral function, abundant experimental and
      clinical evidence demonstrates that endogenously released lactate, rather than glucose, is
      the preferential energy substrate for the brain in conditions of stress and acute injury. In
      patients with severe Traumatic Brain Injury (TBI) and aneurysmal subarachnoid hemorrhage
      (SAH) monitored with cerebral microdialysis and brain tissue oxygen (PbtO2), our preliminary
      data show that increased brain extracellular lactate is frequently observed. Our findings
      indicate that elevated brain lactate more often occurs in the absence of brain
      hypoxia/ischemia and is mainly the consequence of increased cerebral glycolysis, i.e. it
      occurs in association with high extracellular pyruvate. These data suggest that the primary
      source of elevated lactate is activated glycolysis and strongly support the concept that
      endogenously released lactate can be utilized by the injured human brain as energy substrate.
      They prompt further investigation to examine whether exogenous lactate supplementation can be
      a valuable neuroprotective strategy after TBI or SAH. Indeed, in animal models of brain
      injury, administration of exogenous lactate improves neuronal and cognitive recovery.

      Hypothesis: The investigators test the hypothesis that lactate therapy, administered during
      the acute phase of TBI or SAH, might exercise neuroprotective actions by restoring brain
      energetics and improving brain tissue PO2 and cerebral blood flow (CBF).

      Aim of the study: The aim of this single-center study is to examine the effect of sodium
      lactate infusion on cerebral extracellular metabolites, brain tissue PO2 and cerebral blood
      flow, measured with CT perfusion and transcranial doppler (TCD).

      Design: Prospective phase II interventional study examining the effect of a continuous 3-6
      hours infusion of sodium lactate (20-40 µmol/kg/min), administered within 48 hours from TBI
      or SAH, on cerebral extracellular glucose, pyruvate, glutamate, glycerol, PbtO2 and CBF.
    

Detailed description: 
      Study: Prospective, single-centre phase II interventional study. The study will take place at
      the Department of Intensive Care Medicine, Lausanne University Medical Center (Centre
      Hospitalier Universitaire Vaudois, CHUV), Lausanne, Switzerland.

      Patient population:

      Patients will be monitored with an intra-parenchymal monitoring system, consisting of ICP
      (Codman®, Integra Neurosciences), PbtO2 (Licox®, Integra Neurosciences) and cerebral
      microdialysis (CMA Microdialysis®) catheters, based on the protocol for management of TBI
      presently in use at our center.

      Each patient will receive a continuous infusion of sodium lactate (composition: lactate 1'000
      mmol/L, Na 1'000 mmol/L: concentration 20-40 µmol/kg/min) for 3-6 hours. Sodium lactate will
      be prepared locally by the Pharmacie Centrale, CHUV, Lausanne.

      Each patient will serve as his/her internal control, and the effect of sodium lactate on all
      brain physiological variables measured will be anayzed before, during and at the end of
      sodium lactate infusion.

      The main parameters of efficacy are increases of MD glucose, MD pyruvate, PbtO2, and CBF,
      during sodium lactate perfusion.

      For both MD glucose and MD pyruvate, we fixed as the minimal detectable effect of sodium
      lactate infusion a 30% increase of glucose and pyruvate at the end of the study. To obtain a
      power of 0.8 with an alpha of 0.05, the number of patients required to complete the study is
      33. We therefore plan to include 35 patients.

      Statistical analysis: At each time-point (baseline, during perfusion, end of sodium lactate
      infusion), differences of mean MD glucose, lactate, pyruvate, PbtO2, CBF, Mean transit time,
      ICP, CPP will be analyzed. We will also examine the percentage time spent with abnormal
      values (MD glucose < 1 mmol/L, PbtO2 < 20 mm Hg, ICP > 20 mm Hg). Differences will be
      compared using ANOVA for repeated measures.
    

Intervention name(s): sodium lactate infusion
Intervention type(s): Other
Intervention description(s): 3-6 hours continuous infusion of sodium lactate (20-40 mcg/kg/min)
Intervention model: Single Group Assignment
Intervention model description: Hypertonic lactate
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: traumatic brain injury; lactate; brain metabolism; cerebral microdialysis; subarachnoid hemorrhage; transcranial doppler