Lactate Therapy After Traumatic Brain Injury

NCT01573507 | Completed DMC

• 1 other identifier: 237/10
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Traumatic Brain Injury; Subarachnoid Hemorrhage

Keywords

traumatic brain injury; lactate; brain metabolism; cerebral microdialysis; subarachnoid hemorrhage; transcranial doppler

Outcome Measures

Primary Outcomes (1)

• Increase from baseline in brain extracellular lactate, pyruvate and glucose

  Increase from baseline in brain extracellular lactate, pyruvate and glucose measured with intra-parenchymal cerebral microdialysis catheter

  6 hours

Secondary Outcomes (6)

• Increase from baseline in brain tissue PO2

  6 hours

• Increase from baseline in cerebral perfusion pressure

  6 hours

• Decrease from baseline in intracranial pressure

  6 hours

• plasma sodium

  6 hours

• plasma osmolality

  6 hours

Study Arms (1)

sodium lactate infusion

EXPERIMENTAL

Continuous i.v. infusion of Sodium Lactate (2'400 mOsmol/L) over 3 hours

Other: sodium lactate infusion

Interventions

sodium lactate infusion OTHER

3-6 hours continuous infusion of sodium lactate (20-40 mcg/kg/min)

sodium lactate infusion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients admitted to our intensive care unit (ICU) after severe TBI or poor-grade aneurysmal subarachnoid hemorrhage (SAH), defined by a post-resuscitation Glasgow Coma Scale (GCS) \< 9
• Age 18-75 years
• Abnormal head CT-scan (Marshall grade ≥ 2 or Fisher \>2)
• Intracranial pressure (ICP), PbtO2 and cerebral MD monitoring as part of standard care

You may not qualify if:

• Penetrating TBI
• non aneurysmal SAH
• Age \< 18 or \> 75 years,
• More than 1 extra-cranial injury with sustained hemodynamic instability and sustained blood lactate elevation \> 4 mmol/L
• Cognitive handicap due to previous neurological or neurosurgical history
• Non-survivable injury, brain death or expected death within 48 hours
• Pregnancy

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead
• Swiss National Science Foundation: collaborator
• European Society of Intensive Care Medicine: collaborator

Study Sites (1)

CHUV, Lausanne University Hospital

Lausanne, 1011, Switzerland

Location

Related Publications (2)

• Carteron L, Solari D, Patet C, Quintard H, Miroz JP, Bloch J, Daniel RT, Hirt L, Eckert P, Magistretti PJ, Oddo M. Hypertonic Lactate to Improve Cerebral Perfusion and Glucose Availability After Acute Brain Injury. Crit Care Med. 2018 Oct;46(10):1649-1655. doi: 10.1097/CCM.0000000000003274.

  PMID: 29923931 DERIVED

• Bouzat P, Sala N, Suys T, Zerlauth JB, Marques-Vidal P, Feihl F, Bloch J, Messerer M, Levivier M, Meuli R, Magistretti PJ, Oddo M. Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain. Intensive Care Med. 2014 Mar;40(3):412-21. doi: 10.1007/s00134-013-3203-6. Epub 2014 Jan 30.

  PMID: 24477453 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic; Subarachnoid Hemorrhage

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Intracranial Hemorrhages; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mauro Oddo, MD

  CHUV, Lausanne University Hospital, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: médecin adjoint, PD-MER I

Model Details: Hypertonic lactate

Study Record Dates

• First Submitted: April 1, 2012
• First Posted: April 9, 2012
• Study Start: March 1, 2012
• Primary Completion: December 18, 2017
• Study Completion: December 18, 2017
• Last Updated: September 9, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)