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Sodium Lactate and Brain Relaxation (LSD) (LSD)

Primary Purpose

Sodium Lactate, Intracranial Hypertension, Brain Relaxation

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Sodium Lactate
Mannitol 20% Infusion
Sponsored by
Centre Hospitalier Universitaire de Besancon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sodium Lactate focused on measuring Brain relaxation, Sodium lactate, Mannitol 20%, Neurosurgery

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with ASA 1, ASA 2 ou ASA 3, meaning they don't have any unstable comorbidities which could be a threat to life.
  • Scheduled surgery for resection of supratentorial brain tumors by craniotomy under general anesthesia
  • Unilateral brain tumor
  • Deviation of the falx cerebri > 3mm on the preoperative imaging
  • Pharmacological brain relaxation required by the neurosurgeon in charge of the patient.
  • Patient who has been informed and who signed the free informed consent to participate to the study. Meaning the patient understood the purpose and the procedures required by the study and agreed to participate and obey the requirements and restrictions of this study.
  • Affiliation to a social security system or recipient of a such system.

Exclusion Criteria:

  • Emergency surgery
  • Age < 18 years old or > 75 years old
  • ASA score IV-V
  • Legal incapability or limited legal capacity
  • Patient who will unlikely cooperate to the study and/or poor cooperation foreseen by the investigator
  • Preoperative Glasgow score < 13
  • Pregnant woman and/or breastfeeding
  • Body index masse< 18 kg.m-2 ou > 30 kg.m-2
  • Preoperative hyponatremia < 130mmol/l or hypernatremia > 145 mmol/l
  • Osmotherapy in the 24 hours prior to the surgery (Mannitol, Hypertonic saline, Sodium lactate)
  • Congestive heart failure
  • Moderate ou severe chronic kidney disease, defined by a creatinine clearance (MDRD) < 60 ml/min
  • End-stage liver disease (Child Pugh ≥ B7)
  • Myasthenia gravis
  • External ventricular drain or ventriculoperitoneal shunt of cerebrospinal fluid
  • Allergy to Mannitol 20% or one of his excipients
  • Allergy to Sodium Lactate or one of his excipients
  • Contraindication for propofol
  • Allergy to anesthetic agents (propofol, remifentanil, cisatracurium)
  • Refusal of consent
  • Patient within the exclusion period of another study or planned by the "national file of volunteers"
  • Medical history of cognitive disorders or demencia

Sites / Locations

  • CHU de Besançon

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Sodium Lactate

Mannitol 20%

Arm Description

Intravenous Molar Sodium Lactate is administered during the first surgical incision. The dose is 2.5mL/kg.

Intravenous mannitol 20% is administered during the first surgical incision. The dose is 5mL/kg (1g/kg).

Outcomes

Primary Outcome Measures

Quality of brain relaxation
An adequate brain relaxation is evaluated by the neurosurgeon with a stage 1 (perfectly relaxed) or 2 (acceptably relaxed) of the brain swelling score validated by Todd et al. The brain swelling score is a four-point-scale: 1 (normal brain; no swelling); 2 (minimal swelling, but acceptable); 3 (serious swelling but no specific change in management required); or 4 (severe brain swelling requiring some intervention). Todd et al. reported a significant Relationship between intracranial pressure and the brain swelling score. The brain swelling score is the consensual tool used in clinical trials to assess the clinical effectiveness of brain relaxative therapy.

Secondary Outcome Measures

Necessity for "rescue" therapy
Proportion of patients who needed a "rescue" therapy in order to improve the brain relaxation and to enable the surgery. "Rescue" therapy consists of the administration of an additional dose of Mannitol 20% 0.25g/kg, deepening the anesthesia (BIS between 20 and 40) or the administration of an intravenous dose of Thiopental 5mg/kg.
Electrolytes alterations
Variations of natremia (mmol/L), kaliemia (mmol/L), pH and serum osmolarity (mosmol/L) after administration of the osmotherapy.
Changes of lactatemia
Variations of lactatemia (mmol/L) after administration of the osmotherapy
Volume of post operative brain edema
Measurement of the volume of the post operative brain edema by MRI
Glasgow Coma Scale
Assessment of Glasgow coma scale (scale assessing level of conscioussness ranging from 3 = deep unconsciousness to 15 = normal consciousness)
Extubation
Time between the end of anesthesia and extubation (min)
Neurological recovery
Neurological revcovery will be assessed comparing the results of a battery of validated neurocognitive tests performed the day before surgery and at Day 2 after surgery.
Protein S100-β
change in blood level of Protein S100-β
Neuron-Specific Enolase (NSE)
Change in blood level of Neuron-Specific Enolase (NSE)
Glial Fibrillary Acid Protein (GFAP)
Change in blood level of Neuron-Specific Enolase (NSE)
Morbidity
Incidence of heart rhythm disorders during the first 48 hours postoperative, intensive care unit length of stay, hospital length of stay, duration of mechanical ventilation, postoperative complications
Mortality
Mortality within 30 days after surgery
Karnofsky performance scale
The Karnofsky performance scale index is an assessment tool for functional impairment. The lower the Karnofsky score, the worst functional impairment, and in most serious illnesses, the worse likelihood of survival. The Karnofsky performance scale ranges from 0 (dead patient) to 100 (normal no complaints, no evidence of disease).

Full Information

First Posted
April 8, 2019
Last Updated
September 11, 2023
Sponsor
Centre Hospitalier Universitaire de Besancon
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1. Study Identification

Unique Protocol Identification Number
NCT04488874
Brief Title
Sodium Lactate and Brain Relaxation (LSD)
Acronym
LSD
Official Title
Clinical Effectiveness of Hypertonic Sodium Lactate Infusion for Intraoperative Brain Relaxation in Patients Undergoing Scheduled Craniotomy for Supratentorial Brain Tumor Resection: Study Protocol of a Single Center Double-blind Randomized Controlled Phase II Pilot Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
September 29, 2020 (Actual)
Primary Completion Date
May 31, 2023 (Actual)
Study Completion Date
June 30, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Besancon

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Resection surgery of brain tumors by craniotomy requires efficient brain relaxation intraoperatively in order to avoid injuries caused by the brain retractors (such as ischemic-reperfusion and cerebral oedema). The gold standard for the brain relaxation during a surgery is Mannitol 20%. Molar sodium lactate is now used to induce brain relaxation in patients with traumatic brain injury and intracranial hypertension due to its osmotic effect. Furthermore, the injection of sodium lactate may lead to better neuronal metabolism during cerebral aggression, and may participate to the reduction of cerebral oedema and secondary injuries. LSD is a pilot randomised trial which tries to assess the interest of intravenous administration of molar Sodium Lactate on the quality of brain relaxation in surgical resection of supratentorial brain tumors by craniotomy. The primary outcome measure is the quality of brain relaxation, evaluated by neurosurgeon at the opening of the dura, by a validated brain relaxation scale.
Detailed Description
It's a prospective, comparative, randomised, double blinded study. It will enroll 50 patients undergoing resection surgery of supratentorial brain tumor. They will be randomly divided in 2 groups of 25 patients each : Mannitol 20% and molar Sodium Lactate. The only difference between the 2 groups is the drug used for brain relaxation at the surgical incision : Mannitol or Sodium lactate. The outcome measures include quality of brain relaxation, need of "rescue" therapy to get an adequate brain relaxation, electrolytes alterations, change in lactate serum level, quantification of post operative brain swelling by MRI, time of extubation, Glasgow Coma Scale, neuropsychological evaluation, blood levels of Protein S100-β, NSE (Neuron-Specific Enolase) and GFAP Glial Fibrillary Acid Protein), morbidity and mortality during 30 days after surgery.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sodium Lactate, Intracranial Hypertension, Brain Relaxation
Keywords
Brain relaxation, Sodium lactate, Mannitol 20%, Neurosurgery

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Masking Description
Patients will not known which of Sodium lactate or Mannitol will they receive. The drug will be hidden by an opaque drape during its administration and as soon as the administration is over it will be taken out of the operating room, so the neurosurgeon won't know which drug was given.
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sodium Lactate
Arm Type
Experimental
Arm Description
Intravenous Molar Sodium Lactate is administered during the first surgical incision. The dose is 2.5mL/kg.
Arm Title
Mannitol 20%
Arm Type
Active Comparator
Arm Description
Intravenous mannitol 20% is administered during the first surgical incision. The dose is 5mL/kg (1g/kg).
Intervention Type
Drug
Intervention Name(s)
Sodium Lactate
Intervention Description
Sodium lactate is administered at 2.5mL/kg during the first surgical incision. Neurosurgeon will evaluate the brain relaxation using a validated scale once the dura is open. A stage 1(perfectly relaxed) or 2((acceptably relaxed) is considered satisfactory. Sodium Lactate and Mannitol 20% are used at an equimolar dose
Intervention Type
Drug
Intervention Name(s)
Mannitol 20% Infusion
Intervention Description
Mannitol 20% is administered intravenously at a dose of 5mL/kg, so 1g/kg, during the first surgical incision. Neurosurgeon will evaluate the brain relaxation using a validated scale once the dura is open. A stage 1(perfectly relaxed) or 2((acceptably relaxed) is considered satisfactory.
Primary Outcome Measure Information:
Title
Quality of brain relaxation
Description
An adequate brain relaxation is evaluated by the neurosurgeon with a stage 1 (perfectly relaxed) or 2 (acceptably relaxed) of the brain swelling score validated by Todd et al. The brain swelling score is a four-point-scale: 1 (normal brain; no swelling); 2 (minimal swelling, but acceptable); 3 (serious swelling but no specific change in management required); or 4 (severe brain swelling requiring some intervention). Todd et al. reported a significant Relationship between intracranial pressure and the brain swelling score. The brain swelling score is the consensual tool used in clinical trials to assess the clinical effectiveness of brain relaxative therapy.
Time Frame
intraoperative
Secondary Outcome Measure Information:
Title
Necessity for "rescue" therapy
Description
Proportion of patients who needed a "rescue" therapy in order to improve the brain relaxation and to enable the surgery. "Rescue" therapy consists of the administration of an additional dose of Mannitol 20% 0.25g/kg, deepening the anesthesia (BIS between 20 and 40) or the administration of an intravenous dose of Thiopental 5mg/kg.
Time Frame
intraoperative
Title
Electrolytes alterations
Description
Variations of natremia (mmol/L), kaliemia (mmol/L), pH and serum osmolarity (mosmol/L) after administration of the osmotherapy.
Time Frame
30 minutes, 60 minutes, 180 minutes, 24 hours and 48 hours after completion of sodium lactate or mannitol infusion
Title
Changes of lactatemia
Description
Variations of lactatemia (mmol/L) after administration of the osmotherapy
Time Frame
30 minutes, 60 minutes, 180 minutes, 24 hours and 48 hours after completion of sodium lactate or mannitol infusion
Title
Volume of post operative brain edema
Description
Measurement of the volume of the post operative brain edema by MRI
Time Frame
Day 2 after surgery
Title
Glasgow Coma Scale
Description
Assessment of Glasgow coma scale (scale assessing level of conscioussness ranging from 3 = deep unconsciousness to 15 = normal consciousness)
Time Frame
preoperative, at day 1 and day 2 postoperative
Title
Extubation
Description
Time between the end of anesthesia and extubation (min)
Time Frame
Within 2 hours after the end of surgery
Title
Neurological recovery
Description
Neurological revcovery will be assessed comparing the results of a battery of validated neurocognitive tests performed the day before surgery and at Day 2 after surgery.
Time Frame
preoperative and Day 2 after surgery
Title
Protein S100-β
Description
change in blood level of Protein S100-β
Time Frame
Prior to sodium lactate or mannitol infusion and at 24 hours and at 48 hours after completion of sodium lactate or mannitol infusion
Title
Neuron-Specific Enolase (NSE)
Description
Change in blood level of Neuron-Specific Enolase (NSE)
Time Frame
Prior to sodium lactate or mannitol infusion and at 24 hours and at 48 hours after completion of sodium lactate or mannitol infusion
Title
Glial Fibrillary Acid Protein (GFAP)
Description
Change in blood level of Neuron-Specific Enolase (NSE)
Time Frame
Prior to sodium lactate or mannitol infusion and at 24 hours and at 48 hours after completion of sodium lactate or mannitol infusion
Title
Morbidity
Description
Incidence of heart rhythm disorders during the first 48 hours postoperative, intensive care unit length of stay, hospital length of stay, duration of mechanical ventilation, postoperative complications
Time Frame
Within 30 days after surgery
Title
Mortality
Description
Mortality within 30 days after surgery
Time Frame
Within 30 days after surgery
Title
Karnofsky performance scale
Description
The Karnofsky performance scale index is an assessment tool for functional impairment. The lower the Karnofsky score, the worst functional impairment, and in most serious illnesses, the worse likelihood of survival. The Karnofsky performance scale ranges from 0 (dead patient) to 100 (normal no complaints, no evidence of disease).
Time Frame
preoperative and at day 30 after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with ASA 1, ASA 2 ou ASA 3, meaning they don't have any unstable comorbidities which could be a threat to life. Scheduled surgery for resection of supratentorial brain tumors by craniotomy under general anesthesia Unilateral brain tumor Deviation of the falx cerebri > 3mm on the preoperative imaging Pharmacological brain relaxation required by the neurosurgeon in charge of the patient. Patient who has been informed and who signed the free informed consent to participate to the study. Meaning the patient understood the purpose and the procedures required by the study and agreed to participate and obey the requirements and restrictions of this study. Affiliation to a social security system or recipient of a such system. Exclusion Criteria: Emergency surgery Age < 18 years old or > 75 years old ASA score IV-V Legal incapability or limited legal capacity Patient who will unlikely cooperate to the study and/or poor cooperation foreseen by the investigator Preoperative Glasgow score < 13 Pregnant woman and/or breastfeeding Body index masse< 18 kg.m-2 ou > 30 kg.m-2 Preoperative hyponatremia < 130mmol/l or hypernatremia > 145 mmol/l Osmotherapy in the 24 hours prior to the surgery (Mannitol, Hypertonic saline, Sodium lactate) Congestive heart failure Moderate ou severe chronic kidney disease, defined by a creatinine clearance (MDRD) < 60 ml/min End-stage liver disease (Child Pugh ≥ B7) Myasthenia gravis External ventricular drain or ventriculoperitoneal shunt of cerebrospinal fluid Allergy to Mannitol 20% or one of his excipients Allergy to Sodium Lactate or one of his excipients Contraindication for propofol Allergy to anesthetic agents (propofol, remifentanil, cisatracurium) Refusal of consent Patient within the exclusion period of another study or planned by the "national file of volunteers" Medical history of cognitive disorders or demencia
Facility Information:
Facility Name
CHU de Besançon
City
Besancon
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
8512094
Citation
Todd MM, Warner DS, Sokoll MD, Maktabi MA, Hindman BJ, Scamman FL, Kirschner J. A prospective, comparative trial of three anesthetics for elective supratentorial craniotomy. Propofol/fentanyl, isoflurane/nitrous oxide, and fentanyl/nitrous oxide. Anesthesiology. 1993 Jun;78(6):1005-20. doi: 10.1097/00000542-199306000-00002.
Results Reference
background
PubMed Identifier
36221362
Citation
Besch G, Parmentier AL, Berthier F, Jaeg H, Villeneuve J, Hammoudi F, Scaringella N, Clairet AL, Vettoretti L, Chopard G, Thines L, Ferreira D, Samain E, Pili-Floury S. Clinical effectiveness of hypertonic sodium lactate infusion for intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection: A study protocol of a single center double-blind randomized controlled phase II pilot trial. Medicine (Baltimore). 2022 Oct 7;101(40):e31038. doi: 10.1097/MD.0000000000031038.
Results Reference
derived

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Sodium Lactate and Brain Relaxation (LSD)

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