Sodium Lactate and Brain Relaxation (LSD)

NCT04488874 | Completed Phase 3 DMC

• 1 other identifier: API/2017/81
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Sodium Lactate; Intracranial Hypertension; Brain Relaxation

Keywords

Brain relaxation; Sodium lactate; Mannitol 20%; Neurosurgery

Outcome Measures

Primary Outcomes (1)

• 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.

  intraoperative

Secondary Outcomes (13)

• Necessity for "rescue" therapy

  intraoperative

• Electrolytes alterations

  30 minutes, 60 minutes, 180 minutes, 24 hours and 48 hours after completion of sodium lactate or mannitol infusion

• Changes of lactatemia

  30 minutes, 60 minutes, 180 minutes, 24 hours and 48 hours after completion of sodium lactate or mannitol infusion

• Volume of post operative brain edema

  Day 2 after surgery

• Glasgow Coma Scale

  preoperative, at day 1 and day 2 postoperative

Study Arms (2)

Sodium Lactate

EXPERIMENTAL

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

Drug: Sodium Lactate

Mannitol 20%

ACTIVE COMPARATOR

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

Drug: Mannitol 20% Infusion

Interventions

Sodium Lactate DRUG

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

Sodium Lactate

Mannitol 20% Infusion DRUG

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.

Mannitol 20%

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 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead

Study Sites (1)

CHU de Besançon

Besançon, France

Location

Related Publications (2)

• 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.

  PMID: 8512094 BACKGROUND

• 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.

  PMID: 36221362 DERIVED

MeSH Terms

Conditions

Intracranial Hypertension

Interventions

Sodium Lactate; Mannitol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Lactates; Hydroxy Acids; Carboxylic Acids; Organic Chemicals; Sugar Alcohols; Alcohols; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2019
• First Posted: July 28, 2020
• Study Start: September 29, 2020
• Primary Completion: May 31, 2023
• Study Completion: June 30, 2023
• Last Updated: September 13, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)