Sodium Lactate and Brain Relaxation (LSD)

NCT ID: NCT04488874

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-29
• Study Completion Date: 2023-06-30

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.

Conditions

Sodium Lactate; Intracranial Hypertension; Brain Relaxation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sodium Lactate

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

Group Type: EXPERIMENTAL

Sodium Lactate

Intervention Type: 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

Mannitol 20%

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

Group Type: ACTIVE_COMPARATOR

Mannitol 20% Infusion

Intervention Type: 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.

Interventions

Sodium Lactate

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

Mannitol 20% Infusion

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Besancon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU de Besançon

Besançon, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 8512094 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36221362 (View on PubMed)

Other Identifiers

API/2017/81

Identifier Type: -

Identifier Source: org_study_id