Sodium Lactate and Brain Relaxation (LSD) (LSD)

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

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.

Study Overview

• Status: Completed
• Conditions: Intracranial Hypertension; Sodium Lactate; Brain Relaxation
• Intervention / Treatment: Drug: Sodium Lactate; Drug: Mannitol 20% Infusion

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Guillaume BESCH, MD; Phone Number: +33 3 81 21 89 58; Email: gbesch@chu-besancon.fr

Study Locations

• France
  • Besancon, France
    • CHU de Besancon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sodium Lactate; Intravenous Molar Sodium Lactate is administered during the first surgical incision. The dose is 2.5mL/kg.	Drug: 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
Active Comparator: Mannitol 20%; Intravenous mannitol 20% is administered during the first surgical incision. The dose is 5mL/kg (1g/kg).	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	intraoperative
Electrolytes alterations	Variations of natremia (mmol/L), kaliemia (mmol/L), pH and serum osmolarity (mosmol/L) after administration of the osmotherapy.	30 minutes, 60 minutes, 180 minutes, 24 hours and 48 hours after completion of sodium lactate or mannitol infusion
Changes of lactatemia	Variations of lactatemia (mmol/L) after administration of the osmotherapy	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	Measurement of the volume of the post operative brain edema by MRI	Day 2 after surgery
Glasgow Coma Scale	Assessment of Glasgow coma scale (scale assessing level of conscioussness ranging from 3 = deep unconsciousness to 15 = normal consciousness)	preoperative, at day 1 and day 2 postoperative
Extubation	Time between the end of anesthesia and extubation (min)	Within 2 hours after the end of surgery
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.	preoperative and Day 2 after surgery
Protein S100-β	change in blood level of Protein S100-β	Prior to sodium lactate or mannitol infusion and at 24 hours and at 48 hours after completion of sodium lactate or mannitol infusion
Neuron-Specific Enolase (NSE)	Change in blood level of Neuron-Specific Enolase (NSE)	Prior to sodium lactate or mannitol infusion and at 24 hours and at 48 hours after completion of sodium lactate or mannitol infusion
Glial Fibrillary Acid Protein (GFAP)	Change in blood level of Neuron-Specific Enolase (NSE)	Prior to sodium lactate or mannitol infusion and at 24 hours and at 48 hours after completion of sodium lactate or mannitol infusion
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	Within 30 days after surgery
Mortality	Mortality within 30 days after surgery	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).	preoperative and at day 30 after surgery

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2020
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: April 8, 2019
• First Submitted That Met QC Criteria: July 24, 2020
• First Posted (Actual): July 28, 2020

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Neurosurgery; Brain relaxation; Sodium lactate; Mannitol 20%
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hypertension; Physiological Effects of Drugs; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Mannitol
• Other Study ID Numbers: API/2017/81

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No