Sodium Lactate and Brain Relaxation (LSD)

Intracranial Hypertension Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04488874
• Other study ID #: API/2017/81
• Status: Completed
• Phase: Phase 3
• Start date: September 29, 2020
• Est. completion date: June 30, 2023

Study information

• Verified date: August 2023
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 30, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Relaxation
• Intracranial Hypertension
• Sodium Lactate

Intervention

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
• 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.

Locations

Country	Name	City	State
France	CHU de Besançon	Besancon

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon

Country where clinical trial is conducted

France, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Volume of post operative brain edema	Measurement of the volume of the post operative brain edema by MRI	Day 2 after surgery
Secondary	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
Secondary	Extubation	Time between the end of anesthesia and extubation (min)	Within 2 hours after the end of surgery
Secondary	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
Secondary	Protein S100-ß	change in blood level of Protein S100-ß	Prior to sodium lactate or mannitol infusion and at 24 hours and at 48 hours after completion of sodium lactate or mannitol infusion
Secondary	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
Secondary	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
Secondary	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
Secondary	Mortality	Mortality within 30 days after surgery	Within 30 days after surgery
Secondary	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