Clinical trial NCT04488874: Sodium Lactate and Brain Relaxation (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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sodium Lactate
Intracranial Hypertension
Brain Relaxation
Keywords: Brain relaxation
Sodium lactate
Mannitol 20%
Neurosurgery
Lead sponsor: Centre Hospitalier Universitaire de Besancon
Sponsor class: OTHER
First posted: 2020-07-28
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Quality of brain relaxation
timeFrame: intraoperative
Secondary outcomes:
measure: Necessity for "rescue" therapy
timeFrame: intraoperative
measure: Electrolytes alterations
timeFrame: 30 minutes, 60 minutes, 180 minutes, 24 hours and 48 hours after completion of sodium lactate or mannitol infusion
measure: Changes of lactatemia
timeFrame: 30 minutes, 60 minutes, 180 minutes, 24 hours and 48 hours after completion of sodium lactate or mannitol infusion
measure: Volume of post operative brain edema
timeFrame: Day 2 after surgery
measure: Glasgow Coma Scale
timeFrame: preoperative, at day 1 and day 2 postoperative
measure: Extubation
timeFrame: Within 2 hours after the end of surgery
measure: Neurological recovery
timeFrame: preoperative and Day 2 after surgery
measure: Protein S100-β
timeFrame: Prior to sodium lactate or mannitol infusion and at 24 hours and at 48 hours after completion of sodium lactate or mannitol infusion
measure: Neuron-Specific Enolase (NSE)
timeFrame: Prior to sodium lactate or mannitol infusion and at 24 hours and at 48 hours after completion of sodium lactate or mannitol infusion
measure: Glial Fibrillary Acid Protein (GFAP)
timeFrame: Prior to sodium lactate or mannitol infusion and at 24 hours and at 48 hours after completion of sodium lactate or mannitol infusion
measure: Morbidity
timeFrame: Within 30 days after surgery
measure: Mortality
timeFrame: Within 30 days after surgery
measure: Karnofsky performance scale
timeFrame: preoperative and at day 30 after surgery
Other outcomes:
Locations:
city: Besancon
country: France
facility: CHU de Besançon
Study officials:
References:
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.
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.