The Optimal Dose of Mannitol for Intraoperative Brain Relaxation During the Operation of Aneurysmal Subarachnoid Hemorrhage (ODAS)

Study on the Optimal Dosage of Mannitol in Aneurysmal Subarachnoid Hemorrhage Craniotomy

Aneurysmal subarachnoid hemorrhage (aSAH) tended to lead to a sudden increase in intracerebral pressure (ICP), which can cause decreased cerebral perfusion and transient global cerebral ischemia. Early clipping and coiling of aneurysms and surgical evacuation of intracerebral hematoma were recommended for aSAH patients. However, the high ICP made it difficult to separate the subarachnoid space during the operation. Effective reduction of ICP was the key to the succession of the operation. But there is a lack of consensus on the management of raised ICP in aSAH. Mannitol is widely used to reduce ICP in patients with cerebral edema. The potential mechanism including decreasing the viscosity of the blood improving regional cerebral microvascular flow and oxygenation and increasing intravascular volume due to increased plasma osmolality. The magnitude of the pressure reduction was correlated with the intact intracranial automatic adjustment function. However, the hypochloremic metabolic alkalosis, hypernatremia, hypokalemia and renal failure associated with mannitol overdose must be considered and the effective dose and the duration of its administration were still unknown. The aims of this study were to determine the most appropriate mannitol dose to provide adequate brain relaxation in aSAH patients with the fewest adverse effects.

Study Overview

• Status: Active, not recruiting
• Conditions: Aneurysmal Subarachnoid Hemorrhage
• Intervention / Treatment: Drug: Mannitol

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yu Chen, MD; Phone Number: +8618801239327; Email: chenyu_tiantan@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Capital Medical University Affiliated Beijing Tiantan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with acute subarachnoid hemorrhage
• Patients who underwent frontal-temporal craniotomy pterional approach aneurysm clipping surgery under general anesthesia.
• Patients operated by the same surgeon (Dr. Chen Xiaolin).

Exclusion Criteria:

• Patients who do not agree to the surgery.
• Patients who have congestive heart failure and kidney insufficiency.
• Patients who have pre-operative electrolyte imbalance.
• Patients who did not take the frontotemporal pterygoid approach.
• Patients with contraindications to mannitol due to low blood pressure.
• Patients who have had more than 3 days from bleeding to surgery.
• Patients with intracranial hematoma.
• Patients with Hunt-Hess grades 4-5.
• Patients who received intravenous mannitol within 6 hours before surgery.
• Patients who underwent ventricle puncture and drainage surgery before surgery.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose group; 0.5g/kg of 20% mannitol administered at skin incision.	Drug: Mannitol; When the neurosurgeon starts the skin incision, 20% mannitol administered through the venous catheter with fulldrip in 5-10 minutes. Neurosurgeons evaluate the degree of brain relaxation after dura opening in 4 point scale (1=bulging brain, 2=firm brain, 3=satisfactorily relaxed, 4=perfectly relaxed).
Experimental: Medium dose group; 1.0g/kg of 20% mannitol administered at skin incision.	Drug: Mannitol; When the neurosurgeon starts the skin incision, 20% mannitol administered through the venous catheter with fulldrip in 5-10 minutes. Neurosurgeons evaluate the degree of brain relaxation after dura opening in 4 point scale (1=bulging brain, 2=firm brain, 3=satisfactorily relaxed, 4=perfectly relaxed).
Experimental: High dose group; 1.5g/kg of 20% mannitol administered at skin incision.	Drug: Mannitol; When the neurosurgeon starts the skin incision, 20% mannitol administered through the venous catheter with fulldrip in 5-10 minutes. Neurosurgeons evaluate the degree of brain relaxation after dura opening in 4 point scale (1=bulging brain, 2=firm brain, 3=satisfactorily relaxed, 4=perfectly relaxed).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain relaxation score	The degree of brain relaxation after administration was assessed as four grades. denoting bulging or the condition that additional methods for brain relaxation are immediately and always required in order to continue the surgical procedure because of brain swelling; firm or the condition that additional methods for brain relaxation are occasionally required to continue the surgical procedure; adequate; perfectly relaxed. All patients received conventional frontotemporal pterional approach, and the time from skin incision to dural opening was constant for 30 minutes. At the time of dural opening, the degree of cerebral relaxation was evaluated, and the satisfactory cerebral relaxation was defined as 3 or 4 points.	Intraoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
electrolyte change (potassium)	Check the serum laboratory result of potassium (normal range: 3.4-4.5 mmol/L)	before the infusion of mannitol and 30 minutes after the administration of the study drug.
electrolyte change (sodium)	Check the serum laboratory result of sodium (normal range: 136-146 mmol/L)	before the infusion of mannitol and 30 minutes after the administration of the study drug.
electrolyte change (chlorine)	Check the serum laboratory result of chlorine (normal range: 98-106 mmol/L)	before the infusion of mannitol and 30 minutes after the administration of the study drug.
electrolyte change (calcium)	Check the serum laboratory result of calcium (normal range: 1.15-1.29 mmol/L)	before the infusion of mannitol and 30 minutes after the administration of the study drug.
Subdural hematoma	Excessive decrease in intracranial pressure may lead to intraoperative or postoperative subdural hematoma formation	CT scan 6 hours after surgery
modified Rankin Score 3 months after surgery	To evaluate the potential benefits of effective dural lysis and brain relaxation on patient outcomes. The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms. 1 - No significant disability. Able to carry out all usual activities, despite some symptoms. 2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead.	3 months after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
operation duration	Poor intracranial pressure reduction may result in prolonged duration of surgery, and evaluation of the duration of surgery is helpful in the selection of the optimal dose.Poor intracranial pressure reduction may result in prolonged duration of surgery, and evaluation of the duration of surgery is helpful in the selection of the optimal dose.	intraoperative

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Shuo Wang, MD, Beijing Tiantan Hospital; Principal Investigator: Xiaolin Chen, MD, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2019
• Primary Completion (Actual): November 14, 2023
• Study Completion (Estimated): January 14, 2024

Study Registration Dates

• First Submitted: September 11, 2019
• First Submitted That Met QC Criteria: October 21, 2019
• First Posted (Actual): October 22, 2019

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage; Physiological Effects of Drugs; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Mannitol
• Other Study ID Numbers: KY 2019-09

Drug and device information, study documents

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