Mannitol Brain Relaxation Effect

Study Overview
=================
Brief Summary
-----------------
Mannitol is widely used in patients with elevated intracranial pressure. In neurosurgical field, especially in large size or with brain edema, it is necessary to decrease brain volume to facilitate surgical approach. In general, 0.25 -1.5g of mannitol per kilogram has been known to decrease ICP effectively. But there are some debates in regard to appropriate dose of mannitol.

Detailed Description
-----------------
Previous meta-analysis reported that mannitol has dose-response relationship with intracranial pressure. Another study of Sorani showed dose-response relationship between mannitol and intracranial pressure (ICP) in traumatic brain injury patients. In this study, authors would investigate that mannitol increments can provide more brain relaxation in patients undergoing craniotomy for supratentorial brain tumor removal.

Official Title
-----------------
Can Mannitol Increments Provide More Brain Relaxation in Patients Undergoing Craniotomy for Supratentorial Brain Tumor Removal?

Conditions
-----------------
Supratentorial Neoplasms

Intervention / Treatment
-----------------
* Drug: 0.25g/kgof 20% mannitol
* Drug: 0.5g/kg of 20% mannitol
* Drug: 1.0g/kg of 20% mannitol
* Drug: 1.5g/kg of 20% mannitol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who underwent craniotomy for supratentorial brain tumor under general anesthesia Exclusion Criteria: Patient who does not agree to the study Patients with or American Society of Anesthesiologists (ASA) physical status class IV or more Patients with glasgow coma scale (GCS) under 13 points Patients who have hyponatremia or hypernatremia (Na<130 or >150mEq/L) Patients who have congestive heart failure or moderately decreased renal function (GFR <60ml/min/1.73m2) Patients with extraventricular drainage such as external ventricular drain (EVD) or ventriculoperitoneal (VP) shunt Patients who already under mannitolization

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>0.25g/kgof 20% mannitol administered at drilling of skull. | Drug: 0.25g/kgof 20% mannitol<br>* When the neurosurgeon starts the drilling of skull, 0.25g/kg of 20% mannitol administered through the IV catheter with fulldrip. Neurosurgeon 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).<br>|
| Experimental: Group 2<br>0.5g/kg of 20% mannitol administered at drilling of skull. | Drug: 0.5g/kg of 20% mannitol<br>* When the neurosurgeon starts the drilling of skull, 0.5g/kg of 20% mannitol administered through the IV catheter with fulldrip. Neurosurgeon 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).<br>|
| Experimental: Group 3<br>1.0 g/kg of 20% mannitol administered at drilling of skull. | Drug: 1.0g/kg of 20% mannitol<br>* When the neurosurgeon starts the drilling of skull, 1.0g/kg of 20% mannitol administered through the IV catheter with fulldrip. Neurosurgeon 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).<br>|
| Experimental: Group 4<br>1.5g/kg of 20% mannitol administered at drilling of skull. | Drug: 1.5g/kg of 20% mannitol<br>* When the neurosurgeon starts the drilling of skull,1.5g/kg of 20% mannitol administered through the IV catheter with fulldrip. Neurosurgeon 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).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| brain parenchymal relaxation | Brain relaxation was assessed immediately after opening of the dura on a scale range from 1 to 4 (1=bulging brain, 2=firm brain, 3-satisfactorily relaxed, 4=perfectly relaxed) by neurosurgeon who is blinded to dose of mannitol. 3 and 4 scale means brain relaxed. We would analyse if the success proportion of brain relaxation increase according to the mannitol increment 0.25g/kg, 0.5g/kg, 1.0g/kg and 1.5g/kg using Cochran-Armitage trend test. | intraoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemodynamic change | Check the mean arterial blood pressure (ABP), heart rate (HR), central venous pressure (CVP) at baseline, 30min, 60min, and 180 min after skin incision. Baseline value means data of just after anesthetic induction. | at baseline, 30 min, 60min and 180 min after the administration of the study drug | 
| Electrolyte change | Check the serum laboratory result of electrolyte include potassium, sodium immediately before the infusion of mannitol and 30, 60 and 180 min after the administration of the study drug. | at baseline, 30 min, 60min and 180 min after the administration of the study drug | 
| Brain relaxation score | Brain relaxation was assessed immediately after opening of the dura on a scale range from 1 to 4 (1=bulging brain, 2=firm brain, 3-satisfactorily relaxed, 4=perfectly relaxed) by neurosurgeon who is blinded to dose of mannitol. | intraoperative | 
| Urine output | check the urine amount at baseline (just after induction of anesthesia), 30min/60min/180min after mannitol loading. | at just after induction of anesthesia, 30min, 60min and 180 min after mannitl loading | 
| Osmolar gap change | Check the serum osmolarity, blood urea nitrogen (BUN), glucose immediately before the infusion of mannitol and 30, 60, and 180 minutes after the administration of the study drug for calculate the osmolar gap. Osmolar gap (OG) = measured osmolarity - calculated osmolarity Calculated osmolarity = 2x[Na(mMol)]+1.15x([glucose(mg/dL)/18)+([urea(mg/dL)/2.8) | at baseline, 30min, 60min and 180 min after the administration of the study drug |