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Effect of Mannitol 20% Versus Hypertonic Saline 7.5% in Brain Metabolism and Oxygenation

Primary Purpose

Brain Edema, Metabolic Disturbance, Electrolyte and Fluid Balance Conditions

Status
Completed
Phase
Phase 4
Locations
Greece
Study Type
Interventional
Intervention
Mannitol
NaCl 7.5%
Sponsored by
Aristotle University Of Thessaloniki
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Edema focused on measuring mannitol, hypertonic saline, brain metabolism, brain oxygenation

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adult patients aged between 18 and 75 years
  • ASA Physical status 1 to 3
  • Elective or semi-elective supratentorial craniotomy
  • Signed informed consent

Exclusion Criteria:

  • Craniotomy for suprasellar pathologies
  • Re-craniotomy at the same site
  • Perioperative sodium disorders (Na <130 mEq/L or >150 mEq/L)
  • Administration of intravenous mannitol or hypertonic saline 7.5% 24 hours or less before the surgery
  • Preoperative obstructive hydrocephalus
  • Congestive heart failure
  • Renal failure

Sites / Locations

  • AHEPA University Hospital
  • Georgia Tsaousi

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Mannitol 20%

Hypertonic saline 7.5%

Arm Description

Mannitol 20% (4.6ml/kg) will be administered 20 minutes before dura matter opening.

Hypertonic saline 7.5% (2ml/kg) will be administered 20 minutes before dura matter opening

Outcomes

Primary Outcome Measures

Changes of jugular venous oxygen saturation
Alterations in jugular venous oxygen saturation (%) after intravenous infusion of isosmotic doses of mannitol 20% and hypertonic saline 7.5%

Secondary Outcome Measures

Changes of S-100b protein
Alterations in S-100b (μg/L) after intravenous infusion of isosmotic doses of mannitol 20% and hypertonic saline 7.5%
Changes in the cardiac index
Alterations in the cardiac index (L/min/m2) after intravenous infusion of isosmotic doses of mannitol 20% and hypertonic saline 7.5%
Brain tension after intravenous infusion of isosmotic doses of mannitol 20% and hypertonic saline 7.5% assessed by Brain relaxation Score and subdural pressure
Brain tension graded from 1 to 4 (1 indicates satisfactory brain relaxation and 4 serious brain bulking)
Functional outcome of participants
Functional status of the participants assessed by Extended GOS ranginging from 1 to 7 (1 indicates death and 7 neurologically intact patient)

Full Information

First Posted
May 20, 2018
Last Updated
May 5, 2021
Sponsor
Aristotle University Of Thessaloniki
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1. Study Identification

Unique Protocol Identification Number
NCT03573999
Brief Title
Effect of Mannitol 20% Versus Hypertonic Saline 7.5% in Brain Metabolism and Oxygenation
Official Title
Effect of Isosmotic Doses of Mannitol 20% Versus Hypertonic Saline 7.5% in Brain Metabolism and Oxygenation in Supratentorial Craniotomies
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
June 29, 2018 (Actual)
Primary Completion Date
October 31, 2019 (Actual)
Study Completion Date
December 20, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Aristotle University Of Thessaloniki

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Usage of osmotic agents is a standard practice in neuroanesthesia since cerebral edema is a very common situation for patients with pathology in the brain. Cerebral edema is defined as the accumulation of fluid in the intracellular or extracellular compartments of the brain. Among other situations that have nothing to do with the brain, a supratentorial pathology such as a tumor, traumatic injury or an aneurysm, will lead to disruption of blood-brain barrier, and energy crisis of the cells that will cause mainly vasogenic and cytotoxic cerebral edema. The most common monitoring method for "measuring" cerebral edema is ICP (intracranial pressure) in which normal values are (with differences in the bibliography) 10-15 mmHg. The osmotic agents used most in neuroanesthesia are mannitol 20% and hypertonic NaCl 7.5% or 3%. Their brain relaxation effectiveness is supposed to be quite the same between the two different agents. Their main difference is that mannitol induces diuresis. Also, electrolyte disorders are another possibility after mannitol infusion. On the other hand, NaCl 7.5% causes vasodilation, does not induce diuresis and hemodynamically, even though it reduces SBP, it raises CO because of its excessive vasodilation. But both reduce cerebral edema due to the change of osmotic pressure in the vessels, that leads to extracting water from brain cells. A supratentorial craniotomy is de facto worsening the oxygenation and metabolism condition of the surgical site, adding to the problem the intracranial pathology causes in the first place. So if oxygen provided is low and the metabolic rate is high, the rate of anaerobic metabolism will raise. Measuring the oxygen in the jugular bulb is the most reliable monitoring method of cerebral oxygenation and metabolism. It becomes evident that optimization of cerebral oxygenation during a craniotomy will possibly affect the outcome of a patient, by improving it. So, if any superiority of one osmotic agent over the other could be demonstrated this will be very helpful in the decision making in routine clinical practice.
Detailed Description
Each participant will receive standard monitoring (ECG, SpO2, SBP, BIS, urine output, temperature). More detailed hemodynamic monitoring will be obtained by Edwards Lifesciences ClearSight system (CO, CI, SV, SVI, SVV, SVR, SVRI). TCI Propofol and Remifentanil will be the agents of choice for induction and maintenance in anesthesia and cisatracurium will be used for neuromuscular blockade for intubation. Protective mechanical ventilation will be chosen (7ml/kg IBW) with a Respiratory rate to obtain a PaCO2 of 35-40 mmHg. PEEP will be changed for the best PaO2/FiO2 ratio and FiO2 of choice will be 0.5. The radial artery catheterization will be applied for direct blood pressure measurement and arterial blood gas sampling ( pH, PaO2, PaCO2, HCO3, BE, Osmolality, Lactic acid, Hb, Glucose, Na, K will be measured). The jugular bulb ipsilateral to the craniotomy site will be catheterized for receiving blood samples for blood gas analysis. The following oxygenation and metabolic parameters / derivates will be measured or calculated: SjvO2, pH, PjvO2, PjvCO2, HCO3, BE, Osmolality, Lactic acid jv, Hb, Glucose, Na, K, AjvDO2, AjvCO2, O2ERbr, eRQbr, AjvDL, and LOI. The osmotic agent will be administered 20 minutes before dura matter incision. Before the dura mater opening the subdural space pressure will be measured and relevant CPP will be calculated. Brain Relaxation Score will be assessed by the neurosurgeon. Phases T0: 5 minutes before administration of the osmotic agent T15: 15 minutes after administration of the osmotic agent T30: 30 minutes after administration of the osmotic agent T60: 60 minutes after administration of the osmotic agent T90: 90 minutes after administration of the osmotic agent T120: 120 minutes after administration of the osmotic agent T180: 180 minutes after administration of the osmotic agent T240: 240 minutes after administration of the osmotic agent Blood samples for measuring S-100b will be collected at phases T0, T240 and 12 hours after osmotic agent administration. Postoperative complications, length of ICU stay, GOS-E (Glasgow Outcome Scale) and other neurological deficits will be recorded.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Edema, Metabolic Disturbance, Electrolyte and Fluid Balance Conditions
Keywords
mannitol, hypertonic saline, brain metabolism, brain oxygenation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Mannitol 20%
Arm Type
Active Comparator
Arm Description
Mannitol 20% (4.6ml/kg) will be administered 20 minutes before dura matter opening.
Arm Title
Hypertonic saline 7.5%
Arm Type
Experimental
Arm Description
Hypertonic saline 7.5% (2ml/kg) will be administered 20 minutes before dura matter opening
Intervention Type
Drug
Intervention Name(s)
Mannitol
Intervention Description
4.6 ml/kg will be administered before dura opening
Intervention Type
Drug
Intervention Name(s)
NaCl 7.5%
Intervention Description
2 ml/kg will be administered before dura opening
Primary Outcome Measure Information:
Title
Changes of jugular venous oxygen saturation
Description
Alterations in jugular venous oxygen saturation (%) after intravenous infusion of isosmotic doses of mannitol 20% and hypertonic saline 7.5%
Time Frame
15 minutes after the end of the infusion of the tested osmotic agent
Secondary Outcome Measure Information:
Title
Changes of S-100b protein
Description
Alterations in S-100b (μg/L) after intravenous infusion of isosmotic doses of mannitol 20% and hypertonic saline 7.5%
Time Frame
6 hours after the end of the infusion of the tested osmotic agent
Title
Changes in the cardiac index
Description
Alterations in the cardiac index (L/min/m2) after intravenous infusion of isosmotic doses of mannitol 20% and hypertonic saline 7.5%
Time Frame
15 minutes after the end of the infusion of the tested osmotic agent
Title
Brain tension after intravenous infusion of isosmotic doses of mannitol 20% and hypertonic saline 7.5% assessed by Brain relaxation Score and subdural pressure
Description
Brain tension graded from 1 to 4 (1 indicates satisfactory brain relaxation and 4 serious brain bulking)
Time Frame
2 minutes before dura opening
Title
Functional outcome of participants
Description
Functional status of the participants assessed by Extended GOS ranginging from 1 to 7 (1 indicates death and 7 neurologically intact patient)
Time Frame
7 days post surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult patients aged between 18 and 75 years ASA Physical status 1 to 3 Elective or semi-elective supratentorial craniotomy Signed informed consent Exclusion Criteria: Craniotomy for suprasellar pathologies Re-craniotomy at the same site Perioperative sodium disorders (Na <130 mEq/L or >150 mEq/L) Administration of intravenous mannitol or hypertonic saline 7.5% 24 hours or less before the surgery Preoperative obstructive hydrocephalus Congestive heart failure Renal failure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Georgia Tsaousi
Organizational Affiliation
Aristotle University Of Thessaloniki
Official's Role
Principal Investigator
Facility Information:
Facility Name
AHEPA University Hospital
City
Thessaloníki
ZIP/Postal Code
56224
Country
Greece
Facility Name
Georgia Tsaousi
City
Thessaloníki
ZIP/Postal Code
56346
Country
Greece

12. IPD Sharing Statement

Plan to Share IPD
No

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Effect of Mannitol 20% Versus Hypertonic Saline 7.5% in Brain Metabolism and Oxygenation

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