NCT03573999

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

Completed Phase 4 Last updated 7 May 2021

What this trial tests

Phase 4 trial testing Mannitol in Brain Edema in 54 participants. Completed in 20 December 2019.

Timeline

29 June 2018

Primary endpoint
31 October 2019

20 December 2019

Quick facts

Lead sponsor	Aristotle University Of Thessaloniki
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	54
Start date	29 June 2018
Primary completion	31 October 2019
Estimated completion	20 December 2019
Sites	2 locations across Greece

Drugs / interventions tested

• Mannitol (Mannitol) — full drug profile →
• NaCl 7.5%

Conditions studied

• Brain Edema — all drugs for Brain Edema →
• Metabolic Disturbance — all drugs for Metabolic Disturbance →
• Electrolyte and Fluid Balance Conditions — all drugs for Electrolyte and Fluid Balance Conditions →

Sponsor

Aristotle University Of Thessaloniki

Who can join

Adults 18 to 75, any sex, with Brain Edema or Metabolic Disturbance. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. The Medical Management of Cerebral Edema: Past, Present, and Future Therapies.
   Halstead MR, Geocadin RG. · · 2019 · cited 56× · PMID 31512062 · DOI 10.1007/s13311-019-00779-4