How Much Mannitol & Why ?

I got a few comments recently regarding using Mannitol in the prime- and how much people are using per case.

Here is a summary of some casual positions colleagues over the years have laid out for the use of Mannitol:

• Don’t give it for renal failure / insufficiency patients
• Causes skeletal muscle dilation- thus a pressure drop when initiating CPB
• Reduces interstitial edema
• Dosing:  12.5g – 25g in the prime:
• SAA : & Q Hour as an Oxygen Free Radical Scavenger

The Questions I Have are This:

• When do you NOT put Mannitol in the Prime?
• What’s your dosing policy?  (What do you consider too high of a dose?)
• Why is it indispensable in your practice?
• When is it Just Wrong to use?

Transport

“Mannitol can also be used as a facilitating agent for the transportation of pharmaceuticals directly into the brain. The arteries of the blood-brain barrier are much more selective than normal arteries. Normally, molecules can diffuse into tissues through gaps between the endothelial cells of the blood vessels. However, what enters the brain must be much more rigorously controlled. The endothelial cells of the blood-brain barrier are connected by tight junctions, and simple diffusion through them is impossible. Rather, active transport is necessary, requiring energy, and only transporting molecules that the arterial endothelial cells have receptor signals for. Mannitol is capable of opening this barrier by temporarily shrinking the endothelial cells, simultaneously stretching the tight junctions between them.^[8]

An intracarotid injection of high molarity mannitol (1.4-1.6M), causes the contents of the artery to be hyperosmotic to the cell. Water leaves the cell and enters the artery in order to recreate an osmotic equilibrium. This loss of water causes the cells to shrivel and shrink, stretching the tight junctions between the cells.^[9]

The newly formed gap reaches its peak width five minutes after mannitol injection, and stays widely open for thirty minutes. During this timespan, drugs injected into the artery can easily diffuse though the gaps between cells directly into the brain.^[10]

This makes mannitol indispensable for delivering various drugs directly to the brain (e.g., in the treatment of Alzheimer’s disease, or in chemotherapy for brain tumors. ” (Wikipedia)

ICP

“Mannitol is used clinically in osmotherapy to reduce acutely raised intracranial pressure until more definitive treatment can be applied, e.g., after head trauma. It is also used to treat patients with oliguric renal failure. It is administered intravenously, and is filtered by the glomeruli of the kidney, but is incapable of being resorbed from the renal tubule, resulting in decreased water and Na⁺ reabsorption via its osmotic effect. Consequently, mannitol increases water and Na⁺ excretion, thereby decreasing extracellular fluid volume. ” (Wikipedia)

CPB

“Mannitol is a hypertonic, low molecular weight crystalloid widelyused in clinical practice to stimulate diuresis. As a volumeexpander, mannitol draws fluid initially across the capillaryinto the plasma. Then it rapidly diffuses into the interstitialfluid and increases the volume of the whole extracellular phaseby withdrawing water from the body cells. A particular advantage of mannitol is its protective effect on renal function. During cardiopulmonary bypass in adults, priming fluid containing 10 g of mannitol provided only a transient diuresis during the bypass period, compared to control patients who did not receive mannitol. 

However, an increased dose of 20 g of mannitol resulted in a significantly greater diuresis than both the control groupand the 10 g group, and this diuretic effect continued for 3 h during the post bypass period. Furthermore, patients receiving 30 g of mannitol had an even greater diuresis which lasted for about 4 h. The diuretic effect of mannitol lasted for up to 12 h after patients’ arrival in the intensive care unit despite indications that the crystalloid had already been cleared from the body. ” (Multimedia Manual of Cardiothoracic Surgery)

Mannitol is commonly used in the circuit prime of a heart lung machine during cardiopulmonary bypass. The presence of mannitol preserves renal function during the times of low blood flow and pressure, while the patient is on bypass. The solution prevents the swelling of endothelial cells in the kidney, which may have otherwise reduced blood flow to this area and resulted in cell damage.  (Wikipedia)

Hemodynamic and Anti-viscosity Effects

• Decreases the viscosity of blood (not only by decreasing haematocrit, but by decreasing the volume, rigidity, and cohesiveness of RBC membranes thereby decreasing the mechanical resistance to passage through the microvasculature)
• Decreases systemic vascular resistance, mild positive inotropic effect on the heart
• Net effect is an increase in CO and oxygen delivery (ICU Topics)

Free radical scavenging

• An attractive agent for promoting blood flow in areas of focally compromised perfusion
• May also have a role in prevention of no-reflow phenomena
• There are no controlled data supporting the beneficial role of mannitol’s free radical scavenging properties independent of the other well studied actions of mannitol  (ICU Topics)

Pharmacokinetics

• Relatively little information on the pharmacokinetics of mannitol infusions
• Half Life elimination is about 30 to 60 mins for doses of 0.25 to 1.5 g/kg body weight  (ICU Topics)

References

Wikipedia

https://en.wikipedia.org/wiki/Mannitol

Multimedia Manual of Cardiothoracic Surgery

https://mmcts.ctsnetjournals.org/cgi/content/full/2006/0109/mmcts.2005.001198

ICU Topics

https://www.aic.cuhk.edu.hk/web8/mannitol.htm