Manual of mannitol medication, recommended by doctors who have seen it

*Only for medical professionals to read and refer to the precautions for mannitol in the treatment of increased intracranial pressure.
Mannitol is the most commonly used first-line drug for the treatment of increased intracranial pressure (ICP) and has a wide range of clinical applications
.

So when mannitol is used to reduce intracranial pressure, the dosage is 0.
25g/kg? Or 0.
5g/kg? Is it continuous infusion or pulsed administration? Is the drop rate as fast as possible? How to avoid serious adverse reactions as much as possible? Can glycerol fructose replace mannitol? Do you know all these questions? This article will answer you one by one
.

One mannitol infusion program Mannitol infusion program includes continuous infusion or pulsed administration.
Pulsed administration is more effective than continuous infusion.
The conventional recommended dose is 0.
25～1g/kg body weight via peripheral or central venous catheter Intravenous infusion within 10-20min
.

Pulsed administration is generally recommended for small doses of 0.
25g/kg, 100ml of mannitol preparation can cover patients with a body weight of less than 80 kg
.

In the case of sudden increase in intracranial pressure, a higher dose can be used, generally about 60g (1g/kg) is used
.

Short-term use of mannitol (1.
0～2.
0g/kg) can maximize the reduction of brain volume by reducing the extracellular fluid of the brain.
It is often used clinically to urgently reduce intracranial hypertension, such as cerebral hernia patients, during surgical operations In order to increase exposure and so on
.

In the subsequent treatment process, in order to achieve the same dehydration effect of lowering intracranial pressure, it is often necessary to increase the dosage of mannitol in order to achieve the same effect of reducing intracranial pressure
.

Therefore, it is very important to use a small dose of mannitol for pulsed administration of mannitol, especially for those who have a longer period of time
.

 Second, the faster the drip rate, the higher the plasma osmotic pressure, the stronger the dehydration effect, and the better the curative effect
.

However, pay attention to the underlying disease of the patient
.

In patients with cardiac insufficiency, coronary heart disease, and renal insufficiency, the rapid drip rate may lead to fatal diseases
.

It is generally required to finish dripping within 20min
.

It depends on the different conditions of each patient
.

 3.
Regarding the dosage of mannitol 1g of mannitol can produce an osmotic concentration of 5.
5mOsm/L.
Injection of 100g of mannitol can transfer 2000ml of intracellular water to the outside of the cell, and excretion of 50g of sodium in urine [2]
.

According to the Meta analysis by Wang Shu [3], it was pointed out that the half dose group (0.
5g/kg mannitol) and the full dose group (1.
0g/kg mannitol) in the treatment of cerebral edema can be considered to have no significant difference in efficacy, but the half dose group is more safe.
Excellent
.

Therefore, a half dose of mannitol is more recommended to treat patients with cerebral edema and increased intracranial pressure
.

The meta-analysis by Wang Xian et al.
[4] pointed out that the efficacy of half dose of mannitol in acute cerebral hemorrhage is similar to that of full dose, but the safety is better
.

The consensus pointed out that mannitol at a dose of 0.
25 g/kg can achieve the same effect of lowering intracranial pressure as mannitol at doses of 0.
5-1.
0 and 1.
0 g/kg
.

Low-dose mannitol can avoid causing osmotic pressure imbalance and severe dehydration, and can effectively improve cerebral hemodynamics
.

Repeated use of 100ml dose is more effective than the initial 500ml mannitol
.

 Four dosing interval Mannitol has a quick effect, it works within 20 minutes after intravenous injection, and the antihypertensive effect reaches its peak in 2-3 hours and lasts for 4 to 6 hours
.

Therefore, if osmotic therapy is still needed to reduce intracranial pressure after the first administration, the administration should be repeated 4 to 6 hours after monitoring intracranial pressure and plasma osmotic pressure
.

If the ICP control target is still not achieved after repeated administration, other intracranial pressure reduction programs are required
.

After the infusion of mannitol, the brain tissue water began to decrease soon and gradually reached a peak effect.
The patient's hypertonic state can usually be maintained for several hours, but the reduction of intracranial pressure is generally short-lived
.

Common adverse reactions in the treatment of increased ICP with pentamannitol ■ High plasma osmotic pressure When acute plasma osmotic pressure increases rapidly, it will cause loss of water in brain cells, and brain cell shrinkage will cause mechanical cerebrovascular involvement and secondary cerebrovascular damage
.

Therefore, it is even more necessary to use small doses of mannitol to avoid persistently high plasma osmotic pressure
.

■Osmotic nephropathy Mannitol is excreted from the kidney in its original form.
It is easy to cause calcium oxalate in mannitol to precipitate in the renal tubules, leading to renal tubule metabolism disorders, renal tubule absorption function decline, resulting in oliguria and anuria, leading to acute renal failure
.

Elderly patients or patients with existing renal failure are more potentially dangerous, which usually occurs after high doses of mannitol (>0.
2kg/d or the cumulative amount after 48h>0.
4kg)
.

Closely monitor relevant indicators during medication
.

If problems are found, reduce or stop in time
.

Once acute renal failure occurs, hemodialysis should be the first choice [5]
.

■Intracranial pressure rebounds quickly into the extracellular fluid after intravenous injection without entering the cell
.

However, when the blood mannitol concentration is high or there is acidosis, mannitol can pass through the blood-brain barrier and cause a rebound in intracranial pressure
.

Long-term high-dose use of mannitol can lead to a higher concentration in brain tissue, cause aggravation of cerebral edema, and cause a rebound of intracranial pressure
.

The accumulation of mannitol in brain tissue is time-dependent, and low-dose mannitol can reduce the aggravation and rebound of cerebral edema
.

Studies have shown that there is no significant difference in the dehydration effect of using 20% ​​mannitol 250ml and 125ml once, but continuous use more than 5 times can cause the blood-brain osmotic pressure gradient to be reversed.
Therefore, long-term use of 20% mannitol in large doses should be avoided.
It is recommended Sequential use of 20% mannitol combined with glycerol fructose, piracetam (can be used alone later) and/or diuretics, etc.
, to reduce the dosage of 20% mannitol, reduce its impact on renal function and electrolytes, and avoid intracranial pressure Rebound etc.
[6]
.

Whether six glycerol fructose can replace mannitol is similar to mannitol, glycerol fructose can also play a role in dehydration and reduce cerebral edema by changing the intravascular osmotic pressure
.

Because of its "not metabolized by the kidneys" feature, it will not cause damage to the kidneys
.

However, glycerol fructose will not cause significant changes in plasma osmotic pressure, and will not have obvious diuretic effect.
Because of this, if glycerol fructose is used alone, its effect of lowering intracranial pressure will be significantly slower than that of mannitol, and its effect will be slow.
The clinical application of lowering intracranial pressure is very limited [7]
.

Glycerol fructose does not cause electrolyte imbalance or intracranial pressure rebound, so it is more suitable for patients with mild cerebral edema, severe cerebral edema and renal insufficiency after cerebral hemorrhage.
It is often used interchangeably with mannitol
.

 Finally, the precautions for patients with other conditions[8]: The blood pressure may increase due to transient hypervolemia after the application of mannitol.
In the case of coexisting hypertension, the blood pressure may be higher in the short term after using mannitol.

.

Therefore, for patients with concurrent hypertension, before using mannitol, furosemide can be used to adjust the blood volume before using mannitol to avoid adverse reactions
.

Patients with cerebrovascular disease and cardiac insufficiency should use mannitol with caution to avoid heart failure caused by rapid transfusion or increased blood volume
.

When cerebrovascular disease is accompanied by insufficient blood volume, mannitol should be used as appropriate after blood volume supplementation
.

When cerebrovascular disease is accompanied by hypoproteinemia, it is advisable to adjust the plasma protein concentration before using mannitol as appropriate
.

References: [1] Pediatrics Group of Neurosurgery Branch of Chinese Medical Association, Neurosurgery Collaboration Group of Neurosurgery Branch of Chinese Medical Association, "Mannitol Treatment of Intracranial Hypertension Chinese Expert Consensus" writing committee.
Mannitol treatment of intracranial pressure Enhancing the consensus of Chinese experts[J].
Chinese Medical Journal, 2019, 99(023):1763-1766.
[2] National Pharmacopoeia Commission.
The Pharmacopoeia of the People’s Republic of China-Notes on Clinical Use (Volume of Chemical Medicines and Biological Products) (2015 Edition) .
Beijing, China Medical Science and Technology Press, 2017(9): [3] Wang Shu, Yao Xiaoyu, Zhang Yuan, et al.
Meta-analysis of the clinical efficacy of different doses of mannitol on patients with cerebral edema[J].
China Journal of Modern Medicine, 2019 , 021(012):26-31.
[4] Wang Xian, Zeng Liling.
A meta-analysis of the effectiveness and safety of different doses of mannitol in the treatment of acute cerebral hemorrhage[J].
Chinese Journal of Medical Frontiers (Electronic Edition), 2017, 9 (5): 55-61 [5] Wu Yaojiong, Chen Bingliang.
Clinical analysis of acute renal failure caused by mannitol.
Chinese Journal of Critical Care Medicine 1996;8:49_50.
[6] Pu Jingnan, Shi Wei.
Management of cerebral edema after cerebral hemorrhage Expert consensus[J].
Practical Journal of Cardio-Cerebropulmonary Vascular Disease, 2017(08):1-6.
[7] Gao Chao, Huang Jietao, Xie Yanfeng, et al.
Meta-analysis of combined treatment of mannitol and glycerol fructose on cerebral hemorrhage[J].
Chongqing Medicine, 2015, v.
44(32):4541-4543.
[8] Zhao Zhongxin, Shao Fuyuan.
The application and precautions of mannitol in acute cerebrovascular disease[J].
Chinese Journal of New Drugs and Clinics, 1999, 18( 2).