Research Paper on Mannitol vs. Hypertonic Saline in Traumatic Brain Injury

Published: 2023-01-28
Research Paper on Mannitol vs. Hypertonic Saline in Traumatic Brain Injury
Type of paper:  Research paper
Categories:  Pharmacology
Pages: 6
Wordcount: 1443 words
13 min read


Traumatic brain injury (TBI) continues to exist as a significant origin of disability and mortality. In the treatment of TBI, recommendable hyperosmolar agents are used. However, no existence on high-level data explains on the use of specific route of administration or particular agent. For that case, two common agents are used Mannitol and hypertonic saline as bolus therapy. According to smaller researches done, they pinpoint that HTS happens to be a superior agent in minimizing the burden of increased intracranial pressure. However, a point to note is that neither agent (Mannitol nor hypertonic saline) has been proven to enhance on the functional outcome or mortality.

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The Use of Mannitol Administration

Mannitol administration has been commonly used in the treatment of traumatic brain injury despite the many controversies associated with the drug. The drug is under the pharmacological classification of osmotic-diuretic, but in decreasing intracranial pressure, its mechanism of action is multi-factorial. Mannitol administration is efficient in reducing the intracranial pressure since the 1960s leading to its widespread utilization in neurosurgery. Mannitol drug does so from its hyperosmotic action resulting in the water extraction from the edematous brain. Despite such mechanism of action, and on the grounds of following specific observations like instances of ICP falling prior any reduction in the white matter water content occurring, a lot of questions pop as a result of Mannitol use. Research by Hartwell points that after administering Mannitol, it causes the white matter water content to increase then a gradual decrease less than it was before the infusion of Mannitol (P< 0.025) (Wani, Ramzan, Nizami, Malik, Kirmani, Bhatt & Singh, 2008).In the United States, approximately 83% of centers with more than 50% of patients with traumatic brain injury are administered with Mannitol as a means to decrease the increased intracranial pressure.

Mannitol is useful in the control of acute increased ICP after TBI is adequately established, thus less evidence in supporting its prophylactic infusion. However, it is the recommendable drug to serve as a "bridge" to defining the proper treatment in case of traumatic brain injury. Mannitol use lowers effects through two means a slightly delayed effect linked to osmotic action and an immediate impact due to plasma expansion. In the combination of the two effects, it causes an increase in compensatory cerebral vasoconstriction and regional cerebral blood flow in the regions of the brain, reducing ICP. Mannitol is an osmotic diuretic commonly used drug in the management of increased intracranial pressure. However, no studies did so far to give guidance on the treatment duration and the optimal dose. In that case, protocols of management vary; thus, the ICP effect of infusing Mannitol is highly dose-dependent with high doses providing a more permanent reduction in intracranial pressure (Arifianto, Ma'ruf & Ibrahim, 2016).

Additionally, Mannitol use as hyperosmolar therapy is frequently infused to reduce intracranial pressure to hinder worse neurologic outcomes linked to traumatic brain injury. However, when comparing its efficacy to hypertonic saline another hyperosmolar agent, Mannitol appears to be 20% highly considered following its history and not superiority in efficiency. Hypertonic saline overweighs Mannitol based on its theoretical advantages as it is more efficient in decreasing intracranial pressure by the length of reduction and degree. Mannitol use, on the contrary damages more the tissue oxygenation of the brain, unlike HTS. It, therefore, calls for the use of HTS as the initial therapy to the management of traumatic brain injury with increased intracranial pressure among patients.

The Use of Hypertonic Saline

On the other hand, is HTS infusion that treats acute TBI similarly as Mannitol. However, for this hyperosmolar agent, it offers a more durable and robust effect on increased intracranial pressure. According to most recent studies, the main focus establishes HTS superiority against Mannitol as its significant advantage. For example, from some possible single-arm researches among patients with varied intracranial pathologies shows that continuous use of hypertonic saline administration achieves hypernatremia that reduces the ICP making it outstanding in its efficacy, unlike Mannitol. Another Study by Harutjunyan et al., notes HTS is more effective in treating traumatic brain injury with increased intracranial pressure. As the hypertonic saline, it possesses increases the systemic blood pressure consequently increasing the cerebral perfusion pressure. The two means of administration, both Mannitol and HTS have the same mechanisms in reducing increased ICP. Since they work by coming up with an osmotic gradient along the blood-brain barrier to cause fluid shifts. However, so far from various studies done, HTS proves as this kind of administration to have a long-lasting effect on increased intracranial pressure unlike Mannitol and lacks a rebound rise in the ICP. According to a possible randomized study by Vialet et al., of two groups with acute TBI receiving either of the two agents, Mannitol and hypertonic saline. The conclusion based on the effectiveness of the infusion was that those that received Mannitol needed more cerebrospinal fluid drainage unlike those getting HTS (Boone, Oren-Grinberg, Robinson, Chen & Kasper, 2015). In the comparison of HTS to other therapies, it has indicated fast and sustainable volume expansion and its efficacy in reducing ICP. Apart from that, HTS reverses transtentorial herniation improving CPP, cerebral blood flow, and oxygenation. As much as also Mannitol results to increasing of the CPP and CBF and reduction ICP, the seen increases seem smaller than in HTS and are not linked to cerebral oxygenation increase.

In comparing HTS vs. Mannitol administration under the basis of isovolumic doses in the treatment of traumatic brain injury, HTS shows considerable reduction in duration and number of ICP spikes unlike with Mannitol. It ultimately makes hypertonic saline use superior following the combined effect it provides to increased intracranial pressure due to traumatic brain injury. Also is the variation in the adverse effects a patient is likely to endure, Mannitol and hypertonic saline administration cause distinct adverse effects. For hypertonic saline use if not appropriately monitored can cause cardiac failure, volume overload, and renal failure in instances that levels of serum sodium elevate. However, for Mannitol use it may result in just renal failure due to renal tubules precipitation, but still, HTS owns several advantages following how effective it is.

Alternatively administering hypertonic saline to patients with a traumatic brain injury does not have diuresis effects like Mannitol. It is another factor that makes it stand out different from other therapies. Also, HTS inhibits inflammatory cascade mechanism that prevents a second brain injury improving the neurotransmitters restoring levels of electrolyte in the brain tissues (Arifianto, Ma'ruf & Ibrahim, 2016). It is achieved if the administration of hypertonic saline is in patients with a chronic condition of hyponatremia and hypernatremia. It is because it may result in demyelination syndrome. Therefore in avoiding the side effect, there is the need to conducting periodic electrolyte evaluation on serum. Hypertonic saline use has less possibility of rebound phenomenon, unlike Mannitol administration. The reason is hypertonic saline compared to Mannitol has a higher coefficient of penetrating the barriers of the brain. From my perceptive, hypertonic saline use, carries many advantages compared to Mannitol as it can also be infused to hypotensive patients with raised intracranial pressure.


Traumatic brain injury with increased intracranial pressure is fatal as it may result in death. It, therefore, calls for patients to undergo effective early treatment, and in this case, patients can be subjected to infusions of hyperosmolar fluids like Mannitol or hypertonic saline to reduce the ICP. However, it is significant to know of the differences in the use of either Mannitol or hypertonic saline administration thus be conversant with which means serves as more effective. Many studies seem to be in favor of HTS against Mannitol. It remains difficult to pinpoint on the superiority of both due to the heterogeneity of the researches conducted. Thus it calls for more shreds of evidence to gain insights between the two fluids of which one is more effective.


Arifianto, M. R., Ma'ruf, A. Z., & Ibrahim, A. (2016). Efficacy comparison of mannitol and hypertonic saline for Traumatic Brain Injury (TBI) treatment. Bali Med J, 5(3), 516-521.

Boone, M. D., Oren-Grinberg, A., Robinson, T. M., Chen, C. C., & Kasper, E. M. (2015). Mannitol or hypertonic saline in the setting of traumatic brain injury: what have we learned?. Surgical neurology international, 6.

Mangat, H. S., Wu, X., Gerber, L. M., Schwarz, J. T., Fakhar, M., Murthy, S. B., ... & Hartl, R. (2019). Hypertonic Saline is Superior to Mannitol for the Combined Effect on Intracranial Pressure and Cerebral Perfusion Pressure Burdens in Patients With Severe Traumatic Brain Injury. Neurosurgery.

Wani, A. A., Ramzan, A. U., Nizami, F., Malik, N. K., Kirmani, A. R., Bhatt, A. R., & Singh, S. (2008). Controversy in use of mannitol in head injury. The Indian Journal of Neurotrauma, 5(1), 11-13.

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Research Paper on Mannitol vs. Hypertonic Saline in Traumatic Brain Injury. (2023, Jan 28). Retrieved from

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