Episode 4- Guidelines on the acute treatment of cerebral edema

Episode Summary:

In this episode, we discuss hypertonic saline solutions and mannitol for the treatment of cerebral edema in a variety of clinical settings.

Show Notes:

Key Points:

Guidelines on the acute treatment of cerebral edema:
– Hypertonic saline solutions (HTS) are recommended in the settings of subarachnoid and intracerebral hemorrhage due to the potential risk of hematoma expansion when using mannitol
– HTS are recommended over mannitol in the setting of traumatic brain injury and ischemic stroke, with mannitol being a reasonable alternative in patients who are hypernatremic or fluid overloaded
– When using HTS, avoid Na levels > 155-160 mEq/L and Cl levels of 110-115 mEq/L
– When using mannitol, use osmolar gap ( >20 mOsm/kg) as a cut-off for the risk of developing acute kidney injury
Er-Rx Episode 4


Cook, AM, et al. Guidelines for the acute treatment of cerebral edema in neurocritical care patients. Neurocrit care. 2020. https://doi.org/10.1007/s12028-020-00959-7

Mesghali E, et al. Safety of peripheral line administration of 3% hypertonic saline and mannitol in the emergency department. J Emerg Med. 2019; 4: 431-436

Perez, CA, et al. Complication rates of 3% hypertonic saline infusion through peripheral intravenous access. J Neurosci Nurs. 2017; 49(3): 191-195

Mannitol [prescribing information]. Lake Forest, IL: Hospira; 2019


Hello everyone, and welcome back to ER-Rx. In today’s episode, we are going to discuss the recently-published guidelines on the acute treatment of cerebral edema. In this sense, the term “cerebral edema” represents all of; an elevated ICP (intracranial pressure), brain swelling, herniation syndromes, as well as cerebral edema itself. The guidelines do state that there are multiple treatment options for cerebral edema, including hyperosmolar therapies, acute hyperventilation, temperature modulation, CSF (cerebrospinal fluid) diversion, surgical decompression, as well as metabolic suppression. The guidelines and this podcast episode will only focus on the hyperosmolar therapy treatment or the drug therapy of cerebral edema.  

Although multiple guidelines, including those for the treatment of acute ischemic stroke, intracerebral hemorrhage, and traumatic brain injury all discuss the treatment of cerebral edema, they don’t discuss which agent we should use or how to monitor those agents. The authors set out to answer those questions by doing a systematic review of the literature. Now, let’s start with the first scenario of subarachnoid hemorrhage. The authors “suggest,” meaning that there was a low quality of evidence for this recommendation, symptom-based bolus dosing of hypertonic saline solutions over sodium target-based dosing, mostly due to the lack of data on the sodium target-based dosing regimens. The authors, including I’m sure a lot of my listeners, are still under the understanding that some centers are still driving sodiums for example, to a level of 145 to 155 and we will touch more on this later. I did find it interesting that mannitol was not discussed at all in the scenario, and I also found it interesting that hypertonic saline was not shown to improve any neurological outcomes in this scenario. This is something that will come up again and again as we go through these guidelines.  

Next up, in the setting of traumatic brain injury, the authors suggest using hypertonic sodium solutions over mannitol for the initial treatment of elevated ICP or cerebral edema in this scenario. Hypertonic saline was recommended above mannitol, mainly due to the perceived advantages of hypertonic saline solutions. This being a quicker onset, a greater level of ICP reduction, and the fact that hypertonic saline solutions have been shown to work in patients who have failed mannitol. However, the authors stress that although they recommended hypertonic sodium solutions above mannitol, that mannitol can still be used in the scenario and can work well. Mannitol can be used as an alternative to hypertonic saline, specifically for patients who are fluid overloaded or have hypernatremia. And once again, rather disappointingly, neither agent has been shown to improve neurological outcomes.  

In the third scenario, specifically acute ischemic stroke, the authors suggest either hypertonic saline solutions or mannitol. Also, just as in traumatic brain injury, the authors suggest hypertonic saline solutions for those patients who have failed mannitol. Once again, neither agent has been shown to improve neurological outcomes. As a side note, the author stressed the importance of not recommending prophylactic mannitol nor a continuous infusion of hypertonic saline solutions to try to target sodium levels.  

The fourth scenario that we are going to go over in this podcast is cerebral edema in the setting of intracerebral hemorrhage. Now this one was actually kind of interesting. First of all, the authors suggest hypertonic saline solutions above mannitol, citing risks of hematoma expansion in patients who were given mannitol. Also interesting is the fact that the authors state that we can use either symptom-based bolus dosing of hypertonic saline solutions, or we can use hypertonic saline solutions as a continuous infusion targeting specific sodium levels. The studies that they cited mostly targeted levels of 145 to 155.

These guidelines also discussed hyperosmolar therapy in the settings of bacterial meningitis, tuberculosis meningitis,  hepatic encephalopathy. They also discussed some non-pharmacological treatment options of cerebral edema, none of which we are going to cover in this episode due to the lack of time. But, I highly recommend that you read these guidelines for yourselves. These guidelines also discussed some safety and infusion considerations. In the setting of hypertonic saline solutions, they suggest the avoidance of severe hypernatremia or severe hyperchloremia due to the risks of the patient developing an acute kidney injury. The sodium upper range of 155 to 160, and the chloride upper limit range of 110 to 115 is recommended. The authors also state that they cannot recommend specific dosing strategies of hypertonic saline solutions to improve neurological outcomes across a wide variety of neurocritical care patients. The authors admit that although it is a common practice to give hypertonic saline solutions as continuous infusions, this practice has not been well studied, and there is even less data on what that specific target of sodium should be. When they discussed the safety and infusion considerations for mannitol, the authors suggested using an osmolar gap over osmolarity thresholds to monitor for the risk of acute kidney injury. Although the authors do not recommend a particular cut off (of osmolar gap), they state that 20 mOsm/ kg has been used in clinical practice.  

My personal conclusion and the way that I read these guidelines is that hypertonic saline seems to have the slight edge over mannitol. For example, in the setting of traumatic brain injury, the slight edge goes to hypertonic saline. In the setting of intracerebral hemorrhage, not only do the authors recommend hypertonic saline solutions over mannitol, they also express fears of hematoma expansion if using mannitol in this situation. In the setting of subarachnoid hemorrhage, mannitol use was not discussed at all. I also want to point out that per mannitol’s package insert, mannitol is contraindicated in the setting of acute intracranial bleeding, except during craniotomy. Hypertonic saline seems to have a quicker and more robust and sustained response than mannitol does. A couple of times the authors mentioned that hypertonic saline solutions can be used in those patients who have failed mannitol, but they do not say that the reverse is true. Another reason why I like hypertonic saline solutions over mannitol is that we don’t have to worry about hypertonic saline solutions crystallizing, and we also don’t have to add a filter to the tubing when giving hypertonic saline. I know some of you are wondering whether or not it’s safe to give hypertonic saline peripherally; the answer is “yes.” We have personal experience with doing this, and there are actually a couple of studies that have also shown this to be a safe and effective method of administering hypertonic saline. I will post those studies up into the show notes on our website.  

Thank you so much for your time. Please remember to check out our website at errxpodcast.com and please leave us a comment. Anybody who leaves us a comment will be entered into a periodic drawing to win some prizes!

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