John Alexander and Emily Holland examine an alternative in treating increased intracranial pressure.
Traumatic Brain Injury
In the hospital setting, there are multiple pharmacologic and surgical options for treating increased intracranial pressure (ICP) secondary to traumatic brain injury (TBI). In the prehospital arena, however, the choices are limited. Up until the early 1990s, therapeutic hyperventilation for TBI was commonly used because of studies suggesting it might improve outcomes. However, this treatment fell out of favor due to overwhelming evidence that even mild to moderate hyperventilation was detrimental to the brain as it causes vasoconstriction-induced ischemia.1 Additionally, some agencies hyperoxygenated patients suffering from TBIs with the intention to improve cerebral tissue oxygenation, which resulted in cerebral vasoconstriction resulting in poor patient outcomes.2 Administration of certain anesthetic drugs has also resulted in increased morbidity and mortality in this vulnerable patient population.2 Therapeutic hypothermia has had inconclusive outcomes to improve patient outcomes in the in-hospital setting and would prove very difficult to implement in the EMS setting.2 Consequently, it seemed that all the tools available to EMS providers in the treatment of increased ICP had been removed. The purpose of this article is to examine one possible alternative that has received many opinions, both for and against.1
After a TBI occurs, part of the sequelae can be inflammation or bleeding from the insult to brain tissue and blood vessels. This bleeding may occur within the brain itself or in the meninges that surround it, as in an epidural, subdural or subarachnoid hemorrhage.
Related
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- Evidence-based Guidelines for Adult Traumatic Brain Injury Care
The brain is snugly enclosed within the skull, which is unyielding and provides no room for expansion, so any bleeding and/or inflammation will crowd this limited space and cause a rise in ICP, which then compresses and damages the structures confined to this area, recall the Monro-Kellie Doctrine. As ICP increases, sections of the brain may be forced to shift to different areas within the skull, or into the foramen magnum, thus causing herniation which manifests in myriad symptoms. The higher ICP rises, and the longer the increase is sustained, the degree of permanent disability and likelihood of death increases. Signs of increased ICP include altered mental status, unequal or nonreactive pupils, posturing, or seizures, as well as bradycardia and hypertension (Cushing’s Phenomenon).
Traumatic brain injury can be divided into two categories: primary and secondary. Brain tissue does not regenerate, so any damage from the initial injury is generally permanent. This is primary injury and occurs at the time of impact. Primary injury is not reversible and is caused by direct damage involving the transfer of energy. In addition to these mechanical forces to the brain itself, primary injury also occurs to the cerebral vasculature.
Secondary injury refers to further damage to structures that were originally unharmed by the primary injury but involves a cascade of events that were subsequently set in motion. The consequent edema and bleeding from the primary injury spread to other areas of the brain. One of the goals of TBI management is generally aimed at limiting this secondary injury as much as possible. But what treatments exist outside of the hospital that are safe and effective?
Mannitol vs Hypertonic Saline
Currently, mannitol is the more popular choice for a hyperosmolar agent in patients with elevated ICP. It is an osmotic diuretic used to promote the diuresis of excess fluid from the body and the recommended dose is 1.5 to 2 g/kg as a single dose administered as an intravenous infusion over at least 30 minutes. It is available in 50 ml vials but is also supplied in premixed 250- or 500-ml bags, making it readily deployable in EMS. Mannitol, however, can be difficult to maintain on a vehicle that cannot be temperature controlled at all times because it may crystallize when exposed to low temperatures. At higher concentrations, the tendency to crystallize increases. Mannitol needs to be stored between 68- and 86-degrees F, or 20- to 30-degrees C. Essentially, mannitol needs to be stored at room temperature. Because of this risk of crystallization, an administration set with an in-line filter is used for administration. It should also be noted that the drug can be made soluble again by warming the solution, but again, this can be difficult in the out-of-hospital environment.
In addition to the issue of temperature control, mannitol has various side-effects including initial volume expansion leading to an increased risk of heart failure, subsequent hypovolemia and hypotension, metabolic acidosis, and electrolyte imbalance, including hypernatremia and hypokalemia. Most of these are difficult to monitor outside of a hospital, and all are undesirable when attempting to deliver a viable patient to definitive care. There is another hyperosmolar agent available, known as hypertonic saline.
Hypertonic saline refers to any saline solution that has a concentration of sodium chloride (NaCl) that is higher than what matches the normal electrolytes present in blood plasma (0.9%). Preparations commonly used include 2%, 3%, 5%, 7%, and 23.4% NaCl.
The action of hypertonic saline is that it exerts an osmotic effect. It draws fluid out of edematous cerebral tissues because it has a higher concentration of sodium and a lower concentration of water than blood. When hypertonic saline is administered intravenously, plasma osmolarity increases. The higher sodium concentration causes blood to be hypertonic compared to cerebral tissue, which has a lower sodium concentration. These concentration differences promote the flow of excess water from cerebral tissue to the blood via osmosis. Osmosis occurs because water moves passively along the concentration gradient, it moves from an area of lower concentration to an area of higher concentration. Subsequently, this osmotic effect can be used to treat cerebral edema. By reducing the water content of an injured brain, hypertonic saline can help control ICP, leading to a decrease in secondary brain injury. An obstacle, however, is that there is no consensus as to appropriate indications for use, the best concentration, and the best method of delivery.
Hypertonic saline can be used in one of two ways, as a continuous infusion to maintain elevated sodium levels or as a bolus dose to create an intense osmotic effect. Recent studies indicate that peripheral infusion of hypertonic saline is safe, however hypertonic saline is extremely caustic to peripheral vasculature, and infusions sites should be monitored closely during infusion for signs of infiltration. The major caveat to this statement is the administration of 23.4% hypertonic saline. This medication should only be given via central access, which includes interosseous (IO) access. Some research suggests that hypertonic saline is more effective than mannitol at treating refractory increased intercranial pressure. Despite this, the administration of hypertonic saline is not without risk. Table 1 provides a brief comparison of desired and untoward effects.
Rapid administration of hypertonic saline, which could be performed in the event of an intercranial pressure crisis, carries the risk of stripping away the myelin sheath of the pons. This condition is known as central pontine myelinolysis.3 This condition has the potential to leave patients paralyzed and unable to breathe, speak, or move for themselves and dependent on a ventilator to live. It is important to keep this condition in mind when deciding to use hypertonic saline for intercranial pressure management. To prevent this condition from occurring, 23.4% hypertonic saline should be administered via an IV pump over 20 minutes. Lower concentrations can be administered at higher rates, but providers should always be cautious during administration. This is not a medication that you want to slam.
Summary
Overall, researchers have been unable to determine which agent is most effective in treating elevated ICP in patients with TBI, and all available research has been performed in ICU or ED settings.2, 4 Implementing known strategies to reduce secondary trauma are the current best practice guidelines to improve outcomes in patients with TBI.2 However, due to ongoing research for treatment of TBI patients in the EMS setting it is unknown which method is most effective. EMS providers should be aware that these additional therapies exist, and perhaps be ready to administer them should their medical directors determine that one of these therapies would be appropriate to implement in their department or agency.
References
1. Hypertonic saline and mannitol in patients with traumatic brain injury https://journals.lww.com/mdjournal/fulltext/2020/08280/hypertonic_saline_and_mannitol_in_patients_with.22.aspx
2. Prehospital management strategies and secondary risk factors in traumatic brain injury https://research.vumc.nl/ws/files/353888/dissertation.pdf#page=27
3. Osmotic demyelination syndrome https://medlineplus.gov/ency/article/000775.htm
4. Hypertonic saline or mannitol for treating elevated intracranial pressure in traumatic brain injury: a meta-analysis of randomized controlled trials https://link.springer.com/article/10.1007/s10143-018-0991-8
