Continuing Education Activity

Clinicians use hypertonic fluids to increase intravascular fluid volume. Hypertonic saline can be utilized in the treatment of hyponatremia. Hypertonic saline and mannitol are both indicated to reduce intracranial pressure. This activity will highlight the mechanism of action, adverse events, and contraindications of hypertonic fluids in the management of hyponatremia and increased intracranial pressure.

Objectives:

• Describe the mechanisms of action of hypertonic saline and mannitol.
• Review the adverse effects and contraindications of hypertonic saline and mannitol.
• Outline the route of administration and appropriate dosing for hypertonic fluids.
• Explain the importance of improving care coordination among the interprofessional team to improve care for patients with increased intracranial pressure and hypertonic fluids in patient management.

Indications

Hypertonic Saline

Hypertonic saline is a crystalloid intravenous fluid composed of NaCl dissolved in water with a higher sodium concentration than normal blood serum. Both 3% and 5% hypertonic saline (HS) is currently FDA-approved for use in hyponatremia and increased intracranial pressure (ICP). Patients with hyponatremia with severe features should have their serum sodium gradually corrected with boluses of hypertonic saline. Patients should have their serum sodium monitored at regular intervals and can receive multiple boluses a day.[1]

Hypertonic saline should be discontinued once the patient’s symptoms improve or they have an adequate increase in serum sodium. Cerebral edema and elevated intracranial pressure (ICP) are significant causes of morbidity and mortality in patients with intracranial tumors, cerebral hematomas, traumatic brain injuries, cerebral infarcts, and intracranial hemorrhages. Hypertonic saline increases the osmolarity of the blood, which allows fluid from the extravascular space to enter the intravascular space, which leads to decreases in brain edema, improved cerebral blood flow, and decreased CSF production. Research shows that 3% hypertonic saline decreases ICP similarly to 20% mannitol.[2] Both hypertonic fluids have similar effects on hemodynamics. Hypertonic saline leads to increases in serum sodium and has less of a diuretic effect than mannitol, likely due to the increased serum sodium causing ADH release. Hypertonic saline administered after mannitol in traumatic brain injury has also demonstrated improvement of cerebral oxygenation in addition to lowering ICP.[3]

Due to there being no guidelines regarding the administration of hypertonic saline for increased ICP, various studies have used concentrations of 3% to 23.5% NaCl.[4]

Mannitol

Mannitol is a crystalloid intravenous fluid composed of a six-carbon simple sugar dissolved in water. It is FDA-approved for use in decreasing intracranial pressure and brain mass and decreasing intraocular pressure when other interventions have failed to do so. When needed, 15 to 25% mannitol can be given as a bolus to reduce intracranial pressure and intraocular pressure. Mannitol is solely confined to the intravascular space when administered intravenously, unlike hypertonic saline, which can have some movement of electrolytes into the interstitial space.

Mechanism of Action

Hypertonic fluids contain a higher concentration of solute compared to plasma and interstitial fluid; this creates an osmotic gradient and drives fluid from the interstitial space into the intravascular space. This increase in intravascular volume increases mean arterial pressure (MAP), stroke volume (SV), and cardiac output (CO) when compared with equal volumes of normal saline or other isotonic fluids.[5] There is also a significant increase in end-diastolic pressure and a subsequent decrease in pulmonary vascular resistance. Hypertonic saline requires less overall volume administered to achieve similar plasma volumes as larger volumes of normal saline.[6] Hypertonic saline stimulates vasopressin release from the pituitary gland, which decreases water loss through the kidneys.[7] In comparison, when given intravenously, mannitol is only minimally metabolized by the body and is rapidly excreted by the kidney. Less than 10% of mannitol is reabsorbed, increasing the osmolarity of the glomerular filtrate and inducing diuresis.

Administration

Hypertonic fluids are administered parenterally via intravenous infusion. Infusion volumes and rates depend on clinical indication.

Hypertonic Saline

In patients with severe hyponatremia, serum sodium should undergo correction by 4 to 6 mEq/L per day, which can be achieved with 100 mL boluses of 3% HS at 10-minute intervals up to three total boluses. Some authorities recommend up to  8 mEq/L per day.[8] Less severe hyponatremia can achieve control with enough hypertonic saline to manage symptoms.[9] Due to the insufficient number of patients over age 65 in various trials, hypertonic fluids should start at the lowest ends of the dosing scale in the geriatric population. Pediatric traumatic brain injury generally receives treatment with a 6.5 to 10 mL/kg bolus of hypertonic saline.[10] Administration via a peripheral intravenous catheter is acceptable if no other access is available, but central venous access is the preferred route. 

Mannitol

Mannitol boluses should be given as 0.25 to 2 g/kg body weight of 15 to 25% mannitol over 30 minutes to 1 hour for the treatment of increased intracranial or intraocular pressures. Pediatric patients should receive a similar 1 to 2g/kg body weight bolus over the same timeframe. Peripheral intravenous catheters are acceptable routes of administration.

Adverse Effects

Hypertonic Saline

There are few adverse effects associated with hypertonic saline, though most are associated with longer infusion periods, as opposed to boluses. One possible side effect is hyperchloremic metabolic acidosis due to the addition of NaCl. Patients may also develop hypernatremia with long-term administration for the same reasons. One other known effect is osmotic demyelination syndrome, when severe hyponatremia is corrected too rapidly. Hypertonic saline is also pregnancy category C and is only used if necessary. The most common adverse effects are related to the route of administration and include infection at the IV site, thrombophlebitis, extravasation, and hypervolemia.

Mannitol

Common adverse reactions after mannitol administration are pulmonary congestion, electrolyte abnormalities, acidosis, marked diuresis, dehydration, headache, and injection site reactions, among others. There have been no animal reproduction studies performed with mannitol, so it is unknown whether it would harm a human fetus. Mannitol should only be used in pregnant women if necessary.

Contraindications

Hypertonic Saline

There are no known specific contraindications for hypertonic saline, according to the FDA. However, caution is necessary with hypertonic saline in patients with congestive heart failure or renal insufficiency due to their already increased fluid and sodium loads.

Mannitol

Mannitol has several contraindications, including:

• Established anuria due to severe renal disease
• Pulmonary congestion and frank pulmonary edema
• Active internal bleeding
• Severe dehydration
• Hypersensitivity to mannitol

Monitoring

Fluid and electrolytes require monitoring with the administration of all hypertonic fluids, with particular attention paid to serum sodium, potassium, and fluid ins/outs. Evaluation of circulatory and renal function is necessary before administering mannitol and evaluated during treatment. When treating increased ICP with mannitol, a CSF pressure measurement should take place within fifteen minutes after administration.

Enhancing Healthcare Team Outcomes

An interprofessional team approach, comprised of clinicians, nurses, and pharmacists, is most appropriate when administering hypertonic fluids — extra care is necessary to monitor circulatory and renal function as well as serum electrolyte concentrations. Fluid ins and outs must be carefully monitored by nursing staff, particularly with mannitol, reporting abnormalities right away. Hypertonic fluids should be stopped if significant abnormalities in electrolytes or fluid volumes develop. It is noteworthy that there is a lack of research regarding hypertonic fluids. More work remains to determine the value of hypertonic fluids not only in the management of critically ill patients but in the pre-hospital setting for cases of hypovolemia and shock.

In summary, administration of hypertonic saline and/or mannitol requires an interprofessional team approach, including clinicians (MDs, DOs, NPs, PAs), specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. [Level 5]