Hypertonic Fluids


Article Author:
Alexi Mason
Ahmad Malik


Article Editor:
Jacob Ginglen


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Russell McAllister
Jason Widrich
Daniel Sizemore


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Carrie Smith
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Patrick Le
Sobhan Daneshfar
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Saad Nazir
William Gossman
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Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
7/1/2019 10:20:06 AM

Indications

Hypertonic Saline: Hypertonic saline is a crystalloid intravenous fluid composed of NaCl dissolved in water with a higher concentration of sodium compared to 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 been shown to improve 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]. While not FDA-approved, small doses of hypertonic saline are thought to be effective in hypovolemia and shock due to the movement of fluid from the intracellular to intravascular spaces, increasing intravascular fluid volume and improving capillary blood flow.[5]

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 - 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.[6] 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.[7] Hypertonic saline stimulates vasopressin release from the pituitary gland, which decreases water loss through the kidneys.[8] Comparatively, 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. 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 2g/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 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 is most appropriate when administering hypertonic fluids. Extra care needs to be taken to monitor circulatory and renal function as well as serum electrolyte concentrations. Fluid ins and outs need to 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 needs to be done 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 physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. [Level V]


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Hypertonic Fluids - Questions

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A 28-year-old patient is admitted to the ICU following a traumatic brain injury. He was treated in the emergency room with an intravenous drug to prevent the rise in intracranial pressure and cerebral edema. A nurse reports that after the administration of the drug, he is putting out a large amount of urine through his foley catheter. What location of the nephron will this drug effect?



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A 48-year-old woman is undergoing a craniotomy. She was administered a dose of 20% mannitol to decide brain volume during surgery. What is the most likely adverse effect of mannitol?



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A 66-year-old male patient presents to the emergency room following a motor vehicle accident. His medical history is significant for type 2 diabetes and chronic kidney disease. The patient has been unconscious since the arrival and has a GCS of 5. There is a 6 cm laceration across the patient's forehead. What is the most appropriate treatment to prevent increased intracranial pressure?



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A 63-year-old male with a 50 pack-year smoking history is brought to the emergency department by his wife. She says that her husband has been vomiting all day, and has recently started to drift in and out of consciousness. While in the hospital, the patient begins seizing. His serum sodium level is found to be 118 mEq/L. What is the ideal rate of sodium correction for this patient?



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A 12-year-old female with a history of type 1 diabetes mellitus is admitted to the pediatric intensive care unit after being diagnosed with diabetic ketoacidosis in the emergency department. She is currently receiving intravenous 0.9% saline and insulin. She received a head CT due to difficulty arousing which showed a narrowing of the lateral ventricles. What is the most appropriate treatment for the CT findings?



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A 22-year-old male soldier suffers below the knee limb loss and significant blood loss when an explosive went off near him. The patient received a tourniquet in the field as well as multiple doses of 7.5% hypertonic saline. He is airlifted to a military hospital and taken to emergent surgery. Laboratory studies following surgery reveal serum sodium of 153 mEq/L, serum chloride of 124 mEq/L, bicarbonate of 20 mEq/L, a pH of 7.1, and no anion gap. What is the most likely cause of these findings?



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Hypertonic Fluids - References

References

Williams DM,Gallagher M,Handley J,Stephens JW, The clinical management of hyponatraemia. Postgraduate medical journal. 2016 Jul;     [PubMed]
Sokhal N,Rath GP,Chaturvedi A,Singh M,Dash HH, Comparison of 20% mannitol and 3% hypertonic saline on intracranial pressure and systemic hemodynamics. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2017 Aug;     [PubMed]
Witherspoon B,Ashby NE, The Use of Mannitol and Hypertonic Saline Therapies in Patients with Elevated Intracranial Pressure: A Review of the Evidence. The Nursing clinics of North America. 2017 Jun;     [PubMed]
Oddo M,Levine JM,Frangos S,Carrera E,Maloney-Wilensky E,Pascual JL,Kofke WA,Mayer SA,LeRoux PD, Effect of mannitol and hypertonic saline on cerebral oxygenation in patients with severe traumatic brain injury and refractory intracranial hypertension. Journal of neurology, neurosurgery, and psychiatry. 2009 Aug;     [PubMed]
Pfortmueller CA,Schefold JC, Hypertonic saline in critical illness - A systematic review. Journal of critical care. 2017 Dec;     [PubMed]
Joseph B,Aziz H,Snell M,Pandit V,Hays D,Kulvatunyou N,Tang A,O'Keeffe T,Wynne J,Friese RS,Rhee P, The physiological effects of hyperosmolar resuscitation: 5% vs 3% hypertonic saline. American journal of surgery. 2014 Nov;     [PubMed]
Sterns RH, Disorders of plasma sodium--causes, consequences, and correction. The New England journal of medicine. 2015 Jan 1;     [PubMed]
Niknam K,Mistry R,Lumba-Brown A, Pediatric hypertonic saline use in emergency departments. The American journal of emergency medicine. 2019 May;     [PubMed]
Honore PM,Barreto Gutierrez L,Spapen HD, Renal protection in sepsis: Is hypertonic sodium (lactate) the solution? Annals of intensive care. 2019 Feb 8;     [PubMed]
Orbegozo D,Vincent JL,Creteur J,Su F, Hypertonic Saline in Human Sepsis: A Systematic Review of Randomized Controlled Trials. Anesthesia and analgesia. 2019 Feb 27;     [PubMed]

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