(March 22, 2023)

Hypertonic saline solutions (HTS) are electrolyte concentrates of NaCl (over 0.9%) and  considered to be high alert medications (4) that are cautiously used to treat symptomatic hyponatremia (14) and acute intracranial hypertension (IH) secondary to multiple causes, but mainly to traumatic brain injury (3, 5, 10, 12). 

• Recent reviews comparing mannitol versus HTS tend to favor the latter with a weak level of evidence (1, 2, 5, 11, 12). 

• Other causes of cerebral edema that leads to acute IH when HTS usage can be considered includes subarachnoid hemorrhage, hemorrhagic and ischemic stroke and hepatic encephalopathy (5, 6). 

• Ideally HTS should be administered through a central venous access, but in emergency situations, peripheral infusions have been determined to be a safe short-term alternative (7, 8), but a close monitoring of the clinical response and sodium levels is warranted to guide subsequent doses.  

Adult dose for acute intracranial hypertension caused by TBI

NaCl 3%, 2 ml/kg IV in 15 minutes bolus

Adult dose for acute intracranial hypertension caused by TBI

Considerations*

• NaCl 3%, 2 ml/kg IV in 15 minutes bolus

• NaCl 10%, 0,5-1 ml/kg IV in 15 minutes bolus

• NaCl 23.4%, 30ml IV in 15 minutes bolus 

*Considerations

• Treatment of acute intracranial hypertension consists of a multimodal strategy that includes interventions and management of positioning, ventilation, blood pressure, seizures prevention and control, neuroprotective airway approach, hyperosmolar therapy, decompression craniotomy among other neuroinvasive techniques, etc. Hyperosmolar therapy in most cases consists of a bridge therapy prior to the most definite neurosurgical approach. 

• Currently there is no consensus on the optimal concentration or specific dose of each concentration (12), and manufacturers don't specify a dose either (9). To date, available evidence guides us towards bolus administration of 3% NaCl solution with effective doses ranging 1,4-2.5 ml/kg, considering that 3% HTS is the most frequently studied (10).

• Emergency Neurological Life Support for Severe Traumatic Brain Injury by Garvin R et al recommends 30ml of NaCl 23,4% (3).

• Maximum lowering ICP effect usually at 15 minutes, lasting 4 to 12 hours.

Adult dose for symptomatic severe hyponatremia (13, 14)

“Symptomatic” means presenting seizures or coma, having reasonably ruled out other causes. 

“Severe” hyponatremia: Na <125mEq/L.

• NaCl 3% 100-150ml IV over 10-20 minutes. Repeat up to 3 times until symptoms resolve or desired serum sodium level is achieved.

• Raising serum sodium by 5 mEq/L is typically enough to see an improvement in severe neurological symptoms. 

• Measure sodium after each NaCl 3%  hypertonic saline bolus.

If no aggressive management is preferred, correction velocity should be established according to sodium concentration, age, weight, gender, and the specific chosen solution. Recommended calculator: 

• MDCalc® - Sodium Correction Rate in Hyponatremia and Hypernatremia

• HTS does not cause volume depletion nor hypovolemia, which makes this agent safer in the trauma patient with hemorrhagic injuries and hypotension (1).

• HTS has a reflection coefficient of 1.0 (compared with 0.9 for mannitol), making it less likely to leak into the brain tissue (1).

• HTS may have favourable neurochemical effects in reducing the accumulation of extracellular excitatory amino acid (glutamate), thus preventing glutamine toxicity and neuronal damage (1).

Osmotic Demyelination Syndrome (ODS)

• ODS is a rare but potentially catastrophic consequence of rapid correction of hyponatremia of >12 mEq/L/24 hours (13, 14), but rarely occurs after correction by 10 mEq/L/24h or less (14). Water moves from cells to extracellular fluid yielding intracellular dehydration and damage (13). 

• Risk factors (14):

  • Chronic hyponatremia <110 mEq/L

  • Alcoholism

  • Cirrhosis

  • Hypokalemia

  • Malnutrition

• ODS usually affects the pons but can extend to extrapontine structures, occurring between 1 to 7 days after rapid sodium correction (14). 

• Symptoms include a wide range of neurological dysfunction such as dysarthria, dysphagia, lethargy, paraparesis or quadriparesis, seizures and coma (13).

Other significant adverse effects: hypernatremia, hyperchloremia. hyperchloremic metabolic acidosis. (9).

Minor adverse effects: infusion site reactions (9).

Acute Intracranial Hypertension

1. Boone MD, Oren-Grinberg A, Robinson TM, Chen CC, Kasper EM. Mannitol or hypertonic saline in the setting of traumatic brain injury: What have we learned?. Surg Neurol Int. 2015;6:177. Published 2015 Nov 23. doi:10.4103/2152-7806.170248
   Surgical Neurology International (Open Access)

2. Burgess S, Abu-Laban RB, Slavik RS, Vu EN, Zed PJ. A Systematic Review of Randomized Controlled Trials Comparing Hypertonic Sodium Solutions and Mannitol for Traumatic Brain Injury: Implications for Emergency Department Management. Ann Pharmacother. 2016;50(4):291-300. doi:10.1177/1060028016628893
   Pubmed

3. Garvin R, Mangat HS. Emergency Neurological Life Support: Severe Traumatic Brain Injury. Neurocrit Care. 2017;27(Suppl 1):159-169. doi:10.1007/s12028-017-0461-0
   Pubmed

4. Institute for Safe Medication Practices (ISMP). ISMP List of High-Alert Medications in Acute Care Settings. ISMP; 2018. Accessed 13 Dec 2022.
   ISMP

5. Cook AM, Morgan Jones G, Hawryluk GWJ, et al. Guidelines for the Acute Treatment of Cerebral Edema in Neurocritical Care Patients. Neurocrit Care. 2020;32(3):647-666. doi:10.1007/s12028-020-00959-7
   Springer (Open Access)

6. Su Y, Liu Y, Chen Z, Cui L. Comparison of equiosmolar doses of 10% hypertonic saline and 20% mannitol for controlling intracranial hypertension in patients with large hemispheric infarction. Clin Neurol Neurosurg. 2021;200:106359. doi:10.1016/j.clineuro.2020.106359
   Pubmed

7. Alenazi AO, Alhalimi ZM, Almatar MH, Alhajji TA. Safety of Peripheral Administration of 3% Hypertonic Saline in Critically Ill Patients: A Literature Review. Crit Care Nurse. 2021;41(1):25-30. doi:10.4037/ccn2021400
   Pubmed

8. Faiver L, Hensler D, Rush SC, Kashlan O, Williamson CA, Rajajee V. Safety and Efficacy of 23.4% Sodium Chloride Administered via Peripheral Venous Access for the Treatment of Cerebral Herniation and Intracranial Pressure Elevation. Neurocrit Care. 2021;35(3):845-852. doi:10.1007/s12028-021-01248-7
   Pubmed

9. NIH-NLM (National Institutes of Health - National Library of Medicine). DailyMed. Label: 3% sodium chloride injection, solution. Updated January 2021.
   DailyMed

10. Susanto M, Riantri I. Optimal Dose and Concentration of Hypertonic Saline in Traumatic Brain Injury: A Systematic Review. Medeni Med J. 2022;37(2):203-211. doi:10.4274/MMJ.galenos.2022.75725
    Pubmed (Open Access)

11. Han C, Yang F, Guo S, Zhang J. Hypertonic Saline Compared to Mannitol for the Management of Elevated Intracranial Pressure in Traumatic Brain Injury: A Meta-Analysis. Front Surg. 2022;8:765784. Published 2022 Jan 7. doi:10.3389/fsurg.2021.765784
    Pubmed

12. Salasky VR, Chang WW. Neurotrauma Update. Emergency Medicine Clinics of North America. 2023 Feb;41(1):19-33. DOI: 10.1016/j.emc.2022.09.014. PMID: 36424041.
    Elsevier -  Science Direct

Symptomatic Hyponatremia

13. Tintinalli JE, Ma O, Yealy DM, Meckler GD, Stapczynski J, Cline DM, Thomas SH. Tintinalli J.E.). Tintinalli's Emergency Medicine: A Comprehensive Study Guide. 9th edition. McGraw Hill; 2019.
    McGraw-Hill

14. Adrogué HJ, Tucker BM, Madias NE. Diagnosis and Management of Hyponatremia: A Review. JAMA. 2022;328(3):280-291. doi:10.1001/jama.2022.11176
    JAMA (Open Access)