Let’s Get Salty: Hypertonic 3% Saline Through Peripheral IVs in Adult Patients with Traumatic Brain Injury

Background: Elevated intracranial pressure in patients with acute brain injury is a neurologic emergency requiring early recognition and early aggressive treatment to prevent progression to cerebral ischemia, brain herniation, and ultimately death.  There are two primary options for treatment in terms of hyperosmolar agents: mannitol and hypertonic saline (HTS). Both agents have pros and cons, but both are effective in rapidly reducing brain volume and ICP.

Bolus administration of HTS has become favored due to its rapid effect and more transient increase in serum sodium levels compared to mannitol.  Traditionally a central venous catheter has been the preferred route of administration of 3% HTS due to its high osmolarity (1026mOsm/L).  CVC placement is not a benign procedure and time to placement can delay administration of life-saving medications.

Paper: Khasiyev, Farid et al. Safety and Effect on Intracranial Pressure of 3% Hypertonic Saline Bolus Via Peripheral Intravenous Catheter for Neurologic Emergencies. Neurocrit Care. Feb 2024. PMID: 38379103

Clinical Question: What is the safety and effect on ICP of administering rapid boluses of hypertonic 3% saline via peripheral intravenous catheters in patients with neurological emergencies?

What They Did:

  • Retrospective, single-center, descriptive cohort study
  • Patients admitted to Saint Mary Health Saint Louis University Hospital between March 2019 to Sept 2022
  • Adult patients receiving at least one 3% HTS bolus via a 18 or 20g PIV at a rate of 999mL/hr for neurological emergencies


  • Complications related to 3% HTS bolus
  • 3% HTS bolus effect on ICP


  • Admitted between March 2019 to Sept 2022
  • Age ≥18 years
  • Received at least one 3% HTS bolus via a PIV catheter at a rate of 999mL/hr for neurological emergencies



  • Presence of a CVC during the period of 3% HTS administration
  • Continuous infusion of 3% HTS at a rate other than 999mL/hr
  • Administration of 3% HTS for indications other than neurological emergencies


  • 216 3% HTS peripheral boluses administered in 124 patients
    • ICH: 37.9%
    • AIS: 29.0%
    • TBI: 27.4%
    • EVD: 37.1%
    • Decompressive Surgery: 21.8%
    • Median quantity fo each bolus was 250mL
    • 9% of patients also received mannitol in addition to 3% HTS
  • Complications
    • 8 administrations (3.7%)
      • Pain at the injection site (4 administrations – 1.9%)
      • Thrombophlebitis (3 administrations – 1.4%)
      • Vein thrombosis (2 administrations – 0.9%)
      • Extravasation (1 administration – 0.5%)
    • Median ICP reduction: 6mmHg
      • Median ICP Before 3% HTS: 18.4mmHg
      • Median ICP After 3% HTS: 13.8mmHg
    • Median ICP reduction in Patients Not Receiving Mannitol
      • Median ICP Before 3% HTS: 17.5mmHg
      • Median ICP After 3% HTS: 11.5mmHg
    • No severe complications (Hypotension)


  • Asks a clinically important question
  • Complication rate of this study aligns with the complication risk reported in the existing literature
  • Study evaluated safety and effect of 3% HTS via peripheral IV in neurologic emergencies


  • Single-center, retrospective, noncomparative study which could limit generalizability to other institutions
  • Study relied heavily on documentation of adverse events in EMR (complications may have been underreported)
  • No comparison arm (i.e. could 3% HTS via a CVC lower ICP faster or more effectively?)
  • Other medications were given through IVs that 3% HTS was given which could confound the complication analysis
  • Lacked ICP data for every single patient and therefore many patients were excluded for this outcome
  • No discussion of chart review methodology (No review of best practices for data extraction including abstractor training, standardized forms for abstraction, blinding to hypothesis of abstractors, or inter-rater reliability)
  • Too small a study to comment on safety as events will be uncommon and without comparison (i.e. safe compared to what?)


  • Most of the literature reporting patients receiving 3% HTS via PIV catheters are typically at lower infusion rates (<100mL/hr) with prolonged infusion time (>6hr) and infusion related complication rates ranging from 2.9% to 10.7% [2]
    • Daley M et al [3]:
    • Single center, retrospective, cohort study that compared the efficacy and safety of 3% HTS bolus vs continuous infusion to achieve goal sodium amongst patients with TBI
    • 90 patients were included
    • Patients receiving bolus 3% HTS achieved goal sodium quicker than patients who received continuous infusion (2.55hrs vs 14.67hrs)
    • Patients in the bolus 3% HTS received less volume of 3% HTS at 72hrs compared to continuous infusion (750mL vs 2493mL)
    • Percentage of sodium levels at goal at 72hours was not statistically significant but there was a numeric trend favoring bolus 3% HTS (83.3% vs 56%)
    • Additionally, there was no difference in mortality at 72 hours (20% vs 24.4%)

Author Conclusion: “Rapid bolus administration of 3% HTS via PIV catheters presents itself as a relatively safe approach to treat neurological emergencies.  Its implementation could provide an invaluable alternative to the traditional CVC-based administration, potentially minimizing CVC-associate complications and expediting life-saving interventions for patients with neurological emergencies, especially in the field and emergency department settings.”

Clinical Take Home Point: 3% HTS boluses via peripheral IVs has a low risk of complications and successfully lowers ICP in patients with neurologic emergencies. 


  1. Khasiyev, Farid et al. Safety and Effect on Intracranial Pressure of 3% Hypertonic Saline Bolus Via Peripheral Intravenous Catheter for Neurologic Emergencies. Neurocrit Care. Feb 2024. PMID: 38379103
  2. Madieh J et al. The Safety of Intravenous Peripheral Administration of 3% Hypertonic Saline and Mannitol in the Emergency Department. J Emerg Med 2019. PMID: 30745195
  3. Daley M et al. Getting Salty: Infusion vs Bolus Dosing of Hypertonic Saline in Patients With Traumatic Brain Injury. Crit Care Med Jan 2024. [Link is HERE]

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter/X: @EMSwami)

Cite this article as: Salim Rezaie, "Let’s Get Salty: Hypertonic 3% Saline Through Peripheral IVs in Adult Patients with Traumatic Brain Injury", REBEL EM blog, March 14, 2024. Available at: https://rebelem.com/lets-get-salty-hypertonic-3-saline-through-peripheral-ivs-in-adult-patients-with-traumatic-brain-injury/.

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