Links To And Excerpts From “Safety and Efficacy of 3% Hypertonic Saline Bolus Via Peripheral Intravenous Catheter for Neurological Emergencies”

Today, I review, link to, and excerpt from Safety and Efficacy of 3% Hypertonic Saline Bolus Via Peripheral Intravenous Catheter for Neurological Emergencies [PubMed Abstract] [Full-Text HTML] [Full-Text PDF Preprint]. Neurocrit Care. 2024 Feb 20. doi: 10.1007/s12028-024-01941-3. Online ahead of print.

All that follows is from the above PDF Preprint.


Background: Elevated intracranial pressure (ICP) is a neurological emergency in patients with acute brain injuries. Such a state requires immediate and effective interventions to prevent potential neurological deterioration. Current clinical guidelines recommend hypertonic saline (HTS) and mannitol as first-line therapeutic agents. Notably, HTS is conventionally administered through central venous catheters (CVCs), which may introduce delays in treatment due to the complexities associated with CVC placement. These delays can critically affect patient outcomes, necessitating the exploration of more rapid therapeutic avenues. This study aimed to investigate the safety and effect on ICP of administering rapid boluses of 3% HTS via peripheral intravenous (PIV) catheters.

Methods: A retrospective cohort study was performed on patients admitted to Sisters of Saint Mary Health Saint Louis University Hospital from March 2019 to September 2022 who received at least one 3% HTS bolus via PIV at a rate of 999 mL/hour for neurological emergencies. Outcomes assessed included complications related to 3% HTS bolus and its effect on ICP.

Results: Of 216 3% HTS boluses administered in 124 patients, complications occurred in 8 administrations (3.7%). Pain at the injection site (4 administrations; 1.9%) and thrombophlebitis (3 administrations; 1.4%) were most common. The median ICP reduced by 6 mm Hg after 3% HTS bolus administration (p < 0.001).

Conclusions: 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-associated complications and expediting life-saving interventions for patients with neurological emergencies, especially in the field and emergency department settings.

Keywords: 3% hypertonic saline; Intracranial pressure; Neurological emergencies; Peripheral intravenous catheter; Safety.


Signs and symptoms of elevated intracranial pressure (ICP) in patients with acute brain injury are considered neurological emergencies that require immediate recognition and treatment to prevent progression to cerebral ischemia, brain herniation and death. Hyperosmolar agents, such as mannitol and
hypertonic saline (HTS) are considered first-line therapies for the treatment of elevated ICP in current guidelines.1–4 .  .  . Mannitol and HTS were compared in several randomized trials of patients with elevated ICP; meta-analyses of these trials
found that HTS may have greater efficacy in managing elevated ICP, potentially improve cerebral perfusion, and avoid the unwanted side effects of mannitol, such as dehydration (from it is potent diuretic effect), rebound intracranial hypertension, and risk of precipitation during administration.7

Although there was no robust evidence to compare the effectiveness of symptom-based bolus and continuous infusion of HTS in elevated ICP, the current guideline favors symptom-based bolus doses of hypertonic saline (HTS) as first-line intervention, along with other drug therapies, medical, and surgicalinterventions for elevated ICP.1 Bolus administration of HTS has become more favored due to its rapid effect and more transient increase in serum sodium.8 .  .  . Traditionally,
central venous catheter (CVC) was the preferred route of administration.  .  .  . However, it is well reported in the literature that CVC use is associated with complications which are both costly and carry their own risk of morbidity and mortality.16 Furthermore, CVC placement is time-consuming and requires trained personnel, which may delay administration of life-saving interventions, compromising
patient care and worsening outcomes.

This has led to an increased interest in 3% HTS administration through a peripheral intravenous (PIV) catheter. Several prospective and retrospective studies investigated the safety profile of 3% HTS administration via PIV catheter and demonstrated that the complications were relatively minimal.
17–21 However, most of the studies enrolled patients with heterogenous indications for 3% HTS and most of
them received it at a slower infusion rate (< 100 mL/hour) with prolonged infusion time (> 6 hours).22 Recently, the safety of 3% HTS bolus via PIV catheter was established in a single-center retrospective study.16 The purpose of this study is to describe the safety and efficacy of rapid bolus (at a rate of 999
mL/hour) of 3% HTS via PIV catheter for neurological emergencies.


Out of the 241 patients screened, 124 patients, who received a total of 216 times of 3% HTS boluses, met the inclusion criteria (Fig. 1). The most common reason for exclusion was administration of 3% HTS via CVC (n = 84), followed by infusion rate < 999 mL/hour (n = 21) and for indications other than elevated ICP (n = 12) (Fig. 1). Baseline patient characteristics are presented in Table 1. The mean age was 56.9 ± 18.7 years, with 62.9% being male and the majority being Caucasian (54.8%). The most common primary
diagnosis on admission were intracerebral hemorrhage (ICH) (37.9%) and acute ischemic stroke (AIS)
(29%), followed by traumatic brain injury (TBI) (27.4%). The median Glascow Coma Scale (GCS) on admission was 7 (4, 14), the median National Institute of Health Stroke Scale (NIHSS) was 17 (11, 26) and the median ICH score was 3 (2, 4). All 3% HTS boluses were administrated at 999 mL/hour in our
study. The median quantity of each bolus was 250 (250, 250) mL. The median frequency of 3% HTS
bolus was 1 (1, 2). Forty-six patients (37.1%) received external ventricular drain (EVD) placement for cerebrospinal fluid (CSF) diversion and ICP monitoring. A total of 27 patients (21.8%) underwent a decompressive surgery appropriate to the primary diagnosis to relieve elevated ICP.


Our study demonstrates that rapid bolus administration at a rate of 999 mL/hour via either 18- or 20- gauge PIV catheter is relatively safe. Out of 216 bolus administrations of 3% HTS peripherally, complications only occurred in 8 administrations (3.7%). No severe complications, such as hypotension,
osmotic demyelination, or ARDS, were identified with rapid bolus of 3% HTS via PIV catheter. Our study also demonstrated the efficacy of peripheral 3% HTS bolus to treat elevated ICP. In our study, the median ICP decreased by 4.6 mmHg (p < 0.001) after 3% HTS bolus was administered; serum sodium, chloride
and serum osmolality rose as anticipated, in accordance with each bolus (p < 0.001).

To date, our study is the largest retrospective analysis to evaluate the safety and efficacy of 3% HTS administered at a rate of 999 mL/hour peripherally, which provides valuable data to support its application in the setting of neurological emergencies. Although there were no studies that directly
compared the safety or efficacy of centrally administered 3% HTS with that which is given peripherally, it is well reported in the literature that CVCs are associated with costly complications which carry morbidity and mortality risks, regardless of the infused solution.16 Our data may assuredly allow institutions to
consider alteration of restrictions on administration of 3% HTS in neurological emergencies when bolus of hypertonic solution is recommended according to most recent practice guideline.
1 While there is also rising interest in peripheral administration of 23.4% HTS for neurological emergencies, it is not free from
serious adverse events, and most institutions still mandate the use of 23.4% HTS via CVC by slow push over 10 to 15 minutes.
5 23 The use of equiosmolar dose of 3% HTS as a bolus for neurological emergencies might be a more viable alternative to 23.4% HTS when it is unavailable or unsafe to administer, but further studies directly comparing the efficacy of equiosmolar doe of 3% HTS to 23.4% HTS are warranted.


This study represents the largest retrospective analysis to date examining the safety and efficacy of peripheral 3% HTS boluses for neurological emergencies. Our findings emphasize the low risks of peripheral 3% HTS boluses at a rate of 999 mL/hour and their effectiveness in lowering ICP and increasing serum osmolality. There were no severe adverse events – hypotension, osmotic demyelination syndrome or AKI – identified after 3% HTS bolus administration. Three percent HTS boluses via PIV
catheter at a rate of 999 mL/hour may be considered a safe rescue in the setting of neurological emergencies. Further studies are warranted to compare the safety and efficacy profiles of 3% HTS to 23.4% HTS administration in neurological emergencies.

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