Is there evidence to support administering 3% sodium chloride through a peripheral line and if there is evidence to support this, is there a maximum rate at which to administer?

Comment by InpharmD Researcher

While the conventional practice is to administer 3% hypertonic saline through central lines, more institutions are allowing peripheral venous administration in patients without central access or who need emergent therapy. While the incidence of adverse events seen with peripheral administration appears to be low and more greatly associated with administration at higher doses and for extended durations, infusion rates of up to 100 mL/hr have been utilized in studies and newly implemented hospital protocols with minimal adverse effects. For this reason, clinicians suggest that the risks of peripheral IV administration of 3% saline may be overstated, and recommend peripheral administration especially in time-sensitive situations. No specific maximum rate of infusion has been specified in the literature.

A 2021 literature review assessed the safety of continuous intravenous (IV) infusion of 3% hypertonic saline via a peripheral IV catheter in critically ill adult patients. A total of seven studies (3 retrospective studies, 2 prospective studies, 1 case report, and 1 case series) were included in the review with the primary outcomes of interest being the most frequently reported infusion-related adverse events (phlebitis, extravasation, and venous thrombus) and electrolyte disturbances (hypokalemia, hyperchloremia, hypernatremia, and hypobicarbonatemia) related to 3% hypertonic saline peripheral administration. Reviewed studies included patients receiving 3% hypertonic saline at varying infusion rates up to 100 mL/hr and durations ≥ 6 hours. Infusion-related adverse events and electrolyte abnormalities were higher in patients who received 3% hypertonic saline at higher infusion rates (83.3 mL/h) and for longer durations (≥ 6 hours) and included phlebitis, erythema, edema, hyperchloremia, and hypokalemia; therefore, the authors suggest infusion rate and duration of infusion may have an effect on the development of infusion-related adverse events. Of note, the difference in infusion-related adverse event occurrence between patients receiving 3% hypertonic saline at a rate of > 30 mL/hr and ≤ 30 mL/hr, in one included prospective study was not statistically significant. Overall, due to low rates of infusion-related adverse events and electrolyte abnormalities, it was suggested that 3% hypertonic saline is safe and effective when administered peripherally in critically ill patients. [1]

A 2021 study evaluated the incidence of local infusion reactions after peripheral administration of 3% normal saline at a network health system over a 10-year period. A search was conducted through UPMC’s Risk Master database from May 2010 to May 2020 to identify infiltrations or extravasation related to hypertonic saline administration. A total of 23,714 non-chemotherapeutic and non-contrast intravenous (IV) extravasation events were identified with 19% being pediatric related. Intravenous extravasation events included infiltration, site issues, and phlebitis. No infiltration or extravasation reports related to 3% normal saline administration were found. Based on these findings, the authors recommend against delaying life-saving therapy to place a central venous catheter and suggest administering 3% normal saline peripherally if necessary. Of note, the authors were unable to distinguish between peripherally or centrally administered 3% normal saline during the search. [2]

A 2021 study discussed the development and implementation of a hospital protocol for peripheral administration of 3% sodium chloride. The protocol specifications were to insert the peripheral intravenous catheter (PIV) in an upper extremity from the antecubital fossa to the wrist with a catheter ranging from 18 to 22 gauge. If existing PIV sites were utilized, they need to be less than 24 hours old, flush easily, have blood return, and not be a field start. Nurses were required to monitor the PIV site every two hours during administration. The protocol-specified maximum rate of infusion of 3% sodium chloride was 100 mL/hr (bolus maximum: 100 mL for hyponatremia and 250 mL for acute intracranial hypertension), with the total duration of infusion not to exceed 48 hours even if multiple PIV sites were used. The protocol was implemented for a 6-month pilot period during which there were 40 cases of peripherally administered 3% sodium chloride and no adverse events reported. Following the pilot period, data collection and adverse events reporting continued for 19 months after protocol implementation. [3]

A total of 103 patients received 3% sodium chloride through a PIV site and three adverse events were reported; two associated with continuous infusions and one with a bolus infusion. Two events were grade 1 infiltrations based on the Infusion Nurses Society Infiltration and Phlebitis Scale (skin blanching, cold skin, and edema one to six inches in all directions). One was a grade 2 infiltration (cold skin, blanching skin, edema one to six inches in all directions accompanied by grade 1 phlebitis [erythema with pain around the intravenous site]). All events required no further intervention after switching to a new PIV site. In conclusion, the authors suggest implementing an evidence-based PIV administration protocol for 3% sodium chloride has the potential to reduce adverse events related to central venous catheter injury. [3]


[1] 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
[2] Moritz ML, Ayus JC, Nelson JB. Administration of 3% Sodium Chloride and Local Infusion Reactions. Children (Basel). 2022;9(8):1245. Published 2022 Aug 18. doi:10.3390/children9081245
[3] Jannotta GE, Gulek BG, Dempsey JS, et al. Administration of 3% Sodium Chloride Through Peripheral Intravenous Access: Development and Implementation of a Protocol for Clinical Practice. Worldviews Evid Based Nurs. 2021;18(2):147-153. doi:10.1111/wvn.12501

Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

Is there evidence to support administering 3% sodium chloride through a peripheral line and if there is evidence to support this, is there a maximum rate at which to administer?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→

Please see Tables 1-3 for your response.


Safety of Continuous Peripheral Infusion of 3% Sodium Chloride Solution in Neurocritical Care Patients


Retrospective, multicenter, cohort study 

N= 213


To evaluate the incidence of infusion-related reactions and electrolyte abnormalities in neurocritical care patients treated with continuous infusion of 3% hypertonic saline (HTS) via a peripheral venous catheter (PVC).

Study Groups

3% HTS via a PVC (n= 213)


Inclusion criteria: Neurocritical care patients with a continuous infusion of 3% HTS via a PVC

Exclusion criteria: Less than 18 years or more than 89, pregnant, lactating, history of end-stage renal disease, syndrome of inappropriate antidiuretic hormone, diabetes insipidus

Electronic notes on catheter status were reviewed to determine the occurrence of infusion-related reactions. Prespecified thresholds were used to assess electrolyte abnormalities (hypokalemia: serum level of potassium < 3.5 mEq/L; hyperchloremia: serum level of chloride > 110 mEq/L; hypernatremia: serum level of sodium > 155 mEq/L; hypobicarbonatemia: serum level of bicarbonate < 20 mEq/L).


September 2011-September 2014

Outcome Measures

Infusion-related reactions requiring intervention, incidence of electrolyte abnormalities

Baseline Characteristics


3% HTS via a PVC (n=213)

Age, years



89 (41.2%)

African American

114 (53.5%)



3% HTS via a PVC (n=213)

Infusion-related reaction

15 (7%)


100 (46.9%)


105 (49.3%)


47 (22.1%)


19 (8.9%)

Adverse Events

Common Adverse Events: N/A

Study Author Conclusions

Current recommendations that a central catheter is required for continuous infusion of 3% HTS should be reevaluated. Only a few patients who had peripheral infusions had infusion-related reactions. Electrolyte abnormalities occurred frequently with peripheral infusion, but the clinical importance of the abnormalities remains unclear.

InpharmD Researcher Critique

This study is limited by its retrospective nature, but it did present data from two different academic institutions.


Jones GM, Bode L, Riha H, Erdman MJ. Safety of Continuous Peripheral Infusion of 3% Sodium Chloride Solution in Neurocritical Care Patients. Am J Crit Care. 2016;26(1):37-42.


Complication Rates of 3% Hypertonic Saline Infusion Through Peripheral Intravenous Access


Prospective, observational review



To prospectively gather data on patients who received hypertonic saline (HTS) in our surgical ICU to assess the complication rates

Study Groups

3% hypertonic saline (N=28 patients; 34 peripheral catheters)


Inclusion criteria: patients who were administered 3% hypertonic saline via 16- to 20-gauge peripheral intravenous catheters

Exclusion criteria: none

Patients receiving 3% HTS via peripheral catheters were prospectively followed for any adverse events. This study was conducted due to a policy change to allow 3% HTS for patients without central access at a single institution in Texas.


Up to 24 hours after peripheral administration was discontinued

Outcome Measures

Adverse events

Baseline Characteristics


Study population (n=28)

Age, years

39 ± 19


19 (68%)

Peripheral catheters (n=34)

Duration, hours (range)

36 ± 30 (1-124)

Infusion rate, mL/h (range)

39 ± 10 (30-50)

Anatomic placement






23 (68%)

6 (18%)

4 (12%)

1 (3%)

Adverse Events


Peripheral catheters (n=34)*


2 (6%)


1 (3%)

Right brachial vein thrombosis

1 (3%)

*A total of four adverse events occurred in three patients

Study Author Conclusions

There has been a long concern among healthcare providers, including nursing staff, in regard to peripheral IV administration of prolonged 3% HTS infusion therapy. Our study indicates that peripheral administration of 3% HTS carries a low risk of minor, nonlimb, or life-threatening complications. The concern regarding the risks of peripheral IV administration of 3% HTS may be overstated and unfounded.

InpharmD Researcher Critique

Limitations of these data include a small sample size, lack of control or comparison, and intrasubject patient data on lines used. The authors state the case of deep vein thrombosis seen is probably unrelated to the peripheral infusion of the hypertonic saline.


Perez CA, Figueroa SA. Complication Rates of 3% Hypertonic Saline Infusion Through Peripheral Intravenous Access. J Neurosci Nurs. 2017;49(3):191-195.


Incidence of Adverse Events During Peripheral Administration of Sodium Chloride 3%


Retrospective review



To evaluate the safety of peripheral venous administration of sodium chloride 3%

Study Groups

Peripheral venous line (n=66)


Inclusion criteria: greater than 18 years, received an infusion of sodium chloride 3%, only had peripheral venous access

Exclusion criteria: patients with central venous access throughout the entire duration of infusion

This was a retrospective review of a single center in New York.


January 2013 to March 2016

Outcome Measures

Primary: incidence of infusion-related adverse effects (IRAEs)

Secondary: time to IRAE, hospital length of stay, and ICU length of stay

Baseline Characteristics


Peripheral venous access (n=66)

Median Age, years (range)

68 (55-79)


25 (38%)

Duration of administration, hours


Median infusion starting rate, mL/hr


Patient location

Neurosurgical ICU

Medical step-down unit

Medical ICU


33 (50%)

18 (27%)

15 (23%)

Risk factors for IRAE

Presence of altered mental status

Diabetes mellitus

Peripheral vascular disease

History of intravenous drug use


50 (76%)

11 (17%)

3 (5%)

1 (2%)

Adverse Events


Peripheral venous access (n=66)

Total infusion-related adverse events

4 (6%)

Grade 1 events*

Phlebitis and infiltration


Edema (<1 inch)

4 (100%)

2 (50%)

1 (25%)

1 (25%)

Secondary outcomes

Time to IRAE, hours

Hospital length of stay, days

ICU length of stay, days


18 (5-76)

8 (4-12)

4 (2-10)

*Grade 1 injuries and resulted in no permanent tissue injuries

Study Author Conclusions

The rate of infusion-related adverse events related to the infusion of sodium chloride 3% through peripheral venous catheters appears to be similar to those reported with other hyperosmotic agents and could be considered for patients who need time-sensitive therapy.

InpharmD Researcher Critique

This retrospective study had a small sample size and lacked a comparator group.


Dillon RC, Merchan C, Altshuler D, Papadopoulos J. Incidence of Adverse Events During Peripheral Administration of Sodium Chloride 3%. J Intensive Care Med. 2018;33(1):48-53.