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. 
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. 
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. 
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.