SYSTEMATIC REVIEW article
Front. Med.
Sec. Intensive Care Medicine and Anesthesiology
Safety of Peripheral Intravenous Administration of Hypertonic Saline: a Systematic Review and Meta-Analysis
Provisionally accepted
Sih-Shiang Huang
Chih-Wei Sung
Chien-Tai Huang
Mu-Yang Hsieh
Jen-Chung Ko
Wang-Huei Sheng
Edward Pei-Chuan Huang*- National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
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Background: Hypertonic saline solution is critical for managing symptomatic hyponatremia and increased intracranial pressure (IICP). Though administered via central venous catheters (CVCs) traditionally, peripheral administration is a viable alternative, reducing delays and CVC-associated risks. This review evaluates the safety of peripheral hypertonic saline, focusing on infusion-related adverse events. Methods: A systematic search of MEDLINE, Embase, and Cochrane Library (up to December 2024) identified studies on peripheral hypertonic saline in adults. Studies reporting phlebitis, infiltration, extravasation, and thrombosis were included. Two reviewers independently screened studies and extracted data. Quality was assessed using the Newcastle-Ottawa Scale and Risk of Bias 2 tool. The review is registered on PROSPERO (CRD42024612330). Results: Thirteen studies involving 2,354 patients were included, comprising one randomized controlled trial and 12 cohort studies. Quality assessment showed a low risk of bias across all included studies. The pooled incidence of phlebitis was 2.3% (95% CI: 1.2%-4.1%), while infiltration and extravasation occurred at a rate of 2.1% (95% CI: 1.1%-3.9%). Thrombosis was rare, with an incidence of 0.8% (95% CI: 0.3%-1.7%). Most complications were mild and resolved conservatively. Conclusion: Peripheral hypertonic saline is a safe alternative to CVC placement, particularly in urgent situations where rapid intervention is required. Low complication rates support its broader use in clinical practice, enabling timely treatment while minimizing the risks associated with central access. These findings support consideration for updates to clinical guidelines, advocating for peripheral hypertonic saline as a first-line option in appropriate scenarios to enhance patient outcomes and streamline care delivery.
Keywords: hypertonic saline, Peripheral administration, Infusion-related adverse events, Safety, Critical Care
Received: 13 Sep 2025; Accepted: 24 Oct 2025.
Copyright: © 2025 Huang, Sung, Huang, Hsieh, Ko, Sheng and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Edward Pei-Chuan Huang, edward56026@gmail.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.