Introduction: Hypertonic saline (HTS) is used to treat severe hyponatremia and reduce intracranial pressure in spontaneous intracerebral hemorrhage. Although infusion-related adverse events (IRAEs), such as phlebitis and extravasation, are often cited as reasons to prefer central venous catheter (CVC) administration, CVCs carry risks like pneumothorax and thrombosis. Peripheral intravenous (PIV) access is faster to obtain, which is critical in resuscitation scenarios where time to therapy affects outcomes. This systematic review and meta-analysis aimed to identify the IRAE rate associated with PIV administration of HTS. Methods: PubMed, Scopus, and EMBASE were searched through July 2025. Eligible studies included English-language randomized trials or observational studies reporting IRAEs from HTS via PIV in adults. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was performed. Heterogeneity was assessed using the I2 statistic. Subgroup analyses were conducted by saline concentration, and meta-regression evaluated the relationship between IV site and adverse event rate. Publication bias was assessed using Begg and Egger tests. Results: Of 2,518 titles screened, 11 studies met inclusion criteria, encompassing 1,162 patients. The pooled IRAE rate was 8.9% (95% CI: 4.6-16.6%), with high heterogeneity (I2 = 87.1%). Most studies were of moderate quality. Subgroup analysis showed an event rate of 10.2% (95% CI: 4.9-19.9%) for 3% saline vs. 4.8% (95% CI: 1.5-13.8%) for 23.4% saline (p = 0.25). Meta-regression analysis showed that antecubital PIVs were not associated with higher IRAEs (correlation coefficient = -2.996; 95% CI: -7.03 to 1.04; p = 0.146). Phlebitis was the most common IRAE with no cases of severe tissue necrosis reported. Lastly, there was no statistically significant evidence of publication bias, confirmed via funnel plot analysis and Eggers test (intercept = -2.00; p = 0.13). Conclusions: PIV administration of 3% HTS demonstrated an IRAE rate of 10.2% vs 4.8% for 23.4% saline. It may be a time-efficient alternative to CVC in selected patients. As most studies were of moderate quality, additional high-quality studies are needed to compare concentrations and define optimal infusion protocols.
Hintze et al. (Sun,) studied this question.