Hyponatremia in aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis on management approaches

Abstract

Hyponatremia complicates between 32% and 48.9% of aneurysmal subarachnoid hemorrhage (SAH) cases, doubling the risk of cerebral ischemia (24% vs. 12%; p = 0.045) and increasing mortality 2.7-fold. However, only 28% of hospitals use standardized protocols, that it highlights the need for evidence-based management. This PRISMA-compliant systematic review and meta-analysis included 21 studies (1749 patients; 1984–2025) from PubMed, EMBASE, and Scopus. The secondary variables analyzed included sodium correction, protocol adherence, delayed cerebral ischemia (DCI) and ICU length of stay. Three main findings were identified: albumin–fludrocortisone synergy: early combination (<72 h post-SAH) of albumin (60 g/day) and fludrocortisone reduced hyponatremia by 45% (49.2% to 27.0%) and DCI by 29% (adjusted RR = 0.63). This approach yielded an NNT of 4.3 compared to 13 for clot retrieval. Time-Phased Protocol: Phase I (days 1–3): Albumin + fludrocortisone decreased symptomatic vasospasm by 67% (p = 0.02). Phase II (days 4–7): tolvaptan 15 mg/day shortened ICU stay by 3.2 days (p = 0.01) and improved 6-month mRS scores by 41.7% (p = 0.045). Impact of center volume: high-volume centers (>50 SAH cases/year) had 2.1 times higher protocol adherence (89% vs. 23%) and 35% fewer reoperations. The meta-analysis confirmed a significant reduction in symptomatic vasospasm (pooled OR = 0.40; 95% CI: 0.18–0.90; p = 0.026) and a higher likelihood of hyponatremia correction (OR = 3.37; 95% CI: 1.57–7.27; p = 0.002) in groups receiving active protocols (e.g., albumin/fludrocortisone, tolvaptan) compared to standard care or historical controls. Fluid restriction was associated with higher mortality and is discouraged. A bimodal protocol combining early albumin and fludrocortisone followed by later tolvaptan can lead to better clinical outcomes. Greater institutional experience and real-time sodium monitoring are recommended. Phase III trials comparing saline-based strategies vs. albumin-based are needed.