Aneurysmal subarachnoid hemorrhage (SAH) is a life-threatening condition and an important source of neurological disability. Pharmacological interventions over the last few decades have repeatedly failed to improve functional recovery after SAH. However, the status of brain docosahexaenoic acid (DHA) and resolution of inflammation after SAH have been poorly investigated as potential therapeutic targets. The long-chain omega-3 fatty acids (OMG-3), eicosapentaenoic acid (EPA) and DHA, play major roles in both human physiology and the pathophysiology of inflammation. Normal brain structure and function critically depend on high DHA enrichment in neuronal membranes. Resolution of inflammation, innate immune responses and neuroprotective signaling may largely be mediated by a novel superfamily of autacoids termed specialized pro-resolving mediators, which are mainly derived from EPA and DHA. Although substantial loss of brain DHA was identified in patients with SAH two decades ago, the clinical relevance of this pathophysiological process remains unexamined.

Here, we review a pilot RCT of OMG-3 in SAH and a prospective case series of SAH treated with the same OMG-3 intervention, though slightly modified. As of June 2024, 60 patients with SAH have received a bimodal OMG-3 intervention which consists of parenteral fish oil monotherapy (5-10 days) followed by oral administration (8 weeks). This OMG-3 intervention has shown a high safety profile even when administered perioperatively in critically ill patients with SAH. Improved clinical recovery has been observed during in-hospital stay, with reduced severity of both delayed cerebral ischemia and healthcare-related infections; none of the 41 patients of the case series have been treated with invasive endovascular therapy for cerebral vasospasm. Patients admitted in good clinical conditions are generally able to achieve complete functional recovery few months after SAH. This novel OMG-3 intervention is an easy-to-implement and low-cost treatment, which makes it suitable for a wide variety of clinical settings.