Background:Functional recovery after aneurysmal subarachnoid hemorrhage (SAH) remains a significant problem. We tested a novel therapeutic approach with long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) to assess the safety and feasibility of an effectiveness trial.Methods:We conducted a multicentre, parallel, randomized, open-label pilot trial. Patients admitted within 72 hours after SAH with modified Fisher scale scores of 3 or 4 who were selected for scheduled aneurysm clipping were allocated to receive either n-3 PUFA treatment (parenteral perioperative: 5 days; oral: 8 weeks) plus usual care or usual care alone. Exploratory outcome measures included major postoperative intracranial bleeding complications (PIBCs), cerebral infarction caused by delayed cerebral ischemia, shunt-dependent hydrocephalus, and consent rate. The computed tomography evaluator was blinded to the group assignment.Results:Forty-one patients were randomized, but one patient had to be excluded after allocation. Twenty patients remained for intention to treat analysis in each trial arm. No PIBs (95% confidence interval [CI]: 0.00 to 0.16) or other unexpected harm were observed in the intervention group (IG). No patient suspended the intervention due to side effects. There was a trend towards improvements in all benefit-related outcomes in the IG. The overall consent rate was 0.91 (95% CI: 0.78 to 0.96), and there was no consent withdrawal.Conclusions:Although the balance between the benefit and harm of the intervention appears highly favourable, further testing on SAH patients is required. We recommend proceeding with amendments in a dose-finding trial to determine the optimal duration of parenteral treatment.
Aneurysmal subarachnoid hemorrhage (SAH) is a severe life-threatening disease and an important source of neurological disability. Therapeutic interventions over the last few decades have repeatedly failed to improve functional outcome after SAH; however, resolution of inflammation has largely been ignored as a potential therapeutic target. The omega-3 fatty acids (FAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are the precursors of key mediators involved in resolution of inflammation and endogenous neuroprotection. EPA also plays a major role in microvascular function, and DHA accretion in the brain is crucial for normal neuronal function. Although considerable loss of brain DHA has been identified in SAH patients, the pathological significance of this process has also been overlooked. Current Western diets provide insufficient amounts of omega-3 FAs to compensate for the loss of brain DHA following SAH. Here, we review the rationale for future clinical trials of omega-3 FAs in SAH. Furthermore, the potential role of defective resolution of inflammation in the growth and rupture of intracranial aneurysms is inferred from recent findings in atherosclerosis and nutrition. The novel concepts of resolution of inflammation and endogenous neuroprotective signaling may open new avenues for public health interventions and innovative research in intracranial aneurysms and SAH.
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