J Korean Med Sci.  2023 May;38(21):e161. 10.3346/jkms.2023.38.e161.

Efficacy of Acetylcysteine and Selenium in Aneurysmal Subarachnoid Hemorrhage Patients: A Prospective, Multicenter, Single Blind Randomized Controlled Trial

• Kim M
• Jeon H
• Chung Y
• Lee SU
• Park W
• Park JC
• Ahn JS
• Lee S

• KMID: 2542598
• DOI: http://doi.org/10.3346/jkms.2023.38.e161

Abstract

Background
Subarachnoid hemorrhage (SAH) patients have oxidative stress results in inflammation, tissue degeneration and neuronal damage. These deleterious effects cause aggravation of the perihematomal edema (PHE), vasospasm, and even hydrocephalus. We hypothesized that antioxidants may have a neuroprotective role in acute aneurysmal SAH (aSAH) patients.
Methods
We conducted a prospective, multicenter randomized (single blind) trial between January 2017 and October 2019, investigating whether antioxidants (acetylcysteine and selenium) have the potential to improve the neurologic outcome in aSAH patients. The antioxidant patient group received antioxidants of acetylcysteine (2,000 mg/day) and selenium (1,600 µg/day) intravenously (IV) for 14 days. These drugs were administrated within 24 hours of admission. The non-antioxidant patient group received a placebo IV.
Results
In total, 293 patients were enrolled with 103 patients remaining after applying the inclusion and exclusion criteria. No significant differences were observed in the baseline characteristics between the antioxidant (n = 53) and non-antioxidant (n = 50) groups. Among clinical factors, the duration of intensive care unit (ICU) stay was significantly shortened in patients who received antioxidants (11.2, 95% confidence interval [CI], 9.7–14.5 vs. 8.3, 95% CI, 6.2–10.2 days, P = 0.008). However, no beneficial effects were observed on radiological outcomes.
Conclusion
In conclusion, antioxidant treatment failed to show the reduction of PHE volume, mid-line shifting, vasospasm and hydrocephalus in acute SAH patients. A significant reduction in ICU stay was observed but need more optimal dosing schedule and precise outcome targets are required to clarify the clinical impacts of antioxidants in these patients.

Keyword

Antioxidant; Brain; Cerebrovascular; Hemorrhage; Subarachnoid Hemorrhage; Surgery

Figure

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  Fig. 1 Schematic diagram of the framework between antioxidant and subarachnoid hemorrhage.BBB = blood brain barrier.

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  Fig. 2 Enrollment, assignment, and follow-up for study patients.GCS = Glasgow coma scale, ICU = intensive care unit, SAH = subarachnoid hemorrhage.

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  Fig. 3 Non-enhanced brain CT images showing SAH patients with administration of antioxidants. (A) A 74-year-old female patient with aneurysmal SAH due to right middle cerebral artery aneurysm rupture. The patient was treated with craniotomy and clipping of ruptured aneurysm. (B) Post-operative CT on the day of operation showing massive hemorrhage and PHE causing midline shifting (9.33 mm) is observed. Antioxidants were given within 24 hours of admission. (C) One-week follow-up CT shows PHE causing midline shifting (11.58 mm). (D) Two-week follow-up CT showed aggravated PHE causing persistent midline shifting (15.49 mm). The patient underwent decompressive craniectomy for perihematomal edema management.SAH = subarachnoid hemorrhage, CT = computed tomography, PHE = perihematomal edema.

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  Fig. 4 The 30-day neurologic outcomes using modified Rankin scale between with and without antioxidant treated groups.

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