Dexamethasone after subarachnoid hemorrhage

Current guidelines do not support the routine use of corticosteroids in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, corticosteroids use in aSAH has been practiced at some centers by convention. The aim of a study was to determine the incidence of hydrocephalus requiring ventriculoperitoneal shunt (VPS) placement as well as functional outcome on discharge and adverse events attributed to corticosteroids in patients with aSAH treated with different dexamethasone (DXM) treatment schemes.

Methods: We retrospectively analyzed 206 patients with aSAH stratified to three groups based on the DXM treatment scheme: no corticosteroids, short course of DXM (S-DXM; 4 mg every 6 h for 1 day followed by a daily total dose reduction by 25% and then by 50% on last day), and long course of DXM (L-DXM; 4 mg every 6 h for 5-7 days followed by reduction by 50% every other day). The primary outcome measure was the placement of a VPS, and the secondary outcome was a good functional outcome [modified Rankin Scale (mRS) 0-3] at hospital discharge. Safety measures were the incidence of infection (pneumonia, urinary tract infection, ventriculitis, meningitis), presence of delirium, and hyperglycemia.

Results: There was no difference in the rate of external ventricular drain (EVD) (p = 0.164) and VPS placement (p = 0.792), nor in the rate of good outcome (p = 0.928) among three defined treatment regimens. Moreover, the median duration of treatment with EVD did not differ between subjects treated with no corticosteroids, S-DXM, and L-DXM (p = 0.905), and the probability of EVD removal was similar when stratified according to treatment regimens (log-rank; p = 0.256). Patients who received L-DXM had significantly more complications as compared to patients, who received no corticosteroids or S-DXM (78.4% vs. 58.6%; p = 0.005). After adjustment, L-DXM remained independently associated with increased risk of combined adverse events (OR = 2.72; 95%CI, 1.30-5.72; p = 0.008), infection (OR = 3.45; 95%CI, 1.63-7.30; p = 0.001) and hyperglycemia (OR = 2.05; 95%CI, 1.04-4.04; p = 0.039).

Conclusions: DXM use among patients with aSAH did not relate to the rate of EVD and VPS placement, duration of EVD treatment, and functional disability at discharge but increased the risk of medical complications 1).

The role of corticosteroids in the treatment of patients with aneurysmal subarachnoid hemorrhage (SAH) has remained controversial for decades. Studies have suggested that the administration of corticosteroids in SAH patients is associated with favourable outcomes. Given their significant adverse effects, it is essential to identify those patients who will benefit from treatment with corticosteroids.

In a retrospective analysis of a prospectively collected cohort (n = 306) with SAH who were treated by microsurgical clipping or endovascular intervention was performed. The role of dexamethasone administration was analysed with regard to clinical conditions and SAH-related complications. Outcome was assessed at discharge and during follow-up using the Glasgow Outcome Scale (GOS).

Patients treated with dexamethasone presented with more episodes of hyperglycemia (P < 0.001), more overall infections (P < 0.001) and more ventriculostomy-related infections (P = 0.004). Multivariate analysis demonstrated that treatment with dexamethasone was associated with an unfavourable outcome at discharge (GOS 1-3) [odds ratio (OR) 2.814, 95% confidence interval (CI) 1.440-5.497, P = 0.002]. In the subgroup of microsurgically treated patients, dexamethasone administration was associated with a favourable outcome at follow-up (OR 0.193, 95% CI 0.06-0.621, P = 0.006). A higher risk for unfavourable outcome (OR 3.382, 95% CI 1.67-6.849, P = 0.001) at discharge was observed in endovascularly treated patients who received dexamethasone but this had no impact on the outcome at follow-up.

Treatment with dexamethasone seems to be associated with a risk reduction for an unfavourable outcome in those patients who underwent microsurgical clipping. Despite an increased frequency of adverse effects, glucocorticoids may have a potential benefit in this specific surgical subgroup compared to endovascularly treated SAH patients 2).

In a study of Feigin et al. in 2005 there was no evidence of a beneficial or adverse effect of corticosteroids in patients with either SAH or primary intracerebral haemorrhage (PICH). Confidence intervals are wide and include clinically significant effects in both directions 3).

Miller MM, Dakay K, Henninger N, et al. Association of Dexamethasone with Shunt Requirement, Early Disability, and Medical Complications in Aneurysmal Subarachnoid Hemorrhage [published online ahead of print, 2020 Aug 26]. Neurocrit Care. 2020;10.1007/s12028-020-01059-2. doi:10.1007/s12028-020-01059-2
Czorlich P, Sauvigny T, Ricklefs F, Abboud T, Nierhaus A, Vettorazzi E, Reuter DA, Regelsberger J, Westphal M, Schmidt NO. Impact of dexamethasone in patients with aneurysmal subarachnoid haemorrhage. Eur J Neurol. 2017 Apr;24(4):645-651. doi: 10.1111/ene.13265. Epub 2017 Feb 17. PubMed PMID: 28213906.
Feigin VL, Anderson N, Rinkel GJ, Algra A, van Gijn J, Bennett DA. Corticosteroids for aneurysmal subarachnoid haemorrhage and primary intracerebral haemorrhage. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD004583. Review. PubMed PMID: 16034939.
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