Corticosteroids in Patients With Hemorrhagic Stroke
Section Editors: Graeme J. Hankey MD, FRCP
Corticosteroids, particularly dexamethasone, are commonly used for treating patients with subarachnoid hemorrhage (SAH) and primary intracerebral hemorrhage (PICH) despite their being a lack of insight in the evidence on their efficacy.
To review the efficacy and safety of corticosteroids in the treatment of patients with acute SAH and PICH.
All randomized or quasi-randomized clinical trials of corticosteroid therapy in patients with SAH or PICH that had a placebo or standard strategy arm as control were included. Patients of any age and either gender with clinically (bedside) diagnosed PICH and CT or cerebrospinal fluid documented SAH were eligible. The corticosteroid drugs were classified as glucocorticoids (methylprednisolone, hydrocortisone, dexamethasone) and mineralocorticoids (fludrocortisone).
We searched the Cochrane Stroke Group Trials Register (November 2003), MEDLINE (1966 to March 2004), EMBASE (1980 to March 2004), and reference lists of relevant eligible studies identified. We also made an attempt to identify any relevant ongoing or unpublished studies by contacting trialists and pharmaceutical companies.
Data Collection and Analysis
Three reviewers (V.L.F., N.E.A., G.J.E.R.) independently extracted data and assessed trial quality. Data extracted from eligible clinical trials included: (1) death and poor outcome (death, severe disability or vegetative state) within 1 to 6 months of the disease onset (primary outcomes); (2) development of delayed cerebral ischemia, as defined by the study authors, in patients with SAH; and (3) adverse effects of the treatment during the scheduled treatment or follow-up period (secondary outcomes). Primary analyses were based on the intention-to-treat results of the individual trials.
Eight trials that fulfilled the eligibility criteria were identified, with a total of 256 randomized patients in 3 SAH trials, and 206 patients in 5 PICH trials. The studies differed substantially with regard to the study populations and drugs, and methodological quality.
Corticosteroids in PICH
Treatment with glucocorticoids did not reduce death (relative risk [RR] 1.14; 95% CI, 0.91 to 1.42; Figure) or poor outcome at 1 month after randomization (RR 0.95; 95% CI, 0.83 to 1.09). The rate of any adverse effects in the treatment group (13%) was 48% higher than that in the control group patients (8.8%), but the confidence interval was very wide (RR 1.48; 95% CI, 0.87 to 2.51). The most common side effects of dexamethasone treatment were infections (23%), exacerbation of diabetes mellitus (11%), and gastrointestinal bleeding (5%), but none of these side effects was differed statistically significant between the treatment and control groups. The site of the PICH (supratentorial, brain stem or mixed) appeared to play no substantial role in the death outcomes.
Corticosteroids in SAH
Because there was only 1 trial using glucocorticoid treatment with hydrocortisone sodium phosphate, and all the outcome measures except delayed cerebral ischemia and “other adverse effects” were different between the 3 trials, pooled effect estimates for hydrocortisone intervention and most of the outcomes cannot be calculated.
Overall, treatment with corticosteroids (glucocorticoids and mineralocorticoids) had no statistically significant effect on poor outcome at the end of follow-up (RR 0.96; 95% CI, 0.77 to 1.20), but was associated with an increased rate of adverse effects (RR 1.75; 95% CI, 1.03 to 2.95), mainly because of the very high risk of hydrocortisone-induced hyperglycemia.
At present, there is no evidence to support the routine use of corticosteroids (mineralocorticoids or glucocorticoids) in patients with hemorrhagic stroke (SAH or PICH). Treatment of these patients with corticosteroids may be associated with an increased risk of adverse effects. Further randomized controlled trials are warranted to evaluate the efficacy and safety of treatment with corticosteroids in these patients. These should use an intention-to-treat approach to the analysis and should take account of various clinical variables (eg, time and dosage of intervention, timing of aneurysm surgery for SAH, pulse high-dose treatment at very early stages of PICH, supratentorial or brain stem intracerebral hemorrhage).
Note: The full text of this review is available in the Cochrane Library (for subscribers: http://www3.interscience.wiley.com/cgi-bin/mrwhome/106568753/HOME). The full article should be cited as: Feigin VL, Anderson N, Rinkel GJE, Algra A, van Gijn J, Bennett DA. Corticosteroids for aneurysmal subarachnoid hemorrhage and primary intracerebral hemorrhage. Cochrane Database of Syst Rev. 2005, Issue 4.
- Received January 15, 2006.
- Accepted January 24, 2006.