Published Online
on June 21, 2007

A more recent version of this article appeared on August 1, 2007

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Submitted on December 20, 2006
Revised on January 22, 2007
Accepted on February 12, 2007

A Randomized Controlled Trial of Hydrocortisone Against Hyponatremia in Patients With Aneurysmal Subarachnoid Hemorrhage

Yoichi Katayama MD, PhD^*; Jo Haraoka MD, PhD; Hidehiro Hirabayashi MD, PhD; Tatsuro Kawamata MD, PhD; Keiji Kawamoto MD, PhD; Takao Kitahara MD, PhD; Jun Kojima PhD; Toshihiko Kuroiwa MD, PhD; Tatsuro Mori MD, PhD; Nobuhiro Moro MD, PhD; Izumi Nagata MD, PhD; Akira Ogawa MD, PhD; Kikuo Ohno MD, PhD; Yoshikatsu Seiki MD, PhD; Yoshiaki Shiokawa MD, PhD; Akira Teramoto MD, PhD; Teiji Tominaga MD, PhD; and Toshiki Yoshimine MD, PhD

From the Department of Neurological Surgery (Y.K., T. Kawamata, J.K., T.M., N.M.), Nihon University School of Medicine; the Department of Neurosurgery (J.H.), Tokyo Medical University; the Department of Neurosurgery (H.H.), Nara Medical University; the Department of Neurosurgery (K.K.), Kansai Medical University; the Department of Emergency and Critical Care Medicine (T. Kitahara), Kitasato University School of Medicine; the Department of Neurosurgery (T. Kuroiwa), Osaka Medical College; the Department of Neurosurgery (I.N.), Nagasaki University School of Medicine; the Department of Neurosurgery (A.O.), Iwate Medical University; the Department of Neurosurgery (K.O.), Graduate School of Medicine, Tokyo Medical and Dental University; the Department of Neurosurgery (Y. Seiki), Toho University School of Medicine; the Department of Neurosurgery (Y. Shiokawa), Kyorin University School of Medicine, the Department of Neurosurgery (A.T.), Nippon Medical School; the Division of Neurosurgery (T.T.), Department of Neuroscience and Sensory Organs, Tohoku University Graduate School of Medicine; and the Department of Neurosurgery (T.Y.), Osaka University Medical School, Japan.

^* To whom correspondence should be addressed. E-mail: JDW06164{at}nifty.ne.jp.

Background and Purpose--Hyponatremia is common after aneurysmal subarachnoid hemorrhage (SAH). It is caused by natriuresis, which induces osmotic diuresis and decreases blood volume, contributing to symptomatic cerebral vasospasm (SCV). Hypervolemic therapy to prevent SCV will not be efficient under this condition. We conducted a randomized controlled trial to assess the efficacy of hydrocortisone, which promotes sodium retention in the kidneys.

Methods--Seventy-one SAH patients were randomly assigned after surgery to treatment with either a placebo (n=36) or 1200 mg/d of hydrocortisone (n=35) for 10 days and tapered thereafter. Both groups underwent hypervolemic therapy. The primary end point was the prevention of hyponatremia.

Results--Hydrocortisone prevented excess sodium excretion (P=0.04) and urine volume (P=0.04). Hydrocortisone maintained the targeted serum sodium level throughout the 14 days (P<0.001), and achieved the management protocol with lower sodium and fluid (P=0.007) supplementation. Hydrocortisone kept the normal plasma osmolarity (P<0.001). SCV occurred in 9 patients (25%) in the placebo group and in 5 (14%) in the hydrocortisone group. No significant difference in the overall outcome was observed between the 2 groups.

Conclusions--Hydrocortisone overcame excess natriuresis and prevented hyponatremia. Although there was no difference in outcome, hydrocortisone supported efficient hypervolemic therapy.

Key words: hydrocortisone • hyponatremia • multicenter studies • randomized controlled trials • subarachnoid hemorrhage

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