[Intravenous hydrocortisone in large doses in the treatment of delayed ischemic neurological deficits following subarachnoid hemorrhage--results of a multi-center controlled double-blind clinical study]. Cerebrospinal fluid pressure changes with chemotherapy for intracerebral hemorrhage. Dexamethasone is not necessarily unsafe in primary supratentorial intracerebral haemorrhage. Effectiveness of high dose dexamethasone in the treatment of acute stroke. Dexamethasone as treatment in cerebrovascular disease. 1. A controlled study in intracerebral hemorrhage. Effect of fludrocortisone acetate in patients with subarachnoid hemorrhage. Improved efficiency of hypervolemic therapy with inhibition of natriuresis by fludrocortisone in patients with aneurysmal subarachnoid hemorrhage. Effects of dexamethasone in primary supratentorial intracerebral hemorrhage.
Glucocorticoid in high dose has known to reduce vascular sensitivity to various vasoconstrictive stimuli. It inhibits phospholipase to reduce production of prostaglandins. It stabilizes the cell membrane and prevents cerebral edema. All these pharmacological effects indicate possible usefulness of this drug for the treatment of cerebral ischemia due to vasospasm. Based on these theoretical backgrounds a multi-center controlled double blind clinical study was carried out. The patient who showed manifestations of delayed cerebral ischemia due to vasospasm were selected for this study. As soon as the clinical manifestation appeared, the patient was given either 3 grams of hydrocortisone intravenously in a 60 ml solution or the placebo. The administration was repeated 6 times with interval of 12 hours. The patients were allowed to be treated according to the independent protocol of each institute except for the maximum daily use of glucocorticoid. The effect of the therapy was evaluated at 4th, 7th day and 1 month after the initiation. The study involved 52 institutes and a total of 140 patients, seventy-one patients who received hydrocortisone (group A) and 69 patients who received placebo (group P) was analysed. There were no significant differences in background data between both groups. In patients with grade I, II or III on admission, the favorable effects of hydrocortisone were demonstrated on changes in neurological findings. In group A, there were significantly more cases of improvement at 4th day for orientation about place and person. At 1 month or on discharge group A showed significant improvement almost in every aspect of neurological findings including mental, speech and motor functions.(ABSTRACT TRUNCATED AT 250 WORDS) nan nan A prospective double-blind placebo-controlled, randomised clinical trial was carried out to determine the effectiveness of short-course of high dose dexamethasone therapy on mortality and neurological recovery in stroke patients. During a sixteen month period of study, 230 patients with clinical diagnosis of stroke were seen. Of these, 40 were eligible for the study (27 were presumed to have had haemorrhagic stroke; and 13 were presumed to have had cerebral infarction). The commonest cause of exclusion was presentation after 24 hours of the ictus. Patients were sequentially paired and randomised into high dose dexamethasone and placebo groups in a double-blind fashion. There were twenty patients in either group. Of the 27 patients with haemorrhagic stroke, 15 were in the dexamethasone group and 12 in the placebo group. Of the 13 patients with cerebral infarction, 5 were in the dexamethasone group and 8 in the placebo group. Each patient received 100 mg of dexamethasone stat, and 16 mg every 6 hours for a period of 48 hours or equivalent volumes of placebo. Assessment of each patient was done using a neurological score. Sequential analysis by Armitage was employed, using survival at 1 month as the primary criterion of effectiveness. Survivors were followed-up for 6 months. At the end of one month, 16 patients (80%) had died in the dexamethasone group and 17 (85%) in the placebo group. The average day of death was six days in the dexamethasone group and 15 days in the placebo group, but this was not statistically significant. Of the seven survivors at one month, four were in the dexamethasone group and 3 in the placebo group. Five of them had cerebral infarction and two had haemorrhagic stroke. The two in the haemorrhagic subgroup who survived the first month died at the 2nd and 4th month respectively. At the end of six months, only the five patients with cerebral infarction were alive. Of these, 2 in the dexamethasone group were back at work while the third was chair-bound. The 2 survivors in the placebo group were chair and bed bound respectively. In conclusion, this study failed to demonstrate any benefit of a short-course of high dose steroid in improving the mortality of stroke patients and its use should be discouraged. However, possible benefit in the morbidity of survivors in the patients with cerebral infarction requires further studies. nan In this study with randomized controls, we administered fludrocortisone acetate to 46 of 91 patients with subarachnoid hemorrhage in an attempt to prevent excessive natriuresis and plasma volume depletion. Fludrocortisone significantly reduced the frequency of a negative sodium balance during the first 6 days (from 63% to 38%, p = 0.041). A negative sodium balance was significantly correlated with decreased plasma volume during both the first 6 days (p = 0.014) and during the entire 12-day study period (p = 0.004). Although fludrocortisone treatment tended to diminish the decrease in plasma volume, the difference was not significant (p = 0.188). More patients in the control group developed cerebral ischemia (31% vs. 22%) and, consequently, more control patients were treated with plasma volume expanders (24% vs. 15%), which may have masked the effects of fludrocortisone on plasma volume. Fludrocortisone therefore reduces natriuresis and remains of possible therapeutic benefit in the prevention of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. To reduce the risk of ischemic complications in patients with subarachnoid hemorrhage (SAH), hypervolemic therapy is generally advocated. However, such conventional treatment cannot always ensure the maintenance of an effective intravascular volume expansion, because excessive natriuresis and osmotic diuresis occur after SAH. In this prospective study the authors examined the effects of inhibition of natriuresis with fludrocortisone acetate on intravascular volume expansion during hypervolemic therapy.
                Thirty patients with SAH were randomized and divided into two groups: controls (Group 1, 15 patients) and patients treated with 0.3 mg/day of fludrocortisone (Group 2, 15 patients). In all patients sodium and fluid intake levels were in excess of maintenance requirements in an attempt to maintain a positive water balance and a central venous pressure (CVP) of 8 to 12 cm H2O. The mean sodium and water intake levels for 14 days after SAH were significantly reduced by fludrocortisone in Group 2 (487+/-34.52 mEq/day and 5159.2+/-249.29 ml/day, respectively; p<0.01) compared with Group 1 (634.2+/-42.86 mEq/day and 6611.7+/-365.67 ml/day). Fludrocortisone significantly reduced the urinary sodium excretion (p<0.01) and urine volume (p<0.01) in parallel, and effectively prevented a negative shift in the sodium as well as water balance (p<0.01). The serum sodium level tended to decrease in Group 1, reaching 135 mEq/L on average, but not in Group 2 (p<0.01). Hyponatremia in Group 1 was always observed at the optimal range of CVP values. A decrease in serum potassium level within the range of 2.8 to 3.5 mEq/L was transiently noted in 11 patients (73.3%) of Group 2, but was easily corrected. Possible side effects of fludrocortisone, such as pulmonary edema, were not encountered.
                Intravascular volume expansion in the presence of excessive natriuresis requires a large sodium and water intake and is often associated with hyponatremia. Inhibition of natriuresis with fludrocortisone can effectively reduce the sodium and water intake required for hypervolemia and prevent hyponatremia at the same time. To evaluate the efficacy of dexamethasone for treatment of primary supratentorial intracerebral hemorrhage, we studied 93 patients 40 to 80 years old, using a double-blind randomized block design. After the subjects were stratified according to their level of consciousness (Glasgow Coma Scale), those with objectively documented primary supratentorial intracerebral hemorrhage were randomly assigned to either dexamethasone or placebo. For ethical reasons, three interim analyses were planned, to permit early termination of the trial if one study group did better than the other. During the third interim analysis, the death rate at the 21st day was identical in the two groups (dexamethasone vs. placebo, 21 of 46 vs. 21 of 47; chi-square = 0.01, P = 0.93). In contrast, the rate of complications (mostly infections and complications of diabetes) was much higher in the dexamethasone group (chi-square = 10.89, P less than 0.001), leading to early termination of the study. In the light of the absence of a demonstrable beneficial effect and the presence of a significant harmful effect, current practices of using dexamethasone for treatment of primary supratentorial hemorrhage should be reconsidered.
Overall, there is no evidence of a beneficial or adverse effect of corticosteroids in patients with either SAH or PICH. Confidence intervals are wide and include clinically significant effects in both directions.