Nobuhiro Moro

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

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.

Prophylactic Management of Excessive Natriuresis With Hydrocortisone for Efficient Hypervolemic Therapy After Subarachnoid Hemorrhage

Background and Purpose— Hyponatremia caused by excessive natriuresis is common in patients with aneurysmal subarachnoid hemorrhage (SAH). Natriuresis decreases the total blood volume through osmotic diuresis and increases the risk of symptomatic cerebral vasospasm. In such patients, hypervolemic therapy is difficult to achieve without causing hyponatremia because sodium replacement provokes further natriuresis and osmotic diuresis. We examined the effects of hydrocortisone, which promotes sodium retention, in patients with SAH. Methods— Twenty-eight SAH patients were randomized into 2 groups after direct surgery: group 1 patients without hydrocortisone treatment (n=14) and group 2 patients with hydrocortisone treatment (1200 mg/d for 10 days; n=14). Both groups underwent hypervolemic therapy by aggressive sodium and water replacement. The goal of the hypervolemic therapy was to maintain the serum sodium level >140 mEq/L and the central venous pressure (CVP) within 8 to 12 cm H2O. Results— Group 2 demonstrated a lower sodium excretion (P <0.05) and higher serum sodium level (P <0.05) compared with group 1. Hyponatremia developed in 6 patients (43%) in group 1 and 0 patients in group 2 (P <0.05). Group 2 also demonstrated a lower urine volume, lower infusion volume (P <0.05) required for hypervolemic therapy, and higher CVP (P <0.05). Failure to maintain CVP was observed in 12 patients (86%) in group 1 and 3 patients (21%) in group 2 (P <0.05). Hydrocortisone caused no serious side effects. Conclusions— Hydrocortisone clearly attenuates excessive natriuresis. Prophylactic hydrocortisone administration appears to have a therapeutic value in inducing hypervolemia efficiently after SAH.

Prediction of symptomatic cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage: relationship to cerebral salt wasting syndrome.

Abstract Objectives: Symptomatic cerebral vasospasm is a major complication in patients with subarachnoid hemorrhage (SAH). Symptomatic cerebral vasospasm has been reported to be related to the patients blood volume which is influenced by cerebral salt wasting syndrome (CSWS). We undertook a prospective study to assess whether the onset of symptomatic cerebral vasospasm was predictable or not, by observing the phenomena of CSWS (natriuresis and osmotic diuresis). Methods: Sixty-seven consecutive aneurysmal SAH patients were analysed. After surgery, all patients underwent hypervolemic therapy in order to keep central venous pressure (CVP) within 8–12 cmH2O, serum sodium level above 140 mEq/l and a positive water balance. Patients were classified into two groups: those without symptomatic cerebral vasospasm (n=55) and those with symptomatic cerebral vasospasm (n=12). To estimate natriuresis and osmotic diuresis, sodium in/out, water in/out, CVP and other parameters were measured and compared between the two groups. Results: One day before symptomatic cerebral vasospasm, three factors reached statistical difference in the group that experienced symptomatic cerebral vasospasm: sodium balance, urine volume and water balance. On the day of symptomatic cerebral vasospasm, two factors reached statistical difference: sodium excretion and urine volume. No factor was significantly different 2 days before symptomatic cerebral vasospasm. Discussion: Symptomatic cerebral vasospasm has a strong relationship with CSWS. Negative sodium and water balance and increased urine volume indicate a predictor of symptomatic cerebral vasospasm. To predict symptomatic cerebral vasospasm, strict observations are required, because CSWS and symptomatic cerebral vasospasm which follows, develop rapidly.

Is the circulating plasma volume sufficiently maintained? Fluid management of an aneurysmal subarachnoid hemorrhage in the acute phase

Abstract Cerebral vasospasm is a well-known cause of mortality and morbidity following aneurysmal subarachnoid hemorrhage (SAH). Prevention of symptomatic cerebral vasospasm is the basic management after SAH. Numerous pharmaceutical therapies and endovascular treatments are available against cerebral vasospasm, but none of them have so far proven to improve the outcome. We have focused on maintaining the circulation volume in order to prevent cerebral vasospasm. But to maintain the central venous pressure, huge infusion volume was required, and hyponatremia was frequently observed due to natriuresis and osmotic diuresis. Excessive natriuresis and diuresis cannot be managed through sodium and water replacement, since sodium replacement induces further natriuresis and diuresis (desalination), and water replacement induces hyponatremia. We therefore administered fludrocortisone and hydrocortisone to inhibit excessive natriuresis and diuresis. The efficacy of sodium reabsorption therapy is extremely high to maintain the circulation volume that might have a therapeutic effect to prevent cerebral vasospasm. In this article, we review our institution’s experience regarding the management of patients with aneurysmal SAH and also discuss the importance of water and sodium balance when managing such patients.

Experimental model for investigating hyponatremia after subarachnoid hemorrhage in rats.

Hyponatremia is a common complication in patients with aneurysmal subarachnoid hemorrhage (SAH). Such patient demonstrates excessive natriuresis and an increased risk of symptomatic cerebral vasospasm. However, the precise mechanisms underlying SAH induced hyponatremia remain unclear. In the present study, in order to establish an experimental model of hyponatremia following SAH, we induced SAH in rats, and evaluated the serum sodium (Na) levels, Na excretion and physiological parameters. Twenty-four male Wistar rats were used. SAH was induced by an endovascular puncture method. The mean arterial pressure (MAP), intracranial pressure (ICP), and cerebral blood flow (CBF) were monitored continuously. The urine was collected cumulatively for 12 hours after SAH, and the urine Na concentration was determined with a spectrophotometer. The serum Na levels were measured at 12 hrs, 2 and 4 days following the SAH induction. The mean (+/- standard deviation) baseline ICP was 3.5 +/- 2.6 mmHg, and increased to 67.4 +/- 17.6 mmHg immediately following induction of SAH. CBF decreased rapidly, and then gradually recovered to 70-80% of baseline. The urine volume and total Na excretion were significantly increased in comparison to those of the sham (P < 0.05). The serum Na level was significantly decreased at 4 days following SAH (P < 0.05). The present results demonstrated for the first time that rats with SAH exhibited excessive natriuresis. The endovascular puncture model is suitable for investigating hyponatremia that occurs concomitantly with natriuresis and diuresis after SAH.

Inhibitory effect of hydrocortisone on cerebral salt wasting after subarachnoid hemorrhage in rats.

Cerebral salt wasting (CSW) frequently occurs concomitantly with subarachnoid hemorrhage (SAH). CSW induces excessive natriuresis and osmotic diuresis, reduces total blood volume, aggravates cerebral vasospasm and causes cerebral ischemia after SAH. This study examined the inhibitory effect of hydrocortisone on CSW in rat SAH models. Hydrocortisone had an inhibitory effect on CSW because hydrocortisone functioned in a dose-dependent manner to inhibit the increase in sodium excretion and sodium/potassium ratio after SAH onset. We conclude that hydrocortisone is a useful drug for the treatment of CSW after SAH.

Solitary primary intracranial leptomeningeal glioblastoma invading the normal cortex: Case report

Solitary primary intracranial leptomeningeal glioma (PLG) is a rare entity of glioma. PLG arises from the heterotopic glial tissue in the subarachnoid space and usually grows there without parenchymal invasion. The present study reported a case of solitary PLG, pathologically diagnosed as glioblastoma, that invaded the temporal cortex and finally disseminated to the spinal cord. A 55-year-old woman had headaches and visited Nihon University, Itabashi Hospital. Head magnetic resonance imaging showed a solid mass mainly located in the right middle fossa extending to the frontal base with strong enhancement effect after contrast medium injection. A conventional angiogram showed a tumor arising from the middle meningeal artery. Fronto-temporal craniotomy was performed to remove the tumor. During reflection of the dura matter, there were numerous small vessels connecting the dura matter and the cortical surface. The tumor was located in the Sylvian fissure and extended around the middle cerebral artery. The border between the tumor and the normal temporal lobe was unclear. Temporal lobectomy was done, but the tumor was left around the perforators of the middle cerebral artery. Hematoxylin and eosin staining showed typical glioblastoma with high cellularity, mitosis, pseudopallisading and vascular proliferation. The tumor cells were immunohistochemically negative for isocitrate dehydrogenase (IDH)1-R132H indicating glioblastoma, IDH-wild type. The patient received chemotherapy and radiation therapy, and was discharged from the hospital. Six months later, local regrowth and spinal dissemination were found. Despite additional chemotherapy and radiation therapy, the tumor became uncontrollable and the patient succumbed. Only 15 cases of solitary PLGs have been reported previously. The IDH status of these tumors have not been investigated in most cases; however, pathological grading varies from lower to higher grade glioma. Together with the pathological difference of astrocytic or oligodendrocytic tumors, solitary PLGs may develop due to various gene alterations similar to intra-axial gliomas.

Characterization of cerebral salt wasting after subarachnoid hemorrhage model induced by endovascular puncture.

Cerebral salt wasting (CSW) frequently occurs concomitantly with an aneurysmal subarachnoid hemorrhage (SAH). CSW induces excessive natriuresis and osmotic diuresis, and reduces the total volume of blood. We previously reported that a rat model with SAH induced by endovascular puncture (EP) exhibited CSW. Therefore, we investigated the relationship between the spread of bleeding in the subarachnoid space and the intensity of CSW. We also investigated the development of CSW in different SAH models. SAH was induced by EP or by 0.3 mL of blood injection (BI) into the cisterna magna. To evaluate the occurrence of CSW, urine was cumulatively collected at the onset of SAH to 6 h later and analyzed for sodium (Na) excretion. SAH was classified from grade 1 (no bleeding) to grade 4 (severe bleeding) based on the spread of bleeding in the subarachnoid space. In the EP model (SAH grade > 2) as the SAH grade increased, the volume of urine and Na excretion also significantly increased. Although the BI model rats exhibited SAH of grade 4, the volume of urine and Na excretion did not change. Therefore, our conclusion is that the spread of bleeding in the subarachnoid space may not cause CSW.

Response to Letter by Wong and Poon

Response: We are very pleased to see that much thought and attention is being given to this area of treatment, and we would like to provide the following as a response. Our first response is that for the past 20 years, we have been administering hydrocortisone at 1200 mg/d to patients with aneurysmal …

Is cerebral salt wasting after subarachnoid haemorrhage caused by bleeding

Background Cerebral salt wasting (CSW) frequently occurs concomitantly with aneurysmal subarachnoid haemorrhage (SAH). CSW induces excessive natriuresis and osmotic diuresis, and reduces total blood volume. As a result, the risk of symptomatic cerebral vasospasm is elevated. Therefore, we investigated the relationship between the amount of bleeding, the intensity of CSW, and the diameter of the middle cerebral artery (MCA).