Hypervolemic therapy prevents volume contraction but not hyponatremia following subarachnoid hemorrhage.

Hyponatremia is common following subarachnoid hemorrhage and has alternatively been attributed to either the inappropriate secretion of antidiuretic hormone or natriuresis causing intravascular volume contraction. We prospectively studied body sodium and intravascular volume regulation in 19 patients, beginning within 3 days after acute aneurysmal subarachnoid hemorrhage occurred, in order to determine the impact of hypervolemic therapy on both hyponatremia and volume contraction and to ascertain whether humoral factors account for hyponatremia. Serial measurements of plasma arginine vasopressin, atrial natriuretic factor, renin activity, aldosterone, and catecholamines were correlated with body sodium and fluid balance, change in blood volume, serum sodium concentration, and osmolality. Six patients (32%) developed hyponatremia, but only 2 had a negative sodium balance. In most patients, levels of atrial natriuretic factor were elevated, while plasma renin activity and aldosterone concentrations were generally suppressed. Plasma arginine vasopressin levels were not suppressed during hypo-osmolality and did not correlate with serum osmolality in hyponatremic patients. Only 1 patient had a decrease in blood volume, which was associated with marked rises in aldosterone and plasma renin activity, but normal serum sodium and plasma atrial natriuretic factor levels. We conclude that following subarachnoid hemorrhage: (1) Hypervolemic therapy prevents volume contraction but not hyponatremia, (2) humoral factors may favor both sodium loss and water retention, and (3) arginine vasopressin regulation is disturbed and may contribute to hyponatremia.     

Atrial natriuretic factor and salt wasting after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The causes of volume depletion and hyponatremia after subarachnoid hemorrhage are not fully understood but may be in part due to natriuresis or "cerebral salt wasting." Because previous studies using infrequent hormone sampling have given inconsistent results, we determined if elevations in atrial natriuretic factor concentrations preceded negative sodium and fluid balances. METHODS: We measured diurnal atrial natriuretic factor and vasopressin concentrations and sodium balance for 5 days in 14 consecutive patients after aneurysmal subarachnoid hemorrhage. RESULTS: Plasma concentrations of atrial natriuretic factor on admission were elevated in subarachnoid hemorrhage patients (mean +/- SD 106 +/- 59 pg/ml) compared with acutely ill controls (39 +/- 30 pg/ml). In eight patients, high peak concentrations of atrial natriuretic factor, greater than 300 pg/ml or a twofold increase above baseline, were followed by natriuresis and a negative sodium balance. Three patients, two of whom became hyponatremic, developed cerebral infarcts after natriuresis. Vasopressin concentrations were slightly elevated just after hemorrhage but subsequently declined to normal values. CONCLUSIONS: A markedly increased atrial natriuretic factor concentration precedes natriuresis in some patients and, with other abnormalities of water handling possibly including a relatively diminished vasopressin concentration, may cause volume depletion. Patients with natriuresis appear to be at increased risk for delayed cerebral infarction after subarachnoid hemorrhage.     

Hyponatremia and cerebral infarction in patients with ruptured intracranial aneurysms: Is fluid restriction harmful?

We studied retrospectively the relationship between hyponatremia and cerebral infarction in 134 consecutive patients with aneurysmal subarachnoid hemorrhage. In 44 patients sodium levels fell below 135 mmol/L on at least two consecutive days between the second and the tenth day after the hemorrhage. Twenty-five of these patients fulfilled the criteria for the syndrome of inappropriate secretion of antidiuretic hormone. Cerebral infarction developed in 27 of the 44 patients with hyponatremia and in 19 of the 90 patients with normal serum sodium levels (p less than 0.001). Cerebral infarctions were more often fatal in patients with hyponatremia (p less than 0.01). Twenty-six of the 44 patients had been treated with fluid restriction to correct the serum sodium levels, and infarctions developed in 21. Fluid restriction to correct hyponatremia appears to be potentially dangerous in patients with aneurysmal subarachnoid hemorrhage.     

Effect of fludrocortisone acetate in patients with subarachnoid hemorrhage

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.     

Pathogenesis of hyponatremia observed in the treatment of acute subarachnoid hemorrhage]

The cause of hyponatremia following subarachnoid hemorrhage (SAH) has been understood as an inappropriate secretion of antidiuretic hormone (SIADH). Whereas, water restriction for the management of this condition sometimes induces a severe dehydration, resulting in vasospasm. To clarify the pathogenesis of hyponatremia following SAH, we measured the daily sodium and water balance with the plasma concentration of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), and plasma renin activity (PRA) in seventeen cases after subarachnoid hemorrhage. Although the patients received an adequate amount of fluid (more than 4080ml/day; daily average in seventeen cases) and sodium (more than 277 mEq/day; daily average in seventeen cases), eight out of the seventeen cases showed transient hyponatremia of a slight degree beginning on 8.8 days after SAH. ANP values were elevated markedly in fifteen out of the seventeen cases, remaining high during the first two weeks following SAH. ADH values were elevated remarkably in eight out of the seventeen cases. However, these values declined immediately to a normal range within two days following SAH. PRA were increased or came within the normal range, suggesting the lack of water retention. Overall sodium balance and water balance did not differ significantly between hyponatremia cases and normonatremia ones, whereas, sodium balance in acute phase was significantly negative, associated with marked natriuresis in patients with hyponatremia. These correlations suggested that hyponatremia after SAH is the result of natriuresis by an increased ANP rather than ADH. In conclusion, a greater replenishment of water and sodium is required to avoid hyponatremia with dehydration. This technique may be helpful for the prevention of vasospasms following SAH.     

The effect of fludrocortisone acetate on plasma volume and natriuresis in patients with aneurysmal subarachnoid hemorrhage

In order to prevent hypovolemia fludrocortisone acetate treatment was started on admission in 39 consecutive patients with CT evidence of subarachnoid hemorrhage. In 28 patients an aneurysm was proven or probable, and in 21 of these the effects of fludrocortisone acetate on sodium balance and on plasma volume could be studied. In the first five days plasma volume decreased more than 10% in four patients, decreased less than 10% in five and increased in 12. The cumulative sodium balance measured over five days was negative in seven of the 21 patients. Plasma renin values were measured in 15 of the 21 patients and also in stored samples of 18 patients who were not treated with fludrocortisone acetate. Plasma renin values were less high in patients treated with fludrocortisone acetate, regardless of the presence of a negative sodium balance. In three of the 39 patients signs of pulmonary edema developed, and low serum potassium values were observed in four of the 21 patients. In comparison with previous studies, these findings suggest that fludrocortisone acetate is an effective method of decreasing the incidence of volume depletion and negative sodium balance.     

Significance of plasma atrial natriuretic peptide measurement during the management of hyponatremia in neurosurgical patients]

We have examined the total number of admitted cases to clarify the pathogenesis of hyponatremia during the management of neurosurgical patients. We experienced 32 cases of hyponatremia during the past year by measuring the sodium balance and atrial natriuretic peptide (ANP) level. According to these two factors, we divided the cases into three groups. The first group shows normal ANP levels in spite of hyponatremia. Low administration of the sodium was thought to be the cause in these cases. The second group shows the elevated ANP levels with a positive sodium balance. Elevated circulatory volume due to the inadequate level of antidiuretic hormone and mild heart and/or kidney failures cause these conditions. Water restriction and/or diuresis were effective methods in the management of the cases. The last group shows the elevated ANP levels with a negative sodium balance. There is a statistically significant negative correlation between sodium balance and the ANP level. Marked natriuresis due to the elevated ANP causes the decrement of the circulatory volume in these cases. Pathogenesis of the last group is very important in the management of neurosurgical patients in an acute state, especially in subarachnoid hemorrhage cases. The decrement of the systemic circulatory volume would jeopardize the patient's neurological condition. In this group, water restriction that has been commonly recommended is contraindicated. Satisfactory water and sodium replenishment seems to be the best recommended treatment for this group.     

急性脑卒中并发低钠血症的临床意义及机制探讨

目的 探讨急性脑卒中并发低钠血症的机制及临床意义。方法 306例急性脑卒中患者入院后24 h内抽取外周静脉血5 ml,取血清1.5 ml,用全自动生化仪监测血清钠,治疗1周后复查。结果 24 h内有70例发生低钠血症,占22.9％,1周后发生低钠血症者66例,占21.6％,其中脑出血最多,其次蛛网膜下腔出血,脑梗塞最少(P<0.005)。结论 急性脑卒中并发低钠血症与卒中部位和性质有关。急性脑卒中患者并发低钠血症时预后不良。     

Suprasellar and intraventricular blood predict elevated plasma atrial natriuretic factor in subarachnoid hemorrhage.

Following subarachnoid hemorrhage, the plasma concentration of atrial natriuretic factor is elevated and appears to be independent of atrial stretch. While the hypothalamus and circumventricular organs contribute to sodium and intravascular volume regulation, their influence on atrial natriuretic factor is not known. We tested the hypothesis that, following subarachnoid hemorrhage, suprasellar cisternal blood, intraventricular blood, or ventricular enlargement would be associated with elevated plasma levels of atrial natriuretic factor. Computed tomograms of 26 patients performed less than or equal to 3 days after hemorrhage were analyzed to determine the presence of suprasellar or intraventricular blood and enlargement of the third or lateral ventricle. These results were correlated with the plasma atrial natriuretic factor and serum sodium concentrations. The initial atrial natriuretic factor concentration was elevated and was higher in patients with suprasellar or intraventricular blood than in those without (suprasellar: 131 +/- 20 and 54 +/- 10 pg/ml, respectively; intraventricular: 137 +/- 25 and 84 +/- 31 pg/ml, respectively). The atrial natriuretic factor concentration remained higher over the week following hemorrhage in patients with suprasellar blood than in those without (127 +/- 16 and 68 +/- 12 pg/ml, respectively). The atrial natriuretic factor concentration was not correlated with hyponatremia (125-134 meq/l) or age-corrected ventricular size. Hyponatremia did not correlate with the presence of intraventricular or suprasellar blood. Our data suggest that suprasellar and intraventricular blood disturb hypothalamic function, resulting in an elevated plasma atrial natriuretic factor concentration. The presence of a direct relation between atrial natriuretic factor and hyponatremia remains unclear.     

Management of sodium abnormalities in patients with CNS disease.

The CNS plays an integral role in the neuroendocrine regulation of sodium and water homeostasis. Therefore, disturbances of this function are common in patients with CNS disease. The body's sodium and water content are tightly regulated in order to maintain normal osmolality and intravascular volume. Complex neural, humoral, and renal mechanisms integrate information regarding osmolality, intravascular volume, blood pressure, and intake of sodium and water. They act to modify intake and excretion of sodium and water and vascular tone. Most sodium abnormalities in patients with CNS disease result from altered water excretion secondary to disturbed release of antidiuretic hormone (ADH). Insufficient release is seen with lesions in or near the optic chiasm and pituitary gland and results in diabetes insipidus (DI). DI is common following surgery or trauma in this region and care must be exercised in treating these patients because of the potentially variable and transient nature of the disturbance. The syndrome of inappropriate release of ADH is seen in a wide variety of CNS disorders and produces a dilutional hyponatremia. Symptomatic hyponatremia should be managed aggressively with diuretics and hypertonic saline followed by fluid restriction. However, very rapid correction or overcorrection should be avoided. In some patients, especially those with acute subarachnoid hemorrhage, disturbed sodium regulation appears to contribute to hyponatremia. Patients with subarachnoid hemorrhage and hyponatremia should not be fluid restricted, because of the risk of exacerbating vasospasm, but treated with large volumes of isotonic saline.     

Systemic Complications Following Aneurysmal Subarachnoid Hemorrhage

Many systemic complications follow aneurysmal subarachnoid hemorrhage and are primarily due to sympathetic nervous system activation. These complications play an important role in the overall outcome of patients. The purpose of this review is to provide an update on the diagnosis, pathophysiology, and management of systemic complications specifically associated with aneurysmal subarachnoid hemorrhage. Special focus has been made on systemic complications that occur more frequently in patients with aneurysmal subarachnoid hemorrhage compared to other stroke subtypes and in the neurocritical care patient population. These complications include neurogenic pulmonary edema, electrocardiographic changes, troponin elevation, neurogenic stunned myocardium, hyponatremia, and anemia.     

Changes of the plasma ketone body level and arterial ketone body ratio at the onset of mild aneurysmal subarachnoid hemorrhage

Abstract

Objective: The purpose of this study was to investigate the physiologic changes of ketone bodies in patients with aneurysmal subarachnoid hemorrhage. We tested the hypothesis that the plasma ketone bodies are associated with the vasoconstrictor and lipolysis effect of circulating catecholamine.

Methods: Twenty-four patients with mild aneurysmal subarachnoid hemorrhage and 18 healthy volunteers were enrolled in this study. We collected arterial blood samples immediately after admission and 30 days later to measure the levels of 3-hydroxybutyrate, acetoacetate, epinephrine and norepinephrine.

Result: At the onset of aneurysmal subarachnoid hemorrhage, the plasma ketone body (3-hydroxybutyrate + acetoacetate) level and the epinephrine and norepinephrine concentrations were significantly elevated, but the arterial ketone body ratio (acetoacetate/3-hydroxybutyrate) was significantly decreased compared with that of the control group. There was a negative correlation between the plasma ketone body level and the arterial ketone body ratio. There was a positive correlation between the plasma ketone body level and epinephrine level. Thirty days after admission, the ketone body, epinephrine and norepinephrine levels, as well as the arterial ketone body ratio, showed no significant differences between the patients and controls.

Conclusion: At the onset of mild aneurysmal subarachnoid hemorrhage, the plasma ketone body level was significantly increased, while the arterial ketone body ratio was significantly decreased.     

Decreased serum sodium levels predict symptomatic vasospasm in patients with subarachnoid hemorrhage

Background: Symptomatic vasospasm is a major cause of morbidity and mortality in subarachnoid hemorrhage patients. Hyponatremia and dehydration due to natriuresis after subarachnoid hemorrhage are related to symptomatic vasospasm. Therefore, most institutions are currently targeting euvolemia and eunatremia in subarachnoid hemorrhage patients to avoid complications. We retrospectively investigated the predictors of symptomatic vasospasm with respect to water and sodium homeostasis, while maintaining euvolemia and eunatremia after subarachnoid hemorrhage. Methods: We monitored changes in serum sodium levels, serum osmolarity, daily sodium intake, daily urine volume, and daily water balance for 14 days after subarachnoid hemorrhage. Outcomes were assessed using the modified Rankin scale at 1 month after subarachnoid hemorrhage. Results: Among 97 patients, 27 (27.8%) had symptomatic vasospasm. Patients with symptomatic vasospasm were older than those without symptomatic vasospasm; the occurrence of symptomatic vasospasm affected outcomes. Serum sodium levels were sequentially significantly decreased, but within the normal range from 1 day before the occurrence of symptomatic vasospasm. Serum osmolarity of the spasm group was lower than that of the non-spasm group. Conclusions: Symptomatic vasospasm occurs more often in older patients and affects outcomes. A decrease in serum sodium levels occurs a day before symptomatic vasospasm. This observation may help predict symptomatic vasospasm.     

Cerebral salt wasting syndrome in patients with aneurysmal subarachnoid hemorrhage

OBJECTIVE: Hydroelectrolytic disturbances are part of the complications of subarachnoid hemorrhage. Cerebral salt wasting syndrome (CSWS) must be considered when hyponatremia is associated with a decrease in circulating volume. We performed this study to determine the clinical characteristics and management paradigm of patients with serum sodium concentration abnormalities and aneurysmatic subarachnoid hemorrhage. METHODS: We analyzed retrospectively clinical and laboratory data from eight patients with subarachnoid hemorrhage due to rupture of an intracranial saccular aneurysm and cerebral salt wasting syndrome. Their course, as well as their clinical findings and treatment, are described. RESULTS: In eight patients, hyponatremia that lasted for more than 24 hours was detected (serum sodium under 135 mEq/l). The sodium disturbance occurred between day 3 and day 10 in all cases, in six of them in day 7 or day 8. The specific treatment for CSWS was to increase volume delivery according to the characteristics of the patient. Except for one case, none of the remaining patients required more than 72 hours of treatment to correct hyponatremia. No treatment-related complications were found CONCLUSION: Cerebral salt wasting syndrome, occurring in some patients with subarachnoid hemorrhage, is more commonly related to certain specific anatomic locations of the ruptured aneurysm, responds to sodium replacement therapy and fluids and can be diagnosed and treated based on the clinical, hydroelectrolytic and hemodynamic course of the patient. Further studies are needed to define the underlying mechanism of this condition.     

蛛网膜下腔出血钠代谢失衡的临床分析

目的分析蛛网膜下腔出血钠代谢失衡的原因、特点、处理方法及对预后的影响。方法回顾性分析58例蛛网膜下腔出血患者并发钠代谢紊乱的临床资料。结果低钠血症发生率22.41%,高钠血症为5.17%。发生钠代谢失衡的患者意识障碍发生率、脑血管痉挛发生率、病死率均高于正常血钠组,低钠血症发生脑血管痉挛的危险较其他2组高。结论蛛网膜下腔出血患者发生钠代谢失衡与疾病本身的病理生理机制有关。低钠血症的发生率高于高钠血症,高钠血症一旦发生很难纠正,应积极消除造成高钠血症的因素,以预防为主。低钠血症与脑血管痉挛相关,发生后要及时纠正,要注意补钠的方法与速度。     

Clinical significance of natriuretic peptides in patients with aneurysmal subarachnoid hemorrhage]

Hyponatremia and hypovolemia following aneurysmal subarachnoid hemorrhage (SAH) might be speculated by exaggerated secretion of natriuretic peptides and resulted ischemic sequela caused by cerebral vasospasm. We measured serum concentration of natriuretic peptides and investigated their influence on post-SAH hyponatremia. Among 49 patients of SAH, their plasma concentration of the natriuretic peptides (atrial natriuretic peptide: ANP and brain natriuretic peptide: BNP) were measured at the day of ictus and 7th day of SAH. The correlation between concentration of natriuretic peptides and location of aneurysm, severity of SAH, incidence of hyponatremia and symptomatic vasospasm were elucidated. The plasma concentration of ANP did not alter on admission and 7th day post SAH, whereas that of BNP increased in the patients with moribund SAH and those with ruptured A-com aneurysm. The initial increase of BNP following SAH could be attributed to direct damage of SAH on the hypothalamus. Hyponatremia and symptomatic vasospasm tended to occur in the patients who had persistent increase of plasma BNP concentration during one week post SAH. Therapeutic intervention to maintain normonatremia by fluid-management decreased occurrence of symptomatic vasospasm, even though patients with increased plasma BNP concentration. It might be concluded that increased secretion of BNP following SAH is caused by direct effect to the hypothalamus and prolonged hyper secretion of BNP resulted hyponatremia, hypovolemia and exaggerated symptomatic vasospasm.     

Hyponatremia and cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage]

We studied retrospectively the relationship between hyponatremia and cerebral vasospasm in 121 consecutive patients with aneurysmal subarachnoid hemorrhage. In 19 patients sodium levels fell below 130 mEq/l on at least two consecutive days. Hyponatremia developed at average 8.9 hospital day and lasted for 4.4 days. It was mild (126 to 130 mEq/l) in 15 patients, moderate (121 to 125 mEq/l) in 3 patients, and severe (116 to 120 mEq/l) in 1 patient. Cerebral vasospasm was evaluated by angiography, symptoms and CT finding. Angiographical vasospasm was found in 57 patients, symptomatic vasospasm in 38 patients and low density area on CT in 20 patients. Angiographical vasospasm developed in 15 of the 19 patients (78.9%) with hyponatremia, symptomatic vasospasm in 16 patients (84.2%), low density area on CT in 8 patients (42.1%), the difference being significantly high. (respectively, p < 0.01, p < 0.001 and p < 0.01 by chi-square test) Polyuria of 2500 ml or more immediately before the onset of hyponatremia developed in 14 patients (87.5%). When symptomatic vasospasm and hyponatremia coincided, there were only 4 patients in which symptomatic vasospasm was preceded by hyponatremia. So, it is difficult to predict the development of vasospasm from that of hyponatremia. This study found incidence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage to be significantly higher in patients who developed hyponatremia, which raised suspicion about the presence of dehydration. Hyponatremia with central origin generally remains asymptomatic, but it is important to treat positively when the pathology of cerebral vasospasm is taken into consideration.     

Critical care of intracerebral and subarachnoid hemorrhage

The acute management of primary intracerebral or aneurysmal subarachnoid hemorrhage requires a comprehensive approach involving stabilization of the patient, surgical intervention, and continued intensive care treatment of medical and neurologic complications. The are several causes of intracerebral hemorrhage (ICH), including hypertension, cerebral amyloid angiopathy, sympathomimetic drugs, and coagulopathies. More recently, use of thrombolytic agents in the treatment of acute ischemic stroke has increased the risk of ICH. Treatment of intracerebral hemorrhage is based on blood pressure control, and, in selected cases, surgical evacuation of clot. Patients with aneurysmal subarachnoid hemorrhage may experience rebleeding, symptomatic vasospasm, or hydrocephalus. Medical management in the intensive care unit with careful attention to fluid and electrolyte balance, nutrition, cardiopulmonary monitoring, and close observation for changes in the neurologic exam is vital. This review examines the diagnosis and intensive care management of patients with intracerebral or subarachnoid hemorrhage, and reviews some of the newer therapies for treatment of these disorders.     

Hyponatremia and cerebrovascular spasm in aneurysmal subarachnoid hemorrhage

BACKGROUND: Hyponatremia develops in approximately a third of patients with aneurysmal subarachnoid hemorrhage (SAH). Studies have been conflicting about the association between hyponatremia and cerebrovascular spasm (CVS). AIMS: To investigate whether hyponatremia can signal the onset of CVS. SETTINGS AND DESIGN: Retrospective chart review of all patients with SAH treated at a tertiary-care university hospital from January to May 2002. MATERIALS AND METHODS: 106 patients were included in the study. Serum sodium levels were recorded from days 1 to 14 of hospitalization. Hyponatremia was defined as serum sodium level<135 meq/l and a fall in sodium level of >4 meq/l from the admission sodium level. The presence of CVS was determined by transcranial doppler sonography. Patients were assigned to one of four groups based on the presence or absence of CVS and hyponatremia. STATISTICAL ANALYSIS: Student's t-test was used for comparison of means. A logistical regression model was constructed and odds ratios (OR) were calculated. RESULTS: 41 patients developed hyponatremia and 44 developed CVS. Among the 41 with hyponatremia, 22 (54%) had evidence of CVS, whereas among the 65 patients without hyponatremia, 22 (34%) had evidence of CVS (P=0.023). Among those with hyponatremia, the mean sodium drop was 7.9 meq/L in those with CVS compared to 7.0 meq/L in those without CVS (P=0.068). More than half of those with hyponatremia and CVS (13/22) developed hyponatremia at least a day before CVS was diagnosed. CONCLUSION: In patients with SAH, hyponatremia is associated with a significantly greater risk of developing CVS and may precede CVS by at least one day.