Cerebral thrombosis

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 intracraneal 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 W 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. [Neurol Res 2005; 27: 418-422]

Keywords: Cerebral salt wasting syndrome; hyponatremia; natriuresis; subarachnoid hemorrhage; syndrome of inappropriate antidiuretic hormone secretion

INTRODUCTION

Subarachnoid hemorrhage (SAH) is a neurologie catastrophe that may give rise to a long list of neurologic and systemic complications. A number of systemic medical complications leading to approximately 23% of deaths after SAH have been reported in large clinical series1,2, comparable to the death rate from neurologic complications3.

Non-neurologic complications most commonly occur in patients with poor clinical status and in patients with large deposits of subarachnoid blood. In this group, conditions such as systemic hypertension, electrocardiogram disturbances, morphologic subendocardial damage, gastrointestinal bleeding, pulmonary edema, pneumonia, acute respiratory distress syndrome, hyperglycemia, deep venous thrombosis and pulmonary edema are included, among others4,5.

Fluid and electrolyte disturbances are common in the perioperative period after rupture of the aneurysm. The most common abnormality is hyponatremia, which can be seen in up to 35% of patients with SAH, most commonly between day 2 and day 10 after the initial ictus6,7, and most commonly in certain specific aneurysm locations such as the anterior communicating artery and the ophthalmic artery8.

This phenomenon is most relevant and involves several implications: alterations in the state of awareness, possible seizures and exacerbations of cerebral edema9,10. The exact pathophysiology of this phenomenon is unknown11-14 but, in general, it is considered that it may be due to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) or to cerebral salt wasting syndrome (CSWS)15-23.

CSWS can be defined as the clinical picture caused by hyponatremia due to excessive loss of sodium into the urine without an increase in total systemic volume related to acute or chronic damage of the central nervous system24-32. So far, the pathophysiology of this condition is unknown; the natriuretic atrial factor or natriuretic atrial peptide seems to play an important role in central and peripheral sodium regulation and its inappropriate or unregulated secretion is a compelling, yet not proven hypothesis as a causal factor contributing to CSWS. There is no single laboratory test that can establish the diagnosis of CSWS, consequently, the clinical differentiation of natriuresis and SIADH is very important, especially as the treatment of one is the opposite of the other32-38.

MATERIALS AND METHODS

From December 1993 to December 2001, we treated 292 patients with 324 intracranial saccular aneurysms. In 67 cases the aneurysm originated from the anterior communicating artery (67 patients) and in 42 from the ophthalmic artery (40 patients). Sixty-five of the patients with aneurysm of the anterior communicating artery (97%) and 28 of those with ophthalmic aneurysms (70%) presented with SAH.

Among the population of patients with SAH after rupture of a saccular aneurysm of the anterior communicating and the ophthalmic artery (n=93), we found eight cases (8.6%) of hyponatremia due to CSWS. The general epidemiologic and clinical features of these patients are found in Table 1. In all of these eight cases, the patient was admitted with signs of aneurysmal SAH proven with CT scan followed by cerebral angiogram, in which the ruptured aneurysm was revealed; all the patients were taken to the operating room and the aneurysm was successfully excluded from the circulation. Rupture of the aneurysm was considered to be day 0.

Table 2 describes the timing of hospital admission, clipping of the aneurysm, discharge or death. In no case was there evidence of rebleeding. All patients were treated perioperatively in the intensive care unit. None of the patients showed persistent hydrocephalus that would need a permanent shunt system, but in cases 1, 3 and 4 a transient ventriculostomy was performed in order to alleviate ventricular dilatation seen in the initial CT; no complications related to this procedure were observed.

A control angiogram was performed when considered necessary to diagnose angiographie vasospasm or when the patient agreed for clip control. Clinical vasospasm findings were noted in two patients (cases 4 and 5), and angiographic vasospasm in five cases (cases 1, 2, 4, 5 and 8); except in case 4, all were successfully treated with triple-H therapy.

RESULTS

In these eight patients, and only in those, hyponatremia was detected (serum sodium under 135 mEq/l) at some time of the patients course. It was characteristically persistent (in all cases more than 24 hours) and did not subside spontaneously or with moderate fluid restriction; it was accompanied by significant natriuresis, signs of dehydration, central venous pressure and/ or decreased pulmonary artery wedge pressure and elevated serum osmolality. These and other hydroelectrolyte and hemodynamic features on which we have based the diagnosis of CSWS are described on Table 3.

In two cases, levels of antidiuretic hormone were measured by radioimmunoassay and found to be normal. Likewise, in two cases aldosterone was measured, revealing below normal levels in both cases. In three cases, natriuretic atrial factor levels, measured by radioimmunoassay, were found to be above normal. Unfortunately, due to processing conditions, results of these studies were reported in all cases when the hyponatremia had already been treated and resolved. Thyroid and renal function were tested and found normal in the eight patients. The sodium disturbance occurred between day 3 and day 10 in all cases, in six of them in day 7 or 8 as described in Table 4.

In the first two cases, signs of hyponatremia were initially attributed to inappropriate secretion of antidiuretic hormone and were treated for either 12 or 18 hours with volume depletion39. In no case did the clinical picture improve. At that point the diagnosis of CSWS was considered and treatment similar to that of the six remaining cases, in which it had been recognized since the onset of the clinical picture, was initiated. The specific treatment for CSWS was to increase volume delivery according to the characteristics of the patient; in cases 4 and 5, volume was primarily given to increase mean blood pressure to treat the clinical vasospasm, based mainly on the neurologic condition and the pulmonary artery wedge pressure. In the six remaining cases 1 N mixed solution or Hartmann solution at an infusion rate of 50 ml/kg/day was given. In cases 1, 4 and 6, anemia was found in addition to CSWS for which red blood cell concentrates were used to get at least 12 mg% hemoglobin. Crystalloid administration continued for the necessary time until two consecutive daily measurements of serum Na were equal or greater than 130 mEq/l. Except for case 4, none of the remaining cases required more than 72 hours of treatment to correct hyponatremia. No treatment-related complications were found.

DISCUSSION

One of the goals of perioperative medical treatment of SAH is to prevent, diagnose and treat the many problems to which the patient is susceptible. The list of central nervous system diseases capable of creating hydroelectrolytic disturbances is very long and, besides rupture of a saccular aneurysm, it includes meningitis, neoplasias, head trauma, surgical manipulation in the pituitary region and the hypothalamus and others. The abnormality in fluid and electrolyte homeostasis is a common phenomenon in aneurysmal SAH. Hyponatremia is the most common of these abnormalities and its occurrence has been reported in variable indexes, depending on which serum sodium level is considered as abnormal, as well as on how long the disturbance lasts, in up to 50% of patients with SAH.

Its etiology is not clear; however, when it is associated with dehydration signs, it frequently is correlated with high levels of natriuretic atrial factor. The correct management of this hydroelectrolyte disturbance in the broad context of treatment of patients with aneurysmal SAH is of the greatest importance: the condition can severely aggravate the general clinical picture and its occurrence and inadequate management can severely potentiate the disturbances after adrenergic discharge and vasospasm. In patients with aneurysmal SAH, the chronic causes of hyponatremia (psychogenous polydypsia, Bartter syndrome, adrenal failure, etc.) can usually be diagnosed with the clinical history.

The two best-known causes of acute onset hyponatremia related to aneurysm rupture are: syndrome of inappropriate antidiuretic hormone secretion and salt-losing cerebral syndrome. The treatment of each one of these conditions is so different that the wrong diagnosis usually leads to a severe worsening in the condition of the patient. The differential diagnosis is based on the clinical, hydroelectrolytic and hemodynamic clinical features: even though hyponatremia is found in both conditions, in the case of SIADH it is secondary to hemodilution due to volume increase in the intravascular compartment while in CSWS there is lost of urinary sodium and diminished intravascular volume.

In Table 5 the main differences between the two conditions are shown. Measurement of antidiuretic hormone level or natriuretic atrial factor is not essential for establishing the diagnosis of these conditions and its usefulness for treatment is debatable. Therefore, the importance of suspecting the diagnosis and recognizing the clinical condition on sound grounds as well as timely and proper management cannot be stressed enough.

CONCLUSIONS

Cerebral salt wasting syndrome occurring in some patients with aneurysmal SAH, more commonly related to certain specific anatomic locations of the ruptured aneurysm, characterized by hyponatremia with natriuresis and dehydration responds to sodium replacement therapy and fluids and can be diagnosed and treated based on the clinical, hydroelectrolytic and hemodynamic course of the patient.

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Francisco R. Revilla-Pacheco, Tenoch Herrada-Pineda, Mauro Loyo-Varela and Marcos Modiano-Esquenazi

Department of Neurosurgery, The American British Cowdray Medical Center, Mexico City, Mexico

Correspondence and reprint requests to Francisco R. Revilla-Pacheco, MD, Department of Neurosurgery, The American British Cowdray Medical Center, Mexico City, Calle Sur 132 No. 108-101, Colonia Las Américas, Ciudad de México, 01120 México, [frevilla@attglobal.net] Accepted for publication September 2004.

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