We found that 8.7% of children hospitalized for acute surgical management of intracranial malignant neoplasms had a diagnosis code for hyponatremia. Location of the tumor in deep brain structures and obstructive hydrocephalus were associated risk factors, portending a more than 2-fold increase in the odds of hyponatremia. Hyponatremia was associated with more procedures and more complications.
The mechanisms leading to hyponatremia in patients with intracranial neoplasms may be multifactorial. Hyponatremia may be more likely to occur with tumors in deep brain locations due to the manipulation of neurons pivotal in the control of vasopressin and natriuretic peptides, either from the tumor or during neurosurgical treatment. Neurons in the supraoptic and paraventricular nuclei of the hypothalamus control the release of vasopressin, and damage to these neurons may be one cause of SIADH. Manipulation of the neurohypophysial pathways may also result in increased secretion of natriuretic peptides, which have been implicated in the cerebral salt-wasting syndrome.16
Previous smaller studies found trends toward more severe and higher rates of sodium perturbations with suprasellar, thalamic, and hypothalamic lesions, and during surgeries involving manipulation of the neurohypophysis.12,14
Increases in intracranial pressure have been associated with increased release of vasopressin, and SIADH10
and may account in part for the increased incidence of hyponatremia among patients with obstructive hydrocephalus. Previous studies have linked hydrocephalus in children with intracranial neoplasms to adverse long-term neurological deficits and disability.13,17,18
However, no studies have evaluated long-term sequelae of hyponatremia alone or associated with obstructive hydrocephalus in pediatric patients with brain tumors.
Hyponatremia can cause seizures, encephalopathy, and cerebral edema, which can all lead to secondary brain injury.20
Thus, hyponatremia may in part account for increased morbidity in this group of patients, as evidenced by longer hospital stays, higher charges, increased numbers of procedures, and more discharges to intermediate-care facilities. However, development of hyponatremia could also reflect more advanced disease, hydrocephalus, or tumor location; our study cannot ascertain whether hyponatremia reflects more complicated disease or accounts in part for worse brain injury. Other studies have noted increased use of hospital resources and worse outcomes associated with hyponatremia. Al-Zahraa et al.1
evaluated children with various neurological diseases and found that hyponatremia was associated with longer hospital stays and poor neurological outcome. Sherlock et al.19
reported longer hospital stays among adult neurosurgical patients with hyponatremia. Additionally, Moritz and Ayus15
reported that children with intracranial neoplasms and those who had undergone any neurosurgical procedure are more likely to develop encephalopathy if hyponatremia was present.
Previous studies of children with intracranial neoplasms have suggested that delayed diagnosis is associated with worse neurological outcomes.22
Our study found an association between hyponatremia and both admission from the ER and Medicaid insurance. Admission from the ER may suggest the presence of more severe symptoms and greater disease progression. Similarly, patients with Medicaid insurance have been shown to delay seeking medical attention and to use the ER for care.21
Children with Medicaid insurance have higher use of emergency and inpatient services for many common pediatric problems.3,6,11
The association of these factors with hyponatremia may reflect more advanced disease from decreased access to care.
Our study benefited from a large sample size of 2343 weighted cases, which encompasses a large portion of the approximately 4000 new cases of pediatric intracranial neoplasms estimated to occur each year.5
However, our study is limited to retrospective analysis of discharge data and diagnosis codes. Completeness of coding cannot be assured in our data; however, procedures such as CT and MRI studies, which would be expected during the hospitalization for intracranial tumor resection, did not vary between groups. The ICD-9-CM code for hyponatremia does not specify the concentration, so the severity and range of sodium derangement are unknown. The number of occurrences of hyponatremia among individual patients is also not available from this deidentified data set. Additionally, our estimate of just under 9% occurrence of hyponatremia may be imprecise because the completeness of coding is uncertain. However, the association of hyponatremia and potential complications confirms the need to monitor sodium concentrations and urine output in these patients.
The ICD-9-CM codes are not specific for tumor type, and the KID data are deidentified, so review of individual patient data is not possible. Our initial cohort was selected based on patients with codes specifically for malignant lesions (ICD-9 CM 191.0–191.9); however, the accuracy of this coding regarding malignancy may be imprecise, as evidenced by the simultaneous coding of benign neoplasm of the brain (ICD-9 CM 225.0) in 3 of our patients. We are unable to determine whether histological type and grade of tumor play a role in the development of hyponatremia.
We do not have data on the timing of hyponatremia in relation to admission or tumor resection; however, we did attempt to limit one known cause of hyponatremia by excluding patients who received chemotherapy during the same admission. We cannot evaluate for clinical therapies such as hypotonic fluid administration or diuretic use, which may cause or exacerbate hyponatremia. Additionally, patients with intracranial neoplasms are frequently treated with high-dose corticosteroids in the perioperative period to decrease brain edema, and we have no information on the use, duration, or dose in our subset of patients. The different types of corticosteroids have varying degrees of mineralocorticoid effects that would serve to increase serum sodium. Additionally, glucocorticoids are known to inhibit vasopressin release,2
and patients with adrenal insufficiency have been found to have hyponatremia and SIADH.7
The interactions between corticosteroids and sodium are complex, and we are not aware of studies evaluating the impact of corticosteroids on hyponatremia in this population.