Hyponatremia in the Patient With Subarachnoid Hemorrhage

Ellen Dooling; Chris Winkelman


J Neurosci Nurs. 2004;36(3) 

In This Article

Cerebral Salt Wasting

CSW is a transient phenomenon in which kidneys are unable to conserve sodium. CSW leads to serum hyponatremia and hypovolemia as a result of SAH or other intracranial disease (Harrigan, 2001). CSW was first described in 1950, after symptoms of volume contraction and decreased sodium in neurological patients were noted (Peters, Welt, Sims, Orloff, & Needham, 1950). Since that initial observation, clinical and experimental data suggest that patients with SAH and other intracranial diseases experience hypovolemia rather than the euvolemia or hypervolemia of SIADH. Derangements of sympathetic nervous system stimulation of kidneys, production of digoxin-like peptides, and excess natriuretic factors have all been implicated in CSW.

A surge of sympathetic nervous system (SNS) hormones, norepinepherine and epinephrine, may cause renal sodium excretion. Stimulated by the stress response during brain injury, the SNS hormones stimulate both arterial and venous contraction, leading to increased preload, inotropy, and systemic blood pressure. The kidneys could respond to these cardiovascular changes with a pressure-induced natriuresis (Singh et al., 2002). This neural mechanism of hyponatremia is not the most likely scenario, though it may be a contributing factor. Although a pressure natriuresis is associated with an acute stress response, ongoing sodium excretion is less likely with sustained SNS stimulation in the presence of hypovolemia unless renal vasodilation is also sustained. It may be that the initial brain injury and sympathetic response may, instead, contribute to the development of CSW.

Two additional molecular factors have been implicated in the onset of hyponatremia. One potential factor causing CSW is a digoxin-like peptide that has been found in the plasma of a series of patients with SAH. How this peptide causes renal sodium excretion has yet to be to be elucidated, but it was determined that infusing digoxin-specific antibodies directly into the ventricles of the rat brain, blocks the central nervous system response to natriuresis (Wijdicks, Vermulean, van Brummelen, den Boer, & van Gijn, 1987).

A second molecular factor is endogenous natriuretics. Both atrial and brain (or b-type) natriuretic factors have been linked to CSW. Both factors lead to natriuresis or excretion of sodium with subsequent serum hyponatremia. Renal sodium excretion, in turn, leads to a concurrent fluid diuresis and hypovolemia.

Atrial natriuretic peptide (ANP) was the first natriuretic suggested to have a potential role in causing hyponatremia in patients with SAH. It is a polypeptide that is produced in the atria of the heart and activated when the atrial stretch receptors become stimulated in response to hypervolemia, increased sodium, and/or an expanded preload (Braunwald et al., 2001; Sviri, Feinsod, & Soustiel, 2000). Atrial natriuretic peptide results in large amounts of sodium and fluid excretion. The increased excretion of urine occurs due to inhibition of reabsorption of sodium in the collecting duct (Palmer, 2000). At the same time sodium is being blocked from returning to the bloodstream, there is an increased glomerular filtration rate contributing to natriuresis and diuresis. In addition, with the increased glomerular filtration rate, the secretion of renin and aldosterone diminish (Braunwald et al.). The reason for the decrease in aldosterone release is twofold. Its release from the adrenal gland is directly inhibited, and then there is an indirect inhibition due to the suppression of renin release from the juxtaglomerular kidney cells (Palmer). It is this decrease in circulating aldosterone levels that is thought to prevent potassium wasting from occurring in conjunction with the sodium loss (Palmer).

Three studies support the role of ANP in CSW in patients with SAH. Kurokawa et al. (1996) measured daily sodium and water balance and concentrations of ANP, ADH, and plasma renin activity (PRA) in 31 patients with aneurysmal SAH. Because ANP levels can be affected by arrhythmias, they excluded patients experiencing arrhythmias and also those with heart failure or kidney dysfunction. Their results showed a consistent abnormal increase in ANP values up until 14 days after the initial SAH; hyponatremia occurred in nine of these patients. ADH levels also increased within the first few days, but the rise was short-lived. Because sodium levels were low despite adequate sodium and fluid intake in the setting of elevated ANP, the authors concluded that ANP induced natriuresis in their subjects.

Wijdicks et al. (1991) also found elevated levels of ANP in a study done on 14 patients who had experienced SAH. In more than 50% of these patients, there was a sudden increase in ANP level followed by natriuresis with an accompanying net sodium loss. There was also a rise in ANP within the first few days of hospitalization. The researchers reasoned that fluid loss did not occur since there was a coinciding rise in vasopressin. During the natriuretic period, the vasopressin levels were low. Isotani et al. (1994) found similar results. Despite the correlation found between ANP levels and hyponatremia, no explanation of the increased levels of ANP has been established.

Two additional studies did not show a significant correlation between decreased sodium levels and elevated ANP plasma concentration, leading to a suggestion of an alternative contributor to CSW (Diringer, 2001; Okuchi et al., 1996).

Brain natriuretic peptide (BNP), a polypeptide consisting of 32 amino acids, is similar to ANP in many ways (Tomida, Muraki, Uemura, & Yamasaki, 1998). In addition to being found in the atria of the heart and stored in the myocardium of the heart's ventricles, it is stored in the hypothalamus of the brain (Braunwald et al., 2001; Sviri et al., 2000). Its action is similar to ANP; it is a potent vasodilator, causes sodium and fluid excretion, and leads to reduced circulating levels of renin and aldosterone (Braunwald et al.). While it is well known that increased load on the ventricles can result in the release of BNP (Tomida et al.), there is no definitive explanation for its activation after SAH. Palmer (2000) suggested that it may be released as a protective measure for increased intracranial pressure, while Tomida et al. theorized that it may be activated as a stress response to surgery or the intensive care setting or as a result of damage in the hypothalamic region. Sviri et al. reported that unlike the variable findings analyzing the relationship of ANP to hyponatremia, studies measuring levels of BNP have demonstrated more consistent results.

Tomida et al. (1998) studied 18 patients with aneurysmal SAH and found that hyponatremia occurred in 11 patients with a corresponding rise in BNP levels. The rise that occurred between days seven and nine that resulted in natriuresis was not, however, statistically higher than in the patients with normal sodium levels. Despite this, it was concluded that BNP was more than likely responsible for the hyponatremia that resulted from the natriuresis and diuresis after SAH.

Sviri et al. (2000) also found elevated levels of BNP after SAH with the greatest rise between days one and three and seven and nine. While their study focused on the association of BNP levels with cerebral vasospasm, their findings were supportive of SAH-induced elevated levels of BNP and associated hyponatremia. Additional studies of small samples support these findings (Berendes et al., 1997; Nelson, Seif, Maroon, & Robinson, 1981). One study with contradicting results showed no difference between BNP levels in 20 patients with SAH compared to five normal subjects (Isotani et al., 1994). However, this may be the result of different procedures and clinical conditions of patients compared to the other investigations (Tomida et al., 1998).

Thus, three humoral and one neural derangement mechanisms have been suggested as possible causes of CSW. Data support the role of natriuretic factors, particularly BNP, as a mechanism for CSW; further investigation is needed in the role of digoxin-like peptide and sympathetic nervous system stimulation as well as the interaction between these four derangements. Determining the mechanisms of CSW may lead to targeted treatment. To explore current treatment approaches, a case study is presented.