Management of Hyponatremia and Volume Contraction Alejandro A. Rabinstein • Nicolas Bruder Published online: 12 July 2011Ó Springer Science+Business Media, LLC 2011 Hyponatremia is the most common electrolyte imbalance seen in patients with aneurysmal subarachnoid Hydrocortisone Á Saline Á Sodium Á Vasopressin hemorrhage, occurring in one-third to one-half of patients.
Hyponatremia may be caused by cerebral salt wasting andby the syndrome of inappropriate secretion of antidiuretichormone or a combination of both. Limited data are avail- able describing hyponatremia treatment in subarachnoidhemorrhage patients. A Medline search was performed for Hyponatremia is the most common electrolyte imbalance in English-language manuscripts describing original research patients with aneurysmal subarachnoid hemorrhage (SAH), in the treatment for hyponatremia in patients with aneu- occurring in 30-50% of cases Hyponatremia is typ- ically defined as a serum sodium concentration < 135 articles were identified as followed: three testing fludro- mmol/L; some studies require these values to be present cortisone, two hydrocortisone, and one each for hypertonic over two consecutive days to satisfy the definition. Hypo- saline and 5% albumin. Data quality for treatment efficacy natremia typically occurs between days 3 and 14 after and safety were moderate for corticosteroid studies and low aneurysm rupture, but some series have noted that it usually or very low for hypertonic saline and 5% albumin. Avail- presents before the onset of vasospasm in patients who able data, although limited, support early treatment with corticosteroids to limit hyponatremia, with fludrocortisone The mechanisms that likely mediate the development of hyponatremia in SAH are cerebral salt wasting (CSW) andthe syndrome of inappropriate secretion of antidiuretichormone (SIADH) These two processes are dif-ficult to discriminate in clinical practice. Both CSW and Participants: Michael N. Diringer, Thomas P. Bleck, Nicolas Bruder, SIADH are associated with hypotonic hyponatremia and E. Sander Connolly, Jr., Giuseppe Citerio, Daryl Gress, Daniel inappropriately high urinary sodium content; however, they Hanggi, J. Claude Hemphill, III, MAS, Brian Hoh, Giuseppe Lanzino, are fundamentally different in their pathogenesis. CSW is Peter Le Roux, David Menon, Alejandro Rabinstein, Erich thought to be caused by increased secretion of natriuretic Schmutzhard, Lori Shutter, Nino Stocchetti, Jose Suarez, MiriamTreggiari, MY Tseng, Mervyn Vergouwen, Paul Vespa, Stephan peptides (likely mediated by activation of the sympathetic nervous system) leading to excessive excretion of sodiumin the urine. High intratubular sodium content secondarily provokes an osmotic gradient that drags water into the Department of Neurology, Mayo Clinic, 200 First Street,SW-Mayo W8B, Rochester, MN 55905, USA urine. Consequently, CSW is associated with intravascular volume contraction. Conversely, SIADH is caused byexcessive secretion of antidiuretic hormone leading to free water retention. As a result, SIADH is associated with Department of Anesthesiology and Intensive Care,Universite' de la Me'diterrane'e, Marseille, France normal or slightly expanded intravascular volume. Hence, assessment of intravascular volume is the best measure to This review was designed to explore evidence in the differentiate CSW and SIADH at the bedside [, ].
published literature for the treatment for hyponatremia in Discriminating between CSW and SIADH is important patients with aneurysmal SAH. Original research studies as they require different treatments. Fluid restriction, as were evaluated for treatment outcome and safety, with usually recommended in cases of pure SIADH, is danger- study design and quality of evidence assessed for each ous in patients with SAH and vasospasm , Therefore, in practice, this management strategy is dis-couraged. Furthermore, as CSW and SIADH may coexistin the same patient low circulating blood volume is quite prevalent in hyponatremic patients []. Carefulrepletion of volume losses and assessment of circulating A comprehensive electronic Medline literature search evaluating the role and treatment for hyponatremia in The most feared complication of hypotonic hyponatremia aneurysmal SAH was conducted to include English-lan- is cerebral edema. Seizures can occur in severe cases (usu- guage articles published through October 2010. Candidate ally with serum sodium concentrations < 125-120 mmol/ articles were identified by searching for papers that inclu- L). It is, however, difficult to determine the contribution of ded the key words subarachnoid hemorrhage and sodium.
hyponatremia to complications in individual patients. Fur- A separate search was performed using the key word thermore, the relationship between cerebral edema and brain subarachnoid hemorrhage and at least one of the following water content is complex and multiple factors, such as reg- additional key words: fludrocortisone, hydrocortisone, ulation of aquaporin-4 channels, may have a more mineralocorticosteroids, hypertonic saline, 3% sodium determinant role than serum sodium concentration and chloride, 3% sodium acetate, albumin, vasopressin antag- onists, and conivaptan. Titles and abstracts from candidate There is no conclusive evidence that hyponatremia articles were reviewed to select studies focused on man- influences the prognosis in patients with SAH. In a series of agement of hyponatremia in aneurysmal SAH. Among 298 patients, Qureshi et al. [] found that hypernatremia, these articles, selected articles were included if they but not the more common hyponatremia, was independently described original research treatment studies that provided associated with poor outcomes at 3 months. It is unclear information to address at least one of the following whether the association between poor prognosis and hypernatremia is related to a direct detrimental effect of What is the best time for initiation of treatment for hypernatremia or hypernatremia is a surrogate marker of hyponatremia (before hyponatremia occurs or once it other potentially causative or contributory factors (e.g., is established and, if the latter, using what sodium greater hypothalamic damage from the hemorrhage or more frequent use of osmotherapy). Similarly, in their analysis of What are the best treatment alternatives? 580 patients, Wartenberg et al. ] found that hypernatre- mia (defined as serum sodium concentration > 150 mmol/ What are the complications from treatment? L) had a greater prognostic impact than hyponatremia What are the complications from hyponatremia? (defined as serum sodium concentration < 130 mmol/L),although the association between hypernatremia and poor Selected studies were evaluated using the GRADE outcome was not independent and appeared related to the presence of intracranial hypertension. In these studies,hyponatremia was not associated with symptomatic vaso-spasm or delayed cerebral ischemia. The difference with older studies reporting an association between hyponatre-mia and higher risk of cerebral infarctions [] may be A total of 315 articles were identified using the key words explained by the past practice of fluid restriction and the subarachnoid hemorrhage and sodium, with 52 potentially more aggressive fluid replacement protocols used in the pertinent articles for the management of hyponatremia in more contemporary series. A recent study confirmed that aneurysmal SAH identified. The second search using the hyponatremia is not associated with poor outcome in most broader range of key words identified no additional patients with aneurysmal SAH, although an association was potentially pertinent articles that had not been found using found between late-onset hyponatremia (developing after the key word sodium. Among these studies, 8 studies were day 3 post-SAH) in poor-grade cases and higher risk of found to address at least one of the required questions listed cerebral infarction, probably indicating a greater vulnera- above [-One study focused predominantly on bility to volume depletion in these patients [ pathophysiology rather than on treatment and was therefore not included []. Among the remaining 7 studies, the Selected studies did not report evidence about compli- majority tested a corticosteroid (5 studies, 3 fludrocorti- sone, and 2 hydrocortisone), with one study testing aneurysmal SAH. The literature, however, suggests that hypertonic saline infusion and one 5% albumin.
hyponatremia is not associated with worse outcome in No studies were included among the selected articles patients with SAH who receive adequate volume and describing vasopressin receptor antagonists in SAH. Vaso- pressin receptor antagonists, such as conivaptan, have beenshown to be effective for the treatment of hyponatremia associated with euvolemic or hypervolemic conditions[]. Because vasopressin receptor antagonists increase Interpretations about prevention or correction of hypona- urine output and hypovolemia is common in hyponatremic tremia and natriuresis that can be made based on the patients with SAH, there is a concern that these drugs could available literature are limited by problems with the quality aggravate cerebral ischemia in these patients. The safety of the evidence reviewed. The quality of the evidence for and efficacy of these medications have not been properly the end point of prevention or correction of hyponatremia evaluated in clinical studies of SAH patients.
and natriuresis is summarized in Table. Table sum-marizes the quality of the evidence regarding the safety of tested therapies. Overall, the quality of the evidence ismoderate for corticosteroids with mineralocorticoid action Most studies evaluated preventive strategies and aimed for such that further research is likely to have an important maintenance of normal serum sodium concentration impact on our confidence in the estimate of the effect and (i.e., 135-145 mmol/L). Overall, corticosteroids with may change the estimate. Evidence quality is very low to mineralocorticoid action were found to be consistently low for hypertonic saline and albumin; thus, the estimate of effective in preventing excessive natriuresis and hypona- the effect is very uncertain at present and further research is tremia when started early after SAH onset. Side effects very likely to have an important impact on this estimate.
were infrequent and not severe. There was no evidence of Safety data are likewise limited but reassuring, espe- mineralocorticoid escape effect after administration of the cially for corticosteroids with mineralocorticoid action, for corticosteroid for a few days in the studies reviewed.
which more data are available. The number of patients Data were too scant to assess the value of hypertonic included in the available studies, however, is low, and saline or 5% albumin in the management of hyponatremia.
patients deemed to be at high risk of complications fromfluid retention were often excluded from published studies.
Therefore, further research is needed to establish clearsafety.
Corticosteroids with mineralocorticosteroid action areassociated with increased incidence of hyperglycemia(hydrocortisone), hypokalemia (hydrocortisone and flu- which are readily treatable. The incidence of congestive Hyponatremia and volume contraction are common after heart failure/pulmonary edema does not appear to be sig- aneurysmal SAH. Treatment is generally focused on nificantly increased. In some cases, hydrocortisone was maintaining normal serum sodium concentration and selected instead of fludrocortisone because fludrocortisone intravascular volume. Studies show that early treatment has a longer half-life, which could increase the risk of with mineralocorticoids can ameliorate natriuresis and congestive heart failure. The studies testing fludrocorti- hyponatremia, with a better side effect profile seen with sone, however, did not appear to substantiate this concern.
fludrocortisone compared with hydrocortisone, due to Safety data for hypertonic saline and 5% albumin were greater glucocorticoid action with hydrocortisone. Only limited from the selected studies. In general, the literature early institution of these drugs (i.e., within a couple of days suggests that continuous infusion of 3% saline (up to a of aneurysm rupture) has been tested, and the value of serum sodium concentration of 160 mmol/L) can be per- starting a mineralocorticoid once a patient has become formed safely when adequately monitored [ polyuric or hyponatremic is unknown.
Frequent boluses of 5% albumin may also be associated While hypertonic saline may be used to treat severe with low risk of complications [Although these hyponatremia, it is unclear whether this treatment will be data are encouraging, data about the safety of hypertonic helpful for preventing or improving symptomatic vaso- saline and albumin derive mostly from studies not designed spasm. Albumin can ameliorate excessive fluid and sodium to evaluate the management of hyponatremia.
losses in the urine; however, its impact on functional outcome is uncertain. Vasopressin receptor antagonists are aquaporin-4 mediates the effect of osmotherapy in postischemic effective for the treatment for hyponatremia in patients cerebral edema. Crit Care Med. 2008;36:2634-40.
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