Pathogenesis and treatment of hypernatremia

Two aspects of hypernatremia are emphasized in this discussion: pathogenesis and treatment. Hypernatremia rarely develops with increased water loss alone; there must be a mechanism that interferes with water intake. In treating hypernatremia, the speed of correction is important because the volume regulation mechanisms restore the brain volume to normal when hypernatremia is chronic. Thus, too rapid correction of chronic hypernatremia results in brain edema. The calculation of fluid volume needed to correct hypernatremia can be obtained with use of various formulae described here for the fluid that contains dextrose in water or for hypotonic saline solution. Accurate prediction of the fluid volume requirement demands the knowledge of urine output and its electrolyte content, but when the information is not available, urine may be assumed to be isotonic in its electrolyte content.     

Hyponatremia: pathophysiology and treatment,a pediatric perspective

Hyponatremia is the most commonly observed electrolyte abnormality in hospitalized children. The most serious consequences of hyponatremia and its treatment involve the central nervous system (CNS). Important factors determining the development of clinical symptomatology include: the rate of fall in serum sodium, and the severity and duration of hyponatremia. Acute hyponatremia is associated with increased brain water resulting in varying grades of encephalopathy whereas the osmoregulatory mechanism allows normalization of CNS water content in chronic hyponatremia. It is recommended that the therapy for hyponatremia be initiated on the basis of the presence or absence of symptoms. An increase of 4–6 mmol/l in serum sodium over 10–15 min is recommended in symptomatic patients. Rapid correction of chronic hyponatremia may result in osmotic dehydration syndrome and therefore should be avoided.     

Désordres hydroélectrolytiques des agressions cérébrales : mécanismes et traitements

Electrolyte disturbances are frequent after brain injuries, especially dysnatremia and dyskalemia. In neurological patients, usual clinical signs of hyponatremia are frequently confounded with clinical signs of the underlying disease. Natremia absolute value is less important than speed of onset of the trouble. Most often, hyponatremia is associated with hypotonicity and intracellular hyperhydration, which may exacerbate a cerebral edema. Distinction between inappropriate secretion of antidiuretic hormone (SIADH) and cerebral salt wasting syndrome (CSWS) may be difficult and is mainly based on assessment of patient's volemia, SIADH being associated with normal or hypervolemia and CSWS with hypovolemia. After subarachnoid haemorrhage, the most common disorder is CSWS. In this case, fluid restriction is strictly prohibited. Treatment of CSWS needs to compensate for the natriuresis and may justify the use of mineralocorticoid. It is important to avoid excessively rapid correction of hypernatremia, with a maximal speed of correction of 0.5 mmol/l/h. Serum sodium monitoring should be mandatory for the first ten postoperative days after pituitary adenoma surgery. Therapeutic barbiturate may be responsible for life threatening dyskalemia.     

Centropontine myelinolysis after correction of hyponatremia: role of associated hypokalemia

BACKGROUND: Patients with severe hyponatremia have a high risk for centropontine myelinolysis (CPM) during treatment, but the incidence rate and risk factors have not been well-assessed. METHODS: This study was conducted in a medical intensive care unit (ICU) of a university teaching hospital. All patients with a serum sodium concentration < 120 mmol/l and a serum osmolality level < 250 mosmol/kg upon ICU admission were enrolled in this prospective study and were included if they underwent a baseline brain computerized tomography scan (CT scan) and a follow-up brain magnetic resonance imaging 1 month after admission. The diagnosis of CPM was based on cerebral magnetic resonance imaging findings, i.e. T1-weighted images with T2-weighted images showing hyperintense signal in the corresponding areas which were not apparent on the initial cerebral CT scan. RESULTS. Of the 22 patients included, 12 were considered as having acute hyponatremia and 8 were chronic alcoholics. In 12 patients, the increase in serum sodium level was < 12 mmol/I in any 24-hour period. CPM was diagnosed in 7/22 patients (31.8%) and was asymptomatic in 4 of them. CPM was present in 4 patients with acute hyponatremia and in 4 chronic alcoholics. It was associated with a lower baseline potassium level (p = 0.05) and NaCl administration during the first 24 hours (p = 0.005). However, non-acute hyponatremia, chronic alcoholism and rapid correction of serum sodium did not appear as risk factors. CONCLUSION: The incidence rate of CPM following severe hyponatremia is high and can develop even when there is a slow correction of serum sodium level. Hypokalemia is a predisposing factor.     

Continuous venovenous hemodiafiltration in hypernatremic hyperglycemic nonketotic coma

Rapid changes in serum sodium concentration can result in adverse neurological outcome. The gradual correction of hypernatremia in the setting of acute renal failure can be difficult to achieve. We describe an obese female teenager who presented with severe hypernatremia, hyperosmolar hyperglycemic nonketotic coma, acute renal failure, and rhabdomyolysis. Her hypernatremia and other serum chemistries were gradually corrected by repeatedly adjusting the dialysate electrolyte composition used during continuous venovenous hemodiafiltration. She had a full recovery of her renal function. She does not have clinical neurological sequelae from hypernatremia during a 1-year follow-up period.     

How quickly can acute symptomatic hyponatremia be corrected?

The systemic absorption of the flush liquid, including sorbitol, glycine or mannitol, can lead to complications, such as hyponatremia, volume overload and pulmonary or cerebral edema. Acute hyponatremia is defined as a reduction in the plasma sodium level in less than 48 h. Acute symptomatic hyponatremia should be corrected aggressively because it may cause irreversible neurological damage and death. Rapid correction of hyponatremia causes severe neurologic deficits, such as central pontine myelinolysis; thus, the optimal therapeutic approach has been debated. This article examined acute symptomatic hyponatremia in a patient undergoing transcervical myomectomy for a submucosal myoma. A thirty-seven-year-old patient was evaluated in obstetrics and gynecology clinic because of altered mental status and agitation. There was no history of chronic illness or drug use. It was discovered that during the operation, 12 L of the flush fluid, which contained 5 % mannitol, had been infused, but only 7 L of the flush fluid had been collected. On physical examination, the patient’s general condition was moderate, her cooperation was limited, she was agitated, and her blood pressure was 120/70 mmHg. The sodium level was 99 mEq/L. Furosemid and 3 % NaCl solution were given. Her serum sodium returned to normal by increasing 39 mEq/L within 14 h. Her recovery was uneventful, and she was discharged 24 h after her serum sodium returned to normal. In conclusion, if there is a difference between the infused and collected volumes of the mannitol irrigant, severe hyponatremia may develop due to the flush fluid used during transcervical hysteroscopy and myomectomy. In these patients, acute symptomatic hyponatremia may be corrected as rapidly as the sodium level dropped.     

Osmotic cerebral oedema: the role of plasma osmolarity and blood brain barrier

There are five types of oedema: vasogenic, cytotoxic, interstitial, hyperemic and osmotic. The differences lie on the type and localization of the oedema, the state of the blood-brain barrier (BBB) and the pathological context. Under physiological conditions, the osmolarity of extra cellular fluids (ECFs) is equal on both sides of the BBB. However, the pathophysiological variations of circulating osmolarity (including acute hyponatremia and hypernatremia) do not affect, at the same time, the osmolarity of cerebral ECFs. This situation generates an osmotic gradient on either side of the BBB. The latter, if intact, behaves like a semi-permeable membrane allowing water transport according to the osmotic laws. Depending on its direction, water movement could induce cerebral liquid inflation (i.e. osmotic oedema) or cerebral dehydration. In case of osmotic insult, cerebral cell modify their active osmotic molecular contents in order to limit volume variation. There are two types of osmoactive molecules, organic (i.e. ideogenic osmoles: amino acids, polyols and trimethylamines) and non organic (i.e. electrolytes). In the event of plasma hypotonicity, cerebral cells expel active osmotic molecules to reduce the osmotic gradient and water movement thereby reducing edema. The opposite reaction is observed in the case of hypertonic insult. This cerebral osmoregulation becomes more effective, the slower the osmotic disorder. It explains, for example, why patients with chronic and severe hyponatremia could be asymptomatic. Severe osmotic oedema is observed mainly in water intoxication, acute hyponatremia or too rapid reduction of hyperosmolarity. However, osmotic oedema is not limited to extreme clinical circumstances. Hyponatremia, even modest, could modify cerebral blood volume and impair osmoregulation. Generally these minor modifications do not affect normal brain tissue. In the presence of cerebral lesion, osmoregulation operates only in areas of preserved BBB. The pathological zones are therefore exposed to osmotic oedema (even in cases of moderate hyponatremia) with deterioration of both clinical status and intracranial pressure. This authentic phenomenon could be insidious and difficult to differentiate from osmotic central oedema. Hyponatremia constitutes an authentic secondary cerebral insult of systemic origin, an entity clearly identified by experimental studies to justify the choice between crystalloids and colloids in neuroanaesthesia and neurointensive care. These studies have revealed an increase in water content in normal brain tissues after administration of hypotonic solutions. The increase in plasma osmolarity as a treatment modality using mannitol or hypertonic saline is based on the same concepts. The most remote indication is the occurrence of a reactive mydriasis in the context of trauma for example. More recently, therapeutic hypernatremia has been proposed to control intracranial hypertension.     

Hyponatremia with hypoxia: effects on brain adaptation, perfusion, and histology in rodents

Hypoxia appears to be a prominent component of brain damage among patients with hyponatremic encephalopathy. Effects of hypoxia on brain in the presence of hyponatremia are not known. In order to evaluate the contributions of hypoxia to brain damage, three separate experiments were conducted in three groups of rodents. Experiment I evaluated the effects of hypoxia and acute (< 4 h) hyponatremia (plasma Na < 120 mmol/l) on brain adaptation in rabbits. Experiment II evaluated the effects of hypoxia and chronic (4 days) hyponatremia on cerebral perfusion in rats. Experiment III evaluated the effects of hypoxia and chronic hyponatremia on brain histology in rats. In experiment I, rabbits with acute hyponatremia demonstrated brain adaptation with significant falls in brain Na content (by 14.2%, P < 0.01) and osmolality (by 8.3%, P < 0.01), and a rise in brain water (by 10.6%, P < 0.05). Rabbits with combined hypoxia and hyponatremia failed to demonstrate brain adaptation. In experiment II, rats with chronic hyponatremia plus hypoxia had a decrease in cerebral perfusion index by more than 50% (P < 0.01). In experiment III, 23% of hypoxic rats had brain lesions, which were in the cerebellum, thalamus, reticular formation, and basal ganglia. Hyponatremia without hypoxia resulted in no brain lesions. Hypoxia in normonatremic animals results in cerebral edema and histopathologic lesions similar to those found in rats whose plasma Na was overcorrected. Hypoxia in hyponatremic animals aggravates cerebral edema, impairs brain adaptation, and decreases cerebral perfusion.     

Therapeutic relowering of the serum sodium in a patient after excessive correction of hyponatremia.

BACKGROUND: Inappropriate correction of chronic hyponatremia could lead to major neuropathological sequelae. In man, the risk of brain myelinolysis increases strikingly when correction of the serum sodium exceeds 10-15 mEq/l/24 h. No treatment is actually available for this iatrogenic brain injury. However, recent experimental data showed that rapid reinduction of the hyponatremia greatly reduces the incidence of brain damage and death in case of serum sodium overshooting. SUBJECTS AND METHODS: We tested this rescue manoeuver in a 71-year-old woman with nausea, confusion and severe (SNa 106 mEq/l) chronic hyponatremia related to thiazides. It was associated with hypokalemia (SK: 3.2 mEq/l). RESULTS: Treatment with isotonic saline produced inappropriately high SNa correction level of +21 mEq/l after the first 24 h. After initial improvement, the neurological status deteriorated after 72 h. Rapid reinduction of the hyponatremia was then ordered. Administration of hypotonic fluids (by oral and i.v. route) combined with dDAVP induced a prompt decline in the SNa (-16 mEq/l/14 h) with a final gradient of correction of deltaSNa +9 mEq/l. This manoeuver was well tolerated without untoward effects. The natremia then progressively normalized and the patient completely recovered without neurological sequelae. CONCLUSION: Hypotonic fluids may be safely administered to decrease the natremia after excessive correction of hyponatremia for potential prevention of myelinolysis.     

Prognostic significance of hypernatremia and hyponatremia among patients with aneurysmal subarachnoid hemorrhage

OBJECTIVE: Abnormal serum sodium levels (hyponatremia and hypernatremia) are frequently observed during the acute period after aneurysmal subarachnoid hemorrhage (SAH) and may worsen cerebral edema and mass effect. We performed this study to determine the prognostic significance of serum sodium concentration abnormalities. METHODS: We analyzed prospectively collected data for the placebo treatment group in a clinical trial conducted at 54 neurosurgical centers in North America. The presence of hypernatremia (serum sodium concentration of >145 mmol/L) and hyponatremia (serum sodium concentration of <135 mmol/L) was determined with serum sodium measurements obtained at admission and 3, 6, and 9 days after SAH. The effects of hypernatremia and hyponatremia on the risk of symptomatic vasospasm and on 3-month outcomes were analyzed after adjustment for the following potential confounding factors: age, sex, preexisting hypertension, admission Glasgow Coma Scale score, initial mean arterial pressure, subarachnoid clot thickness, intraventricular blood or intraparenchymal hematoma, ventricular dilation, and aneurysm size and location. RESULTS: Of 298 patients in the analysis, 58 (19%) developed hypernatremia and 88 (30%) developed hyponatremia. Hypernatremia was significantly associated with poor outcomes (odds ratio, 2.7; 95% confidence interval, 1.2-6.1). A positive correlation was observed between the highest sodium values recorded and Glasgow Outcome Scale scores at 3 months (P < 0.0001 by analysis of variance). Hyponatremia was not associated with 3-month outcomes (odds ratio, 1.9; 95% confidence interval, 0.9-4.3). Neither hypernatremia nor hyponatremia was associated with the risk of symptomatic vasospasm. CONCLUSION: Hyponatremia seems to be more common than hypernatremia after SAH. However, hypernatremia after SAH is independently associated with poor outcomes, and this association is independent of previously identified outcome predictors, including age and admission Glasgow Coma Scale scores. Further studies are needed to define the underlying mechanism of this association.     

Fluid and electrolyte disturbances in patients with intracranial aneurysms.

Eighty-eight cases with water and electrolyte disturbances, including polyuria, hyper- or hyponatremia, were found in 1,000 cases of surgically treated cerebral aneurysms and 80 nonoperated cases. In this paper, the clinical courses of the 88 cases were studied and an investigation was made of the hypothalamic lesions seen in ten autopsy cases. Water and electrolyte disturbances were most numerous in cases of anterior communicating aneurysms, and the prognosis was poor. Those with hypernatremia had a poor prognosis, with a 42% mortality rate during hospitalization. In contrast, the mortality rate for those with hyponatremia was 15%. Post-mortem studies showed various hemorrhagic and/or ischemic changes in the hypothalamus, with a high incidence of cerebral vasospasm. Massive hemorrhages in the hypothalamus tended to be associated with hypernatremia.     

Störungen des Natriumhaushalts beim Notfallpatienten

Electrolyte disorders are common and potentially fatal laboratory findings in emergency patients. Approximately 20?% of patients in the emergency department present with either hyponatremia or hypernatremia. Recently it was shown that disorders of serum sodium are not only an expression of the severity of the underlying disease but independent predictors for the outcome of patients. They directly influence patient daily life by causing not only gait and concentration disturbances but also an increased tendency to fall together with a reduced bone mass. Given these new data it is even more important to detect and adequately correct dysnatremia in patients in the emergency department. Acute, symptomatic dysnatremia should be corrected promptly by use of 3?% NaCl for hyponatremia and 5?% glucose for hypernatremia. A close monitoring of serum sodium concentration is, however, essential in any case of correction of hyponatremia or hypernatremia in order to avoid rapid overcorrection and subsequent complications. A profound knowledge of the mechanisms underlying the development of hyponatremia, e.g. diuretics, syndrome of inappropriate antidiuretic hormone secretion (SIADH), heart failure and cirrhosis of the liver and hypernatremia, e.g. dehydration, infusions, diuretics and osmotic diuresis is essential. The present article describes the epidemiology, etiology and correction of hyponatremia and hypernatremia on the basis of current knowledge with special emphasis on emergency department patients.     

A mathematical approach to severe hyponatremia and hypernatremia in renal replacement therapies

Severe dysnatremias are perplexing problems in patients undergoing renal replacement therapy on a chronic or acute basis. The ability to manipulate sodium concentration in the dialysate or replacement solutions is limited. Compounding dialysate or replacement fluids to alter sodium concentration could result in errors. Rapid correction of hyponatremia or hypernatremia due to equilibrium with dialysate or replacement solutions could lead to osmotic demyelination syndrome or cerebral edema respectively. Continuous renal replacement therapy is the preferred dialysis modality in patients with severe dysnatremias. In this article, we present simple formulas to determine the rate of hypotonic or hypertonic solutions needed to mitigate rapid correction of dysnatremias. These formulas can be used readily by the clinician at bedside.     

Physiologic acid-base and electrolyte changes in acute and chronic renal failure patients

Patients with acute and chronic renal failure are vulnerable to a wide variety of acid-base and electrolyte disturbances. The variety is related not only to predictable disturbances that arise as a consequence of impaired urinary excretion, but also to associated factors, such as intercurrent disease processes, chronic medications, and renal replacement therapy. This article emphasizes the pathogenesis, diagnosis, and treatment of common problems, including metabolic acidosis, hyponatremia, hypernatremia, hyperkalemia, hyperphosphatemia, and hypocalcemia.     

Medical costs of abnormal serum sodium levels

An abnormal serum sodium level is the most common electrolyte disorder in the United States and can have a significant impact on morbidity and mortality. The direct medical costs of abnormal serum sodium levels are not well understood. The impact of hyponatremia and hypernatremia on 6-mo and 1-yr direct medical costs was examined by analyzing data from the Integrated HealthCare Information Services National Managed Care Benchmark Database. During the period analyzed, there were 1274 patients (0.8%) with hyponatremia (serum sodium <135 mmol/L), 162,829 (97.3%) with normal serum sodium levels, and 3196 (1.9%) with hypernatremia (>145 mmol/L). Controlling for age, sex, region, and comorbidities, hyponatremia was a significant independent predictor of costs at 6 mo (41.2% increase in costs; 95% confidence interval, 30.3% to 53.0%) and at 1 yr (45.7% increase; 95% confidence interval, 34.2% to 58.2%). Costs associated with hypernatremia were not significantly different from those incurred by patients with normal serum sodium. In conclusion, hyponatremia is a significant independent predictor of 6-mo and 1-yr direct medical costs.     

L’hypernatrémie contrôlée est-elle utile en neuroréanimation ?

Hypernatremia invariably denotes hyperosmolarity and, at least transiently, causes cellular dehydratation. Because of blood brain barrier properties, cerebral tissue volume is modified by acute changes in osmolarity. An acute hyperosmolarity (by intravenous sodium or mannitol) temporally decreases intracranial pressure. This treatment is thus useful in critical situations, allowing time for diagnosis and, if possible, other treatment. But in cases of sustained hypernatremia, cellular dehydratation is rapidly counterbalanced by an increase in cellular osmolarity. For the brain, it has been shown that cerebral volume is restored in a few hours during prolonged hypernatremia. Moreover, the plasmatic osmotic load induces an increase in diuresis and natriuresis. A tight control is then necessary to prevent hypovolemia and electrolytes disorders. Teams using this treatment should undertake controlled randomized studies to ascertain any beneficial effect that cannot be explained by physiology.     

A new quantitative approach to the treatment of the dysnatremias

Rapid correction of the dysnatremias can result in significant patient morbidity and mortality. To avoid overly rapid correction of the dysnatremias, the sodium deficit equation, water deficit equation, and Adrogue–Madias equation are frequently utilized to predict the change in plasma sodium concentration ([Na⁺]_p) following a therapeutic maneuver. However, there are significant limitations inherent in these equations. Specifically, the sodium deficit equation assumes that total body water (TBW) remains unchanged. Similarly, when using the Adrogue–Madias equation, the volume of infusate required to induce a given [Na⁺]_p is determined by dividing the target [Na⁺]_p by the result of this formula. This calculation also assumes that TBW remains constant. In addition, neither of these equations are applicable in the management of symptomatic syndrome of inappropriate antidiuretic hormone secretion (SIADH) because they fail to consider the subsequent increase in sodium excretion following the administration of infusate. Furthermore, in the treatment of hypernatremia, the water deficit equation is only applicable if the hypernatremia is caused by pure water loss. In hypernatremia caused by hypotonic fluid losses, the water deficit equation does not provide any information on the differential effect of infusates of variable [Na⁺] and [K⁺] on the [Na⁺]_p. Finally, all these equations fail to consider any ongoing Na⁺, K⁺, or H₂O losses. Taking all these limitations into consideration, we have derived two new equations which determine the volume of a given infusate required to induce a target [Na⁺]_p. These equations consider the mass balance of Na⁺, K⁺, and H₂O, as well as therapy-induced changes in TBW. The first equation is applicable to both hypernatremia and hyponatremia. The second equation is applicable to the management of severe symptomatic SIADH requiring intravenous therapy.     

Fellows’ Forum in Dialysisedited by Mark A. Perazella: Does Uremia Protect against the Demyelination Associated with Correction of Hyponatremia during Hemodialysis? A Case Report and Literature Review

Rapid correction of chronic hyponatremia is known to cause demyelination syndromes, which are attributed to the rapid shift of water out of the brain. In uremic patients with hyponatremia, depending on the dialysate sodium concentration and delivered Kt/V, serum sodium levels may be rapidly corrected inadvertently during the hemodialysis (HD) session. It is not known whether uremic patients are as susceptible to the development of demyelination as patients with normal renal function. Since urea diffuses slowly across the blood-brain barrier, it can act as an effective osmole between plasma and the brain if levels are changed abruptly. During HD, blood urea levels drop suddenly and significantly and cerebral edema may develop (dialysis disequilibrium syndrome). This effect may counteract the fluid shift out of the brain during correction of hyponatremia. Therefore, theoretically, uremic patients may be less prone to develop demyelination. We present a patient with renal failure whose hyponatremia was corrected rapidly during HD to illustrate the potential problem. The patient tolerated rapid correction of hyponatremia without sustaining any neurologic damage. We performed a literature search looking for similar case reports and reviewed the scientific evidence behind the above hypothesis.     

Central pontine and extrapontine myelinolysis after rapid correction of hyponatremia by hemodialysis in a uremic patient

Osmotic demyelination syndrome, a well-known entity, is characterized by demyelination in the pons and extrapontine areas. Rapid correction of chronic hyponatremia is its most important cause. This report presents a 52-year-old man with uremia and hyponatremia. Demyelination syndrome developed after the first hemodialysis session. Brain images showed central pontine myelinolysis and extrapontine myelinolysis. This case emphasizes the fact that demyelination syndrome can occur when hyponatremia is corrected too rapidly, even in uremic patients. Lowering dialysate sodium with multiple, short durations of hemodialysis at a low blood flow rate should be prescribed during hemodialysis in select hyponatremic patients.