Osmotic demyelination syndrome is a devastating neurologic condition that occurs after rapid correction of serum sodium in patients with hyponatremia. Pathologic features of this injury include a ...well-demarcated region of myelin loss, a breakdown of the blood-brain barrier, and infiltration of microglia. The semisynthetic tetracycline minocycline is protective in some animal models of central nervous system injury, including demyelination, suggesting that it may also protect against demyelination resulting from rapid correction of chronic hyponatremia. Using a rat model of osmotic demyelination syndrome, we found that treatment with minocycline significantly decreases brain demyelination, alleviates neurologic manifestations, and reduces mortality associated with rapid correction of hyponatremia. Mechanistically, minocycline decreased the permeability of the blood-brain barrier, inhibited microglial activation, decreased both the expression of IL1α and protein nitrosylation, and reduced the loss of GFAP immunoreactivity. In conclusion, minocycline modifies the course of osmotic demyelination in rats, suggesting its possible therapeutic use in the setting of inadvertent rapid correction of chronic hyponatremia in humans.
Treatment of symptomatic hyponatremia Decaux, Guy; Soupart, Alain
The American journal of the medical sciences,
2003-July, Letnik:
326, Številka:
1
Journal Article
Recenzirano
Inadequate treatment of severe hyponatremia (<120 mEq/L) can be associated with severe neurological damage. In acute (<48 hours) hyponatremia, usually observed in the postoperative period, prompt ...treatment with hypertonic saline (3%) can prevent seizures and respiratory arrest. For patients with chronic (>48-72 hours) symptomatic hyponatremia, correction must be rapid during the first few hours (to decrease brain edema) followed by a slow correction limited to 10 mmol/L over 24 hours to avoid the development of osmotic demyelinating syndrome. In patients with asymptomatic hyponatremia, slow correction is the appropriate approach. When patients are overtreated, neurologic damage can be prevented by relowering the serum sodium (SNa) so that the daily increase in SNa remains below 10 mmol/L/24 hours. Frequent measurements of SNa during the correction phase of SNa are mandatory to avoid overcorrection. The use of urea to treat hyponatremia represents an advantageous alternative to hypertonic saline.
Prevention of brain demyelination in rats after excessive correction of chronic hyponatremia by serum sodium lowering. Brain myelinolysis occurs after correction of chronic hyponatremia in rats when ...the magnitude of increase in serum sodium (ΔSNa) exceeds 20 to 25 mEq/liter/24 hr (the critical threshold for brain). We tested the hypothesis that after a sustained excessive correction, brain lesions (BL) could be prevented by subsequently decreasing the serum sodium below the critical threshold for brain through the administration of hypotonic fluids. After three days of severe (< 115 mEq/liter) chronic (3 days) hyponatremia, 55 rats were submitted to an excessive correction (ΔSNa > 25 mEq/liter) by a single i.p. infusion of hypertonic saline (NaCl). This osmotic stress was maintained during 12 hours before the serum sodium decrease was initiated. Thirty-two rats reached the twelfth post-correction hour without symptoms. In group 1 after a large (ΔSNa 32 mEq/liter) and sustained (12 hr) osmotic stress, the natremia was rapidly (2 hr) decreased by the administration of oral tap water and, at the end of the first 24 hours, the magnitude of correction was maintained below 20 mEq/liter/24 hr. All the rats fared well in this group and were free of neurologic symptoms. Mild BL were noticed in only 20% of them. On the contrary, in controls (no hypotonic fluids administration at the twelfth hour) whose serum sodium was left overcorrected, all the rats became symptomatic and 57% of them died rapidly. Brain damage developed in 100% of the surviving rats. In group 2, despite hypotonic fluids administration, the serum sodium decreased insufficiently and the correction was > 20 mEq/liter at the end of the first 24 hours (ΔSNa 25 mEq/liter). The majority of these rats also presented a poor outcome. Finally, a group of rats developed very early (< 12 hr) neurologic symptoms (N = 23, 42%), and all of them died rapidly (< 24 hr) if the natremia was not decreased. Hypotonic fluids administration in some of these rats allowed them a longer survival, and brain analysis also demonstrated severe demyelination. This work demonstrates that the process leading to brain demyelination remains reversible in hyponatremic rats despite a sustained (12 hr) exposure to an excessive correction. Indeed, subsequent brain damage can be completely prevented in asymptomatic rats by early (12 hr) serum sodium lowering provided that the final correction was maintained below 20 mEq/liter/24 hr. Our results also show that the osmotic stress must be maintained a minimum period of time to induce brain lesions.
International guidelines designed to minimize the risk of complications that can occur when correcting severe hyponatremia have been widely accepted for a decade. On the basis of the results of a ...recent large retrospective study of patients hospitalized with hyponatremia, it has been suggested that hyponatremia guidelines have gone too far in limiting the rate of rise of the serum sodium concentration; the need for therapeutic caution and frequent monitoring of the serum sodium concentration has been questioned. These assertions are reminiscent of a controversy that began many years ago. After reviewing the history of that controversy, the evidence supporting the guidelines, and the validity of data challenging them, we conclude that current safeguards should not be abandoned. To do so would be akin to discarding your umbrella because you remained dry in a rainstorm. The authors of this review, who represent 20 medical centers in nine countries, have all contributed significantly to the literature on the subject. We urge clinicians to continue to treat severe hyponatremia cautiously and to wait for better evidence before adopting less stringent therapeutic limits.
Sudden cardiac death (SCD) is a major public health concern, but data regarding epidemiology of this disease in Western European countries are outdated.This study reports the first results from a ...large registry of SCD. A population-based registry was established in May 2011 using multiple sources to collect every case of SCD in Paris and its suburbs, covering a population of 6.6 million. Utstein variables were recorded. Prehospital and in-hospital data were considered, and the main outcome was survival at hospital discharge. Neurologic status at discharge was established as well. Of the 6,165 cases of SCD recorded over 2 years, 3,816 had a resuscitation attempt and represent the study population. Most patients were male (69 %), the SCD occurred at home (72 %) with bystanders in 80 % of cases, and cardiopulmonary resuscitation(CPR) was performed in 45 %of cases. Initial rhythm was shockable in 26 % of cases. A total of 1,332 patients (35 %) were admitted alive to hospital. Among hospitalized patients, 58 % had a coronary angiogram,and the same proportion had therapeutic hypothermia. Finally, 279 patients (7.5 %) were discharged alive, of whom 96 % had a favorable neurological outcome. In multivariate analysis, bystander CPR (OR 2.1, 95 % CI 1.5-3.1) and initial shockable rhythm (OR 11.5, 95 % CI 7.6-17.3) were positively associated with survival at hospital discharge, whereas age (OR 0.97 per year, 95 % CI 0.96-0.98), longer response time (OR 0.93 per minute, 95 % CI 0.89-0.97), occurrence at home (OR 0.4, 95 % CI 0.3-0.6), and epinephrine dose greater than 3 mg (OR 0.05, 95 % CI 0.03-0.08) were inversely associated with survival. Despite being conducted in the therapeutic hypothermia and early coronary angiogram era,hospital discharge survival rate of resuscitated SCD remains poor. The current registry suggests ways to improve pre-hospital and in-hospital care of these patients.
Hyponatremia, defined as a serum sodium concentration <135mmol/l, is the most common water-electrolyte imbalance encountered in clinical practice. It can lead to a wide spectrum of clinical symptoms, ...from mild to severe or even life threatening, and is associated with increased mortality, morbidity and length of hospital stay. Despite this, the management of hyponatremia patients remains problematic. The prevalence of hyponatremia in a wide variety of conditions and the fact that hyponatremia is managed by clinicians with a broad variety of backgrounds have fostered diverse institution- and specialty-based approaches to diagnosis and treatment. To obtain a common and holistic view, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA), represented by European Renal Best Practice (ERBP), have developed clinical practice guidelines on the diagnostic approach and treatment of hyponatremia as a joint venture of 3societies representing specialists with a natural interest in hyponatremia. In addition to a rigorous approach to the methodology and evaluation of the evidence, the document focuses on patient-positive outcomes and on providing a useful tool for clinicians involved in everyday practice. In this article, we present an abridged version of the recommendations and suggestions for the diagnosis and treatment of hyponatremia extracted from the full guide.
It was recently demonstrated that renal failure and exogenous urea prevent myelinolysis induced by rapid correction of experimental hyponatremia. To determine why elevated blood urea levels favorably ...affect brain tolerance to osmotic stress, the changes in brain solute composition that occur when chronic hyponatremia is rapidly corrected were studied in rats with or without mercuric chloride-induced renal failure. After 48 h of hyponatremia, the brains of azotemic and nonazotemic animals became depleted of sodium, potassium, and organic osmolytes. Twenty-four hours after rapid correction of hyponatremia, the brains of animals without azotemia remained depleted of organic osmolytes, with little increase in myo-inositol or taurine contents above those observed in animals with uncorrected hyponatremia; brain electrolytes were rapidly reaccumulated, increasing the brain sodium content to a level 17% higher than values for normonatremic control animals. In contrast, within 2 h after correction of hyponatremia, brain myo-inositol contents in azotemic rats returned to control levels and brain taurine levels were significantly higher than those in azotemic animals with uncorrected hyponatremia (16.5 versus 9 micromol/g dry weight). There was no "overshooting" of brain sodium and water contents after rapid correction in the azotemic animals. Rapid reaccumulation of brain organic osmolytes after correction of hyponatremia could explain why azotemia protects against myelinolysis.
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