Central pontine and extrapontine myelinolysis following correction of severe hyponatremia

A chronically hyponatremic patient developed neurological features of pontine level disconnection following the raising of serum sodium. At autopsy histopathological examination confirmed the presence of myelinolysis in the central pons and similar symmetrical lesions in the thalamus. In chronic hyponatremic patients, more than the rapidity of correction, the magnitude of the osmolar change may predispose to development of these lesions.     

Cerebral pathology and hyponatremia. Cerebral damage with central pontine myelinolysis after rapid correction

Hyponatremia is a state of relatively common observation among neurosurgical patients and it may determine or precipitate a condition of brain swelling in the head-injured. The quick reversal to normal values of serum sodium concentration may cause relevant neurological disturbances: they are related to peculiar neuropathological changes, the most representative of which is central pontine myelonilysis. Two cases (one in pediatric age) of head injured patients with brain damage resulting from rapid correction of a SIADH related hyponatremia are presented.     

Central pontine myelinolysis following rapid correction of hyponatremia in an alcoholic

An alcoholic patient presented with profound hyponatremia of uncertain etiology. Despite partial correction of hyponatremia within 24 hours, central pontine myelinolysis (CPM) ensued and the patient subsequently died. The optimal rate of correction of severe, symptomatic hyponatremia has not yet been elucidated.     

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.     

Central and extrapontine myelinolysis in a patient in spite of a careful correction of hyponatremia

We report the case of a 54-year-old alcoholic female patient who was hospitalized for neurologic alterations along with a severe hyponatremia (plasma Na+: 97 mEq/l). She suffered from potomania and was given, a few days before admission, a thiazide diuretic for hypertension. A careful correction of plasma Na+ levels was initiated over a 48-hour period (rate of correction < 10 mEq/l/24h) in order to avoid brain demyelination. After a 2-day period of clinical improvement, her neurologic condition started to deteriorate. By the 5th day of admission, she became tetraplegic, presented pseudobulbar palsy, ataxia, strabism, extrapyramidal stiffness and clouding of consciousness. Scintigraphic and MRI investigations demonstrated pontine and extrapontine lesions associated with Gayet-Wernicke encephalopathy. After correction of ionic disorders (hyponatremia, hypokaliemia) and vitamin B (thiamine) deficiency, the patient almost completely recovered without notable disabilities. This case illustrates that profound hyponatremia, in a paradigm of slow onset, can be compatible with life. It also demonstrates that demyelinating lesions, usually considered as a consequence of a too fast correction of hyponatremia, may occur despite the strict observance of recent guidelines. There is increasing evidence to suggest that pontine swelling and dysfunction may sometimes occur in alcoholic patients even in absence of disturbance in plasma Na+ levels. It is therefore of importance, while managing a hyponatremic alcoholic patient, to identify additional risk factors (hypokaliemia, hypophosphoremia, seizure-induced hypoxemia, malnutrition with vitamin B deficiency) for brain demyelination and to correct them appropriately.     

Central pontine myelinolysis: sequele of hyponatremia during transcervical resection of endometrium

Transcervical resection of endometrium is an alternative to hysterectomy for women with menorrhagia. The procedure involves the use of cutting loop diathermy to resect the endometrium while the uterine cavity is irrigated with 1.5% glycine which can absorb consequent fluid and electrolyte shifts. Severe hyponatremia leading to central pontine myelinolysis is an extremely rare complication of this procedure. We report a case of a young female undergoing transcervical resection of endometrium for menorrhagia, who developed central pontine myelinolysis but made a complete recovery after three months.     

Brain dehydration and neurologic deterioration after rapid correction of hyponatremia

We made rats severely hyponatremic, varying the rate of onset and duration of the disturbance, and then compared rapid correction to slow correction. An acute fall in the plasma Na to 106 mEq/liter within seven hours caused seizures and coma, but these findings resolved and survival was 100% after either rapid or slow correction. A more gradual fall in plasma Na to 95 mEq/liter in three days caused neither seizures nor coma. Measurements of brain water and electrolytes showed that adaptive losses of brain Na and K (maximally depleted within seven hours) and slower losses of non-electrolyte solutes progressively reduced brain edema. After three days of hyponatremia, rapid correction to 119 mEq/liter with 1 M NaCl or to 129 mEq/liter by withdrawing DDAVP caused brain dehydration because lost brain K and non-electrolyte solutes were recovered slowly. This treatment was followed by a delayed onset of severe neurologic findings, demyelinating brain lesions and a mortality rate of over 40%. Slow correction (0.3 mEq/liter/hr) avoided these complications and permitted 100% survival. We conclude that the rat adapts quickly to hyponatremia and can survive with extremely low plasma sodium concentrations for prolonged periods. Although rapid correction is well tolerated when hyponatremia is of brief duration, it may cause brain damage in animals that have had time to more fully adapt to the disturbance.     

Rhabdomyolysis associated with severe hyponatremia after prostatic surgery

Transurethral resection of the prostate gland (TURP) has long been associated with disturbances of plasma sodium concentration. Relatively recent substitution of isotonic irrigation solutions has transformed the predominant laboratory abnormality reported from one of hypotonic hyponatremia to one of nearly isotonic hyponatremia with infrequent clinically significant manifestations. We report the unique association of acute and very severe isotonic hyponatremia with rhabdomyolysis and acute renal failure in the post-TURP setting. The mechanism for rhabdomyolysis is postulated to be an impairment of normal maintenance of cellular integrity by virtue of the acuteness and severity of hyponatremia, in the absence of a disturbance of tonicity. Survival after hyponatremia of this severity has not, to our knowledge, been previously reported.     

DDAVP to prevent rapid correction in hyponatremia

Correction of hyponatremia can be complicated by brisk free water diuresis with a rise in the serum sodium (s-Na) in excess of the generally accepted rate of 10-15 mmol/l/24 hours. We describe this complication and its treatment with desmopressin (dD-AVP), in a 56-year-old female with severe hyponatremia secondary to polydipsia and antidiuretic (ADH) activity. The patient developed a large free water diuresis with a markedly dilute urine (urine osmolality 61 mmol/kg) and a rise in the serum sodium of 19 mmol/l in 19 hours despite the addition of large volumes of free water intravenously and orally. To reduce the free water excretion, desmopressin (dD-AVP) 8 microg was given intravenously. This resulted in a rise in the urinary osmolality, a reduction in the urine volume, and a 2 mmol/l reduction in the serum sodium. Thereafter, the serum sodium rose 4 mmol/l in 24 hours. There were no neurological sequellae. In cases of appropriate but rapid correction of hyponatremia secondary to rapid free water diuresis, dD-AVP can safely reduce the free water excretion, slow the rate of correction of the serum sodium and simplify the fluid therapy of the patient.     

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.     

Neurological and neuropathological sequelae of correction of chronic hyponatremia

The effect of correction of chronic hyponatremia at different rates was studied in 91 rats maintained at a plasma [Na+] of 112 +/- 1 mmol/liter for 19 +/- 1 days. Hyponatremia was corrected into normal ranges (140 to 145 mmol/liter) using three different methods. Rats corrected by water restriction achieved normal plasma [Na+] by 2.1 +/- 0.2 day and had a maximal (4 hr) correction rate of 1.0 +/- 0.1 mmol/liter.hr; rats corrected by water diuresis achieved normal plasma [Na+] by 1.6 +/- 0.1 day and had a maximal correction rate of 2.8 +/- 0.2 mmol/liter.hr; rats corrected by hypertonic saline infusion achieved normal plasma [Na+] by 5.4 +/- 0.3 hr and had a maximal correction rate of 5.7 +/- 0.4 mmol/liter.hr. A fourth control group was not corrected. No demyelinative lesions were found in the brains from the uncorrected rats, whereas the occurrence of such lesions in the brains of the corrected rats was highly correlated with the maximal rate of increase in plasma [Na+] (r = 0.68, P less than 0.001), and to a lesser degree with the magnitude of the increase in plasma [Na+] over the first 24 hours of correction (r = 0.41, P less than 0.001). Brain myelinolysis was first observed in animals whose maximal (4 hr) rate of correction exceeded 1.75 mmol/liter.hr, and the incidence of demyelination increased progressively in rats with more rapid rates of correction. Similarly, myelinolysis was first observed in rats whose magnitude of correction at 24 hours exceeded 16 mmol/liter and also increased in rats with larger 24 hour magnitudes of correction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vasopressin antagonists: role in the management of hyponatremia

Hyponatremia is a common electrolyte disorder associated with potentially serious or life-threatening consequences. Serum osmolality and sodium concentration [Na+] are regulated by thirst, the hormone arginine vasopressin (AVP), and renal water and sodium handling. Hyponatremia is frequently caused by dysregulation of AVP, which accompanies disorders of water retention, such as congestive heart failure (CHF) and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Clinical trials with AVP receptor antagonists have confirmed the important role of AVP in the pathophysiology of hyponatremia and suggest these agents are efficacious in treating hyponatremia associated with SIADH, cirrhosis, and CHF. Acting directly at AVP receptors in the renal tubules, these agents promote aquaresis - the electrolyte-sparing excretion of free water - in patients with hyponatremia. In clinical trials, AVP receptor antagonists have been shown to increase the serum [Na+] and urine output while decreasing urine osmolality.     

肝移植后脑桥中央髓鞘溶解1例报告

肝移植后脑桥中央髓鞘溶解（centralpontinemyelinolysis,CPM）是受者死亡的主要原因之一。西安交通大学医学院第一附属医院成功诊治了1例肝移植后CPM患者。现报道如下。     

Pretransplant hyponatremia could be associated with a poor prognosis after liver transplantation

Introduction

Predicting the prognosis of hepatic cirrhosis is the most accurate method to achieve a fair allocation among the liver transplant waiting list thereby reducing overall mortality rates.

Aim

To study the survival rates of recipients who undergo liver transplantation in association with hyponatremia rates.

Methods

This retrospective study used a prospectively collected database. The characteristics of liver donors and recipients were: age (years), Model for End-stage Liver Disease (MELD), MELD Na score, recipient body mass index (kg/m²), warm ischemia time (minutes), cold ischemia time (minutes), intensive care unit time (days), hemocomponents transfused, recipient glycemia (mg/dL) and serum sodium (mEq/L), Child-Pugh-Turcotte classification (points), and survival time (months). We analyzed all 318 consecutive liver transplantations from February 1994 to May 2010 divided into two groups: A (Na > 130 mEq/L) and B (Na ≤ 130 mEq/L). The Kaplan-Meier method was used to evaluate survival rate and the Cox regression test to identify predictive factors.

Results

Hyponatremic patients displayed shorter survival (P = .04). The Cox regression for survival time showed that patients with low serum sodium values (group B) had: Child-Pugh scores with 1.13% plus risk of death for each point; cold ischemia time with 1.001% less risk of death for each minute; glycemia with 0.6% for each mg/dL; 0.66% use of cell-saver; plus a risk of death for each 100 mL plus 1.02% risk of death for each year of donor age.

Conclusion

Hyponatremic cirrhotic patients show more advanced stages of disease compared to normonatremic cirrhotics. They usually display metabolic or cirrhotic decompensation and comorbidities. When these symptoms were associated with the use of extended criteria donors, increased cold ischemia time, and intraoperative bleeding, we observed lower survival rates.