Pathogenesis of hyponatremic encephalopathy. Current concepts.
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Adaptation, Physiological↗
Biomedical subjects
A I Arieff
Publications and source records attributed to A I Arieff.
Pathogenesis and prevention of hyponatremic encephalopathy.
Hyponatremia is the most common in-hospital electrolyte abnormality, and it has recently become apparent that there are at least two hyponatremia-associated mechanisms that may induce brain injury. They are hyponatremic encephalopathy and brain damage associated with therapy. The diagnosis of hyponatremia is established easily at virtually no risk to the patient by evaluation of plasma electrolytes. Rapid and appropriate therapy with hypertonic NaCl is indicated prior to respiratory insufficiency to prevent brain damage.
Brain Diseases, Metabolic↗
Safety of low-dose intraoperative bicarbonate therapy: a prospective, double-blind, randomized study. The Study of Perioperative Ischemia (SPI) Research Group.
OBJECTIVES: Recent recommendations suggest that sodium bicarbonate may not be useful for the treatment of metabolic acidosis. However, these recommendations are based primarily on both clinical studies and animal models of metabolic acidosis with arterial hypoxemia (PaO2 of < 80 torr [< 10.7 kPa]). This study was designed to determine the safety and physiologic effects of low-dose sodium bicarbonate in humans who developed intraoperative metabolic acidosis in the absence of hypoxemia. DESIGN: Prospective, double-blind, randomized trial. SETTING: Veterans Affairs Medical Center (a teaching hospital of the University of California, San Francisco). PATIENTS: We prospectively studied 40 patients with coronary artery disease who underwent major surgery and developed mild intraoperative metabolic acidosis (decrease of plasma bicarbonate by > 3 mM). INTERVENTIONS: Patients were randomly assigned to receive either sodium bicarbonate (n = 20) or sodium chloride (n = 20) by intravenous bolus, up to a maximum dose of 88 mmol of sodium. MEASUREMENTS AND MAIN RESULTS: Bicarbonate treatment significantly increased the mean arterial pH from 7.36 to 7.39; the mean serum bicarbonate concentration from 21 to 25 mmol/L; and PCO2 from 41 to 44 torr (5.5 to 5.9 kPa). Total body oxygen consumption and lactate production did not change. Similarly, no adverse changes occurred in systemic or pulmonary arterial pressures or in cardiac ejection fraction. After bicarbonate administration, both the cardiac output and systemic oxygen consumption decreased by 8% to 11%, while both variables increased by 13% after sodium chloride administration; but, none of the changes was significant. One patient in the bicarbonate group developed myocardial ischemia, compared with three patients in the saline group. CONCLUSIONS: Administration of sodium bicarbonate to well-oxygenated patients with mild metabolic acidosis resulted in a correction of the acidosis, without significant changes in cardiac output, total body oxygen use, or PaO2 (oxygen tension). These effects remain to be validated in patients with hypoxemia, more severe acidosis, or less stable circulation.
Acidosis, Lactic↗
Postoperative hyponatremic encephalopathy in menstruant women.
OBJECTIVES: To determine factors associated with the development of encephalopathy and with its clinical course in patients with postoperative hyponatremia. SETTING: Consultation and referral services of two university medical centers and community hospitals. DESIGN: Case-control study (risk factors for encephalopathy) and cohort study (clinical course among patients with encephalopathy). PATIENTS: Case patients included 65 adults with postoperative hyponatremic encephalopathy; controls included 674 adult patients who had postoperative hyponatremia without encephalopathy and who were selected from 76,678 consecutive adult surgical inpatients. MEASUREMENTS: Age, gender, menstrual status, neurologic symptoms, time to development and degree of hyponatremia, arterial blood gas determinations, serum chemistries, morbidity and mortality. RESULTS: Case patients included 40 women (62%) and 25 men (38%) (P > 0.05); controls included 367 women (54%) and 307 men (46%) (P > 0.1). Of the 34 case patients who developed permanent brain damage or died, 33 (97%) were women (P < 0.001). Among the women with brain damage, 25 (76%) were menstruant (P < 0.001). The relative risk for death or permanent brain damage from hyponatremic encephalopathy in women compared with men was 28 (95% Cl, 5 to 141) and in menstruant women compared with postmenopausal women, 26 (Cl, 11 to 62). Arterial PO2 at diagnosis was significantly lower in female than in male case patients (34 +/- 5 compared with 91 +/- 3 mm Hg; P < 0.001). Further, of the 38 case patients who had respiratory arrest before the diagnosis of hyponatremic encephalopathy, 36 (95%) were women. Extent of or time to development of hyponatremia did not correlate with subsequent brain damage (P > 0.1). CONCLUSIONS: Women and men are equally likely to develop hyponatremia and hyponatremic encephalopathy after surgery. However, when hyponatremic encephalopathy develops, menstruant women are about 25 times more likely to die or have permanent brain damage compared with either men or postmenopausal women.
Adult↗
Hyponatraemia and death or permanent brain damage in healthy children.
OBJECTIVE: To determine if hyponatraemia causes permanent brain damage in healthy children and, if so, if the disorder is primarily limited to females, as occurs in adults. DESIGN: Prospective clinical case study of 16 affected children and a review of 24,412 consecutive surgical admissions at one medical centre. PATIENTS: 16 children (nine male, seven female; age 7 (SD 5) years) with generally minor illness were electively hospitalised for primary care. Consultation was obtained for the combination of respiratory arrest with symptomatic hyponatraemia (serum sodium concentration less than or equal to 128 mmol/l). MAIN OUTCOME MEASURES: Presence, gender distribution, and classification of permanent brain damage in children with symptomatic hyponatraemia in both prospective and retrospective studies. RESULTS: By retrospective evaluation the incidence of postoperative hyponatraemia among 24,412 patients was 0.34% (83 cases) and mortality of those afflicted was 8.4% (seven deaths). In the prospective population the serum sodium concentration on admission was 138 (SD 2) mmol/l. From three to 120 inpatient hours after hypotonic fluid administration patients developed progressive lethargy, headache, nausea, and emesis with an explosive onset of respiratory arrest. At the time serum sodium concentration was 115 (7) mmol/l and arterial oxygen tension 6 (1.5) kPa. The hyponatraemia was primarily caused by extrarenal loss of electrolytes with replacement by hypotonic fluids. All 16 patients had cerebral oedema detected at either radiological or postmortem examination. All 15 patients not treated for their hyponatraemia in a timely manner either died or were permanently incapacitated by brain damage. The only patient treated in a timely manner was alive but mentally retarded. CONCLUSIONS: Symptomatic hyponatraemia can result in high morbidity in children of both genders, which is due in large part to inadequate brain adaptation and lack of timely treatment.
Adolescent↗
Biguanide-associated lactic acidosis. Case report and review of the literature.
PURPOSE: The biguanides are a class of oral hypoglycemic agents that are commonly used in the treatment of diabetes mellitus. Such agents include metformin, phenformin, and buformin. The use of phenformin was discontinued in the United States in 1976 because of probable association with lactic acidosis. However, metformin is currently in common use in many parts of the world. In this report, we describe a patient with severe lactic acidosis secondary to metformin administration, and review the literature relevant to biguanide-associated lactic acidosis. PATIENT: We describe a diabetic man with end-stage renal failure and diabetes mellitus who was hospitalized with life-threatening lactic acidosis (lactate, 10.9 mmol/L). Unbeknownst to the hospital staff, he was being treated with metformin, which had been prescribed in Indonesia. RESULTS: Arterial blood gas analysis revealed a pH of 6.76 and a bicarbonate level of 1.6 mmol/L prior to treatment. Following therapy, which included oxygen, volume expansion, other supportive therapy, and hemodialysis, the patient completely recovered and was discharged from the hospital. CONCLUSIONS: Lactic acidosis can complicate biguanide therapy in diabetic patients with renal insufficiency. We review the literature relevant to the pathogenesis and therapy of biguanide-associated lactic acidosis. Physicians who have completed their training after 1976 may not be familiar with metformin and other biguanides, but with the increasing numbers of immigrants to the United States, physicians should be aware of the potential complications of these medications.
Acidosis, Lactic↗
Is measurement of venous oxygen saturation useful in the diagnosis of cyanide poisoning?
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Aged↗
Hyponatremic encephalopathy: is central pontine myelinolysis a component?
PURPOSE: Severe hyponatremia is often associated with permanent brain damage. There has been substantial controversy about whether central pontine myelinolysis (CPM), a rare neurologic disorder of uncertain etiology, can complicate either hyponatremia or its therapy. This study was undertaken to determine how often hyponatremic patients with the clinical diagnosis of CPM actually have the disorder as an integral structural component of their encephalopathy. PATIENTS: Analyses were carried out in 20 patients who had severe symptomatic hyponatremia and a presumptive diagnosis of CPM, based on clinical and/or neuroradiologic findings. All had been referred for neuroradiology consultation. The mean age (+/- SD) was 47 +/- 14 years, the lowest serum sodium level was 104 +/- 8 mM, and 85% of the patients were female. The etiologies were diverse and included postoperative status, thiazide diuretics, polydipsia, infection, acute renal failure, chronic alcoholism with emesis, and beer potomania. METHODS: The original and subsequent films of 20 patients were reevaluated retrospectively by two neuroradiologists. The clinical course was also reevaluated, and in eight patients, the postmortem brain findings were reviewed. The diagnosis of CPM was made only on the basis of strict criteria relating to either (1) pathologic findings of CPM on postmortem examination; or (2) computed tomographic scan and/or magnetic resonance imaging findings diagnostic of CPM. RESULTS: No pontine lesions were present in 15 of 20 patients in whom the diagnosis of CPM had initially been made. All 15 had extrapontine demyelinating lesions but the pons was normal. Two others had only lateral pontine lesions, so that only three of 20 patients had definite CPM. All but one of the 20 hyponatremic patients had a definite hypoxic event prior to any therapy with intravenous sodium chloride. The involved brain areas included basal ganglia, thalamus, cortical gray matter, and periventricular white matter, areas often affected by hypoxia. Each of the three patients in whom unequivocal findings of CPM were present had long histories of chronic alcoholism and hepatic cirrhosis. CONCLUSIONS: These results suggest that: (1) Neither hyponatremic encephalopathy nor its therapy is commonly associated with CPM; (2) Patients with chronic alcoholism who also become hyponatremic can develop pontine demyelinating lesions; (3) Most patients with symptomatic hyponatremia who are diagnosed as having CPM in fact have diffuse cerebral demyelinating lesions with a normal pons; (4) The distribution of cerebral demyelinating lesions in patients with hyponatremic encephalopathy is compatible with hypoxic damage.
Adult↗
Cytotoxic brain edema: assessment with diffusion-weighted MR imaging.
To determine whether cytotoxic brain edema is associated with a decrease in diffusion, it was induced in rats, in the absence of ischemia, with an established model of acute hyponatremic encephalopathy. Cytotoxic brain edema secondary to acute hyponatremia was induced with intraperitoneal injections of 2.5% dextrose in water and subcutaneous injection of arginine-vasopressin. Coronal spin-echo magnetic resonance (MR) images were obtained with and without strong diffusion-sensitizing gradients before and after induction of acute hyponatremia. The apparent diffusion coefficient (ADC) was measured at two coronal section locations. In hyponatremic rats, the brain ADC was significantly reduced (P = .0153 and .0001) and was positively correlated with increased total brain water content (P = .0011). Plots of ADC versus total brain water showed a statistically significant inverse linear relationship between ADC and increasing brain water at the anterior coronal section location. The results indicate that the ADC may be a sensitive indicator of cytotoxic brain edema and thus may enable quantitative evaluation of such edema with diffusion-weighted MR imaging.
Animals↗
Atrial natriuretic peptide inhibits amiloride-sensitive sodium uptake in rat brain.
Both atrial natriuretic peptide (ANP) and its receptors are present in the central nervous system, but effects of ANP on brain are unclear. In the present study, we evaluated both the effects of ANP on sodium uptake, and a possible effector mechanism, the putative intracellular second messenger guanosine 3',5'-cyclic monophosphate (cGMP), in rat brain synaptosomes. In the presence of ANP (10(-7) M), the basal level of sodium uptake in synaptosomes was reduced (n = 6) from the control value of 1.90 +/- 0.06 to 1.73 +/- 0.04 (SE) nmol/mg protein at 5 min, P less than 0.05. The observed reduction of sodium uptake by ANP was not influenced by blockade of the other important pathways for sodium uptake. Addition of either a sodium channel blocker (tetrodotoxin) or an inhibitor of Na(+)-K(+)-adenosinetriphosphatase (ATPase) (ouabain) did not affect sodium uptake in the presence of ANP. However, the reduction of sodium uptake was completely blocked by addition of amiloride. These findings suggest that ANP reduced sodium uptake via inhibition of an amiloride-sensitive pathway for sodium uptake. cGMP is a major intracellular second messenger for ANP in other tissues. We found that after stimulation with 10(-7) M ANP, synaptosomal cGMP increased significantly from 58.0 +/- 9.5 to 73.5 +/- 10.6 fmol/mg protein (P less than 0.01). When an analogue of cGMP, 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP), was added to synaptosomes, amiloride-sensitive sodium uptake was again inhibited, by a similar amount as occurred with ANP. It appears that in rat brain, ANP inhibits amiloride-sensitive sodium uptake via a pathway involving intracellular production of cGMP.
Amiloride↗
Proteinuria and microalbuminuria as predictors of nephropathy.
Measurement of proteinuria, microalbuminuria, and sodium-lithium countertransport in red cells has no practical value. A low-protein diet and ACE inhibitor therapy are currently the best way to retard progression of diabetic renal disease.
Albuminuria↗
Indications for use of bicarbonate in patients with metabolic acidosis.
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Acidosis↗
Treatment of symptomatic hyponatremia: neither haste nor waste.
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Brain Diseases↗
Fatal central diabetes mellitus and insipidus resulting from untreated hyponatremia: a new syndrome.
After elective hospitalization, eleven healthy young women developed symptomatic hyponatremia that was rapidly followed by polyuria, hypernatremia, hyperglycemia, and death. The patients were 30 +/- 2 years old (+/- SE) with initial serum sodium of 140 +/- 1 mmol/L. They all awoke from analgesia but, 32 hours after completion of the procedure, they went from alertness to respiratory arrest in less than 1 hour. At this time, serum sodium was 116 +/- 2 mmol/L and blood glucose was 6.7 +/- 0.7 mmol/L. Without treatment for the hyponatremia, urine output spontaneously increased from 38 to 689 mL/h and urine osmolality fell from 546 to 83 mmol/kg body weight. Over the next 51 hours, blood glucose rose to a high of 24.1 +/- 2.5 mmol/L while serum sodium rose to a high of 167 +/- 2 mmol/L. None of the patients regained consciousness. At autopsy, all patients had cerebral edema with herniation along with hypoxic brain damage. The pituitary showed infarction of both anterior and posterior lobes in 7 of 7 patients examined, while 8 of 11 had necrosis of the medulla and 8 of 8 patients examined had hypothalamic necrosis. All had normal pancreas and kidneys at autopsy. Soon after respiratory arrest, all of the patients developed fixed, dilated pupils that often led to the diagnosis of brain death. Autopsy showed compression of the third cranial nerve (oculomotor) because of cerebral herniation. Thus, all of the patients were diagnosed as being brain dead when some may have been saved. These data suggest that in otherwise healthy young women, untreated symptomatic hyponatremia may lead to brain edema, cerebral herniation, and infarction of pituitary and hypothalamus, resulting in central diabetes insipidus and mellitus.
Adult↗
Hyponatraemia in patients with cirrhosis.
Hyponatraemia occurs in nearly half of patients in hospital with cirrhosis and ascites, and is due to the excessive retention of free water which results from the kidney's inability to excrete it normally. The morbidity and mortality associated with hyponatraemia is largely attributable to central nervous system disturbances. The degree to which brain water content increases depends on the duration of hyponatraemia and on compensatory mechanisms. Altered steroid and peptide hormones in cirrhotic patients may contribute to the development of hyponatraemic encephalopathy, symptoms of which overlap with hepatic encephalopathy and uraemia. The occurrence of central pontine myelinolysis is unrelated to the rate of correction of hyponatraemia. The appearance of hyponatraemia in cirrhotic patients, long regarded as a poor prognostic sign, may be a function of unrecognized underlying impaired renal function. Therapy for hyponatraemia remains suboptimal.
Brain↗
Pathogenesis of lactic acidosis.
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Acidosis, Lactic↗
Metabolic and hemodynamic consequences of sodium bicarbonate administration in patients with heart disease.
PURPOSE: The use of sodium bicarbonate (NaHCO3) in cardiopulmonary arrest has been questioned, but the effects of NaHCO3 in patients with heart disease are not known. We therefore prospectively evaluated the effects of NaHCO3 in patients with congestive heart failure. PATIENTS AND METHODS: Ten patients received NaHCO3 and control infusions of equimolar sodium chloride (NaCl). Measurements were made of blood gases, 2,3-diphosphoglyceric acid (2,3-DPG), glucose, lactate, cardiac hemodynamics, and oxygen consumption. RESULTS: The arterial oxygen tension (pO2) fell an average of 10 mm Hg after NaHCO3 administration in patients with congestive heart failure, whereas it rose with NaCl (p less than 0.005). Myocardial oxygen consumption decreased by 17% (p less than 0.002) without an accompanying change in oxygen demand. Systemic oxygen consumption fell by 21%. Red blood cell 2,3-DPG levels were elevated at baseline, but did not change with NaHCO3 administration. The oxygen pressure at 50% hemoglobin saturation (P50) was correspondingly elevated at baseline in these patients and decreased significantly with NaHCO3 (Bohr effect) (p less than 0.003). The arterial and mixed venous carbon dioxide tensions increased with NaHCO3 but decreased with NaCl administration (p less than 0.05). Blood glucose concentrations fell by 1.7 mmol/L with NaHCO3 (p less than 0.003) and blood lactate concentrations increased uniformly (p less than 0.001). Three patients developed net myocardial lactate generation during NaHCO3 administration; two of these three developed symptoms of angina. Coronary blood flow did not change with NaHCO3 but increased with NaCl (p less than 0.04). Two patients developed transient pump failure. CONCLUSION: These data demonstrate that NaHCO3 impairs arterial oxygenation and reduces systemic and myocardial oxygen consumption. The decrease in oxygen utilization is associated with anaerobic metabolism, enhanced glycolysis, and elevation of the blood lactate level, and may lead to transient myocardial ischemia in some patients. Thus, the use of NaHCO3 in such patients warrants re-evaluation.
Aged↗