Neurological impact of vasopressin dysregulation and hyponatremia

Authors

  • Anish Bhardwaj MD, FAHA, FCCM

    Corresponding author
    1. Neurosciences Critical Care Division, Departments of Neurology, Neurological Surgery, Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
    • Department of Neurology, Oregon Health and Science University, Mackenzie Hall, Room 2204, 3181 SW Sam Jackson Park Road, L-226, Portland, OR 97239
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Abstract

Hyponatremia is frequently associated with neurological disease, neurosurgical procedures, and use of psychoactive drugs. Arginine vasopressin (AVP), or antidiuretic hormone, is the principal physiological regulator of water and electrolyte balance, and disruption of the normal AVP response to osmotic stimuli is a common cause of dilutional hyponatremia in neurological disorders. The hyponatremia-induced shift in water from the extracellular to the intracellular compartment can lead to cerebral edema and serious neurological complications, especially if the decrease in serum sodium concentration ([Na+]) is large or rapid. Overly rapid correction of the serum [Na+] may lead to osmotic demyelination and irreversible brain injury. Fluid restriction is considered first-line treatment and pharmacological agents currently used in the treatment of hyponatremia are limited by inconsistent response and adverse side effects. AVP receptor antagonists represent a new approach to the treatment of hyponatremia by blocking tubular reabsorption of water by binding to V2 receptors in the renal collecting ducts, resulting in aquaresis. Initial clinical experience with AVP receptor antagonists for hyponatremia has shown that these agents augment free water clearance, decrease urine osmolality, and correct serum [Na+] and serum osmolality. Controlled clinical trials now underway will help elucidate the role of AVP receptor antagonism in the treatment of hyponatremia. Ann Neurol 2006;59:229–236

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