MEDizzy - Mr. Jones, a previously healthy 45-year-old man, presents to

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Cardinal Manifestations and Presentation of Diseases 2

Mr. Jones, a previously healthy 45-year-old man, presents to the emergency department after he became acutely obtunded and sufered a seizure after completing a marathon race. After establishing an endotracheal airway and beginning mechanical ventilation, you send basic laboratory studies and obtain a head CT. You receive two back-to-back “panic value” calls. On the frst, the laboratory informs you that the patient’s sodium level is 115 mEq/dL. On the second, the radiologist informs you that the patient has difuse cerebral edema with efacement of sulci without cerebral herniation. What therapy is most appropriate?

ExplanationExercise-associated hyponatremia, an important clinical issue at marathons and other endurance events, has similarly been linked to both a “nonosmotic” increase in circulating AVP and excessive free water intake. The frst major consideration guiding the therapy of hyponatremia is the presence and/or severity of symptoms. This determines the urgency and goals of therapy. Patients with acute hyponatremia, such as Mr. Jones, present with symptoms that can range from headache, nausea, and/or vomiting, to seizures, obtundation, and central herniation; patients with chronic hyponatremia, present for >48 hours, are less likely to have severe symptoms. Treatment of acute symptomatic hyponatremia should include hypertonic 3% saline (513 mM) to acutely increase plasma Na+ concentration by 1–2 mM/hr to a total of 4–6 mM; this modest increase is typically sufcient to alleviate severe acute symptoms, after which corrective guidelines for chronic hyponatremia are appropriate (see below). A number of equations have been developed to estimate the required rate of hypertonic saline, which has an Na+-Cl– concentration of 513 mM. The traditional approach is to calculate an Na+ defcit, where the Na+ defcit = 0.6 × body weight × (target plasma Na+ concentration – starting plasma Na+ concentration), followed by a calculation of the required rate. Regardless of the method used to determine the rate of administration, the increase in plasma Na+ concentration can be highly unpredictable during treatment with hypertonic saline, due to rapid changes in the underlying physiology; plasma Na+ concentration should be monitored every 2–4 hours during treatment, with appropriate changes in therapy based on the observed rate of change. The administration of supplemental oxygen and ventilatory support are also critical in acute hyponatremia, in the event that patients develop acute pulmonary edema or hypercapneic respiratory failure. Intravenous loop diuretics will help treat acute pulmonary edema and will also increase free water excretion, by interfering with the renal countercurrent multiplication system. AVP antagonists do not have an approved role in the management of acute hyponatremia. The rate of correction should be comparatively slow in chronic hyponatremia (<8–10 mM in the frst 24 hours and <18 mM in the frst 48 hours), so as to avoid osmotic demyelination syndrome (ODS); lower target rates are appropriate in patients at particular risk for ODS, such as alcoholics or hypokalemic patients. Overcorrection of the plasma Na+ concentration can occur when AVP levels rapidly normalize, for example following the treatment of patients with chronic hypovolemic hyponatremia with intravenous saline or following glucocorticoid replacement of patients with hypopituitarism and secondary adrenal failure. Approximately 10% of patients treated with vaptans, such as conivaptan, will overcorrect; the risk is increased if water intake is not liberalized. In the event that the plasma Na+ concentration overcorrects following therapy, be it with hypertonic saline, isotonic saline, or a vaptan, hyponatremia can be safely reinduced or stabilized by the administration of the AVP agonist desmopressin acetate (DDAVP) and/or the administration of free water, typically intravenous D5W; the goal is to prevent or reverse the development of ODS. Alternatively, the treatment of patients with marked hyponatremia can be initiated with the twice-daily administration of DDAVP to maintain constant AVP bioactivity, combined with the administration of hypertonic saline to slowly correct the serum sodium in a more controlled fashion, thus reducing upfront the risk of overcorrection.