Metabolic Alkalosis

Chloride-Resistant Alkaloses
When potassium depletion is associated with a mild-to-moderate metabolic alkalosis, oral KCl 40 to 60 mEq four or five times per day usually will suffice for correction. If, however, a cardiac arrhythmia or generalized weakness is present, intravenous KCl may be given at rates as high as 40 mEq/h in concentrations not to exceed 60 mEq/L. These very high rates should be used only when life-threatening situations are encountered. The patient should be monitored by electrocardiogram and frequent determinations of plasma potassium concentration because muscle uptake of potassium may initially be diminished by downregulation of muscle Na,K-ATPase. Glucose should be omitted initially from the solution used to administer potassium because stimulated insulin secretion may cause plasma potassium concentration to decrease even further. However, once potassium repletion has begun, the presence of glucose in the infusion will facilitate cellular potassium repletion. Because nephropathy due to potassium depletion may impair free water excretion, plasma sodium should be monitored, particularly if hypotonic fluids are administered.

When mineralocorticoid excess is the proximate cause, therapy is directed at either removal of the source or its blockade. Potassium-sparing diuretics, specifically spironolactone with hyperaldosteronism, will effectively reverse the adverse effects of mineralocorticoid excess on sodium, potassium, and bicarbonate excretion. Restriction of sodium and the addition of potassium to the diet will also ameliorate the alkalosis and the hypertension. Correction of the potassium deficit reverses the alkalinizing effects, but elimination of aldosterone excess is essential to permanent correction. In glucocorticoid-suppressible hyperaldosteronism, dexamethasone (0.25 mg mornings and 0.75 mg evenings) is the agent of choice to suppress ACTH secretion.

Many primary disorders of mineralocorticoid excess are definitively treated by tumor ablation. ACTH-secreting pituitary tumors may be removed by trans-sphenoidal resection or irradiation. With adrenal tumors, adrenalectomy, either unilateral or bilateral as appropriate, may be curative. In the ectopic ACTH syndrome, the ideal treatment of the secreting tumor can rarely be accomplished. In this instance and in metastatic adrenal tumors, metyrapone, which inhibits the final step in cortisol synthesis, or aminoglutethimide, which inhibits the initial step in steroid biosynthesis, will blunt the myriad manifestations of hypercortisolism. In those disorders in which curative surgery cannot be carried out, mitotane (o,p-DDD), which produces selective destruction of the zona fasiculata and reticularis and leaves aldosterone production intact, or cisplatin has also been used to control effectively many of the manifestations of the disease. However, to the extent that severe fluid and electrolyte disturbances are due solely to aldosterone production, mitotane may not suffice when hypokalemic alkalosis is present; metyrapone or aminoglutethimide would be better choices. Detailed discussion of the use of these drugs is beyond the scope of this review.

In BS and GS syndromes, the principal goal of therapy is to minimize urinary potassium loss. In BS, converting enzyme inhibitors, which reduce angiotensin II production and decrease aldosterone secretion, have been shown to be effective and should be tried first [42] . Because renal prostaglandin production is increased in BS and may contribute to sodium, chloride, and potassium wasting, prostaglandin synthase inhibitors may ameliorate, but usually will not completely correct, the hypokalemic alkalosis. Magnesium depletion, which may also increase urinary potassium wasting, should be corrected. However, the degree to which magnesium repletion corrects alkalosis is uncertain, and magnesium salts often produce an unacceptable degree of gastrointestinal irritation that may compound the patient’s problems.

In GS, potassium-sparing diuretics, such as amiloride 5 or 10 mg daily, triamterene 100 mg twice a day, or spironolactone 25 to 50 mg four times a day, will blunt the urinary losses but dietary potassium supplementation may also be needed. When causative, licorice intake or carbenoxolone should be stopped. In Liddle syndrome, amiloride is a reasonable first choice.

Miscellaneous
In the milk-alkali syndrome, cessation of alkali ingestion and the calcium sources (often milk and calcium carbonate), and chloride and volume repletion for the commonly associated vomiting, usually will lead to the prompt resolution of these abnormalities.

Journal of the American Society of Nephrology, Volume 11 Number 2 February 2000
Copyright 2000 American Society of Nephrology

John H. Galla
Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Copyright ? 2000 by the American Society of Nephrology

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