Practical Therapeutics Drugs 39 (6): 841-855, 1990 0012-6667/90/0006-0841/$07.50/0 © ADlS Press Limited All rights reserved. DRUG03353 Rational Treatment of Acid-Base Disorders Margaret L. McLaughlin and Jerome P. Kassirer Nephrology Division, Department of Medicine, New England Medical Center, and Department of Med icine, Tufts Un iversity School of Medi cine, Boston , Massachusetts, USA Contents Summary , ,.., , ,.., ,.., ,..,.. 842 I. Metabolic Acidosis 843 1.1 Clinical Manifestations 843 1.2 Causes of Metabolic Acidosis 843 1.3 Treatment of Metabolic Acidosis 844 1.3.1 General Remarks 844 1.3.2 Loss of Alkaline Gastrointestinal Fluids 845 1.3.3 Carbonic Anhydrase Inhibitors 845 1.3.4 Urinary Diversion , 845 1.3.5 Lactic Acidosis 845 1.3.6 Diabetic Ketoacidosis 846 1.3.7 Alcoholic Ketoacidosis 846 1.3.8 Renal Tubular Acidosis ll47 1.3.9 Renal Acidosis (Uraemic Acidosis) 848 2. Metabolic Alkalosis , 848 2.1 Clinical Manifestations 848 2.2 Causes of Metabolic Alkalosis 848 2.3 Treatment of Metabolic Alkalosis 849 2.3.1 Milk-Alkali Syndrome 850 2.3.2 Combined Therapy with Nonabsorbabl e Alkali and Exchange Resins 850 2.3.3 Acute Alkali Loading 850 2.3.4 Gastric Fluid Losses 850 2.3.5 Diuretic Therapy , 851 2.3.6 Posthypercapnic Alkalosis 851 2.3.7 Primary Aldosteron ism 851 2.3.8 Bartter's Syndrom e 85I 2.3.9 Cushing's Syndrome 852 3. Respiratory Acidosis 852 3.1 Clinical Manifestations 852 3.2 Causes of Respiratory Acidosis , 852 3.3 Treatment of Respiratory Acidosis , 852 4. Respiratory Alkalosis 852 842 Drugs 39 (6) 1990 4.1 Clinical Manifestations 853 4.2 Causes of Respiratory Alkalosis 853 4.3 Treatment of Respiratory Alkalosis 853 5. Mixed Acid-Base Disturbances 853 5.1 Metabolic and Respiratory Acidosis 853 5.2 Metabolic and Respiratory Alkalosis 853 5.3 Metabolic Acidosis and Respiratory Alkalosis 854 5.4 Metabolic Alkalosis and Respiratory Acidosis 854 6. Conclusions 854 Summary Acid-base derangements are encountered frequently in clinical practice and many have life-threatening implications. Treatment is dependent on correctly identifying the acid­ base disorder and , whenever possible, repairing the underlying causal process. Bicarb­ onate is the agent of choice for the treatment of acute metabolic acidosis. Controversy surrounds the use of alkali therapy in lactic acidosis and diabetic ketoacidosis, but bi­ carbonate should clearly be administered for severe acidos is. In most patients with mild to moderate chloride-responsive metabolic alkalosis, providing an adequate amount of a chloride salt will restore acid-base balance to normal over a matter of days. In contrast, therapy of the chloride-resistant metabolic alkaloses is best directed at the underlying disease . When alkalaemia is severe, administering hydrochloric acid or a hydrochloric acid precursor may be necessary. Treatment of respiratory acidosis should be targeted at restoring ventilation; alkali should be administered only for superimposed metabolic acidosis . The therapy of res­ piratory alkalosis is centred on reversal of the root cause; short of this goal, there is no effective treatment of primary hypocapnia. The coexistence of more than one acid-base disorder (i.e. a mixed disorder) is not uncommon. When plasma bicarbonate concentration and arterial carbon dioxide tension (paCOl) are altered in opposite directions, extreme shifts in pH may occur. In such cases, it is imperative that the nature of the disturbance is identified early and therapy directed at both disorders. Disturbances of acid-base balance are wide­ ical reactions rapidly achieve equilibrium condi­ spread in practice and many pose serious threats tions, allowing a simple expression of their rela­ to the well-being of patients. A rational approach tionship (Henderson 1908): to the treatment of acid-base disorders is depend­ (Eq. I) ent on an understanding of the basic pathophys­ iological mechanisms that give rise to them. Cor­ Thus, hydrogen ion concentration is a function rect identification of the underlying disturbance of the ratio of the arterial carbon dioxide tension may suggest new diagnostic avenues, as well as (paC02) to the bicarbonate concentration. It fol­ provide a guide to specific, and often life-saving, lows that changes in hydrogen ion concentration therapy. and, consequently, all acid-base disorders, result The carbonic acid-bicarbonate buffer system from changes in one or other of these 2 variables. plays a central role in acid-base balance because of Acid-base disturbances are classified into 4 pri­ its prevalence and its relation to physiological reg­ mary disorders - metabolic acidosis, metabolic al­ ulatory mechanisms. The hydration of dissolved kalosis, respiratory acidosis and respiratory alka­ C02 forms carbonic acid which then dissociates to losis - and various combinations of these disorders yield bicarbonate and hydrogen ions. These chem- categorised as mixed disturbances. Treatment of Acid-Base Disorders 843 1. Metabolic Acidosis duced capacity of the kidneys to excrete acid (see table I). Metabolic acidosis is initiated by a reduction in Loss of bicarbonate-rich fluid results in deple­ plasma bicarbonate concentration. The most im­ tion of extracellular fluid volume and a reduction mediate consequence of a fall in bicarbonate con­ in bicarbonate concentration. At the same time, centration is an increase in plasma acidity. Cor­ chloride concentration rises as the remaining responding changes in cerebral hydrogen ion chloride is confined to a smaller volume of distri­ concentration are sensed by central chemorecep­ bution. Such a hyperchloraemic metabolic acidosis tors, giving rise to reflex hyperventilation, a fall in results from diarrhoea (Darrow et al. 1949), pan­ paC02, and a consequent attenuation in the degree creatic or biliary drainage, administration of car­ of acidification. bonic anhydrase inhibitors, and certain forms of urinary diversion . Administration of hydrochloric 1.1 Clinical Manifestations acid and substances which give rise to hydrochloric The clinical manifestations of metabolic acid­ acid when metabolised (e.g. ammonium chloride, osis include effects on the cardiovascular and pul­ monary systems, the circulation, oxygen transport, Table I. Causes of metabolic acidosis (from Kassirer et al. 1989. and potassium metabolism (Mitchell et al. 1972; with permission) Relman 1972). Hyperventilation, or Kussmaul res­ Normal anion gap pirations, is one of the most readily apparent Loss of bicarbonate manifestations of severe acidosis. Myocardial dys­ Diarrhoea function due to acidosis and a reduced threshold Small bowel losses for ventricular fibrillation also occur. Acidosis has Carbonic anhydrase inhibitors several effects on vascular tone, producing direct Ureterosigmoidostomy Ileal loop bladder arterial vasodilatation, indirect sympathetic-me­ Dilutional acidosis diated vasoconstriction, and direct venous vaso­ Addition of hydrochloric acid constriction. In addition, acute acidaemia shifts the Ammonium chloride haemoglobin dissociation curve to the right, but Arginine-HCI acidosis-induced depletion in cellular 2,3-diphos­ Lysine-HCI Total parenteral nutrition phoglycerate shifts the curve back in a matter of Disproportionate failure of renal tubular function hours (Mitchell et al. 1972). Hyperkalaemia is a Renal tubular acidosis frequent accompaniment of acute metabolic acid­ Mild renal failure osis and has been attributed to transcellular shifts Hyporeninaemic hypoaldosteronism Adrenal insufficiency ofpotassium in response to acidosis. However, cer­ tain types of metabolic acidosis due to organic acids Increased anion gap (e.g, lactic acid and acetoacetic acid) have little or Overproduction of organic acids no direct effect on serum potassium concentration Lactic acidosis (Fulop 1979). When hyperkalaemia does occur in Diabetic ketoacidosis Starvation ketosis these kinds of acidosis, decreased renal function or Alcoholic ketoacidosis insulin deficiency is probably more important in Methyl alcohol ingestion its genesis. Ethylene glycol ingestion Paraldehyde ingestion 1.2 Causes of Metabolic Acidosis Salicylate intoxication Infantile organic acidosis Three distinct pathological processes work alone Severe renal failure or in concert to produce metabolic acidosis: (a) loss Acute Chronic of bicarbonate; (b) addition of acid; and (c) re- 844 Drugs 39 (6) 1990 lysine-HC1, and arginine-HCl) also produce hy­ small additional decrement in bicarbonate concen­ perchloraemic acidosis. The normal kidney re­ tration or increase in paC02. In normal individ­ sponds to the reduction in plasma bicarbonate by uals, administered bicarbonate distributes through augmenting net acid excretion, resulting in the con­ a space of approximately 40 to 50%of bodyweight, servation of sodium with newly generated bicarb­ but the space of distribution may be more than onate and in the excretion of chloride and hydro­ twice that large when plasma bicarbonate is ex­ gen ion. tremely low (Garella et al. 1973). In addition , there Overproduction of organic acids results in a fall is often no way to assess the magnitude of organic in plasma bicarbonate concentration and an in­ acid production or on-going alkali loss. Conse­ crease in the plasma concentration of the anion of quently, estimates of bicarbonate space to predict that acid. In contrast to the pattern seen with direct a desired increment in plasma bicarbonate must be loss of bicarbonate or administration of substances considered a first approximation only. Given the that yield hydrochloric acid, the acidosis