Bicarbonate Therapy in Severe Metabolic Acidosis
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CLINICAL COMMENTARY www.jasn.org Bicarbonate Therapy in Severe Metabolic Acidosis Sandra Sabatini and Neil A. Kurtzman Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas ABSTRACT monly termed “potential” bicarbonate. The utility of bicarbonate administration to patients with severe metabolic acidosis Giving bicarbonate to a patient with a remains controversial. Chronic bicarbonate replacement is obviously indicated for true bicarbonate deficit is not controver- patients who continue to lose bicarbonate in the ambulatory setting, particularly sial. Controversy arises when the de- patients with renal tubular acidosis syndromes or diarrhea. In patients with acute crease in bicarbonate concentration is lactic acidosis and ketoacidosis, lactate and ketone bodies can be converted back the result of its conversion to another to bicarbonate if the clinical situation improves. For these patients, therapy must base, which, given time, can be converted be individualized. In general, bicarbonate should be given at an arterial blood pH back to bicarbonate. If one knew that the of Յ7.0. The amount given should be what is calculated to bring the pH up to 7.2. timely and efficient conversion of aceto- The urge to give bicarbonate to a patient with severe acidemia is apt to be all but acetate and -hydroxybutyrate or lactate irresistible. Intervention should be restrained, however, unless the clinical situation back to bicarbonate would occur with- clearly suggests benefit. Here we discuss the pros and cons of bicarbonate therapy out morbidity or mortality, then there for patients with severe metabolic acidosis. would be no reason even to contemplate giving bicarbonate. J Am Soc Nephrol 20: 692–695, 2009. doi: 10.1681/ASN.2007121329 In considering acute bicarbonate re- placement, four questions should be considered: (1) What are the deleterious Metabolic acidosis is an acid-base disor- Ͻ Ͼ (P 0.01). Also, 80% of nephrologists effects of acidemia, and when are they der characterized by a primary con- CO would consider the P 2 in making their manifest? (2) When is acidemia severe sumption of body buffers including a fall decision to treat, whereas only 59% of enough to warrant therapy? (3) How in blood bicarbonate concentration. intensivists would (P Ͻ 0.02). For pa- much bicarbonate should be given, and There are many causes (Table 1), and tients with lactic acidosis, 86% of neph- how is that amount calculated? (4) What there are multiple mechanisms that min- rologists would treat with bicarbonate, are the deleterious effects of bicarbonate imize the fall in arterial pH. A patient whereas two thirds of intensivists would therapy? with metabolic acidosis may have a nor- give bicarbonate (P Ͻ 0.05). A wider Severe acidemia causes a decrease in mal or even high pH if there is another variance was noted in the therapy of dia- myocardial contractility, a fall in cardiac primary, contravening event that raises betic ketoacidosis. Sixty percent of neph- output, and a fall in BP. Acidemia also the bicarbonate concentration (vomit- rologists would treat with bicarbonate decreases the binding of norepinephrine ing) or lowers the arterial PCO - versus 28% of intensivists (P Ͻ 0.01). 2 (respira to its receptors. It also shifts the oxyhe- tory alkalosis). Metabolic acidosis differs Both groups would administer bicarbon- moglobin curve to the right, allowing from “acidemia” in that the latter refers ate by constant infusion, targeting an ar- more O2 to be released—the Bohr Effect. solely to a fall in blood pH and not the terial pH of 7.2 as a goal. Seventy-five Protons bind to intracellular proteins as process. percent of nephrologists would calculate well as extracellular proteins, especially A recent online survey by Kraut and the amount of bicarbonate required, Kurtz1 highlighted the uncertainty over whereas only one third of intensivists when to give bicarbonate to patients with would do this. Published online ahead of print. Publication date metabolic acidosis. They reported that Metabolic acidosis results from a loss available at www.jasn.org. nephrologists will prescribe therapy at a of bicarbonate from the body (e.g., diar- Correspondence: Dr. Neil A. Kurtzman, Depart- higher pH compared with critical care rhea) or from its titration to an anionic ment of Internal Medicine, 3601 4th MS 9410, Texas Tech University Health Sciences Center, Lubbock, physicians. Forty percent of the intensiv- base that often can be converted back to TX 79430. Phone: 806-743-3181; Fax: 806-743- ists would not give bicarbonate unless bicarbonate, such as seen in diabetic ke- 1092; E-mail: [email protected] Ͻ the pH were 7.0; only 6% of nephrolo- toacidosis or lactic acidosis (Table 1). Copyright ᮊ 2009 by the American Society of gists would wait until pH gets this low This nonbicarbonate base anion is com- Nephrology 692 ISSN : 1046-6673/2004-692 J Am Soc Nephrol 20: 692–695, 2009 www.jasn.org CLINICAL COMMENTARY Table 1. Causes of severe metabolic acidosis is given (1.5 mmol/kg over 5 min).8 By General Mechanism Specific Clinical Examples contrast, infusion with THAM® (Hos- pira Inc., Lake Forest, IL) or CarbiCarb® True HCO3 deficit kidney Renal tubular acidosis (International Medication System, gastrointestinal Diarrhea South El Monte, CA) does not affect ar- ϩ 8,9 H gain terial PCO2. These observations have exogenous acid NH4Cl administration, toxins led some investigators to recommend ei- abnormal lipid metabolism Diabetic ketoacidosisa ther of these compounds as preferred abnormal carbohydrate metabolism Lactic acid therapy.2 normal protein metabolism Uremic acidosis Bicarbonate therapy is also associated a Љ Љ Also a component of true HCO3 deficit because ketone bodies ( potential HCO3) are lost in the urine with an increase in mortality. This has both before and after admission. been noted in humans and experimental albumin and hemoglobin. Thus, aci- The volume of distribution of bicar- animals under a variety of acidemic con- demia may adversely affect cell functions bonate is approximately that of total ditions.10–12 The increase in mortality is such as enzymatic reactions, ATP gener- body water. In patients with metabolic blamed on a fall in BP and cardiac out- ation, fatty acid biosynthesis, and bone acidosis, it is said to vary from 50% to put. There are also shifts in ionized cal- formation/resorption.2–4 Ͼ100%, depending on the severity of the cium; in strong acid acidosis, potassium All drugs that are the salts of weak acidemia.6 This distribution will obvi- also shifts out of the cell sensitizing the bases or acids have a dissociation con- ously affect the calculated bicarbonate heart to abnormal electrical activity and stant. Those that are the salts of a weak deficit. Any calculated amount will be subsequent arrhythmias. Moreover, a acid will have more of the drug in the only approximate, of course. The patient “paradoxic” intracellular acidosis may nonionized form in an acid environment should be carefully monitored and bicar- occur when giving bicarbonate therapy and, thus, may manifest increased toxic- bonate administration altered, when because CO2 generated from its titration ity. One such example of enhanced tox- given, to suit the course. Fernandez et al.7 freely diffuses across the cell membrane. icity during acidemia is that of acetylsal- derived a more precise formula for calcu- In addition, both volume expansion and icylic acid. Other salts of weak acids are lating the bicarbonate space: (0.4 ϩ 2.6/ hypernatremia can occur; in patients tolbutamide, methotrexate, phenobarbi- PHCO3) (body weight). A graphic repre- with compromised cardiac output, ful- tal, and phenytoin. The degree of ioniza- sentation of the formula (Figure 5 in minate congestive heart failure with flash tion is only one of the factors that deter- reference7) shows that the “apparent” bi- pulmonary edema may result. mine a drug’s solubility across cell carbonate space increases quite mark- Many in vitro studies show that intra- membranes, but it is crucial in those edly with acidemia but decreases very lit- cellular alkalinization hastens cell death body compartments in which pH may tle with alkalemia. Although they used after anoxia13; if cell water is maintained change.5 actual data from several human studies, at pH 6.8, for example, more tissue re- The optimum extracellular pH for all it is not clear that renal response to aci- mains viable.14,15 Bicarbonate adminis- physiologic mechanisms and organ demia was accounted for as they ana- tration may stimulate superoxide forma- functions is 7.4. By contrast, intracellular lyzed acute acid-base disorders. This for- tion, increase proinflammatory cytokine pH is approximately 7.1 in virtually every mula, like any other guide to bicarbonate release, or enhance apoptosis. Whether tissue studied. Many diverse mecha- treatment, should just be a starting point, these observations relate to human dis- nisms are in place to maintain both ex- which is modified as events unfold. orders with acidemia is unknown. Re- tracellular and intracellular pH within In some patients, only a small amount bound alkalemia may also occur after this very narrow range. Deviations from of bicarbonate may be required. For ex- base administration, especially when the normal pH will obviously decrease the ample, if a patient has a PCO2 of 13 PCO2 is low. Giving bicarbonate to both efficiency of all reactions, although the mmHg and bicarbonate of 4 mEq/L, animals and humans increases blood lac- degree will vary depending on the spe- then his arterial pH is 7.1. If the bicar- tate and ketone bodies.6,16–18 This “po- cific event. For example, whereas aci- bonate is doubled (raised to only 8 mEq/ tential” bicarbonate will be converted demia protects the central nervous sys- L), then the blood pH will increase to 7.4. back to actual bicarbonate unless it lost tem against seizures, it sensitizes the This is true only if the PCO2 does not in the urine.