Bicarbonate therapy in lactic acidosis
- Michael Wiederkehr, MD
Michael Wiederkehr, MD
- Attending Physician, Division of Nephrology
- Baylor University Medical Center
- Michael Emmett, MD
Michael Emmett, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Chief of Internal Medicine
- Baylor University Medical Center
Lactic acidosis causes a decrease in serum bicarbonate concentration that is similar in magnitude to the increase in the lactate concentration. Lactate is a metabolizable organic anion that, when oxidized, will generate bicarbonate. Thus, if the stimulus to lactic acid production is eliminated by successful treatment of the underlying disease (eg, restoration of perfusion in a patient with shock), oxidative processes will metabolize the accumulated lactate and regenerate bicarbonate. This will correct the metabolic acidosis and reduce the anion gap.
The role of exogenous bicarbonate therapy in patients with lactic acidosis is controversial [1-5]. Most, but not all, experts believe that it is appropriate to use bicarbonate in acutely ill patients with profound lactic acidosis and acidemia (arterial pH less than 7.1). Such severe acidemia may produce hemodynamic instability as a result of reduced left ventricular contractility, arterial vasodilation, and impaired responsiveness to catecholamines [1,5-10].
The role of bicarbonate therapy and alternative buffering agents in patients with lactic acidosis will be discussed in this topic. The causes of lactic acidosis, the approach to the adult with metabolic acidosis, and the treatment of shock in adults are presented elsewhere. (See "Causes of lactic acidosis" and "Approach to the adult with metabolic acidosis" and "Treatment of severe hypovolemia or hypovolemic shock in adults".)
The use of bicarbonate dialysis to correct lactic acidosis caused by metformin is discussed separately. (See "Metformin poisoning".)
OVERVIEW OF THERAPY
The following general approach applies to the use of bicarbonate therapy in patients with lactic acidosis:
- Kraut JA, Kurtz I. Use of base in the treatment of severe acidemic states. Am J Kidney Dis 2001; 38:703.
- Forsythe SM, Schmidt GA. Sodium bicarbonate for the treatment of lactic acidosis. Chest 2000; 117:260.
- Stacpoole PW. Lactic acidosis: the case against bicarbonate therapy. Ann Intern Med 1986; 105:276.
- Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med 2010; 36:222.
- Kraut JA, Madias NE. Treatment of acute metabolic acidosis: a pathophysiologic approach. Nat Rev Nephrol 2012; 8:589.
- Marsh JD, Margolis TI, Kim D. Mechanism of diminished contractile response to catecholamines during acidosis. Am J Physiol 1988; 254:H20.
- Mitchell JH, Wildenthal K, Johnson RL Jr. The effects of acid-base disturbances on cardiovascular and pulmonary function. Kidney Int 1972; 1:375.
- Teplinsky K, O'Toole M, Olman M, et al. Effect of lactic acidosis on canine hemodynamics and left ventricular function. Am J Physiol 1990; 258:H1193.
- Orchard CH, Kentish JC. Effects of changes of pH on the contractile function of cardiac muscle. Am J Physiol 1990; 258:C967.
- Mathieu D, Neviere R, Billard V, et al. Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: a prospective, controlled clinical study. Crit Care Med 1991; 19:1352.
- Orchard CH, Cingolani HE. Acidosis and arrhythmias in cardiac muscle. Cardiovasc Res 1994; 28:1312.
- Cooper DJ, Walley KR, Wiggs BR, Russell JA. Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study. Ann Intern Med 1990; 112:492.
- Weil MH, Rackow EC, Trevino R, et al. Difference in acid-base state between venous and arterial blood during cardiopulmonary resuscitation. N Engl J Med 1986; 315:153.
- Adrogué HJ, Rashad MN, Gorin AB, et al. Assessing acid-base status in circulatory failure. Differences between arterial and central venous blood. N Engl J Med 1989; 320:1312.
- Posner JB, Plum F. Spinal-fluid pH and neurologic symptoms in systemic acidosis. N Engl J Med 1967; 277:605.
- Morris LR, Murphy MB, Kitabchi AE. Bicarbonate therapy in severe diabetic ketoacidosis. Ann Intern Med 1986; 105:836.
- Hood VL, Tannen RL. Protection of acid-base balance by pH regulation of acid production. N Engl J Med 1998; 339:819.
- Lang RM, Fellner SK, Neumann A, et al. Left ventricular contractility varies directly with blood ionized calcium. Ann Intern Med 1988; 108:524.
- Nahas GG, Sutin KM, Fermon C, et al. Guidelines for the treatment of acidaemia with THAM. Drugs 1998; 55:191.
- Kallet RH, Jasmer RM, Luce JM, et al. The treatment of acidosis in acute lung injury with tris-hydroxymethyl aminomethane (THAM). Am J Respir Crit Care Med 2000; 161:1149.
- Weber T, Tschernich H, Sitzwohl C, et al. Tromethamine buffer modifies the depressant effect of permissive hypercapnia on myocardial contractility in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2000; 162:1361.
- Filley GF, Kindig NB. Carbicarb, an alkalinizing ion-generating agent of possible clinical usefulness. Trans Am Clin Climatol Assoc 1985; 96:141.
- Shapiro JI, Elkins N, Logan J, et al. Effects of sodium bicarbonate, disodium carbonate, and a sodium bicarbonate/carbonate mixture on the PCO2 of blood in a closed system. J Lab Clin Med 1995; 126:65.
- Gazmuri RJ, von Planta M, Weil MH, Rackow EC. Cardiac effects of carbon dioxide-consuming and carbon dioxide-generating buffers during cardiopulmonary resuscitation. J Am Coll Cardiol 1990; 15:482.
- Bersin RM, Arieff AI. Improved hemodynamic function during hypoxia with Carbicarb, a new agent for the management of acidosis. Circulation 1988; 77:227.
- Blecic S, De Backer D, Deleuze M, et al. Correction of metabolic acidosis in experimental CPR: a comparative study of sodium bicarbonate, carbicarb, and dextrose. Ann Emerg Med 1991; 20:235.
- Kette F, Weil MH, von Planta M, et al. Buffer agents do not reverse intramyocardial acidosis during cardiac resuscitation. Circulation 1990; 81:1660.
- Leung JM, Landow L, Franks M, et al. Safety and efficacy of intravenous Carbicarb in patients undergoing surgery: comparison with sodium bicarbonate in the treatment of mild metabolic acidosis. SPI Research Group. Study of Perioperative Ischemia. Crit Care Med 1994; 22:1540.
- Park R, Arieff AI. Treatment of lactic acidosis with dichloroacetate in dogs. J Clin Invest 1982; 70:853.
- Stacpoole PW, Harman EM, Curry SH, et al. Treatment of lactic acidosis with dichloroacetate. N Engl J Med 1983; 309:390.
- Stacpoole PW, Wright EC, Baumgartner TG, et al. A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group. N Engl J Med 1992; 327:1564.
- Mori M, Yamagata T, Goto T, et al. Dichloroacetate treatment for mitochondrial cytopathy: long-term effects in MELAS. Brain Dev 2004; 26:453.
- Michelakis ED, Webster L, Mackey JR. Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Br J Cancer 2008; 99:989.
- Stacpoole PW, Nagaraja NV, Hutson AD. Efficacy of dichloroacetate as a lactate-lowering drug. J Clin Pharmacol 2003; 43:683.
- OVERVIEW OF THERAPY
- WHICH PATIENTS SHOULD RECEIVE BICARBONATE THERAPY
- THERAPEUTIC GOAL
- POTENTIAL HARMS OF BICARBONATE AND ALTERNATIVE AGENTS
- Potential harms of bicarbonate therapy
- - Increased PCO2
- - Acceleration of lactate generation
- - Effects on calcium and sodium
- Alternatives to bicarbonate therapy
- - Tromethamine
- - Carbicarb
- - Dichloroacetate
- SUMMARY AND RECOMMENDATIONS