Lactic Acidosis Workup
- Author: Kyle J Gunnerson, MD; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM more...
In many cases, the suggestion of lactic acidosis arises because of laboratory evidence of metabolic acidosis without an obvious etiology. Because the mortality rate of patients who develop lactic acidosis is high, prompt recognition and treatment of the underlying cause remain the only realistic hope for improving survival.
Biochemical markers of impaired tissue perfusion may be useful, because they are indicative of end-organ failure, whereas hemodynamic patterns can vary in different patient groups.[13, 14]
Emerging technologies, such as noninvasive near-infrared spectroscopy, that look at the correlation between tissue perfusion and lactate levels, continue to be studied. At this time, several studies have identified good correlation with tissue perfusion and lactate clearance as markers of improved resuscitation and outcomes.
During the workup of a patient with metabolic acidosis, as indicated by low plasma bicarbonate and low pH on arterial blood gas (ABG) determinations (bicarbonate less than 22 mmol/L and pH less than 7.35), calculation of the serum anion gap may provide further clues to the etiology. The anion gap is the difference between measured cations and measured anions and is calculated by the following formula:
Anion gap = sodium - (chloride + bicarbonate)
The normal anion gap may vary depending on the laboratory, but it generally ranges from 8-12 mmol/L. Furthermore, the normal value for the anion gap must be adjusted in patients with hypoalbuminemia. Reduction in serum albumin by 10 g/L (1 g/dL) reduces the normal value for anion gap by 2.5 mmol/L.
An elevated anion gap can be observed with renal failure and organic acidosis, such as lactic acidosis, ketoacidosis, and certain poisonings. However, clinically significant hyperlactatemia may occur in the absence of an increased anion gap. Hypoalbuminemia may falsely normalize the anion gap. Albumin has a strongly negative charge and makes up a substantial portion of the clinically unmeasured anion concentration. The decrease in anion gap caused by hypoalbuminemia also may mask coexisting hyperlactatemia.
In many patients, neither the anion gap nor the arterial pH may reflect the presence or severity of lactic acidosis. Therefore, the most accurate assessment of the severity of lactic acidosis is direct measurement of lactic level.
In the past, lactate assays were difficult and tedious. Newer autoanalyzers can rapidly and accurately measure blood, serum, or plasma lactate levels within minutes.
Either arterial blood or a mixed venous sample is preferable, because the peripheral venous specimen may reflect regional, rather than systemic, lactate concentrations. The blood specimen should be immediately transported on ice and analyzed without delay, because blood cells continue to produce lactate in vitro and falsely elevate the concentration.
In some instances, the sample can be collected in special tubes containing a glycolytic inhibitor, such as sodium fluoride or iodoacetic acid.
In patients with circulatory shock, lactate elevation above 2.5 mmol/L is associated with excessive mortality. If circulatory failure develops, serial lactate values are helpful in following the course of the hypoperfusion state and the response to therapeutic interventions.
Serum Lactate Level
No significant differences in lactate levels are noted in arterial and venous blood samples. The concentration of serum lactate must be measured as quickly as possible (within 4 h of collection) in a sample transported on ice. The advent of bedside point-of-care testing has allowed for more rapid evaluation and management of resuscitation. The normal serum lactate level is less than 2 mmol/L. Values above 4-5 mmol/L in the setting of acidemia are indicative of lactic acidosis.
In hypoperfused states, persistent lactate elevation is associated with excessive mortality. If circulatory failure develops, serial lactate values are helpful in following the response to therapeutic interventions. Currently, lactate clearance of at least 10% at 2 hours after initiation of resuscitation is a proposed method to assess this response. Additionally, lactate clearance has been shown to be noninferior to ScvO2 as an endpoint in sepsis resuscitation, which is beneficial to those patients who have no other indication for central venous catheter placement. However, lactate clearance itself cannot discriminate between oxygen delivery–dependent or oxygen delivery–independent states of hypoperfusion and therefore specific shock therapies (volume resuscitation, red blood cell transfusion, inotrope, vasopressor) cannot be determined from lactate alone.
Arterial Blood Gas Analysis
The base deficit, derived from blood gas analysis, gives an approximation of tissue acidosis, an indirect evaluation tissue perfusion. However, several studies have been conducted finding poor correlation between serum lactate and base deficit levels. However, the presence of an acidemia is required for the diagnosis.
Strong Ion Gap
In 1981, Canadian chemist Peter Stewart introduced a novel approach to acid-base physiology. He rationalized that acid-base disturbances were due to more than simply hydrogen ion concentration and identified various independent and dependent variables in vivo.
Stewart’s independent variables include partial pressure of carbon dioxide (PCO2), total weak nonvolatile acids (ATOT), and net strong ion difference (SID). The dependent variables are the ions (H+), (OH-), (HCO3-), (CO3--), (HA), and (A-). This differs from traditional acid-base teaching in that other plasma constituents, such as calcium, magnesium, phosphate, albumin, and lactate are considered. Although generally well-accepted on a scientific basis, Stewart’s approach has not been routinely used clinically because of the complexity of calculation and lack of any studies demonstrating any clinical benefit.
The strong ion gap (SIG) refers to the difference between the SID effective (SIDe) and strong ion difference apparent (SIDa), as follows:
SIG = [A- +HCO3-] – [(Na+ +K+ +CA++ +Mg++)–(Cl- +Lactate-)]
where A- includes the buffers albumin and phosphate. Normally, the SIDe and SIDa are equal, and no SIG is present. Therefore, the presence of a SIG indicates unmeasured ions in the blood but, unlike the anion gap, is not affected by any derangements in albumin, calcium, magnesium, phosphate, or lactate.
Multiple studies have attempted to predict mortality based on acid-base data, such as pH, anion gap, and standard base excess, although none has been shown to be accurate or reliable.[28, 29] A 2004 study of patients sustaining vascular injury found that the presence of SIG was a strong predictor of mortality. A more recent retrospective review by the same authors of unselected trauma patients at one center also demonstrated that SIG was strongly associated with hospital mortality. More data are needed to determine if the use of SIG to guide therapeutic interventions improves patient outcomes.
Mizock BA, Falk JL. Lactic acidosis in critical illness. Crit Care Med. 1992 Jan. 20(1):80-93. [Medline].
Stacpoole PW, Wright EC, Baumgartner TG, Bersin RM, Buchalter S, Curry SH, et al. Natural history and course of acquired lactic acidosis in adults. DCA-Lactic Acidosis Study Group. Am J Med. 1994 Jul. 97(1):47-54. [Medline].
Uribarri J, Oh MS, Carroll HJ. D-lactic acidosis. A review of clinical presentation, biochemical features, and pathophysiologic mechanisms. Medicine (Baltimore). 1998 Mar. 77(2):73-82. [Medline].
Cohen R, Woods H. Clinical and Biochemical Aspects of Lactic Acidosis. Blackwell Scientific Publications; 1976.
Forrest DM, Russell JA. Metabolic acidosis. In: Oxford Textbook of Critical Care. 1999. 573-577.
Stacpoole PW. Lactic acidosis and other mitochondrial disorders. Metabolism. 1997 Mar. 46(3):306-21. [Medline].
Sia P, Plumb TJ, Fillaus JA. Type B Lactic Acidosis Associated With Multiple Myeloma. Am J Kidney Dis. 2013 Jun 4. [Medline].
Mégarbane B, Brivet F, Guérin JM, Baud FJ. [Lactic acidosis and multi-organ failure secondary to anti-retroviral therapy in HIV-infected patients]. Presse Med. 1999 Dec 18-25. 28(40):2257-64. [Medline].
Abramson D, Scalea TM, Hitchcock R, Trooskin SZ, Henry SM, Greenspan J. Lactate clearance and survival following injury. J Trauma. 1993 Oct. 35(4):584-8; discussion 588-9. [Medline].
Fall PJ, Szerlip HM. Lactic acidosis: from sour milk to septic shock. J Intensive Care Med. 2005 Sep-Oct. 20(5):255-71. [Medline].
Gore DC, Jahoor F, Hibbert JM, DeMaria EJ. Lactic acidosis during sepsis is related to increased pyruvate production, not deficits in tissue oxygen availability. Ann Surg. 1996 Jul. 224(1):97-102. [Medline]. [Full Text].
Levraut J, Bounatirou T, Ichai C, Ciais JF, Jambou P, Hechema R, et al. Reliability of anion gap as an indicator of blood lactate in critically ill patients. Intensive Care Med. 1997 Apr. 23(4):417-22. [Medline].
Gabow PA, Kaehny WD, Fennessey PV, Goodman SI, Gross PA, Schrier RW. Diagnostic importance of an increased serum anion gap. N Engl J Med. 1980 Oct 9. 303(15):854-8. [Medline].
Siegel JH, Cerra FB, Coleman B, et al. Physiological and metabolic correlations in human sepsis. Invited commentary. Surgery. 1979 Aug. 86(2):163-93. [Medline].
Vary TC, Drnevich D, Jurasinski C, Brennan WA Jr. Mechanisms regulating skeletal muscle glucose metabolism in sepsis. Shock. 1995 Jun. 3(6):403-10. [Medline].
Bloos F, Reinhart K. Venous oximetry. Intensive Care Med. 2005 Jul. 31(7):911-3. [Medline].
Salpeter SR, Greyber E, Pasternak GA, Salpeter Posthumous EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev. 2010 Jan 20. CD002967. [Medline].
Gunnerson KJ, Saul M, He S, Kellum JA. Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients. Crit Care. 2006 Feb 10. 10(1):R22. [Medline].
Donnino MW, Andersen LW, Giberson T, Gaieski DF, Abella BS, Peberdy MA, et al. Initial lactate and lactate change in post-cardiac arrest: a multicenter validation study. Crit Care Med. 2014 Aug. 42(8):1804-11. [Medline]. [Full Text].
[Guideline] Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb. 41(2):580-637. [Medline].
Puskarich MA, Illich BM, Jones AE. Prognosis of emergency department patients with suspected infection and intermediate lactate levels: a systematic review. J Crit Care. 2014 Jun. 29(3):334-9. [Medline].
Puskarich MA, Trzeciak S, Shapiro NI, Albers AB, Heffner AC, Kline JA, et al. Whole blood lactate kinetics in patients undergoing quantitative resuscitation for severe sepsis and septic shock. Chest. 2013 Jun. 143(6):1548-53. [Medline]. [Full Text].
Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010 Feb 24. 303(8):739-46. [Medline]. [Full Text].
Lima A, van Bommel J, Jansen TC, Ince C, Bakker J. Low tissue oxygen saturation at the end of early goal-directed therapy is associated with worse outcome in critically ill patients. Crit Care. 2009. 13 Suppl 5:S13. [Medline]. [Full Text].
Stewart PA. How to Understand Acid-Base. New York, NY: Elsevier; 1981.
Tremblay LN, Feliciano DV, Rozycki GS. Assessment of initial base deficit as a predictor of outcome: mechanism of injury does make a difference. Am Surg. 2002 Aug. 68(8):689-93; discussion 693-4. [Medline].
Brill SA, Stewart TR, Brundage SI, Schreiber MA. Base deficit does not predict mortality when secondary to hyperchloremic acidosis. Shock. 2002 Jun. 17(6):459-62. [Medline].
Kaplan LJ, Kellum JA. Initial pH, base deficit, lactate, anion gap, strong ion difference, and strong ion gap predict outcome from major vascular injury. Crit Care Med. 2004 May. 32(5):1120-4. [Medline].
Kaplan LJ, Kellum JA. Comparison of acid-base models for prediction of hospital mortality after trauma. Shock. 2008 Jun. 29(6):662-6. [Medline].
Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA. 2012 Oct 17. 308(15):1566-72. [Medline].
Myburgh JA, Mythen MG. Resuscitation fluids. N Engl J Med. 2013. 369:1243-51. [Medline].
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 Apr 1. 112(7):492-8. [Medline].
Mathieu D, Neviere R, Billard V, Fleyfel M, Wattel F. Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: a prospective, controlled clinical study. Crit Care Med. 1991 Nov. 19(11):1352-6. [Medline].
Calello DP, Liu KD, Wiegand TJ, Roberts DM, Lavergne V, Gosselin S, et al. Extracorporeal Treatment for Metformin Poisoning: Systematic Review and Recommendations From the Extracorporeal Treatments in Poisoning Workgroup. Crit Care Med. 2015 Aug. 43(8):1716-30. [Medline].
Levin PD, Levin V, Weissman C, Sprung CL, Rund D. Therapeutic plasma exchange as treatment for propofol infusion syndrome. J Clin Apher. 2015 Oct. 30(5):311-3. [Medline].
Kraut JA, Madias NE. Lactic Acidosis. New Engl J Med. 2014 Dec 11. 371(24):2309-19. [Medline].