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Lactic Acidosis Workup

  • Author: Kyle J Gunnerson, MD; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM  more...
Updated: Apr 25, 2016

Approach Considerations

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]


Other Tests

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.[25]


Anion Gap

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.


Lactate Assay

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.[26] 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.[24] 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.[27] 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.[30] 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.[31] More data are needed to determine if the use of SIG to guide therapeutic interventions improves patient outcomes.

Contributor Information and Disclosures

Kyle J Gunnerson, MD Associate Professor, Departments of Emergency Medicine, Anesthesiology, and Internal Medicine, University of Michigan Health System; Chief, Division of Emergency Critical Care; Medical Director of the Emergency Critical Care Center, University of Michigan Health System

Kyle J Gunnerson, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Medical Association, Society for Academic Emergency Medicine, Society of Critical Care Medicine

Disclosure: Nothing to disclose.


Carrie E Harvey, MD, MS Critical Care Fellow, Department of Anesthesiology, University of Michigan Health System

Carrie E Harvey, MD, MS is a member of the following medical societies: American College of Chest Physicians, American College of Emergency Physicians, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease, Clinical and Translational Science and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine

Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM is a member of the following medical societies: American College of Chest Physicians, Association of University Anesthetists, European Society of Intensive Care Medicine, American College of Critical Care Medicine, American Heart Association, American Thoracic Society, Shock Society, Society of Critical Care Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: Masimo<br/>Received honoraria from LiDCO Ltd for consulting; Received intellectual property rights from iNTELOMED for board membership; Received honoraria from Edwards Lifesciences for consulting; Received honoraria from Masimo, Inc for board membership.

Additional Contributors

Cory Franklin, MD Professor, Department of Medicine, Chicago Medical School at Rosalind Franklin University of Medicine and Science; Director, Division of Critical Care Medicine, Cook County Hospital

Cory Franklin, MD is a member of the following medical societies: New York Academy of Sciences, Society of Critical Care Medicine

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Sat Sharma, MD, FRCPC, to the development and writing of the source article.

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Pathophysiologic classification of lactic acidosis.
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