REVIEW ARTICLE Year : 2022  |  Volume : 49  |  Issue : 3  |  Page : 246-250

Serum lactate levels in critically Ill patients: An early marker to be targeted

Ruchita Kabra, Sourya Acharya, Sunil Kumar
Department of Medicine, Datta Meghe Institute of Medical Sciences (Deemed to be University), Wardha, Maharashtra, India

Date of Submission06-Jun-2022Date of Acceptance11-Sep-2022Date of Web Publication27-Dec-2022

Correspondence Address:
Dr. Ruchita Kabra
Department of Medicine, Datta Meghe Institute of Medical Sciences (Deemed to be University), Wardha, Maharashtra
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jss.jss_113_22

Hyperlactatemia (excess blood lactate) is common in severely unwell individuals. Although lactate levels are routinely used to indicate insufficient tissue oxygenation, they can also be elevated by mechanisms unrelated to tissue oxygenation. Increased glycolysis may be a major cause of hyperlactatemia, especially in critically sick individuals. Despite this, elevated lactate levels have serious consequences for the morbidity and mortality of hyperlactatemia individuals. Despite the widespread use of the phrase lactic acidosis, a substantial link between lactate and pH appears only at higher lactate levels. As a result, the phrase lactate-related acidosis is more suitable. In early resuscitation, two recent studies have emphasized the necessity of monitoring lactate levels and adjusting treatment to changes in lactate levels. Structured lactate measures should be included in resuscitation protocols since lactate levels may be assessed quickly at the bedside from a variety of sources.

Keywords: Critically sick, hyperlactatemia, morbidity

How to cite this article:
Kabra R, Acharya S, Kumar S. Serum lactate levels in critically Ill patients: An early marker to be targeted. J Sci Soc 2022;49:246-50
  Introduction 

Critically ill patients treated in intensive care units (ICUs) have a mortality rate of 10%30%.[1],[2] The ability to identify therapy responders and reliably forecast death will aid in risk categorization. ICU, on the other hand, houses a diverse group of critically sick patients, including those recovering from surgery as well as those suffering from cardiovascular disease, trauma, or sepsis. This complicates the use of biomarkers to predict outcomes.[3],[4] Furthermore, repeated measures, rather than single-point measurements, may provide more information in a heterogeneous patient population.

Serum lactate concentrations have been frequently used as a measure of altered tissue perfusion in critically ill patients from the early investigations by Weil and others.[5],[6],[7] Various organs, including the muscle, the intestine, the red blood cells, the brain, and the skin, produce roughly 1500 mmol of lactate every day in normal settings.[8] Lactate is produced mostly by the liver (60%) and kidneys (30%), as well as other organs.[8] Lactate concentration in the blood is normally around 1 mEq/l.[9] Lactate concentrations of >1.5 mEq/l are linked to greater death rates.[9],[10] Because hyperlactatemia does not always reflect the development of anaerobic metabolism, the specific pathophysiologic causes of the illness have been vigorously contested.[11] In sepsis, metabolic changes such as enhanced glycolysis, catecholamine-stimulated Na–K pump activity, changes in pyruvate dehydrogenase activity, and impaired lactate clearance (LC), mostly due to hepatic hypoperfusion, can all contribute to raised blood lactate concentrations. Regardless of these causes, hyperlactatemia is a common symptom of shock,[12],[13] and the degree of rise in lactate concentrations is proportional to the severity of the shock and death rates.[14],[15]

Lactate levels in the blood can be high for a variety of reasons, including increased production, slower removal, or both. A dynamic analysis of successive lactate concentrations, rather than a single number, may thus be more revealing. This concept of repeating blood lactate concentrations over time as a measure of therapy response was first proposed in 1983,[16] based on an idea sparked by a 1977 publication by Orringer et al.[17] showing that the decrease in lactate levels following the cessation of grand mal seizures was actually quite rapid, with a half-life of about 50% in 1 h. Changes in lactate during the initial hours of treatment have now been highlighted in a number of publications as a useful monitoring tool. Changes in lactate concentrations have even been proposed as a target in treatment protocols[18],[19],[20],[21] or as one of the sepsis resuscitation “bundles”[22] in several investigations. The term “lactate clearance” has been used by a number of researchers to describe lowering lactate levels, although this is erroneous for two reasons. The first is that changes in lactate concentrations over time are a reflection of production and elimination changes. Lactate reduction over time may be due to decreased (over) production rather than greater liver and other organ clearance.[23],[24] LC research would necessitate intravenous injection of radiolabeled lactate, as has been done in multiple investigations.[25],[26] The second reason for the inaccurate use of the phrase is that “clearing” or “elimination” imply a gradual leveling of blood lactate concentrations, which is oversimplified. Lactate concentrations in the blood can have a complicated evolution and can rise over time, a phenomenon known as “negative LC.” Clinical investigations have recently moved their focus to lactate kinetics as a prognostic indicator. The goal of this study was to determine the serum lactate levels in critically ill individuals.

  Methods 

In April 2022, a literature search was conducted in several electronic databases to find the articles needed for this narrative review on serum lactate in critically ill patients. MeSH terms/keywords such as “serum lactate,” “critically sick,” “lactate,” and “serum lactate in critically ill” were used to search electronic databases including PubMed, Scopus, Embase, Cochrane library, ScienceDirect, and a manual search using cross-references and textbooks. Articles published in English between 2000 and April 2022 that met the study's criteria were included in the study.

Article selection criteria

The review's articles were chosen based on the criteria for inclusion and exclusion. To choose the articles for this evaluation, a quality assessment was performed.

Inclusion principles

Studies on serum lactateStudies on lactateStudies on lactate in critically illClinical trials, randomized controlled studies, and investigative reports.

Exclusion principles

Animal-based studiesNarrative reviews on serum lactate.

After reading the titles and abstracts, 79 articles were chosen from the 190 that were found. Hand searching resulted in the addition of 12 articles, bringing the total number of articles to 81. After reviewing the full-text articles and applying the inclusion and exclusion criteria, 34 publications that met the study's goals were chosen for the review [Figure 1].

Normal lactate metabolism

The metabolic endproduct of anaerobic glycolysis is lactate. When pyruvate cannot enter the mitochondria due to low flow or cellular hypoxia, it is preferentially converted to lactate, leading arterial lactate concentrations to rise.[27],[28] This is an adaptive strategy for generating energy, but it comes at the cost of acidosis deteriorating. Lactate is produced in all tissues, although skeletal muscle, brain, gut, and red blood cells produce the most. Lactate production rises as a result of increased lactate generation in the lungs, white blood cells, and splanchnic organs during critical illness. Lactate production is approximately 1300 mmol/day, while arterial lactate concentration is approximately 2 mmol/L reflecting net production and clearance. Lactate is predominantly metabolized and cleared by the liver and kidneys, and failure of these organs has been linked to varied degrees of decreased clearance.[27],[28] When production outnumbers use and removal, lactic acidosis develops. Type A lactic acidosis is defined as an insufficient oxygen delivery/consumption match with anaerobic glycolysis, while type B lactic acidosis is defined as hyperlactatemia without anaerobic glycolysis.[27]

Lactate for risk stratification

Lactate has long been used as a predictor of critical illness severity.[6] Lactate synthesis, clearance, and kinetics are not always easy to understand, although hyperlactatemia is frequently associated with delivery-dependent oxygen demand. Hyperlactatemia is not connected with a specific essential amount of oxygen supply or central venous oxygen saturation. This is assumed to be connected to the role of localized oxygen delivery in tissue perfusion rather than global oxygen delivery. Due to chronic cellular hypoperfusion, a considerable number of patients remain in “cryptic” or “occult” shock even after the microcirculation has been normalized.[29] As a result, because the connection between lactate increase and surrogate measures of hypoperfusion, such as physical examination and anion gap, is minimal,[30] a low threshold for evaluating lactate levels should be maintained.

Lactate clearance as a hemodynamic endpoint

Similarly, to all monitoring devices or biomarkers, merely examining or monitoring lactate levels will not enhance results unless they are coupled to a medication that does. The goal of any therapy should be to reverse global tissue hypoxia, and a return to normal lactate values can be used as a surrogate for this. LC data are also quite consistent: (1) Patients who clear elevated lactate levels have better results than those who do not and (2) the slower LC is done, the worse the outcome.[31]

In single-center research, chronic hyperlactatemia was 100% predictive of mortality in surgical ICU patients.[32] The death rate dropped to 3.9% in patients who cleared their lactate within 24 h. An LC regimen was linked to a shorter hospital stay in elective heart surgery patients.[18] Early and more prominent lactate elimination has been linked to lower mortality in critically sick septic patients.[33] In septic patients, a multicenter research study found that lactate clearing (a 10% reduction in lactate from the baseline measurement) was associated with a 41% reduction in absolute mortality compared to lactate nonclearers.[34] Serial lactate monitoring, along with a protocolized treatment approach aiming at correcting both macrocirculatory and microcirculatory dysfunction, resulted in a decrease in mortality, organ failure, and ICU days in another multicenter trial with a mixed ICU population.[19]

Lactate measurement serves three purposes: (1) to diagnose severe sepsis (infection plus elevated lactate); (2) if less than 4 mmol/L, to initiate early goal-directed therapy; and (3) if elevated, to establish a baseline for tailoring resuscitation to LC. The literature clearly shows that increased lactate is a cause for concern and that serial lactate monitoring with the goal of clearance should be a goal for resuscitation in the severely unwell.

  Discussion 

The appropriate threshold for single static arterial lactate measurements in terms of outcome prediction varies widely in the present literature. In this context, the volatility of blood lactate levels has piqued physicians' and academics' interest in recent years. Because serum lactate levels are linked to tissue hypoxia and anaerobic metabolism, they are also strongly linked to death. According to the sepsis guidelines from 2012, it is critical to normalize lactate in patients with high lactate. Lactate has been shown to have predictive value in critically ill patients in several investigations.[35]

Lactate has been discovered to perform well in the laboratory: The measurement is precise, and doctors at the bedside may rely on the numerical value of lactate levels collected. For the right interpretation of hyperlactatemia, however, a thorough understanding of anaerobic and aerobic production and clearance pathways is required. Although lactate's prognostic accuracy varied, it typically improved the ability to predict nonsurvival in both the ED and the ICU.

Although we were unable to locate studies on the clinical impact of lactate monitoring, it appears plausible that it can boost health-care personnel's confidence. Hyperlactatemia in critically sick patients is frequently misinterpreted as a result of systemic oxygen imbalance, triggering goal-directed D O2 therapy. Lactate monitoring has the potential to change therapeutic decisions. Lactate monitoring has a therapeutic benefit, according to indirect evidence. However, there are few clinical trials examining the clinical utility of lactate-directed treatment; the only single-center clinical research demonstrating its efficacy was conducted in patients undergoing postcardiac surgery, and this cannot be easily extended to other critical care populations. Furthermore, while the cost of lactate measurement is modest, the cost-effectiveness of lactate measurements is unknown.[36]

Nguyen and colleagues found that a higher early LC, as the kinetics of lactate has been defined in several studies, obtained by comparing blood lactate concentrations at and 6 h after admission to the emergency department, was significantly associated with a lower mortality rate in a study of 111 patients with severe sepsis or septic shock.[33] Donnino and coworkers demonstrated the significance of LC as an independent predictor of 24-h survival in a group of 79 patients with cardiac arrest in a 2007 study.[37]

  Conclusion 

The goal of critical care resuscitation should be to reverse early tissue hypoxia rather than to achieve predetermined static hemodynamic values. While the cause of hyperlactatemia is unknown, a large body of evidence links it to an elevated risk of morbidity and mortality in critically sick patients. Lactate readings have also been demonstrated to be reliable for risk classification, and LC has been linked to better outcomes. In the early stages of shock, a quantitative resuscitation technique is indicated to reverse global tissue hypoxia. Depending on the patient's features and response to therapy, the clinician should monitor LC and/or ScvO2. When global tissue hypoxia is reversed, vigorous resuscitation should be discontinued and saving time and money. Lactate levels are elevated in a variety of clinical presentations and disease conditions. Patients with high lactate levels are at risk for substantial morbidity and mortality, thus diagnosis and therapy must be done quickly, thoughtfully, and methodically.

Implication for future

Simple investigations such as serum lactate can anticipate the complications, outcomes, morbidity, and mortality of the patients. It is important for clinicians and intensivists to triage patients so that early treatment could be targeted to prevent certain complications and adverse outcomes. As it is cost friendly, it can be used widely.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

  References 
1.Harrison DA, Brady AR, Rowan K. Case mix, outcome and length of stay for admissions to adult, general critical care units in England, Wales and Northern Ireland: The intensive care national audit and research Centre case mix programme database. Crit Care 2004;8:R99-111.  
    2.Wallace DJ, Angus DC, Barnato AE, Kramer AA, Kahn JM. Nighttime intensivist staffing and mortality among critically ill patients. N Engl J Med 2012;366:2093-101.  
    3.Power GS, Harrison DA. Why try to predict ICU outcomes? Curr Opin Crit Care 2014;20:544-9.  
    4.Kahn JM. Predicting outcome in critical care: Past, present and future. Curr Opin Crit Care 2014;20:542-3.  
    5.Lee SM, An WS. New clinical criteria for septic shock: Serum lactate level as new emerging vital sign. J Thorac Dis 2016;8:1388-90.  
    6.Weil MH, Afifi AA. Experimental and clinical studies on lactate and pyruvate as indicators of the severity of acute circulatory failure (shock). Circulation 1970;41:989-1001.  
    7.Peretz DI, Mcgregor M, Dossetor JB. Lacticacidosis: A clinically significant aspect of shock. Can Med Assoc J 1964;90:673-5.  
    8.Levy B. Lactate and shock state: The metabolic view. Curr Opin Crit Care 2006;12:315-21.  
    9.Nichol AD, Egi M, Pettila V, Bellomo R, French C, Hart G, et al. Relative hyperlactatemia and hospital mortality in critically ill patients: A retrospective multi-Centre study. Crit Care 2010;14:R25.  
    10.Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 2016;315:801-10.  
    11.Kraut JA, Madias NE. Lactic acidosis. N Engl J Med 2015;372:1078-9.  
    12.Vincent JL, De Backer D. Circulatory shock. N Engl J Med 2013;369:1726-34.  
    13.Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C, et al. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European society of intensive care medicine. Intensive Care Med 2014;40:1795-815.  
    14.Nichol A, Bailey M, Egi M, Pettila V, French C, Stachowski E, et al. Dynamic lactate indices as predictors of outcome in critically ill patients. Crit Care 2011;15:R242.  
    15.Haas SA, Lange T, Saugel B, Petzoldt M, Fuhrmann V, Metschke M, et al. Severe hyperlactatemia, lactate clearance and mortality in unselected critically ill patients. Intensive Care Med 2016;42:202-10.  
    16.Vincent JL, Dufaye P, Berré J, Leeman M, Degaute JP, Kahn RJ. Serial lactate determinations during circulatory shock. Crit Care Med 1983;11:449-51.  
    17.Orringer CE, Eustace JC, Wunsch CD, Gardner LB. Natural history of lactic acidosis after grand-mal seizures. A model for the study of an anion-gap acidosis not associated with hyperkalemia. N Engl J Med 1977;297:796-9.  
    18.Pölönen P, Ruokonen E, Hippeläinen M, Pöyhönen M, Takala J. A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients. Anesth Analg 2000;90:1052-9.  
    19.Jansen TC, van Bommel J, Schoonderbeek FJ, Sleeswijk Visser SJ, van der Klooster JM, Lima AP, et al. Early lactate-guided therapy in intensive care unit patients: A multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med 2010;182:752-61.  
    20.Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: A randomized clinical trial. JAMA 2010;303:739-46.  
    21.Dettmer M, Holthaus CV, Fuller BM. The impact of serial lactate monitoring on emergency department resuscitation interventions and clinical outcomes in severe sepsis and septic shock: An observational cohort study. Shock 2015;43:55-61.  
    22.Nguyen HB, Kuan WS, Batech M, Shrikhande P, Mahadevan M, Li CH, et al. Outcome effectiveness of the severe sepsis resuscitation bundle with addition of lactate clearance as a bundle item: A multi-national evaluation. Crit Care 2011;15:R229.  
    23.Vincent JL. Serial blood lactate levels reflect both lactate production and clearance. Crit Care Med 2015;43:e209.  
    24.Vincent JL, Quintairos E Silva A, Couto L Jr., Taccone FS. The value of blood lactate kinetics in critically ill patients: A systematic review. Crit Care 2016;20:257.  
    25.Levraut J, Ciebiera JP, Chave S, Rabary O, Jambou P, Carles M, et al. Mild hyperlactatemia in stable septic patients is due to impaired lactate clearance rather than overproduction. Am J Respir Crit Care Med 1998;157:1021-6.  
    26.Revelly JP, Tappy L, Martinez A, Bollmann M, Cayeux MC, Berger MM, et al. Lactate and glucose metabolism in severe sepsis and cardiogenic shock. Crit Care Med 2005;33:2235-40.  
    27.Fall PJ, Szerlip HM. Lactic acidosis: From sour milk to septic shock. J Intensive Care Med 2005;20:255-71.  
    28.Okorie ON, Dellinger P. Lactate: Biomarker and potential therapeutic target. Crit Care Clin 2011;27:299-326.  
    29.Rady MY, Rivers EP, Nowak RM. Resuscitation of the critically ill in the ED: Responses of blood pressure, heart rate, shock index, central venous oxygen saturation, and lactate. Am J Emerg Med 1996;14:218-25.  
    30.Iberti TJ, Leibowitz AB, Papadakos PJ, Fischer EP. Low sensitivity of the anion gap as a screen to detect hyperlactatemia in critically ill patients. Crit Care Med 1990;18:275-7.  
    31.Abramson D, Scalea TM, Hitchcock R, Trooskin SZ, Henry SM, Greenspan J. Lactate clearance and survival following injury. J Trauma 1993;35:584-8.  
    32.McNelis J, Marini CP, Jurkiewicz A, Szomstein S, Simms HH, Ritter G, et al. Prolonged lactate clearance is associated with increased mortality in the surgical intensive care unit. Am J Surg 2001;182:481-5.  
    33.Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med 2004;32:1637-42.  
    34.Arnold RC, Shapiro NI, Jones AE, Schorr C, Pope J, Casner E, et al. Multicenter study of early lactate clearance as a determinant of survival in patients with presumed sepsis. Shock 2009;32:35-9.  
    35.Sun DQ, Zheng CF, Lu FB, Van Poucke S, Chen XM, Chen YP, et al. Serum lactate level accurately predicts mortality in critically ill patients with cirrhosis with acute kidney injury. Eur J Gastroenterol Hepatol 2018;30:1361-7.  
    36.Jansen TC, van Bommel J, Bakker J. Blood lactate monitoring in critically ill patients: A systematic health technology assessment. Crit Care Med 2009;37:2827-39.  
    37.Donnino MW, Miller J, Goyal N, Loomba M, Sankey SS, Dolcourt B, et al. Effective lactate clearance is associated with improved outcome in post-cardiac arrest patients. Resuscitation 2007;75:229-34.  
    
  [Figure 1]