Abstract Acute metabolic acidosis is frequently encountered in critically ill patients. Metabolic acidosis can occur as a result of either the accumulation of endogenous acids that consumes bicarbonate (high anion gap metabolic acidosis) or loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic or normal anion gap metabolic acidosis). The cause of high anion gap metabolic acidosis includes lactic acidosis, ketoacidosis, renal failure and intoxication with ethylene glycol, methanol, salicylate and less commonly with pyroglutamic acid (5-oxoproline), propylene glycole or djenkol bean (gjenkolism). The most common causes of hyperchloremic metabolic acidosis are gastrointestinal bicarbonate loss, renal tubular acidosis, drugs-induced hyperkalemia, early renal failure and administration of acids. The appropriate treatment of acute metabolic acidosis, in particular organic form of acidosis such as lactic acidosis, has been very controversial. The only effective treatment for organic acidosis is cessation of acid production via improvement of tissue oxygenation. Treatment of acute organic acidosis with sodium bicarbonate failed to reduce the morbidity and mortality despite improvement in acid-base parameters. Further studies are required to determine the optimal treatment strategies for acute metabolic acidosis. Continue reading >>
Metabolic Acidosis In The Critically Ill: Part 2. Causes And Treatment.
Abstract The correct identification of the cause, and ideally the individual acid, responsible for metabolic acidosis in the critically ill ensures rational management. In Part 2 of this review, we examine the elevated (corrected) anion gap acidoses (lactic, ketones, uraemic and toxin ingestion) and contrast them with nonelevated conditions (bicarbonate wasting, renal tubular acidoses and iatrogenic hyperchloraemia) using readily available base excess and anion gap techniques. The potentially erroneous interpretation of elevated lactate signifying cell ischaemia is highlighted. We provide diagnostic and therapeutic guidance when faced with a high anion gap acidosis, for example pyroglutamate, in the common clinical scenario 'I can't identify the acid--but I know it's there'. The evidence that metabolic acidosis affects outcomes and thus warrants correction is considered and we provide management guidance including extracorporeal removal and fomepizole therapy. Continue reading >>
Hemodialysis For Lactic Acidosis
Department of Critical Care Medicine, Apollo First Med Hospital, Chennai, Tamil Nadu, India 1Department of Critical Care Medicine, Apollo Hospitals, Chennai, Tamil Nadu, India Address for correspondence: Dr. Ashwin K. Mani, Department of Critical Care Medicine, Apollo First Med Hospital, 154, PH Road, Chennai - 600 010, Tamil Nadu, India. E-mail: [email protected] Author information Copyright and License information Disclaimer Copyright : 2017 Indian Journal of Critical Care Medicine This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. Lactic acidosis (Type A) is common in critically ill patients and usually treated by correcting the underlying etiology. We present the case of a young female who presented with life-threatening lactic acidosis secondary to hematological malignancy. Timely initiation of hemodialysis was lifesaving. The case highlights the importance of considering Type B lactic acidosis (in this case secondary to a hematological malignancy) and also initiating renal replacement therapy when routine measures are ineffective. Keywords: Hematological malignancy, hemodialysis, hyperlactatemia, lactic acidosis, malignancy Lactic acidosis is very commonly encountered in the critical care units. Treatments are generally focused on improving oxygen delivery and restoring tissue perfusion. We present a patient with grossly elevated lactate levels associated with lymphoma which improved only after initiation of dialysis. A 21-year-old female patient was transferred from an outside hospital to our tertiary Crit Continue reading >>
Lactic Acidosis Update For Critical Care Clinicians.
J Am Soc Nephrol. 2001 Feb;12 Suppl 17:S15-9. Lactic acidosis update for critical care clinicians. Franz Volhard Clinic and Max Delbrck Center for Molecular Medicine, Medical Faculty of the Charit Humboldt University of Berlin, Berlin, Germany. [email protected] Lactic acidosis is a broad-anion gap metabolic acidosis caused by lactic acid overproduction or underutilization. The quantitative dimensions of these two mechanisms commonly differ by 1 order of magnitude. Overproduction of lactic acid, also termed type A lactic acidosis, occurs when the body must regenerate ATP without oxygen (tissue hypoxia). Circulatory, pulmonary, or hemoglobin transfer disorders are commonly responsible. Overproduction of lactate also occurs with cyanide poisoning or certain malignancies. Underutilization involves removal of lactic acid by oxidation or conversion to glucose. Liver disease, inhibition of gluconeogenesis, pyruvate dehydrogenase (thiamine) deficiency, and uncoupling of oxidative phosphorylation are the most common causes. The kidneys also contribute to lactate removal. Concerns have been raised regarding the role of metformin in the production of lactic acidosis, on the basis of individual case reports. The risk appears to be considerably less than with phenformin and involves patients with underlying severe renal and cardiac dysfunction. Drugs used to treat lactic acidosis can aggravate the condition. NaHCO(3) increases lactate production. Treatment of type A lactic acidosis is particularly unsatisfactory. NaHCO(3) is of little value. Carbicarb is a mixture of Na(2)CO(3) and NaHCO(3) that buffers similarly to NaHCO(3) but without net generation of CO(2). The results from animal studies are promising; however, clinical trials are sparse. Dichloroacetate stimulates pyruvate Continue reading >>
Lactate Versus Non-lactate Metabolic Acidosis: A Retrospective Outcome Evaluation Of Critically Ill Patients
Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients 1Assistant Professor, VCURES (Virginia Commonwealth University Reanimation Engineering Shock Center) Laboratory, Departments of Anesthesiology/Critical Care and Emergency Medicine, Medical College of Virginia/Virginia Commonwealth University, 1200 East Broad Street, Richmond, VA, 23298, USA 2Director, Clinical Research Informatics Service, University of Pittsburgh, 450 Scaife Hall, 200 Lothrop St. Pittsburgh, PA, 15213, USA 3Research Assistant, Department of Biostatistics, University of Pittsburgh, Graduate School of Public Health, Crabtree Hall, Pittsburgh, PA, 15213, USA 4Professor, CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute illness) Laboratory, Department of Critical Care Medicine, University of Pittsburgh, 608, Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA 1Assistant Professor, VCURES (Virginia Commonwealth University Reanimation Engineering Shock Center) Laboratory, Departments of Anesthesiology/Critical Care and Emergency Medicine, Medical College of Virginia/Virginia Commonwealth University, 1200 East Broad Street, Richmond, VA, 23298, USA 2Director, Clinical Research Informatics Service, University of Pittsburgh, 450 Scaife Hall, 200 Lothrop St. Pittsburgh, PA, 15213, USA 3Research Assistant, Department of Biostatistics, University of Pittsburgh, Graduate School of Public Health, Crabtree Hall, Pittsburgh, PA, 15213, USA 4Professor, CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute illness) Laboratory, Department of Critical Care Medicine, University of Pittsburgh, 608, Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA Received 2005 Aug 8; Revisions requested 2005 Sep 23; Revised Continue reading >>
Lactic Acidosis Induced By Metformin: Incidence, Management And Prevention.
Abstract Lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical. First, this potential event still influences treatment strategies in type 2 diabetes mellitus, particularly in the many patients at risk of kidney failure, in those presenting contraindications to metformin and in the elderly. Second, the relationship between metformin and lactic acidosis is complex, since use of the drug may be causal, co-responsible or coincidental. The present review is divided into three parts, dealing with the incidence, management and prevention of lactic acidosis occurring during metformin treatment. In terms of incidence, the objective of this article is to counter the conventional view of the link between metformin and lactic acidosis, according to which metformin-associated lactic acidosis is rare but is still associated with a high rate of mortality. In fact, the direct metformin-related mortality is close to zero and metformin may even be protective in cases of very severe lactic acidosis unrelated to the drug. Metformin has also inherited a negative class effect, since the early biguanide, phenformin, was associated with more frequent and sometimes fatal lactic acidosis. In the second part of this review, the objective is to identify the most efficient patient management methods based on our knowledge of how metformin acts on glucose/lactate metabolism and how lactic acidosis may occur (at the organ and cellular levels) during metformin treatment. The liver appears to be a key organ for both the antidiabetic effect of metformin and the development of lactic acidosis; the latter is attributed to mitochondrial impairment and subsequent adenosine triphosphate depletion, acceleration of the glycolytic flux Continue reading >>
G Ital Nefrol. 2016 Nov-Dec;33(6). pii: gin/33.6.1. Regolisti G , Fani F , Antoniotti R , Castellano G , Cremaschi E , Greco P , Parenti E , Morabito S , Sabatino A , Fiaccadori E . Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy. Continue reading >>
Etiology And Therapeutic Approach To Elevated Lactate
Etiology and therapeutic approach to elevated lactate aResearch Center for Emergency Medicine, Aarhus University Hospital, Denmark bDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States cDepartment of Medicine, Division of Pulmonary Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States bDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States dDepartment of Anesthesia Critical Care, Beth Israel Deaconess Medical Center, Boston, MA, United States bDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States cDepartment of Medicine, Division of Pulmonary Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States aResearch Center for Emergency Medicine, Aarhus University Hospital, Denmark bDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States cDepartment of Medicine, Division of Pulmonary Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States dDepartment of Anesthesia Critical Care, Beth Israel Deaconess Medical Center, Boston, MA, United States Corresponding author: Michael W. Donnino Beth Israel Deaconess Medical Center One Deaconess Road, W/CC 2 Boston, Boston, MA 02215 Phone: 617-754-2450 Fax: 617-754-2350 [email protected] The publisher's final edited version of this article is available at Mayo Clin Proc See other articles in PMC that cite the published article. Lactate levels are commonly evaluated in acutely ill patients. Although most commonly used in the context of evaluating shock, lactate can be elevated for many reasons. While tissue hypoperfusion is probably the most common cause of elevation Continue reading >>
Treatment Of Lactic Acidosis: Appropriate Confusion.
J Hosp Med. 2010 Apr;5(4):E1-7. doi: 10.1002/jhm.600. Treatment of lactic acidosis: appropriate confusion. Division of Nephrology, Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Cooper University Hospital, Camden, New Jersey 08103, USA. [email protected] Lactic acidosis (LA) is common in hospitalized patients and is associated with poor clinical outcomes. There have been major recent advances in our understanding of lactate generation and physiology. However, treatment of LA is an area of controversy and uncertainty, and the use of agents to raise pH is not clearly beneficial. We reviewed animal and human studies on the pathogenesis, impact, and treatment of LA, published in the English language and available through the PubMed/MEDLINE database. Our aim was to clarify the physiology of the generation of LA, its impact on outcomes, and the different treatment modalities available. We also examined relevant data regarding LA induced by medications commonly prescribed by hospitalists: biguanides, nucleoside analog reverse-transcriptase inhibitors (NRTIs), linezolid, and lorazepam. Lactic acid is a marker of tissue ischemia but it also may accumulate without tissue hypoperfusion. In the latter circumstance, lactic acid accumulation may be an adaptive mechanism-a novel possibility quite in contrast to the traditional view of lactic acid as only a marker of tissue ischemia. Studies on the treatment of LA with sodium bicarbonate or other buffers fail to show consistent clinical benefit. Severe acidemia in the setting of LA is a particularly poorly studied area. In the settings of medication-induced LA, optimal treatment, apart from prompt cessation of the offending agent, is still unclear. Continue reading >>
This article has been cited by other articles in PMC. Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References . These references are in PubMed. This may not be the complete list of references from this article. Park R, Arieff AI. Lactic acidosis. Adv Intern Med. 1980;25:3368. [ PubMed ] PERETZ DI, MCGREGOR M, DOSSETOR JB. LACTICACIDOSIS: A CLINICALLY SIGNIFICANT ASPECT OF SHOCK. Can Med Assoc J. 1964 Mar 14;90:673675. [ PMC free article ] [ PubMed ] 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 Oct 13;297(15):796799. [ PubMed ] Arieff AI, Park R, Leach WJ, Lazarowitz VC. Pathophysiology of experimental lactic acidosis in dogs. Am J Physiol. 1980 Aug;239(2):F135F142. [ PubMed ] Berry MN. The liver and lactic acidosis. Proc R Soc Med. 1967 Dec;60(12):12601262. [ PMC free article ] [ PubMed ] Berry MN, Scheuer J. Splanchnic lactic acid metabolism in hyperventilation, metabolic alkalosis and shock. Metabolism. 1967 Jun;16(6):537547. [ PubMed ] Lloyd MH, Iles RA, Simpson BR, Strunin JM, Layton JM, Cohen RD. The effect of simulated metabolic acidosis on intracellular pH and lactate metabolism in the isolated perfused rat liver. Clin Sci Mol Med. 1973 Oct;45(4):543549. [ PubMed ] Misbin RI. Phenformin-associated lactic acidosis: pathogenesis and treatment. Ann Intern Med. 1977 Nov;87(5):591595. [ PubMed ] Blackshear PJ, Holloway PA, Alberti KG. The metabolic effects of sodium dichloroacetate in the starved rat. Biochem J. 197 Continue reading >>
Lactic Acidosis In Sepsis: It's Not All Anaerobic: Implications For Diagnosis Andmanagement.
1. Chest. 2016 Jan;149(1):252-61. doi: 10.1378/chest.15-1703. Epub 2016 Jan 6. Lactic Acidosis in Sepsis: It's Not All Anaerobic: Implications for Diagnosis andManagement. (1)Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada. (2)Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada. Electronic address: [email protected] Increased blood lactate concentration (hyperlactatemia) and lactic acidosis(hyperlactatemia and serum pH< 7.35) arecommon in patients with severe sepsisorseptic shock and are associated with significant morbidity and mortality. Insome patients, most of the lactate that is produced in shock states is due toinadequate oxygen delivery resulting in tissue hypoxia and causing anaerobicglycolysis. However, lactate formation during sepsis is not entirely related totissue hypoxia or reversible by increasing oxygen delivery. In this review,weinitially outline the metabolism of lactateand etiology of lactic acidosis;we thenaddress the pathophysiology of lacticacidosis in sepsis. We discuss the clinical implications of serum lactate measurement in diagnosis, monitoring, and prognostication in acute and intensive care settings. Finally, we exploretreatment of lactic acidosis and its impact on clinical outcome.Copyright 2016 American College of Chest Physicians. Published by Elsevier Inc.All rights reserved. Continue reading >>
Lactic Acidosis. - Pubmed - Ncbi
Division of Critical Care Medicine, Chicago Medical School, Illinois. An understanding of the pathophysiology of lactic acidosis is crucial in facilitating the optimal care of critically ill patients. The relevant biochemistry of lactic acidosis is reviewed, and the more controversial aspects relating to the genesis of the acidosis are highlighted. The current system of classification of lactic acidosis divides etiologies on the basis of the presence or absence of clinical signs of tissue hypoperfusion. Several types of lactic acidosis in which clinical evidence of tissue hypoperfusion is lacking demonstrate hemodynamic evidence of occult hypoperfusion. The diagnostic and therapeutic implications of this observation are discussed. Current diagnostic criteria for lactic acidosis include a pH less than 7.35 and blood lactate concentration greater than 5 to 6 mM/L. An important issue relates to the implications of lactate values that are greater than normal but below this diagnostic range. The use of the oxygen flux test may be valuable in the diagnosis of occult tissue hypoperfusion in patients with low-grade elevations in lactate levels. The current therapy for lactic acidosis involves addressing the primary cause and supportive management. The use of bicarbonate in the therapy for lactic acidosis is controversial due to potential adverse effects on cardiac function. The specifics of this controversy are outlined, and newer therapeutic alternatives are reviewed. The use of blood lactate concentration as a prognostic index may be more useful in patients with shock than without shock. Continue reading >>
Lactic Acidosis - Statpearls - Ncbi Bookshelf
Christopher D. Foucher1; Robert E. Tubben2. 2 McLaren Greater Lansing/ Michigan State Lactic acid is produced in physiologically normal processes, andasa common finding in disease states. When increased production is comorbid with decreased clearance, the severity of the clinical course escalates. Importantly, the effects of severely elevated levels of lactic acid can have profound hemodynamic consequences and can lead to death. Serum lactate levels can be both a marker for risk as well as a therapeutic target. The higher the level and the longer the time to normalization of elevated serum lactate, the greater the risk of death. Lactic acid is normally produced in excess by about 20 mmol/kg/day, which enters the bloodstream. It is then metabolized mostly via the liver and the kidney. Some tissues can use lactate as a substrate and oxidize it to carbon dioxide (C02) and water, but only the liver and kidney have the necessary enzymes to utilize lactate for the process of gluconeogenesis. The tissues which normally produce excess lactic acid include the skin, red cells, brain tissue, muscle, and the gastrointestinal (GI) tract. During heavy exercise, it is the skeletal muscles which produce the most excess circulating lactate, which normalizes in the absence of impaired hepatic metabolism. In general, elevated lactate can be the result of increased production, decreased clearance, or both. Pyruvate production as a result of glycolysis gets shunted into two main metabolic pathways. Under aerobic conditions, it enters the citric acid cycle after having been converted to acetyl-CoA by pyruvate dehydrogenase, and a series of reactions occur to form ATP and NADH, which goes on to the process of oxidative phosphorylation which produces the majority of ATP in a cell. However, un Continue reading >>
Dichloroacetate In The Treatment Of Lactic Acidosis.
1. Ann Intern Med. 1988 Jan;108(1):58-63. Dichloroacetate in the treatment of lactic acidosis. Stacpoole PW(1), Lorenz AC, Thomas RG, Harman EM. (1)Department of Medicine, University of Florida, Gainesville. An open, prospective evaluation of the effects of dichloroacetate on morbidityand survival time was done in 29 pediatric and adult patients with lacticacidosis. Dichloroacetate was administered intravenously over 30 minutes as two50 mg/kg body weight doses separated by 2 hours. Five patients underwentretreatment with two additional drug doses and were considered new cases whenanalyzing for treatment response. Survival, however, was determined from the timeof initial entry into the study. Patients were considered to respond to treatmentif arterial lactate concentration decreased at least 20% from the pretreatmentlevel within 6 hours of beginning the first dichloroacetate infusion. Using this criterion, 26 cases responded to therapy with dichloroacetate. For all cases,patients' mean arterial lactate concentration decreased 52% (P = 0.0009),arterial bicarbonate concentration increased 35% (P = 0.0003), and arterial pHincreased (P = 0.024) to normal, defined as the range 7.35 to 7.45. Amongresponders, however, arterial lactate concentration decreased 74% (P = 0.0001),arterial bicarbonate level increased 47% (P = 0.0001), and arterial pH increased (P = 0.0004) to the normal range. Median survival time among responders was 60hours, compared to 26 hours among nonresponders (P less than 0.001). There was noevidence of toxicity to dichloroacetate. Continue reading >>
Metformin-associated Lactic Acidosis: Current Perspectives On Causes And Risk.
Metformin-associated lactic acidosis: Current perspectives on causes and risk. University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Elcelyx Therapeutics, Inc., San Diego, CA, USA. Elcelyx Therapeutics, Inc., San Diego, CA, USA. Electronic address: [email protected] Metabolism. 2016 Feb;65(2):20-9. doi: 10.1016/j.metabol.2015.10.014. Epub 2015 Oct 9. Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment since its FDA approval in patients with normal renal function or mild renal insufficiency to minimize the potential for toxic metformin levels and MALA. However, the reported incidence of lactic acidosis in clinical practice has proved to be very low (<10 cases per 100,000 patient-years). Several groups have suggested that current renal function cutoffs for metformin are too conservative, thus depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy. On the other hand, the success of metformin as the first-line diabete Continue reading >>