You are in: eMedicine Specialties > Emergency Medicine > ENDOCRINE AND METABOLIC Lactic AcidosisArticle Last Updated: Apr 9, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Bret A Nicks, MD, Assistant Professor, Assistant Medical Director, Department of Emergency Medicine, Wake Forest University Health Sciences Bret A Nicks is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, Christian Medical & Dental Society, Society for Academic Emergency Medicine, and Wilderness Medical Society Coauthor(s): Henderson D McGinnis, MD, Assistant Medical Director, AirCare Critical Care Transport Services; Clinical Instructor, Department of Emergency Medicine, Wake Forest University Baptist Medical Center; Stephen W Borron, MD, MS, International Toxicology Consultants; Bruno Mégarbane, MD, Fellow, Medical and Toxicological Intensive Care Unit, Lariboisière University Hospital Editors: Erik D Schraga, MD, Consulting Staff, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates; Consulting Staff, Permanente Medical Group, Kaiser Permanente, Santa Clara Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Howard A Bessen, MD, Professor of Medicine, Department of Emergency Medicine, UCLA School of Medicine; Program Director, Harbor-UCLA Medical Center; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital Author and Editor Disclosure Synonyms and related keywords: metabolic acidosis, arterial blood pH less than 7.35, plasma bicarbonate concentration less than 22 mmol/L, hyperlactatemia, hypoperfusion, hypoxia, cardiopulmonary failure, inborn errors of metabolism, multiple organ failure, cyanosis, cold extremities, INTRODUCTIONSection 2 of 12
  Metabolic acidosis is defined as a state of decreased systemic pH resulting from either a primary increase in hydrogen ion (H+) or a reduction in bicarbonate (HCO3-) concentrations. In the acute state, respiratory compensation of acidosis occurs by hyperventilation resulting in a relative reduction in PaCO2. Chronically, renal compensation occurs by means of reabsorption of HCO3. Acidosis arises from an increased production of acids, a loss of alkali, or a decreased renal excretion of acids (see Metabolic Acidosis). The underlying etiology of metabolic acidosis is classically categorized into those that cause an elevated anion gap (AG) and those that do not. Lactic acidosis, identified by a state of acidosis and an elevated plasma lactate concentration is one type of anion gap metabolic acidosis and may result from numerous conditions. PATHOPHYSIOLOGYSection 3 of 12
Lactate, a product of anaerobic glucose metabolism, is generated from pyruvate with lactate dehydrogenase as a catalyst. Pyruvate is normally aerobically metabolized to CO2 and H2O in the mitochondrion in the process of gluconeogenesis. Additionally, pyruvate is in a state of equilibrium with lactate that, under certain conditions, can shift toward the overproduction of lactate. Lactic acidosis results from an increase in blood lactate levels when lactate production exceeds consumption and body buffer systems become overburdened. This occurs when tissue oxygenation is inadequate to meet metabolic requirements as a result of either hypoperfusion or hypoxia. Lactate is cleared from blood, primarily by the liver, with the kidneys (10-20%) and skeletal muscles to a lesser degree. Cardiopulmonary failure, sepsis, trauma, thiamine deficiency, side effects of drugs and toxins, oncologic pathology, and various acquired and congenital diseases can lead to lactic acidosis. Types of lactic acidosis Classically, lactic acidosis was described and classified by Cohen and Woods into 2 categories1:
In basic terms, lactic acid is the normal endpoint of the anaerobic breakdown of glucose in the tissues. The lactate exits the cells and is transported to the liver where it is oxidized back to glucose. In the setting of decreased tissue oxygenation, lactic acid is produced as the anaerobic cycle is utilized for energy production. With a persistent oxygen debt and overwhelming of the body's buffering abilities (whether from chronic dysfunction or excessive production), lactic acidosis ensues. See Media file 1 for a classification table of lactic acidosis types. Frequency/limitations Aberrant lactate metabolism is frequently encountered among critically ill patients. Those with predisposing underlying disease states and medications portend an increased occurrence. The overall incidence of lactic acidosis in critically ill patients is unknown; however, increasing acid-base evaluations of critically ill patients indicate its persistence increases associated morbidity and mortality. The use of lactate as an index of tissue perfusion has several limitations as briefly identified above. Chronic underutilization states, such as liver disease, can cause a decreased ability to clear lactate during periods of increased production whether acidemic or not. Various causes of type B lactate acidosis may produce hyperlactemia and lactate acidosis in the absence of tissue hypoperfusion. Regional hypoperfusion of tissues may be present despite a normal lactate if metabolism remains intact and reperfusion has not occurred. Further tests are ongoing at this time to better delineate the value of lactate measurements in this patient population and how it interrelates to other markers of resuscitation and acid-base abnormalities. Mortality/morbidity Patients exhibiting a disorder of lactate metabolism are typically significantly ill and are at risk for developing multiple organ failure. Patients suffer a hospital mortality rate that increases nearly linearly with the concentration of serum lactate. Several studies have shown that vigilant correction of hyperlactemia is associated with decreased morbidity and mortality. The mortality rate of patients with a serum lactate level greater than 2 mmol/L persisting after 24 hours with an associated acidemia approaches 70%. CLINICALSection 4 of 12
History No single historical feature itself is indicative of the presence of lactic acidosis, as symptoms are dependent on the underlying etiology. Nevertheless, a careful history is vital to determine the underlying pathology. The onset of acidosis may be rapid (ie, within minutes to hours) or progressive (ie, over a period of several days). Physical findings The physical examination also depends on the underlying cause of lactic acidosis. Signs of cardiovascular compromise frequently include cyanosis, cool extremities, tachycardia, hypotension, dry mucous membranes, dyspnea, confusion, lethargy, stupor, or coma. Hyperventilation is common as a compensatory mechanism causing respiratory alkalosis. Systemic effects of acidosis
ETIOLOGYSection 5 of 12
Classification of lactic acidosis The most frequent cause of lactic acidosis is poor tissue perfusion, which is induced by various shock states causing tissue hypoxia. In ischemic tissues of the skeletal muscle (and less significantly intestine, erythrocytes, and brain), production of lactate is accelerated with a concomitant fall in lactate consumption by the liver, kidney, and myocardium. The accumulation of a normally balanced level of serum lactate overwhelms the body's buffering capacity and results in acidosis. Lactic acidosis occurring from associated underlying diseases, known as type B1, has been identified with diabetes mellitus, bowel ischemia, severe iron-deficiency anemia, liver disease, alcoholic ketoacidosis, pancreatitis, malignancy (leukemia, lymphoma, lung cancer), infection, renal failure, seizures, heat stroke, pheochromocytoma, thiamine deficiency, short gut syndrome, and other carbohydrate malabsorption syndromes. Medicinal and toxic causes of lactic acidosis, known as type B2, are numerous, including acetaminophen, alcohols and glycols (ethanol, ethylene glycol, methanol, propylene glycol), antiretroviral nucleoside analogs (zidovudine, didanosine, lamivudine), beta-adrenergic agents (epinephrine, ritodrine, terbutaline), biguanides (phenformin, metformin), cocaine, cyanogenic compounds (cyanide, aliphatic nitriles, nitroprusside), diethyl ether, 5-fluorouracil, halothane, iron, isoniazid, propofol, sugars and sugar alcohols (fructose, sorbitol, and xylitol), salicylates, strychnine, sulfasalazine, and valproic acid. Type B3 lactic acidosis may result in those with inborn errors of metabolism. These include glucose-6-phosphatase deficiency (von Gierke disease), fructose-1,6-diphosphatase deficiency, pyruvate carboxylase deficiency, pyruvate dehydrogenase deficiency, oxidative phosphorylation deficiency, and methylmalonic aciduria. Lactic acidosis rarely may present in the MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes), which appears to be caused by a point mutation in mitochondrial DNA tRNALeu (UUR) gene. This syndrome is characterized by migrainelike headaches, dementia, hearing loss, ataxia, and episodic vomiting. WORKUPSection 6 of 12
Laboratory studies 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.
New devices (near-infrared spectroscopy) that look noninvasively at the correlation between tissue perfusion and lactate levels are currently being studied. Other tests Additional laboratory tests may be selected on the basis of the suspected underlying etiology of lactic acidosis. TREATMENTSection 7 of 12
Prehospital care Initial treatment predicates an understanding of basic resuscitation. Airway assessment and stabilization is essential for all patients. Supplemental oxygen may be required, and the airway must be repeatedly reassessed, especially if the patient's mental status or vital signs decline. An intravenous (IV) line should be established, and fluid repletion with normal saline may be initiated if the patient exhibits tachycardia, hypotension, or other signs of poor tissue perfusion (eg, poor capillary refill, cool extremities). Vital signs and cardiac rhythm must be monitored closely because acidosis predisposes to dysrhythmias including tachydysrhythmias and fibrillation. Established prehospital treatment protocols should be followed, and nonprotocol medications, such as sodium bicarbonate, should be administered only in conjunction with medical control. Transport all patients to the appropriate emergency facility for further management. Emergency department care Lactic acidosis is typically associated with tissue hypoperfusion and states of acute circulatory failure. Treatment of lactic acidosis requires identification of the primary illness and directed therapy. Restoration of tissue oxygen delivery, thereby causing cessation of acid production, remains the primary therapeutic focus. Goal-directed therapy for sepsis is well described and is associated with improved outcomes. Appropriate measures include treatment of shock, restoration of circulating fluid volume, improved cardiac function, identification of sepsis source and appropriate therapy, and resection of any potential ischemic regions. Continuing care In addition to general supportive measures, treatments must be directed at correction of the underlying disorder and may include the administration of appropriate antibiotics, surgical drainage or debridement, chemotherapy for malignancy, discontinuation of potentially causative medications, and dietary modification in inborn errors of metabolism. Procedures Aside from resuscitation measures including adequate intravenous access and airway stabilization in all potentially ill patients, hemoperfusion or hemodialysis may be indicated in association with ethylene glycol and methanol poisoning. Dialysis may also be useful when severe lactic acidosis exists in the setting of renal failure or congestive heart failure and additionally with metformin intoxication. MEDICATIONSSection 8 of 12
One of the primary goals in treating critically ill patients is maximizing systemic oxygen delivery. Much debate has surrounded the potential use of buffering agents (specifically bicarbonate) to reverse the potentially negative effects of acidosis, but their use is generally advocated in the setting of severe acidosis. It seems somewhat intuitive that acidosis should be corrected and homeostasis maintained for physiologic functions to return. However, large studies have been conducted that do not necessarily support this approach. Prior to the initiation of pharmacologic therapy, consultation with a critical care specialist and/or nephrologist is recommended to determine the optimal course of action. The starting dose is one third to one half of the calculated extracellular bicarbonate deficit:
Metabolic alkalosis can ensue after bicarbonate administration if correction is complete rather than partial. This result can be avoided by titration of the bicarbonate dose to modest therapeutic end points (eg, arterial pH of 7.20). In severe hypoxemia, sodium bicarbonate should be administered by slow infusion to minimize any increase in PvCO2. Minute ventilation must be increased in order to expel CO2 generated by bicarbonate administration. Because of increased CO2 production, sodium bicarbonate may precipitate ventilatory failure and, as such, must be given with caution. Toxic etiologies of lactic acidosis, such as methanol, ethylene glycol, and cyanide poisoning may justify administration of bicarbonate (see articles on Toxicity, Cyanide, Toxicity, Ethylene Glycol, and Toxicity, Alcohols). Tris-[hydroxymethyl] aminomethane Tris-[hydroxymethyl] aminomethane (THAM) has theoretical advantages over bicarbonate because CO2 is not generated. It has been studied in animals and humans but has not been proven to be more effective than bicarbonate. Carbicarb Carbicarb is a combination of sodium carbonate and sodium bicarbonate that buffers comparably to bicarbonate but does not generate CO2. While this theoretical advantage should favor its use over bicarbonate, there is no evidence in humans to support improved outcomes. Dichloroacetate This agent is not a buffer, but it stimulates the oxidation of pyruvate. This has resulted in improved lactate utilization and increased tissue levels of ATP. Prospective studies have failed to demonstrate its efficacy. Thiamine Thiamine deficiency may be associated with cardiovascular compromise and lactic acidosis. The response to thiamine repletion (given as 50-100 mg IV followed by 50 mg/d PO for 1-2 wk) may be dramatic and potentially life saving. Miscellaneous agents Coenzyme Q, l-carnitine, and riboflavin have been used to treat lactic acidosis due to antiretroviral therapy, without definitive demonstration of efficacy. PROGNOSISSection 9 of 12
Lactate levels have been well described to correlate with the presence of tissue hypoperfusion in shock. Elevated levels have been shown to be correlated with increased mortality. Serum lactate levels above 4 mmol/L were associated with a survival of only 11% in critically ill ICU patients if persistent after 24 hours. Further studies have demonstrated an association between a 12-hour rise in lactate concentration above 2.5 mmol/L and multisystem organ failure. The duration and degree of increased serum lactic acid appear to predict morbidity and mortality. Abramson et al identified 100% survival with normalization of serum lactate concentration (<2 mmol/L) within the first 24 hours following multiple trauma, 78% survival if normalization occurred in 24-48 hours, and only 14% survival if after 48 hours.2 With the onset of bedside serum lactate analyzers, measurements can be obtained in minutes with excellent correlation with traditional measurements. Studies have been performed to predict required hospital admission and mortality, but they were unable to define a lactate level below which a patient could be safely discharged from the ED. The lactate level should be used only as a single tool in combination with clinical findings and other measures of circulatory failure rather than as a decisive indicator of disease severity. SUMMARYSection 10 of 12
Lactic acidosis is characterized by an excess of serum lactate due to lactate production that exceeds systemic consumption. Numerous etiologies may be responsible for its presence, most commonly circulatory failure and hypoxia. Evidence suggests increased morbidity and mortality for patients with persistently elevated or increasing lactate levels. Identification and discontinuation of any offending agents and treatment of known pathology should occur promptly. Although treatment with buffering agents remains controversial, their use should be considered in certain instances with the assistance of critical care consultation. Elevated lactate levels as a marker for inadequate tissue perfusion should be considered within the confines of each patient individually because it alone cannot provide definitive confirmation of disease presence, severity, or prognosis. MULTIMEDIASection 11 of 12
REFERENCESSection 12 of 12
Article Last Updated: Apr 9, 2008 | ||||||||||||
