Acute Lactic Acidosis: Overview, Treatment Overview, Prehospital Care (original) (raw)

Overview

Overview

When, in the setting of acidosis, lactic acid clearance is outstripped by lactic acid production, this is known as lactic acidosis. Physiologically, 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 the partial pressure of carbon dioxide (PaCO2). Chronically, renal compensation occurs via HCO3- reabsorption. [1, 2, 3]

Acidosis arises from an increased production of acids, a loss of alkali, or a decreased renal excretion of acids. The underlying etiology of metabolic acidosis is classically categorized into causes that result in an elevated anion gap (AG) (see the Anion Gap calculator) and those that do not. Lactic acidosis (LA), identified by an accumulation of plasma lactate concentration, is one type of anion gap metabolic acidosis and may manifest from numerous conditions. [2, 4, 5] Clinical context and severity govern the effect of lactic acidosis, with mortality increasing by a factor of about three when the condition is associated with sepsis or low-flow states. Lactic acidosis remains the most common cause of metabolic acidosis in hospitalized patients, and the higher the level and the longer the time to normalization, the greater the morbidity and mortality.

The normal blood lactate concentration in an unstressed patient is 0.5-1 mmol/L. Hyperlactemia is defined as a mild to moderate increase in blood lactate concentration (2-4 mmol/L) without concurrent acidosis, whereas lactic acidosis is characterized by a metabolic acidosis concurrent with an elevated lactate. Some characterize increased blood lactate levels of over 4 mmol/L as severe hyperlactemia. [1, 6] Elevated lactate levels, while typically thought of as a marker of inadequate tissue perfusion with concurrent shift toward increased anaerobic metabolism, can be present in patients in whom systemic hypoperfusion is not present and therefore should be considered within the confines of each patient individually. Lactate levels alone cannot provide definitive confirmation of disease presence, severity, or prognosis.

See also the following:

eMedicine Logo

Treatment Overview

Lactic acidosis is characterized by an excess of serum lactate occurring when lactate production is augmented, lactate utilization and clearance are decreased, or both. Numerous etiologies may be responsible for its presence, most commonly circulatory failure and hypoxia, although regional ischemia or impairment of cellular metabolism are additional causes. Evidence suggests increased morbidity and mortality for patients with increasing lactate levels or a decreased rate of lactate clearance. [7, 8] Serial lactate assessments concurrent with focused intervention can help to guide adequate resuscitation. [9]

In addition to acute resuscitative and general supportive measures, identification and discontinuation of any offending agents and treatment of known pathology should occur promptly. Treatment should include source control (ie, administration of appropriate antibiotics, surgical drainage or debridement, chemotherapy for malignancy, discontinuation of potentially causative medications, dietary modification in inborn errors of metabolism), fluid resuscitation, management of embolic obstructive processes, and further differential diagnosis, exploration, and reassessment.

Treatment with buffering agents for acute lactic acidosis remains controversial. Support is limited except in literature showing the benefit in specific, acute medical interventions and optimal resuscitation (including condition-specific, goal-directed therapies). [9]

Aside from resuscitation measures, including adequate intravenous access, fluid resuscitation, and airway stabilization in all potentially critically ill patients, hemoperfusion or hemodialysis may be indicated in association with ethylene glycol, methanol, salicylate, and other related poisonings. Dialysis may also be useful when severe lactic acidosis exists in the setting of renal failure or congestive heart failure, as well as with severe metformin intoxication. Several studies related to sodium-glucose cotransporter-2 (SGLT2) and metformin-related lactic acidosis and acute kidney failure found significantly reduced morbidity and mortality in relation to continuous renal replacement therapy (CRRT) or hemodialysis. [10, 11] Molecular adsorbent recirculating system (MARS) therapy, a hepatic hemofiltration method deployed for acute hepatic failure, has shown utility in decreasing lactic acidosis secondary to hepatic failure. [12]

eMedicine Logo

Prehospital Care

Initial treatment of lactic acidosis predicates an understanding of basic resuscitation, macrohemodynamic monitoring, and the ability to have testing modalities present to identify the elevation. The prognostic value of point-of-care lactate testing in prehospital care has been shown to be a complementary tool that can be used to guide early detection of critical patients. [13, 14] While in most circumstances, hypoperfusion follows sustained hypotension, there are patients with cryptic shock in whom, as assessed using the macrohemodynamic-monitoring guidelines, lactic acidosis may not be detected as early as in other patients. Evidence-based, protocol-driven care in the prehospital setting emergently addresses early resuscitation concurrent with emergent facility transport. Airway assessment, including oxygenation and ventilation considerations, and stabilization are essential for all patients. Supplemental oxygen should be considered concurrent with serial reassessments, especially with any decline in a patient's mental status or vital signs.

Acute resuscitation, including intravenous (IV) fluid repletion with crystalloids, may be initiated if the patient exhibits tachycardia, hypotension, or other signs of poor tissue perfusion (eg, poor capillary refill, cool extremities, altered mentation). Vital signs and cardiac rhythm must be monitored closely because acidosis predisposes patients to dysrhythmias, including tachydysrhythmia and fibrillation (see Normal Vital Signs). While several different noninvasive devices can provide continuous monitoring of tissue perfusion, including those that monitor microhemodynamic parameters, and may represent a surrogate for lactate monitoring, [15] these remain rare in the prehospital setting.

Established prehospital treatment protocols should be followed, and non-protocol medications, such as sodium bicarbonate, should be administered only in conjunction with medical control. Transport all patients to the appropriate emergency or predesignated facility for further management.

eMedicine Logo

Emergency Department Care

Lactic acidosis, the combination of elevated blood lactate and concurrent acidosis, has been traditionally viewed as a marker of tissue hypoxia resulting from inadequate oxygen delivery, and as a predictor of adverse outcomes. However, while it is most commonly associated with tissue hypoperfusion related to acute circulatory failure, this view of lactic acidosis is overly simplified and does not take into account the myriad causes of increased lactate accumulation occurring in addition to (type A lactic acidosis) or in the absence of (type B lactic acidosis) tissue hypoxia. [16] Anticipating the prognosis of patients depends on identifying and reversing the cause and the level (as well as the persistence) of lactate.

Physiologically, it has been suggested that a numerical relationship between lactate and pyruvate levels can potentially differentiate causes of type A versus type B lactic acidosis. In normal conditions, a ratio of 10 lactate to 1 pyruvate (L/P ratio=10) is expected. In type A lactic acidosis, hypoperfusion and hypoxia generate significant levels of lactate disproportionate to pyruvate, resulting in higher L/P ratios. Type B causes generally result in normal or low L/P ratios because they typically do not involve anerobic glycolysis; therefore, they maintain proportional changes of lactate and pyruvate. Additionally, the L/P ratio may also serve as a prognostic tool, with studies suggesting that a normal L/P ratio is linked to better health outcomes compared with high L/P ratios. However more research is required to further elucidate this relationship. [17]

Treatment of lactic acidosis requires prompt identification of the underlying illness, directed resuscitative and therapeutic interventions, and serial reassessment. Restoration of tissue oxygen delivery, thereby causing cessation of acid production and enhancing lactate clearance, remains the primary therapeutic focus when tissue hypoperfusion is the cause of the lactic acidemia. Resuscitative efforts should be complemented by measures targeting the cause or causes of lactic acidosis. Such strategies can include the treatment of sepsis (recognizing current goal-directed therapies), restoration of circulating fluid volume, improvement of cardiac function, source identification and control, early antimicrobial intervention, and reperfusion or resection of any potential ischemic regions. [7, 18] Reassessment for ongoing lactate clearance assists ongoing medical management, but treatment success or failure cannot be determined by lactate alone. [19, 16] Also recognize that an increase in blood lactate following pressor use in septic shock (eg, epinephrine) may occur secondary to increased glycolysis concurrent with improved oxygen delivery. [20, 16]

In the absence of systemic hypoperfusion, consider possible toxin-induced or bowel-associated impairment of cellular metabolism as the cause of lactic acidosis, as can occur with biguanide therapy (metformin-associated lactic acidosis), malignancy (lymphoma, leukemia, solid malignancies), alcoholism, human immunodeficiency virus (HIV) medications (reverse transcriptase inhibitors), or short-gut (malabsorptive) syndromes. Other commonly prescribed medications that can cause lactic acidosis include beta-adrenergic agonists, [21] valproic acid, [22] linezolid, [23] and isoniazid. [24]

Several case reports have documented lactic acidosis occurring as a result of beta-adrenergic therapies in patients with status asthmaticus. Continuous albuterol is frequently utilized in acute management of severe asthma exacerbations. When administered to patients with respiratory acidosis, there is a potential risk of increased metabolic demand, leading to upregulation of biochemical processes favoring pyruvate production and resultant hyperlactemia. [21]

When considering ongoing laboratory assessments, recognize that anion gap screening does not predict lactate levels. A normal anion gap does not exclude the possibility of lactic acidosis, which can present with a normal anion gap up to 50% of the time. Moreover, even in the setting of lactic acidosis, additional causes of an elevated anion gap should be explored. [25]

eMedicine Logo

Pharmacotherapy

One of the primary goals in treating critically ill patients is optimizing 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 only advocated in the setting of severe acidosis when physiologic uncoupling occurs, as well as in unique toxicologic situations and specific renal dysfunction. Additionally, it has been demonstrated that bicarbonate therapy alone does not improve hemodynamics in the critically ill patient with lactic acidosis, and this treatment may induce a harmful paradoxical acidosis in brain tissues. [26, 27] In patients unable to reclaim bicarbonate (eg, renal failure, renal tubular acidosis), treatment concurrent with ongoing resuscitative measures based on the acute disease process identified should be considered when appropriate.

While it is physiologically intuitive that acidosis should be correctable through buffering interventions and homeostasis optimized for physiologic functions, large studies do not uniformly support this generalized approach. Below are some unique considerations regarding when such treatment may be appropriate. However, before the initiation of pharmacologic buffering therapy, consultation with a critical care specialist and/or nephrologist should be considered to determine the optimal course of action, so as to avoid paradoxical acidosis.

Sodium bicarbonate

The starting dose of sodium bicarbonate (NaHCO3-) is one third to one half of the calculated extracellular bicarbonate (HCO3-) deficit, as illustrated by the following formula:

HCO3 deficit (in mEq) = 0.5 × (Wt in kg) × (Desired HCO3 – Measured HCO3)

Metabolic alkalosis can ensue after bicarbonate administration if the 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 central venous carbon dioxide tension (PvCO2). Minute ventilation must be increased in order to expel carbon dioxide (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 Cyanide Toxicity, Ethylene Glycol Toxicity, and Toxicity, Alcohols). These are unique circumstances that require bicarbonate therapy to facilitate the detoxification processes.

Thiamine

Thiamine deficiency may be associated with cardiovascular compromise and lactic acidosis. The response to thiamine repletion (given as 50-100 mg intravenously [IV] followed by 50 mg/d orally [PO] for 1-2 wk) may be dramatic and potentially lifesaving.

Other agents

The following agents have theoretical advantages but either have not been proven to be more effective than bicarbonate or have not been demonstrated to be effective in humans.

Tris-[hydroxymethyl] aminomethane

Tris-[hydroxymethyl] aminomethane (THAM) has theoretical advantages over bicarbonate because CO2 is not generated. This agent 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. Although this theoretical advantage should favor its use over bicarbonate, there is no evidence in humans to support improved outcomes.

Dichloroacetate

Dichloroacetate is not a buffer, but this agent stimulates the oxidation of pyruvate. This has resulted in improved lactate utilization and increased tissue levels of adenosine-triphosphate (ATP). However, prospective studies have failed to demonstrate its efficacy.

Miscellaneous agents

Coenzyme Q, l-carnitine, and riboflavin have been used to treat lactic acidosis due to antiretroviral therapy, without definitive demonstration of efficacy.

eMedicine Logo

Outcomes

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 are associated with an 11% survival rate in critically ill intensive care unit (ICU) patients if persistent after 24 hours. The concept of lactate clearance remains a topic of focus in sepsis management. [9, 20, 28, 19] Further studies have demonstrated an association between a 12-hour rise in lactate concentration above 2.5 mmol/L and multisystem organ failure. [6, 7]

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. [28]

A retrospective, single-center study by Van De Ginste et al identified a 90-day mortality rate of 34.5% in ICU patients with lactate levels above 5 mmol/L. Additionally, the odds of 90-day mortality were 2.3 times greater in those patients receiving renal replacement therapy (RRT) within 24 hours after reaching those levels, likely reflecting the severity of illness. The investigators stated that “without being a bridge to correction of the underlying condition, dialysis is unlikely to affect the outcome” in such cases of severe lactic acidosis. [29]

A meta-analysis by Zeng et al reported a relationship between elevated lactate and negative outcomes in patients with upper gastrointestinal bleeding (UGIB). Eleven observational studies elucidated data suggesting that elevated lactate levels in UGIB correlate with significantly higher ICU admissions, need for blood transfusions, increased rebleeding risk, and mortality. [30]

The coronavirus disease 2019 (COVID-19) pandemic may further highlight lactic acidosis as one of many markers that may indicate intensive care admission or prognosis in disease. A literature review by Carpenè et al found that in patients with COVID-19, blood lactate levels were often higher in patients with worse outcomes. However, baseline hyperlactemia was not found in most of the study’s patients, and many patients with unfavorable outcomes lacked substantial lactate elevation. According to the investigators, this suggests that severe COVID-19 has a multifactorial pathogenesis that is “in part independent from severe ischemia and hyperlactemia.” Confirmation of this, they state, comes from findings that blood lactate levels tend to be lower in patients with COVID-19–related pneumonia or acute respiratory distress syndrome (ARDS) than in individuals whose pneumonia or ARDS is not associated with COVID-19. [31]

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 emergency department. The lactate level should be used in combination with clinical findings and other measures of circulatory failure rather than as a decisive indicator of disease severity. It provides unique information related to improving perfusion and resuscitation, but this must be taken in the context of the clinical scenario and may require serial assessments concurrent with the changes in the patient's clinical presentation.

eMedicine Logo

Summary

While lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients, the etiology of impaired tissue oxygenation varies. Typically associated with systemic hypoperfusion (type A) leading to increased anaerobic metabolism, early recognition of the clinical signs of hypoperfusion is essential. Additionally, if hypoperfusion is present, early perfusion restoration remains integral to protecting organ function, reducing morbidity, mortality, hospital length of stay, and associated cost. In those circumstances in which hypotension or systemic hypoperfusion are not present (type B), the underlying cause should be further investigated. Ongoing research into lactic acidosis and lactate clearance, as well as noninvasive surrogate measures for early detection of lactic acidosis and guided intervention for critical illnesses, may add further insight into outcome-based practices and future care considerations.

eMedicine Logo

Questions & Answers

  1. Kraut JA, Madias NE. Lactic acidosis. N Engl J Med. 2014 Dec 11. 371 (24):2309-19. [QxMD MEDLINE Link]. [Full Text].
  2. Suetrong B, Walley KR. Lactic acidosis in sepsis: It's not all anaerobic. Implications for diagnosis and management. Chest. 2015 Sep 17. [QxMD MEDLINE Link].
  3. Foucher CD, Tubben RE. Lactic Acidosis. StatPearls. 2023 Jul 17. [QxMD MEDLINE Link]. [Full Text].
  4. Forrest DM, Russell JA. Metabolic acidosis. Webb A, Shapiro M, Singer M, Suter P, eds. Oxford Textbook of Critical Care. Oxford, United Kingdom: Oxford University Press; 1999. 573-7.
  5. Seheult J, Fitzpatrick G, Boran G. Lactic acidosis: an update. Clin Chem Lab Med. 2017 Mar 1. 55 (3):322-33. [QxMD MEDLINE Link]. [Full Text].
  6. Bellomo R, Marik P, Kellum JA. Lactic acidosis. N Engl J Med. 2015 Mar 12. 372 (11):1076. [QxMD MEDLINE Link].
  7. 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. [QxMD MEDLINE Link].
  8. Lee SW, Hong YS, Park DW, Choi SH, Moon SW, Park JS, et al. Lactic acidosis not hyperlactatemia as a predictor of in hospital mortality in septic emergency patients. Emerg Med J. 2008 Oct. 25 (10):659-65. [QxMD MEDLINE Link].
  9. Jones AE. Point: should lactate clearance be substituted for central venous oxygen saturation as goals of early severe sepsis and septic shock therapy? Yes. Chest. 2011 Dec. 140(6):1406-8. [QxMD MEDLINE Link]. [Full Text].
  10. Angioi A, Cabiddu G, Conti M, et al. Metformin associated lactic acidosis: a case series of 28 patients treated with sustained low-efficiency dialysis (SLED) and long-term follow-up. BMC Nephrol. 2018 Apr 2. 19 (1):77. [QxMD MEDLINE Link]. [Full Text].
  11. Uusalo P, Jarvisalo MJ. Mortality and renal prognosis in isolated metformin-associated lactic acidosis treated with continuous renal replacement therapy and citrate-calcium-anticoagulation. Acta Anaesthesiol Scand. 2020 Jun 21. [QxMD MEDLINE Link]. [Full Text].
  12. Monet C, De Jong A, Aarab Y, et al. Adverse events, short- and long-term outcomes of extra corporeal liver therapy in the intensive care unit: 16 years experience with MARS® in a single center. Crit Care. 2022 Sep 19. 26 (1):282. [QxMD MEDLINE Link]. [Full Text].
  13. Martin-Rodriguez F, Lopez-Izquierdo R, Castro Villamor MA, et al. Prognostic value of lactate in prehospital care as a predictor of early mortality. Am J Emerg Med. 2019 Sep. 37 (9):1627-32. [QxMD MEDLINE Link].
  14. St John AE, McCoy AM, Moyes AG, Guyette FX, Bulger EM, Sayre MR. Prehospital Lactate Predicts Need for Resuscitative Care in Non-hypotensive Trauma Patients. West J Emerg Med. 2018 Mar. 19 (2):224-31. [QxMD MEDLINE Link]. [Full Text].
  15. Shapiro NI, Arnold R, Sherwin R, O'Connor J, Najarro G, Singh S. The association of near-infrared spectroscopy-derived tissue oxygenation measurements with sepsis syndromes, organ dysfunction and mortality in emergency department patients with sepsis. Crit Care. 2011. 15(5):R223. [QxMD MEDLINE Link].
  16. Suetrong B, Walley KR. Lactic Acidosis in Sepsis: It's Not All Anaerobic: Implications for Diagnosis and Management. Chest. 2016 Jan. 149 (1):252-61. [QxMD MEDLINE Link].
  17. Redant S, Hussein H, Mugisha A, et al. Differentiating Hyperlactatemia Type A From Type B: How Does the Lactate/pyruvate Ratio Help?. J Transl Int Med. 2019 Jun. 7 (2):43-5. [QxMD MEDLINE Link]. [Full Text].
  18. 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. [QxMD MEDLINE Link]. [Full Text].
  19. Reddy AJ, Lam SW, Bauer SR, Guzman JA. Lactic acidosis: Clinical implications and management strategies. Cleve Clin J Med. 2015 Sep. 82 (9):615-24. [QxMD MEDLINE Link].
  20. 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. [QxMD MEDLINE Link].
  21. Claret PG, Bobbia X, Boutin C, Rougier M, de la Coussaye JE. Lactic acidosis as a complication of β-adrenergic aerosols. Am J Emerg Med. 2012 Sep. 30 (7):1319.e5-6. [QxMD MEDLINE Link].
  22. Chaudhry N, Patidar Y, Puri V. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes unveiled by valproate. J Pediatr Neurosci. 2013 May. 8 (2):135-7. [QxMD MEDLINE Link]. [Full Text].
  23. Ramesh V, Gattu S, Maqsood M, Rao V. Linezolid-induced lactic acidosis. BMJ Case Rep. 2024 Feb 7. 17 (2):[QxMD MEDLINE Link].
  24. Neff TA. Isoniazid toxicity: reports of lactic acidosis and keratitis. Chest. 1971 Mar. 59 (3):245-8. [QxMD MEDLINE Link].
  25. Xu Q, HowlettClyne S, Fuezery A, Cembrowski GS. Low sensitivity of anion gap to detect clinically significant lactic acidosis in the emergency department. Clin Biochem. 2017 Dec. 50 (18):1164-7. [QxMD MEDLINE Link].
  26. 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. [QxMD MEDLINE Link].
  27. Forsythe SM, Schmidt GA. Sodium bicarbonate for the treatment of lactic acidosis. Chest. 2000 Jan. 117(1):260-7. [QxMD MEDLINE Link].
  28. 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. [QxMD MEDLINE Link].
  29. Van De Ginste L, Vanommeslaeghe F, Hoste EAJ, Kruse JM, Van Biesen W, Verbeke F. Patients with Severe Lactic Acidosis in the Intensive Care Unit: A Retrospective Study of Contributing Factors and Impact of Renal Replacement Therapy. Blood Purif. 2022. 51 (7):577-83. [QxMD MEDLINE Link].
  30. Zeng F, Du L, Ling L. Lactate level as a predictor of outcomes in patients with acute upper gastrointestinal bleeding: A systematic review and meta‑analysis. Exp Ther Med. 2024 Mar. 27 (3):113. [QxMD MEDLINE Link]. [Full Text].
  31. Carpene G, Onorato D, Nocini R, et al. Blood lactate concentration in COVID-19: a systematic literature review. Clin Chem Lab Med. 2022 Feb 23. 60 (3):332-7. [QxMD MEDLINE Link]. [Full Text].

Previous

Next

Author

Bret A Nicks, MD, MHA, FACEP Professor and EVC, Department of Emergency Medicine, Davie Medical Center, Atrium Health Wake Forest Baptist, Wake Forest University School of Medicine

Bret A Nicks, MD, MHA, FACEP is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, Christian Medical and Dental Associations, International Federation for Emergency Medicine, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

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.

Howard A Bessen, MD Professor of Medicine, Department of Emergency Medicine, University of California, Los Angeles, David Geffen School of Medicine; Program Director, Harbor-UCLA Medical Center

Howard A Bessen, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP (Retired) Professor, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinology, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Stephen W Borron, MD, MS, FAAEM, FACEP, FAACT, FACMT Professor of Emergency Medicine and Medical Toxicology, Division of Medical Toxicology, Department of Emergency Medicine, Paul L Foster School of Medicine, Texas Tech University Health Sciences Center; Associate Medical Director, West Texas Regional Poison Center

Stephen W Borron, MD, MS, FAAEM, FACEP, FAACT, FACMT is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American Industrial Hygiene Association, American College of Occupational and Environmental Medicine, European Association of Poisons Centres and Clinical Toxicologists, American College of Medical Toxicology

Disclosure: Received consulting fee from Meridian Pharmaceuticals for consulting.

Bruno Mégarbane, MD, PhD Professor of Critical Care Medicine, Paris-Diderot University; Senior Physician, Medical and Toxicological Intensive Care Unit, Lariboisière Hospital, France

Disclosure: Nothing to disclose.

Henderson D McGinnis, MD Assistant Medical Director, AirCare Critical Care Transport Services; Clinical Instructor, Department of Emergency Medicine, Wake Forest University Baptist Medical Center

Disclosure: Nothing to disclose.

Erik D Schraga, MD Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates

Disclosure: Nothing to disclose.