Acute Lactic Acidosis

Updated: Sep 26, 2022
  • Author: Bret A Nicks, MD, MHA; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Classically, 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 by means of reabsorption of HCO3. [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 those 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.

The normal blood lactate concentration in an unstressed patient is 0.5-1 mmol/L. Patients with critical illness can be considered to have normal lactate concentrations of less than 2 mmol/L. Hyperlactatemia is defined as a mild to moderate persistent increase in blood lactate concentration (2-4 mmol/L) without metabolic acidosis, whereas lactic acidosis is characterized by persistently increased blood lactate levels (usually >4-5 mmol/L) in association with metabolic acidosis. [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, because it alone cannot provide definitive confirmation of disease presence, severity, or prognosis.

See also the following:


Treatment Overview

Lactic acidosis is characterized by an excess of serum lactate 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, embolic obstructive processes, and further differential diagnosis, exploration, and reassessment.

Treatment with buffering agents for acute lactic acidosis remains controversial.  However, there is a growing body of literature showing the benefit of acute medical intervention, optimal resuscitation (including condition-specific, goal-directed therapies) and lactate clearance. [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 metformin-related lactic acidosis and acute kidney failure found significantly reduced morbidity and mortality related to continuous renal replacement therapy (CRRT) or hemodialysis. [10, 11]


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. [12, 13] 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. 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). 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, [14] these remain rare in the prehospital setting.

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 or predesignated facility for further management.


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 predictory of adverse outcomes. However, while it is most commonly associated with tissue hypoperfusion related to acute circulatory failure, this view of lactic acidosis is too simplified and does not take into account the myriad causes related to increased lactate accumulation that can occur in addition to (type A) or in the absence of (type B) tissue hypoxia. [15]

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 common goal-directed therapies), restoration of circulating fluid volume, improvement of cardiac function, source identification and control, early antimicrobial intervention, and resection of any potential ischemic regions. [7, 16]  Reassessment for ongoing lactate clearance assists ongoing medical management, but treatment success or failure cannot be determined by lactate alone. [17, 15]  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. [18, 15]

When findings of systemic hypoperfusion are not present, 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.

In addition, 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. Even in the setting of lactic acidosis, additional causes of an elevated anion gap should be explored. [19]



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 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 paradoxic worsening acidosis in brain tissues. [20, 21] 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 have been conducted that do not necessarily support this 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 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 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 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.



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 patients in the intensive care unit (ICU) if persistent after 24 hours. The concept of lactate clearance remains a topic of focus in sepsis management. [9, 18, 22, 17] 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. [22]

A retrospective, single-center study by Van De Ginste et al looked at ICU patients with lactate levels of 5 mmol/L or above, finding the 90-day mortality rate in this cohort to be 34.5%. It also reported that the odds of 90-day mortality were 2.3 times greater in patients who began renal replacement therapy (RRT) within 24 hours after reaching those levels. 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. [23]

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 hyperlactatemia 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 hyperlactatemia.” 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. [24]

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 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. It provides unique information related to improving perfusion and resuscitation, but this must be taken in context of the clinical scenario and may require serial assessments concurrent with the changes in the patient's clinical presentation.



While lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients, the etiology of impaired tissue oxygenation is variable. 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 exists, early restoration of perfusion is necessary to prevent or limit multiple organ dysfunction, as well as to reduce morbidity, mortality, hospital length of stay, and, often, 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.