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. [1, 2]
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 that cause an elevated anion gap (AG) (see the Anion Gap calculator) 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. [2, 3] It remains the most common cause of metabolic acidosis in hospitalized patients.
The normal blood lactate concentration in unstressed patients 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, 4] 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.
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As mentioned earlier, 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. [5, 6]
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, and further differential diagnosis exploration and reassessment.
Although treatment with buffering agents remains controversial, their use should be considered in certain instances with the assistance of appropriate medical consultation. In addition, there is a growing body of literature showing the benefit of acute medical management, appropriate intervention (including early goal directed therapy) and lactate clearance. 
Aside from resuscitation measures, including adequate intravenous access, fluid resuscitation, and airway stabilization in all potentially 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 and, additionally, with severe metformin intoxication.
Initial treatment of lactic acidosis predicates an understanding of basic resuscitation and the ability to have testing modalities present to identify the elevation. In most circumstances, this refers to patients being emergently transferred between facilities to a higher level of care, or presumptive care in the prehospital setting. Airway assessment, including oxygenation and ventilation considerations, and stabilization are essential for all patients. Supplemental oxygen should be considered concurrent with serial reassessments, especially if the patient's mental status or vital signs decline.
An intravenous (IV) line should be established, and 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 to dysrhythmias, including tachydysrhythmia and fibrillation. While several different noninvasive devices can provide continuous monitoring of tissue perfusion, a surrogate for lactate monitoring,  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 is most commonly associated with tissue hypoperfusion and states of acute circulatory failure. Treatment of lactic acidosis requires prompt identification of the primary illness, appropriately directed therapy, and serial reassessment. Restoration of tissue oxygen delivery, thereby causing cessation of acid production, remains the primary therapeutic focus when tissue hypoperfusion is the cause of the lactic acidemia. Many aspects of early goal-directed therapy (EGDT) for sepsis are well described and associated with improved outcomes. Appropriate measures include treatment of shock, restoration of circulating fluid volume, improved cardiac function, identification of sepsis source, early antimicrobial intervention, and resection of any potential ischemic regions. [5, 9] Reassessment of lactate levels for clearance assists ongoing medical management.
When findings of systemic hypoperfusion are not present, consider possible toxin-induced or bowel-associated impairment of cellular metabolism causing a lactic acidosis, such as biguanide therapy (metformin), malignancy (lymphoma, leukemia, solid malignancies), alcoholism, HIV medications (reverse transcriptase inhibitors), or short gut (malabsorptive) syndromes.
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 when physiologic uncoupling occurs. In addition, it has also been demonstrated that bicarbonate therapy alone does not improve hemodynamics in the critically ill patient with lactic acidosis, and this treatment may induce a paradoxical worsening acidosis in brain tissues. [10, 11] 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.
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. 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.
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.
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 (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.
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. [7, 12, 13, 14] Further studies have demonstrated an association between a 12-hour rise in lactate concentration above 2.5 mmol/L and multisystem organ failure. [4, 5, 15]
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. 
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 lactic acidosis) 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 mortality. In those circumstances in which hypotension or systemic hypoperfusion are not present, type B lactic acidosis and its causes should be investigated.Ongoing research into lactate clearance, and perhaps noninvasive surrogate measures, in many disease modalities will certainly add further insight into outcome-based practices and further considerations.