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Lactic acidosis


1.1 Incidence, risk factors and pathophysiology

Lactic acidosis is a life-threatening metabolic acidosis, characterized by a decreased arterial pH (< 7.37) secondary to accumulation of blood lactate (more than 2 mEq/L). It often occurs as a consequence of hypoperfusion and severe tissue hypoxia as seen in patients with shock and septicaemia or is associated with a number of predisposing diseases (e.g. diabetes mellitus, renal disease, alcoholism, liver disease). It has been described occasionally in cancer patients with rapidly progressive leukaemia or lymphoma with possible tumour overproduction of lactate under anaerobic circumstances or for a high rate of glycolysis, whereas patients with solid tumours (e.g. lung cancer) may present with extensive liver metastases and reduced hepatic clearance of lactate.
Other causes of lactate acidosis are cardiopulmonary failure, sepsis, trauma, thiamine deficiency, side effects of drugs and toxins, and various acquired and congenital diseases.

Lactate is a product of anaerobic glucose metabolism and is generated from pyruvate by lactate dehydrogenase. Pyruvate is normally aerobically metabolized to CO2 and H2O in the mitochondrion by 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 the 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, kidney, and skeletal muscles.

Lactic acid exists in two forms
•    L-lactate is the most commonly measured level as it is the only form produced in human metabolism. Its excess represents increased anaerobic metabolism due to tissue hypoperfusion.
•    D-lactate is a by-product of bacterial metabolism and may accumulate in patients with short-gut syndrome or in those with a history of gastric bypass or small bowel resection.

There are 2 types of lactate acidosis
•    Type A lactic acidosis with decreased tissue adenosine triphosphate (ATP) due to poor tissue perfusion or oxygenation
•    Type B lactic acidosis without poor tissue perfusion or oxygenation although occult tissue hypoperfusion may be present.
o    Type B1 occurs in association with systemic disease such as renal and hepatic failure, diabetes and cancer
o    Type B2 is caused by several classes of drugs (antiretroviral nucleoside analogs (zidovudine, didanosine, lamivudine), beta-adrenergic agents (epinephrine, ritodrine, terbutaline), biguanides (phenformin, metformin), cyanogenic compounds (aliphatic nitriles, nitroprusside), 5-fluorouracil, halothane, iron, isoniazid, propofol, sugars and sugar alcohols (fructose, sorbitol, and xylitol), sulfasalazine, salicylates and valproic acid) and toxins (cocaine, cyanide, strychnine diethyl ether, ethanol, ethylene glycol, methanol, propylene glycol)
o    Type B3 is due to inborn errors of metabolism.


2.1 Clinical presentation

Patients with lactate acidosis are critically ill and are at risk for developing multiple organ failure.
They may show dyspnoea with an increased minute ventilation to compensate with respiratory alkalosis, decreased diaphragm contractility; decreased catecholamine responsiveness of the heart with a decreased fibrillation threshold and a decreased contractility at pH 7.2; increased cerebral blood flow, decreased cerebral metabolism, altered mental status; decreased renal and hepatic perfusion and increased metabolic rate with increased protein catabolism.
They show hyperventilation, hypotension, tachycardia, nausea, confusion and rapidly progressive shock as the acidosis worsens.

2.2 Diagnosis

Biochemical evaluation reveals a decreased arterial pH ( 2 mEq/L).
There is an increased anion gap calculated as: sodium – [CO2 + chloride] and arterial blood gas analysis shows acidosis (pH < 7.4) with a base deficit. Serum lactate might be determined in arterial and venous blood samples. The normal serum lactate level is approximately 1 mmol/L with a range up to 2 mmol/L. Values above 4-5 mmol/L are indicative of lactic acidosis.
Since lactic acidosis secondary to cancer is rare, a diagnostic work-up to seek other potentially treatable causes is recommended.


Lactate levels correlate with the presence of tissue hypoperfusion and elevated levels have been shown to be correlated with increased mortality during shock. The mortality rate of patients with a serum lactate level greater than 2 mmol/L persisting after 24 hours with an associated acidaemia approaches 70%.


3.1 Treatment of lactic acidosis

Initial treatment is that of basic resuscitation, as a standard option, on a type C basis.
•    Airway assessment and stabilization and supplemental oxygen.
•    Intravenous fluid repletion with normal saline in case of tachycardia, hypotension, or other signs of poor tissue perfusion.
•    The use of buffering agents is only indicated in the setting of severe acidosis
o    Sodium bicarbonate in a starting dose of 1/3-1/2 of the calculated extracellular bicarbonate deficit: HCO3 deficit (mEq) = 0.5 X (wt in kg) X (desired HCO3 – measured HCO3).
•    Thiamine deficiency may be associated with cardiovascular compromise and lactic acidosis. Thiamine repletion (50-100 mg IV followed by 50 mg/d orally for 1-2 wk) is potentially life saving.
•    Identification of the primary illness and specific therapy. Chemotherapy of the underlying haematological cancer can be started, as a standard option, on a type C basis and may lead to a resolution of the lactic acidosis in chemotherapy-sensitive tumours


Morris CG, Low J. Metabolic acidosis in the critically ill: part 1. Classification and pathophysiology. Anaesthesia 2008; 63: 294-301 [Medline]

Morris CG, Low J. Metabolic acidosis in the critically ill: part 2. Causes and treatment. Anaesthesia 2008; 63: 396-411 [Medline]

Dr. Dirk Schrijvers (Reviewer)
University Hospital Antwerp – Antwerp, Belgium

Dr. Silvia Spinazzé (Associate Editor)
START Programme