Lactic Acidosis

Lactic acidosis is a form of metabolic acidosis (which is defined as arterial blood pH <7.35 with plasma bicarbonate <22 mmol/l), due to the inadequate clearance of lactic acid from the blood. Lactate is a by-product of anaerobic respiration and is normally cleared from the blood by the liver, kidney and skeletal muscle. Lactic acidosis occurs when the body's buffering systems are overloaded and tends to cause a pH of ≤7.25 with plasma lactate ≥5 mmol/l. It is usually caused by a state of tissue hypoperfusion and/or hypoxia. This causes pyruvic acid to be preferentially converted to lactate during anaerobic respiration. Hyperlactataemia is defined as plasma lactate >2 mmol/l.

• The prevalence is very difficult to estimate as it occurs in critically ill patients, who are not often suitable subjects for research. It is certainly a common occurrence in patients in high dependency areas of hospitals.^2,3
• The incidence of symptomatic hyperlactataemia appears to be rising as a consequence of the use of anti-retroviral therapy to treat HIV infection. An incidence of 35.8 cases per 1000 person-years was found in those taking stavudine (d4T) regimens.³

The list of causes is virtually endless, but the major causes are covered below. Lactic acidosis may occur in conjunction with a wide variety of underlying disease, in extremis, and indeed is a marker for severe progression and deterioration of the primary illness. Lactic acidosis is commonly found in cardiopulmonary failure, other causes of tissue ischaemia, or due to the effects of drugs/toxins/severe illness. A variety of acquired and congenital diseases may cause it, or contribute to its presence in ill patients. Lactic acidosis may occur as a consequence of vigorous or prolonged exercise but is usually of no consequence and self-correcting, unless other pathology such as hyperthermia is present.

• Type A - Tissue hypoxia:
  • Hypoperfusion; left ventricular failure, impaired cardiac output, myocardial suppression due to toxicity, abnormal vascular tone or hyperpermeability
  • Hypoxaemia; asphyxiation, respiratory failure, acute anaemia, haemorrhage, carbon monoxide poisoning, methaemoglobinaemia

• Type B - Tissue hypoxia absent:
  • Type B1; underlying disease, e.g. sepsis, renal failure, hepatic failure, diabetes, cancer or consequences of its treatment, diabetes mellitus, acute severe viral illness, malaria, cholera
  • Type B2; drug or toxin mediated, e.g. biguanides*, paracetamol, anticonvulsants, alcohol, aspirin, anti-tuberculous therapy, ethylene glycol, cyanide, sorbitol, sodium nitroprusside, overzealous TPN regimen, lactulose, theophylline, adrenaline, noradrenaline, cocaine, amphetamines, papaverine, paraldehyde
  • Type B3; inborn errors of metabolism⁴ (or rarely, acquired metabolic errors), e.g. organic acidaemias, primary lactic acidoses (e.g. pyruvate dehydrogenase deficiency, pyruvate carboxylase deficiency, cytochrome oxidase deficiency), severe vitamin deficiency (particularly thiamine), aminoacidopathies, glycogen storage disorders, mitochondrial disease (e.g. MELAS mitochondrial encephalomyelopathy with lactic acidosis and stroke), D-lactic acidosis in short gut syndrome, overexertion, prolonged generalised seizures

*The reputation of the biguanide metformin for causing lactic acidosis may be overstated, and largely based on experience with its more toxic predecessor phenformin. It can cause lactic acidosis in overdose, or if continued in severely ill diabetics who become dehydrated, but seems to be well tolerated on the whole, with many of the current cautions for conditions such as heart failure probably being overzealous and denying a safe and useful therapy to many patients.⁵ A Cochrane systematic review found no evidence of an association with lactic acidosis or hyperlactataemia in study-based use.⁶

History

Lactic acidosis occurring in the face of concomitant illness is an ominous sign and a relatively grave prognostic indicator. It signifies a critical, acute illness and the history should be directed at finding the underlying cause of shock. It is important to enquire – from the patient if possible; if not from friends/family – about antecedent symptoms of:

• Infection
• Cardiorespiratory disease
• Abdominal complaints
• Trauma
• Recent prescribed or non-prescribed drug ingestion (particularly anti-retroviral therapy)
• Exposure to toxins at work or in the home
• Episodes of overdose or self-poisoning
• Family history of similar problems

Physical examination

There are no specific signs indicating lactic acidosis but its aetiology may be determined through careful examination.

• Look for signs of hypovolaemic, cardiogenic, septic or toxic shock.
• To classify the lactic acidosis look for signs of tissue hypoperfusion such as hypotension, tachypnoea, confusion, peripheral shutdown (check capillary refill) and oliguria.
• Look for evidence of a septic focus and hyperthermia, or even hypothermia in advanced sepsis.
• Kussmaul's breathing (rhythmic, deep, gasping breaths at normal or reduced frequency) indicates severe acidosis with attempted respiratory compensation.

Arterial blood gases will reveal a metabolic acidosis (normal pCO₂ with pH < 7.35) and electrolytes reveal a low plasma bicarbonate (< 22mmol/l). Lactic acidosis is suggested by the presence of metabolic acidosis without an obvious cause, such as ketosis or the presence of other acidic toxins. The anion gap should be calculated as below:

• The normal anion gap varies between different laboratories but is usually 8–12 mmol/l.
• Hypoalbuminaemia lowers the normal anion gap by ~ 2.5 mmol/l for every 10g/l reduction in serum albumin.
• The anion gap will be elevated in lactic acidosis.
• It is also elevated in renal failure and other organic acidoses, ketoacidosis, and some poisoning/drug-induced acidoses.
• Plasma lactate should be measured to confirm that this is the likely anion causing the acidosis, to help distinguish from these other causes.
• Values in the range 2–5 mmol/l are significant.
• Clinically significant hyperlactataemia can occur in the absence of a raised anion gap.
• Samples for lactate estimation should be taken from arterial or mixed central venous sites. Peripheral values may reflect local rather than systemic concentrations. The sample should be transported to the lab on ice and may utilise a special reagent that inhibits glycolysis, giving a true spot reading.
• In shocked patients, particularly those with cardiogenic shock, lactate concentrations >2.5 mmol/l are associated with a poor prognosis and the lactate level can be measured as a semi-quantitative marker of deterioration or improvement.
• Further investigations aimed at detecting the underlying cause should be requested as thought necessary. Blood, urine and other cultures are useful for detecting occult septic causes.

Any other cause of metabolic acidosis, particularly those due to diabetic ketoacidosis, other organic acidosis, renal failure, alcoholic ketoacidosis, hyperosmolar hyperglycaemic non-ketotic coma (HONK), poisoning or drug toxicity.

The principles of management of lactic acidosis are:

• Diagnose and correct any underlying cause if possible.
• Restore adequate oxygen delivery to the tissues, especially adequate tissue perfusion.

Emergency management

• Check airway, breathing and circulation.
• Put patient on SaO₂ monitor.
• Give 100% oxygen.
• Consider intubation and ventilatory support for patients with deteriorating SaO₂ (take senior-A&E/medical/anaesthetic advice).
• Obtain IV access and give a fluid bolus of crystalloid or colloid if there is tachycardia, hypotension or signs of hypoperfusion such as poor capillary refill.
• If cardiac failure is the suspected aetiology, be cautious about fluid infusion.
• Put patient on a cardiac monitor as there is a predisposition to arrhythmia.
• Refer urgently to acute medical team.
• Arrange transfer to high dependency area as soon as feasible.
• Treat any obvious underlying causes – e.g. IV antibiotics for infection, intravenous thiamine if suspected deficiency.

Further management⁷

• Sodium bicarbonate is used by some to correct the acidosis but its use should not be routine and remains controversial. It generates CO₂ that may worsen acidosis if there is insufficient respiratory balance. There are no good, reliable trials that support its efficacy in routine use.
• Dichloroacetate may be used to stimulate pyruvate dehydrogenase, the alternative aerobic respiratory pathway. It also has positive inotropic effects. It has been shown to improve acid-base status but this did not translate into improved outcome or survival.
• Carbicarb (equimolar mixture of sodium bicarbonate and sodium carbonate) is a promising buffering agent that appears to effectively reduce lactate levels without CO₂ generation, but no randomised controlled trials have yet reported.
• Dialysis is an effective treatment in expert critical care/nephrology hands.

• The major problem is the increasing myocardial suppression that occurs with decreasing blood pH. A vicious cycle of lactic acidosis, further hypoperfusion and multi-organ failure may lead to death.
• There is an increased risk of a variety of cardiac arrhythmias.

• Very poor overall, especially in severe cases.
• Critically ill patients with blood lactate level of >5 mmol/l and arterial pH <7.35 have a 75% mortality at 6 months.