Hyperlactataemia

Elevation in serum lactate >2mmol/L, which may be:

Pathophysiology

Lactate is an organic acid produced:

  • From pyruvate, via glucose and alanine
  • In order to regenerate NAD+, which:
    • Allows further conversion from glucose into pyruvate
    • Facilitates ATP production in the absence of oxygen

Lactate occurs in two isomers:

  • L-lactate
    • Produced by multicellular organisms, including humans
      • At ~0.8mmol/kg/hr
        • Predominantly by skeletal muscle (~40%)
        • Also skin/brain/gut/RBC
    • Metabolised by:
      • Liver
      • Kidneys
      • Brain
        Hypothesised as substrate for ATP generation, particularly when neuronal uptake of ATP is ↓ in brain injury.
  • D-lactate
    • Normally produced by some colonic flora
      Not usually significant, however overproduction can occur with:
      • Short bowel syndrome
      • Post-pancreatectomy
      • Colonic overgrowth
      • Malabsorbed carbohydrate loads
    • Leads to ↓ cellular ATP generation
      D-lactate:
      • Competes with pyruvate and L-lactate for mitochondrial uptake
      • Metabolism is limited and tissue dependent
        The liver is the only organ whose mitochondria are able to clear reasonable quantities.
      • Toxicity may be:
        • Neurotoxic
          • Confusion
          • Ataxia
          • Slurred speech
          • Obtundation → coma
        • Cardiotoxic
          • Arrhythmias
          • Heart block
    • Not detected by routine lactate testing
      Blood gas or laboratory.

An ↑ in brain lactate is associated with ↓ mortality.

Lactate may be pathologically elevated by:

  • ↑ Production
    • Tissue hypoxia (Type A)
      Anaerobic metabolism.
    • Altered metabolism (Type B)
      Catecholamines ↑↑ cellular ATP requirement and generation, ↑ lactate production even with normal cellular DO2.
  • ↓ Clearance
    • Microvascular shunting
    • Hepatic dysfunction
    • Renal dysfunction

Aetiology

Type A:

  • Shock
  • Mesenteric ischaemia
    Although this is just localised ischaemia, it is important enough to be mentioned separately.
  • ↓ O2 carriage
    • Hypoxia
    • Anaemia
      Severe.
    • CO poisoning

Type B:

  • Disease
    • Sepsis
    • Failures
      • Liver failure
      • Renal failure
    • Malignancy
      ↑ Anaerobic glycolysis, possible liver parenchymal destruction.
      • Phaeochromocytoma
      • Haematological
    • Thiamine deficiency
    • Diabetes
  • Drugs
    • Catecholamines
      • Adrenaline
      • Salbutamol
    • Analgesics
      • Paracetamol
      • Salicylates
    • Energy sources
      • Alcohols
        • Methanol
        • Ethanol
      • Sugars
        • Fructose
        • Sorbitol
    • Glycols
    • Metformin
    • SNP
  • Inborn Error of Metabolism
    • G6PD

Investigations

Bloods:

  • Lactate
    This is by default L-lactate, which is the isomer produced by human metabolism. D-lactate is:
    • Not detected by standard assays
    • Produced by gut organisms
    • May be raised in:
      • Mesenteric ischaemia
        Translocation through ischaemic bowel.
      • Short gut syndrome
      • Pancreatic insufficiency

Management

Treating an elevated lactate in isolation is unhelpful.

An elevated lactate should prompt a search for evidence of systemic or regional malperfusion, and any underlying abnormality corrected to restore DO2.

  • Treat the primary disorder
  • Correct acidosis
    Bicarbonate is reasonable if:
    • pH < 7.2
    • Disorder exacerbated by acidosis is present:
      • Pulmonary hypertension
      • Arrhythmia risk
      • High-dose vasoactives

Prognosis

Hyperlactataemia is associated with:

  • ↑ Mortality in sepsis/shock
    Level is proportional to mortality; >4 is highly significant.
  • ↑ Mortality in severe cardiac disease
    Post-arrest, post-CABG, AMI, heart failure.

References

  1. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.