Outline the causes, and the principles of management of lactic acidosis in the critically ill.

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College Answer

•    Causes can be divided into increased lactate production (including enhanced pyruvate production, reduced pyruvate conversion to CO2 & water or glucose, or preferential conversion of pyruvate to lactate), and diminished lactate utilisation.
•    Most causes in the critically ill are due to the many causes of tissue hypoperfusion [Type A] (resulting in increased production and decreased utilisation), or decreased utilisation due to liver disease (especially with use of lactate containing fluids in renal replacement therapy). Other common causes include seizures, beta-2 adrenergic agonists (eg. adrenaline and salbutamol), metformin (uncertain mechanism) and post-cardiac surgery. Consider also d- lactic acidosis associated with the short bowel syndrome.
•    Principles of management include correcting hypoperfusion (fluids, inotropes, vasopressors), and if possible, correction of underlying disorder (treat seizures, shivering, glucose abnormalities, etc.) and removal of offending drugs (including metformin, adrenaline, renal replacement fluid).

Discussion

Causes of lactic acidosis  are discussed at length in another chapter.

In brief, one may classify it according to several classification systems, of which the Cohen-Woods classification is for some reason the more popular.

The Cohen-Woods classification is as follows:

  • Type A (lactic acidosis due to impaired tissue perfusion)
  • Type B (lactic acidosis with adequate tissue perfusion).
    • Type B1 (lactic acidosis a result of “disease states”)
    • Type B2 (drug-related)
    • Type B3 ( the consequence of inborn errors of metabolism)

Causes of lactic acidosis can be better classified according to the lesser-known (but biochemically superior) Phuypers and Pierce system:

A Mechanism-based Classification of Lactic Acidosis

Increased rate of glycolysis due to lack of ATP

  • Shock: circulatory collapse or regional ischaemia
  • Lactic acidosis due to severe hypoxia
  • Lactic acidosis due to severe anaemia
  • Carbon monoxide poisoning and tissue hypoxia
  • Regional hypoxia and microvascular shunting in sepsis

Increased rate of glycolysis due to exogenous pro-glycolytic stimulus

  • Beta-2 adrenoceptor agonists: salbutamol, adrenaline, isoprenaline  
  • Catecholamine excess in hypovolemic shock
  • Lactic acidosis due to excess glycolysis in malignancy

Unregulated substrate entry into glycolysis

  • Xylitol, sorbitol, fructose infusions

Pyruvate dehydrogenase inactivity

  • Thiamine deficiency as a cause of lactic acidosis
  • Inhibition of pyruvate dehydrogenase in sepsis
  • Lactic acidosis due to inborn errors of metabolism

Defects of oxidative phosphorylation

  • Cyanide (and by extension nitroprusside) toxicity
  • Paracetamol toxicity
  • Salicylate toxicity
  • Lactic acidosis due to inborn errors of metabolism
  • Metformin
  • Propofol
  • Isoniazid
  • The toxic alcohols - ethanol, methanol and ethylene glycol
  • NRTIs (nucleoside reverse transcriptase inhibitors)

Decreased lactate clearance

  • Lactic acidosis due to impaired hepatic or renal function
  • Decreased gluconeogenesis due to the ethanol and methanol
  • Decreased gluconeogenesis due to ketoacidosis

The approach to the management of lactic acidosis can be divided into two main approaches:

  • Manage the underlying cause of the lactic acidosis - and the precise management strategy obviously depends on the aetiology
  • Increase the clearance of lactate artificially using CVVHDF (which is probably not a very effective strategy, and represents immature "lactate-centric" management).

References

References

Narins RG, Krishna GG, Yee J, Idemiyashiro D, Schmidt RJ: The metabolic acidoses. In: Maxwell & Kleeman's Clinical Disorders of Fluid and Electrolyte Metabolism, edited by Narins RG, New York, McGraw-Hill, 1994, pp769 -825

 

Luft FC. Lactic acidosis update for critical care clinicians. J Am Soc Nephrol 2001 Feb; 12 Suppl 17 S15-9.

 

Ohs manual – Chapter 15 by D J (Jamie) Cooper and Alistair D Nichol, titled “Lactic acidosis” (pp. 145)

 

Cohen RD, Woods HF. Lactic acidosis revisited. Diabetes 1983; 32: 181–91.

 

Reichard, George A., et al. "Quantitative estimation of the Cori cycle in the human." Journal of Biological Chemistry 238.2 (1963): 495-501.

 

Andres, Reubin, Gordon Cader, and Kenneth L. Zierler. "The quantitatively minor role of carbohydrate in oxidative metabolism by skeletal muscle in intact man in the basal state. Measurements of oxygen and glucose uptake and carbon dioxide and lactate production in the forearm." Journal of Clinical Investigation 35.6 (1956): 671.

 

Phypers, Barrie, and JM Tom Pierce. "Lactate physiology in health and disease." Continuing Education in Anaesthesia, Critical Care & Pain 6.3 (2006): 128-132.