Lactate Physiology and Pathophysiology. Is Lactate always Bad? A Janus-Faced Compound – Dr James Day

  1. Prognostication with lactate levels and clearance: Fuhrmann
  2. The muscle is a lactate producer: Weber-carstens
  3. How do the changes in lactate production affect outcome: Blaser
  4. Lactate as an internal substrate: Druml
  5. Exogenous lactate as a therapeutic intervention: Ichai

 

A look at the role of lactate in physiology and pathophysiology.

Lactate has long been studied.

It has a reputation as a toxin due to its association with unwell patients in sepsis.

Its measurement is mandated in sepsis guidelines and raised levels have been associated with poorer outcomes in many conditions from sepsis to trauma.

It is widely measured in hospital patients and in critically ill patients with debates about how and when to measure it

 

Clinical use of lactate monitoring in critically ill patients

http://www.annalsofintensivecare.com/content/3/1/12

 

Top tip: Measuring lactate: if doing serial measurements try to use the same site and technique

Top tip: Measuring lactate: turn around time of 15 mins or put sample on ice

 

When assessing lactate dynamic lactate indices may be more relevant such as lactate clearance than static lactate point measurements. They are more predictive for mortality.

 

Dynamic Lactate Indices as Predictors of Outcome in Critically Ill Patients

http://ccforum.com/content/15/5/R242

 

Lactate levels must be put in context. Significant mortality is associated with a lactate level>4 in sepsis but not so in DKA.

In exercising athletes lactate levels have been shown to peak at levels>15 but then clear rapidly afterwards.

High lactate levels are not all bad. An early increase in lactate levels with adrenaline administration is a good sign in shock.

 

Shock. 2010 Jul;34(1):4-9.

http://www.ncbi.nlm.nih.gov/pubmed/20016405

 

The skeletal muscle is involved in lactate storage, with lactate release and uptake.

Skeletal muscle is part of the cell-cell lactate shuttle, and thereby providing substrate for energy production in other organs.

The mechanisms of lactate production during critical illness within the skeletal muscle are incompletely understood.

Adrenergic driven aerobic glycolysis through stimulation of the Na+/K+ ATPase may be one mechanism contributing to net lactate production in skeletal muscle

Lactate is an important metabolic substrate for many tissues and we have evolved over millions of years and is integral to our homeostasis.

 

Top tip: If there is thiamine deficiency then lactate production is increased.

 

Lactate turnover is already high at basal rate.

Lactate elimination in the liver is extremely high and can be upto 500mmol/h. Lactate is still cleared by the liver even in those with liver impairment.

Lactate clearance is reduced by the presence of alkalosis and administration of exogenous bicarbonate

 

Crit Care Med. 1991 Sep;19(9):1120-4.

http://www.ncbi.nlm.nih.gov/pubmed/1884611

 

 

Protection of Acid–Base Balance by pH Regulation of Acid Production

Lactate clearance should probably be changed to Plasma Lactate kinetics.

The following studies look at the potential benefits of administering exogenous lactate.

 

Half-molar sodium lactate infusion improves cardiac performance in acute heart failure

http://ccforum.com/content/18/2/R48

 

 

Lactate and the brain

Am J Clin Nutr. 2009 Sep;90(3):875S-880S.

Role of glutamate in neuron-glia metabolic coupling.

http://www.ncbi.nlm.nih.gov/pubmed/19571222

 

Lancet. 1994 Jan 1;343(8888):16-20.

Protection by lactate of cerebral function during hypoglycaemia.

http://dx.doi.org/10.1016/S0140-6736(94)90876-1

 

 

Lactate vs mannitol in raised ICP

Intensive Care Med. 2009 Mar; 35(3):471-9

http://dx.doi.org/10.1007/s00134-008-1283-5

 

 

Lactate has pleiotropic effects. It is an energetic substrate decreases cell volume, anti inflammatory, promotes intravascular expansion.

 

It has one problem: its name

 

Lactate is glucose without its toxicity and no need for insulin for its metabolism.

 

References:

Review article: Protection of Acid–Base Balance by pH Regulation of Acid Production

N Engl J Med 1998; 339:819-826

http://www.nejm.org/doi/full/10.1056/NEJM199809173391207

 

Review article: Sepsis associated hyperlactataemia

Garcia-Alvarez et al. Critical Care 2014, 18:503

http://ccforum.com/content/18/5/503

 

Lactate kinetics and mitochondrial respiration in skeletal muscle of healthy humans under the influence of adrenaline.

Clinical Science . Aug2015, Vol. 129 Issue 4, p375-384

http://www.clinsci.org/content/129/4/375