Category Archives: LIVES 2015 – BERLIN

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


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


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.


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.



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



Lactate and the brain

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

Role of glutamate in neuron-glia metabolic coupling.


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

Protection by lactate of cerebral function during hypoglycaemia.



Lactate vs mannitol in raised ICP

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



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.



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

N Engl J Med 1998; 339:819-826


Review article: Sepsis associated hyperlactataemia

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


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



Basic Bundle

  • Hand hygeine
  • Surgical asepsis insertion conditions
  • Avoid aqueous iodine
  • Subclavian and radial preferred
  • Remove useless catheters
  • Immediate change of soiled dressings

What about alcohol-iodine versus chlorhexidine-alcohol? Scrubbing or no-scrubbing of line areas?

2×2 factorial design

Muticentre RCT, primary outcome CRBSI

2349 enrolled with 5159 catheters!

Patients generally matched, mainly medical patients with 70% mechanically ventilated

Most patients had radial catheters (68%)

Chlorhexidine was significantly better than alcohol-PVI in reducing CRBSI. Addition of scrubbing of area added no real benefit. Chlorhexidine group had more skin reactions but they were slight.

Conclusion: 2% chlorhexidine is superior to iodine in reducing the risk of CRBSI

Skin antisepsis with chlorhexidine–alcohol versus povidone iodine–alcohol, with and without skin scrubbing, for prevention of intravascular-catheter-related infection (CLEAN): an open-label, multicentre, randomised, controlled, two-by-two factorial trial


A number of injuries can produce a GCS 3 and interventions are multiple with varying evidence of efficacy

Pragmatic, multicentre multinational RCT

Open-label with blinded follow-up

Could be randomised up to 10/7 post injury and must have had first-level interventions to treat it (head up, CSF drainage, etc)

If could not be controlled with hypothermia had barbiturates or hypertonic

Screen 2498 patients, 387 randomised

  • 188 randomised and analysed in hypothermia
  • 187 randomised and analysed in controls

No significant differences in baseline characteristics including age, severity of injury, APACHE, etc AND neurosurgical intervention prior to randomisation

Hypothermia did control ICP more than standard interventions in control group

Stopped early as greater incidence of unfavourable outcome (poor GOSE score) in hypothermia compared with controls

Unadjusted hazard ratio for mortality 1.45 (1.01,2.10) at 6/12

No difference in pneumonia rate between two groups


Conclusion: Titrated hypothermia to reduce raised ICP in addition to standard care did not improve outcomes but and increased mortality

Hypothermia for Intracranial Hypertension after Traumatic Brain Injury


Vasopressin may show benefit in less severe shock in VASS trial

  • ? Weans noradrenaline early
  • ? Dose to low
  • ? Harmful interaction

May reflect beneficial effects on renal function

VASS also suggested that vasopressin + steroids better than noradrenaline + steroids

Questions therefore

  • Should we use earlier?
  • Should we use higher doses?
  • Should we use it with steroids

Factorial 2X2 double blinded RCT < 6/24

  • Vasopressin 0.0-0.06 u/min OR noradrenaline 0-12mch/min
  • When maxed out added either Hydrocort 50mg q6h or placebo

After this, open label catecholamines could be added but would be weaned first

Included adult septic patients, first episode of shock

Exclusions other reasons for steroids, CKD needing RRT

Primary outcome renal failure free days as defined by Stage 3 AKIN

414 randomised, even split

Matched groups

  • Men > women
  • APACHE mean 22
  • 80-90% received noradrenaline pre-randomisation
  • Usually included within 3/24
  • Typical creatinine around 120-130

No difference in haemodynamics between the two groups but noradrenaline group needed more noradrenaline to do so

Fluid requirements and lactate concentrations much this same

Median creatinine level lower in vasopressin patients than noradrenaline

  • No difference in distribution of renal failure
  • No difference in survivors who ever developed renal failure
  • No difference in non-survivors or survivors who did develop renal failure

No difference in mortality. No benefit to adding steroids.

Number of patients who required RRT was significantly lower (ARR 10%) than those who didn’t but once you needed dialysis, duration of that was the same

Conclusion: Early vasopressin maintained BP and reduced noradrenaline requirements as well as reducing the need for RRT but did not reduce the number of renal failure free days