Tag Archives: acid base

The Lactate Conspiracy: Part 2

So in the last post I established:

  • Lactate is a base.
  • Lactate production retards cellular acidosis.
  • Lactate is produced all the time.
  • Lactate is fuel.

I have suggested that the traditional lactate hypothesis

“Lactate is a byproduct of anaerobic respiration that is produced in response to cellular hypoxia secondary to inadequate oxygen delivery.  It is a marker of tissue hypoperfusion and shock”

 Is not correct.

However we all see, and all know that when people are sick their lactates go up, and when their lactates go up they become acidotic.

Why is this?

There are two reasons.

The first is the simplest.  When people are sick they are generally metabolically very active because they are trying to deal with whatever is making them sick.  At a very basic level that means that each person’s cell is recycling ATP as fast as it can.

The extra protons come from this reaction.

However there are some points to make to this approach of ‘counting’ protons when it comes to cellular chemistry.  The first is that these reactions don’t occur in isolation, they occur in a complex network, and they occur in a solution that is mostly water.  As such this is a slightly reductive way of thinking about cellular respiration.  Water can supply and buffer excess hydrogen to a certain degree (though it’s pKa is 14 so it doesn’t do much of this).  However we upregulate this reaction enough you can see that excess protons can be produced, and they will need to go somewhere.

We can say that the acidosis associated with lactate production is due to an induced hypermetabolic state.  Once the cells own intrinsic attempts at buffering (making more lactate, bicarbonate etc etc) are exhausted those excess protons leak out and make the cell, and the surrounding tissue fluid more acidotic.

The second reason, and this I think is the best reason, is because of the laws of physics.  Essentially when we upregulate the production of lactate, we increase the strong ion difference as lactate is a anion.  Lactate sits alongside, chloride, bicarbonate, and phosphate in the buffer base, and to obey the law of electrochemical neutrality some of the buffer base has to release some free hydrogen into solution to balance things.

If you have no idea what this paragraph or image mean, then you need to read this article.

So the lactate makes you acidotic, in the same way that excess chloride infusion can make you acidotic.  It’s not ‘to blame’ it’s just the last step in a chain reaction that started when cellular metabolism got kicked into first gear and the accelerator got floored.

Now just to summarise (again):

  • Lactate is a base.
  • Lactate production retards cellular acidosis.
  • Lactate is produced all the time.
  • Lactate is fuel.

Lactate is produced as part of normal glycoylsis. An elevated lactate indicates a HYPERMETABOLIC state, IT CAUSES ACIDOSIS by INCREASING the STRONG ION DIFFERENCE.

If Lactate is produced in response to badness, and there is experimental evidence that suggests it is metabolised by the heart, lungs, kidney, and brain during times of physiological stress why oh why would we try to ‘clear’ it?

Clearing lactate essentially means doing things to increase oxygen delivery to cells, but we know that it’s not hypoxia that is really driving lactate production it is the energy demand of the cell exceeding the supply available to it, so dumping fluid, and blood into someone’s circulation isn’t necessarily going to improve things (apart from by diluting the lactate when you do your next gas)

This has interesting implications.  If lactate is a fuel.  Can it be a treatment?

Couple of interesting properties of lactate – it can be thought of as a consumable anion, this means you can give a load of cation (ie sodium) without having to give a lot of chloride, or a lot of bicarbonate.  As the cells eat the lactate and turn it into glucose, or break it down completely.

I didn’t find much out there, but I did find 5 studies.  They are recent, small, and of variable quality, but I think they point to a few uses:

In one pilot single blind RCT in Austrailia1.  Patients with pretty horrific heart failure (ICU admissions, needs inotropes, or ventilation) were given 3ml/kg bolus of half-molar sodium lactate and an infusion of 1ml/kg/24hrs versus a hartmanns bolus and infusion.  Their CO was measured by ultransonographers blinded to the treatment arm.  The results show a significant increase in CO at 24 hours.

Intervention Control
CO at baseline 4.05 +/- 1.37  L/min 4.72 +/- 1.3 L/min
CO at 24 hours 5.49 +/- 1.9 L/min 4.96 +/- 1.21 L/min
CO at 48 hours 4.87 +/- 2.38 L/min 4.76 +/- 1.58 L/min

In two studies conducted in the UK on people who has sustained TBI half molar sodium lactate infusion was shown to decrease episodes of raised ICP3, and decrease ICP2 more effectively than mannitol.

In patients with TBI and ICP monitors with the kind of brain injury we can’t do much about other than prevent secondary insult they gave either normal saline or 0.5ml/kg/hr of half molar sodium lactate for 48 hours.  There were 11 episodes of RICP in the SL group and 20 in the control group (p=<0.05).  The other interesting thing was these people’s cumulative fluid balance.  It was much lower. 

They also looked at people’s neurological outcome at 6 months, they showed no significant difference between the two groups: 12 patients (SL group) versus 15 patients (control group) had a poor outcome at 6 months. However, more survivors from the control group had poorer neurological outcome compared to the SL group: nine versus four patients, although this difference did not reach significance (P = 0.14).  Though it is an interesting signal, and were this a paper on stroke thrombolysis probably picked up as hugely significant.

When they compared sodium lactate to mannitol, the effect of the lactate solution on ICP was significantly more pronounced (7 vs. 4 mmHg, P = 0.016), more prolonged (fourth-hour-ICP decrease: −5.9 ± 1 vs. −3.2 ± 0.9 mmHg, P = 0.009) and more frequently successful (90.4 vs. 70.4%, P = 0.053)2.

 

Another study in Indonesia4 looked at the efficacy of lactate bolus and infusion as a treatment for the horrifically dehydrated patients with dengue shock syndrome.  50 patients aged 2-14 years old received wither 5ml/kg of sodium lactate with a 1ml/kg infusion or ringers lactate 20ml/kg bolus plus standard maintanence therapy.  They looked at the measurement of a endothelial enzyme called SVCAM 1 (they found no difference).  There was no significant difference in outcome between groups (1 death in lactate group, 3 in control group), but the cumulative fluid balance between these groups with similar outcome was vastly different – the control group was 107 ml/kg +ve in 24 hours, whereas the lactate group was 35 ml/kg +ve in 24 hours.

Just a little context for you, the current direction of travel with research into fluid resuscitation is that too much can cause problems with acidosis, acute lung injury, and renal problems so volume sparing fluids that either exert an osmotic effect or do something else (like provide fuel) might be the ‘next’ thing.  Now I’m not saying that this is anything approaching a silver bullet, but if we can resuscitate people with less volume, we probably should.

What about sepsis?  I could only find a study on pigs, it was elegantly done however.  15 pigs were given the same challenge with e-coli endotoxin, and then resucicated over 300 minutes with either 5ml/kg/hr of 11.2% Na lactate, 5ml/kg/hr N saline, or 5ml/kg/hr of 8.4% sodium bicarbonate.  They measured lots of things, but MAP was their primary outcome.  As you can see, there was a significant improvement in MAP in the sodium lactate group.

I’ve subsequently found a similar study in sheep6, that suggests that sodium lactate infusion is harmful, so I’m not raising hypertonic sodium lactate as a panacea by any means, but the research into it’s volume sparing effects, and ability to decrease ICP needs to continue.

In Summary

The general textbook understanding of lactate physiology makes a number of basic errors which lead to inaccurate assumptions by medical staff, which can lead to inappropriate or inadvisable treatment strategies which are perpetrated throughout the world by the most junior doctor to the most senior critical care physician.

That is the lactate conspiracy.

Lactate is a fuel of last resort, and it may have therapeutic uses as a volume sparing resuscitation fluid.

References:

  1. Nalos, Marek, et al. “Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomised controlled clinical trial.” Critical Care2 (2014): R48.
  2. Ichai C, Armando G, Orban JC, Berthier F, Rami L, Samat-Long C, Grimaud D, Leverve X: Sodium-lactate vs mannitol in the treatment of intracranial hypertensive episodes in severe traumatic brain-injured patients. Intensive Care Med. 2009, 35: 471-479. 10.1007/s00134-008-1283-5.
  3. Ichai C, Armando G, Orban JC, Berthier F, Rami L, Samat-Long C, Grimaud D, Leverve X: Sodium-lactate vs mannitol in the treatment of intracranial hypertensive episodes in severe traumatic brain-injured patients. Intensive Care Med. 2009, 35: 471-479. 10.1007/s00134-008-1283-5.
  4. Somasetia et al. Critical Care 2014, 18:466 http://ccforum.com/content/18/5/466
  5. Duburcq, Thibault, et al. “Hypertonic sodium lactate improves fluid balance and hemodynamics in porcine endotoxic shock.” Critical Care 18.4 (2014): 467.
  6. Su, Fuhong, et al. “The harmful effects of hypertonic sodium lactate administration in hyperdynamic septic shock.” Shock: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches6 (2016): 663-671.