Rant: Lactate is your friend

It’s 0200 in a rural ED. Sixty-three-year-old bloke, let’s call him Gary. He’s come in feeling a bit flat, mildly short of breath, no fever, no rigors. He looks okay. Obs are almost okay — HR 98, BP 118/76, RR 18, sats 96% on room air, temp 37.4. You’re thinking COPD exacerbation, maybe early LVF. You’re not thinking sepsis.

Then the VBG comes back.

Lactate: 3.1 mmol/L.

And suddenly Gary is getting a sepsis workup, a 30ml/kg fluid bolus is being contemplated, and someone is calling the ICU at a regional centre three hours away.

His chest X-ray shows a right lower lobe consolidation. He has pneumonia. He is, by the loosest technical definition, septic.

Here’s the thing. Gary has also been huffing away on his salbutamol inhaler for two hours.

What Lactate Actually Is

Lactate is produced constantly, by nearly every cell in your body. It’s not a waste product — it’s a fuel. The heart, brain, and skeletal muscle all use lactate as an energy substrate. At rest, a healthy person produces around 1500 mmol of lactate per day, clearing it mostly through the liver and to a lesser degree the kidneys and heart.

The normal serum range is up to around 2 mmol/L, though this varies by lab and method.

The classic teaching — lactate rises when tissues are underperfused, switch to anaerobic metabolism, pyruvate backs up, and lactate floods the blood — is Type A lactic acidosis. Shock. Ischaemia. Real badness.

But Type A is only a small part of the story, and arguably the less interesting part. To be honest, picking a patient with type A lactic acidosis is pretty easy in practice.

The Fallacies

Fallacy 1: Elevated lactate = tissue hypoxia = underperfusion = needs more fluid.

This is the one that causes the most harm. Type B lactic acidosis has nothing to do with oxygen delivery. Lactate rises in the absence of any perfusion problem at all. Common culprits:

• Beta-agonists — salbutamol, adrenaline. To understand why, it helps to know about the Cori cycle: the normal housekeeping loop where lactate produced in peripheral tissues — working muscle, red blood cells — is shuttled to the liver, converted back to glucose via gluconeogenesis, and returned to circulation. It’s an elegant recycling system, and under normal conditions it keeps lactate levels tightly controlled.
• Beta-2 receptor stimulation short-circuits this. Activation of beta-2 receptors on skeletal muscle cells drives Na⁺/K⁺-ATPase activity, which ramps up ATP consumption and in turn accelerates glycolysis. More pyruvate is produced than the mitochondria can handle — so lactate dehydrogenase mops up the excess, converting it to lactate. This happens with adequate oxygen delivery — it’s aerobic glycolysis, the same metabolic trick tumour cells use (the Warburg effect). The Cori cycle tries to keep up, but hepatic clearance has a ceiling. A few salbutamol nebs and a lactate of 2.5–4 mmol/L is a completely expected pharmacological consequence. It is not a distress signal from your patient’s tissues — it’s a readout of their medication.
• Infection and systemic inflammation — activated neutrophils, macrophages, and other immune cells are metabolically ravenous. They upregulate aerobic glycolysis as part of their inflammatory response — producing lactate not because they’re starved of oxygen, but because rapid ATP generation via glycolysis suits their function. Add the endogenous catecholamine surge of any acute illness and you have another beta-2 mediated push on top. A lactate of 2–3 in a patient with pneumonia who is otherwise haemodynamically stable may simply reflect an immune system doing its job.
• Thiamine deficiency — blocks pyruvate dehydrogenase, pyruvate can’t enter the Krebs cycle, and shunts instead to lactate. Relevant in your malnourished, alcohol-dependent, or post-bariatric patients.
• Metformin toxicity — inhibits complex I of the mitochondrial respiratory chain, again shunting pyruvate away from oxidative metabolism.
• Liver disease — impaired clearance. The Cori cycle depends on a functioning liver. In cirrhosis or acute hepatic failure, lactate may be elevated simply because the recycling system is broken, not because production is excessive.
• Malignancy — Warburg physiology again. Tumour cells produce lactate aerobically as a feature, not a bug.
• Seizures — transient massive rise from muscular activity, self-resolving within an hour or so.

In Gary’s case — COPD exacerbation, pneumonia, salbutamol nebs — he has at least three concurrent Type B mechanisms running simultaneously. The lactate is over 3 – the result of multiple pathways, none type A hypoxemia. Gary himself is sitting up, talking in full sentences, and asking when he can have a cup of tea.

Fallacy 2: Lactate clearance is a resuscitation target.

The Surviving Sepsis Campaign’s use of serial lactate as a guide to resuscitation adequacy has embedded this deeply. And there is an association between lactate normalisation and improved outcomes in septic shock. But association is not mechanism, and lactate clearance is almost certainly a marker of physiological recovery, not a driver of it. Treating the number — giving more fluid, more pressors — because the lactate hasn’t normalised yet is treating a proxy, not the patient.

The most recent (2026) Surviving Sepsis guidelines reframed lactate clearance to specifiy that it only applies in patients who are already in septic shock. So the sickest of the sick. Not Gary.

The ANDROMEDA-SHOCK trial found peripheral perfusion targets were non-inferior to lactate-guided resuscitation. The point is not that lactate is useless — it’s that it tells you something has gone wrong somewhere, not specifically that you need to pour in more saline.

Fallacy 3: Any lactate above 2 is clinically significant.

The Sepsis-3 criteria use >2 mmol/L as a criterion for septic shock in a patient with suspected infection and vasopressor requirement. That’s an appropriate clinical context with a narrow application. It is not a population-level trigger for aggressive resuscitation in any undifferentiated patient who looks vaguely unwell.

Spurious elevations from delayed sample processing, tight tourniquet application, prolonged transport in the sample tube — these are all real. Lab artefact can push a normal lactate into the “abnormal” range without a single struggling mitochondrion involved.

What to Actually Do

When you see an elevated lactate, ask yourself five questions before you reach for the fluid bag:

1. Is this patient in shock? Not the number — the patient. Mentation, skin perfusion, cap refill, pulse pressure, urine output. Treat the human.
2. What’s the clinical context? Beta-agonists on board? Liver disease? Metformin? Seizure in the last hour? Known malignancy? Active infection driving an inflammatory response?
3. Is there a perfusion problem I’m missing? Mesenteric ischaemia, massive PE, cardiogenic shock — these do cause Type A lactataemia and deserve urgent attention.
4. What does the trajectory look like? A lactate trending down in a patient who is improving clinically is reassuring. A lactate climbing despite initial resuscitation in a sick patient is alarming. Context and direction matter more than a single value.
5. Will volume actually help, or possibly harm my patient? Before embarking on a large volume resuscitation it behooves us to spend a minute thinking about where our patient sits on the spectrum of fluid tolerance and the possible downsides of “another litre”. This does require one to get off of one’s chair, but it can save a lot of time down the line if we get this right.

Back to Gary

Gary got a salbutamol cease, appropriate antibiotics for his pneumonia, a repeat lactate two hours later of 1.8, and admission for treatment of his chest infection. He did not need 3L of normal saline, a central line, or an ICU transfer.

He had pneumonia. He needed antibiotics. His lactate told us his immune system and his puffer were both working — not that his organs were failing.

Lactate is a useful tool with a narrow range of meaningful applications. It is not a substitute for clinical assessment, and a mildly elevated result should prompt thinking, not reflexive escalation.

Know what the number means. Know what it doesn’t.

Casey

Further reading

A fantastic PK presentation on Lactate in ED by Dr Laura Castle in 2013 CLICK HERE

• Garcia-Alvarez et al.: Garcia-Alvarez M, Marik P, Bellomo R. Sepsis-associated hyperlactatemia. Crit Care. 2014;18(5):503. doi: 10.1186/s13054-014-0503-3. PMID: 25394679
• Hernandez et al. (ANDROMEDA-SHOCK): Hernández G, Ospina-Tascón GA, Petri Damiani L, et al. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA. 2019;321(7):654–664. doi: 10.1001/jama.2019.0071. PMID: 30772908
• Levy B. Lactate and shock state: the metabolic view. Curr Opin Crit Care. 2006;12(4):315–321. doi: 10.1097/01.ccx.0000235208.77542.39. PMID: 16810041
• Kraut & Madias: Kraut JA, Madias NE. Lactic acidosis. N Engl J Med. 2014;371(24):2309–2319. doi: 10.1056/NEJMra1309483. PMID: 25494270
• Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026. Crit Care Med. 2026;54(4):725–812. DOI: 10.1097/CCM.0000000000007075