TABLE OF CONTENTS
You were about to discharge the patient.
Then the nurse hands you an ABG.
Lactate: 4 mmol/L.
Now what?
Panic? Fluids? Admission? ICU call?
Before reacting to the number, let’s demystify lactate.
First: what is lactate?
Glucose metabolism begins with glycolysis, producing pyruvate.
Under normal conditions, pyruvate is converted to acetyl-CoA and enters the Krebs cycle for oxidative phosphorylation.
When there is insufficient oxygen, or when glycolysis outpaces mitochondrial capacity, pyruvate is converted to lactate.
This reaction is catalysed by lactate dehydrogenase (LDH):
pyruvate ↔ lactate
When glycolysis accelerates — stress, catecholamines, exercise, illness — lactate production increases.
What happens to all the lactate produced?
- Used for energy: It is continuously converted back to pyruvate and used for energy
- Converted to glucose: It is metabolised mainly by the liver (and to a lesser extent the kidneys), where it is converted back to glucose
Lactate is not a waste product. It is a metabolic fuel.
Is lactate toxic?
No.
Lactate itself is not harmful.
In some settings — such as traumatic brain injury or severe hypoglycaemia — elevated lactate may even be protective, acting as an alternative energy substrate.
What is hyperlactataemia?
Normal lactate = 0.3–1.8 mmol/L.
Hyperlactataemia = > 2 mmol/L
When lactate rises above baseline, it reflects either:
- increased production, or
- decreased clearance.
This alteration may be adaptive, not pathological.
But doesn’t lactate cause acidosis?
This is commonly misunderstood.
The idea that “lactic acidosis = lactate causes acidosis” is an oversimplification.
- Lactate production does not generate hydrogen ions
- The acidosis seen with hyperlactataemia results from ATP hydrolysis when oxidative phosphorylation is impaired.
Under normal conditions, hydrogen ions generated during glycolysis are consumed during mitochondrial oxidative phosphorylation.
When oxidative pathways fail or cannot keep up with metabolic demand:
- hydrogen ions accumulate
- acidosis develops
- Lactate rises in parallel
So, lactate is a marker, not the poison.
Why does lactate increase?
This is traditionally explained using the Cohen & Woods classification.
- Type A — Inadequate oxygen delivery
- Type B — No evidence of tissue hypoxia
- B1 -Disease-related
- B2 - Drugs & toxin
- (B3 exists, but is beyond the scope of this article.)
This classification is useful — but not always ED-friendly.
A more ED-useful way to think about lactate
In the ED, lactate accumulates because of an imbalance between production and clearance.
Broad mechanisms
1️⃣ Increased production
2️⃣ Decreased clearance
3️⃣ Mixed pathology
1️⃣ Increased lactate production
Type A: With inadequate oxygen delivery (Hypoperfusion or Hypoxia)
This is the category we fear most.
- Any shock state
- Cardiac arrest
- Regional hypoperfusion (e.g. mesenteric ischaemia)
- Severe hypoxaemia or anaemia
- Impaired oxygen utilisation (e.g. carbon monoxide poisoning)
- Generalised seizures
- Intense anaerobic muscular activity
Here, lactate reflects true tissue hypoxia.
Type B: Without tissue hypoxia
B1 : Disease-related
- LUKE — leukaemia, lymphoma
- TIPS — thiamine deficiency, infection, pancreatitis, short bowel
- DKA
B2: Drugs & toxins (common ED offenders)
- β-agonists (salbutamol)
- Adrenaline
- Salicylates
- Ethanol (especially chronic use)
2️⃣ Decreased clearance
Lactate clearance is primarily hepatic, with a smaller renal contribution.
Causes include:
- Hepatic failure
- Renal Failure
These patients are:
- less tolerant of hypotension
- more prone to sepsis
- poorly equipped to handle physiological stress
An elevated lactate here often warrants aggressive evaluation, even if vital signs appear acceptable.
3️⃣ Mixed pathology
(Impaired oxidative phosphorylation ± impaired clearance)
Examples:
- Sepsis
- Ethanol
- Metformin
- Severe pancreatitis
Sepsis — a special case
This explains why lactate can be elevated even when blood pressure and oxygenation look normal.
Why are we so concerned about lactate?
Because lactate predicts death
Regardless of the underlying cause, not just sepsis.
At higher levels, lactate usually signals:
- severe physiological stress
- impaired oxygen delivery or utilisation
- or failure of clearance
Across multiple studies:
- Elevated lactate is consistently associated with increased mortality
- Lactate clearance is associated with improved outcomes
This is why lactate features prominently in sepsis guidelines, though the controversies are beyond the scope of this article.
Lactate and occult sepsis
Lactate is especially useful for detecting occult severe sepsis, particularly when ≥ 4 mmol/L.
These patients may have normal blood pressure and appear “not that sick”
Yet carry a high risk of deterioration and death.
Lactate often flags danger before vital signs do.
A lactate ≥ 4 usually means something bad is happening — even if the patient looks fine.
But not all high lactates mean the same thing
So let’s simplify this into two ED questions:
- When does lactate lie?
- When does lactate kill?
When does lactate lie?
Some ED situations cause transient hyperlactataemia.
Examples:
- β-agonist use (acute asthma)
- Post-ictal state
- Extreme physical exertion
In these cases:
- Lactate may be markedly elevated
- Rapid clearance is expected in 1-2 hrs
- The degree of lactate elevation does not correlate with outcome
But failure to clear should prompt re-evaluation.
Any test showing an elevated lactate level should be repeated.
When does lactate kill?
- Sepsis
- Any shock state (cardiogenic, hypovolaemic, obstructive)
- Mesenteric ischaemia
- Necrotising soft-tissue infection
- Toxicological causes
In many of these, lactate is not just a marker —
it may be the earliest warning sign.
Lactate levels may also provide false reassurance because not all patients with hypoperfusion will generate elevated lactate levels.
What matters
Instead of reacting to the number, ask three questions.
1️⃣ Is this shock or hypoperfusion — overt or occult?
Think broadly:
- Cardiac arrest
- Any shock state
- Limb or mesenteric ischaemia
- Compartment syndrome
- Major trauma
- Burns and inhalational injury
- Cyanide or other cellular hypoxia states
Do not be reassured by normal vital signs.
If you are unsure → assume hypoperfusion until proven otherwise and resuscitate.
2️⃣ Does this lactate reflect dangerous pathology that needs treatment or admission?
If lactate is not from hypoperfusion, decide whether it is signalling disease.
Ask:
- Is there ongoing overproduction?
(Malignancy, Pancreatitis, Toxicologic causes)
- Is there impaired clearance?
(Hepatic failure, Renal failure)
- Is this a mixed picture?
(Sepsis, Ethanol, Metformin, Severe pancreatitis)
In these cases:
- Lactate is not benign
- Have a low threshold for admission
- Continue resuscitation and targeted therapy
(e.g. thiamine, source control, stop offending agents)
3️⃣ Can this lactate be explained by a reversible cause — and does it clear?
Only ask this after the first two.
Examples:
- β-agonist use
- Post-ictal state
- Exertional lactate
Here, lactate may be high — but rapid clearance is expected.
Prove it.
- Repeat lactate after time or resuscitation
- Failure to clear = wrong diagnosis until proven otherwise
Want to Read More?
- Wardi, Gabriel, et al. "Demystifying lactate in the emergency department." Annals of Emergency Medicine 75.2 (2020): 287-298.
(Highly recommended for a practical ED-focused understanding of lactate, it is well worth your time.)
- Yartsev A. Causes of acidosis in hyperlactataemia Deranged Physiology Published January 15, 2018.
- Farkas J. Understanding lactate in sepsis & Using it to our advantage. EMCrit PulmCrit. Published July 5, 2015.
- Carden R. Lactate = LactHATE. St Emlyn’s. September 5, 2015.
- Yartsev A. Metabolic origins and metabolic fate of lactate. Deranged Physiology. Published June 14, 2015
- Stiller RH, Luks AM, Çoruh B. All that raises lactate is not sepsis. ATS Scholar. 2023 Jun 12;4(3):385-386. doi:10.34197/ats-scholar.2023-0032OT. PMID: 37795127.
- García-Álvarez M, Marik P, Bellomo R. Sepsis-associated hyperlactatemia. Critical Care. 2014;18(5):503. doi:10.1186/s13054-014-0503-3.
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