Your ICP is 14. Your CPP is sitting where the autoregulation index says it should. PbtO2 is comfortable. And the lactate/pyruvate ratio from the microdialysis catheter has been climbing all night.
This is the moment microdialysis earns its place, because it is telling you something no pressure-based monitor can. The question is what to do next — and the instinct to push the pressure up is often wrong.
📌 The hook: High LPR with low pyruvate means no oxygen. High LPR with normal or high pyruvate means sick mitochondria. The first responds to flow and oxygen. The second does not.
🔬 What the catheter actually measures
A 20 kDa membrane perfused at 0.3 µL/min, giving roughly 70% recovery, with vials collected hourly. Three properties follow from that, and all three matter at the bedside: the readout is focal, it is delayed, and it is labour-intensive. You are sampling one small volume of brain, an hour behind events.
📊 Thresholds worth knowing
From the 2014 international consensus statement:
| Analyte | Threshold |
|---|---|
| Lactate/pyruvate ratio | > 25 abnormal; > 40 metabolic crisis |
| Brain glucose | < 0.8 mmol/L low; < 0.2 mmol/L critical |
| Glutamate | Adjunct — excitotoxicity, seizures |
| Glycerol | Adjunct — membrane breakdown |
🎯 Where the catheter sits decides what it means
The tip belongs in at-risk tissue: pericontusional brain, or territory prone to vasospasm. Not in the dead core, where the numbers are meaningless, and not in distant normal brain, where they are reassuring and irrelevant. Confirm the gold tip on CT before you believe anything the analyser tells you.
🩺 Type 1 or Type 2?
Type 1, ischaemic. High LPR with low pyruvate. Oxygen or flow is not arriving. This one you treat with delivery.
Type 2, non-ischaemic. High LPR with normal or high pyruvate. Substrate is arriving; the cell cannot use it. Raising CPP here buys you nothing, and the oedema and cardiac cost of chasing pressure are real. The rest of this post is about Type 2.
1️⃣ Exclude hidden ischaemia first
Mixed pictures exist, and a focal catheter can miss a regional supply problem. Before you accept a mitochondrial label, go back through the delivery chain: PbtO2, CPP measured against the autoregulation-guided optimum rather than a protocol number, ICP, haemoglobin, PaO2 and PaCO2.
If you find a supply deficit, fix it regardless. It is cheap, and it is the safe default when you are not sure which picture you are looking at.
2️⃣ Hunt for the cause of the metabolic stress
- Seizures or non-convulsive status. Get continuous EEG. A high LPR with high glutamate points here, and non-convulsive status is easy to miss in a sedated patient.
- Fever or hyperthermia. Treat to normothermia to cut demand.
- Glucose. Read brain glucose alongside the LPR, never alone. Low brain glucose with tight systemic control is neuroglycopenia, and the answer is to liberalise.
- Sepsis, or a mitochondrial toxin. This includes propofol above 4 mg/kg/h — the propofol infusion syndrome link. Reduce the dose and change agent.
- Catecholamine- and glutamate-driven hyperglycolysis. This raises lactate without any true mitochondrial failure, and it is worth recognising before you escalate.
3️⃣ Cut demand, support the substrate
- Deepen sedation, or use a barbiturate if the ICP situation allows it.
- Avoid tight glycaemic control. Aim for roughly 140–180 mg/dL, following the NICE-SUGAR logic. The injured brain tolerates tight control badly.
- Start nutrition early.
4️⃣ Experimental options — name them, and say so
In a viva, knowing these exist is worth marks. Claiming they are standard is not.
- Hypertonic sodium lactate as an alternative fuel (Ichai, Bouzat).
- Normobaric hyperoxia. Small studies improved the LPR, but PET showed no gain in CMRO2. The evidence is genuinely mixed.
- Cyclosporin, as a blocker of the mitochondrial permeability transition pore.
🗣️ Viva essentials
Q. What do the lactate/pyruvate ratio and glucose tell you that ICP cannot, and why must the catheter not sit in the contusion core?
Say: LPR > 25 and > 40 · type 1 versus type 2 · penumbral placement · 0.3 µL/min. ICP and CPP describe the plumbing; microdialysis describes whether the cell is actually making ATP. In dead core tissue there is no metabolism left to measure, so the numbers mean nothing.
Probe: how does tight insulin therapy show up? As falling brain glucose with a rising LPR — neuroglycopenia in a patient whose blood sugar looks respectable.
🧾 Take-home
Pyruvate is the discriminator. Low pyruvate sends you to the delivery chain; normal pyruvate sends you looking for seizures, fever, sepsis, propofol and tight glycaemic control. The temptation with a rising LPR is always to push the pressure higher. In the Type 2 picture that is effort spent on the wrong organ system.
For education only. Follow your local neurocritical care protocols.