The Astrup ischemic cascade
As cerebral blood flow falls, EEG morphology degrades through stereotyped thresholds, and synaptic activity fails before cell death.
1. Bedside vignette: post-arrest day 2 aEEG burst-suppression
A 7-year-old post-asystolic cardiac arrest from drowning, now day 2, cooled to 33.5 °C and re-warmed yesterday. The bedside cEEG shows burst-suppression with a 50% interburst interval at 3 second bursts. NIRS rSO₂ 78%; arterial line MAP 75; no ICP probe. Quantitative aEEG shows a narrow band hovering between 2 and 8 microvolts.
The team asks: what CBF range is this child likely in? On the Astrup ladder, burst-suppression sits between mild slowing (~25–35 mL/100g/min) and electrical silence (~15–25). The mixed flow-and-metabolism picture is consistent with a region partly above and partly below the synaptic-failure threshold, with cooling itself contributing to the suppression. The actionable point is whether the suppression is fixed or reactive: a burst-suppression that opens out into continuous activity with reduced sedation suggests metabolic suppression, while a fixed pattern despite gas, temperature, and sedation correction suggests structural injury.
This is what the Astrup cascade looks like at the bedside: each modality samples a different stretch of the same axis, and bringing them together is what tells you whether you are looking at a salvageable penumbra or a dead core.
2. The thresholds
| CBF (mL/100g/min) | EEG | Function | Reversibility |
|---|---|---|---|
| ≥ 50 | normal | intact | full |
| 35–49 | drowsy / mild slowing | mild deficit | full |
| 25–34 | slow delta dominance | impaired | hours |
| 15–24 | suppressed / low voltage | Na/K pump failing | tight window |
| < 15 | isoelectric | cell death imminent | minutes |
Founders of this framework include Astrup, Siesjö, Symon, Hossmann, and Strong; the operational thresholds have been refined in successive PET, microdialysis, and ECoG cohorts.
3. The clinical implication
EEG goes flat before cells die. That window, between "synaptic silence" and "membrane failure", is the penumbra. It is salvageable. Time-to-perfusion is the lever, which is why thrombectomy windows, decompressive craniectomy timing, and rapid CSF diversion all turn on hours and minutes, not days.
Quantitative EEG detects DCI before clinicians. Alpha-delta ratio falls hours before bedside deterioration in SAH patients.
4. CBF and EEG: a translation table
| CBF (mL/100g/min) | EEG / aEEG signature | PbtO₂ (BOOST-II frame) | MD L/P |
|---|---|---|---|
| ≥ 50 | continuous activity; sleep-wake cycling on aEEG | > 20 (target) | < 25 |
| 35–49 | mild slowing; ADR slightly down | 15–20 (caution) | < 25 |
| 25–34 | delta dominance; ADR clearly down | 10–15 (action) | 25–40 |
| 15–24 | burst-suppression; aEEG narrow band | < 10 (critical) | 40–80 |
| < 15 | isoelectric / inverted aEEG | < 10 (critical) | > 80 |
This is the table that lets you back-infer flow from EEG when you cannot measure flow directly, and to triangulate when two modalities agree. The numbers are bedside heuristics; the boundaries shift with age, sedation, temperature, and underlying pathology. PbtO2 reflects local tissue oxygen tension; the correlation to regional CBF on the Astrup axis is a teaching frame, not a strict measurement equivalence. Probe location, microvascular shunting, and mitochondrial dysfunction can all dissociate PbtO2 from regional flow.
5. Where electrical failure meets membrane failure: the SD generation zone
At CBF ~15 mL/100g/min, Na⁺/K⁺-ATPase begins to fail and cells start to depolarise. Glutamate spills into the extracellular space. The threshold for a spreading depolarisation is now approached, and SDs can be triggered by additional small insults (a transient pressure drop, a focal hypotension). Once an SD has fired, it propagates outward at 2–5 mm/min and consumes a large amount of ATP behind itself; in already-injured cortex this energy bill cannot be paid, and the depolarisation becomes terminal. SDs convert "salvageable" penumbra into infarct, and clusters of SDs are independent predictors of poor outcome in TBI and SAH.
The bedside take is the spreading-depolarisations foundation page and the ECoG-SD modality page; the Astrup cascade is where the cellular conditions that birth SDs are established.
Pediatric thresholds shift, the cascade order does not. Children have higher resting CBF and CMRO₂; the absolute CBF numbers in the table are best treated as adult heuristics, with the order (synaptic, then pump, then membrane) preserved. Neonates are particularly vulnerable to glutamate excitotoxicity, which is part of the rationale for therapeutic hypothermia in HIE. Pediatric microdialysis and ECoG-SD data are sparse, so the cascade is best read off aEEG and PbtO₂ at the bedside.
6. Pattern library
- Slow widespread delta with reactive bursting: 25–35 mL/100g/min territory; reversible if perfusion restored.
- Continuous burst-suppression, fixed: 15–25 territory; ion-pump-failure threshold being crossed. Treat aggressively.
- Isoelectric, no reactivity, normothermic, off sedation: < 15 territory. Membrane failure imminent or established. Goals-of-care conversations enter the room.
- Focal aEEG narrowing in SAH day 5: classic DCI signature; ADR has been falling for hours.
- NIRS rSO₂ falls + aEEG narrows + PbtO₂ falls: convergent crash; multimodal alarm; act.
7. Combine with…
- Modality: EEG / cEEG: the cleanest readout of the synaptic-failure transition.
- Modality: qEEG: alpha-delta ratio for DCI detection.
- Modality: aEEG: bedside summary trace, neonatal HIE and post-arrest.
- Modality: PbtO₂: tissue O₂ at the membrane-failure threshold.
- Modality: microdialysis: L/P at the metabolic-failure threshold.
- Foundation: spreading depolarisations: what happens when the cascade reaches membrane failure.
- Foundation: cerebral metabolism: the demand half of the supply-demand mismatch.
8. What fails when
- At 50 mL/100g/min: normal. Synaptic function intact; oxygen extraction ratio ~30%.
- 35–49: neuronal pH falls. Synaptic transmission becomes intermittent. Cognition degrades but ions still fine.
- 25–34: protein synthesis stops. Action potentials become sparse. EEG slows into delta. Patient is symptomatic but reversible.
- 15–24: Na⁺/K⁺-ATPase begins to fail. Cells depolarise. Glutamate is released; spreading depolarisations begin. Microdialysis shows L/P > 40 with low glucose.
- < 15: anoxic depolarisation. Cell death begins within minutes via mitochondrial calcium overload, excitotoxicity, and reactive oxygen species.
9. Why the EEG fails first
Synaptic activity is the most expensive bucket in CMRO₂. The cell can preserve its membrane potential (cheaper) by stopping firing. EEG goes silent; cell stays alive. This is the basis for burst-suppression as a metabolic protection strategy: induce silence, preserve cell.
10. Penumbra and core
In focal ischaemia (stroke), the core is below 15 mL/100g/min and dies fast. The penumbra is at 15–25, symptomatic but viable, the substrate for recanalisation. CT and MR perfusion can map this; bedside qEEG and NIRS are the closest continuous surrogates.
11. Implications by modality
- EEG / qEEG: picks up the 25–35 transition (early).
- PbtO₂: falls at the 15–25 transition.
- Microdialysis L/P: rises at the 15–25 transition.
- NIRS: integrated regional signal; less specific.
- TCD: drops at any threshold but most pathognomonic at the 15 boundary (oscillating flow).
12. Evidence summary
| Topic | Source | Grade |
|---|---|---|
| Pediatric brain injury review | review | |
| qEEG / ADR for DCI | B | |
| ACNS continuous-EEG terminology | expert | |
| PbtO₂ at membrane-failure threshold | C | |
| BOOST-II / BOOST-III PbtO₂ trials | A/B | |
| Microdialysis consensus | expert | |
| SD biology and detection | B | |
| Strong 2002 ECoG-SD validation | B | |
| Pediatric PbtO₂ review | review |
13. Self-check
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