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Chapter question: The patient is on pump, the cause has been found, the temperature is being held, and the family is asking the only question they care about. Every instrument that could answer it was validated in a population where doctors withdrew treatment on the basis of that same instrument — and half of those instruments behave differently on a circuit. What can honestly be said, and when?
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Evidence search date: 14 September 2026.
Primary sources: ELSO Red Book 6th edition — Chapter 32 (neuroprognostication aligned with conventional CPR practice, the neurological care bundle), the adult systematic-review complication figures, and the paediatric and neonatal neuromonitoring chapters. ECPR and Resuscitative ECMO (Shinar and Badulak), Chapter 3 — the clinical examination findings at hospital arrival and the signs-of-life literature.
External evidence: the ECPR brain-injury epidemiology (an autopsy series, three ELSO Registry analyses, two meta-analyses), the neuroprognostication literature in full (the ERC/ESICM algorithm and its two validation cohorts, the two no-withdrawal cohorts, the ECMO-specific comparisons, the PRAGUE-OHCA biomarker sub-analysis, the SAVE-J II imaging analysis of 1,146 patients, the ECPR electroencephalography studies, and the good-outcome literature).
Everything external in this chapter comes from a structured abstract. Nothing was retrieved in full text. Every database row seeded from this chapter is marked Verified = No.
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Chapter 22 ended where prediction begins. This chapter is about inference: what can be concluded about a brain from the instruments available, and with what confidence. It is not about the instruments themselves, and it is not about what is then done.
| This chapter owns | Owned elsewhere — cite, do not re-argue |
|---|---|
| What actually happens to ECPR patients neurologically, and how much of it is never detected | Cerebral monitoring as a set of instruments — near-infrared spectroscopy, transcranial Doppler, electroencephalography — Chapter 28 |
| The self-fulfilling prophecy, and which studies escape it | The decision to stop, and the conversation with the family — Chapter 24 |
| What the circuit does to each prognostic instrument | Futility and non-beneficial ECMO as a concept — Chapter 74; withdrawal of ECMO as a procedure — Chapter 75 |
| Neuron-specific enolase on ECMO, and why its threshold is not the published one | Laboratory monitoring generally — Chapter 29; haemolysis — Chapter 37 |
| Electroencephalography as an instrument of prognosis | Electroencephalography as a seizure monitor, and the treatment of seizures — Chapter 22 §22.12, Chapter 28, Chapter 51 |
| Brain imaging for prediction, and the grey-white matter ratio in ECPR specifically | Brain imaging to find the cause of the arrest — Chapter 22 §22.8 |
| When prediction may begin, and why sedation moves the clock | Sedation, analgesia and the ECMO sequestration problem — Chapter 57, Chapter 49 |
| Predicting a good outcome — the neglected half of the problem | Pre-cannulation selection scores (TiPS65, the Pre-ECPR score) — Chapter 20; scores as a class — Chapter 30 |
| How to run a prognostication process, and the errors that recur | Long-term functional and cognitive recovery — Chapter 59; palliative care — Chapter 76 |
The boundary with Chapter 24 is the one that matters. This chapter produces a probability. Chapter 24 decides what to do about it. Those are different acts, performed by overlapping people at the same bedside, and conflating them is the single commonest error in this field — because a prediction that is made in order to justify a decision has already stopped being a prediction.
Begin with base rates, because almost every conversation in this chapter goes wrong when they are not known.
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Evidence · Low certainty · Where ECPR patients end up
The largest synthesis covers 78 studies and 50,049 patients, of whom 6,261 (12.5%) received ECPR — median age 56, 63% male, 48% out-of-hospital, 37% initial shockable rhythm, median support duration 3.2 days.
Neurological events: at least one neurological complication in 27% (17–39%); hypoxic-ischaemic brain injury 23% (14–32%); ischaemic stroke 6% (2–11%); seizures 6% (1–16%); intracerebral haemorrhage 4% (1–10%); and brain death in 17% (12–23%).
Outcomes: survival 29% (26–33%); good neurological outcome 24% (21–28%).
Those last two numbers are the ones to hold. Survival 29%, good outcome 24% — which means roughly five in six survivors had a good neurological outcome.
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That ratio is not an artefact of one synthesis. It recurs everywhere it is measured.
| Cohort | Survival | Good outcome | Good outcome as a share of survivors |
|---|---|---|---|
| Migdady 2020, 78 studies, 6,261 ECPR patients | 29% | 24% | ~83% |
| Gravesteijn 2020, in-hospital arrest, 19 studies | 30% (28–33%) | — | 84% (80–88%), stated directly |
| Pozzi 2026, 295 consecutive patients over 14 years, outcome at 6 months | 21.7% | 17.3% (28.2% in-hospital arrest vs 10.1% out-of-hospital) | ~80% — only 4.4% of the whole cohort survived with severe sequelae |
| Rojas-Salvador 2023, 361 patients, single centre | 47% | 40% | 85% (145 of 170) |
| Han 2019, 100 patients (Chapter 22 §22.1) | 14% | 12% | 85.7% (12 of 14) |
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Clinical pearl · The outcome distribution in ECPR is close to bimodal, and this is not what most clinicians expect
Ask a clinician what they fear most about ECPR and the answer is usually the same: creating a survivor with a devastated brain. That outcome is the rarest of the three destinations. In the largest long-term series, 17.3% of patients reached a good neurological outcome at six months and 4.4% survived with severe sequelae — roughly a four-to-one ratio in favour of the outcome everyone wants.
The practical form: when a patient survives ECPR, the strong prior is that they will be neurologically reasonable. The uncertainty in this population is overwhelmingly about whether they will survive, not about what state they will survive in.
This is a prior, not a prediction, and §23.2 explains why it may be partly manufactured. But it is the correct starting point for a family conversation on day one, and it is very often not what the family is told.
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Danger · The bimodality may be manufactured by the very practice this chapter describes
If a unit withdraws treatment from every patient whose neurological indicators look bad, and does so before those patients could have declared themselves, then the severely disabled survivor is rare because the unit prevented them from existing. The observed distribution would look exactly the same either way.
Two observations keep this from being a purely theoretical worry. First, in the 45-patient Prague sub-analysis with brain imaging, brain death accounted for 41% of deaths among poor-outcome patients, multiorgan failure 38% and recurrent cardiac arrest 13% — so a substantial share of deaths were not neurological at all, and a substantial share were irreversible by any definition. Second, and cutting the other way, Chapter 22 §22.9 recorded a registry analysis in which hypothermia was associated with survival but not with a favourable neurological outcome — the signature of additional survivors in poor neurological states.
Both facts are true at once. This book records the bimodality as the best available description of what happens, and records that its magnitude is not independently verifiable in a system that withdraws treatment.
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There is a second problem with the base rates, and it is larger than it looks.
| How brain injury was looked for | Population | How much was found |
|---|---|---|
| ELSO Registry, voluntary reporting, no protocol | 10,775 ECPR patients | 16.5% |
| ELSO Registry, same analysis, non-ECPR venoarterial | 35,855 patients | 7.7% |
| Meta-analysis of published series | 6,261 ECPR patients | 27% any neurological complication; 23% hypoxic-ischaemic |
| Standardised multimodal neuromonitoring at one centre | 123 venoarterial patients | 33% |
| Electroencephalography actually applied | 92 ECMO patients monitored, 28% of them ECPR | 63% had epileptiform activity or ictal-interictal continuum patterns |
| Post-mortem brain autopsy | 25 ECMO decedents, 22 venoarterial | 68% had acute brain injury — hypoxic-ischaemic 44%, intracranial haemorrhage 24%, ischaemic infarct 16%. Only 8 of 25 had none |
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Physiology · The detection gradient is the finding
Read that table downwards and the prevalence of brain injury rises from 16.5% to 68% — and nothing about the brains changed. Only the intensity of looking changed.
The registry figure is a floor, and its own authors say so: the machine-learning analysis of the venovenous registry concluded that performance was suboptimal "likely due to lack of standardization of neuromonitoring/imaging protocols and data granularity," and called for standardised monitoring "to detect the true prevalence." The Red Book makes the same point about paediatric registry data: complications reported to ELSO "should be viewed as minimal estimates" because reporting is voluntary and evaluation is not systematic.
The operational consequence for this chapter is uncomfortable. A clinician predicting outcome from a registry-derived risk figure is using a denominator built from unsystematic detection. It also means that a unit which begins monitoring systematically will appear to get worse before it appears to get better.
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Evidence · Low certainty · ECPR is the reason venoarterial ECMO looks neurologically dangerous
A meta-analysis of 73 studies and 16,063 patients compared brain injury between modes: venoarterial 19% versus venovenous 10% (P = 0.002), with ischaemic stroke 10% versus 1%, hypoxic-ischaemic injury 13% versus 1% and brain death 11% versus 1%. Intracerebral haemorrhage did not differ (6% versus 8%).
Then the authors excluded the studies containing ECPR — and the overall difference vanished: 13% versus 10%, P = 0.4.
The registry analysis makes the same point with different arithmetic: acute brain injury in 16.5% of ECPR patients against 7.7% of non-ECPR venoarterial patients.
The brain injury in this population is a property of the cardiac arrest, not of the venoarterial configuration. Chapter 17's vascular complications belong to the cannula; these belong to the forty minutes before it.
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Pitfall · Two different injuries with two different clocks
The ECPR patient is at risk of hypoxic-ischaemic injury that was inflicted before cannulation, and of stroke and haemorrhage that occur on support. They do not arrive at the same time, and a single scan does not exclude both.
In an 878-patient venoarterial cohort, ischaemic stroke occurred after a median of 11 days (6–18) and intracranial bleeding after 5 days (2–9). Intracranial bleeding, not ischaemic stroke, was associated with higher mortality. Female sex, central cannulation and a platelet count below 100 at initiation were independently associated with bleeding — as, in a nested analysis, was a rapid carbon dioxide change at ECMO start, which is Chapter 22 §22.3 arriving from the haemorrhagic side.
A normal brain CT on day one says nothing about day eleven.
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