Results and conclusions
- 1.The AAN 2006 review was based on studies conducted before the advent of therapeutic hypothermia (TH) for post-resuscitation care. Both TH itself and sedatives or neuromuscular blocking drugs used to maintain it may potentially interfere with prognostication indices, especially clinical examination.3The predictive value of those indices therefore needs to be re-evaluated in TH-treated patients.
- 2.Studies conducted both before4and after
Early prediction of neurological outcome after cardiopulmonary resuscitation: a multimodal approach combining neurobiochemical and electrophysiological investigations may provide high prognostic certainty in patients after cardiac arrest.Eur Neurol. 2003; 49: 79-845,6the AAN 2006 review showed that the previously recommended thresholds for outcome prediction using biomarkers were inconsistent.7
- Zingler V.C.
- Krumm B.
- Bertsch T.
- Fassbender K.
- Pohlmann-Eden B.
- 3.Evidence for some prognostic tools such as EEG8and imaging studies was limited at the time of the 2006 AAN review, and needs re-evaluation.
- 4.The AAN 2006 review and previous reviews did not adequately address some important limitations of prognostication studies, such as the risk of ‘self-fulfilling prophecy’, which is a bias occurring when the treating physicians are not blinded to the results of the outcome predictor and use it to make a decision to withdraw life-sustaining treatment (WLST).9
- 1.Update and summarise the available evidence on this topic, including that on TH-treated patients;
- 2.Provide practical recommendations on the most reliable prognostication strategies, based on a more robust analysis of the evidence, in anticipation of the next ERC Guidelines on Resuscitation to be published in October 2015;
- 3.Identify knowledge gaps and suggest directions for future research.
2.1 Panel selection
2.2 Group process
2.3 Inclusion criteria and definitions
2.4 Data source
2.5.1 Quality of evidence
3. Clinical examination
3.1 Evidence (ESM table 1)
3.1.1 Ocular reflexes
3.1.2 Motor response to pain
- •Using the bilateral absence of both pupillary and corneal reflexes at 72 h or more from ROSC to predict poor outcome in comatose survivors from cardiac arrest, either TH-treated or non-TH-treated.
- •Prolonging observation of clinical signs beyond 72 h when interference from residual sedation or paralysis is suspected, so that the possibility of obtaining false positive results is minimised.
3.3 Knowledge gaps
- •Prospective studies are needed to investigate the pharmacokinetics of sedative drugs and neuromuscular blocking drugs in post-cardiac arrest patients, especially those treated with controlled temperature.
- •Clinical studies are needed to evaluate the reproducibility of clinical signs used to predict outcome in comatose post-arrest patients. In particular, clinical examination tends to underestimate the presence of pupillary reflex, which can be detected and quantified using pupillometry.46,47
4. Myoclonus and status myoclonus
4.1 Evidence (ESM table 1)
- Zingler V.C.
- Krumm B.
- Bertsch T.
- Fassbender K.
- Pohlmann-Eden B.
- •Using the term status myoclonus52to indicate a continuous and generalised myoclonus persisting for ≥30 min in comatose survivors of cardiac arrest
- •Using the presence of a status myoclonus within 48 h from ROSC in combination with other predictors to predict poor outcome in comatose survivors of cardiac arrest, either TH-treated or non-TH-treated
- •Evaluating patients with post-arrest status myoclonus off sedation whenever possible; in those patients, EEG recording can be useful to identify EEG signs of awareness and reactivity61and to reveal a coexistent epileptiform activity.
4.3 Knowledge gaps
- •A consensus-based, uniform nomenclature and definition for status myoclonus is needed.
- •The distinctive pathophysiological and electrophysiological features of postanoxic status myoclonus, in comparison with more benign forms of myoclonus, like the Lance-Adams syndrome, need to be further investigated.
5. Bilateral absence of SSEP N20 wave
5.1 Evidence (ESM table 2)
- Zingler V.C.
- Krumm B.
- Bertsch T.
- Fassbender K.
- Pohlmann-Eden B.
- •Using bilateral absence of N20 SSEP wave at ≥72 h from ROSC to predict poor outcome in comatose survivors from cardiac arrest treated with controlled temperature.
- •Using SSEP at ≥24 h after ROSC to predict poor outcome in comatose survivors from cardiac arrest not treated with controlled temperature.
5.3 Knowledge gaps
- •Most of prognostic accuracy studies on SSEPs in post-anoxic coma were not blinded, which may have led to an overestimation of the SSEP prognostic accuracy due to a self-fulfilling prophecy. Blinded studies will be needed to assess the relevance of this bias.
6. Electroencephalogram (EEG)
6.1 Evidence (ESM table 2)
6.1.1 Absence of EEG reactivity
6.1.2 Status epilepticus
6.1.3 Low voltage EEG
- •Using EEG-based predictors such as absence of EEG reactivity to external stimuli, presence of burst-suppression or status epilepticus at ≥72 h after ROSC to predict poor outcome in comatose survivors from cardiac arrest.
- •Using these predictors only in combination (i.e. presence of burst-suppression or status epilepticus plus an unreactive background) and combining them with other predictors, since these criteria lack standardisation and the relevant evidence is limited to a few studies performed by experienced electrophysiologists
- •Not using a low EEG voltage to predict outcome in comatose survivors of cardiac arrest, because of the limited evidence and the risk of interference from hypothermia, ongoing sedation and technical factors.
6.3 Knowledge gaps
- •Larger prospective studies on the prevalence and the predictive value of EEG changes in comatose survivors of cardiac arrest are needed, especially in patients who have been rewarmed from controlled temperature.
- •The definition of SE and the modalities for eliciting and evaluating EEG reactivity need standardisation. In future studies, definitions of burst suppression and low-voltage EEG should comply with recent recommendations.77
- •It is not clear whether postanoxic SE is only a marker of brain injury or whether it contributes directly to neurological injury, nor if antiepileptic treatments may potentially improve its outcome.
7.1 Evidence (ESM table 3)
7.1.1 Neuron-specific enolase (NSE)
- Zingler V.C.
- Krumm B.
- Bertsch T.
- Fassbender K.
- Pohlmann-Eden B.
- Zingler V.C.
- Krumm B.
- Bertsch T.
- Fassbender K.
- Pohlmann-Eden B.
- •Using high serum values of NSE at 48–72 h from ROSC in combination with other predictors for prognosticating a poor neurological outcome in comatose survivors from cardiac arrest, either TH-treated or non-TH-treated. However, no threshold enabling prediction with zero FPR can be recommended.
- •Using utmost care and preferably sampling at multiple time-points when assessing NSE to avoid false positive results due to haemolysis.
7.3 Knowledge gaps
- •There is a need for standardisation of the measuring techniques for NSE and S-100 in cardiac arrest patients.
- •Little information is available on the kinetics of the blood concentrations of biomarkers in the first few days after cardiac arrest.
8.1 Evidence (ESM table 4)
8.1.1 Brain CT
- •Using the presence of a marked reduction of the GM/WM ratio or sulcal effacement on brain CT within 24 h after ROSC or the presence of extensive reduction in diffusion on brain MRI at 2-5 days after ROSC to predict a poor outcome in patients who are comatose after resuscitation from cardiac arrest both TH-treated or non-TH-treated
- •Using brain CT and MRI for prognosticating poor outcome after cardiac arrest only in combination with other predictors.
- •Using brain imaging studies for prognostication only in centres where specific experience is available, given the limited number of studied patients, the spatial and temporal variability of post-anoxic changes in both CT and MRI, and the lack of standardisation for quantitative measures of these changes.
8.3 Knowledge gaps
- •Evidence on imaging studies in comatose survivors of cardiac arrest is limited by small sample size and likely selection bias. Larger prospective studies are needed to confirm the results of the currently available studies.
- •The severity of brain CT and MRI changes after global ischaemic injury will need a standardised description, e.g. using scoring systems similar to those used for traumatic brain injury.115
Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and combinations of computed tomographic predictors.Neurosurgery. 2005; 57 (discussion 1173–1182): 1173-1182
- Maas A.I.
- Hukkelhoven C.W.
- Marshall L.F.
- Steyerberg E.W.
- •The prognostic value of quantitative vector indices derived from DT imaging, such as fractional anisotropy and axial diffusivity need to be evaluated in future studies.
9. Self-fulfilling prophecy
10. Practical approach: suggested prognostication strategy
Conflict of interest statement
- •Claudio Sandroni is a member of the Editorial Board, Resuscitation Journal (unpaid); evidence reviewer of the Advanced Life Support Task Force, International Liaison Committee on Resuscitation (ILCOR) (unpaid). He is the first author of two systematic reviews on prognostication in comatose patients resuscitated from cardiac arrest.
- •Alain Cariou is the Deputy of Trauma and Emergency Medicine (TEM) Section of the European Society of Intensive Care Medicine (ESICM); Delegate from the ESICM in the General Assembly of the European Resuscitation Council (ERC). He received academic research grants from French Ministry of Health for conducting clinical research in the field of cardiac arrest (all data controlled by the investigators).
- •Fabio Cavallaro is a co-author of two systematic reviews on prognostication in comatose patients resuscitated from cardiac arrest.
- •Tobias Cronberg is the Coordinator of recommendations on prognostication after cardiac arrest, Swedish Resuscitation Council. He received academic research grants from multiple non-profit organisations for the conduct of a cognitive sub-study and EEG sub-study of the Target Temperature Management trial (all data controlled by the investigators).
- •Hans Friberg received lecture fees from Natus Inc (manufacturer of NervusMonitor, cont. EEG/aEEG) and from Bard Medical. He received grants from the EU Interreg. Programme IV A and academic research grants from multiple non-profit organisations for the Target Temperature Management trial (all data controlled by the investigators). He is the chair of the working party “Care after cardiac arrest”, Swedish Resuscitation Council.
- •Cornelia Hoedemaekers is co-author of a systematic review on diagnostic tools for prediction of poor outcome after cardiopulmonary resuscitation.
- •Janneke Horn received a Grant from the Dutch Heart Foundation (2007B039) for PROPAC II study and from the Dutch Brain Foundation (14F06.48) for research on SSEP during hypothermia treatment after cardiac arrest (data controlled by investigator and no restrictions on publication). She is the principal investigator of PROPACII study and co-author of a systematic review on diagnostic tool for prediction of poor outcome after cardiopulmonary resuscitation.
- •Jerry Nolan is the Editor-in-Chief, Journal Resuscitation and Vice-Chair, European Resuscitation Council.
- •Andrea Rossetti received a grant from the Swiss National Science Foundation (grant no. CR32I3_143780).
- •Jasmeet Soar is the Editor, Journal Resuscitation (Honorarium). He is member of the Executive Committee, Resuscitation Council (UK) (unpaid); Chair of the ERC ALS Working Group (unpaid); Co-chair of the ALS ILCOR Task Force (unpaid).
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☆This manuscript has been endorsed by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM). This article is being simultaneously published in Resuscitation and Intensive Care Medicine [ISSN: 0342-4642 (print version) ISSN: 1432-1238 (electronic version)].
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