Prognostication in comatose survivors of cardiac arrest. An Advisory Statement from the European Resuscitation Council and the European Society of Intensive Care Medicine

Intensive Care Medicine, 2014.

Claudio Sandroni, Alain Cariou, Fabio Cavallaro, Tobias Cronberg, Hans Friberg, Cornelia Hoedemaekers, Janneke Horn, Jerry P. Nolan, Andrea O. Rossetti and Jasmeet Soar

Corresponding author:

Claudio Sandroni

Department of Anaesthesiology and Intensive Care

Catholic University School of Medicine,

Largo Gemelli, 8 - 00168 Rome, Italy

ESM Table 5. Blinding of treating team and criteria for treatment suspension in included studies.

Author, year / Indexes / Blinding (treating team) / Criteria for treatment suspension or limitation of care / Minimal duration of support
Clinical Examination
Al Thenayan 2008 / PLR, CR, MR, Status myoclonus / No / - / -
Bertini 1989 / PLR, MR / - / - / -
Bouwes BMC 2012 / Status myoclonus / Yes (1) / At discretion of treating physician; in most cases, based on absent N20 SSEP after rewarming / -
Earnest 1979 / PLR, OCR, MR / - / - / -
Greer 2013 / PLR, CR, MR / No / At discretion of treating team / -
Hui 2005 / Status myoclonus / - / - / -
Krumholz 1988 / Status myoclonus / - / - / -
Okada 2012 / PLR, MR / No / - / -
Pfeifer 2005 / GCS / - / - / -
Thomke 2005 / Myoclonus / No / Clinical examination, EEG, NSE / 3-4 d
Wijdicks 1994 / Status myoclonus / No / Withdrawal of life support reported but the criteria are not specified / -
Wu 2011 / PLR, CR, MR / - / - / -
Young 1990 / Status myoclonus / - / - / -
Electrophysiology
Bauer 2003 / SSEPs / - / Treatment and management “were not influenced by the results of the SEP recordings” / -
Berkhoff 2000 / Alpha coma / - / - / -
Cloostermans 2012 / cEEG / Yes, partial (2) / Absent N20 SSEP at 72h / -
Kawai 2011 / EEG / No / - / -
Leary 2010 / BIS / No / Perception of moribund condition / -
Leithner 2010 / SSEP / No / - / -
Oh 2012 / aEEG / No / - / -
Rothstein 2000 / SSEPs / - / “In no patient was a decision to abandon medical support based on the results of SSEPs” / -
Rundgren 2010 / aEEG / No / M≤2 and absent N20 SSEP after rewarming / 3 d
Seder 2010 / BIS, SR / No / - / -
Stammet 2009 / BIS / No / No PLR on day 3, seizures or M=1 on day 5 and/or absent N20 SSEP and/or signs of brain damage on CT or MRI / 5 d after suspension of sedation
Stelzl 1995 / SSEPs / - / - / -
Tiainen 2005 / SSEPs / Yes / Clinical status (not on electrophysiological tests) / 3-7 d
Zanatta 2012 / EEG, SSEP / No / - / -
Biomarkers
Hachimi-Idrissi 2002 / S-100 / Yes / - / -
Mortberg 2011 / NSE, S-100B / No / - / -
Mussack 2002 / S-100B / - / - / -
Oksanen 2009 / NSE / No / Clinical status, absent N20 SSEP, myoclonus, nonreactive EEG, brain damage on CT / 3-5 d
Reisinger 2007 / NSE / No / Irreversible multiple organ failure or brain death / -
Rosen 1998 / S-100 / - / - / -
Rosen 2001 / NSE, S-100B / - / - / -
Rundgren 2009 / NSE / No / GCS / 3 d after RW
Steffen 2010 / NSE / No / SSEP, PLR, MR, NSE / 3 d
Storm 2012 / NSE / No / SSEP, PLR, MR, NSE / -
Tiainen 2003 / NSE, S-100B / No / - / 3-7 d (3)
Imaging
Choi 2008 / BrainCT / - / - / -
Choi 2010 / Brain MRI / No / No withdrawal / unlimited
Els 2004 / Brain MRI / - / - / -
Inamasu 2010 / Brain CT / - / - / -
Kim 2013 / Brain CT / - / Patients in whom intensive care was withdrawn were excluded / -
Mlynash 2010 / Brain MRI / - (4) / No withdrawal / unlimited
Morimoto 1993 / BrainCT / - / - / -
Wijdicks 2001 / Brain MRI / - / Withdrawal of life support reported but the criteria are not specified / -
Wijman 2009 / Brain MRI / Yes / Based on the AAN 2006 review / -
Wu 2009 / Brain MRI / No / Withdrawal of life support reported but the criteria are not specified / -
Multimodal
Bassetti 1996 / BR, GCS, MR, EEG, SSEPs / No / Withdrawal of life support reported but the criteria are not specified / 3 d
Bisschops 2011 / Myoclonus, PLR, MR, SSEP, EEG / No / N20 SSEP absent after rewarming or absent CR and PLR + M≤2 / 3 d
Bouwes 2009 / PLR, CR, MR, SSEP / Yes (1) / At discretion of treating physician; in most cases, based on absent N20 SSEP after rewarming / -
Bouwes AN 2012 / PLR, CR, MR, NSE, SSEP / Yes (1) / At discretion of treating physician; in most cases, based on N20 SSEP absent after RW / -
Choi 2012 / MRI, SSEP / No / - / -
Crepeau 2013 / Myoclonus, cEEG / No / Family request in some cases. / < 2 days
Cronberg 2011 / PLR, CR, MRI, SSEP, EEG, NSE (5) / No / M≤2 or absent PLR or absent N20 SSEP on day 3 / 3 d
Edgren 1987 / BR, MR, EEG / No / Severe brain damage and no improvement / 3 d
Fugate 2010 / PLR, CR, MR, SSEP / No / Neurologic assessment, critical illness state / -
Kim 2012 / NSE, MRI / No / At the discretion of the treating physicians / -
Lee 2013 / NSE, brain CT / No / No withdrawal / -
Legriel 2013 / Myoclonus, PSE / No / Bilaterally absent PLR or CR or MR or bilaterally absent N20 / 7 d
Oddo 2014 / BR, Myoclonus, EEG, SSEP, NSE / No / 2 criteria in normothermia: unreactive EEG (7), treatment-resistant myoclonus, N20 bilaterally absent (8), incomplete brainstem reflexes / 3 d
Rittenberger 2012 / EEG, Status myoclonus / No / - / -
Rossetti AN 2010 / Myoclonus, BR, MR, EEG, SSEP / No / AAN criteria (2006) (6), based on BR, EEG (7), SSEP at ≥24h after weaning from sedation / 3 d
Rossetti CC 2010 / MR, SSEP / - / Incomplete recovery of brainstem reflexes, bilaterally absent N20 / 3 d
Rossetti 2012 / BR, MR, myoclonus, SSEP, EEG, NSE / No / At least 2 of the following: 1) incomplete recovery of BR; 2) early myoclonus; 3) unreactive EEG; 4) absent N20 SSEP.(8). / 3 d after RW
Samaniego 2011 / PLR, CR, MR, status myoclonus, NSE, SSEP / No / Multiple clinical and neurophysiological testing "In accordance with patient's next of kin" / 3 d
Stammet 2013 / BIS, S-100B / Yes / clinical signs of brain death / 5 days after suspension of sedation
Topcuoglu 2009 / GCS, FOUR score, brain MRI / No / No withdrawal / unlimited
Wennervirta 2009 / NSE, EEG / No / - / -
Young 2005 / PLR, CR, OVR, MR, myoclonus, SSEPs, EEG / - / - / -
Zandbergen 2006 (a) / BR, MR, status myoclonus, NSE, S-100B, SSEPs, EEG / Yes (9) / SSEPs, EEG, PLR, MR / 1-2 d
Zellner 2013 / MR, S100B / No / Decision was taken together with the family and the neurological consultation service / -
Zingler 2003 / NSE, S-100B, SSEPs / - / - / -

Indexesused for treatment suspension are in bold.

Abbreviations

BAEPs = Brain stem Auditory Evoked Potentials; BIS = Bispectral Index; BR: Brain Reflexes; CR = Corneal Reflex; CT = Computed tomography; d = days; EEG = Electroencephalogram; GCS= Glasgow Coma Score; M= GCS motor score; MR = Motor Response; MRI = Magnetic Resonance Imaging; N/A = Not Available; NSE = Neuron-Specific Enolase; OVR = Oculo-vestibular reflex PLR = Pupillary Light Response; RW: rewarming; SR = Suppression Ratio; SSEPs = Short-latency Somatosensory Evoked Potentials; TH = Therapeutic Hypothermia.

Notes

(1) Results of SSEP recorded during normothermia were not disclosed to the treating physician. In patients who remained in coma after rewarming, a second SSEP was performed and its results were disclosed to the treating physician.

(2) The treating physicians were not completely blinded to the EEG to allow treatment of epileptiform discharges, and also had access to SSEP results

(3) Life support was maintained for at least 3 days in all patients and at least 7 days in patients responding to pain in any manner

(4) An unspecified number of patients underwent withdrawal of life support and were excluded from the study. The study included only patients who were alive at 6 months or died while meeting the following criteria: absent PLR or motor response on day 3, and/or bilaterally absent SSEP cortical response on day 2, and/or vegetative after 1 month.

(5) This is a retrospective study aimed to investigate the correlation among NSE and other prognostic markers.

(6) Wijdicks EF et al. Neurology 2006; 67:203-10. SSEP and a routine EEG were obtained at 72 ± 8 hours following resuscitation.

(7) “EEG reactivity did not influence the decision” on termination of life support.

(8) Criteria were assessed at NT ≥48–72 hours after CA. Results of EEGduring HT and NSE did not influence decisions on withdrawal.

(9) The treating physicians were blinded to the SSEP only for 48 h. At 72h SSEP results were disclosed. Treatment limitations were based, among others, on SSEP results.