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1. EEG for good outcome prediction after cardiac arrest: A multicentre cohort study

Author

Turella, S., Dankiewicz, J., Ben-Hamouda, N., Nilsen, KB, Düring, J., Endisch, C., Engstrøm, M., Flügel, D., Gaspard, N., Grejs, A.M., Haenggi, M., Haffey, S., Imbach, L., Johnsen, B., Kemlink, D., Leithner, C., Legriel, S., Lindehammar, H., Mazzon, G., Nielsen, N., Peyre, A., Ribalta Stanford, B., Roman-Pognuz, E., Rossetti, A.O., Schrag, C., Valeriánová, A., Wendel-Garcia, P., Zubler, F., Cronberg, T., and Westhall, E.

Published
2024
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2. The predictive value of highly malignant EEG patterns after cardiac arrest: evaluation of the ERC-ESICM recommendations

Author

Turella, Sara, Dankiewicz, J., Friberg, H., Jakobsen, J. C., Leithner, C., Levin, H., Lilja, G., Moseby-Knappe, M., Nielsen, N., Rossetti, A. O., Sandroni, Claudio, Zubler, F., Cronberg, T., Westhall, E., Turella S., Sandroni C. (ORCID:0000-0002-8878-2611), Turella, Sara, Dankiewicz, J., Friberg, H., Jakobsen, J. C., Leithner, C., Levin, H., Lilja, G., Moseby-Knappe, M., Nielsen, N., Rossetti, A. O., Sandroni, Claudio, Zubler, F., Cronberg, T., Westhall, E., Turella S., and Sandroni C. (ORCID:0000-0002-8878-2611)

Abstract

Purpose: The 2021 guidelines endorsed by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) recommend using highly malignant electroencephalogram (EEG) patterns (HMEP; suppression or burst-suppression) at > 24 h after cardiac arrest (CA) in combination with at least one other concordant predictor to prognosticate poor neurological outcome. We evaluated the prognostic accuracy of HMEP in a large multicentre cohort and investigated the added value of absent EEG reactivity. Methods: This is a pre-planned prognostic substudy of the Targeted Temperature Management trial 2. The presence of HMEP and background reactivity to external stimuli on EEG recorded > 24 h after CA was prospectively reported. Poor outcome was measured at 6 months and defined as a modified Rankin Scale score of 4–6. Prognostication was multimodal, and withdrawal of life-sustaining therapy (WLST) was not allowed before 96 h after CA. Results: 845 patients at 59 sites were included. Of these, 579 (69%) had poor outcome, including 304 (36%) with WLST due to poor neurological prognosis. EEG was recorded at a median of 71 h (interquartile range [IQR] 52–93) after CA. HMEP at > 24 h from CA had 50% [95% confidence interval [CI] 46–54] sensitivity and 93% [90–96] specificity to predict poor outcome. Specificity was similar (93%) in 541 patients without WLST. When HMEP were unreactive, specificity improved to 97% [94–99] (p = 0.008). Conclusion: The specificity of the ERC-ESICM-recommended EEG patterns for predicting poor outcome after CA exceeds 90% but is lower than in previous studies, suggesting that large-scale implementation may reduce their accuracy. Combining HMEP with an unreactive EEG background significantly improved specificity. As in other prognostication studies, a self-fulfilling prophecy bias may have contributed to observed results.

Published
2024

4. Assessment of physical activity in out-of-hospital cardiac arrest survivors: a sub-study of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial

Author

Heimburg, K, primary, Lilja, G, additional, Blennow Nordstrom, E, additional, Gregersen Ostergaard, L, additional, Grejs, A M, additional, Keeble, T R, additional, Mion, M, additional, Rylander, C, additional, Segerstrom, M, additional, Thomsen, I K, additional, Ullen, S, additional, Unden, J, additional, Wise, M P, additional, Cronberg, T, additional, and Tornberg, A B, additional

Published
2023
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5. Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest

Author

Eastwood, G, Nichol, AD, Hodgson, C, Parke, RL, McGuinness, S, Nielsen, N, Bernard, S, Skrifvars, MB, Stub, D, Taccone, FS, Archer, J, Kutsogiannis, D, Dankiewicz, J, Lilja, G, Cronberg, T, Kirkegaard, H, Capellier, G, Landoni, G, Horn, J, Olasveengen, T, Arabi, Y, Chia, YW, Markota, A, Haenggi, M, Wise, MP, Grejs, AM, Christensen, S, Munk-Andersen, H, Granfeldt, A, Andersen, GO, Qvigstad, E, Flaa, A, Thomas, M, Sweet, K, Bewley, J, Backlund, M, Tiainen, M, Iten, M, Levis, A, Peck, L, Walsham, J, Deane, A, Ghosh, A, Annoni, F, Chen, Y, Knight, D, Lesona, E, Tlayjeh, H, Svensek, F, McGuigan, PJ, Cole, J, Pogson, D, Hilty, MP, During, JP, Bailey, MJ, Paul, E, Ady, B, Ainscough, K, Hunt, A, Monahan, S, Trapani, T, Fahey, C, Bellomo, R, Eastwood, G, Nichol, AD, Hodgson, C, Parke, RL, McGuinness, S, Nielsen, N, Bernard, S, Skrifvars, MB, Stub, D, Taccone, FS, Archer, J, Kutsogiannis, D, Dankiewicz, J, Lilja, G, Cronberg, T, Kirkegaard, H, Capellier, G, Landoni, G, Horn, J, Olasveengen, T, Arabi, Y, Chia, YW, Markota, A, Haenggi, M, Wise, MP, Grejs, AM, Christensen, S, Munk-Andersen, H, Granfeldt, A, Andersen, GO, Qvigstad, E, Flaa, A, Thomas, M, Sweet, K, Bewley, J, Backlund, M, Tiainen, M, Iten, M, Levis, A, Peck, L, Walsham, J, Deane, A, Ghosh, A, Annoni, F, Chen, Y, Knight, D, Lesona, E, Tlayjeh, H, Svensek, F, McGuigan, PJ, Cole, J, Pogson, D, Hilty, MP, During, JP, Bailey, MJ, Paul, E, Ady, B, Ainscough, K, Hunt, A, Monahan, S, Trapani, T, Fahey, C, and Bellomo, R

Abstract

BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

Published
2023

6. Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

Author

Dankiewicz J., Cronberg T., Lilja G., Jakobsen J. C., Levin H., Ullen S., Rylander C., Wise M. P., Oddo M., Cariou A., Belohlavek J., Hovdenes J., Saxena M., Kirkegaard H., Young P. J., Pelosi P., Storm C., Taccone F. S., Joannidis M., Callaway C., Eastwood G. M., Morgan M. P. G., Nordberg P., Erlinge D., Nichol A. D., Chew M. S., Hollenberg J., Thomas M., Bewley J., Sweet K., Grejs A. M., Christensen S., Haenggi M., Levis A., Lundin A., During J., Schmidbauer S., Keeble T. R., Karamasis G. V., Schrag C., Faessler E., Smid O., Otahal M., Maggiorini M., Wendel Garcia P. D., Jaubert P., Cole J. M., Solar M., Borgquist O., Leithner C., Abed-Maillard S., Navarra L., Annborn M., Unden J., Brunetti I., Awad A., McGuigan P., Olsen R. B., Cassina T., Vignon P., Langeland H., Lange T., Friberg H., Nielsen N. Collaborators, Erik Roman Pognuz, Umberto Lucangelo, Giorgio Berlot, Elisabetta Macchini., Dankiewicz, J., Cronberg, T., Lilja, G., Jakobsen, J. C., Levin, H., Ullen, S., Rylander, C., Wise, M. P., Oddo, M., Cariou, A., Belohlavek, J., Hovdenes, J., Saxena, M., Kirkegaard, H., Young, P. J., Pelosi, P., Storm, C., Taccone, F. S., Joannidis, M., Callaway, C., Eastwood, G. M., Morgan, M. P. G., Nordberg, P., Erlinge, D., Nichol, A. D., Chew, M. S., Hollenberg, J., Thomas, M., Bewley, J., Sweet, K., Grejs, A. M., Christensen, S., Haenggi, M., Levis, A., Lundin, A., During, J., Schmidbauer, S., Keeble, T. R., Karamasis, G. V., Schrag, C., Faessler, E., Smid, O., Otahal, M., Maggiorini, M., Wendel Garcia, P. D., Jaubert, P., Cole, J. M., Solar, M., Borgquist, O., Leithner, C., Abed-Maillard, S., Navarra, L., Annborn, M., Unden, J., Brunetti, I., Awad, A., Mcguigan, P., Olsen, R. B., Cassina, T., Vignon, P., Langeland, H., Lange, T., Friberg, H., Collaborators:, Nielsen N., ROMAN-POGNUZ, Erik, Lucangelo, Umberto, Berlot, Giorgio, and Macchini, Elisabetta

Subjects
Male, Fever, Heart disease, medicine.medical_treatment, Coma/etiology, Hypothermia, Kaplan-Meier Estimate, Targeted temperature management, GUIDELINES, Out of hospital cardiac arrest, Body Temperature, law.invention, TARGETED TEMPERATURE MANAGEMENT, Randomized controlled trial, Hypothermia, Induced, law, AMERICAN-HEART-ASSOCIATION, EUROPEAN RESUSCITATION COUNCIL, medicine, Humans, Single-Blind Method, Cardiopulmonary resuscitation, Coma, 610 Medicine & health, Aged, Cardiopulmonary Resuscitation, Female, Middle Aged, Out-of-Hospital Cardiac Arrest, Treatment Outcome, business.industry, Induced, General Medicine, medicine.disease, Out-of-Hospital Cardiac Arrest/complications, Fever/etiology, Clinical research, Hypothermia, Induced/adverse effects, CARDIOPULMONARY-RESUSCITATION, Anesthesia, Cardiopulmonary Resuscitation/methods, medicine.symptom, business, Human
Abstract

Hypothermia or Normothermia after Cardiac ArrestThis trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes.BackgroundTargeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty.MethodsIn an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device.ResultsA total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, PConclusionsIn patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)

Published
2021

11. Prediction of good neurological outcome in comatose survivors of cardiac arrest: a systematic review

Author

Sandroni, C., D'Arrigo, S., Cacciola, S., Hoedemaekers, C.W.E., Westhall, E., Kamps, M.J., Taccone, F.S., Poole, D., Meijer, F.J.A., Antonelli, M., Hirsch, K.G., Soar, J., Nolan, J.P., Cronberg, T., Sandroni, C., D'Arrigo, S., Cacciola, S., Hoedemaekers, C.W.E., Westhall, E., Kamps, M.J., Taccone, F.S., Poole, D., Meijer, F.J.A., Antonelli, M., Hirsch, K.G., Soar, J., Nolan, J.P., and Cronberg, T.

Abstract

Item does not contain fulltext, PURPOSE: To assess the ability of clinical examination, blood biomarkers, electrophysiology or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict good neurological outcome, defined as no, mild, or moderate disability (CPC 1-2 or mRS 0-3) at discharge from intensive care unit or later, in comatose adult survivors from cardiac arrest (CA). METHODS: PubMed, EMBASE, Web of Science and the Cochrane Database of Systematic Reviews were searched. Sensitivity and specificity for good outcome were calculated for each predictor. The risk of bias was assessed using the QUIPS tool. RESULTS: A total of 37 studies were included. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed. A withdrawal or localisation motor response to pain immediately or at 72-96 h after ROSC, normal blood values of neuron-specific enolase (NSE) at 24 h-72 h after ROSC, a short-latency somatosensory evoked potentials (SSEPs) N20 wave amplitude > 4 microV or a continuous background without discharges on electroencephalogram (EEG) within 72 h from ROSC, and absent diffusion restriction in the cortex or deep grey matter on MRI on days 2-7 after ROSC predicted good neurological outcome with more than 80% specificity and a sensitivity above 40% in most studies. Most studies had moderate or high risk of bias. CONCLUSIONS: In comatose cardiac arrest survivors, clinical, biomarker, electrophysiology, and imaging studies identified patients destined to a good neurological outcome with high specificity within the first week after cardiac arrest (CA).

Published
2022

12. Biomarkers of brain injury after cardiac arrest; a statistical analysis plan from the TTM2 trial biobank investigators.

Author

Moseby-Knappe, M, Levin, H, Blennow, K, Ullén, S, Zetterberg, H, Lilja, G, Dankiewicz, J, Jakobsen, JC, Lagebrant, A, Friberg, H, Nichol, A, Ainschough, K, Eastwood, GM, Wise, MP, Thomas, M, Keeble, T, Cariou, A, Leithner, C, Rylander, C, Düring, J, Bělohlávek, J, Grejs, A, Borgquist, O, Undén, J, Simon, M, Rolny, V, Piehler, A, Cronberg, T, Nielsen, N, Moseby-Knappe, M, Levin, H, Blennow, K, Ullén, S, Zetterberg, H, Lilja, G, Dankiewicz, J, Jakobsen, JC, Lagebrant, A, Friberg, H, Nichol, A, Ainschough, K, Eastwood, GM, Wise, MP, Thomas, M, Keeble, T, Cariou, A, Leithner, C, Rylander, C, Düring, J, Bělohlávek, J, Grejs, A, Borgquist, O, Undén, J, Simon, M, Rolny, V, Piehler, A, Cronberg, T, and Nielsen, N

Abstract

BACKGROUND: Several biochemical markers in blood correlate with the magnitude of brain injury and may be used to predict neurological outcome after cardiac arrest. We present a protocol for the evaluation of prognostic accuracy of brain injury markers after cardiac arrest. The aim is to define the best predictive marker and to establish clinically useful cut-off levels for routine implementation. METHODS: Prospective international multicenter trial within the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial in collaboration with Roche Diagnostics International AG. Samples were collected 0, 24, 48, and 72 hours after randomisation (serum) and 0 and 48 hours after randomisation (plasma), and pre-analytically processed at each site before storage in a central biobank. Routine markers neuron-specific enolase (NSE) and S100B, and neurofilament light, total-tau and glial fibrillary acidic protein will be batch analysed using novel Elecsys® electrochemiluminescence immunoassays on a Cobas e601 instrument. RESULTS: Statistical analysis will be reported according to the Standards for Reporting Diagnostic accuracy studies (STARD) and will include comparisons for prediction of good versus poor functional outcome at six months post-arrest, by modified Rankin Scale (0-3 vs. 4-6), using logistic regression models and receiver operating characteristics curves, evaluation of mortality at six months according to biomarker levels and establishment of cut-off values for prediction of poor neurological outcome at 95-100% specificities. CONCLUSIONS: This prospective trial may establish a standard methodology and clinically appropriate cut-off levels for the optimal biomarker of brain injury which predicts poor neurological outcome after cardiac arrest.

Published
2022

13. EEG monitoring after cardiac arrest

Author

Sandroni, Claudio, Cronberg, T., Hofmeijer, J., Sandroni C. (ORCID:0000-0002-8878-2611), Sandroni, Claudio, Cronberg, T., Hofmeijer, J., and Sandroni C. (ORCID:0000-0002-8878-2611)

Abstract

Hypoxic-ischaemic brain injury (HIBI) is the main cause of death and disability in patients who are comatose after return of spontaneous circulation (ROSC) from cardiac arrest. The electroencephalogram (EEG) is a useful tool to assess the severity of HIBI and provide prognostic information. In addition, EEG can be used to diagnose epileptiform activity in patients with suspected seizures and monitor the effectiveness of antiepileptic treatment. The EEG signal is complex and the information from EEG experts may be difficult to interpret for the intensive care unit (ICU) physicians. However, continuous EEG (cEEG), facilitating the assessment of the evolution of brain activity over time, allows instantaneous detection of electrographic seizures. These innovative approaches may facilitate bedside EEG monitoring in the future.

Published
2022

14. ERC-ESICM guidelines on temperature control after cardiac arrest in adults

Author

Sandroni, Claudio, Nolan, J. P., Andersen, L. W., Bottiger, B. W., Cariou, A., Cronberg, T., Friberg, H., Genbrugge, C., Lilja, G., Morley, P. T., Nikolaou, N., Olasveengen, T. M., Skrifvars, M. B., Taccone, F. S., Soar, J., Sandroni C. (ORCID:0000-0002-8878-2611), Sandroni, Claudio, Nolan, J. P., Andersen, L. W., Bottiger, B. W., Cariou, A., Cronberg, T., Friberg, H., Genbrugge, C., Lilja, G., Morley, P. T., Nikolaou, N., Olasveengen, T. M., Skrifvars, M. B., Taccone, F. S., Soar, J., and Sandroni C. (ORCID:0000-0002-8878-2611)

Abstract

The aim of these guidelines is to provide evidence‐based guidance for temperature control in adults who are comatose after resuscitation from either in-hospital or out-of-hospital cardiac arrest, regardless of the underlying cardiac rhythm. These guidelines replace the recommendations on temperature management after cardiac arrest included in the 2021 post-resuscitation care guidelines co-issued by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM). The guideline panel included thirteen international clinical experts who authored the 2021 ERC-ESICM guidelines and two methodologists who participated in the evidence review completed on behalf of the International Liaison Committee on Resuscitation (ILCOR) of whom ERC is a member society. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations. The panel provided suggestions on guideline implementation and identified priorities for future research. The certainty of evidence ranged from moderate to low. In patients who remain comatose after cardiac arrest, we recommend continuous monitoring of core temperature and actively preventing fever (defined as a temperature > 37.7 °C) for at least 72 h. There was insufficient evidence to recommend for or against temperature control at 32–36 °C or early cooling after cardiac arrest. We recommend not actively rewarming comatose patients with mild hypothermia after return of spontaneous circulation (ROSC) to achieve normothermia. We recommend not using prehospital cooling with rapid infusion of large volumes of cold intravenous fluids immediately after ROSC.

Published
2022

15. Survival in patients without acute ST elevation after cardiac arrest and association with early coronary angiography: a post hoc analysis from the TTM trial

Author

Dankiewicz, J., Nielsen, N., Annborn, M., Cronberg, T., Erlinge, D., Gasche, Y., and Hassager, C.

Subjects
Mortality -- Sweden, Angiography -- Analysis, Electrocardiography -- Analysis, Electrocardiogram -- Analysis, Cardiac patients -- Patient outcomes, Cardiac arrest -- Patient outcomes, Health care industry
Abstract

Purpose To investigate whether early coronary angiography (CAG) after out-of-hospital cardiac arrest of a presumed cardiac cause is associated with improved outcomes in patients without acute ST elevation. Methods The target temperature management after out-of-hospital cardiac arrest (TTM) trial showed no difference in all-cause mortality or neurological outcome between an intervention of 33 and 36 °C. In this post hoc analysis, 544 patients where the admission electrocardiogram did not show acute ST elevation were included. Early CAG was defined as being performed on admission or within the first 6 h after arrest. Primary outcome was mortality at the end of trial. A Cox proportional hazard model was created to estimate hazard of death, adjusting for covariates. In addition, a propensity score matched analysis was performed. Results A total of 252 patients (46 %) received early CAG, whereas 292 (54 %) did not. At the end of the trial, 122 of 252 patients who received an early CAG (48 %) and 159 of 292 patients who did not (54 %) had died. The adjusted hazard ratio for death was 1.03 in the group that received an early CAG; 95 % CI 0.80-1.32, p = 0.82. In the propensity score analysis early CAG was not significantly associated with survival. Conclusions In this post hoc observational study of a large randomized trial, early coronary angiography for patients without acute ST elevation after out-of-hospital cardiac arrest of a presumed cardiac cause was not associated with improved survival. A randomized trial is warranted to guide clinical practice., Author(s): J. Dankiewicz [sup.1] [sup.2], N. Nielsen [sup.2], M. Annborn [sup.1] [sup.2], T. Cronberg [sup.2] [sup.3], D. Erlinge [sup.2] [sup.4], Y. Gasche [sup.5], C. Hassager [sup.6], J. Kjaergaard [sup.6], T. [...]

Published
2015
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16. Post-resuscitation care European Resuscitation Council and European Society of Intensive Care Medicine Guidelines 2021

Author

Nolan, JP, Sandroni, C, Bottiger, BW, Cariou, A, Cronberg, T, Friberg, H, Genbrugge, C, Haywood, K, Lilja, G, Moulaert, VRM, Nikolaou, N, Olasveengen, TM, Skrifvars, MB, Taccone, F, Soar, J, Faculteit Medische Wetenschappen/UMCG, HUS Akuten, Diagnostisk-terapeutiska avdelningen, and Clinicum

Subjects
VENOUS THROMBOEMBOLISM PROPHYLAXIS, Haemodynamic management, 33 DEGREES-C, Post-cardiac arrest syndrome, 2015 INTERNATIONAL CONSENSUS, NEURON-SPECIFIC ENOLASE, education, HOSPITAL CARDIAC-ARREST, 3126 Surgery, anesthesiology, intensive care, radiology, CONTROLLED AUTOMATED REPERFUSION, Settore MED/26 - NEUROLOGIA, Ventilatory support, TARGETED TEMPERATURE MANAGEMENT, QUALITY-OF-LIFE, Settore MED/41 - ANESTESIOLOGIA, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Intensive care medicine, MULTIMODAL OUTCOME PREDICTION, MEAN ARTERIAL-PRESSURE
Abstract

The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) have collaborated to produce these post-resuscitation phase guidelines for adults, which are based on the 2020 International Liaison Committee on Resuscitation consensus on cardiopulmonary resuscitation. The topics covered include post-cardiac arrest syndrome, the differential diagnosis of the causes of cardiac arrest, control of oxygenation and ventilation, coronary reperfusion, haemodynamic monitoring and management, control of seizures, temperature control, general intensive care management, prognostication, long-term outcome, rehabilitation and organ donation.

Published
2021

17. Corrigendum to 'European Resuscitation Council Guidelines 2021: Executive summary' [Resuscitation (2021) 1–60] (Resuscitation (2021) 161 (1–60), (S0300957221000551), (10.1016/j.resuscitation.2021.02.003))

Author

Perkins, Gavin D., Gräsner, Jan-Thortsen, Semeraro, Federico, Olasveengen, Theresa, Soar, Jasmeet, Lott, Carsten, Voorde, Patrick, Madar, John, Zideman, David, Mentzelopoulos, Spyridon, Bossaert, Leo, Greif, Robert, Monsieurs, Koen, Svavarsdóttir, Hildigunnur, Nolan, Jerry P., Ainsworth, S., Deakin, C. D., Lippert, F., Sandroni, C., Akin, S., Delchef, J., Lockey, A. S., Sari, F., Alfonzo, A., Dirks, B., Lott, C., Scapigliati, A., Andres, J., Djakow, J., Lulic, I., Schilder, S., Attard Montalto, S., Djarv, T., Maas, M., Schlieber, J., Barelli, A., Druwe, P., Maconochie, I., Schnaubelt, S., Baubin, M., Eldin, G., Madar, J., Semeraro, F., Behringer, W., Ersdal, H., Martinez-Mejias, A., Shammet, S., Bein, B., Friberg, H., Masterson, S., Singletary, E. M., Biarent, D., Genbrugge, C., Mentzelopoulos, S. D., Skåre, C., Bingham, R., Georgiou, M., Meyran, D., Skrifvars, M. B., Blom, M., Goemans, E., Monsieurs, K. G., Smyth, M., Boccuzzi, A., González-Salvado, V., Morley, C., Soar, J., Borra, V., Gradisek, P., Moulaert, V. R. M., Svavarsdóttir, H., Bossaert, L., Gräsner, J. T., Mpotos, N., Szczapa, T., Böttiger, B. W., Greif, R., Nikolaou, N., Taccone, F., Breckwoldt, J., Handley, A. J., Nolan, J. P., Tageldin Mustafa, M., Brissaud, O., Hassager, C., Olasveengen, T. M., Te Pas, A., Burkart, R., Haywood, K., Oliver, E., Karl-Christian Thies, Cariou, A., Heltne, J. K., Paal, P., Tjelmeland, I. B. M., Carli, P., Hendrickx, D., Pellis, T., Trevisanuto, D., Carmona, F., Herlitz, J., Perkins, G. D., Truhlár, A., Cassan, P., Hinkelbein, J., Pflanzl-Knizacek, L., Trummer, G., Castren, M., Hoffmann, F., Pitches, K., Turner, N. M., Christophides, T., Hunyadi Anticevic, S., Poole, K., Urlesberger, B., Cimpoesu, C. D., Johannesdottir, G. B., Raffay, V., Vaahersalo, J., Clarens, C., Khalifa, G., Renier, W., Voorde, P., Conaghan, P., Klaassen, B., Ristagno, G., Grootven, H., Couper, K., Koppl, J., Roehr, C. C., Wilkinson, D., Cronberg, T., Kreimeier, U., Rosell-Ortiz, F., Wnent, J., Buck, E., Kuzovlev, A., Rüdiger, M., Wyllie, J. P., Lucas, N., Lauritsen, T., Safri, A., Yeung, J., Roovere, A., Lilja, G., Sanchez Santos, L., Zideman, D. A., Radiology and Nuclear Medicine, AMS - Rehabilitation & Development, AMS - Sports, Amsterdam Gastroenterology Endocrinology Metabolism, Cardiology, ACS - Heart failure & arrhythmias, and APH - Health Behaviors & Chronic Diseases

Abstract

The authors regret that the list of the ERC 2021 Guidelines Collaborators which were included in Appendix A was incomplete. The complete list of collaborators is provided below: [Table presented] The authors would like to apologise for any inconvenience caused.

Published
2021

19. Prognostication of neurologic outcome in cardiac arrest patients after mild therapeutic hypothermia: a meta-analysis of the current literature

Author

Kamps, M. J. A., Horn, J., Oddo, M., Fugate, J. E., Storm, C., Cronberg, T., and Wijman, C. A.

Subjects
Medical research, Medicine, Experimental, Hypothermia -- Care and treatment -- Patient outcomes -- Prognosis, Medical colleges, Cardiac patients -- Patient outcomes -- Care and treatment -- Prognosis, Persistent vegetative state -- Prognosis -- Patient outcomes -- Care and treatment, Health care industry
Abstract

Purpose To assess the sensitivity and false positive rate (FPR) of neurological examination and somatosensory evoked potentials (SSEPs) to predict poor outcome in adult patients treated with therapeutic hypothermia after cardiopulmonary resuscitation (CPR). Methods MEDLINE and EMBASE were searched for cohort studies describing the association of clinical neurological examination or SSEPs after return of spontaneous circulation with neurological outcome. Poor outcome was defined as severe disability, vegetative state and death. Sensitivity and FPR were determined. Results A total of 1,153 patients from ten studies were included. The FPR of a bilaterally absent cortical N20 response of the SSEP could be calculated from nine studies including 492 patients. The SSEP had an FPR of 0.007 (confidence interval, CI, 0.001-0.047) to predict poor outcome. The Glasgow coma score (GCS) motor response was assessed in 811 patients from nine studies. A GCS motor score of 1-2 at 72 h had a high FPR of 0.21 (CI 0.08-0.43). Corneal reflex and pupillary reactivity at 72 h after the arrest were available in 429 and 566 patients, respectively. Bilaterally absent corneal reflexes had an FPR of 0.02 (CI 0.002-0.13). Bilaterally absent pupillary reflexes had an FPR of 0.004 (CI 0.001-0.03). Conclusions At 72 h after the arrest the motor response to painful stimuli and the corneal reflexes are not a reliable tool for the early prediction of poor outcome in patients treated with hypothermia. The reliability of the pupillary response to light and the SSEP is comparable to that in patients not treated with hypothermia., Author(s): M. J. A. Kamps [sup.1], J. Horn [sup.2], M. Oddo [sup.3], J. E. Fugate [sup.4], C. Storm [sup.5], T. Cronberg [sup.6], C. A. Wijman [sup.7], O. Wu [sup.8], J. [...]

Published
2013
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20. Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

Author

Dankiewicz, J, Cronberg, T, Lilja, G, Jakobsen, JC, Levin, H, Ullen, S, Rylander, C, Wise, MP, Oddo, M, Cariou, A, Belohlavek, J, Hovdenes, J, Saxena, M, Kirkegaard, H, Young, PJ, Pelosi, P, Storm, C, Taccone, FS, Joannidis, M, Callaway, C, Eastwood, GM, Morgan, MPG, Nordberg, P, Erlinge, D, Nichol, AD, Chew, MS, Hollenberg, J, Thomas, M, Bewley, J, Sweet, K, Grejs, AM, Christensen, S, Haenggi, M, Levis, A, Lundin, A, During, J, Schmidbauer, S, Keeble, TR, Karamasis, GV, Schrag, C, Faessler, E, Smid, O, Otahal, M, Maggiorini, M, Wendel Garcia, PD, Jaubert, P, Cole, JM, Solar, M, Borgquist, O, Leithner, C, Abed-Maillard, S, Navarra, L, Annborn, M, Unden, J, Brunetti, I, Awad, A, McGuigan, P, Bjorkholt Olsen, R, Cassina, T, Vignon, P, Langeland, H, Lange, T, Friberg, H, Nielsen, N, Dankiewicz, J, Cronberg, T, Lilja, G, Jakobsen, JC, Levin, H, Ullen, S, Rylander, C, Wise, MP, Oddo, M, Cariou, A, Belohlavek, J, Hovdenes, J, Saxena, M, Kirkegaard, H, Young, PJ, Pelosi, P, Storm, C, Taccone, FS, Joannidis, M, Callaway, C, Eastwood, GM, Morgan, MPG, Nordberg, P, Erlinge, D, Nichol, AD, Chew, MS, Hollenberg, J, Thomas, M, Bewley, J, Sweet, K, Grejs, AM, Christensen, S, Haenggi, M, Levis, A, Lundin, A, During, J, Schmidbauer, S, Keeble, TR, Karamasis, GV, Schrag, C, Faessler, E, Smid, O, Otahal, M, Maggiorini, M, Wendel Garcia, PD, Jaubert, P, Cole, JM, Solar, M, Borgquist, O, Leithner, C, Abed-Maillard, S, Navarra, L, Annborn, M, Unden, J, Brunetti, I, Awad, A, McGuigan, P, Bjorkholt Olsen, R, Cassina, T, Vignon, P, Langeland, H, Lange, T, Friberg, H, and Nielsen, N

Abstract

BACKGROUND: Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. METHODS: In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. RESULTS: A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score ≥4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. CONCLUSIONS: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermi

Published
2021

21. Post-resuscitation care: European Resuscitation Council and European Society of Intensive Care Medicine Guidelines 2021

Author

Nolan, J. P., Sandroni, Claudio, Bottiger, B. W., Cariou, A., Cronberg, T., Friberg, H., Genbrugge, C., Haywood, K., Lilja, G., Moulaert, V. R. M., Nikolaou, N., Olasveengen, T. M., Skrifvars, M. B., Taccone, F., Soar, J., Sandroni C. (ORCID:0000-0002-8878-2611), Nolan, J. P., Sandroni, Claudio, Bottiger, B. W., Cariou, A., Cronberg, T., Friberg, H., Genbrugge, C., Haywood, K., Lilja, G., Moulaert, V. R. M., Nikolaou, N., Olasveengen, T. M., Skrifvars, M. B., Taccone, F., Soar, J., and Sandroni C. (ORCID:0000-0002-8878-2611)

Abstract

The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) have collaborated to produce these post-resuscitation phase guidelines for adults, which are based on the 2020 International Liaison Committee on Resuscitation consensus on cardiopulmonary resuscitation. The topics covered include post-cardiac arrest syndrome, the differential diagnosis of the causes of cardiac arrest, control of oxygenation and ventilation, coronary reperfusion, haemodynamic monitoring and management, control of seizures, temperature control, general intensive care management, prognostication, long-term outcome, rehabilitation and organ donation.

Published
2021

22. Brain injury after cardiac arrest: pathophysiology, treatment, and prognosis

Author

Sandroni, Claudio, Cronberg, T., Sekhon, M., Sandroni C. (ORCID:0000-0002-8878-2611), Sandroni, Claudio, Cronberg, T., Sekhon, M., and Sandroni C. (ORCID:0000-0002-8878-2611)

Abstract

Post-cardiac arrest brain injury (PCABI) is caused by initial ischaemia and subsequent reperfusion of the brain following resuscitation. In those who are admitted to intensive care unit after cardiac arrest, PCABI manifests as coma, and is the main cause of mortality and long-term disability. This review describes the mechanisms of PCABI, its treatment options, its outcomes, and the suggested strategies for outcome prediction.

Published
2021

23. European Resuscitation Council and European Society of Intensive Care Medicine guidelines 2021: post-resuscitation care

Author

Nolan, J. P., Sandroni, Claudio, Bottiger, B. W., Cariou, A., Cronberg, T., Friberg, H., Genbrugge, C., Haywood, K., Lilja, G., Moulaert, V. R. M., Nikolaou, N., Olasveengen, T. M., Skrifvars, M. B., Taccone, F., Soar, J., Sandroni C. (ORCID:0000-0002-8878-2611), Nolan, J. P., Sandroni, Claudio, Bottiger, B. W., Cariou, A., Cronberg, T., Friberg, H., Genbrugge, C., Haywood, K., Lilja, G., Moulaert, V. R. M., Nikolaou, N., Olasveengen, T. M., Skrifvars, M. B., Taccone, F., Soar, J., and Sandroni C. (ORCID:0000-0002-8878-2611)

Abstract

The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) have collaborated to produce these post-resuscitation care guidelines for adults, which are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. The topics covered include the post-cardiac arrest syndrome, diagnosis of cause of cardiac arrest, control of oxygenation and ventilation, coronary reperfusion, haemodynamic monitoring and management, control of seizures, temperature control, general intensive care management, prognostication, long-term outcome, rehabilitation and organ donation.

Published
2021

25. European Resuscitation Council Guidelines 2021: Executive summary

Author

Perkins, Gavin D., primary, Gräsner, Jan-Thorsen, additional, Semeraro, Federico, additional, Olasveengen, Theresa, additional, Soar, Jasmeet, additional, Lott, Carsten, additional, Van de Voorde, Patrick, additional, Madar, John, additional, Zideman, David, additional, Mentzelopoulos, Spyridon, additional, Bossaert, Leo, additional, Greif, Robert, additional, Monsieurs, Koen, additional, Svavarsdóttir, Hildigunnur, additional, Nolan, Jerry P., additional, Ainsworth, S., additional, Akin, S., additional, Alfonzo, A., additional, Andres, J., additional, Attard Montalto, S., additional, Barelli, A., additional, Baubin, M., additional, Behringer, W., additional, Bein, B., additional, Biarent, D., additional, Bingham, R., additional, Blom, M., additional, Boccuzzi, A., additional, Borra, V., additional, Bossaert, L., additional, Böttiger, B.W., additional, Breckwoldt, J., additional, Brissaud, O., additional, Burkart, R., additional, Cariou, A., additional, Carli, P., additional, Carmona, F., additional, Cassan, P., additional, Castren, M., additional, Christophides, T., additional, Cimpoesu, C.D., additional, Clarens, C., additional, Conaghan, P., additional, Couper, K., additional, Cronberg, T., additional, De Buck, E., additional, de Lucas, N., additional, De Roovere, A., additional, Deakin, C.D., additional, Delchef, J., additional, Dirks, B., additional, Djakow, J., additional, Djarv, T., additional, Druwe, P., additional, Eldin, G., additional, Ersdal, H., additional, Friberg, H., additional, Genbrugge, C., additional, Georgiou, M., additional, Goemans, E., additional, Gonzalez-Salvado, V., additional, Gradisek, P., additional, Graesner, J.T., additional, Greif, R., additional, Handley, A.J., additional, Hassager, C., additional, Haywood, K., additional, Heltne, J.K., additional, Hendrickx, D., additional, Herlitz, J., additional, Hinkelbein, J., additional, Hoffmann, F., additional, Hunyadi Anticevic, S., additional, Johannesdottir, G.B., additional, Khalifa, G., additional, Klaassen, B., additional, Koppl, J., additional, Kreimeier, U., additional, Kuzovlev, A., additional, Lauritsen, T., additional, Lilja, G., additional, Lippert, F., additional, Lockey, A., additional, Lott, C., additional, Lulic, I., additional, Maas, M., additional, Maconochie, I., additional, Madar, J., additional, Martinez-Mejias, A., additional, Masterson, S., additional, Mentzelopoulos, S.D., additional, Meyran, D., additional, Monsieurs, K.G., additional, Morley, C., additional, Moulaert, V.R.M., additional, Mpotos, N., additional, Nikolaou, N., additional, Nolan, J.P., additional, Olasveengen, T.M., additional, Oliver, E., additional, Paal, P., additional, Pellis, T., additional, Perkins, G.D., additional, Pflanzl-Knizacek, L., additional, Pitches, K., additional, Poole, K., additional, Raffay, V., additional, Renier, W., additional, Ristagno, G., additional, Roehr, C.C., additional, Rosell-Ortiz, F., additional, Rudiger, M., additional, Safri, A., additional, Sanchez Santos, L., additional, Sandroni, C., additional, Sari, F., additional, Scapigliati, A., additional, Schilder, S., additional, Schlieber, J., additional, Schnaubelt, S., additional, Semeraro, F., additional, Shammet, S., additional, Singletary, E.M., additional, Skare, C., additional, Skrifvars, M.B., additional, Smyth, M., additional, Soar, J., additional, Svavarsdottir, H., additional, Szczapa, T., additional, Taccone, F., additional, Tageldin Mustafa, M., additional, Te Pas, A., additional, Thies, K.C., additional, Tjelmeland, I.B.M., additional, Trevisanuto, D., additional, Truhlar, A., additional, Trummer, G., additional, Turner, N.M., additional, Urlesberger, B., additional, Vaahersalo, J., additional, Van de Voorde, P., additional, Van Grootven, H., additional, Wilkinson, D., additional, Wnent, J., additional, Wyllie, J.P., additional, Yeung, J., additional, and Zideman, D.A., additional

Published
2021
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26. Prediction of poor neurological outcome in comatose survivors of cardiac arrest: a systematic review

Author

Sandroni, C., D'Arrigo, S., Cacciola, S., Hoedemaekers, C.W.E., Kamps, M.J., Oddo, M., Taccone, F.S., Rocco, A. Di, Meijer, F.J.A., Westhall, E., Antonelli, M., Soar, J., Nolan, J.P., Cronberg, T., Sandroni, C., D'Arrigo, S., Cacciola, S., Hoedemaekers, C.W.E., Kamps, M.J., Oddo, M., Taccone, F.S., Rocco, A. Di, Meijer, F.J.A., Westhall, E., Antonelli, M., Soar, J., Nolan, J.P., and Cronberg, T.

Abstract

Contains fulltext : 229478.pdf (Publisher’s version ) (Open Access), PURPOSE: To assess the ability of clinical examination, blood biomarkers, electrophysiology, or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict poor neurological outcome, defined as death, vegetative state, or severe disability (CPC 3-5) at hospital discharge/1 month or later, in comatose adult survivors from cardiac arrest (CA). METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews (January 2013-April 2020) were searched. Sensitivity and false-positive rate (FPR) for each predictor were calculated. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed. RESULTS: Ninety-four studies (30,200 patients) were included. Bilaterally absent pupillary or corneal reflexes after day 4 from ROSC, high blood values of neuron-specific enolase from 24 h after ROSC, absent N20 waves of short-latency somatosensory-evoked potentials (SSEPs) or unequivocal seizures on electroencephalogram (EEG) from the day of ROSC, EEG background suppression or burst-suppression from 24 h after ROSC, diffuse cerebral oedema on brain CT from 2 h after ROSC, or reduced diffusion on brain MRI at 2-5 days after ROSC had 0% FPR for poor outcome in most studies. Risk of bias assessed using the QUIPS tool was high for all predictors. CONCLUSION: In comatose resuscitated patients, clinical, biochemical, neurophysiological, and radiological tests have a potential to predict poor neurological outcome with no false-positive predictions within the first week after CA. Guidelines should consider the methodological concerns and limited sensitivity for individual modalities. (PROSPERO CRD42019141169).

Published
2020

27. Adult Advanced Life Support 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations

Author

Soar, J, Berg, KM, Andersen, LW, Bottiger, BW, Cacciola, S, Callaway, CW, Couper, K, Cronberg, T, D'Arrigo, S, Deakin, CD, Donnino, MW, Drennan, IR, Granfeldt, A, Hoedemaekers, CWE, Holmberg, MJ, Hsu, CH, Kamps, M, Musiol, S, Nation, KJ, Neumar, RW, Nicholson, T, O'Neil, BJ, Otto, Q, de Paiva, EF, Parr, MJA, Reynolds, JC, Sandroni, C, Scholefield, BR, Skrifvars, MB, Wang, T-L, Wetsch, WA, Yeung, J, Morley, PT, Morrison, LJ, Welsford, M, Hazinski, MF, Nolan, JP, Soar, J, Berg, KM, Andersen, LW, Bottiger, BW, Cacciola, S, Callaway, CW, Couper, K, Cronberg, T, D'Arrigo, S, Deakin, CD, Donnino, MW, Drennan, IR, Granfeldt, A, Hoedemaekers, CWE, Holmberg, MJ, Hsu, CH, Kamps, M, Musiol, S, Nation, KJ, Neumar, RW, Nicholson, T, O'Neil, BJ, Otto, Q, de Paiva, EF, Parr, MJA, Reynolds, JC, Sandroni, C, Scholefield, BR, Skrifvars, MB, Wang, T-L, Wetsch, WA, Yeung, J, Morley, PT, Morrison, LJ, Welsford, M, Hazinski, MF, and Nolan, JP

Abstract

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations for advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.

Published
2020

28. Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: a statistical analysis plan.

Author

Jakobsen, JC, Dankiewicz, J, Lange, T, Cronberg, T, Lilja, G, Levin, H, Bělohlávek, J, Callaway, C, Cariou, A, Erlinge, D, Hovdenes, J, Joannidis, M, Nordberg, P, Oddo, M, Pelosi, P, Kirkegaard, H, Eastwood, G, Rylander, C, Saxena, M, Storm, C, Taccone, FS, Wise, MP, Morgan, MPG, Young, P, Nichol, A, Friberg, H, Ullén, S, Nielsen, N, Jakobsen, JC, Dankiewicz, J, Lange, T, Cronberg, T, Lilja, G, Levin, H, Bělohlávek, J, Callaway, C, Cariou, A, Erlinge, D, Hovdenes, J, Joannidis, M, Nordberg, P, Oddo, M, Pelosi, P, Kirkegaard, H, Eastwood, G, Rylander, C, Saxena, M, Storm, C, Taccone, FS, Wise, MP, Morgan, MPG, Young, P, Nichol, A, Friberg, H, Ullén, S, and Nielsen, N

Abstract

BACKGROUND: To date, targeted temperature management (TTM) is the only neuroprotective intervention after resuscitation from cardiac arrest that is recommended by guidelines. The evidence on the effects of TTM is unclear. METHODS/DESIGN: The Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) trial is an international, multicentre, parallel group, investigator-initiated, randomised, superiority trial in which TTM with a target temperature of 33 °C after cardiac arrest will be compared with a strategy to maintain normothermia and active treatment of fever (≥ 37.8 °C). Prognosticators, outcome assessors, the steering group, the trial coordinating team, and trial statisticians will be blinded to treatment allocation. The primary outcome will be all-cause mortality at 180 days after randomisation. We estimate a 55% mortality in the targeted normothermia group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The secondary neurological outcome will be poor functional outcome (modified Rankin scale 4-6) at 180 days after cardiac arrest. In this paper, a detailed statistical analysis plan is presented, including a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Final analyses will be conducted independently by two qualified statisticians following the present plan. DISCUSSION: This SAP, which was prepared before completion of enrolment, should increase the validity of the TTM trial by mitigation of analysis-bias.

Published
2020

29. Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

Author

Berg, K. M., Soar, J., Andersen, L. W., Bottiger, B. W., Cacciola, S., Callaway, C. W., Couper, K., Cronberg, T., D'Arrigo, S., Deakin, C. D., Donnino, M. W., Drennan, I. R., Granfeldt, A., Hoedemaekers, C. W. E., Holmberg, M. J., Hsu, C. H., Kamps, M., Musiol, S., Nation, K. J., Neumar, R. W., Nicholson, T., O'Neil, B. J., Otto, Q., de Paiva, E. F., Parr, M. J. A., Reynolds, J. C., Sandroni, C., Scholefield, B. R., Skrifvars, M. B., Wang, T. -L., Wetsch, W. A., Yeung, J., Morley, P. T., Morrison, L. J., Welsford, M., Hazinski, M. F., Nolan, J. P., Cacciola S., D'Arrigo S. (ORCID:0000-0001-6740-3195), Sandroni C. (ORCID:0000-0002-8878-2611), Berg, K. M., Soar, J., Andersen, L. W., Bottiger, B. W., Cacciola, S., Callaway, C. W., Couper, K., Cronberg, T., D'Arrigo, S., Deakin, C. D., Donnino, M. W., Drennan, I. R., Granfeldt, A., Hoedemaekers, C. W. E., Holmberg, M. J., Hsu, C. H., Kamps, M., Musiol, S., Nation, K. J., Neumar, R. W., Nicholson, T., O'Neil, B. J., Otto, Q., de Paiva, E. F., Parr, M. J. A., Reynolds, J. C., Sandroni, C., Scholefield, B. R., Skrifvars, M. B., Wang, T. -L., Wetsch, W. A., Yeung, J., Morley, P. T., Morrison, L. J., Welsford, M., Hazinski, M. F., Nolan, J. P., Cacciola S., D'Arrigo S. (ORCID:0000-0001-6740-3195), and Sandroni C. (ORCID:0000-0002-8878-2611)

Abstract

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations for advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.

Published
2020

41. Lactate, lactate clearance and outcome after cardiac arrest:A post-hoc analysis of the TTM-Trial

Author

Düring, J., Dankiewicz, J., Cronberg, T., Hassager, C., Hovdenes, J., Kjaergaard, J., Kuiper, M., Nielsen, N., Pellis, T., Stammet, P., Vulto, J., Wanscher, M., Wise, M., Åneman, A., Friberg, H., Düring, J., Dankiewicz, J., Cronberg, T., Hassager, C., Hovdenes, J., Kjaergaard, J., Kuiper, M., Nielsen, N., Pellis, T., Stammet, P., Vulto, J., Wanscher, M., Wise, M., Åneman, A., and Friberg, H.

Published
2018

42. Lactate, lactate clearance and outcome after cardiac arrest: A post‐hoc analysis of the TTM ‐Trial

Author

Düring, J., primary, Dankiewicz, J., additional, Cronberg, T., additional, Hassager, C., additional, Hovdenes, J., additional, Kjaergaard, J., additional, Kuiper, M., additional, Nielsen, N., additional, Pellis, T., additional, Stammet, P., additional, Vulto, J., additional, Wanscher, M., additional, Wise, M., additional, Åneman, A., additional, and Friberg, H., additional

Published
2018
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43. Single versus serial measurements of neuron-specific enolase and prediction of poor neurological outcome in persistently unconscious patients after out-of-hospital cardiac arrest - A TTM-trial substudy

Author

Wiberg, S, Hassager, C, Stammet, P, Winther-Jensen, M, Thomsen, JH, Erlinge, D, Wanscher, M, Nielsen, N, Pellis, T, Åneman, A, Friberg, H, Hovdenes, J, Horn, J, Wetterslev, J, Bro-Jeppesen, J, Wise, MP, Kuiper, M, Cronberg, T, Gasche, Y, Devaux, Y, Kjaergaard, J, Wiberg, S, Hassager, C, Stammet, P, Winther-Jensen, M, Thomsen, JH, Erlinge, D, Wanscher, M, Nielsen, N, Pellis, T, Åneman, A, Friberg, H, Hovdenes, J, Horn, J, Wetterslev, J, Bro-Jeppesen, J, Wise, MP, Kuiper, M, Cronberg, T, Gasche, Y, Devaux, Y, and Kjaergaard, J

Abstract

© 2017 Wiberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Prediction of neurological outcome is a crucial part of post cardiac arrest care and prediction in patients remaining unconscious and/or sedated after rewarming from targeted temperature management (TTM) remains difficult. Current guidelines suggest the use of serial measurements of the biomarker neuron-specific enolase (NSE) in combination with other predictors of outcome in patients admitted after out-of-hospital cardiac arrest (OHCA). This study sought to investigate the ability of NSE to predict poor outcome in patients remaining unconscious at day three after OHCA. In addition, this study sought to investigate if serial NSE measurements add incremental prognostic information compared to a single NSE measurement at 48 hours in this population. Methods: This study is a post-hoc sub-study of the TTM trial, randomizing OHCA patients to a course of TTM at either 33°C or 36°C. Patients were included from sites participating in the TTMPLOS trial biobank sub study. NSE was measured at 24, 48 and 72 hours after ROSC and followup was concluded after 180 days. The primary end point was poor neurological function or death defined by a cerebral performance category score (CPC-score) of 3 to 5. Results: A total of 685 (73%) patients participated in the study. At day three after OHCA 63 (9%) patients had died and 473 (69%) patients were not awake. In these patients, a single NSE measurement at 48 hours predicted poor outcome with an area under the receiver operating characteristics curve (AUC) of 0.83. A combination of all three NSE measurements yielded the highest discovered AUC (0.88, p = .0002). Easily applicable combinations of serial NSE measurements did not significantly improve prediction over a single me

Published
2017

46. Protocol for meta-analysis of temperature reduction in animal models of cardiac arrest

Author

Olai H, Thornéus G, Watson H, Malcolm Robert Macleod, Friberg H, Rhodes J, Nielsen N, Cronberg T, and Deierborg T

Subjects
Methods Articles, animals, meta‐analysis, Methods Article, cardiac arrest, hypothermia, global ischaemia, temperature management
Abstract

Targeted temperature management (TTM) of 32–34 °C has been the standard treatment for out‐of‐hospital cardiac arrest since clinical trials in 2002 showed benefits to survival and neurological outcome. Recently, this treatment has been challenged by another clinical trial showing no difference in outcome between TTM of 33 °C and 36 °C. This protocol describes the methodology for a meta‐analysis detailing temperature‐reducing interventions to treat global ischaemia in animal models. By combining relevant data sets in the literature, we will explore the experimental evidence for TTM. Our aims are to explain possible translational gaps and provide methodological considerations for future experimental research and clinical trials.

Published
2016

47. Postreanimationsbehandlung

Author

Nolan, J.P., primary, Soar, J., additional, Cariou, A., additional, Cronberg, T., additional, Moulaert, V.R.M., additional, Deakin, C., additional, Böttiger, B.W., additional, Friberg, H., additional, Sunde, K., additional, and Sandroni, C., additional

Published
2017
Full Text
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48. 37th International Symposium on Intensive Care and Emergency Medicine (part 2 of 3)

Author

Rob, D., primary, Špunda, R., additional, Lindner, J., additional, Šmalcová, J., additional, Šmíd, O., additional, Kovárník, T., additional, Linhart, A., additional, Bìlohlávek, J., additional, Marinoni, M. M., additional, Cianchi, G., additional, Trapani, S., additional, Migliaccio, M. L., additional, Gucci, L., additional, Bonizzoli, M., additional, Cramaro, A., additional, Cozzolino, M., additional, Valente, S., additional, Peris, A., additional, Grins, E., additional, Kort, E., additional, Weiland, M., additional, Shresta, N. Manandhar, additional, Davidson, P., additional, Algotsson, L., additional, Fitch, S., additional, Marco, G., additional, Sturgill, J., additional, Lee, S., additional, Dickinson, M., additional, Boeve, T., additional, Khaghani, A., additional, Wilton, P., additional, Jovinge, S., additional, Ahmad, A. N., additional, Loveridge, R., additional, Vlachos, S., additional, Patel, S., additional, Gelandt, E., additional, Morgan, L., additional, Butt, S., additional, Whitehorne, M., additional, Kakar, V., additional, Park, C., additional, Hayes, M., additional, Willars, C., additional, Hurst, T., additional, Best, T., additional, Vercueil, A., additional, Auzinger, G., additional, Adibelli, B., additional, Akovali, N., additional, Torgay, A., additional, Zeyneloglu, P., additional, Pirat, A., additional, Kayhan, Z., additional, Schmidbauer, S. S., additional, Herlitz, J., additional, Karlsson, T., additional, Friberg, H., additional, Knafelj, R., additional, Radsel, P., additional, Duprez, F., additional, Bonus, T., additional, Cuvelier, G., additional, Mashayekhi, S., additional, Maka, M., additional, Ollieuz, S., additional, Reychler, G., additional, Mosaddegh, R., additional, Abbasi, S., additional, Talaee, S., additional, Zotzmann, V. Z., additional, Staudacher, D. S., additional, Wengenmayer, T. W., additional, Dürschmied, D. D., additional, Bode, C. B., additional, Nelskylä, A., additional, Nurmi, J., additional, Jousi, M., additional, Schramko, A., additional, Mervaala, E., additional, Ristagno, G., additional, Skrifvars, M., additional, Ozsoy, G., additional, Kendirli, T., additional, Azapagasi, E., additional, Perk, O., additional, Gadirova, U., additional, Ozcinar, E., additional, Cakici, M., additional, Baran, C., additional, Durdu, S., additional, Uysalel, A., additional, Dogan, M., additional, Ramoglu, M., additional, Ucar, T., additional, Tutar, E., additional, Atalay, S., additional, Akar, R., additional, Kamps, M., additional, Leeuwerink, G., additional, Hofmeijer, J., additional, Hoiting, O., additional, Van der Hoeven, J., additional, Hoedemaekers, C., additional, Konkayev, A., additional, Kuklin, V., additional, Kondratyev, T., additional, Konkayeva, M., additional, Akhatov, N., additional, Sovershaev, M., additional, Tveita, T., additional, Dahl, V., additional, Wihersaari, L., additional, Skrifvars, M. B., additional, Bendel, S., additional, Kaukonen, K. M., additional, Vaahersalo, J., additional, Romppanen, J., additional, Pettilä, V., additional, Reinikainen, M., additional, Lybeck, A., additional, Cronberg, T., additional, Nielsen, N., additional, Rauber, M., additional, Steblovnik, K., additional, Jazbec, A., additional, Noc, M., additional, Kalasbail, P., additional, Garrett, F., additional, Kulstad, E., additional, Bergström, D. J., additional, Olsson, H. R., additional, Schmidbauer, S., additional, Mandel, I., additional, Mikheev, S., additional, Podoxenov, Y., additional, Suhodolo, I., additional, Podoxenov, A., additional, Svirko, J., additional, Sementsov, A., additional, Maslov, L., additional, Shipulin, V., additional, Vammen, L. V., additional, Rahbek, S. R., additional, Secher, N. S., additional, Povlsen, J. P., additional, Jessen, N. J., additional, Løfgren, B. L., additional, Granfeldt, A. G., additional, Grossestreuer, A., additional, Perman, S., additional, Patel, P., additional, Ganley, S., additional, Portmann, J., additional, Cocchi, M., additional, Donnino, M., additional, Nassar, Y., additional, Fathy, S., additional, Gaber, A., additional, Mokhtar, S., additional, Chia, Y. C., additional, Lewis-Cuthbertson, R., additional, Mustafa, K., additional, Sabra, A., additional, Evans, A., additional, Bennett, P., additional, Eertmans, W., additional, Genbrugge, C., additional, Boer, W., additional, Dens, J., additional, De Deyne, C., additional, Jans, F., additional, Skorko, A., additional, Thomas, M., additional, Casadio, M., additional, Coppo, A., additional, Vargiolu, A., additional, Villa, J., additional, Rota, M., additional, Avalli, L., additional, Citerio, G., additional, Moon, J. B., additional, Cho, J. H., additional, Park, C. W., additional, Ohk, T. G., additional, Shin, M. C., additional, Won, M. H., additional, Papamichalis, P., additional, Zisopoulou, V., additional, Dardiotis, E., additional, Karagiannis, S., additional, Papadopoulos, D., additional, Zafeiridis, T., additional, Babalis, D., additional, Skoura, A., additional, Staikos, I., additional, Komnos, A., additional, Passos, S. Silva, additional, Maeda, F., additional, Souza, L. Silva, additional, Filho, A. Amato, additional, Granjeia, T. Araújo Guerra, additional, Schweller, M., additional, Franci, D., additional, De Carvalho Filho, M., additional, Santos, T. Martins, additional, De Azevedo, P., additional, Wall, R., additional, Welters, I., additional, Tansuwannarat, P., additional, Sanguanwit, P., additional, Langer, T., additional, Carbonara, M., additional, Caccioppola, A., additional, Fusarini, C. Ferraris, additional, Carlesso, E., additional, Paradiso, E., additional, Battistini, M., additional, Cattaneo, E., additional, Zadek, F., additional, Maiavacca, R., additional, Stocchetti, N., additional, Pesenti, A., additional, Ramos, A., additional, Acharta, F., additional, Toledo, J., additional, Perezlindo, M., additional, Lovesio, L., additional, Dogliotti, A., additional, Lovesio, C., additional, Schroten, N., additional, Van der Veen, B., additional, De Vries, M. C., additional, Veenstra, J., additional, Abulhasan, Y. B., additional, Rachel, S., additional, Châtillon-Angle, M., additional, Alabdulraheem, N., additional, Schiller, I., additional, Dendukuri, N., additional, Angle, M., additional, Frenette, C., additional, Lahiri, S., additional, Schlick, K., additional, Mayer, S. A., additional, Lyden, P., additional, Akatsuka, M., additional, Arakawa, J., additional, Yamakage, M., additional, Rubio, J., additional, Mateo-Sidron, J. A. Rubio, additional, Sierra, R., additional, Celaya, M., additional, Benitez, L., additional, Alvarez-Ossorio, S., additional, Fernandez, A., additional, Gonzalez, O., additional, Engquist, H., additional, Rostami, E., additional, Enblad, P., additional, Canullo, L., additional, Nallino, J., additional, Perreault, M., additional, Talic, J., additional, Frenette, A. J., additional, Burry, L., additional, Bernard, F., additional, Williamson, D. R., additional, Adukauskiene, D., additional, Cyziute, J., additional, Adukauskaite, A., additional, Malciene, L., additional, Luca, L., additional, Rogobete, A., additional, Bedreag, O., additional, Papurica, M., additional, Sarandan, M., additional, Cradigati, C., additional, Popovici, S., additional, Vernic, C., additional, Sandesc, D., additional, Avakov, V., additional, Shakhova, I., additional, Trimmel, H., additional, Majdan, M., additional, Herzer, G. H., additional, Sokoloff, C. S., additional, Albert, M., additional, Williamson, D., additional, Odier, C., additional, Giguère, J., additional, Charbonney, E., additional, Husti, Z., additional, Kaptás, T., additional, Fülep, Z., additional, Gaál, Z., additional, Tusa, M., additional, Donnelly, J., additional, Aries, M., additional, Czosnyka, M., additional, Robba, C., additional, Liu, M., additional, Ercole, A., additional, Menon, D., additional, Hutchinson, P., additional, Smielewski, P., additional, López, R., additional, Graf, J., additional, Montes, J. M., additional, Kenawi, M., additional, Kandil, A., additional, Husein, K., additional, Samir, A., additional, Heijneman, J., additional, Huijben, J., additional, Abid-Ali, F., additional, Stolk, M., additional, Van Bommel, J., additional, Lingsma, H., additional, Van der Jagt, M., additional, Cihlar, R. C., additional, Mancino, G., additional, Bertini, P., additional, Forfori, F., additional, Guarracino, F., additional, Pavelescu, D., additional, Grintescu, I., additional, Mirea, L., additional, Alamri, S., additional, Tharwat, M., additional, Kono, N., additional, Okamoto, H., additional, Uchino, H., additional, Ikegami, T., additional, Fukuoka, T., additional, Simoes, M., additional, Trigo, E., additional, Coutinho, P., additional, Pimentel, J., additional, Franci, A., additional, Basagni, D., additional, Boddi, M., additional, Anichini, V., additional, Cecchi, A., additional, Markopoulou, D., additional, Venetsanou, K., additional, Papanikolaou, I., additional, Barkouri, T., additional, Chroni, D., additional, Alamanos, I., additional, Cingolani, E., additional, Bocci, M. G., additional, Pisapia, L., additional, Tersali, A., additional, Cutuli, S. L., additional, Fiore, V., additional, Palma, A., additional, Nardi, G., additional, Antonelli, M., additional, Coke, R., additional, Kwong, A., additional, Dwivedi, D. J., additional, Xu, M., additional, McDonald, E., additional, Marshall, J. C., additional, Fox-Robichaud, A. E., additional, Liaw, P. C., additional, Kuchynska, I., additional, Malysh, I. R., additional, Zgrzheblovska, L. V., additional, Mestdagh, L., additional, Verhoeven, E. F., additional, Hubloue, I., additional, Ruel-laliberte, J., additional, Zarychanski, R., additional, Lauzier, F., additional, Bonaventure, P. Lessard, additional, Green, R., additional, Griesdale, D., additional, Fowler, R., additional, Kramer, A., additional, Zygun, D., additional, Walsh, T., additional, Stanworth, S., additional, Léger, C., additional, Turgeon, A. F., additional, Baron, D. M., additional, Baron-Stefaniak, J., additional, Leitner, G. C., additional, Ullrich, R., additional, Tarabrin, O., additional, Mazurenko, A., additional, Potapchuk, Y., additional, Sazhyn, D., additional, Tarabrin, P., additional, Pérez, A. González, additional, Silva, J., additional, Artemenko, V., additional, Bugaev, A., additional, Tokar, I., additional, Konashevskaya, S., additional, Kolesnikova, I. M., additional, Roitman, E. V., additional, Kiss, T. Rengeiné, additional, Máthé, Z., additional, Piros, L., additional, Dinya, E., additional, Tihanyi, E., additional, Smudla, A., additional, Fazakas, J., additional, Ubbink, R., additional, Boekhorst te, P., additional, Mik, E., additional, Caneva, L., additional, Ticozzelli, G., additional, Pirrelli, S., additional, Passador, D., additional, Riccardi, F., additional, Ferrari, F., additional, Roldi, E. M., additional, Di Matteo, M., additional, Bianchi, I., additional, Iotti, G. A., additional, Zurauskaite, G., additional, Voegeli, A., additional, Meier, M., additional, Koch, D., additional, Haubitz, S., additional, Kutz, A., additional, Bargetzi, M., additional, Mueller, B., additional, Schuetz, P., additional, Von Meijenfeldt, G., additional, Van der Laan, M., additional, Zeebregts, C., additional, Christopher, K. B., additional, Vernikos, P., additional, Melissopoulou, T., additional, Kanellopoulou, G., additional, Panoutsopoulou, M., additional, Xanthis, D., additional, Kolovou, K., additional, Kypraiou, T., additional, Floros, J., additional, Broady, H., additional, Pritchett, C., additional, Marshman, M., additional, Jannaway, N., additional, Ralph, C., additional, Lehane, C. L., additional, Keyl, C. K., additional, Zimmer, E. Z., additional, Trenk, D. T., additional, Ducloy-Bouthors, A. S., additional, Jonard, M. J., additional, Fourrier, F., additional, Piza, F., additional, Correa, T., additional, Marra, A., additional, Guerra, J., additional, Rodrigues, R., additional, Vilarinho, A., additional, Aranda, V., additional, Shiramizo, S., additional, Lima, M. R., additional, Kallas, E., additional, Cavalcanti, A. B., additional, Donoso, M., additional, Vargas, P., additional, McCartney, J., additional, Ramsay, S., additional, McDowall, K., additional, Novitzky-Basso, I., additional, Wright, C., additional, Medic, M Grgic, additional, Bielen, L, additional, Radonic, V, additional, Zlopasa, O, additional, Vrdoljak, N Gubarev, additional, Gasparovic, V, additional, Radonic, R, additional, Narváez, G., additional, Cabestrero, D., additional, Rey, L., additional, Aroca, M., additional, Gallego, S., additional, Higuera, J., additional, De Pablo, R., additional, González, L. Rey, additional, Chávez, G. Narváez, additional, Lucas, J. Higuera, additional, Alonso, D. Cabestrero, additional, Ruiz, M. Aroca, additional, Valarezo, L. Jaramillo, additional, De Pablo Sánchez, R., additional, Real, A. Quinza, additional, Wigmore, T. W., additional, Bendavid, I., additional, Cohen, J., additional, Avisar, I., additional, Serov, I., additional, Kagan, I., additional, Singer, P., additional, Hanison, J, additional, Mirza, U, additional, Conway, D, additional, Takasu, A., additional, Tanaka, H., additional, Otani, N., additional, Ohde, S., additional, Ishimatsu, S., additional, Coffey, F, additional, Dissmann, P, additional, Mirza, K, additional, Lomax, M, additional, Dissmann, P., additional, Coffey, F., additional, Mirza, K., additional, Lomax, M., additional, Miner, JR, additional, Leto, R, additional, Markota, AM, additional, Gradišek, PG, additional, Aleksejev, VA, additional, Sinkovič, AS, additional, Romagnoli, S., additional, Chelazzi, C., additional, Zagli, G., additional, Benvenuti, F., additional, Mancinelli, P., additional, Boninsegni, P., additional, Paparella, L., additional, Bos, A. T., additional, Thomas, O., additional, Goslar, T., additional, Martone, A., additional, Sandu, P. R., additional, Rosu, V. A., additional, Capilnean, A., additional, Murgoi, P., additional, Lecavalier, A., additional, Jayaraman, D., additional, Rico, P., additional, Bellemare, P., additional, Gelinas, C., additional, Nishida, T., additional, Kinoshita, T., additional, Iwata, N., additional, Yamakawa, K., additional, Fujimi, S., additional, Maggi, L., additional, Sposato, F., additional, Citterio, G., additional, Bonarrigo, C., additional, Rocco, M., additional, Zani, V., additional, De Blasi, R. A., additional, Alcorn, D, additional, Barry, L, additional, Riedijk, M. A., additional, Milstein, D. M., additional, Caldas, J., additional, Panerai, R., additional, Camara, L., additional, Ferreira, G., additional, Bor-Seng-Shu, E., additional, Lima, M., additional, Galas, F., additional, Mian, N., additional, Nogueira, R., additional, de Oliveira, G. Queiroz, additional, Almeida, J., additional, Jardim, J., additional, Robinson, T. G., additional, Gaioto, F., additional, Hajjar, L. A., additional, Zabolotskikh, I., additional, Musaeva, T., additional, Saasouh, W., additional, Freeman, J., additional, Turan, A., additional, Saseedharan, S., additional, Pathrose, E., additional, Poojary, S., additional, Messika, J., additional, Martin, Y., additional, Maquigneau, N., additional, Henry-Lagarrigue, M., additional, Puechberty, C., additional, Stoclin, A., additional, Martin-Lefevre, L., additional, Blot, F., additional, Dreyfuss, D., additional, Dechanet, A., additional, Hajage, D., additional, Ricard, J., additional, Almeida, E., additional, Landoni, G., additional, Fukushima, J., additional, Fominskiy, E., additional, De Brito, C., additional, Cavichio, L., additional, Almeida, L., additional, Ribeiro, U., additional, Osawa, E., additional, Boltes, R., additional, Battistella, L., additional, Hajjar, L., additional, Fontela, P., additional, Lisboa, T., additional, Junior, L. Forgiarini, additional, Friedman, G. F., additional, Abruzzi, F., additional, Primo, J. Azevedo Peixoto, additional, Filho, P. Marques, additional, de Andrade, J. Stormorvski, additional, Brenner, K. Matos, additional, boeira, M. Scorsato, additional, Leães, C., additional, Rodrigues, C., additional, Vessozi, A., additional, Machado, A. SantAnna, additional, Weiler, M., additional, Bryce, H., additional, Hudson, A., additional, Law, T., additional, Reece-Anthony, R., additional, Molokhia, A., additional, Abtahinezhadmoghaddam, F., additional, Cumber, E., additional, Channon, L., additional, Wong, A., additional, Groome, R., additional, Gearon, D., additional, Varley, J., additional, Wilson, A., additional, Reading, J., additional, Zampieri, F. G., additional, Bozza, F. A., additional, Ferez, M., additional, Fernandes, H., additional, Japiassú, A., additional, Verdeal, J., additional, Carvalho, A. C., additional, Knibel, M., additional, Salluh, J. I., additional, Soares, M., additional, Gao, J., additional, Ahmadnia, E., additional, Patel, B., additional, MacKay, A., additional, Binning, S., additional, Pugh, R. J., additional, Battle, C., additional, Hancock, C., additional, Harrison, W., additional, Szakmany, T., additional, Mulders, F., additional, Vandenbrande, J., additional, Dubois, J., additional, Stessel, B., additional, Siborgs, K., additional, Ramaekers, D., additional, Silva, U. V., additional, Homena, W. S., additional, Fernandes, G. C., additional, Moraes, A. P., additional, Brauer, L., additional, Lima, M. F., additional, De Marco, F., additional, Maric, N., additional, Mackovic, M., additional, Udiljak, N., additional, Bosso, CE, additional, Caetano, RD, additional, Cardoso, AP, additional, Souza, OA, additional, Pena, R, additional, Mescolotte, MM, additional, Souza, IA, additional, Mescolotte, GM, additional, Bangalore, H., additional, Borrows, E., additional, Barnes, D., additional, Ferreira, V., additional, Azevedo, L., additional, Alencar, G., additional, Andrade, A., additional, Bierrenbach, A., additional, Buoninsegni, L. Tadini, additional, Cecci, L., additional, Lindskog, J., additional, Rowland, K., additional, Sturgess, P., additional, Ankuli, A., additional, Rosa, R, additional, Tonietto, T, additional, Ascoli, A, additional, Madeira, L, additional, Rutzen, W, additional, Falavigna, M, additional, Robinson, C, additional, Salluh, J, additional, Cavalcanti, A, additional, Azevedo, L, additional, Cremonese, R, additional, Da Silva, D, additional, Dornelles, A, additional, Skrobik, Y, additional, Teles, J, additional, Ribeiro, T, additional, Eugênio, C, additional, Teixeira, C, additional, Zarei, M., additional, Hashemizadeh, H., additional, Eriksson, M., additional, Strandberg, G., additional, Lipcsey, M., additional, Larsson, A., additional, Lignos, M., additional, Crissanthopoulou, E., additional, Flevari, K., additional, Dimopoulos, P., additional, Armaganidis, A., additional, Golub, JG, additional, Stožer, AS, additional, Rüddel, H., additional, Ehrlich, C., additional, Burghold, C. M., additional, Hohenstein, C., additional, Winning, J., additional, Sellami, W., additional, Hajjej, Z., additional, Bousselmi, M., additional, Gharsallah, H., additional, Labbene, I., additional, Ferjani, M., additional, Sattler, J., additional, Steinbrunner, D., additional, Poppert, H., additional, Schneider, G., additional, Blobner, M., additional, Kanz, K. G., additional, Schaller, S. J., additional, Apap, K., additional, Xuereb, G., additional, Massa, L., additional, Delvau, N., additional, Penaloza, A, additional, Liistro, G, additional, Thys, F, additional, Delattre, I. K., additional, Hantson, P., additional, Roy, P. M., additional, Gianello, P., additional, Hadîrcă, L, additional, Ghidirimschi, A, additional, Catanoi, N, additional, Scurtov, N, additional, Bagrinovschi, M, additional, Sohn, Y. S., additional, Cho, Y. C., additional, Golovin, B., additional, Creciun, O., additional, Ghidirimschi, A., additional, Bagrinovschi, M., additional, Tabbara, R., additional, Whitgift, J. Z., additional, Ishimaru, A., additional, Yaguchi, A., additional, Akiduki, N., additional, Namiki, M., additional, Takeda, M., additional, Tamminen, J. N., additional, Uusaro, A., additional, Taylor, C. G., additional, Mills, E. D., additional, Mackay, A. D., additional, Ponzoni, C., additional, Rabello, R., additional, Serpa, A., additional, Assunção, M., additional, Pardini, A., additional, Shettino, G., additional, Corrêa, T., additional, Vidal-Cortés, P. V., additional, Álvarez-Rocha, L., additional, Fernández-Ugidos, P., additional, Virgós-Pedreira, A., additional, Pérez-Veloso, M. A., additional, Suárez-Paul, I. M., additional, Del Río-Carbajo, L., additional, Fernández, S. Pita, additional, Castro-Iglesias, A., additional, Butt, A., additional, Alghabban, A. A., additional, Khurshid, S. K., additional, Ali, Z. A., additional, Nizami, I. N., additional, Salahuddin, N. S., additional, Alshahrani, M., additional, Alsubaie, A. W., additional, Alshamsy, A. S., additional, Alkhiliwi, B. A., additional, Alshammari, H. K., additional, Alshammari, M. B., additional, Telmesani, N. K., additional, Alshammari, R. B., additional, Asonto, L. P., additional, Damiani, L. P., additional, Bozza, F, additional, El Khattate, A., additional, Bizrane, M., additional, Madani, N., additional, Belayachi, J., additional, Abouqal, R., additional, Ramnarain, D., additional, Gouw-Donders, B., additional, Benstoem, C., additional, Moza, A., additional, Meybohm, P., additional, Stoppe, C., additional, Autschbach, R., additional, Devane, D., additional, Goetzenich, A., additional, Taniguchi, L. U., additional, Araujo, L., additional, Salgado, G., additional, Vieira, J. M., additional, Viana, J., additional, Ziviani, N., additional, Pessach, I., additional, Lipsky, A., additional, Nimrod, A., additional, O´Connor, M., additional, Matot, I., additional, Segal, E., additional, Kluzik, A., additional, Gradys, A., additional, Smuszkiewicz, P., additional, Trojanowska, I., additional, Cybulski, M., additional, De Jong, A., additional, Sebbane, M., additional, Chanques, G., additional, Jaber, S., additional, Rosa, R., additional, Robinson, C., additional, Bessel, M., additional, Cavalheiro, L., additional, Madeira, L., additional, Rutzen, W., additional, Oliveira, R., additional, Maccari, J., additional, Falavigna, M., additional, Sanchez, E., additional, Dutra, F., additional, Dietrich, C., additional, Balzano, P., additional, Rezende, J., additional, Teixeira, C., additional, Sinha, S., additional, Majhi, K., additional, Gorlicki, J. G., additional, Pousset, F. P., additional, Kelly, J., additional, Aron, J., additional, Gilbert, A. Crerar, additional, Urankar, N. Prevec, additional, Irazabal, M., additional, Bosque, M., additional, Manciño, J., additional, Kotsopoulos, A., additional, Jansen, N., additional, Abdo, W., additional, Casey, Ú. M., additional, O’Brien, B., additional, Plant, R., additional, and Doyle, B., additional

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2017
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