| 1. |
- Backman, Sofia, et al.
(författare)
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Electroencephalographic characteristics of status epilepticus after cardiac arrest
- 2017
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457. ; 128:4, s. 681-688
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the electrophysiological characteristics and pathophysiological significance of electrographic status epilepticus (ESE) after cardiac arrest and specifically compare patients with unequivocal ESE to patients with rhythmic or periodic borderline patterns defined as possible ESE. Methods: Retrospective cohort study of consecutive patients treated with targeted temperature management and monitored with simplified continuous EEG. Patients with ESE were identified and electrographically characterised until 72. h after ESE start using the standardised terminology of the American Clinical Neurophysiology Society. Results: ESE occurred in 41 of 127 patients and 22 fulfilled the criteria for unequivocal ESE, which typically appeared early and transiently. Three of the four survivors had unequivocal ESE, starting after rewarming from a continuous background. There were no differences between the groups of unequivocal ESE and possible ESE regarding outcome, neuron-specific enolase levels or prevalence of reported clinical convulsions. Conclusion: ESE is common after cardiac arrest. The distinction between unequivocal and possible ESE patterns was not reflected by differences in clinical features or survival. Significance: A favourable outcome is seen infrequently in patients with ESE, regardless of using strict or liberal ESE definitions.
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| 2. |
- Grindegård, Linnéa, et al.
(författare)
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Association Between EEG Patterns and Serum Neurofilament Light After Cardiac Arrest: A Post Hoc Analysis of the TTM Trial.
- 2022
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 98:24
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Tidskriftsartikel (refereegranskat)abstract
- Electroencephalography (EEG) is widely used for prediction of neurological outcome after cardiac arrest. To better understand the relationship between EEG and neuronal injury, we explore the association between EEG and neurofilament light (NFL) as a marker of neuroaxonal injury. We evaluate whether highly malignant EEG patterns are reflected by high NFL levels. Additionally, we explore the association of EEG backgrounds and EEG discharges with NFL.Post-hoc analysis of the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Routine EEGs were prospectively performed after the temperature intervention ≥36 hours post-arrest. Patients who awoke or died prior to 36 hours post-arrest were excluded. EEG-experts blinded to clinical information classified EEG background, amount of discharges and highly malignant EEG patterns according to the standardized American Clinical Neurophysiology Society terminology. Prospectively collected serum samples were analyzed for NFL after trial completion. The highest available concentration at 48 or 72-hours post-arrest was used.262/939 patients with EEG and NFL data were included. Patients with highly malignant EEG patterns had 2.9 times higher NFL levels than patients with malignant patterns and NFL levels were 13 times higher in patients with malignant patterns than those with benign patterns (95% CI: 1.4-6.1 and 6.5-26.2 respectively, effect size 0.47, p<0.001). Both background and the amount of discharges were independently strongly associated with NFL levels (p<0.001). The EEG background had a stronger association with NFL levels than EEG discharges (R2=0.30 and R2=0.10, respectively). NFL levels in patients with a continuous background were lower than for any other background (95% CI for discontinuous, burst-suppression and suppression, respectively: 2.26-18.06, 3.91-41.71 and 5.74-41.74, effect size 0.30 and p<0.001 for all). NFL levels did not differ between suppression and burst-suppression. Superimposed discharges were only associated with higher NFL levels if the EEG background was continuous.Benign, malignant, and highly malignant EEG patterns reflect the extent of brain injury as measured by NFL in serum. The extent of brain injury is more strongly related to the EEG background than superimposed discharges. Combining EEG and NFL may be useful to better identify patients misclassified by single methods.clinicaltrials.gov, NCT01020916.
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| 3. |
- Lybeck, Anna, et al.
(författare)
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Postanoxic electrographic status epilepticus and serum biomarkers of brain injury
- 2021
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 158, s. 253-257
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To explore if electrographic status epilepticus (ESE) after cardiac arrest causes additional secondary brain injury reflected by serum levels of two novel biomarkers of brain injury: neurofilament light chain (NfL) originating from neurons and glial fibrillary acidic protein (GFAP) from glial cells. Methods: Simplified continuous EEG (cEEG) and serum levels of NfL and GFAP, sampled at 24, 48 and 72 h after cardiac arrest, were collected during the Target Temperature Management (TTM)-trial. Two statistical methods were used: multivariable regresssion analysis; and a matched control group of patients without ESE matched for early predictors of poor neurological outcome. Results: 128 patients had available biomarkers and cEEG. Twenty-six (20%) patients developed ESE, the majority (69%) within 24 h. ESE was an independent predictor of elevated serum NfL (p < 0.001) but not of serum GFAP (p = 0.16) at 72 h after cardiac arrest. Compared to a control group matched for early predictors of poor neurological outcome, patients who developed ESE had higher levels of serum NfL (p = 0.03) and GFAP (p = 0.04) at 72 h after cardiac arrest. Conclusion: ESE after cardiac arrest is associated with higher levels of serum NfL which may suggest increased secondary neuronal injury compared to matched patients without ESE but similar initial brain injury. Associations with GFAP reflecting glial injury are less clear. The study design cannot exclude imperfect matching or other mechanisms of secondary brain injury contributing to the higher levels of biomarkers of brain injury seen in the patients with ESE.
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| 4. |
- Lybeck, Anna, et al.
(författare)
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Prognostic significance of clinical seizures after cardiac arrest and target temperature management
- 2017
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 114, s. 146-151
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Clinical seizures are common after cardiac arrest and predictive of a poor neurological outcome. Seizures may be myoclonic, tonic-clonic or a combination of seizure types. This study reports the incidence and prognostic significance of clinical seizures in the target temperature management (TTM) after cardiac arrest trial. Our hypotheses were that seizures are associated with a poor prognosis and that the incidence of seizures is not affected by the target temperature. Methods: Post-hoc analysis of reported clinical seizures during day 1-7 in the TTM-trial including their treatment, EEG-findings, and long-term neurological outcome. The trial randomised 939 comatose survivors to TTM at 33. °C or 36. °C with strict criteria for withdrawal of life-sustaining therapies. Sensitivity, specificity and false positive rate for poor outcome were reported for different types of seizures. Results: Clinical seizures were registered in 268 patients (29%), similarly distributed in both intervention arms. Early and late seizures were equally predictive of poor outcome. Myoclonic seizures were the most common (240 patients, 26%) and the most predictive of a poor outcome (sensitivity 36.1%, false positive rate 4.3%). Two patients with status myoclonus regained consciousness, one with a good neurological outcome, generating a false positive rate of poor outcome of 0.2% (95%CI 0.0-1.0). Conclusion: Clinical seizures are common after cardiac arrest and indicate poor outcome with limited specificity. Prolonged seizures are a very grave sign but occasional patients may have a good outcome. The level of the target temperature does not affect the prevalence or prognostic significance of seizures.
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| 5. |
- Moseby-Knappe, Marion, et al.
(författare)
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Performance of a guideline-recommended algorithm for prognostication of poor neurological outcome after cardiac arrest
- 2020
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 46:10, s. 1852-62
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Tidskriftsartikel (refereegranskat)abstract
- © 2020, The Author(s). Purpose: To assess the performance of a 4-step algorithm for neurological prognostication after cardiac arrest recommended by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM). Methods: Retrospective descriptive analysis with data from the Target Temperature Management (TTM) Trial. Associations between predicted and actual neurological outcome were investigated for each step of the algorithm with results from clinical neurological examinations, neuroradiology (CT or MRI), neurophysiology (EEG and SSEP) and serum neuron-specific enolase. Patients examined with Glasgow Coma Scale Motor Score (GCS-M) on day 4 (72–96h) post-arrest and available 6-month outcome were included. Poor outcome was defined as Cerebral Performance Category 3–5. Variations of the ERC/ESICM algorithm were explored within the same cohort. Results: The ERC/ESICM algorithm identified poor outcome patients with 38.7% sensitivity (95% CI 33.1–44.7) and 100% specificity (95% CI 98.8–100) in a cohort of 585 patients. An alternative cut-off for serum neuron-specific enolase, an alternative EEG-classification and variations of the GCS-M had minor effects on the sensitivity without causing false positive predictions. The highest overall sensitivity, 42.5% (95% CI 36.7–48.5), was achieved when prognosticating patients irrespective of GCS-M score, with 100% specificity (95% CI 98.8–100) remaining. Conclusion: The ERC/ESICM algorithm and all exploratory multimodal variations thereof investigated in this study predicted poor outcome without false positive predictions and with sensitivities 34.6–42.5%. Our results should be validated prospectively, preferably in patients where withdrawal of life-sustaining therapy is uncommon to exclude any confounding from self-fulfilling prophecies.
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| 6. |
- Moseby-Knappe, Marion, et al.
(författare)
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Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest
- 2021
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 47, s. 984-994
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered "indeterminate". We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines. Methods Retrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1-2) at 6 months. Results Seven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2-98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87-95% of patients). Normal S100B and NSE predicted good outcome with NPV 76-82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as "indeterminate outcome" by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome. Conclusion Low levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy.
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| 7. |
- Robba, Chiara, et al.
(författare)
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Oxygen targets and 6-month outcome after out of hospital cardiac arrest : a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial
- 2022
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 26, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients’ outcome. Methods: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308, Registered September 20, 2016.
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| 8. |
- Robba, Chiara, et al.
(författare)
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Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients : a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
- 2022
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 48:8, s. 1024-1038
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes. Methods: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization. Results: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2–8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5–9) cmH20, plateau pressure was 20 cmH20 (IQR = 17–23), driving pressure was 12 cmH20 (IQR = 10–15), mechanical power 16.2 J/min (IQR = 12.1–21.8), ventilatory ratio was 1.27 (IQR = 1.04–1.6), and respiratory rate was 17 breaths/minute (IQR = 14–20). Median partial pressure of oxygen was 87 mmHg (IQR = 75–105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36–45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003–1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001–1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome. Conclusions: Protective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes.
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| 9. |
- Westhall, Erik, et al.
(författare)
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Electroencephalography (EEG) for neurological prognostication after cardiac arrest and targeted temperature management; rationale and study design
- 2014
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Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Electroencephalography (EEG) is widely used to assess neurological prognosis in patients who are comatose after cardiac arrest, but its value is limited by varying definitions of pathological patterns and by inter-rater variability. The American Clinical Neurophysiology Society (ACNS) has recently proposed a standardized EEG-terminology for critical care to address these limitations. In the Target Temperature Management (TTM) trial, a large international trial on temperature management after cardiac arrest, EEG-examinations were part of the prospective study design. The main objective of this study is to evaluate EEG-data from the TTM-trial and to identify malignant EEG-patterns reliably predicting a poor neurological outcome. Methods/Design: In the TTM-trial, 399 post cardiac arrest patients who remained comatose after rewarming underwent a routine EEG. The presence of clinical seizures, use of sedatives and antiepileptic drugs during the EEG-registration were prospectively documented. After the end of the trial, the EEGs were retrieved to form a central EEG-database. The EEG-data will be analysed using the ACNS EEG terminology. We designed an electronic case record form (eCRF). Four EEG-specialists from different countries, blinded to patient outcome, will independently classify the EEGs and report through the eCRF. We will describe the prognostic values of pre-specified EEG patterns to predict poor as well as good outcome. We hypothesise three patterns to always be associated with a poor outcome (suppressed background without discharges, suppressed background with continuous periodic discharges and burst-suppression). Inter- and intra-rater variability and whether sedation or level of temperature affects the prognostic values will also be analyzed. Discussion: A well-defined terminology for interpreting post cardiac arrest EEGs is critical for the use of EEG as a prognostic tool. The results of this study may help to validate the ACNS terminology for assessing post cardiac arrest EEGs and identify patterns that could reliably predict outcome.
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| 10. |
- Westhall, Erik, et al.
(författare)
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Interrater agreement of EEG interpretation in comatose post cardiac arrest patients
- 2015
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457. ; 126:8, s. 171-171
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Konferensbidrag (refereegranskat)abstract
- Question: What is the interrater agreement of EEG interpretation in adult comatose post cardiac arrest patients using the American Clinical Neurophysiology Society (ACNS) standardized critical care EEG terminology? Methods: The EEG-data were obtained from patients included in the Target Temperature Management trial (TTM), an international, multicenter, clinical trial of temperature management in comatose cardiac arrest patients [N Engl J Med 2013]. In the TTM trial a routine EEG was performed in patients still comatose 12-36. h after rewarming.For this study, one EEG-specialist (IR) chose 20 EEGs, covering important aspects of the ACNS EEG terminology. Four EEG-specialists with different nationalities (Sweden: EW, Denmark: TWK, The Netherlands: AFvR and Switzerland: AOR) acquired the ACNS EEG terminology [J Clin Neurophys 2013;30:1-27] and studied a web-based training-module. The four EEG-specialists subsequently interpreted (blinded to patients' identity) the 20 EEGs, reporting the findings according to the ACNS EEG terminology. Percent agreement and Fleiss kappa values for every category in the terminology were calculated. Percent agreement was defined as the proportion of the 20 EEGs in which all interpreters reported identical findings. Results: There was 65% agreement on whether a rhythmic or periodic pattern was present or not (Kappa 0.44). If a rhythmic or periodic pattern was present there was 93% agreement on which type of pattern (periodic discharges, rhythmic delta activity, rhythmic spike-and-wave/polyspike-and-wave/sharp-and-slow-wave) (Kappa 0.65). Conclusions: Using the ACNS EEG terminology in adult comatose post cardiac arrest patients there was moderate agreement on the presence and type of periodic and rhythmic patterns.
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