| 1. |
- Endisch, Christian, et al.
(författare)
-
Hypoxic-Ischemic Encephalopathy Evaluated by Brain Autopsy and Neuroprognostication after Cardiac Arrest
- 2020
-
Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 77:11, s. 1430-1439
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Neuroprognostication studies are potentially susceptible to a self-fulfilling prophecy as investigated prognostic parameters may affect withdrawal of life-sustaining therapy. Objective: To compare the results of prognostic parameters after cardiac arrest (CA) with the histopathologically determined severity of hypoxic-ischemic encephalopathy (HIE) obtained from autopsy results. Design, Setting, and Participants: In a retrospective, 3-center cohort study of all patients who died following cardiac arrest during their intensive care unit stay and underwent autopsy between 2003 and 2015, postmortem brain histopathologic findings were compared with post-CA brain computed tomographic imaging, electroencephalographic (EEG) findings, somatosensory-evoked potentials, and serum neuron-specific enolase levels obtained during the intensive care unit stay. Data analysis was conducted from 2015 to 2020. Main Outcomes and Measures: The severity of HIE was evaluated according to the selective eosinophilic neuronal death (SEND) classification and patients were dichotomized into categories of histopathologically severe and no/mild HIE. Results: Of 187 included patients, 117 were men (63%) and median age was 65 (interquartile range, 58-74) years. Severe HIE was found in 114 patients (61%) and no/mild HIE was identified in 73 patients (39%). Severe HIE was found in all 21 patients with bilaterally absent somatosensory-evoked potentials, all 15 patients with gray-white matter ratio less than 1.10 on brain computed tomographic imaging, all 9 patients with suppressed EEG, 15 of 16 patients with burst-suppression EEG, and all 29 patients with neuron-specific enolase levels greater than 67 μg/L more than 48 hours after CA without confounders. Three of 7 patients with generalized periodic discharges on suppressed background and 1 patient with burst-suppression EEG had a SEND 1 score (<30% dead neurons) in the cerebral cortex, but higher SEND scores (>30% dead neurons) in other oxygen-sensitive brain regions. Conclusions and Relevance: In this study, histopathologic findings suggested severe HIE after cardiac arrest in patients with bilaterally absent cortical somatosensory-evoked potentials, gray-white matter ratio less than 1.10, highly malignant EEG, and serum neuron-specific enolase concentration greater than 67 μg/L.
|
|
| 2. |
- Holgersson, Johan, et al.
(författare)
-
Hypothermic versus Normothermic Temperature Control after Cardiac Arrest
- 2022
-
Ingår i: NEJM Evidence. - 2766-5526. ; 1:11, s. 1-13
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDThe evidence for temperature control for comatose survivors of cardiac arrest is inconclusive. Controversy exists as to whether the effects of hypothermia differ per the circumstances of the cardiac arrest or patient characteristics.METHODSAn individual patient data meta-analysis of the Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest (TTM) and Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trials was conducted. The intervention was hypothermia at 33°C and the comparator was normothermia. The primary outcome was all-cause mortality at 6 months. Secondary outcomes included poor functional outcome (modified Rankin scale score of 4 to 6) at 6 months. Predefined subgroups based on the design variables in the original trials were tested for interaction with the intervention as follows: age (older or younger than the median), sex (female or male), initial cardiac rhythm (shockable or nonshockable), time to return of spontaneous circulation (above or below the median), and circulatory shock on admission (presence or absence).RESULTSThe primary analyses included 2800 patients, with 1403 assigned to hypothermia and 1397 to normothermia. Death occurred for 691 of 1398 participants (49.4%) in the hypothermia group and 666 of 1391 participants (47.9%) in the normothermia group (relative risk with hypothermia, 1.03; 95% confidence interval [CI], 0.96 to 1.11; P=0.41). A poor functional outcome occurred for 733 of 1350 participants (54.3%) in the hypothermia group and 718 of 1330 participants (54.0%) in the normothermia group (relative risk with hypothermia, 1.01; 95% CI, 0.94 to 1.08; P=0.88). Outcomes were consistent in the predefined subgroups.CONCLUSIONSHypothermia at 33°C did not decrease 6-month mortality compared with normothermia after out-of-hospital cardiac arrest. (Funded by Vetenskapsrådet; ClinicalTrials.gov numbers NCT02908308 and NCT01020916.)
|
|
| 3. |
- Lang, Margareta, et al.
(författare)
-
A pilot study of methods for prediction of poor outcome by head computed tomography after cardiac arrest
- 2022
-
Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 179, s. 61-70
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: In Sweden, head computed tomography (CT) is commonly used for prediction of neurological outcome after cardiac arrest, as recommended by guidelines. We compare the prognostic ability and interrater variability of routine and novel CT methods for prediction of poor outcome. Methods: Retrospective study including patients from Swedish sites within the Target Temperature Management after out-of-hospital cardiac arrest trial examined with CT. Original images were assessed by two independent radiologists blinded from clinical data with eye-balling without pre-specified criteria, and with a semi-quantitative assessment. Grey-white-matter ratios (GWR) were quantified using models with 4–20 manually placed regions of interest. Prognostic abilities and interrater variability were calculated for prediction of poor outcome (modified Rankin Scale 4–6 at 6 months) for early (<24 h) and late (≥24 h) examinations. Results: 68/106 (64 %) of included patients were examined < 24 h post-arrest. Eye-balling predicted poor outcome with 89–100 % specificity and 15–78 % sensitivity. GWR < 24 h predicted neurological outcome with unsatisfactory to satisfactory Area Under the Receiver Operating Characteristics Curve (AUROC: 0.54–0.64). GWR ≥ 24 h yielded very good to excellent AUROC (0.80–0.93). Sensitivities increased > 2–3-fold in examinations performed after 24 h compared to early examinations. Combining eye-balling with GWR < 1.15 predicted poor outcome without false positives with sensitivities remaining acceptable. Conclusion: In our cohort, qualitative and quantitative CT methods predicted poor outcome with high specificity and low to moderate sensitivity. Sensitivity increased relevantly after the first 24 h after CA. Interrater variability poses a problem and indicates the need to standardise brain CT evaluation to increase the methods’ safety.
|
|
| 4. |
- Lang, Margareta, et al.
(författare)
-
Prognostic accuracy of head computed tomography for prediction of functional outcome after out-of-hospital cardiac arrest : Rationale and design of the prospective TTM2-CT-substudy
- 2022
-
Ingår i: Resuscitation Plus. - : Elsevier. - 2666-5204. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Head computed tomography (CT) is a guideline recommended method to predict functional outcome after cardiac arrest (CA), but standardized criteria for evaluation are lacking. To date, no prospective trial has systematically validated methods for diagnosing hypoxic-ischaemic encephalopathy (HIE) on CT after CA. We present a protocol for validation of pre-specified radiological criteria for assessment of HIE on CT for neuroprognostication after CA.Methods/design: This is a prospective observational international multicentre substudy of the Targeted Hypothermia versus Targeted Normother-mia after out-of-hospital cardiac arrest (TTM2) trial. Patients still unconscious 48 hours post-arrest at 13 participating hospitals were routinely exam-ined with CT. Original images will be evaluated by examiners blinded to clinical data using a standardized protocol. Qualitative assessment will include evaluation of absence/presence of "severe HIE". Radiodensities will be quantified in pre-specified regions of interest for calculation of grey-white matter ratios (GWR) at the basal ganglia level. Functional outcome will be dichotomized into good (modified Rankin Scale 0-3) and poor (modified Rankin Scale 4-6) at six months post-arrest. Prognostic accuracies for good and poor outcome will be presented as sensitivities and speci-ficities with 95% confidence intervals (using pre-specified cut-offs for quantitative analysis), descriptive statistics (Area Under the Receiver Operating Characteristics Curve), inter-and intra-rater reliabilities according to STARD guidelines.Conclusions: The results from this prospective trial will validate a standardized approach to radiological evaluations of HIE on CT for prediction of functional outcome in comatose CA patients.The TTM2 trial and the TTM2 CT substudy are registered at ClinicalTrials.gov NCT02908308 and NCT03913065.
|
|
| 5. |
- Lilja, Gisela, et al.
(författare)
-
Protocol for outcome reporting and follow-up in the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2)
- 2020
-
Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 150, s. 104-112
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: The TTM2-trial is a multi-centre randomised clinical trial where targeted temperature management (TTM) at 33 °C will be compared with normothermia and early treatment of fever (≥37.8 °C) after Out-of-Hospital Cardiac Arrest (OHCA). This paper presents the design and rationale of the TTM2-trial follow-up, where information on secondary and exploratory outcomes will be collected. We also present the explorative outcome analyses which will focus on neurocognitive function and societal participation in OHCA-survivors. Methods: Blinded outcome-assessors will perform follow-up at 30-days after the OHCA with a telephone interview, including the modified Rankin Scale (mRS) and the Glasgow Outcome Scale Extended (GOSE). Face-to-face meetings will be performed at 6 and 24-months, and include reports on outcome from several sources of information: clinician-reported: mRS, GOSE; patient-reported: EuroQol-5 Dimensions-5 Level responses version (EQ-5D-5L), Life satisfaction, Two Simple Questions; observer-reported: Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest version (IQCODE-CA) and neurocognitive performance measures: Montreal Cognitive Assessment, (MoCA), Symbol Digit Modalities Test (SDMT). Exploratory analyses will be performed with an emphasis on brain injury in the survivors, where the two intervention groups will be compared for potential differences in neuro-cognitive function (MoCA, SDMT) and societal participation (GOSE). Strategies to increase inter-rater reliability and decrease missing data are described. Discussion: The TTM2-trial follow-up is a pragmatic yet detailed pre-planned and standardised assessment of patient's outcome designed to ensure data-quality, decrease missing data and provide optimal conditions to investigate clinically relevant effects of TTM, including OHCA-survivors’ neurocognitive function and societal participation.
|
|
| 6. |
- Moseby-Knappe, Marion, et al.
(författare)
-
Biomarkers of brain injury after cardiac arrest; a statistical analysis plan from the TTM2 trial biobank investigators
- 2022
-
Ingår i: Resuscitation Plus. - : Elsevier. - 2666-5204. ; 10
-
Tidskriftsartikel (refereegranskat)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 (R) 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.
|
|
| 7. |
- Turella, Sara, et al.
(författare)
-
The predictive value of highly malignant EEG patterns after cardiac arrest : evaluation of the ERC-ESICM recommendations
-
Ingår i: Intensive Care Medicine. - 0342-4642.
-
Tidskriftsartikel (refereegranskat)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.
|
|
