| 1. |
- Holgersson, Johan, et al.
(författare)
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Hypothermic versus Normothermic Temperature Control after Cardiac Arrest
- 2022
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Ingår i: NEJM Evidence. - 2766-5526. ; 1:11, s. 1-13
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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.)
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| 2. |
- Lagebrant, Alice, et al.
(författare)
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Brain injury markers in blood predict signs of hypoxic ischaemic encephalopathy on head computed tomography after cardiac arrest
- 2023
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Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 184
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Signs of hypoxic ischaemic encephalopathy (HIE) on head computed tomography (CT) predicts poor neurological outcome after cardiac arrest. We explore whether levels of brain injury markers in blood could predict the likelihood of HIE on CT.Methods: Retrospective analysis of CT performed at 24-168 h post cardiac arrest on clinical indication within the Target Temperature Management after out-of-hospital cardiac arrest-trial. Biomarkers prospectively collected at 24-and 48 h post-arrest were analysed for neuron specific enolase (NSE), neurofilament light (NFL), total-tau and glial fibrillary acidic protein (GFAP). HIE was assessed through visual evaluation and quantitative grey-white-matter ratio (GWR) was retrospectively calculated on Swedish subjects with original images available.Results: In total, 95 patients were included. The performance to predict HIE on CT (performed at IQR 73-116 h) at 48 h was similar for all biomark-ers, assessed as area under the receiving operating characteristic curve (AUC) NSE 0.82 (0.71-0.94), NFL 0.79 (0.67-0.91), total-tau 0.84 (0.74- 0.95), GFAP 0.79 (0.67-0.90). The predictive performance of biomarker levels at 24 h was AUC 0.72-0.81. At 48 h biomarker levels below Youden Index accurately excluded HIE in 77.3-91.7% (negative predictive value) and levels above Youden Index correctly predicted HIE in 73.3-83.7% (positive predictive value). NSE cut-off at 48 h was 48 ng/ml. Elevated biomarker levels irrespective of timepoint significantly correlated with lower GWR.Conclusion: Biomarker levels can assess the likelihood of a patient presenting with HIE on CT and could be used to select suitable patients for CT-examination during neurological prognostication in unconscious cardiac arrest patients.
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| 3. |
- Lilja, Gisela, et al.
(författare)
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Cognitive Function in Survivors of Out-of-Hospital Cardiac Arrest After Target Temperature Management at 33ºC Versus 36ºC.
- 2015
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Ingår i: Circulation. - 1524-4539. ; 131:15, s. 77-1340
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Tidskriftsartikel (refereegranskat)abstract
- -Target temperature management is recommended as a neuro-protective strategy after out-of-hospital cardiac arrest. Potential effects of different target temperatures on cognitive impairment commonly described in survivors are not sufficiently investigated. The primary aim of this study was to evaluate whether a target temperature of 33ºC compared to 36ºC was favourable for cognitive function, and secondary to describe cognitive impairment in cardiac arrest survivors in general.
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| 4. |
- Lilja, Gisela, et al.
(författare)
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Cognitive Function in Survivors of Out-of-Hospital Cardiac Arrest After Target Temperature Management at 33 degrees C Versus 36 degrees C
- 2015
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Ingår i: Circulation. - 0009-7322. ; 131:15, s. 1340-1349
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Tidskriftsartikel (refereegranskat)abstract
- -Target temperature management is recommended as a neuro-protective strategy after out-of-hospital cardiac arrest. Potential effects of different target temperatures on cognitive impairment commonly described in survivors are not sufficiently investigated. The primary aim of this study was to evaluate whether a target temperature of 33ºC compared to 36ºC was favourable for cognitive function, and secondary to describe cognitive impairment in cardiac arrest survivors in general.
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| 5. |
- Mattsson, Niklas, et al.
(författare)
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Serum tau and neurological outcome in cardiac arrest.
- 2017
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Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 82:5, s. 665-675
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Tidskriftsartikel (refereegranskat)abstract
- To test serum tau as a predictor of neurological outcome after cardiac arrest.We measured the neuronal protein tau in serum at 24, 48, and 72 hours after cardiac arrest in 689 patients in the prospective international Target Temperature Management trial. The main outcome was poor neurological outcome, defined as Cerebral Performance Categories 3-5 at 6 months.Increased tau was associated with poor outcome at 6 months after cardiac arrest (median = 38.5, interquartile range [IQR] = 5.7-245ng/l in poor vs median = 1.5, IQR = 0.7-2.4ng/l in good outcome, for tau at 72 hours, p < 0.0001). Tau improved prediction of poor outcome compared to using clinical information (p < 0.0001). Tau cutoffs had low false-positive rates (FPRs) for good outcome while retaining high sensitivity for poor outcome. For example, tau at 72 hours had FPR = 2% (95% CI = 1-4%) with sensitivity = 66% (95% CI = 61-70%). Tau had higher accuracy than serum neuron-specific enolase (NSE; the area under the receiver operating characteristic curve was 0.91 for tau vs 0.86 for NSE at 72 hours, p = 0.00024). During follow-up (up to 956 days), tau was significantly associated with overall survival. The accuracy in predicting outcome by serum tau was equally high for patients randomized to 33 °C and 36 °C targeted temperature after cardiac arrest.Serum tau is a promising novel biomarker for prediction of neurological outcome in patients with cardiac arrest. It may be significantly better than serum NSE, which is recommended in guidelines and currently used in clinical practice in several countries to predict outcome after cardiac arrest. Ann Neurol 2017;82:665-675.
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| 6. |
- 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 (72–96 h) 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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| 7. |
- Moseby-Knappe, Marion, et al.
(författare)
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Serum Neurofilament Light Chain for Prognosis of Outcome after Cardiac Arrest
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:1, s. 64-64
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Prognostication of neurologic outcome after cardiac arrest is an important but challenging aspect of patient therapy management in critical care units. Objective: To determine whether serum neurofilament light chain (NFL) levels can be used for prognostication of neurologic outcome after cardiac arrest. Design, Setting and Participants: Prospective clinical biobank study of data from the randomized Target Temperature Management After Cardiac Arrest trial, an international, multicenter study with 29 participating sites. Patients were included between November 11, 2010, and January 10, 2013. Serum NFL levels were analyzed between August 1 and August 23, 2017, after trial completion. A total of 782 unconscious patients with out-of-hospital cardiac arrest of presumed cardiac origin were eligible. Exposures: Serum NFL concentrations analyzed at 24, 48, and 72 hours after cardiac arrest with an ultrasensitive immunoassay. Main Outcomes and Measures: Poor neurologic outcome at 6-month follow-up, defined according to the Cerebral Performance Category Scale as cerebral performance category 3 (severe cerebral disability), 4 (coma), or 5 (brain death). Results: Of 782 eligible patients, 65 patients (8.3%) were excluded because of issues with aliquoting, missing sampling, missing outcome, or transport problems of samples. Of the 717 patients included (91.7%), 580 were men (80.9%) and median (interquartile range [IQR]) age was 65 (56-73) years. A total of 360 patients (50.2%) had poor neurologic outcome at 6 months. Median (IQR) serum NFL level was significantly increased in the patients with poor outcome vs good outcome at 24 hours (1426 [299-3577] vs 37 [20-70] pg/mL), 48 hours (3240 [623-8271] vs 46 [26-101] pg/mL), and 72 hours (3344 [845-7838] vs 54 [30-122] pg/mL) (P <.001 at all time points), with high overall performance (area under the curve, 0.94-0.95) and high sensitivities at high specificities (eg, 69% sensitivity with 98% specificity at 24 hours). Serum NFL levels had significantly greater performance than the other biochemical serum markers (ie, tau, neuron-specific enolase, and S100). At comparable specificities, serum NFL levels had greater sensitivity for poor outcome compared with routine electroencephalogram, somatosensory-evoked potentials, head computed tomography, and both pupillary and corneal reflexes (ranging from 29.2% to 49.0% greater for serum NFL level). Conclusions and Relevance: Findings from this study suggest that the serum NFL level is a highly predictive marker of long-term poor neurologic outcome at 24 hours after cardiac arrest and may be a useful complement to currently available neurologic prognostication methods.
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| 8. |
- Nielsen, Niklas, et al.
(författare)
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Targeted Temperature Management at 33 degrees C versus 36 degrees C after Cardiac Arrest
- 2013
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 369:23, s. 2197-2206
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundUnconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. MethodsIn an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33 degrees C or 36 degrees C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. ResultsIn total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33 degrees C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36 degrees C group (225 of 466 patients) (hazard ratio with a temperature of 33 degrees C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33 degrees C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36 degrees C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. ConclusionsIn unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33 degrees C did not confer a benefit as compared with a targeted temperature of 36 degrees C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.)
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| 9. |
- Wiberg, Sebastian, et al.
(författare)
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Biomarkers of Cerebral Injury for Prediction of Postoperative Cognitive Dysfunction in Patients Undergoing Cardiac Surgery.
- 2022
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Ingår i: Journal of cardiothoracic and vascular anesthesia. - : Elsevier BV. - 1532-8422 .- 1053-0770. ; 36:1, s. 125-132
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Tidskriftsartikel (refereegranskat)abstract
- To assess the ability of the biomarkers neuron-specific enolase (NSE), tau, neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP) to predict postoperative cognitive dysfunction (POCD) at discharge in patients who underwent cardiac surgery.Post hoc analyses (with tests being prespecified before data analyses) from a randomized clinical trial.Single-center study from a primary heart center in Denmark.Adult patients undergoing elective or subacute on-pump coronary artery bypass grafting and/or aortic valve replacement.Blood was collected before induction of anesthesia, after 24 hours, after 48 hours, and at discharge from the surgical ward. The International Study of Postoperative Cognitive Dysfunction test battery was applied to diagnose POCD at discharge and after three months. Linear mixed models of covariance were used to assess whether repeated measurements of biomarker levels were associated with POCD. Receiver operating characteristic (ROC) curves were applied to assess the predictive value of each biomarker measurement for POCD.A total of 168 patients had biomarkers measured at baseline, and 47 (28%) fulfilled the POCD criteria at discharge. Patients with POCD at discharge had significantly higher levels of tau (p = 0.02) and GFAP (p = 0.01) from baseline to discharge. The biomarker measurements achieving the highest area under the ROC curve for prediction of POCD at discharge were NFL measured at discharge (AUC, 0.64; 95% confidence interval [CI], 0.54-0.73), GFAP measured 48 hours after induction (AUC, 0.64; 95% CI, 0.55-0.73), and GFAP measured at discharge (AUC, 0.64; 95% CI, 0.54-0.74), corresponding to a moderate predictive ability.Postoperative serum levels of tau and GFAP were elevated significantly in patients with POCD who underwent cardiac surgery at discharge; however, the biomarkers achieved only modest predictive abilities for POCD at discharge. Postoperative levels of NSE were not associated with POCD at discharge.
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| 10. |
- Andréll, Cecilia, et al.
(författare)
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Out-of-hospital cardiac arrest at place of residence is associated with worse outcomes in patients admitted to intensive care : a post-hoc analysis of the Targeted Temperature Management trial
- 2019
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Ingår i: Minerva Anestesiologica. - 1827-1596. ; 85:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The majority of out-of-hospital cardiac arrests (OHCAs) occur at place residence, which is associated with worse outcomes in unselected prehospital populations. Our aim was to investigate whether location of arrest was associated with outcome in a selected group of initial survivors admitted to intensive care.METHODS: This is a post-hoc analysis of the Targeted Temperature Management after cardiac arrest trial (TTM trial), a multicenter controlled trial, randomizing 950 OHCA patients to an intervention of 33°C or 36°C. The location of cardiac arrest was defined as place of residence vs. public place or other. The outcome measures were mortality and neurological outcome, as defined by the Cerebral Performance Category scale, at 180 days.RESULTS: Approximately half of 938 included patients arrested at place of residence (53%). Location groups did not differ with respect to age (p=0.11) or witnessed arrests (p=0.48) but bystander CPR was less common (p=0.02) at place of residence. OHCA at place of residence was associated with higher 180-day mortality, 55% vs. 38% (p<0.001) and worse neurological outcome, 61% vs. 43% (p<0.001) compared with a public place or other. After adjusting for known confounders, OHCA at place of residence remained an independent predictor of mortality (p=0.007).CONCLUSIONS: Half of all initial survivors after OHCA admitted to intensive care had an at place of residence which was independently associated with poor outcomes. Actions improve outcomes after OHCA at place of residence should be addressed in future trials.
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