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1.
  • Andréll, Cecilia, et al. (författare)
  • 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
  • Ingår i: Minerva Anestesiologica. - 1827-1596. ; 85:7
  • 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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2.
  • Boileau, Adeline, et al. (författare)
  • Circulating Levels of miR-574-5p Are Associated with Neurological Outcome after Cardiac Arrest in Women : A Target Temperature Management (TTM) Trial Substudy
  • 2019
  • Ingår i: Disease Markers. - : Hindawi Limited. - 0278-0240 .- 1875-8630. ; 2019
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Postresuscitation neuroprognostication is guided by neurophysiological tests, biomarker measurement, and clinical examination. Recent investigations suggest that circulating microRNAs (miRNA) may help in outcome prediction after cardiac arrest. We assessed the ability of miR-574-5p to predict neurological outcome after cardiac arrest, in a sex-specific manner. Methods: In this substudy of the Target Temperature Management (TTM) Trial, we enrolled 590 cardiac arrest patients for which blood samples were available. Expression levels of miR-574-5p were measured by quantitative PCR in plasma samples collected 48 h after cardiac arrest. The endpoint of the study was poor neurological outcome at 6 months (cerebral performance category scores 3 to 5). Results: Eighty-one percent of patients were men, and 49% had a poor neurological outcome. Circulating levels of miR-574-5p at 48 h were higher in patients with a poor neurological outcome at 6 months (p < 0.001), both in women and in men. Circulating levels of miR-574-5p were univariate predictors of neurological outcome (odds ratio (OR) [95% confidence interval (CI)]: 1.5 [1.26-1.78]). After adjustment with clinical variables and NSE, circulating levels of miR-574-5p predicted neurological outcome in women (OR [95% CI]: 1.9 [1.09-3.45]), but not in men (OR [95% CI]: 1.0 [0.74-1.28]). Conclusion: miR-574-5p is associated with neurological outcome after cardiac arrest in women.
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5.
  • Cronberg, Tobias, et al. (författare)
  • Neurologic Function and Health-Related Quality of Life in Patients Following Targeted Temperature Management at 33 degrees C vs 36 degrees C After Out-of-Hospital Cardiac Arrest A Randomized Clinical Trial
  • 2015
  • Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 72:6, s. 634-641
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Brain injury affects neurologic function and quality of life in survivors after cardiac arrest. OBJECTIVE To compare the effects of 2 target temperature regimens on long-term cognitive function and quality of life after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS In this multicenter, international, parallel group, assessor-masked randomized clinical trial performed from November 11, 2010, through January 10, 2013, we enrolled 950 unconscious adults with cardiac arrest of presumed cardiac cause from 36 intensive care units in Europe and Australia. Eleven patients were excluded from analysis for a total sample size of 939. INTERVENTIONS Targeted temperature management at 33 degrees C vs 36 degrees C. MAIN OUTCOMES AND MEASURES Cognitive function was measured by the Mini-Mental State Examination (MMSE) and assessed by observers through the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Patients reported their activities in daily life and mental recovery through Two Simple Questions and their quality of life through the Medical Outcomes Study 36-Item Short Form Health Survey, version 2. RESULTS In the modified intent-to-treat population, including nonsurvivors, the median MMSE score was 14 in the 33 degrees C group (interquartile range [IQR], 0-28) vs 17 in the 36 degrees C group (IQR, 0-29) (P = .77), and the IQCODE score was 115 (IQR, 79-130) vs 115 (IQR, 80-130) (P = .57) in the 33 degrees C and 36 degrees C groups, respectively. The median MMSE score for survivors was within the reference range and similar (33 degrees C group median, 28; IQR, 26-30; vs 36 degrees C group median, 28; IQR, 25-30; P = .61). The median IQCODE score was within the minor deficit range (33 degrees C group median, 79.5; IQR, 78.0-85.9; vs 36 degrees C group median, 80.7; IQR, 78.0-86.9; P = .04). A total of 18.8% vs 17.5% of survivors reported needing help with everyday activities (P = .71), and 66.5% in the 33 degrees C group vs 61.8% in the 36 degrees C group reported that they thought they had made a complete mental recovery (P = .32). The mean (SD) mental component summary score was 49.1 (12.5) vs 49.0 (12.2) (P = .79), and the mean (SD) physical component summary score was 46.8 (13.8) and 47.5 (13.8) (P = .45), comparable to the population norm. CONCLUSIONS AND RELEVANCE Quality of life was good and similar in patients with cardiac arrest receiving targeted temperature management at 33 degrees C or 36 degrees C. Cognitive function was similar in both intervention groups, but many patients and observers reported impairment not detected previously by standard outcome scales.
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6.
  • Dankiewicz, Josef, et al. (författare)
  • Infectious complications after out-of-hospital cardiac arrest—A comparison between two target temperatures
  • 2017
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 113, s. 70-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Background It has been suggested that target temperature management (TTM) increases the probability of infectious complications after cardiac arrest. We aimed to compare the incidence of pneumonia, severe sepsis and septic shock after out-of-hospital cardiac arrest (OHCA) in patients with two target temperatures and to describe changes in biomarkers and possible mortality associated with these infectious complications. Methods Post-hoc analysis of the TTM-trial which randomized patients resuscitated from OHCA to a target temperature of 33 °C or 36 °C. Prospective data on infectious complications were recorded daily during the ICU-stay. Pneumonia, severe sepsis and septic shock were considered infectious complications. Procalcitonin (PCT) and C-reactive-protein (CRP) levels were measured at 24 h, 48 h and 72 h after cardiac arrest. Results There were 939 patients in the modified intention-to-treat population. Five-hundred patients (53%) developed pneumonia, severe sepsis or septic shock which was associated with mortality in multivariate analysis (Hazard ratio [HR] 1.39; 95%CI 1.13–1.70; p = 0.001). There was no statistically significant difference in the incidence of infectious complications between temperature groups (sub-distribution hazard ratio [SHR] 0.88; 95%CI 0.75–1.03; p = 0.12). PCT and CRP were significantly higher for patients with infections at all times (p < 0.001), but there was considerable overlap. Conclusions Patients who develop pneumonia, severe sepsis or septic shock after OHCA might have an increased mortality. A target temperature of 33 °C after OHCA was not associated with an increased risk of infectious complications compared to a target temperature of 36 °C. PCT and CRP are of limited value for diagnosing infectious complications after cardiac arrest.
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7.
  • Dankiewicz, Josef, et al. (författare)
  • Safety, Feasibility, and Outcomes of Induced Hypothermia Therapy Following In-Hospital Cardiac Arrest-Evaluation of a Large Prospective Registry
  • 2014
  • Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 42:12, s. 2537-2545
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Despite a lack of randomized trials, practice guidelines recommend that mild induced hypothermia be considered for comatose survivors of in-hospital cardiac arrest. This study describes the safety, feasibility, and outcomes of mild induced hypothermia treatment following in-hospital cardiac arrest. Design: Prospective, observational, registry-based study. Setting: Forty-six critical care facilities in eight countries in Europe and the United States reporting in the Hypothermia Network Registry and the International Cardiac Arrest Registry. Patients: A total of 663 patients with in-hospital cardiac arrest and treated with mild induced hypothermia were included between January 2004 and February 2012. Interventions: None. Measurements and Main Results: A cerebral performance category of 1 or 2 was considered a good outcome. At hospital discharge 41% of patients had a good outcome. At median 6-month follow-up, 34% had a good outcome. Among in-hospital deaths, 52% were of cardiac causes and 44% of cerebral cause. A higher initial body temperature was associated with reduced odds of a good outcome (odds ratio, 0.79; 95% CI, 0.68-0.92). Adverse events were common; bleeding requiring transfusion (odds ratio, 0.56; 95% CI, 0.31-1.00) and sepsis (odds ratio, 0.52; 95% CI, 0.30-0.91) were associated with reduced odds for a good outcome. Conclusions: In this registry study of an in-hospital cardiac arrest population treated with mild induced hypothermia, we found a 41% good outcome at hospital discharge and 34% at follow-up. Infectious complications occurred in 43% of cases, and 11% of patients required a transfusion for bleeding. The majority of deaths were of cardiac origin.
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8.
  • Dankiewicz, Josef, et al. (författare)
  • Time to start of cardiopulmonary resuscitation and the effect of target temperature management at 33°C and 36°C.
  • 2016
  • Ingår i: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 99, s. 44-49
  • Tidskriftsartikel (refereegranskat)abstract
    • The optimal temperature during targeted temperature management (TTM) for comatose patients resuscitated from out-of-hospital cardiac arrest is unknown. It has been hypothesized that patients with long no-flow times, for example those without bystander CPR would have the most to gain from temperature management at lower temperatures.
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9.
  • Devaux, Yvan, et al. (författare)
  • Association of circulating MicroRNA-124-3p levels with outcomes after out-of-hospital cardiac arrest : A substudy of a randomized clinical trial
  • 2016
  • Ingår i: JAMA Cardiology. - : American Medical Association (AMA). - 2380-6583. ; 1:3, s. 305-313
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: The value of microRNAs (miRNAs) as biomarkers has been investigated in various clinical contexts. Initial small-scale studies suggested that miRNAs might be useful indicators of outcome after cardiac arrest. OBJECTIVE: To address the prognostic value of circulating miRNAs in a large cohort of comatose patients with out-of-hospital cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: This substudy of the Target Temperature Management After Cardiac Arrest (TTM) trial, a multicenter randomized, parallel-group, assessor-blinded clinical trial, compared the 6-month neurologic outcomes and survival of patients with cardiac arrest after targeted temperature management at 33°C or 36°C. Five hundred seventy-nine patients who survived the first 24 hours after the return of spontaneous circulation and who had blood samples available for miRNA assessment were enrolled from 29 intensive care units in 9 countries from November 11, 2010, to January 10, 2013. Final follow-up was completed on July 3, 2013, and data were assessed from February 1, 2014, to February 1, 2016. INTERVENTIONS: Blood sampling at 48 hours after the return of spontaneous circulation. MAINOUTCOMES AND MEASURES: The primary end point was poor neurologic outcomeat6 months (cerebral performance category score, 3 [severe neurologic sequelae], 4 [coma], or 5 [death]). The secondary end point was survival until the end of the trial. Circulating levels of miRNAs were measured by sequencing and polymerase chain reaction. RESULTS: Of the 579 patients (265 men [80.3%]; mean [SD] age, 63 [12] years), 304 patients (52.5%) hada poor neurologic outcomeat 6months. Inthe discovery phase with short RNA sequencing in 50 patients, the brain-enriched miR-124-3p level was identified as a candidate prognostic variable for neurologic outcomes. In the validation cohort of 529 patients, mean (SD) levels of miR-124-3p were higher in patients with a poor outcome (8408 [12 465] copies/μL) compared with patients with a good outcome (1842 [3025] copies/μL; P < .001). The miR-124-3p level was significantly associated with neurologic outcomes in the univariable analysis (odds ratio, 6.72; 95% CI, 4.53-9.97). In multivariable analyses using logistic regression, miR-124-3p levels were independently associated with neurologic outcomes (odds ratio, 1.62; 95% CI, 1.13-2.32). In Cox proportional hazards models, higher levels of miR-124-3p were significantly associated with lower survival (hazard ratio, 1.63; 95% CI, 1.37-1.93). CONCLUSIONS AND RELEVANCE: Levels of miR-124-3p can be used as prognostication tools for neurologic outcome and survival after out-of-hospital cardiac arrest. Thus, miRNA levels may aid in tailoring health care for patients with cardiac arrest.
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10.
  • Devaux, Yvan, et al. (författare)
  • Incremental value of circulating MiR-122-5P to predict outcome after out of hospital cardiac arrest
  • 2017
  • Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 7:10, s. 2555-2564
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale. The value of microRNAs (miRNAs) as biomarkers has been addressed in various clinical contexts. Initial studies suggested that miRNAs, such as the brain-enriched miR-124-3p, might improve outcome prediction after out-of-hospital cardiac arrest. The aim of this study is to determine the prognostic value of miR-122-5p in a large cohort of comatose survivors of out-of-hospital cardiac arrest. Methods. We analyzed 590 patients from the Targeted Temperature Management trial (TTM-trial). Circulating levels of miR-122-5p were measured in serum samples obtained 48 hours after return of spontaneous circulation. The primary end-point was poor neurological outcome at 6 months evaluated by the cerebral performance category score. The secondary end-point was survival at the end of the trial. Results. Forty-eight percent of patients had a poor neurological outcome at 6 months and 43% were dead at the end of the trial. Levels of miR-122-5p were lower in patients with poor neurological outcome compared to patients with good neurological outcome (p < 0.001), independently of targeted temperature management regimen. Levels of miR-122-5p were significant univariate predictors of neurological outcome (odds ratios (OR), 95% confidence intervals (CI): 0.71 [0.57-0.88]). In multivariable analyses, miR-122-5p was an independent predictor of neurological outcome and improved the predictive value of a clinical model including miR-124-3p (integrated discrimination improvement of 0.03 [0.02-0.04]). In Cox proportional hazards models, miR-122-5p was a significant predictor of survival at the end of the trial. Conclusion. Circulating levels of miR-122-5p improve the prediction of outcome after out-of-hospital cardiac arrest.
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11.
  • Devaux, Yvan, et al. (författare)
  • MicroRNAs: new biomarkers and therapeutic targets after cardiac arrest?
  • 2015
  • Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 19:1
  • Forskningsöversikt (refereegranskat)abstract
    • Despite advances in resuscitation medicine, including target temperature management as part of postcardiac arrest care, many patients will have a poor neurological outcome, most often resulting in death. It is a commonly held belief that the ability to prognosticate outcome at an early stage after cardiac arrest would allow subsequent health care delivery to be tailored to individual patients. However, currently available predictive methods and biomarkers lack sufficient accuracy and therefore cannot be generally recommended in clinical practice. MicroRNAs have recently emerged as potential biomarkers of cardiovascular diseases. While the biomarker value of microRNAs for myocardial infarction or heart failure has been extensively studied, less attention has been devoted to their prognostic value after cardiac arrest. This review highlights the recent discoveries suggesting that microRNAs may be useful both to predict outcome and to treat patients after cardiac arrest.
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12.
  • Düring, Joachim, et al. (författare)
  • Copeptin as a marker of outcome after cardiac arrest : A sub-study of the TTM trial
  • 2020
  • Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Arginine vasopressin has complex actions in critically ill patients, involving vasoregulatory status, plasma volume, and cortisol levels. Copeptin, a surrogate marker for arginine vasopressin, has shown promising prognostic features in small observational studies and is used clinically for early rule out of acute coronary syndrome. The objective of this study was to explore the association between early measurements of copeptin, circulatory status, and short-term survival after out-of-hospital cardiac arrest. Methods: Serial blood samples were collected at 24, 48, and 72 h as part of the target temperature management at 33 °C versus 36 °C after cardiac arrest trial, an international multicenter randomized trial where unconscious survivors after out-of-hospital cardiac arrest were allocated to an intervention of 33 or 36 °C for 24 h. Primary outcome was 30-day survival with secondary endpoints circulatory cause of death and cardiovascular deterioration composite; in addition, we examined the correlation with extended the cardiovascular sequential organ failure assessment (eCvSOFA) score. Results: Six hundred ninety patients were included in the analyses, of whom 203 (30.3%) developed cardiovascular deterioration within 24 h, and 273 (39.6%) died within 30 days. Copeptin measured at 24 h was found to be independently associated with 30-day survival, hazard ratio 1.17 [1.06-1.28], p = 0.001; circulatory cause of death, odds ratio 1.03 [1.01-1.04], p = 0.001; and cardiovascular deterioration composite, odds ratio of 1.05 [1.02-1.08], p < 0.001. Copeptin at 24 h was correlated with eCvSOFA score with rho 0.19 [0.12-0.27], p < 0.001. Conclusion: Copeptin is an independent marker of severity of the post cardiac arrest syndrome, partially related to circulatory failure. Trial registration: Clinical Trials, NCT01020916. Registered November 26, 2009.
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  • Düring, Joachim, et al. (författare)
  • Influence of circulatory shock at hospital admission on outcome after out-of-hospital cardiac arrest
  • 2022
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypotension after cardiac arrest could aggravate prolonged hypoxic ischemic encephalopathy. The association of circulatory shock at hospital admission with outcome after cardiac arrest has not been well studied. The objective of this study was to investigate the independent association of circulatory shock at hospital admission with neurologic outcome, and to evaluate whether cardiovascular comorbidities interact with circulatory shock. 4004 adult patients with out-of-hospital cardiac arrest enrolled in the International Cardiac Arrest Registry 2006–2017 were included in analysis. Circulatory shock was defined as a systolic blood pressure below 90 mmHg and/or medical or mechanical supportive measures to maintain adequate perfusion during hospital admission. Primary outcome was cerebral performance category (CPC) dichotomized as good, (CPC 1–2) versus poor (CPC 3–5) outcome at hospital discharge. 38% of included patients were in circulatory shock at hospital admission, 32% had good neurologic outcome at hospital discharge. The adjusted odds ratio for good neurologic outcome in patients without preexisting cardiovascular disease with circulatory shock at hospital admission was 0.60 [0.46–0.79]. No significant interaction was detected with preexisting comorbidities in the main analysis. We conclude that circulatory shock at hospital admission after out-of-hospital cardiac arrest is independently associated with poor neurologic outcome.
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14.
  • Ebner, Florian, et al. (författare)
  • Serum GFAP and UCH-L1 for the prediction of neurological outcome in comatose cardiac arrest patients
  • 2020
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 154, s. 61-68
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Neurological outcome prediction is crucial early after cardiac arrest. Serum biomarkers released from brain cells after hypoxic-ischaemic injury may aid in outcome prediction. The only serum biomarker presently recommended in the European Resuscitation Council prognostication guidelines is neuron-specific enolase (NSE), but NSE has limitations. In this study, we therefore analyzed the outcome predictive accuracy of the serum biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in patients after cardiac arrest. Methods: Serum GFAP and UCH-L1 were collected at 24, 48 and 72 h after cardiac arrest. The primary outcome was neurological function at 6-month follow-up assessed by the cerebral performance category scale (CPC), dichotomized into good (CPC1-2) and poor (CPC3-5). Prognostic accuracies were tested with receiver-operating characteristics by calculating the area under the receiver-operating curve (AUROC) and compared to the AUROC of NSE. Results: 717 patients were included in the study. GFAP and UCH-L1 discriminated between good and poor neurological outcome at all time-points when used alone (AUROC GFAP 0.88–0.89; UCH-L1 0.85–0.87) or in combination (AUROC 0.90–0.91). The combined model was superior to GFAP and UCH-L1 separately and NSE (AUROC 0.75–0.85) at all time-points. At specificities ≥95%, the combined model predicted poor outcome with a higher sensitivity than NSE at 24 h and with similar sensitivities at 48 and 72 h. Conclusion: GFAP and UCH-L1 predicted poor neurological outcome with high accuracy. Their combination may be of special interest for early prognostication after cardiac arrest where it performed significantly better than the currently recommended biomarker NSE.
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  • Ebner, Florian, et al. (författare)
  • The association of partial pressures of oxygen and carbon dioxide with neurological outcome after out-of-hospital cardiac arrest : an explorative International Cardiac Arrest Registry 2.0 study
  • 2020
  • Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 28:1, s. 67-67
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Exposure to extreme arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) following the return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) is common and may affect neurological outcome but results of previous studies are conflicting.METHODS: Exploratory study of the International Cardiac Arrest Registry (INTCAR) 2.0 database, including 2162 OHCA patients with ROSC in 22 intensive care units in North America and Europe. We tested the hypothesis that exposure to extreme PaO2 or PaCO2 values within 24 h after OHCA is associated with poor neurological outcome at discharge. Our primary analyses investigated the association between extreme PaO2 and PaCO2 values, defined as hyperoxemia (PaO2 > 40 kPa), hypoxemia (PaO2 < 8.0 kPa), hypercapnemia (PaCO2 > 6.7 kPa) and hypocapnemia (PaCO2 < 4.0 kPa) and neurological outcome. The secondary analyses tested the association between the exposure combinations of PaO2 > 40 kPa with PaCO2 < 4.0 kPa and PaO2 8.0-40 kPa with PaCO2 > 6.7 kPa and neurological outcome. To define a cut point for the onset of poor neurological outcome, we tested a model with increasing and decreasing PaO2 levels and decreasing PaCO2 levels. Cerebral Performance Category (CPC), dichotomized to good (CPC 1-2) and poor (CPC 3-5) was used as outcome measure.RESULTS: Of 2135 patients eligible for analysis, 700 were exposed to hyperoxemia or hypoxemia and 1128 to hypercapnemia or hypocapnemia. Our primary analyses did not reveal significant associations between exposure to extreme PaO2 or PaCO2 values and neurological outcome (P = 0.13-0.49). Our secondary analyses showed no significant associations between combinations of PaO2 and PaCO2 and neurological outcome (P = 0.11-0.86). There was no PaO2 or PaCO2 level significantly associated with poor neurological outcome. All analyses were adjusted for relevant co-variates.CONCLUSIONS: Exposure to extreme PaO2 or PaCO2 values in the first 24 h after OHCA was common, but not independently associated with neurological outcome at discharge.
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17.
  • Frydland, Martin, et al. (författare)
  • Usefulness of Serum B-Type Natriuretic Peptide Levels in Comatose Patients Resuscitated from Out-of-Hospital Cardiac Arrest to Predict Outcome
  • 2016
  • Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 118:7, s. 998-1005
  • Tidskriftsartikel (refereegranskat)abstract
    • N-terminal pro-B-type natriuretic (NT-proBNP) is expressed in the heart and brain, and serum levels are elevated in acute heart and brain diseases. We aimed to assess the possible association between serum levels and neurological outcome and death in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). Of the 939 comatose OHCA patients enrolled and randomized in the Targeted Temperature Management (TTM) trial to TTM at 33°C or 36°C for 24 hours, 700 were included in the biomarker substudy. Of these, 647 (92%) had serum levels of NT-proBNP measured 24, 48, and 72 hours after return of spontaneous circulation (ROSC). Neurological outcome was evaluated by the Cerebral Performance Category (CPC) score and modified Rankin Scale (mRS) at 6 months. Six hundred thirty-eight patients (99%) had serum NT-proBNP levels ≥125 pg/ml. Patients with TTM at 33°C had significantly lower NT-proBNP serum levels (median 1,472 pg/ml) than those in the 36°C group (1,914 pg/ml) at 24 hours after ROSC, p <0.01 but not at 48 and 72 hours. At 24 hours, an increase in NT-proBNP quartile was associated with death (Plogrank <0.0001). In addition, NT-proBNP serum levels > median were independently associated with poor neurological outcome (odds ratio, ORCPC 2.02, CI 1.34 to 3.05, p <0.001; ORmRS 2.28, CI 1.50 to 3.46, p <0.001) adjusted for potential confounders. The association was diminished at 48 and 72 hours after ROSC. In conclusion, NT-proBNP serum levels are increased in comatose OHCA patients. Furthermore, serum NT-proBNP levels are affected by level of TTM and are associated with death and poor neurological outcome.
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18.
  • Gagnon, David J., et al. (författare)
  • Prophylactic antibiotics are associated with a lower incidence of pneumonia in cardiac arrest survivors treated with targeted temperature management
  • 2015
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 92, s. 154-159
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Prophylactic antibiotics (PRO) reduce the incidence of early-onset pneumonia in comatose patients with structural brain injury, but have not been examined in cardiac arrest survivors undergoing targeted temperature management (TTM). We investigated the effect of PRO on the development of pneumonia in that population. Methods: We conducted a retrospective cohort study comparing patients treated with PRO to those not receiving PRO (no-PRO) using Northern Hypothermia Network registry data. Cardiac arrest survivors >= 18 years of age with a GCS < 8 at hospital admission and treated with TTM at 32-34 degrees C were enrolled in the registry. Differences were analyzed in univariate analyses and with logistic regression models to evaluate independent associations of clinical factors with incidence of pneumonia and good functional outcome. Results: 416 of 1240 patients (33.5%) received PRO. Groups were similar in age, gender, arrest location, initial rhythm, and time from collapse to return of spontaneous circulation. PRO patients had less pneumonia (12.6% vs. 54.9%, p < 0.001) and less sepsis (1.2 vs. 5.7%, p < 0.001) compared to no-PRO patients. ICU length of stay (98 vs. 100 h, p = 0.2) and incidence of a good functional outcome (41.1 vs. 36.6%, p = 0.19) were similar between groups. Backwards stepwise logistic regression demonstrated PRO were independently associated with a lower incidence of pneumonia (OR 0.09, 95% 0.06-0.14, p < 0.001) and a similar incidence of good functional outcome. Conclusions: Prophylactic antibiotics were associated with a reduced incidence of pneumonia but a similar rate of good functional outcome.
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19.
  • Gilje, Patrik, et al. (författare)
  • High-sensitivity troponin-T as a prognostic marker after out-of-hospital cardiac arrest – A targeted temperature management (TTM) trial substudy
  • 2016
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 107, s. 156-161
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim of the study Predicting outcome of unconscious patients after successful resuscitation is challenging and better prognostic markers are highly needed. Ischemic heart disease is a common cause of out-of-hospital cardiac arrest (OHCA). Whether or not high-sensitivity troponin T (hs-TnT) is a prognostic marker among survivors of OHCA with both ischemic and non-ischemic aetiologies remains to be determined. We sought to evaluate the ability of hs-TnT to prognosticate all-cause mortality, death due to cardiovascular causes or multi-organ failure and death due to cerebral causes after OHCA. The influence of the level of target temperature management on hs-TnT as a marker of infarct size was also assessed. Methods A total of 699 patients from the targeted temperature management (TTM) trial were included and hs-TnT was analyzed in blood samples from 24, 48 and 72 h after return of spontaneous circulation (ROSC). The endpoints were 180 day all-cause mortality, death due to cardiovascular causes or multi-organ failure and death due to cerebral causes. Subgroups based on the initial ECG after ROSC (STEMI vs all other ECG presentations) were analyzed. Results Hs-TnT was independently associated with all-cause mortality which was driven by death due to cardiovascular causes or multi-organ failure and not cerebral causes (at 48 h: OR 1.10, CI 1.01–1.20, p < 0.05). Hs-TnT was also an independent predictor of death due to cardiovascular causes or multi-organ failure (at 48 h: OR 1.13, CI 1.01–1.26, p < 0.05). In patients with STEMI, hs-TnT was independently associated with death due to cardiovascular causes or multi-organ failure (at 48 h: OR 1.47, CI 1.10–1.95, p < 0.01). Targeted temperature management at 33 °C was not associated with hs-TnT compared to 36 °C. Conclusions After OHCA due to both ischemic and non-ischemic causes, hs-TnT is an independent marker of both all-cause mortality and death due to cardiovascular causes or multi-organ failure. Targeted temperature management at 33 °C did not reduce hs-TnT compared to 36 °C. Hs-TnT may be a marker of poor prognosis after OHCA and this should be taken into consideration in patients that present with high troponin levels. Trial registration The TTM-trial is registered and accessible at Clinicaltrials.gov (identifier: NCT01020916).
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20.
  • Gilje, Patrik, et al. (författare)
  • The association between plasma miR-122-5p release pattern at admission and all-cause mortality or shock after out-of-hospital cardiac arrest
  • 2019
  • Ingår i: Biomarkers. - 1354-750X. ; 24:1, s. 29-35
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Data suggests that the plasma levels of the liver-specific miR-122-5p might both be a marker of cardiogenic shock and a prognostic marker of out-of-hospital cardiac arrest (OHCA). Our aim was to characterize plasma miR-122-5p at admission after OHCA and to assess the association between miR-122-5p and relevant clinical factors such all-cause mortality and shock at admission after OHCA. Methods: In the pilot trial, 10 survivors after OHCA were compared to 10 age- and sex-matched controls. In the main trial, 167 unconscious survivors of OHCA from the Targeted Temperature Management (TTM) trial were included. Results: In the pilot trial, plasma miR-122-5p at admission after OHCA was 400-fold elevated compared to controls. In the main trial, plasma miR-122-5p at admission was independently associated with lactate and bystander cardiopulmonary resuscitation. miR-122-5p at admission was not associated with shock at admission (p = 0.14) or all-cause mortality (p = 0.35). Target temperature (33 °C vs 36 °C) was not associated with miR-122-5p levels at any time point. Conclusions: After OHCA, miR-122-5p demonstrated a marked acute increase in plasma and was independently associated with lactate and bystander resuscitation. However, miR-122-5p at admission was not associated with all-cause mortality or shock at admission.
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21.
  • Glover, Guy W., et al. (författare)
  • Intravascular versus surface cooling for targeted temperature management after out-of-hospital cardiac arrest - an analysis of the TTM trial data
  • 2016
  • Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Targeted temperature management is recommended after out-of-hospital cardiac arrest and may be achieved using a variety of cooling devices. This study was conducted to explore the performance and outcomes for intravascular versus surface devices for targeted temperature management after out-of-hospital cardiac arrest. Method: A retrospective analysis of data from the Targeted Temperature Management trial. N=934. A total of 240 patients (26%) managed with intravascular versus 694 (74%) with surface devices. Devices were assessed for speed and precision during the induction, maintenance and rewarming phases in addition to adverse events. All-cause mortality, as well as a composite of poor neurological function or death, as evaluated by the Cerebral Performance Category and modified Rankin scale were analysed. Results: For patients managed at 33°C there was no difference between intravascular and surface groups in the median time taken to achieve target temperature (210 [interquartile range (IQR) 180] minutes vs. 240 [IQR 180] minutes, p=0.58), maximum rate of cooling (1.0 [0.7] vs. 1.0 [0.9] °C/hr, p=0.44), the number of patients who reached target temperature (within 4hours (65% vs. 60%, p=0.30); or ever (100% vs. 97%, p=0.47), or episodes of overcooling (8% vs. 34%, p=0.15). In the maintenance phase, cumulative temperature deviation (median 3.2 [IQR 5.0] °C hr vs. 9.3 [IQR 8.0] °C hr, p=<0.001), number of patients ever out of range (57.0% vs. 91.5%, p=0.006) and median time out of range (1 [IQR 4.0] hours vs. 8.0 [IQR 9.0] hours, p=<0.001) were all significantly greater in the surface group although there was no difference in the occurrence of pyrexia. Adverse events were not different between intravascular and surface groups. There was no statistically significant difference in mortality (intravascular 46.3% vs. surface 50.0%; p=0.32), Cerebral Performance Category scale 3-5 (49.0% vs. 54.3%; p=0.18) or modified Rankin scale 4-6 (49.0% vs. 53.0%; p=0.48). Conclusions: Intravascular and surface cooling was equally effective during induction of mild hypothermia. However, surface cooling was associated with less precision during the maintenance phase. There was no difference in adverse events, mortality or poor neurological outcomes between patients treated with intravascular and surface cooling devices. Trial registration: TTM trial ClinicalTrials.gov number https://clinicaltrials.gov/ct2/show/NCT01020916 NCT01020916; 25 November 2009
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22.
  • Grindegård, Linnéa, et al. (författare)
  • Association Between EEG Patterns and Serum Neurofilament Light After Cardiac Arrest: A Post Hoc Analysis of the TTM Trial.
  • 2022
  • Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 98:24
  • 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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23.
  • Harhash, Ahmed A., et al. (författare)
  • Incidence of cardiac interventions and associated cardiac arrest outcomes in patients with nonshockable initial rhythms and no ST elevation post resuscitation
  • 2021
  • Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 167, s. 188-197
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Out of Hospital Cardiac arrest (OHCA) survivors with ST elevation (STE) with or without shockable rhythms often benefit from coronary angiography (CAG) and, if indicated, percutaneous coronary intervention (PCI). However, the benefits of CAG and PCI in OHCA survivors with nonshockable rhythms (PEA/asystole) and no STE are debated.Methods: Using the International Cardiac Arrest Registry (INTCAR 2.0), representing 44 centers in the US and Europe, comatose OHCA survivors with known presenting rhythms and post resuscitation ECGs were identified. Survival to hospital discharge, neurological recovery on discharge, and impact of CAG with or without PCI on such outcome were assessed and compared with other groups (shockable rhythms with or without STE).Results: Total of 2113 OHCA survivors were identified and described as; nonshockable/no STE (Nsh-NST) (n = 940, 44.5%), shockable/no STE (Sh-NST) (n = 716, 33.9%), nonshockable/STE (Nsh-ST) (n = 110, 5.2%), and shockable/STE (Sh-ST) (n = 347, 16.4%). Of Nsh-NST, 13.7% (129) were previously healthy before CA and only 17.3% (161) underwent CAG; of those, 30.4% (52) underwent PCI. A total of 18.6% (174) Nsh-NST patients survived to hospital discharge, with 57.5% (100) of such survivors having good neurological recovery (cerebral performance category 1 or 2) on discharge. Coronary angiography was associated with improved odds for survival and neurological recovery among all groups, including those with NSh-NST.Conclusions: Nonshockable initial rhythms with no ST elevation post resuscitation was the most common presentation after OHCA. Although most of these patients did not undergo coronary angiography, among those who did, 1 in 4 patients had a culprit lesion and underwent revascularization. Invasive CAG should be at least considered for all OHCA survivors, including those with nonshockable rhythms and no ST elevation post resuscitation.
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24.
  • Harhash, Ahmed A., et al. (författare)
  • Risk Stratification Among Survivors of Cardiac Arrest Considered for Coronary Angiography
  • 2021
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 77:4, s. 360-371
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe American College of Cardiology Interventional Council published consensus-based recommendations to help identify resuscitated cardiac arrest patients with unfavorable clinical features in whom invasive procedures are unlikely to improve survival.ObjectivesThis study sought to identify how many unfavorable features are required before prognosis is significantly worsened and which features are most impactful in predicting prognosis.MethodsUsing the INTCAR (International Cardiac Arrest Registry), the impact of each proposed “unfavorable feature” on survival to hospital discharge was individually analyzed. Logistic regression was performed to assess the association of such unfavorable features with poor outcomes.ResultsSeven unfavorable features (of 10 total) were captured in 2,508 patients successfully resuscitated after cardiac arrest (ongoing cardiopulmonary resuscitation and noncardiac etiology were exclusion criteria in our registry). Chronic kidney disease was used in lieu of end-stage renal disease. In total, 39% survived to hospital discharge. The odds ratio (OR) of survival to hospital discharge for each unfavorable feature was as follows: age >85 years OR: 0.30 (95% CI: 0.15 to 0.61), time-to-ROSC >30 min OR: 0.30 (95% CI: 0.23 to 0.39), nonshockable rhythm OR: 0.39 (95% CI: 0.29 to 0.54), no bystander cardiopulmonary resuscitation OR: 0.49 (95% CI: 0.38 to 0.64), lactate >7 mmol/l OR: 0.50 (95% CI: 0.40 to 0.63), unwitnessed arrest OR: 0.58 (95% CI: 0.44 to 0.78), pH <7.2 OR: 0.78 (95% CI: 0.63 to 0.98), and chronic kidney disease OR: 0.96 (95% CI: 0.70 to 1.33). The presence of any 3 or more unfavorable features predicted <40% survival. Presence of the 3 strongest risk factors (age >85 years, time-to-ROSC >30 min, and non-ventricular tachycardia/ventricular fibrillation) together or ≥6 unfavorable features predicted a ≤10% chance of survival to discharge.ConclusionsPatients successfully resuscitated from cardiac arrest with 6 or more unfavorable features have a poor long-term prognosis. Delaying or even forgoing invasive procedures in such patients is reasonable.
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25.
  • 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.)
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26.
  • Hovdenes, Jan, et al. (författare)
  • A low body temperature on arrival at hospital following out-of-hospital-cardiac-arrest is associated with increased mortality in the TTM-study
  • 2016
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 107, s. 102-106
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim To investigate the association of temperature on arrival to hospital after out-of-hospital-cardiac arrest (OHCA) with the primary outcome of mortality, in the targeted temperature management (TTM) trial. Methods The TTM trial randomized 939 patients to TTM at 33 or 36 °C for 24 h. Patients were categorized according to their recorded body temperature on arrival and also categorized to groups of patients being actively cooled or passively rewarmed. Results OHCA patients having a temperature ≤34.0 °C on arrival at hospital had a significantly higher mortality compared to the OHCA patients with a higher temperature on arrival. A low body temperature on arrival was associated with a longer time to return of spontaneous circulation (ROSC) and duration of transport time to hospital. Patients who were actively cooled or passively rewarmed during the first 4 h had similar mortality. In a multivariate logistic regression model mortality was significantly related to time from OHCA to ROSC, time from OHCA to advanced life support (ALS), age, sex and first registered rhythm. None of the temperature related variables (included the TTM-groups) were significantly related to mortality. Conclusion OHCA patients with a temperature ≤34.0 °C on arrival have a higher mortality than patients with a temperature ≥34.1 °C on arrival. A low temperature on arrival is associated with a long time to ROSC. Temperature changes and TTM-groups were not associated with mortality in a regression model.
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27.
  • Johnsson, Jesper, et al. (författare)
  • Functional outcomes associated with varying levels of targeted temperature management after out-of-hospital cardiac arrest — An INTCAR2 registry analysis
  • 2020
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 146, s. 229-236
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) has been recommended in international guidelines since 2005. The TTM-trial published in 2013 showed no difference in survival or neurological outcome for patients randomised to 33 °C or 36 °C, and many hospitals have changed practice. The optimal utilization of TTM is still debated. This study aimed to analyse if a difference in temperature goal was associated with outcome in an unselected international registry population. Methods: This is a retrospective observational study based on a prospective registry — the International Cardiac Arrest Registry 2. Patients were categorized as receiving TTM in the lower range at 32–34 °C (TTM-low) or at 35–37 °C (TTM-high). Primary outcome was good functional status defined as cerebral performance category (CPC) of 1–2 at hospital discharge and secondary outcome was adverse events related to TTM. A logistic regression model was created to evaluate the independent effect of temperature by correcting for clinical and demographic factors associated with outcome. Results: Of 1710 patients included, 1242 (72,6%) received TTM-low and 468 (27,4%) TTM-high. In patients receiving TTM-low, 31.3% survived with good outcome compared to 28.8% in the TTM-high group. There was no significant association between temperature and outcome (p = 0.352). In analyses adjusted for baseline differences the OR for a good outcome with TTM-low was 1.27, 95% CI (0.94–1.73). Haemodynamic instability leading to discontinuation of TTM was more common in TTM-low. Conclusions: No significant difference in functional outcome at hospital discharge was found in patients receiving lower- versus higher targeted temperature management.
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28.
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29.
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30.
  • Lagebrant, Alice, et al. (författare)
  • Brain injury markers in blood associate with generalised oedema on computed tomography after cardiac arrest
  • 2021
  • Ingår i: - : Springer Science and Business Media LLC. ; , s. 203-204
  • Konferensbidrag (refereegranskat)abstract
    • Introduction. According to the 2021 ERC/ESICM guideline recommen-dations, elevated neuron-specific enolase [NSE] levels as well as diffuseand extensive anoxic damage on neuroimaging are predictors of poorneurological outcome after cardiac arrest.(1) We previously describedthat NSE is elevated in patients with generalised oedema on com-puted tomography [CT]. (2).Objectives. In this study, we aim to examine the novel brain injurymarkers serum neurofilament light [NFL], glial fibrillary acidic protein[GFAP] and total-tau [tau] to predict the presence of generalised brainoedema.Methods. Retrospective analysis of patients examined with CT onclinical indication within the Target Temperature Management afterout-of-hospital cardiac arrest [TTM] trial. (2,3) Serum samples fromthe biobank sub study were prospectively collected at 48 h post arrestand analysed after trial completion as published. (4–7) The neuronalmarker NSE, the neuroaxonal injury markers NFL and tau and theastrocytic injury marker GFAP were correlated with the presence ofgeneralised oedema on CT, assessed by local radiologists through vis-ual evaluation. The prognostic accuracy of NSE ≥ 60 ug/l for predictinggeneralised oedema was also analysed.Results. 192 patients had data available on all four biomarkers at 48 hand were examined with CT < 168 h post arrest. Brain injury markerswere significantly higher in patients with generalised oedema as com-pared to patients without oedema on CT scans performed 24–168 hafter ROSC (p < 0.001) (Fig. 1A–D). For CT scans performed < 24 h, onlyNSE levels showed a significant correlation (p < 0.05). Biomarkers pre -dicted generalised oedema with area under the receiver operatingcharacteristics curve [AUC] 67.5–73.2% for CT scans performed < 24 h(n = 111), with no statistically significant difference between themarkers ( Fig. 2A). For scans performed 24–168 h (n = 81) AUC for pre -dicting generalised oedema was 78.1%-82.9%, with no statisticallysignificant difference between the markers. NSE ≥ 60 ug/l at 48 h, asrecommended by guidelines, predicted generalised oedema with 81%(95%CI 67–90%) sensitivity and 77% (95%CI 62–87%) specificity.Conclusion. Concentrations of all evaluated brain injury markerswere significantly higher in patients with generalised oedema on CTperformed after the first 24 h post arrest. Biomarker concentrationsindicate whether generalised oedema on CT is likely and may thus beclinically useful for deciding if a CT scan is sufficient for prognostica-tion or if a MRI is more appropriate.
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31.
  • Lagebrant, Alice, et al. (författare)
  • Brain injury markers in blood predict signs of hypoxic ischaemic encephalopathy on head computed tomography after cardiac arrest
  • 2023
  • Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 184
  • 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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32.
  • Lybeck, Anna, et al. (författare)
  • Time to awakening after cardiac arrest and the association with target temperature management
  • 2018
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 126, s. 166-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Target temperature management (TTM) at 32-36 °C is recommended in unconscious survivors of cardiac arrest. This study reports awakening in the TTM-trial. Our predefined hypotheses were that time until awakening correlates with long-term neurological outcome and is not affected by level of TTM. Methods: Post-hoc analysis of time until awakening after cardiac arrest, its association with long-term (180-days) neurological outcome and predictors of late awakening (day 5 or later. ). The trial randomized 939 comatose survivors to TTM at 33 °C or 36 °C with strict criteria for withdrawal of life-sustaining therapies. Administered sedation in the treatment groups was compared. Awakening was defined as a Glasgow Coma Scale motor score 6. Results: 496 patients had registered day of awakening in the ICU, another 43 awoke after ICU discharge. Good neurological outcome was more common in early (275/308, 89%) vs late awakening (142/188, 76%), p < 0.001. Awakening occurred later in TTM33 than in TTM36 (p = 0.002) with no difference in neurological outcome, or cumulative doses of sedative drugs at 12, 24 or 48 h. TTM33 (p = 0.006), clinical seizures (p = 0.004), and lower GCS-M on admission (p = 0.03) were independent predictors of late awakening. Conclusion: Late awakening is common and often has a good neurological outcome. Time to awakening was longer in TTM33 than in TTM36, this difference could not be attributed to differences in sedative drugs administered during the first 48 h.
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33.
  • Mattsson, Niklas, et al. (författare)
  • Serum tau and neurological outcome in cardiac arrest.
  • 2017
  • Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 82:5, s. 665-675
  • 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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34.
  • May, Teresa L., et al. (författare)
  • Early withdrawal of life support after resuscitation from cardiac arrest is common and may result in additional deaths
  • 2019
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 139, s. 308-313
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: “Early” withdrawal of life support therapies (eWLST) within the first 3 calendar days after resuscitation from cardiac arrest (CA) is discouraged. We evaluated a prospective multicenter registry of patients admitted to hospitals after resuscitation from CA to determine predictors of eWLST and estimate its impact on outcomes. Methods: CA survivors enrolled from 2012–2017 in the International Cardiac Arrest Registry (INTCAR) were included. We developed a propensity score for eWLST and matched a cohort with similar probabilities of eWLST who received ongoing care. The incidence of good outcome (Cerebral Performance Category of 1 or 2) was measured across deciles of eWLST in the matched cohort. Results: 2688 patients from 24 hospitals were included. Median ischemic time was 20 (IQR 11, 30) minutes, and 1148 (43%) had an initial shockable rhythm. Withdrawal of life support occurred in 1162 (43%) cases, with 459 (17%) classified as eWLST. Older age, initial non-shockable rhythm, increased ischemic time, shock on admission, out-of-hospital arrest, and admission in the United States were each independently associated with eWLST. All patients with eWLST died, while the matched cohort, good outcome occurred in 21% of patients. 19% of patients within the eWLST group were predicted to have a good outcome, had eWLST not occurred. Conclusions: Early withdrawal of life support occurs frequently after cardiac arrest. Although the mortality of patients matched to those with eWLST was high, these data showed excess mortality with eWLST.
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35.
  • May, Teresa L., et al. (författare)
  • Variability in functional outcome and treatment practices by treatment center after out-of-hospital cardiac arrest : analysis of International Cardiac Arrest Registry
  • 2019
  • Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 45:5, s. 637-646
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposeFunctional outcomes vary between centers after out-of-hospital cardiac arrest (OHCA) and are partially explained by pre-existing health status and arrest characteristics, while the effects of in-hospital treatments on functional outcome are less understood. We examined variation in functional outcomes by center after adjusting for patient- and arrest-specific characteristics and evaluated how in-hospital management differs between high- and low-performing centers.MethodsAnalysis of observational registry data within the International Cardiac Arrest Registry was used to perform a hierarchical model of center-specific risk standardized rates for good outcome, adjusted for demographics, pre-existing functional status, and arrest-related factors with treatment center as a random effect variable. We described the variability in treatments and diagnostic tests that may influence outcome at centers with adjusted rates significantly above and below registry average.ResultsA total of 3855 patients were admitted to an ICU following cardiac arrest with return of spontaneous circulation. The overall prevalence of good outcome was 11-63% among centers. After adjustment, center-specific risk standardized rates for good functional outcome ranged from 0.47 (0.37-0.58) to 0.20 (0.12-0.26). High-performing centers had faster time to goal temperature, were more likely to have goal temperature of 33 degrees C, more likely to perform unconscious cardiac catheterization and percutaneous coronary intervention, and had differing prognostication practices than low-performing centers.ConclusionsCenter-specific differences in outcomes after OHCA after adjusting for patient-specific factors exist. This variation could partially be explained by in-hospital management differences. Future research should address the contribution of these factors to the differences in outcomes after resuscitation.
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36.
  • Moseby-Knappe, Marion, et al. (författare)
  • Performance of a guideline-recommended algorithm for prognostication of poor neurological outcome after cardiac arrest
  • 2020
  • Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 46:10, s. 1852-62
  • 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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37.
  • Moseby-Knappe, Marion, et al. (författare)
  • Serum Neurofilament Light Chain for Prognosis of Outcome after Cardiac Arrest
  • 2019
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:1, s. 64-64
  • 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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38.
  • Nielsen, Niklas, et al. (författare)
  • Adverse events and their relation to mortality in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia
  • 2011
  • Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 39:1, s. 57-64
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To investigate the association between adverse events recorded during critical care and mortality in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia. Design: Prospective, observational, registry-based study. Setting: Twenty-two hospitals in Europe and the United States. Patients: Between October 2004 and October 2008, 765 patients were included. Interventions: None. Measurements and Main Results: Arrhythmias (7%-14%), pneumonia (48%), metabolic and electrolyte disorders (5%-37%), and seizures (24%) were common adverse events in the critical care period in cardiac arrest patients treated with therapeutic hypothermia, whereas sepsis (4%) and bleeding (6%) were less frequent. Sustained hyperglycemia (blood glucose >8 mmol/L for >4 hrs; odds ratio 2.3, 95% confidence interval 1.6-3.6, p < .001) and seizures treated with anticonvulsants (odds ratio 4.8, 95% confidence interval 2.9-8.1, p < .001) were associated with increased mortality in a multivariate model. An increased frequency of bleeding and sepsis occurred after invasive procedures (coronary angiography, intravascular devices for cooling, intra-aortic balloon pump), but bleeding and sepsis were not associated with increased mortality (odds ratio 1.0, 95% confidence interval 0.46-2.2, p = .91, and odds ratio 0.30, 95% confidence interval 0.12-0.79, p = .01, respectively). Conclusions: Adverse events were common after out-of-hospital cardiac arrest. Sustained hyperglycemia and seizures treated with anticonvulsants were associated with increased mortality. Bleeding and infection were more common after invasive procedures, but these adverse events were not associated with increased mortality in our study.
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39.
  • Nielsen, Niklas, et al. (författare)
  • Detailed statistical analysis plan for the target temperature management after out-of-hospital cardiac arrest trial
  • 2013
  • Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Animal experimental studies and previous randomized trials suggest an improvement in mortality and neurological function with temperature regulation to hypothermia after cardiac arrest. According to a systematic review, previous trials were small, had a risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management (TTM) strategy is not known. To prevent outcome reporting bias, selective reporting and data-driven results, we present the a priori defined detailed statistical analysis plan as an update to the previously published outline of the design and rationale for the TTM trial. Methods: The TTM trial is an investigator-initiated, multicenter, international, randomized, parallel-group, and assessor-blinded clinical trial of temperature management in 950 adult unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients are randomized to a TTM of either 33 degrees C or 36 degrees C after return of spontaneous circulation. The primary outcome is all-cause mortality at maximal follow-up (until end of the trial and a minimum of 180 days). The main secondary outcomes are the composite outcome of all-cause mortality and poor neurological function (Cerebral Performance Category (CPC) 3 and 4, and modified Rankin Scale (mRS) 4 and 5) at hospital discharge and at 180 days; and assessment of safety and harm: bleeding, infections, electrolyte and metabolic disorders, seizures, cardiac arrhythmia, and renal replacement therapy. Conclusion: The TTM trial investigates potential benefit and harm of two target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.
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40.
  • Nielsen, Niklas, et al. (författare)
  • Target temperature management after out-of-hospital cardiac arrest-a randomized, parallel-group, assessor-blinded clinical trial-rationale and design
  • 2012
  • Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 163:4, s. 541-548
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Experimental animal studies and previous randomized trials suggest an improvement in mortality and neurologic function with induced hypothermia after cardiac arrest. International guidelines advocate the use of a target temperature management of 32 degrees C to 34 degrees C for 12 to 24 hours after resuscitation from out-of-hospital cardiac arrest. A systematic review indicates that the evidence for recommending this intervention is inconclusive, and the GRADE level of evidence is low. Previous trials were small, with high risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management strategy is not known. less thanbrgreater than less thanbrgreater thanMethods The TTM trial is an investigator-initiated, international, randomized, parallel-group, and assessor-blinded clinical trial designed to enroll at least 850 adult, unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized to a target temperature management of either 33 degrees C or 36 degrees C after return of spontaneous circulation. In both groups, the intervention will last 36 hours. The primary outcome is all-cause mortality at maximal follow-up. The main secondary outcomes are the composite outcome of all-cause mortality and poor neurologic function (cerebral performance categories 3 and 4) at hospital discharge and at 180 days, cognitive status and quality of life at 180 days, assessment of safety and harm. less thanbrgreater than less thanbrgreater thanDiscussion The TTM trial will investigate potential benefit and harm of 2 target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.
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41.
  • Nielsen, Niklas, et al. (författare)
  • Targeted Temperature Management at 33 degrees C versus 36 degrees C after Cardiac Arrest
  • 2013
  • Ingår i: New England Journal of Medicine. - 0028-4793. ; 369:23, s. 2197-2206
  • 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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42.
  • Oddo, Mauro, et al. (författare)
  • Quantitative versus standard pupillary light reflex for early prognostication in comatose cardiac arrest patients : an international prospective multicenter double-blinded study
  • 2018
  • Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 44:12, s. 2102-2111
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To assess the ability of quantitative pupillometry [using the Neurological Pupil index (NPi)] to predict an unfavorable neurological outcome after cardiac arrest (CA). Methods: We performed a prospective international multicenter study (10 centers) in adult comatose CA patients. Quantitative NPi and standard manual pupillary light reflex (sPLR)—blinded to clinicians and outcome assessors—were recorded in parallel from day 1 to 3 after CA. Primary study endpoint was to compare the value of NPi versus sPLR to predict 3-month Cerebral Performance Category (CPC), dichotomized as favorable (CPC 1–2: full recovery or moderate disability) versus unfavorable outcome (CPC 3–5: severe disability, vegetative state, or death). Results: At any time between day 1 and 3, an NPi ≤ 2 (n = 456 patients) had a 51% (95% CI 49–53) negative predictive value and a 100% positive predictive value [PPV; 0% (0–2) false-positive rate], with a 100% (98–100) specificity and 32% (27–38) sensitivity for the prediction of unfavorable outcome. Compared with NPi, sPLR had significantly lower PPV and significantly lower specificity (p < 0.001 at day 1 and 2; p = 0.06 at day 3). The combination of NPi ≤ 2 with bilaterally absent somatosensory evoked potentials (SSEP; n = 188 patients) provided higher sensitivity [58% (49–67) vs. 48% (39–57) for SSEP alone], with comparable specificity [100% (94–100)]. Conclusions: Quantitative NPi had excellent ability to predict an unfavorable outcome from day 1 after CA, with no false positives, and significantly higher specificity than standard manual pupillary examination. The addition of NPi to SSEP increased sensitivity of outcome prediction, while maintaining 100% specificity.
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43.
  • Peluso, Lorenzo, et al. (författare)
  • Neurological pupil index and its association with other prognostic tools after cardiac arrest : A post hoc analysis
  • 2022
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 179, s. 259-266
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: We evaluated the concordance of the Neurological pupil Index (NPi) with other predictors of outcome after cardiac arrest (CA). Methods: Post hoc analysis of a prospective, international, multicenter study including adult CA patients. Predictors of unfavorable outcome (UO, Cerebral Performance Category of 3–5 at 3 months) included: a) worst NPi ≤ 2; b) presence of discontinuous encephalography (EEG) background; c) bilateral absence of N20 waves on somatosensory evoked potentials (N20ABS); d) peak neuron-specific enolase (NSE) blood levels > 60 mcg/L; e) myoclonus, which were all tested in a subset of patients who underwent complete multimodal assessment (MMM). Results: A total of 269/456 (59 %) patients had UO and 186 (41 %) underwent MMM. The presence of myoclonus was assessed in all patients, EEG in 358 (78 %), N20 in 186 (41 %) and NSE measurement in 228 (50 %). Patients with discontinuous EEG, N20ABS or high NSE had a higher proportion of worst NPi ≤ 2. The accuracy for NPi to predict a discontinuous EEG, N20ABS, high NSE and the presence of myoclonus was moderate. Concordance with NPi ≤ 2 was high for NSE, and moderate for discontinuous EEG and N20ABS. Also, the higher the number of concordant predictors of poor outcome, the lower the observed NPi. Conclusions: In this study, NPi ≤ 2 had moderate to high concordance with other unfavorable outcome prognosticators of hypoxic-ischemic brain injury. This indicates that NPi measurement could be considered as a valid tool for coma prognostication after cardiac arrest.
  •  
44.
  • Salgado-Somoza, Antonio, et al. (författare)
  • Non-coding RNAs to aid in neurological prognosis after cardiac arrest
  • 2018
  • Ingår i: Non-coding RNA. - : MDPI AG. - 2311-553X. ; 4:4
  • Forskningsöversikt (refereegranskat)abstract
    • Cardiovascular disease in general, and sudden cardiac death in particular, have an enormous socio-economic burden worldwide. Despite significant efforts to improve cardiopulmonary resuscitation, survival rates remain low. Moreover, patients who survive to hospital discharge have a high risk of developing severe physical or neurological symptoms. Being able to predict outcomes after resuscitation from cardiac arrest would make it possible to tailor healthcare approaches, thereby maximising efforts for those who would mostly benefit from aggressive therapy. However, the identification of patients at risk of poor recovery after cardiac arrest is still a challenging task which could be facilitated by novel biomarkers. Recent investigations have recognised the potential of non-coding RNAs to aid in outcome prediction after cardiac arrest. In this review, we summarize recent discoveries and propose a handful of novel perspectives for the use of non-coding RNAs to predict outcome after cardiac arrest, discussing their use for precision medicine.
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45.
  • Seder, David B., et al. (författare)
  • Neurologic Outcomes and Postresuscitation Care of Patients With Myoclonus Following Cardiac Arrest
  • 2015
  • Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 43:5, s. 965-972
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To evaluate the outcomes of cardiac arrest survivors with myoclonus receiving modern postresuscitation care. Design: Retrospective review of registry data. Setting: Cardiac arrest receiving centers in Europe and the United States from 2002 to 2012. Patients: Two thousand five hundred thirty-two cardiac arrest survivors 18 years or older enrolled in the International Cardiac Arrest Registry. Interventions: None. Measurements and Main Results: Eighty-eight percent of patients underwent therapeutic hypothermia and 471 (18%) exhibited myoclonus. Patients with myoclonus had longer time to professional cardiopulmonary resuscitation (8.6 vs 7.0 min; p < 0.001) and total ischemic time (25.6 vs 22.3 min; p < 0.001) and less often presented with ventricular tachycardia/ventricular fibrillation, a witnessed arrest, or had bystander cardiopulmonary resuscitation. Electroencephalography demonstrated myoclonus with epileptiform activity in 209 of 374 (55%), including status epilepticus in 102 of 374 (27%). Good outcome (Cerebral Performance Category 1-2) at hospital discharge was noted in 9% of patients with myoclonus, less frequently in myoclonus with epileptiform activity (2% vs 15%; p < 0.001). Patients with myoclonus with good outcome were younger (53.7 vs 62.7 yr; p < 0.001), had more ventricular tachycardia/ventricular fibrillation (81% vs 46%; p < 0.001), shorter ischemic time (18.9 vs 26.4 min; p = 0.003), more witnessed arrests (91% vs 77%; p = 0.02), and fewer "do-not-resuscitate" orders (7% vs 78%; p < 0.001). Life support was withdrawn in 330 of 427 patients (78%) with myoclonus and poor outcome, due to neurological futility in 293 of 330 (89%), at 5 days (3-8 d) after resuscitation. With myoclonus and good outcome, median ICU length of stay was 8 days (5-11 d) and hospital length of stay was 14.5 days (9-22 d). Conclusions: Nine percent of cardiac arrest survivors with myoclonus after cardiac arrest had good functional outcomes, usually in patients without associated epileptiform activity and after prolonged hospitalization. Deaths occurred early and primarily after withdrawal of life support. It is uncertain whether prolonged care would yield a higher percentage of good outcomes, but myoclonus of itself should not be considered a sign of futility.
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46.
  •  
47.
  • Stammet, Pascal, et al. (författare)
  • Protein S100 as outcome predictor after out-of-hospital cardiac arrest and targeted temperature management at 33 °C and 36 °C
  • 2017
  • Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to investigate the diagnostic performance of S100 as an outcome predictor after out-of-hospital cardiac arrest (OHCA) and the potential influence of two target temperatures (33 °C and 36 °C) on serum levels of S100. Methods: This is a substudy of the Target Temperature Management after Out-of-Hospital Cardiac Arrest (TTM) trial. Serum levels of S100 were measured a posteriori in a core laboratory in samples collected at 24, 48, and 72 h after OHCA. Outcome at 6 months was assessed using the Cerebral Performance Categories Scale (CPC 1-2 = good outcome, CPC 3-5 = poor outcome). Results: We included 687 patients from 29 sites in Europe. Median S100 values were higher in patients with a poor outcome at 24, 48, and 72 h: 0.19 (IQR 0.10-0.49) versus 0.08 (IQR 0.06-0.11) μg/ml, 0.16 (IQR 0.10-0.44) versus 0.07 (IQR 0.06-0.11) μg/L, and 0.13 (IQR 0.08-0.26) versus 0.06 (IQR 0.05-0.09) μg/L (p < 0.001), respectively. The ability to predict outcome was best at 24 h with an AUC of 0.80 (95% CI 0.77-0.83). S100 values were higher at 24 and 72 h in the 33 °C group than in the 36 °C group (0.12 [0.07-0.22] versus 0.10 [0.07-0.21] μg/L and 0.09 [0.06-0.17] versus 0.08 [0.05-0.10], respectively) (p < 0.02). In multivariable analyses including baseline variables and the allocated target temperature, the addition of S100 improved the AUC from 0.80 to 0.84 (95% CI 0.81-0.87) (p < 0.001), but S100 was not an independent outcome predictor. Adding S100 to the same model including neuron-specific enolase (NSE) did not further improve the AUC. Conclusions: The allocated target temperature did not affect S100 to a clinically relevant degree. High S100 values are predictive of poor outcome but do not add value to present prognostication models with or without NSE. S100 measured at 24 h and afterward is of limited value in clinical outcome prediction after OHCA. Trial registration: ClinicalTrials.gov identifier: NCT01020916. Registered on 25 November 2009.
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48.
  • Stefanizzi, Francesca M., et al. (författare)
  • Circular RNAs to predict clinical outcome after cardiac arrest
  • 2022
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cardiac arrest (CA) represents the third leading cause of death worldwide. Among patients resuscitated and admitted to hospital, death and severe neurological sequelae are frequent but difficult to predict. Blood biomarkers offer clinicians the potential to improve prognostication. Previous studies suggest that circulating non-coding RNAs constitute a reservoir of novel biomarkers. Therefore, this study aims to identify circulating circular RNAs (circRNAs) associated with clinical outcome after CA. Results: Whole blood samples obtained 48 h after return of spontaneous circulation in 588 survivors from CA enrolled in the Target Temperature Management trial (TTM) were used in this study. Whole transcriptome RNA sequencing in 2 groups of 23 sex-matched patients identified 28 circRNAs associated with neurological outcome and survival. The circRNA circNFAT5 was selected for further analysis using quantitative PCR. In the TTM-trial (n = 542), circNFAT5 was upregulated in patients with poor outcome as compared to patients with good neurological outcome (p < 0.001). This increase was independent of TTM regimen and sex. The adjusted odds ratio of circNFAT5 to predict neurological outcome was 1.39 [1.07–1.83] (OR [95% confidence interval]). CircNFAT5 predicted 6-month survival with an adjusted hazard ratio of 1.31 [1.13–1.52]. Conclusion: We identified circulating circRNAs associated with clinical outcome after CA, among which circNFAT5 may have potential to aid in predicting neurological outcome and survival when used in combination with established biomarkers of CA.
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49.
  • Stefanizzi, Francesca Maria, et al. (författare)
  • Circulating Levels of Brain-Enriched MicroRNAs Correlate with Neuron Specific Enolase after Cardiac Arrest-A Substudy of the Target Temperature Management Trial
  • 2020
  • Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 21:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Outcome prognostication after cardiac arrest (CA) is challenging. Current multimodal prediction approaches would benefit from new biomarkers. MicroRNAs constitute a novel class of disease markers and circulating levels of brain-enriched ones have been associated with outcome after CA. To determine whether these levels reflect the extent of brain damage in CA patients, we assessed their correlation with neuron-specific enolase (NSE), a marker of brain damage. Blood samples taken 48 h after return of spontaneous circulation from two groups of patients from the Targeted Temperature Management trial were used. Patients were grouped depending on their neurological outcome at six months. Circulating levels of microRNAs were assessed by sequencing. NSE was measured at the same time-point. Among the 673 microRNAs detected, brain-enriched miR9-3p, miR124-3p and miR129-5p positively correlated with NSE levels (all p < 0.001). Interestingly, these correlations were absent when only the good outcome group was analyzed (p > 0.5). Moreover, these correlations were unaffected by demographic and clinical characteristics. All three microRNAs predicted neurological outcome at 6 months. Circulating levels of brain-enriched microRNAs are correlated with NSE levels and hence can reflect the extent of brain injury in patients after CA. This observation strengthens the potential of brain-enriched microRNAs to aid in outcome prognostication after CA.
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50.
  • Vogelsong, Melissa A., et al. (författare)
  • Influence of sex on survival, neurologic outcomes, and neurodiagnostic testing after out-of-hospital cardiac arrest
  • 2021
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 167, s. 66-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Previous studies evaluating the relationship between sex and post-resuscitation care and outcomes following out-of-hospital cardiac arrest (OHCA) are conflicting. We investigated the association between sex and outcomes as well as neurodiagnostic testing in a prospective multicenter international registry of patients admitted to intensive care units following OHCA. Methods: OHCA survivors enrolled in the International Cardiac Arrest Registry (INTCAR) from 2012 to 2017 were included. We assessed the independent association between sex and survival to hospital discharge, good neurologic outcome (Cerebral Performance Category 1 or 2), neurodiagnostic testing, and withdrawal of life-sustaining therapy (WLST). Results: Of 2407 eligible patients, 809 (33.6%) were women. Baseline characteristics differed by sex, with less bystander CPR and initial shockable rhythms among women. Women were less likely to survive to hospital discharge, however significance abated following adjusted analysis (30.1% vs 42.7%, adjusted OR 0.85, 95% CI 0.67–1.08). Women were less likely to have good neurologic outcome at discharge (21.4% vs 34.0%, adjusted OR 0.74, 95% CI 0.57–0.96) and at six months post-arrest (16.7% vs 29.4%, adjusted OR 0.73, 95% CI 0.54–0.98) that persisted after adjustment. Neuroimaging (75.5% vs 74.3%, p = 0.54) and other neurophysiologic testing (78.8% vs 78.6%, p = 0.91) was similar across sex. Women were more likely to undergo WLST (55.6% vs 42.8%, adjusted OR 1.35, 95% CI 1.09–1.66). Conclusions: Women with cardiac arrest have lower odds of good neurologic outcomes and higher odds of WLST, despite comparable rates of neurodiagnostic testing and after controlling for baseline differences in clinical characteristics and cardiac arrest features.
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