| 1. |
- Lilja, Gisela, et al.
(författare)
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Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest A Predefined Analysis of the TTM2 Randomized Clinical Trial
- 2023
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Ingår i: Jama Neurology. - 2168-6149 .- 2168-6157. ; 80:10, s. 1070-1079
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. OBJECTIVES To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. DESIGN, SETTING, AND PARTICIPANTS This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. INTERVENTIONS Randomization 1:1 to temperature control with targeted hypothermia at 33 degrees C or targeted normothermia and early treatment of fever (37.8 degrees C or higher). MAIN OUTCOMES AND MEASURES Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. RESULTS At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P =.46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P =.37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P =.62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). CONCLUSIONS In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.
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| 2. |
- Moseby-Knappe, Marion, et al.
(författare)
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Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest
- 2021
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 47, s. 984-994
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered "indeterminate". We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines. Methods Retrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1-2) at 6 months. Results Seven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2-98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87-95% of patients). Normal S100B and NSE predicted good outcome with NPV 76-82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as "indeterminate outcome" by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome. Conclusion Low levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy.
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| 3. |
- Andersson, Peder, et al.
(författare)
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Predicting neurological outcome after out-of-hospital cardiac arrest with cumulative information; development and internal validation of an artificial neural network algorithm
- 2021
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrognostication of neurological outcome in patients who remain comatose after cardiac arrest resuscitation is complex. Clinical variables, as well as biomarkers of brain injury, cardiac injury, and systemic inflammation, all yield some prognostic value. We hypothesised that cumulative information obtained during the first three days of intensive care could produce a reliable model for predicting neurological outcome following out-of-hospital cardiac arrest (OHCA) using artificial neural network (ANN) with and without biomarkers.MethodsWe performed a post hoc analysis of 932 patients from the Target Temperature Management trial. We focused on comatose patients at 24, 48, and 72 h post-cardiac arrest and excluded patients who were awake or deceased at these time points. 80% of the patients were allocated for model development (training set) and 20% for internal validation (test set). To investigate the prognostic potential of different levels of biomarkers (clinically available and research-grade), patients' background information, and intensive care observation and treatment, we created three models for each time point: (1) clinical variables, (2) adding clinically accessible biomarkers, e.g., neuron-specific enolase (NSE) and (3) adding research-grade biomarkers, e.g., neurofilament light (NFL). Patient outcome was the dichotomised Cerebral Performance Category (CPC) at six months; a good outcome was defined as CPC 1-2 whilst a poor outcome was defined as CPC 3-5. The area under the receiver operating characteristic curve (AUROC) was calculated for all test sets.ResultsAUROC remained below 90% when using only clinical variables throughout the first three days in the ICU. Adding clinically accessible biomarkers such as NSE, AUROC increased from 82 to 94% (p<0.01). The prognostic accuracy remained excellent from day 1 to day 3 with an AUROC at approximately 95% when adding research-grade biomarkers. The models which included NSE after 72 h and NFL on any of the three days had a low risk of false-positive predictions while retaining a low number of false-negative predictions.ConclusionsIn this exploratory study, ANNs provided good to excellent prognostic accuracy in predicting neurological outcome in comatose patients post OHCA. The models which included NSE after 72 h and NFL on all days showed promising prognostic performance.
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| 4. |
- Ashton, Nicholas J., et al.
(författare)
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Alzheimer Disease Blood Biomarkers in Patients With Out-of-Hospital Cardiac Arrest
- 2023
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Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149. ; 80:4, s. 388-396
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Blood phosphorylated tau (p-tau) and amyloid-13 peptides (A13) are promising peripheral biomarkers of Alzheimer disease (AD) pathology. However, their potential alterations due to alternative mechanisms, such as hypoxia in patients resuscitated from cardiac arrest, are not known. OBJECTIVE To evaluate whether the levels and trajectories of blood p-tau, A1342, and A1340 following cardiac arrest, in comparison with neural injury markers neurofilament light (NfL) and total tau (t-tau), can be used for neurological prognostication following cardiac arrest.DESIGN, SETTING, AND PARTICIPANTS This prospective clinical biobank study used data from the randomized Target Temperature Management After Out-of-Hospital Cardiac Arrest (TTM) trial. Unconscious patients with cardiac arrest of presumed cardiac origin were included between November 11, 2010, and January 10, 2013, from 29 international sites. Serum analysis for serum NfL and t-tau were performed between August 1 and August 23, 2017. Serum p-tau, A1342, and A1340 were analyzed between July 1 and July 15, 2021, and between May 13 and May 25, 2022. A total of 717 participants from the TTM cohort were examined: an initial discovery subset (n = 80) and a validation subset. Both subsets were evenly distributed for good and poor neurological outcome after cardiac arrest.EXPOSURES Serum p-tau, A1342, and A1340 concentrations using single molecule array technology. Serum levels of NfL and t-tau were included as comparators.MAIN OUTCOMES AND MEASURES Blood biomarker levels at 24 hours, 48 hours, and 72 hours after cardiac arrest. Poor neurologic outcome at 6-month follow-up, defined according to the cerebral performance category scale as category 3 (severe cerebral disability), 4 (coma), or 5 (brain death).RESULTS This study included 717 participants (137 [19.1%] female and 580 male [80.9%]; mean [SD] age, 63.9 [13.5] years) who experienced out-of-hospital cardiac arrest. Significantly elevated serum p-tau levels were observed at 24 hours, 48 hours, and 72 hours in cardiac arrest patients with poor neurological outcome. The magnitude and prognostication of the change was greater at 24 hours (area under the receiver operating characteristic curve [AUC], 0.96; 95% CI, 0.95-0.97), which was similar to NfL (AUC, 0.94; 95% CI, 0.92-0.96). However, at later time points, p-tau levels decreased and were weakly associated with neurological outcome. In contrast, NfL and t-tau maintained high diagnostic accuracies, even 72 hours after cardiac arrest. Serum A1342 and A1340 concentrations increased over time in most patients but were only weakly associated with neurological outcome.CONCLUSIONS AND RELEVANCE In this case-control study, blood biomarkers indicative of AD pathology demonstrated different dynamics of change after cardiac arrest. The increase of p-tau at 24 hours after cardiac arrest suggests a rapid secretion from the interstitial fluid following hypoxic-ischemic brain injury rather than ongoing neuronal injury like NfL or t-tau. In contrast, delayed increases of A13 peptides after cardiac arrest indicate activation of amyloidogenic processing in response to ischemia.
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| 5. |
- Dankiewicz, Josef, et al.
(författare)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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| 6. |
- Dankiewicz, Josef, et al.
(författare)
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Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2): A randomized clinical trial - Rationale and design
- 2019
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 217, s. 23-31
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Tidskriftsartikel (refereegranskat)abstract
- Background: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore warranted. Methods: The TTM2-trial is an international, multicenter, parallel group, investigator-initiated, randomized, superiority trial in which a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and early treatment of fever (≥37.8°C). Participants will be randomized within 3 hours of return of spontaneous circulation with the intervention period lasting 40 hours in both groups. Sedation will be mandatory for all patients throughout the intervention period. The clinical team involved with direct patient care will not be blinded to allocation group due to the inherent difficulty in blinding the intervention. Prognosticators, outcome-assessors, the steering group, the trial coordinating team, and trial statistician will be blinded. The primary outcome will be all-cause mortality at 180 days after randomization. We estimate a 55% mortality in the control group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The main secondary neurological outcome will be poor functional outcome (modified Rankin Scale 4–6) at 180 days after arrest. Discussion: The TTM2-trial will compare hypothermia to 33°C with normothermia and early treatment of fever (≥37.8°C) after out-of-hospital cardiac arrest. © 2019
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| 7. |
- Gisela, Lilja, et al.
(författare)
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Return to Work and Participation in Society After Out-of-Hospital Cardiac Arrest
- 2018
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Ingår i: Circulation-Cardiovascular Quality and Outcomes. - : Ovid Technologies (Wolters Kluwer Health). - 1941-7705 .- 1941-7713. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to describe out-of-hospital cardiac arrest (OHCA) survivors' ability to participate in activities of everyday life and society, including return to work. The specific aim was to evaluate potential effects of cognitive impairment. METHODS AND RESULTS: Two hundred eighty-seven OHCA survivors included in the TTM trial (Target Temperature Management) and 119 matched control patients with ST-segment-elevation myocardial infarction participated in a follow-up 180 days post-event that included assessments of participation, return to work, emotional problems, and cognitive impairment. On the Mayo-Portland Adaptability Inventory-4 Participation Index, OHCA survivors (n=270) reported more restricted participation In everyday life and in society (47% versus 30%; P<0.001) compared with ST-segment-elevation myocardial infarction controls (n=118). Furthermore, 27% (n=36) of pre-event working OHCA survivors (n=135) compared with 7% (n=3) of pre-event working ST-segment-elevation myocardial infarction controls (n=45) were on sick leave (odds ratio, 4.9; 95% confidence interval, 1.4-16.8; P=0.01). Among the OHCA survivors assumed to return to work (n=135), those with cognitive impairment (n=55) were 3x more likely (odds ratio, 3.3; 95% confidence interval, 1.2-9.3; P=0.02) to be on sick leave compared with those without cognitive impairment (n=40; 36%, n=20, versus 15%, n=6). For OHCA survivors, the variables that were found most predictive for a lower participation were depression, restricted mobility, memory impairment, novel problem-solving difficulties, fatigue, and slower processing speed. CONCLUSIONS: OHCA survivors reported a more restricted societal participation 6 months post-arrest, and their return to work was lower compared with ST-segment-elevation myocardial infarction controls. Cognitive impairment was significantly associated with lower participation, together with the closely related symptoms of fatigue, depression, and restricted mobility. These predictive variables may be used during follow-up to identify OHCA survivors at risk of a less successful recovery that may benefit from further support and rehabilitation.
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| 8. |
- Heimburg, Katarina, et al.
(författare)
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Physical activity after cardiac arrest; protocol of a sub-study in the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2)
- 2021
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Ingår i: Resuscitation Plus. - : Elsevier BV. - 2666-5204. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The primary aim of this study is to investigate whether out-of-hospital cardiac arrest (OHCA) survivors have lower levels of self-reported physical activity compared to a non-cardiac arrest (CA) control group who had acute myocardial infarction (MI). Additional aims are to explore potential predictors of physical inactivity (older age, female gender, problems with general physical function, global cognition, mental processing speed/attention, anxiety symptoms, depression symptoms, kinesiophobia, fatigue), and to investigate the relationship between self-reported and objectively measured physical activity among OHCA-survivors. Methods: The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial) collects information regarding age, gender, self-reported physical activity, general physical function, global cognition and mental processing speed/attention at 6 months after OHCA. In this TTM2-trial cross-sectional prospective sub-study, participants at selected sites are invited to an additional follow-up meeting within 4 weeks from the main study follow-up. At this meeting, information regarding anxiety symptoms, depression symptoms, kinesiophobia and fatigue is collected. The OHCA-survivors are then provided with an objective measure of physical activity, a hip-placed accelerometer, to wear for one week, together with a training diary. At the end of the week, participants are asked to once again answer two self-reported questions regarding physical activity for that specific week. MI-controls attend a single follow-up meeting and perform the same assessments as the OHCA-survivors, except from wearing the accelerometer. We aim to include 110 OHCA-survivors and 110 MI-controls in Sweden, Denmark and the United Kingdom. Conclusion: The results from this sub-study will provide novel information about physical activity among OHCA-survivors.
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| 9. |
- Heimburg, Katarina, et al.
(författare)
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Self-reported limitations in physical function are common 6 months after out-of-hospital cardiac arrest
- 2022
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Ingår i: Resuscitation Plus. - : Elsevier BV. - 2666-5204. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Out-of-hospital cardiac arrest (OHCA) survivors generally report good health-related quality of life, but physical aspects of health seem more affected than other domains. Limitations in physical function after surviving OHCA have received little attention. Aims: To describe physical function 6 months after OHCA and compare it with a group of ST elevation myocardial infarction (STEMI) controls, matched for country, age, sex and time of the cardiac event. A second aim was to explore variables potentially associated with self-reported limitations in physical function in OHCA survivors. Methods: A cross-sectional sub-study of the Targeted Temperature Management at 33 degrees C versus 36 degrees C (TTM) trial with a follow-up 6 months post-event. Physical function was the main outcome assessed with the self-reported Physical Functioning-10 items scale (PF-10). PF-10 is presented as T-scores (0-100), where 50 represents the norm mean. Scores <47 at a group level, or <45 at an individual level indicate limitations in physical function. Results: 287 OHCA survivors and 119 STEMI controls participated. Self-reported physical function by PF-10 was significantly lower for OHCA survivors compared to STEMI controls (mean 46.0, SD 11.2 vs. 48.8, SD 9.0, p= 0.025). 38% of OHCA survivors compared to 26% of STEMI controls reported limitations in physical function at an individual level (p = 0.022). The most predictive variables for self-reported limitations in physical function in OHCA survivors were older age, female sex, cognitive impairment, and symptoms of anxiety and depression after 6 months. Conclusion: Self-reported limitations in physical function are more common in OHCA survivors compared to STEMI controls.
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| 10. |
- Krag, M., et al.
(författare)
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Stress ulcer prophylaxis in the intensive care unit: an international survey of 97 units in 11 countries
- 2015
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 59:5, s. 576-585
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Tidskriftsartikel (refereegranskat)abstract
- Background: Stress ulcer prophylaxis (SUP) may decrease the incidence of gastrointestinal bleeding in patients in the intensive care unit (ICU), but the risk of infection may be increased. In this study, we aimed to describe SUP practices in adult ICUs. We hypothesised that patient selection for SUP varies both within and between countries. MethodsAdult ICUs were invited to participate in the survey. We registered country, type of hospital, type and size of ICU, preferred SUP agent, presence of local guideline, reported indications for SUP, criteria for discontinuing SUP, and concerns about adverse effects. Fisher's exact test was used to assess differences between groups. ResultsNinety-seven adult ICUs in 11 countries participated (eight European). All but one ICU used SUP, and 64% (62/97) reported having a guideline for the use of SUP. Proton pump inhibitors were the most common SUP agent, used in 66% of ICUs (64/97), and H2-receptor antagonists were used 31% (30/97) of the units. Twenty-three different indications for SUP were reported, the most frequent being mechanical ventilation. All patients were prescribed SUP in 26% (25/97) of the ICUs. Adequate enteral feeding was the most frequent reason for discontinuing SUP, but 19% (18/97) continued SUP upon ICU discharge. The majority expressed concern about nosocomial pneumonia and Clostridium difficile infection with the use of SUP. ConclusionsIn this international survey, most participating ICUs reported using SUP, primarily proton pump inhibitors, but many did not have a guideline; indications varied considerably and concern existed about infectious complications.
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