| 1. |
- Jakobsen, Janus Christian, et al.
(författare)
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Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: a statistical analysis plan.
- 2020
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- To date, targeted temperature management (TTM) is the only neuroprotective intervention after resuscitation from cardiac arrest that is recommended by guidelines. The evidence on the effects of TTM is unclear.The Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) trial is an international, multicentre, parallel group, investigator-initiated, randomised, superiority trial in which TTM with a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and active treatment of fever (≥37.8°C). Prognosticators, outcome assessors, the steering group, the trial coordinating team, and trial statisticians will be blinded to treatment allocation. The primary outcome will be all-cause mortality at 180days after randomisation. We estimate a 55% mortality in the targeted normothermia 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 secondary neurological outcome will be poor functional outcome (modified Rankin scale 4-6) at 180days after cardiac arrest. In this paper, a detailed statistical analysis plan is presented, including a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Final analyses will be conducted independently by two qualified statisticians following the present plan.This SAP, which was prepared before completion of enrolment, should increase the validity of the TTM trial by mitigation of analysis-bias.
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| 2. |
- Lilja, Gisela, et al.
(författare)
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Cognitive Function in Survivors of Out-of-Hospital Cardiac Arrest After Target Temperature Management at 33 degrees C Versus 36 degrees C
- 2015
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Ingår i: Circulation. - 0009-7322. ; 131:15, s. 1340-1349
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Tidskriftsartikel (refereegranskat)abstract
- -Target temperature management is recommended as a neuro-protective strategy after out-of-hospital cardiac arrest. Potential effects of different target temperatures on cognitive impairment commonly described in survivors are not sufficiently investigated. The primary aim of this study was to evaluate whether a target temperature of 33ºC compared to 36ºC was favourable for cognitive function, and secondary to describe cognitive impairment in cardiac arrest survivors in general.
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| 3. |
- Lilja, Gisela, et al.
(författare)
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Protocol for outcome reporting and follow-up in the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2)
- 2020
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 150, s. 104-112
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The TTM2-trial is a multi-centre randomised clinical trial where targeted temperature management (TTM) at 33 °C will be compared with normothermia and early treatment of fever (≥37.8 °C) after Out-of-Hospital Cardiac Arrest (OHCA). This paper presents the design and rationale of the TTM2-trial follow-up, where information on secondary and exploratory outcomes will be collected. We also present the explorative outcome analyses which will focus on neurocognitive function and societal participation in OHCA-survivors. Methods: Blinded outcome-assessors will perform follow-up at 30-days after the OHCA with a telephone interview, including the modified Rankin Scale (mRS) and the Glasgow Outcome Scale Extended (GOSE). Face-to-face meetings will be performed at 6 and 24-months, and include reports on outcome from several sources of information: clinician-reported: mRS, GOSE; patient-reported: EuroQol-5 Dimensions-5 Level responses version (EQ-5D-5L), Life satisfaction, Two Simple Questions; observer-reported: Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest version (IQCODE-CA) and neurocognitive performance measures: Montreal Cognitive Assessment, (MoCA), Symbol Digit Modalities Test (SDMT). Exploratory analyses will be performed with an emphasis on brain injury in the survivors, where the two intervention groups will be compared for potential differences in neuro-cognitive function (MoCA, SDMT) and societal participation (GOSE). Strategies to increase inter-rater reliability and decrease missing data are described. Discussion: The TTM2-trial follow-up is a pragmatic yet detailed pre-planned and standardised assessment of patient's outcome designed to ensure data-quality, decrease missing data and provide optimal conditions to investigate clinically relevant effects of TTM, including OHCA-survivors’ neurocognitive function and societal participation.
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| 4. |
- Mattsson, Niklas, et al.
(författare)
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Serum tau and neurological outcome in cardiac arrest.
- 2017
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Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 82:5, s. 665-675
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Tidskriftsartikel (refereegranskat)abstract
- To test serum tau as a predictor of neurological outcome after cardiac arrest.We measured the neuronal protein tau in serum at 24, 48, and 72 hours after cardiac arrest in 689 patients in the prospective international Target Temperature Management trial. The main outcome was poor neurological outcome, defined as Cerebral Performance Categories 3-5 at 6 months.Increased tau was associated with poor outcome at 6 months after cardiac arrest (median=38.5, interquartile range [IQR]=5.7-245ng/l in poor vs median=1.5, IQR=0.7-2.4ng/l in good outcome, for tau at 72 hours, p<0.0001). Tau improved prediction of poor outcome compared to using clinical information (p<0.0001). Tau cutoffs had low false-positive rates (FPRs) for good outcome while retaining high sensitivity for poor outcome. For example, tau at 72 hours had FPR=2% (95% CI=1-4%) with sensitivity=66% (95% CI=61-70%). Tau had higher accuracy than serum neuron-specific enolase (NSE; the area under the receiver operating characteristic curve was 0.91 for tau vs 0.86 for NSE at 72 hours, p=0.00024). During follow-up (up to 956 days), tau was significantly associated with overall survival. The accuracy in predicting outcome by serum tau was equally high for patients randomized to 33°C and 36°C targeted temperature after cardiac arrest.Serum tau is a promising novel biomarker for prediction of neurological outcome in patients with cardiac arrest. It may be significantly better than serum NSE, which is recommended in guidelines and currently used in clinical practice in several countries to predict outcome after cardiac arrest. Ann Neurol 2017;82:665-675.
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| 5. |
- Moseby-Knappe, Marion, et al.
(författare)
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Performance of a guideline-recommended algorithm for prognostication of poor neurological outcome after cardiac arrest
- 2020
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 46:10, s. 1852-62
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Tidskriftsartikel (refereegranskat)abstract
- © 2020, The Author(s). Purpose: To assess the performance of a 4-step algorithm for neurological prognostication after cardiac arrest recommended by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM). Methods: Retrospective descriptive analysis with data from the Target Temperature Management (TTM) Trial. Associations between predicted and actual neurological outcome were investigated for each step of the algorithm with results from clinical neurological examinations, neuroradiology (CT or MRI), neurophysiology (EEG and SSEP) and serum neuron-specific enolase. Patients examined with Glasgow Coma Scale Motor Score (GCS-M) on day 4 (72–96h) post-arrest and available 6-month outcome were included. Poor outcome was defined as Cerebral Performance Category 3–5. Variations of the ERC/ESICM algorithm were explored within the same cohort. Results: The ERC/ESICM algorithm identified poor outcome patients with 38.7% sensitivity (95% CI 33.1–44.7) and 100% specificity (95% CI 98.8–100) in a cohort of 585 patients. An alternative cut-off for serum neuron-specific enolase, an alternative EEG-classification and variations of the GCS-M had minor effects on the sensitivity without causing false positive predictions. The highest overall sensitivity, 42.5% (95% CI 36.7–48.5), was achieved when prognosticating patients irrespective of GCS-M score, with 100% specificity (95% CI 98.8–100) remaining. Conclusion: The ERC/ESICM algorithm and all exploratory multimodal variations thereof investigated in this study predicted poor outcome without false positive predictions and with sensitivities 34.6–42.5%. Our results should be validated prospectively, preferably in patients where withdrawal of life-sustaining therapy is uncommon to exclude any confounding from self-fulfilling prophecies.
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| 6. |
- Moseby-Knappe, Marion, et al.
(författare)
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Serum Neurofilament Light Chain for Prognosis of Outcome after Cardiac Arrest
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:1, s. 64-64
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Prognostication of neurologic outcome after cardiac arrest is an important but challenging aspect of patient therapy management in critical care units. Objective: To determine whether serum neurofilament light chain (NFL) levels can be used for prognostication of neurologic outcome after cardiac arrest. Design, Setting and Participants: Prospective clinical biobank study of data from the randomized Target Temperature Management After Cardiac Arrest trial, an international, multicenter study with 29 participating sites. Patients were included between November 11, 2010, and January 10, 2013. Serum NFL levels were analyzed between August 1 and August 23, 2017, after trial completion. A total of 782 unconscious patients with out-of-hospital cardiac arrest of presumed cardiac origin were eligible. Exposures: Serum NFL concentrations analyzed at 24, 48, and 72 hours after cardiac arrest with an ultrasensitive immunoassay. Main Outcomes and Measures: Poor neurologic outcome at 6-month follow-up, defined according to the Cerebral Performance Category Scale as cerebral performance category 3 (severe cerebral disability), 4 (coma), or 5 (brain death). Results: Of 782 eligible patients, 65 patients (8.3%) were excluded because of issues with aliquoting, missing sampling, missing outcome, or transport problems of samples. Of the 717 patients included (91.7%), 580 were men (80.9%) and median (interquartile range [IQR]) age was 65 (56-73) years. A total of 360 patients (50.2%) had poor neurologic outcome at 6 months. Median (IQR) serum NFL level was significantly increased in the patients with poor outcome vs good outcome at 24 hours (1426 [299-3577] vs 37 [20-70] pg/mL), 48 hours (3240 [623-8271] vs 46 [26-101] pg/mL), and 72 hours (3344 [845-7838] vs 54 [30-122] pg/mL) (P <.001 at all time points), with high overall performance (area under the curve, 0.94-0.95) and high sensitivities at high specificities (eg, 69% sensitivity with 98% specificity at 24 hours). Serum NFL levels had significantly greater performance than the other biochemical serum markers (ie, tau, neuron-specific enolase, and S100). At comparable specificities, serum NFL levels had greater sensitivity for poor outcome compared with routine electroencephalogram, somatosensory-evoked potentials, head computed tomography, and both pupillary and corneal reflexes (ranging from 29.2% to 49.0% greater for serum NFL level). Conclusions and Relevance: Findings from this study suggest that the serum NFL level is a highly predictive marker of long-term poor neurologic outcome at 24 hours after cardiac arrest and may be a useful complement to currently available neurologic prognostication methods.
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| 7. |
- Bergquist, Maria, et al.
(författare)
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Expression of the glucocorticoid receptor is decreased in experimental Staphylococcus aureus sepsis
- 2013
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Ingår i: Journal of Infection. - : Elsevier BV. - 0163-4453 .- 1532-2742. ; 67:6, s. 574-583
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Glucocorticoid treatment in septic shock remains controversial after recent trials. We hypothesized that failure to respond to steroid therapy may be caused by decreased expression and/or function of glucocorticoid receptors (GR) and studied this in a mouse model of Staphylococcus aureus sepsis. The impact of timing of dexamethasone treatment was also investigated. Methods: Male C57BL/6J mice were intravenously inoculated with S. aureus and GR expression and binding ability in blood, spleen and lymph nodes were analysed by means of flow cytometry. GR translocation was analysed using Image Stream. Septic mice were administered dexamethasone at 22, 26, 48, 72 and 96 h after inoculation and body weight, as a sign of dehydration, was observed. Results: GR expression was decreased in septic animals, but not the ligand binding capacity. GR translocation was decreased in septic mice compared to control animals. Early dexamethasone treatment (22 and 26 h) improved clinical outcome as studied by weight gain compared to when treatment was started at later time points (48, 72 and 96 h). Conclusion: Our data provide evidence that GR expression is progressively decreased in experimental sepsis and that dexamethasone has a decreased ability to translocate into the cell nucleus. This may explain why steroid treatment is only beneficial when administered early in sepsis and septic shock.
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| 8. |
- Bergquist, Maria, et al.
(författare)
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Glucocorticoid receptor expression and binding capacity in patients with burn injury.
- 2016
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Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 60:2, s. 213-221
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Tidskriftsartikel (refereegranskat)abstract
- Burn injuries are associated with strong inflammation and risk of secondary sepsis which both may affect the function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in leucocytes from patients admitted to a tertiary burn center.
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| 9. |
- Bergquist, Maria, et al.
(författare)
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Glucocorticoid receptor function is decreased in neutrophils during endotoxic shock
- 2014
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Ingår i: Journal of Infection. - : Elsevier BV. - 0163-4453 .- 1532-2742. ; 69:2, s. 113-122
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: It remains unclear whether glucocorticoid treatment can improve the outcome of sepsis. The aim of the present study was to investigate if glucocorticoid receptor (GR) expression and function is impaired in lipopolysaccharide (LPS) induced shock, and whether the time point for start of glucocorticoid treatment affects the outcome.METHODS: Male C57BL/6J mice were administered LPS i.p. and GR expression and binding ability in blood and spleen leukocytes were analysed by flow cytometry. GR translocation was analysed using Image Stream technique. The effect of dexamethasone treatment started 2 h before or 2, 12 or 36 h after LPS administration on survival was studied.RESULTS: Despite increased GR expression in neutrophils after LPS administration, the GR binding capacity was reduced. In addition, GR translocation was decreased in neutrophils and T lymphocytes from endotoxic mice at 12 h compared to control animals. Dexamethasone treatment improved survival only when started early (2 h) after LPS administration.CONCLUSION: The decreased glucocorticoid responsiveness displayed by neutrophils, in combination with their increased numbers, may explain why survival is increased only when dexamethasone treatment is given early during LPS induced shock.
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| 10. |
- Bergquist, Maria, et al.
(författare)
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Impairment of neutrophilic glucocorticoid receptor function in patients treated with steroids for septic shock
- 2015
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Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Glucocorticoid (GC) treatment has variable effect in sepsis. This may be explained by decreased expression or function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in patients during and after sepsis.METHODS: In this prospective, non-interventional clinical study, peripheral blood and clinical data were collected from 20 adult patients at five timepoints during sepsis and 5-13 months after recovery. GR expression and binding capacity were assessed by flow cytometry.RESULTS: GR expression was higher in T lymphocytes from patients with septic shock compared to healthy subjects (p = 0.01). While there was no difference in GR expression between GC-treated and non-treated patients, GR binding capacity was lower in GC-treated patients at admission compared to healthy subjects (p ≤ 0.03). After the acute inflammation inflammatory phase, GR binding capacity was still lower in neutrophils of GC-treated patients, compared to healthy subjects (p = 0.01). On admission, GR binding capacity in T lymphocytes and neutrophils was inversely correlated with noradrenaline dose and lactate (p ≤ 0.03).CONCLUSIONS: Our data suggest that GR expression is increased in T lymphocytes during septic shock regardless of GC treatment, while GR binding capacity is decreased in neutrophils in GC-treated patients. As neutrophils are the predominant circulating leucocyte in septic shock, their decreased GR binding capacity may impede the response to exogenous or endogenous glucocorticoids.
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| 11. |
- Bergquist, Maria, et al.
(författare)
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Increased RANKL/OPG ratio and sclerostin in patients with septic shock
- 2017
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Ingår i: Clinical Microbiology and Infectious Diseases. - 2398-8096. ; 2:1, s. 1-3
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Tidskriftsartikel (refereegranskat)abstract
- We report an increased RANKL/OPG ratio and increased sclerostin levels in patients with septic shock one day after admission compared to healthy subjects,indicating an increased risk for bone loss in survivors of septic shock. No increase in RANKL/OPG ratio was observed in patients treated with hydrocortisone during septic shock.
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| 12. |
- Blennow Nordström, Erik, et al.
(författare)
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Neuropsychological outcome after cardiac arrest : A prospective case control sub-study of the Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2)
- 2020
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA. Methods: This longitudinal multi-center clinical study is a sub-study of the TTM2-trial, in which a comprehensive neuropsychological examination is performed in addition to the main TTM2-trial neurocognitive screening. Approximately 7 and 24 months after OHCA, survivors at selected study sites are invited to a standardized assessment, including performance-based tests of cognition and questionnaires of emotional problems, fatigue, executive function and insomnia. At 1:1 ratio, a matched control group from a cohort of acute myocardial infarction (MI) patients is recruited to perform the same assessment. We aim to include 100 patients per group. Potential differences between the OHCA patients and the MI controls at 7 and 24 months will be analyzed with a linear regression, using composite z-scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions) as primary outcome measures. Results from OHCA survivors on the main TTM2-trial neurocognitive screening battery will be compared with neuropsychological test results at 7 months, using sensitivity and specificity analyses. Discussion: In this study we collect detailed information on cognitive impairment after OHCA and compare this to a control group of patients with acute MI. The validation of the TTM2 neurocognitive screening battery could justify its inclusion in routine follow-up. Our results may have a potential to impact on the design of future follow-up strategies and interventions after OHCA. Trial registration: ClinicalTrials.gov, NCT03543371. Registered 1 June 2018
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| 13. |
- Cronberg, Tobias, et al.
(författare)
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Neurological prognostication after cardiac arrest : Recommendations from the Swedish Resuscitation Council
- 2013
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 84:7, s. 867-872
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary resuscitation is started in 5000 victims of out-of-hospital cardiac arrest in Sweden each year and the survival rate is approximately 10%. The subsequent development of a global ischaemic brain injury is the major determinant of the neurological prognosis for those patients who reach the hospital alive. Induced hypothermia is a recommended treatment after cardiac arrest and has been implemented in most Swedish hospitals.Recent studies indicate that induced hypothermia may affect neurological prognostication and previous international recommendations are therefore no longer valid when hypothermia is applied. An expert group from the Swedish Resuscitation Council has reviewed the literature and made recommendations taking into account the effects of induced hypothermia and concomitant sedation.A delayed neurological evaluation at 72h after rewarming is recommended for hypothermia treated patients. This evaluation should be based on several independent methods and the possibility of lingering pharmacological effects should be considered.
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| 14. |
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| 15. |
- 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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| 16. |
- 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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| 17. |
- Einarsson, Freyr, et al.
(författare)
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Outcomes of catheter-directed interventions in high-risk pulmonary embolism-a retrospective analysis
- 2021
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 65:4, s. 499-506
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Tidskriftsartikel (refereegranskat)abstract
- Background First-line treatment of high-risk pulmonary embolism with persistent hypotension and/or signs of shock is intravenous thrombolysis. However, if thrombolysis is contraindicated due to risk of serious bleeding, or if it yields insufficient effect, surgical thrombectomy or catheter-directed intervention (CDI) plus anticoagulation is recommended. The aim of this study was to assess the outcomes of the CDI modality introduced in a tertiary referral centre in 2013. Methods Retrospective comparison between patients treated with CDI plus anticoagulation (n = 22) and patients treated with anticoagulation only (n = 23) as used before the CDI technique was available. The main outcomes of interest were 90-day survival and reduction of right to left ventricle diameter (RV/LV) ratio, using the Fischer's exact test and a mixed model, respectively, for statistical analysis. Results Ninety-day survival was 59% after CDI and 61% after anticoagulation only; P = .903. The rate of RV/LV ratio reduction was 0.4 units higher per 24 hours in the CDI group (median 2.1 pre-treatment), than in the anticoagulation only group (median 1.3 pre-treatment); P = .007. Conclusion In patients with high-risk pulmonary embolism, 90-day survival was similar after treatment with CDI plus anticoagulation compared to anticoagulation only. The mean reduction in RV/LV ratio was larger in the CDI group. Our results support the use of CDI in selected patients, respecting the limitations and potential side effects of each technical device used.
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| 18. |
- Elfwen, Ludvig, et al.
(författare)
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Direct or subacute coronary angiography in out-of-hospital cardiac arrest (DISCO)-An initial pilot-study of a randomized clinical trial
- 2019
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Ingår i: Resuscitation. - : ELSEVIER IRELAND LTD. - 0300-9572 .- 1873-1570. ; 139, s. 253-261
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Tidskriftsartikel (refereegranskat)abstract
- Background: The clinical importance of immediate coronary angiography, with potentially subsequent percutaneous coronary intervention (PCI), in out-of-hospital cardiac arrest (OHCA) patients without ST-elevation on the ECG is unclear. In this study, we assessed feasibility and safety aspects of performing immediate coronary angiography in a pre-specified pilot phase of the 'DIrect or Subacute Coronary angiography in Out-of-hospital cardiac arrest' (DISCO) randomized controlled trial (ClinicalTrials.gov ID: NCT02309151). Methods: Resuscitated bystander witnessed OHCA patients > 18 years without ST-elevation on the ECG were randomized to immediate coronary angiography versus standard of care. Event times, procedure related adverse events and safety variables within 7 days were recorded. Results: In total, 79 patients were randomized to immediate angiography (n = 39) or standard of care (n = 40). No major differences in baseline characteristics between the groups were found. There were no differences in the proportion of bleedings and renal failure. Three patients randomized to immediate angiography and six patients randomized to standard care died within 24 h. The median time from EMS arrival to coronary angiography was 135 min in the immediate angiography group. In patients randomized to immediate angiography a culprit lesion was found in 14/38 (36.8%) and PCI was performed in all these patients. In 6/40 (15%) patients randomized to standard of care, coronary angiography was performed before the stipulated 3 days. Conclusion: In this out-of-hospital cardiac arrest population without ST-elevation, randomization to a strategy to perform immediate coronary angiography was feasible although the time window of 120 min from EMS arrival at the scene of the arrest to start of coronary angiography was not achieved. No significant safety issues were reported.
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| 19. |
- Gudmundsson, Magni, et al.
(författare)
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Atelectasis is inversely proportional to transpulmonary pressure during weaning from ventilator support in a large animal model
- 2018
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 62:1, s. 94-104
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn mechanically ventilated, lung injured, patients without spontaneous breathing effort, atelectasis with shunt and desaturation may appear suddenly when ventilator pressures are decreased. It is not known how such a formation of atelectasis is related to transpulmonary pressure (P-L) during weaning from mechanical ventilation when the spontaneous breathing effort is increased. If the relation between P-L and atelectasis were known, monitoring of P-L might help to avoid formation of atelectasis and cyclic collapse during weaning. The main purpose of this study was to determine the relation between P-L and atelectasis in an experimental model representing weaning from mechanical ventilation. MethodsDynamic transverse computed tomography scans were acquired in ten anaesthetized, surfactant-depleted pigs with preserved spontaneous breathing, as ventilator support was lowered by sequentially reducing inspiratory pressure and positive end expiratory pressure in steps. The volumes of gas and atelectasis in the lungs were correlated with P-L obtained using oesophageal pressure recordings. Work of breathing (WOB) was assessed from Campbell diagrams. ResultsGradual decrease in P-L in both end-expiration and end-inspiration caused a proportional increase in atelectasis and decrease in the gas content (linear mixed model with an autoregressive correlation matrix; P<0.001) as the WOB increased. However, cyclic alveolar collapse during tidal ventilation did not increase significantly. ConclusionWe found a proportional correlation between atelectasis and P-L during the weaning process' in experimental mild lung injury. If confirmed in the clinical setting, a gradual tapering of ventilator support can be recommended for weaning without risk of sudden formation of atelectasis.
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| 20. |
- Gudmundsson, Magni, et al.
(författare)
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Transpulmonary driving pressure during mechanical ventilation-validation of a non-invasive measurement method
- 2020
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 64:2, s. 211-215
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Tidskriftsartikel (refereegranskat)abstract
- Background Transpulmonary driving pressure plays an important role in today's understanding of ventilator induced lung injury. We have previously validated a novel non‐invasive method based on stepwise increments of PEEP to assess transpulmonary driving pressure in anaesthetised patients with healthy lungs. The aim of this study was to validate the method in patients who were mechanically ventilated for different diagnoses requiring intensive care. Methods We measured transpulmonary pressure (Ptp) and calculated transpulmonary driving pressure (ΔPtp) in 31 patients undergoing mechanical ventilation in an intensive care unit. Parallel triplicate measurements were performed with the PEEP step method (PtpPSM) and the conventional oesophageal balloon method (Ptpconv). Their agreement was compared using the intraclass correlation coefficient (ICC) and the Bland Altman plot. Result The coefficient of variation for the repeated measurements was 4,3 for ΔPtpPSM and 9,2 for ΔPtpconv. The ICC of 0,864 and the Bland Altman plot indicate good agreement between the two methods. Conclusion The non‐invasive method can be applied in mechanically ventilated patients to measure transpulmonary driving pressure with good repeatability and accuracy comparable to the traditional oesophageal balloon method.
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| 21. |
- 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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| 22. |
- 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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| 23. |
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| 24. |
- Jones, C, et al.
(författare)
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Precipitants of post-traumatic stress disorder following intensive care: a hypothesis generating study of diversity in care.
- 2007
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Ingår i: Intensive care medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 33:6, s. 978-85
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Tidskriftsartikel (refereegranskat)abstract
- This prospective observational study was designed to explore the relationships between post-traumatic stress disorder (PTSD), patients' memories of the intensive care unit (ICU) and sedation practices.Prospective multi-centre follow-up study out to 3 months after ICU discharge.Two district general hospitals and three teaching hospitals across Europe.Two hundred and thirty-eight recovering, post-ventilated ICU patients.None.Assessment of patients' memories of ICU was undertaken at 1-2 weeks post ICU discharge. Patients' psychological recovery was assessed by examining the level of PTSD-related symptoms and rate of PTSD by 3 months post ICU. The rate of defined PTSD was 9.2%, ranging from 3.2% to 14.8% in the different study ICUs. Independent of case mix and illness severity, the factors found to be related to the development of PTSD were recall of delusional memories, prolonged sedation, and physical restraint with no sedation.The development of PTSD following critical illness is associated with a number of different precipitating factors that are in part related to how patients are cared for within intensive care. This study raises the hypothesis that the impact of care within the ICU has an impact on subsequent psychological morbidity and therefore must be assessed in future studies looking at the way patients are sedated in the ICU and how physical restraint is used.
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| 25. |
- Lilja, Linus, et al.
(författare)
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Application of a standardized EEG pattern classification in the assessment of neurological prognosis after cardiac arrest: A retrospective analysis
- 2021
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 165, s. 38-44
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Electroencephalogram (EEG) is used in the neurological prognostication after cardiac arrest. “Highly malignant” EEG patterns classified according to Westhall have a high specificity for poor neurological outcome when applied within protocols of recent studies. However, their predictive performance when applied in everyday clinical practice has not been investigated. We studied the prognostic accuracy and the interrater agreement when standardized EEG patterns were analysed and compared to neurological outcome in a patient cohort at a tertiary centre not involved in the original study of the standardized EEG pattern classification. Methods: Comatose patients treated for out-of-hospital cardiac arrest were included. Poor outcome was defined as Cerebral Performance Category 3–5. Two senior consultants and one resident in clinical neurophysiology, blinded to clinical data and outcome, independently reviewed their EEG registrations and categorised the pattern as “highly malignant”, “malignant” or “benign”. These categories were compared to neurological outcome at hospital discharge. Interrater agreement was assessed using Cohen's Kappa. Results: In total, 62 patients were included. The median (IQR) time to EEG was 59 (42–91) h after return of spontaneous circulation. Poor outcome was found in 52 (84%) patients. In 21 patients at least one of the raters considered the EEG to contain a “highly malignant” pattern, all with poor outcome (42% sensitivity, 100% specificity). The interrater agreement varied from kappa 0.62 to 0.29. Conclusion: “Highly malignant” patterns predict poor neurological outcome with a high specificity in everyday practice. However, interrater agreement may vary substantially even between experienced EEG interpreters. © 2021
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