| 1. |
- 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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| 2. |
- Frigyesi, Attila, et al.
(författare)
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Circulating dipeptidyl peptidase 3 on intensive care unit admission is a predictor of organ dysfunction and mortality
- 2021
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Ingår i: Journal of Intensive Care. - : Springer Science and Business Media LLC. - 2052-0492. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Our aim was to investigate the prognostic potential of circulating dipeptidyl peptidase 3 (cDPP3) to predict mortality and development of organ dysfunction in a mixed intensive care unit (ICU) population, and for this reason, we analysed prospectively collected admission blood samples from adult ICU patients at four Swedish hospitals. Blood samples were stored in a biobank for later batch analysis. The association of cDPP3 levels with 30-day mortality and Sequential Organ Failure Assessment (SOFA) scores on day two was investigated before and after adjustment for the simplified acute physiology score III (SAPS-3), using multivariable (ordinal) logistic regression. The predictive power of cDPP3 was assessed using the area under the receiver operating characteristic curve (AUROC).RESULTS: Of 1978 included consecutive patients in 1 year (2016), 632 fulfilled the sepsis 3-criteria, 190 were admitted after cardiac arrest, and 157 because of trauma. Admission cDPP3 was independently (of SAPS-3) associated with 30-day mortality with odds ratios of 1.45 (95% confidence interval (CI) 1.28-1.64) in the entire ICU population, 1.30 (95% CI 1.08-1.57) in the sepsis subgroup and 2.28 (95% CI 1.50-3.62) in cardiac arrest. For trauma, there was no clear association. Circulating DPP3 alone was a moderate predictor of 30-day mortality with AUROCs of 0.68, 0.62, and 0.72 in the entire group, the sepsis subgroup, and the cardiac arrest subgroup, respectively. By adding cDPP3 to SAPS-3, AUROC improved for the entire group, the sepsis subgroup, and the cardiac arrest subgroup (p = 0.023).CONCLUSION: Circulating DPP3 on admission is a SAPS-3 independent prognostic factor of day-two organ dysfunction and 30-day mortality in a mixed ICU population and needs further evaluation.
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| 3. |
- Frigyesi, Attila, et al.
(författare)
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Plasma proenkephalin A 119-159 on intensive care unit admission is a predictor of organ failure and 30-day mortality
- 2021
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Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Proenkephalin A 119-159 (penKid) has been suggested as a marker of renal failure and poor outcome. We aimed to investigate the association of penKid on ICU admission with organ dysfunction and mortality in a mixed ICU population. In this retrospective, observational study, admission penKid levels from prospectively collected blood samples of consecutive patients admitted to four Swedish ICUs were analysed. The association of penKid with day-two sequential organ failure assessment (SOFA) scores and 30-day mortality was investigated using (ordinal) logistic regression. The predictive power of penKid for 30-day mortality and dialysis was assessed using the area under the receiver operating characteristic curve (AUC).RESULTS: Of 1978 included patients, 632 fulfilled the sepsis 3-criteria, 190 had a cardiac arrest, and 157 had experienced trauma. Admission penKid was positively associated with 30-day mortality with an odds ratio of 1.95 (95% confidence interval 1.75-2.18, p < 0.001), and predicted 30-day mortality in the entire ICU population with an AUC of 0.71 (95% confidence interval 0.68-0.73) as well as in the sepsis, cardiac arrest and trauma subgroups (AUCs of 0.61-0.84). Correction for admission plasma creatinine revealed that penKid correlated with neurological dysfunction.CONCLUSION: Plasma penKid on ICU admission is associated with day-two organ dysfunction and predictive of 30-day mortality in a mixed ICU-population, as well as in sepsis, cardiac arrest and trauma subgroups. In addition to being a marker of renal dysfunction, plasma penKid is associated with neurologic dysfunction in the entire ICU population, and cardiovascular dysfunction in sepsis.
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| 4. |
- Lang, Margareta, et al.
(författare)
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Prognostic accuracy of head computed tomography for prediction of functional outcome after out-of-hospital cardiac arrest : Rationale and design of the prospective TTM2-CT-substudy
- 2022
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Ingår i: Resuscitation Plus. - : Elsevier. - 2666-5204. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Head computed tomography (CT) is a guideline recommended method to predict functional outcome after cardiac arrest (CA), but standardized criteria for evaluation are lacking. To date, no prospective trial has systematically validated methods for diagnosing hypoxic-ischaemic encephalopathy (HIE) on CT after CA. We present a protocol for validation of pre-specified radiological criteria for assessment of HIE on CT for neuroprognostication after CA.Methods/design: This is a prospective observational international multicentre substudy of the Targeted Hypothermia versus Targeted Normother-mia after out-of-hospital cardiac arrest (TTM2) trial. Patients still unconscious 48 hours post-arrest at 13 participating hospitals were routinely exam-ined with CT. Original images will be evaluated by examiners blinded to clinical data using a standardized protocol. Qualitative assessment will include evaluation of absence/presence of "severe HIE". Radiodensities will be quantified in pre-specified regions of interest for calculation of grey-white matter ratios (GWR) at the basal ganglia level. Functional outcome will be dichotomized into good (modified Rankin Scale 0-3) and poor (modified Rankin Scale 4-6) at six months post-arrest. Prognostic accuracies for good and poor outcome will be presented as sensitivities and speci-ficities with 95% confidence intervals (using pre-specified cut-offs for quantitative analysis), descriptive statistics (Area Under the Receiver Operating Characteristics Curve), inter-and intra-rater reliabilities according to STARD guidelines.Conclusions: The results from this prospective trial will validate a standardized approach to radiological evaluations of HIE on CT for prediction of functional outcome in comatose CA patients.The TTM2 trial and the TTM2 CT substudy are registered at ClinicalTrials.gov NCT02908308 and NCT03913065.
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| 5. |
- Lengquist, Maria, et al.
(författare)
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Sepsis Is Underreported in Swedish Intensive Care Units: A Retrospective Observational Multicentre Study
- 2020
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; , s. 1167-1167
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSepsis is a common indication for admission to the intensive care unit (ICU). Since definitions vary across studies, comparisons of prevalence and outcomes have been challenging. We aimed to compare sepsis according to ICU discharge codes with sepsis according to Sepsis‐3 criteria and to investigate the epidemiology of sepsis in the ICU. We hypothesized that sepsis using discharge codes is underreported.MethodsAdult ICU admissions to four ICUs in Sweden between 2015 and 2017 were screened for sepsis according to the Sepsis‐3 criteria. Medical records were reviewed and data extracted from the Swedish Intensive Care Registry.ResultsOf 5990 adult ICU patients, 28% fulfilled the Sepsis‐3 criteria on admission, but only 31% of them had sepsis as the registered main diagnosis at ICU discharge. Of the 1654 Sepsis‐3 patients, 38% met the septic shock criteria. The Sepsis‐3 in‐hospital mortality was 26% compared to 33% in patients with septic shock. The incidence rate for ICU‐treated sepsis was 81 cases per 100 000 person‐years. One in four had a positive blood culture, and 44% were culture negative.ConclusionThis large Swedish multicentre study showed that 28% of adult ICU patients fulfilled the Sepsis‐3 criteria, but only one third of them had sepsis according to ICU discharge codes. We could confirm our hypothesis, that sepsis is severely underreported in Swedish ICUs, and we conclude that discharge codes should not be used for quality control or research purposes.
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| 6. |
- Lundberg, Oscar H.M., et al.
(författare)
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Circulating bioactive adrenomedullin as a marker of sepsis, septic shock and critical illness
- 2020
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Biomarkers can be of help to understand critical illness and to identify and stratify sepsis. Adrenomedullin is a vasoactive hormone, with reported prognostic and potentially therapeutic value in sepsis. The primary aim of this study was to investigate the association of circulating bioactive adrenomedullin (bio-ADM) levels at intensive care unit (ICU) admission with mortality in sepsis patients and in a general ICU population. Secondary aims included the association of bio-ADM with organ failure and the ability of bio-ADM to identify sepsis. Methods: In this retrospective observational study, adult patients admitted to one of four ICUs during 2016 had admission bio-ADM levels analysed. Age-adjusted odds ratios (OR) with 95% CI for log-2 transformed bio-ADM, and Youden’s index derived cut-offs were calculated. The primary outcome was 30-day mortality, and secondary outcomes included the need for organ support and the ability to identify sepsis. Results: Bio-ADM in 1867 consecutive patients were analysed; 632 patients fulfilled the sepsis-3 criteria of whom 267 had septic shock. The median bio-ADM in the entire ICU population was 40 pg/mL, 74 pg/mL in sepsis patients, 107 pg/mL in septic shock and 29 pg/mL in non-septic patients. The association of elevated bio-ADM and mortality in sepsis patients and the ICU population resulted in ORs of 1.23 (95% CI 1.07–1.41) and 1.22 (95% CI 1.12–1.32), respectively. The association with mortality remained after additional adjustment for lactate in sepsis patients. Elevated bio-ADM was associated with an increased need for dialysis with ORs of 2.28 (95% CI 2.01–2.59) and 1.97 (95% CI 1.64–2.36) for the ICU population and sepsis patients, respectively, and with increased need of vasopressors, OR 1.33 (95% CI 1.23–1.42) (95% CI 1.17–1.50) for both populations. Sepsis was identified with an OR of 1.78 (95% CI 1.64–1.94) for bio-ADM, after additional adjustment for severity of disease. A bio-ADM cut-off of 70 pg/mL differentiated between survivors and non-survivors in sepsis, but a Youden’s index derived threshold of 108 pg/mL performed better. Conclusions: Admission bio-ADM is associated with 30-day mortality and organ failure in sepsis patients as well as in a general ICU population. Bio-ADM may be a morbidity-independent sepsis biomarker.
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| 7. |
- Thorgeirsdóttir, Bergthóra, et al.
(författare)
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Plasma proenkephalin A 119-159 and dipeptidyl peptidase 3 on admission after cardiac arrest help predict long-term neurological outcome
- 2021
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Ingår i: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 163, s. 108-115
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A large proportion of adult survivors of cardiac arrest have a poor neurological outcome. Guidelines recommend multimodal neuro-prognostication no earlier than 72-96 hours after cardiac arrest. There is great interest in earlier prognostic markers, including very early markers at admission. The novel blood biomarkers proenkephalin A 119-159 (penKid), bioactive adrenomedullin (bio-ADM) and circulating dipeptidyl peptidase 3 (cDPP3) have not been previously investigated for the early prognosis of cardiac arrest survivors.METHODS: This multicentre observational study included adult survivors of cardiac arrest admitted to intensive care at four Swedish intensive care units (ICUs) during 2016. Blood samples were collected at ICU admission and batch analysed. The association between admission plasma penKid, bio-ADM and cDPP3 and poor long-term neurological outcome, according to the Cerebral Performance Category (CPC) scale, was assessed by binary logistic regression. Their prognostic performance was assessed using the area under the receiver operating characteristic curve (AUC).RESULTS: A total of 190 patients were included, of which 136 patients had suffered out-of-hospital and 54 patients in-hospital cardiac arrest. Poor long-term neurological outcome was associated with elevated admission plasma concentrations of penKid and cDPP3, but not with bio-ADM. The association for penKid, but not for cDPP3, remained after adjusting for clinical cardiac arrest variables with prognostic value (time to return of spontaneous circulation (ROSC), initial rhythm, admission Glasgow Coma Scale (GCS) motor score and absence of pupillary reflexes). The prognostic performance of above mentioned clinical cardiac arrest variables alone was very good with an AUC of 0.90 (95% confidence interval, CI, 0.86-0.95), but improved further with the addition of penKid resulting in an AUC of 0.93 (95% CI 0.89-0.97, p < 0.026). Plasma penKid and cDPP3 alone provided moderate long-term prognostic information with AUCs of 0.70 and 0.71, respectively.CONCLUSION: After cardiac arrest, admission plasma levels of penKid and cDPP3, but not bio-ADM, predicted long-term neurological outcome. When added to clinical cardiac arrest variables, penKid further improved prognostic performance.
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| 8. |
- Annborn, Martin
(författare)
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Cardiac arrest – prognostic biomarkers and aspects of shock
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Some improvement has been seen in survival after cardiac arrest but the outcome is still poor and 50-70% of patients do not survive despite successful return of spontaneous circulation (ROSC). The cause of death is multifactorial. The majority of patients die from brain injury, but up to 35% die as a result of circulatory failure. Purpose: First, to investigate the release profiles of an array of biomarkers in patients treated with mild induced hypothermia after cardiac arrest and study their correlation to the post-cardiac arrest syndrome (PCAS) and long-term outcome; Second, to investigate the effect of two different target temperatures (33°C and 36°C) on hemodynamics and vasopressor requirement in cardiac arrest patients and; Third, to investigate the association of target temperature with outcome in patients with shock in admission. Methods: The biomarkers were collected serially at 8 time points during the first 72 hours following cardiac arrest in 84 still comatose post-resuscitation cardiac arrest patients treated with mild induced hypothermia. We analysed markers of inflammation; procalcitonin (PCT) and c-reactive protein (CRP), oxidation; peroxiredoxin 4 (prx4), cardiac stress; MR-proANP, cardiac injury; Troponin T (TnT), brain injury; Neuron specific enlolase (NSE), and the stress hormone; CT-proAVP (copeptin). Outcome was assessed at 6 months with the cerebral performance category scale (CPC) where CPC 1-2 was considered a good outcome. The cardiovascular sequential organ failure assessment score (SOFA-score) and the time to ROSC were used as surrogate markers for the PCAS. Three different definitions of infection were used to assess occurrence of infection. The effect of a target temperature of 33°C or 36°C on hemodynamics was investigated in all patients with available vasopressor data (n=920) in the ‘Targeted temperature management at 33°C versus 36°C after cardiac arrest’ trial and in patients with shock on admission (n=139). Primary outcome was mortality. Secondary outcomes were vasopressor requirements as assessed by the cardiovascular SOFA-score, serum lactate concentrations, mean arterial pressure, and heart rate. Results: PCT, CT-proAVP and MR-proANP were all significantly higher in patients with poor outcome and correlated to surrogate markers of the PCAS. No specific cut-off levels were identified. PCT release was not associated to infection. Combinations of biomarkers may be a promising concept to improve prognostication. A targeted temperature of 33°C was associated with increased vasopressor requirements and increased lactate levels in both our investigated cohorts. A low MAP during the intervention (0-36 hours) was associated with poor outcome after adjustment for baseline characteristics. Conclusion: Biomarkers from other sources than the brain are associated to the PCAS and may be promising biomarkers to prognosticate outcome, alone or in combination. Targeted temperature management at 33°C is associated with increased vasopressor requirements and severity of shock and does not improve outcome as compared to 36°C.
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| 9. |
- Annborn, Martin, et al.
(författare)
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CT-proAVP (copeptin), MR-proANP and Peroxiredoxin 4 after cardiac arrest: release profiles and correlation to outcome.
- 2014
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 58:4, s. 428-436
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Tidskriftsartikel (refereegranskat)abstract
- Further characterization of the post-cardiac arrest syndrome (PCAS) is essential to better understand the mechanisms resulting in injury and death. We investigated serial serum concentrations of the stress hormone c-terminal provasopressin (CT-proAVP or copeptin), the cardiac biomarker MR-proANP and a biomarker of oxidation injury, Peroxiredoxin 4 (Prx4) in patients treated with mild hypothermia (MHT) after cardiac arrest, and studied their association to the PCAS and long-term outcome.
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| 10. |
- Annborn, Martin, et al.
(författare)
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Hypothermia versus normothermia after out-of-hospital cardiac arrest; the effect on post-intervention serum concentrations of sedatives and analgesics and time to awakening
- 2023
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Ingår i: Resuscitation. - 0300-9572. ; 188
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study investigated the association of two levels of targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) with administered doses of sedative and analgesic drugs, serum concentrations, and the effect on time to awakening. Methods: This substudy of the TTM2-trial was conducted at three centers in Sweden, with patients randomized to either hypothermia or normothermia. Deep sedation was mandatory during the 40-hour intervention. Blood samples were collected at the end of TTM and end of protocolized fever prevention (72 hours). Samples were analysed for concentrations of propofol, midazolam, clonidine, dexmedetomidine, morphine, oxycodone, ketamine and esketamine. Cumulative doses of administered sedative and analgesic drugs were recorded. Results: Seventy-one patients were alive at 40 hours and had received the TTM-intervention according to protocol. 33 patients were treated at hypothermia and 38 at normothermia. There were no differences between cumulative doses and concentration and of sedatives/analgesics between the intervention groups at any timepoint. Time until awakening was 53 hours in the hypothermia group compared to 46 hours in the normothermia group (p = 0.09). Conclusion: This study of OHCA patients treated at normothermia versus hypothermia found no significant differences in dosing or concentration of sedatives or analgesic drugs in blood samples drawn at the end of the TTM intervention, or at end of protocolized fever prevention, nor the time to awakening.
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