| 1. |
- Lundberg, Oscar, et al.
(författare)
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Adrenomedullin and endothelin-1 are associated with myocardial injury and death in septic shock patients
- 2016
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- AbstractBackgroundAdrenomedullin and endothelin-1 are hormones with opposing effects on the cardiovascular system. Adrenomedullin acts as a vasodilator and seems to be important for the initiation and continuation of the hyperdynamic circulatory response in sepsis. Endothelin-1 is a vasoconstrictor and has been linked to decreased cardiac performance. Few studies have studied the relationship between adrenomedullin and endothelin-1, and morbidity and mortality in septic shock patients. High-sensitivity troponin T (hsTNT) is normally used to diagnose acute cardiac injury but is also prognostic for outcome in intensive care. We investigated the relationship between mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and myocardial injury, measured using transthoracic echocardiography and hsTNT in septic shock patients. We were also interested in the development of different biomarkers throughout the ICU stay, and how early measurements were related to mortality. Further, we assessed if a positive biomarker panel, consisting of MR-proADM, CT-proET-1, and hsTNT changed the odds for mortality.MethodsA cohort of 53 consecutive patients with septic shock had their levels of MR-proADM, CT-proET-1, hsTNT, and left ventricular systolic functions prospectively measured over 7 days. The relationship between day 1 levels of MR-proADM/CT-proET-1 and myocardial injury was studied. We also investigated the relationship between biomarkers and early (7-day) and later (28-day) mortality. Likelihood ratios, and pretest and posttest odds for mortality were calculated.ResultsLevels of MR-proADM and CT-proET-1 were significantly higher among patients with myocardial injury and were correlated with left ventricular systolic dysfunction. MR-proADM and hsTNT were significantly higher among 7-day and 28-day non-survivors. CT-proET-1 was also significantly higher among 28-day but not 7-day non-survivors. A positive biomarker panel consisting of the three biomarkers increased the odds for mortality 13-fold to 20-fold.ConclusionsMR-proADM and CT-proET-1 are associated with myocardial injury. A biomarker panel combining MR-proADM, CT-proET-1, and hsTNT increases the odds ratio for death, and may improve currently available scoring systems in critical care.Keywords: Sepsis, Shock, Adrenomedullin, Endothelin-1, High-sensitivity troponin, Echocardiography, Myocardial injury, Mortality, Likelihood ratio
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| 2. |
- Lundberg, Oscar, et al.
(författare)
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Bioactive adrenomedullin in sepsis patients in the emergency department is associated with mortality, organ failure and admission to intensive care
- 2022
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:4, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAdrenomedullin is a vasoactive hormone with potentially prognostic and therapeutic value, which mainly has been investigated in intensive care unit (ICU) settings. The triaging in the emergency department (ED) of patients to the right level of care is crucial for patient outcome.ObjectivesThe primary aim of this study was to investigate the association of bioactive adrenomedullin (bio-ADM) with mortality among sepsis patients in the ED. Secondary aims were to investigate the association of bio-ADM with multiple organ failure (MOF), ICU admission and ED discharge.MethodsIn this prospective observational cohort study, adult sepsis patients in the ED (2013–2015) had blood samples collected for later batch analysis of bio-ADM. Odds ratios (OR) with 95% confidence interval (CI) for bio-ADM were calculated.ResultsBio-ADM in 594 sepsis patients was analyzed of whom 51 died within 28 days (8.6%), 34 developed severe MOF, 27 were ICU admitted and 67 were discharged from the ED. The median (interquartile range) bio-ADM was 36 (26–56) and 63 (42–132) pg/mL among survivors and non-survivors, respectively, 81 (56–156) pg/mL for patients with severe MOF and 77 (42–133) pg/mL for ICU admitted patients. Each log-2 increment of bio-ADM conferred an OR of 2.30 (95% CI 1.74–3.04) for mortality, the adjusted OR was 2.39 (95% CI 1.69–3.39). The area under the receiver operating characteristic curve of a prognostic mortality model based on demographics and biomarkers increased from 0.80 to 0.86 (p = 0.02) when bio-ADM was added. Increasing bio-ADM was associated with severe MOF, ICU admission and ED discharge with adjusted ORs of 3.30 (95% CI 2.13–5.11), 1.75 (95% CI 1.11–2.77) and 0.46 (95% CI 0.32–0.68), respectively.ConclusionBio-ADM in sepsis patients in the ED is associated with mortality, severe MOF, ICU admission and ED discharge, and may be of clinical importance for triage of sepsis patients in the ED.
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| 3. |
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| 4. |
- Rosenqvist, Mari, et al.
(författare)
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Improved Outcomes After Regional Implementation of Sepsis Alert : A Novel Triage Model
- 2020
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Ingår i: Critical Care Medicine. - 1530-0293. ; 48:4, s. 484-490
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To assess whether the triage model Sepsis Alert for Emergency Departments results in improved initial care of patients with severe infections. DESIGN: Interventional study comparing patient care before and after the start of a new triage model, including 90-day follow-up. SETTING: Eight emergency departments in Skåne County, Sweden. SUBJECTS: Patients with suspected severe infection. INTERVENTIONS: Patients with severely deviating vital signs and suspected infection were triaged into a designated sepsis line called Sepsis Alert, for rapid evaluation supported by an infectious disease specialist. Also, all emergency department staff participated in a designated sepsis education before the model was introduced. MEASUREMENTS AND MAIN RESULTS: Medical records were evaluated for a 3-month period 1 year before the triage system was started in 2016 and for a 3-month period 1 year after. Of 195,607 patients admitted to these emergency departments during two 3-month periods, a total of 5,321 patients presented severely abnormal vital signs. Of these, 1,066 patients who presented with fever greater thanor equal to 38°C or history of fever/chills were considered to be patients at risk of having severe sepsis. Among patients triaged according to Sepsis Alert, 89.3% received antibiotic treatment within 1 hour after arrival to the emergency department (median time to antibiotics, 26 min), which was significantly better than before the start of the new triage: 67.9% (median time to antibiotics, 37 min) (p < 0.001). Additionally, sepsis treatment quality markers were significantly improved after the introduction of Sepsis Alert, including number of blood cultures and lactate measurements taken, percentage of patients receiving IV fluids, and appropriate initial antibiotic treatment. There were no differences in 28- or 90-day mortality rates. CONCLUSIONS: The implementation of the new triage model Sepsis Alert with special attention to severe sepsis patients led to faster and more accurate antibiotic treatment and improved diagnostic procedures and supportive care.
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| 5. |
- Rosenqvist, Mari, et al.
(författare)
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Proenkephalin a 119-159 (penKid) - a novel biomarker for acute kidney injury in sepsis : an observational study
- 2019
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Ingår i: BMC Emergency Medicine. - : Springer Science and Business Media LLC. - 1471-227X. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sepsis is a leading cause of death worldwide and a major challenge for physicians to predict and manage. Proenkephalin A 119-159 (penKid) is a reliable surrogate marker for the more unstable endogenous opioid peptide enkephalin, which has previously been shown to predict both acute and chronic kidney disease. The aim of this prospective observational study was to assess penKid as a predictor of acute kidney injury (AKI), multi-organ failure and mortality in sepsis among unselected sepsis patients presenting to the emergency department (ED). Method: We enrolled 644 patients consecutively during office-hours (6 AM-6 PM) between December 1, 2013 and February 1, 2015. Fifty-six patients were excluded due to incomplete data. We measured penKid in 588 adult patients (patients under 18 years of age were excluded) with sepsis (≥2SIRS criteria + suspected infection) upon admission to the ED at Skåne University Hospital, Malmö, Sweden. Logistic regression analysis was used to relate levels of penKid at presentation to AKI, multi-organ failure, 28-day mortality and progression of renal SOFA subscore. Odds ratios are presented as the number of standard deviations from the mean of log-transformed penKid. Results: In age and sex adjusted models, penKid predicted AKI within 48 h and 7 days, but these associations were attenuated after additional adjustment for estimated creatinine-based glomerular filtration rate (eGFR). In models adjusted for age, sex and eGFR, penKid significantly predicted progression from rSOFA = 0 and ≤ 1 to higher rSOFA scores as well as multi-organ failure and mortality. In contrast, eGFR did not predict 28-day mortality. Conclusion: PenKid is an effective predictor of renal injury, severe multi-organ failure and mortality in unselected sepsis patients presenting to the emergency department.
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| 6. |
- Rosenqvist, Mari, et al.
(författare)
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Sepsis Alert – a triage model that reduces time to antibiotics and length of hospital stay
- 2017
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 49:7, s. 507-513
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study if a modified triage system at an Emergency Department (ED) combined with educational efforts resulted in reduced time to antibiotics and decreased length of hospital stay (LOS) for patients with severe infection. Methods: A retrospective, observational study comparing patients before and after the start of a new triage model at the ED of a University Hospital. After the implementation of the model, patients with fever and abnormal vital signs were triaged into a designated sepsis line (Sepsis Alert) for rapid evaluation by the attending physician supported by a infectious diseases (IDs) specialist. Also, all ED staff participated in a designated sepsis education before Sepsis Alert was introduced. Medical records were evaluated for patients during a 3-month period after the triage system was started in 2012, and also during the corresponding months in 2010 and 2014. Results: A total of 1837 patients presented with abnormal vital signs. Of these, 221 patients presented with fever and thus at risk of having severe sepsis. Among patients triaged according to the new model, median time to antibiotics was 58.5 at startup and 24.5 minutes at follow-up two years later. This was significantly less than for patients treated before the new model, 190 minutes. Also, median LOS was significantly decreased after introduction of the new triage model, from nine to seven days. Conclusions: A triage model at the ED with special attention to severe sepsis patients, led to sustained improvements of time to antibiotic treatment and LOS.
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| 7. |
- Rosenqvist, Mari
(författare)
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Sepsis - an ED perspective. Sepsis Alert & Biomarkers.
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Sepsis, the life-threatening organ dysfunction due to dysregulated host response to an infection, is a medical emergency. Early diagnosis and treatment are important factors to prevent mortality and morbidity. However, sepsis can be diffuse and difficult to interpret. Therefore, it is important to define models for early identification applicable in the Emergency Department (ED), in order to meet the therapeutic goals of the Surviving Sepsis Campaign (SSC).Aim: To improve initial sepsis care at the ED by identifying biomarkers for risk stratification and by a region-wide implementation of the novel triage model Sepsis Alert. Methods: In the first study we retrospectively evaluated the implementation of the Sepsis Alert at the ED, SUS Malmö. The second study was a post-hoc analysis of the biomarker mid-regional proadrenomedullin (MR-proADM) ́s ability to guide antibiotic administration at the ED. In the third study, a prospective observational study, we investigated the biomarker proenkephalin A 119-159 (penKid) as a predictor of acute kidney injury, multi-organ failure (MOF) and mortality in unselected sepsis patients at the ED. The fourth study was a before-and-after multicenter study to assess whether the Sepsis Alert resulted in improved initial care of patients with severe infections at the ED. Results: We found that the implementation of Sepsis Alert led to shorter time to (appropriate) antibiotics, improvement of quality markers of sepsis care in accordance with SSC, and decreased length of hospital stay. Also, in a subgroup of 5/8 EDs, ICU care decreased after the intervention (Studies I & IV). In Study II, MR-proADM on arrival at the ED had the strongest association with the requirement for antibiotic administration, compared to other biomarkers. Also, ICU care and 28-day mortality was zero in patients with low concentrations of MR-proADM. In study III, penKid in unselected sepsis patients at the ED significantly predicted progression from renal-SOFA ≤ 1 to higher renal-SOFA scores, MOF, and mortality. Conclusions: The triage model Sepsis Alert improves sepsis care and is today an integrated part of the daily routine at the EDs in Skåne Region, and the experiences from this work are applied in the national mandatory guidelines “Personcentrerat och sammanhållet vårdförlopp för sepsis”. Moreover, the biomarker studied in this thesis may identify sepsis patients with good (low MR-proADM), and poor (high penKid) prognosis.
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| 8. |
- Rosenqvist, Mari, et al.
(författare)
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The authors reply
- 2020
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Ingår i: Critical Care Medicine. - 0090-3493. ; 48:7, s. 633-634
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Saeed, Kordo, et al.
(författare)
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The early identification of disease progression in patients with suspected infection presenting to the emergency department : A multi-centre derivation and validation study
- 2019
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a lack of validated tools to assess potential disease progression and hospitalisation decisions in patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify suitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-65) to fulfil this unmet clinical need. Methods: An observational derivation patient cohort validated by an independent secondary analysis across nine EDs. Logistic and Cox regression, area under the receiver operating characteristic (AUROC) and Kaplan-Meier curves were used to assess performance. Disease progression was identified using a composite endpoint of 28-day mortality, ICU admission and hospitalisation > 10 days. Results: One thousand one hundred seventy-five derivation and 896 validation patients were analysed with respective 28-day mortality rates of 7.1% and 5.0%, and hospitalisation rates of 77.9% and 76.2%. MR-proADM showed greatest accuracy in predicting 28-day mortality and hospitalisation requirement across both cohorts. Patient subgroups with high MR-proADM concentrations (≥ 1.54 nmol/L) and low biomarker (PCT < 0.25 ng/mL, lactate < 2.0 mmol/L or CRP < 67 mg/L) or clinical score (SOFA < 2 points, qSOFA < 2 points, NEWS < 4 points or CRB-65 < 2 points) values were characterised by a significantly longer length of hospitalisation (p < 0.001), rate of ICU admission (p < 0.001), elevated mortality risk (e.g. SOFA, qSOFA and NEWS HR [95%CI], 45.5 [10.0-207.6], 23.4 [11.1-49.3] and 32.6 [9.4-113.6], respectively) and a greater number of disease progression events (p < 0.001), compared to similar subgroups with low MR-proADM concentrations (< 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MR-proADM cut-off of < 0.87 nmol/L (15.0% and 16.6%), with decreased readmission rates and no mortalities. Conclusions: In patients presenting to the ED with a suspected infection, the blood biomarker MR-proADM could most accurately identify the likelihood of further disease progression. Incorporation into an early sepsis management protocol may therefore aid rapid decision-making in order to either initiate, escalate or intensify early treatment strategies, or identify patients suitable for safe out-patient treatment.
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| 10. |
- Strålin, Kristoffer, et al.
(författare)
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Design of a national patient-centred clinical pathway for sepsis in Sweden
- 2023
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Ingår i: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 55:10, s. 716-724
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The World Health Organization has adopted a resolution on sepsis and urged member states to develop national processes to improve sepsis care. In Sweden, sepsis was selected as one of the ten first diagnoses to be addressed, when the Swedish government in 2019 allocated funds for patient-centred clinical pathways in healthcare. A national multidisciplinary working group, including a patient representative, was appointed to develop the patient-centred clinical pathway for sepsis.METHODS: The working group mapped challenges and needs surrounding sepsis care and included a survey sent to all emergency departments (ED) in Sweden, and then designed a patient-centred clinical pathway for sepsis.RESULTS: The working group decided to focus on the following four areas: (1) sepsis alert for early detection and management optimisation for the most severely ill sepsis patients in the ED; (2) accurate sepsis diagnosis coding; (3) structured information to patients at discharge after sepsis care and (4) structured telephone follow-up after sepsis care. A health-economic analysis indicated that the implementation of the clinical pathway for sepsis will most likely not drive costs. An important aspect of the clinical pathway is implementing continuous monitoring of performance and process indicators. A national working group is currently building up such a system for monitoring, focusing on extraction of this information from the electronic health records systems.CONCLUSION: A national patient-centred clinical pathway for sepsis has been developed and is currently being implemented in Swedish healthcare. We believe that the clinical pathway and the accompanying monitoring will provide a more efficient and equal sepsis care and improved possibilities to monitor and further develop sepsis care in Sweden.
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