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Cardiac dysfunction in septic shock: Observational studies on characteristics and outcome
Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Cardiac dysfunction is a well-known complication of sepsis, but its characteristics and consequences, especially on a longer term, remain unclear. The aim of this thesis was to study the characteristics and the implications of cardiac dysfunction for outcome in intensive care unit (ICU) patients with septic shock.

Purpose: First, to assess the ability of a cardiac biomarker to predict outcome in ICU patients. Second, to characterise cardiac dysfunction in septic shock using speckle tracking echocardiography. Third, to investigate the reliability of echocardiographic methods used to describe cardiac dysfunction in septic shock. Fourth, to study long-term cardiac outcome in severe sepsis and septic shock patients.

Materials and methods: The cardiac biomarker amino-terminal pro-brain natriuretic peptide (NTproBNP) was collected in 481 patients on ICU admission and its ability to predict death was assessed. In 50 patients with septic shock, echocardiography was performed on ICU admission and was repeated during and after ICU stay. Measurements of cardiac strain using speckle tracking echocardiography were assessed in relation to other echocardiographic function parameters, NT-proBNP and severity of illness scores, and their change over time was analysed. Echocardiograms from patients with septic shock were independently evaluated by two physicians and the results analysed regarding measurement variability. A nationwide-registry-based open cohort of 9,520 severe sepsis and septic shock ICU patients discharged alive from the ICU was analysed together with a non-septic control group matched for age, sex and severity of illness. In patients who died after ICU discharge, information on causes of death was collected.

Results: A discriminatory level of significance of NT-proBNP on ICU admission was identified at ≥1,380 ng/L, above which NT-proBNP was an independent predictor of death. With increasing levels of NT-proBNP, patients were more severely ill, had a longer ICU stay and were more often admitted with septic shock. Cardiac strain was frequently impaired in septic shock patients but was not superior to other echocardiographic measurements in detecting cardiac dysfunction. Cardiac strain correlated with other echocardiographic function parameters and with NT-proBNP, and was the least user-dependent echocardiographic parameter in septic shock patients. Cardiac strain remained unchanged over time, did not differ between survivors and non-survivors and could not predict an increased risk of death. During a follow-up of up to nearly 6 years after ICU discharge, 3,954 (42%) of sepsis patients died, 654 (17%) with cardiac failure as the cause of death. With increasing severity of illness on admission, the risk of death with cardiac failure as the cause of death after ICU discharge increased. In comparison to other ICU patients with similar severity of illness, however, the risk of death due to cardiac was not increased in patients with severe sepsis or septic shock.

Conclusions: Laboratory or echocardiographic signs of cardiac dysfunction are commonly seen in ICU patients in general and in septic shock patients in particular. The assessment of cardiac dysfunction in patients with septic shock is, however, complicated by pre-existing comorbidities, by treatment given in the ICU and by critical illness in itself. Signs of cardiac dysfunction, and the increasing risk of death related to cardiac failure seen after remission of sepsis, may therefore be reflections of critical illness per se, rather than of sepsis.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. , 50 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1485
National Category
Anesthesiology and Intensive Care Cardiac and Cardiovascular Systems Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-122759DOI: 10.3384/diss.diva-122759ISBN: 978-91-7685-938-4 (print)OAI: oai:DiVA.org:liu-122759DiVA: diva2:872800
Public defence
2016-01-22, Berzeliussalen, Campus US, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2015-11-20 Created: 2015-11-20 Last updated: 2015-12-11Bibliographically approved
List of papers
1. Amino-terminal pro-brain natriuretic peptide as a predictor of outcome in patients admitted to intensive care. A prospective observational study
Open this publication in new window or tab >>Amino-terminal pro-brain natriuretic peptide as a predictor of outcome in patients admitted to intensive care. A prospective observational study
2012 (English)In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 29, no 6, 275-279 p.Article in journal (Refereed) Published
Abstract [en]

Context: Amino-terminal pro-brain-type natriuretic peptide is known to predict outcome in patients with heart failure, but its role in an intensive care setting is not yet fully established. Objective: To assess the incidence of elevated amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) on admission to intensive care and its relation to death in the ICU and within 30 days. Design: Prospective, observational cohort study. Setting: A mixed noncardiothoracic tertiary ICU in Sweden. Patients and main outcome measures NT-pro-BNP was collected from 481 consecutive patients on admission to intensive care, in addition to data on patient characteristics and outcome. A receiver-operating characteristic curve was used to identify a discriminatory level of significance, a stepwise logistic regression analysis to correct for other clinical factors and a Kaplan-Meier analysis to assess survival. The correlation between Simplified Acute Physiology Score (SAPS) 3, Sequential Organ Failure Assessment score (SOFA) and NT-pro-BNP was analysed using Spearmans correlation test. Quartiles of NT-pro-BNP elevation were compared for baseline data and outcome using a logistic regression model. Results: An NT-pro-BNP more than 1380 ng l(-1) on admission was an independent predictor of death in the ICU and within 30 days [odds ratio (OR) 2.6; 95% confidence interval (CI), 1.5 to 4.4] and was present in 44% of patients. Thirty-three percent of patients with NT-pro-BNP more than 1380 ng l(-1), and 14.6% of patients below that threshold died within 30 days (log rank P 0.005). NT-pro-BNP correlated moderately with SAPS 3 and with SOFA on admission (Spearmans rho 0.5552 and 0.5129, respectively). In quartiles of NT-pro-BNP elevation on admission, severity of illness and mortality increased significantly (30-day mortality 36.1%; OR 3.9; 95% CI, 2.0 to 7.3 in the quartile with the highest values, vs. 12.8% in the lowest quartile). Conclusion: We conclude that NT-pro-BNP is commonly elevated on admission to intensive care, that it increases with severity of illness and that it is an independent predictor of mortality.

Place, publisher, year, edition, pages
Lippincott, Williams and Wilkins / Wiley-Blackwell, 2012
Keyword
brain natriuretic peptide, intensive care, survival rate
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-78569 (URN)10.1097/EJA.0b013e32835470a8 (DOI)000304436100005 ()
Available from: 2012-06-15 Created: 2012-06-15 Last updated: 2017-12-07Bibliographically approved
2. Strain echocardiography in septic shock - a comparison with systolic and diastolic function parameters, cardiac biomarkers and outcome
Open this publication in new window or tab >>Strain echocardiography in septic shock - a comparison with systolic and diastolic function parameters, cardiac biomarkers and outcome
2015 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, 122Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Myocardial dysfunction is a well-known complication in septic shock but its characteristics and frequency remains elusive. Here, we evaluate global longitudinal peak strain (GLPS) of the left ventricle as a diagnostic and prognostic tool in septic shock.

METHODS: Fifty adult patients with septic shock admitted to a general intensive care unit were included. Transthoracic echocardiography was performed on the first day, and repeated during and after ICU stay. Laboratory and clinical data and data on outcome were collected daily from admission and up to 7 days, shorter in cases of death or ICU discharge. The correlation of GLPS to left ventricular systolic and diastolic function parameters, cardiac biomarkers and clinical data were compared using Spearman's correlation test and linear regression analysis, and the ability of GLPS to predict outcome was evaluated using a logistic regression model.

RESULTS: On the day of admission, there was a strong correlation and co-linearity of GLPS to left ventricular ejection fraction (LVEF), mitral annular motion velocity (é) and to amino-terminal pro-brain natriuretic peptide (NT-proBNP) (Spearman's ρ -0.70, -0.53 and 0.54, and R(2) 0.49, 0.20 and 0.24, respectively). In LVEF and NT-proBNP there was a significant improvement during the study period (analysis of variance (ANOVA) with repeated measures, p = 0.05 and p < 0.001, respectively), but not in GLPS, which remained unchanged over time (p = 0.10). GLPS did not correlate to the improvement in clinical characteristics over time, did not differ significantly between survivors and non-survivors (-17.4 (-20.5-(-13.7)) vs. -14.7 (-19.0 - (-10.6)), p = 0.11), and could not predict mortality.

CONCLUSIONS: GLPS is frequently reduced in septic shock patients, alone or in combination with reduced LVEF and/or é. It correlates with LVEF, é and NT-proBNP, and remains affected over time. GLPS may provide further understanding on the character of myocardial dysfunction in septic shock.

Place, publisher, year, edition, pages
BioMed Central, 2015
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-115750 (URN)10.1186/s13054-015-0857-1 (DOI)000352053300001 ()25777932 (PubMedID)
Available from: 2015-03-18 Created: 2015-03-18 Last updated: 2017-12-04
3. Variability in echocardiographic measurements of left ventricular function in septic shock patients
Open this publication in new window or tab >>Variability in echocardiographic measurements of left ventricular function in septic shock patients
2015 (English)In: Cardiovascular Ultrasound, ISSN 1476-7120, E-ISSN 1476-7120, Vol. 13, no 1, 19- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Echocardiography is increasingly used for haemodynamic evaluation and titration of therapy in intensive care, warranting reliable and reproducible measurements. The aim of this study was to evaluate the observer dependence of echocardiographic findings of left ventricular (LV) diastolic and systolic dysfunction in patients with septic shock.

METHODS: Echocardiograms performed in 47 adult patients admitted with septic shock to a general intensive care unit (ICU) were independently evaluated by one cardiologist and one intensivist for the following signs: decreased diastolic tissue velocity of the base of the LV septum (e), increased early mitral inflow (E) to e ratio (E/e), decreased LV ejection fraction (EF) and decreased LV global longitudinal peak strain (GLPS). Diastolic dysfunction was defined as e <8.0cm/s and/or E/e [greater than or equal to]15 and systolic dysfunction as EF <50% and/or GLPS>15%. Ten randomly selected examinations were re-analysed two months later. Pearson’s r was used to test the correlation and Bland-Altman plots to assess the agreement between observers. Kappa statistics were used to test the consistency between readers and intraclass correlation coefficients (ICC) for inter- and intraobserver variability.

RESULTS: In 44 patients (94%), image quality was sufficient for echocardiographic measurements. The agreement between observers was moderate (k=0.60 for e, k=0.50 for E/e and k=0.60 for EF) to good (k=0.71 for GLPS). Pearson’s r was 0.76 for e, 0.85 for E/e, 0.78 for EF and 0.84 for GLPS (p<0.001 for all four). The ICC between observers for e was very good (0.85; 95% confidence interval (CI) 0.73-0.92), good for E/e (0.70; 95% CI 0.45 - 0.84), very good for EF (0.87; 95% CI 0.77 - 0.93), excellent for GLPS (0.91; 95% CI 0.74 - 0.95), and very good for all measures repeated by one of the observers. On Bland-Altman analysis, the mean differences and 95% limits of agreement for e, E/e, EF and GLPS were 0.01 (0.04 - 0.07), 2.0 (14.2 - 18.1), 0.86 (16 - 14.3) and 0.04 (5.04 - 5.12), respectively.

CONCLUSIONS: Moderate observer-related differences in assessing LV dysfunction were seen. GLPS is the least user dependent and most reproducible echocardiographic measurement of LV function in septic shock.

Place, publisher, year, edition, pages
BioMed Central, 2015
National Category
Nursing Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-117725 (URN)10.1186/s12947-015-0015-6 (DOI)000352845000001 ()25880324 (PubMedID)
Available from: 2015-05-07 Created: 2015-05-07 Last updated: 2017-12-04Bibliographically approved
4. Cardiac mortality after severe sepsis and septic shock: A nationwide observational cohort study
Open this publication in new window or tab >>Cardiac mortality after severe sepsis and septic shock: A nationwide observational cohort study
2015 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Introduction: Cardiac dysfunction is a well-known complication of sepsis, but its long-term consequences remain unclear. The aim of this study was to investigate cardiac outcome after sepsis by assessing causes of death in a nationwide register-based cohort.

Methods: A cohort of 9,520 severe sepsis and septic shock intensive care (ICU) patients without preceding severe cardiac failure and discharged alive from the ICU was collected from the Swedish Intensive Care Registry (SIR) from 2008 to 2013, together with a nonseptic control group (n = 4,577). Patients were matched according to age, sex and severity of illness. Information on cause of death after ICU discharge was sought in the Swedish National Board of Health and Welfare’s Cause of Death Registry.

Results: After ICU discharge, 3,954 (42%) of severe sepsis or septic shock patients died. In 654 (16%) of these, cardiac failure was registered as the cause of death. The follow-up time was 17,693 person-years (median 583 days/person; maximum 5.7 years) and the median (IQR) time from ICU discharge to cardiac failure-related death 81 (17 - 379) days. With increasing severity of illness (quartiles of SAPS3), the hazard rate for cardiac failure-related death increased (hazard ratio (HR) 1.58 (95% CI 1.19 - 2.09, p <0.001) in the highest quartile compared to the lowest). In a matched comparison between severe sepsis or septic shock patients and controls, survival was similar, and the hazard rate for cardiac failurerelated death did not differ between groups (HR 0.97, 95% CI 0.88 – 1.10, p = 0.62).

Conclusions: The risk of death with cardiac failure as the cause of death after severe sepsis or septic shock increases with severity of illness on admission. Patients with severe sepsis or septic shock are not, however, at an increased risk of death with cardiac failure as the cause of death when compared to other ICU patients with similar severity of illness.

Keyword
Shock, septic; Heart failure; Intensive care; Outcome
National Category
Nursing Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-122757 (URN)
Available from: 2015-11-20 Created: 2015-11-20 Last updated: 2015-11-20Bibliographically approved

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