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Severe sepsis: epidemiology and sex-related differences in inflammatory markers
Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
2014 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Background.  Sepsis is a syndrome associated with high mortality rates, substantial morbidity and high costs of care. The incidents of sepsis is reported to be high and controversy exists whether gender affect severity or outcome. Little is known about factors determining suscepti­bility for developing the syndrome and severity of the syndrome once developed. Early detection and adequate antibiotic administration are the mainstay of treatment and means to identify patients with particular high risk of adverse outcome are desirable. There are data to suggest that the course of sepsis and outcome from the syndrome may be influenced by inherited differences in the immunological response among humans

Aims: Paper I: Assess incidence and outcome for ICU-treated sepsis patients in this region; Paper II: Assess if there are gender differences related to characteristics, aspects of treatment or out­come in sepsis in this region. Paper III: Assess the association of baseline levels of leptin and adiponectin and future sepsis event, and association of these adipokines in the cute phase and sepsis severity and outcome. Paper IV: Assess association of baseline levels of mannose-binding lectin (MBL) and future sepsis event, and MBL levels in the acute phase in relation to sepsis severity and outcome.

Results. Paper I:  Overall ICU mortality rate was 25%, while the ICU mortality for patients with septic shock was 58% in this retrospective single university hospital cohort analysis. Cardio­vascular disease and diabetes were the most prevalent comorbidities among patients who died during hospital stay.  Paper II:  No gender-related differences in mortality or length of stay was found in this prospective single center observational study. Differences in aspects of treatment were related to differences in site of infection. Men had more often infections in skin and skin-structures, whereas women more often had abdominal infections. Early organ dysfunction asses­sed as SOFA score at admission was a stronger predictor for hospital mortality for women than for men. The discrepancy was related to the SOFA coagulation-sub score.  Paper III: In this nes­ted case-referent study hyperleptinemia at baseline predicted a first-ever sepsis event, even after adjustment for BMI and other cardiovascular risk factors. Hyperleptinemia in the acute sepsis phase was associated with reduced risk of in-hospital death in men, but associated with increased risk of in-hospital   death in women.  Paper IV: In the same matched cohort as in Paper III high baseline levels of MBL predicted a first ever sepsis event. High MBL levels in the acute phase or an increase from baseline to the acute phase associate with increased in-hospital death in women but not in men. Low MBL levels was not identified as a risk for acute sepsis or in-hospital death.

Conclusions. Mortality from severe sepsis is high, equally affecting men and women. There are differences in patient characteristics and inflammatory markers, which associate with in-hospital mortality differentially in men and women. Aspects of gender should be mandatory, and genetic analysis are desired in future sepsis research.

sted, utgiver, år, opplag, sider
Umeå: Umeå Universitet , 2014. , s. 110
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1680
Emneord [en]
Severe sepsis, Leptin, Adiponectin, Mannose-binding lectin, Sex
HSV kategori
Forskningsprogram
anestesiologi
Identifikatorer
URN: urn:nbn:se:umu:diva-96214ISBN: 978-91-7601-149-2 (tryckt)OAI: oai:DiVA.org:umu-96214DiVA, id: diva2:762652
Disputas
2014-12-04, Sal B, Unod T, 9 tr, Norrlands Universitetssjukhus, Umeå, 09:00 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2014-11-13 Laget: 2014-11-12 Sist oppdatert: 2024-07-02bibliografisk kontrollert
Delarbeid
1. Primary sepsis in a university hospital in northern Sweden: a retrospective study
Åpne denne publikasjonen i ny fane eller vindu >>Primary sepsis in a university hospital in northern Sweden: a retrospective study
2004 (engelsk)Inngår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 48, nr 8, s. 960-967Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: Severe sepsis and septic shock are associated with high mortality rates. Data on sepsis outcome from Scandinavian countries are sparse. The aim of this study was to examine the length of stay (LOS) in the ICU, ICU mortality and costs of care for adult patients with primary sepsis in a university hospital in northern Sweden.

METHODS: We performed a retrospective data analysis of records of 92 patients admitted over a 3-year period, under the diagnosis of sepsis or urosepsis. Demographic data, admission category, APACHE II score, aetiology and severity of sepsis, ICU LOS, mortality and TISS were analyzed.

RESULTS: Eighty-one adult patients were identified by standard definitions as suffering from sepsis. The median ICU length of stay was 4.2 days, 6 days for survivors and 2.1 days for non-survivors. Thirteen out of 20 deaths occurred within the first 3 days after admission. Overall ICU mortality rate was 24.7% while the ICU mortality for patients with septic shock was 57.7%. The mean costs of care for patients with sepsis were 3139 Euros day(-1) and the cost of care per patient surviving sepsis was 38,494 Euros.

CONCLUSION: The incidence of primary sepsis in our ICU was low. Previous reports on high mortality in association with severe sepsis and septic shock are valid also at our hospital. The ICU-LOS was shorter than previously reported, while our costs of care were in the same range as stated by others. This retrospective analysis is valid for interpretation of the applicability of currently available sepsis therapies.

sted, utgiver, år, opplag, sider
John Wiley & Sons, 2004
Emneord
Adolescent, Adult, Age Factors, Aged, Aged; 80 and over, Cause of Death, Child, Child; Preschool, Costs and Cost Analysis, Female, Hospitals; University, Humans, Infant, Infant; Newborn, Intensive Care Units/economics/statistics & numerical data, Male, Middle Aged, Referral and Consultation, Retrospective Studies, Sepsis/economics/*epidemiology/mortality, Shock; Septic/economics/*epidemiology/mortality, Survival Analysis, Sweden/epidemiology, Treatment Outcome
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-6801 (URN)10.1111/j.0001-5172.2004.00458.x (DOI)000223378800005 ()15315612 (PubMedID)
Tilgjengelig fra: 2008-01-12 Laget: 2008-01-12 Sist oppdatert: 2023-05-02bibliografisk kontrollert
2. Sequential organ failure assessment score (SOFA) scores differ between genders in a sepsis cohort: cause or effect?
Åpne denne publikasjonen i ny fane eller vindu >>Sequential organ failure assessment score (SOFA) scores differ between genders in a sepsis cohort: cause or effect?
Vise andre…
2012 (engelsk)Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, nr 4, s. 415-425Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: Controversy exists regarding the influence of gender on sepsis events and out­come. Epidemiological data from other countries may not always apply to local circum­stances.  The aim of this study was to identify gender differences in patient characteristics, treatment and outcome related to the occurrence of sepsis at admission to the ICU.

Methods: A prospective observational cohort study on patients admitted to the ICU over a three-year period fulfilling sepsis criteria during the first 24 hours. Demographic data, APACHE II score, SOFA score, TISS 76, aetiology, length of stay (LOS), mortality rate and aspects of treatment were collected and then analysed with respect to gender differences.

Results: There were no gender related differences in mortality or length of stay. Early organ dysfunction assessed as SOFA score at admission was a stronger risk factor for hospital mor­tality for women than for men. This discrepancy was mainly associated with the coagulation sub score. CRP-levels differed between genders in relation to hospital mortality. Infection from the abdominopelvic region was more common among women whereas infection from skin or skin structures were more common in men.

Conclusion: In this cohort, gender was not associated with increased mortality during a two year follow up period.  SOFA score at ICU-admission was a stronger risk factor for hospital mortality for women than for men. The discrepancy was mainly related to the coagulation SOFA sub score. Together with differences in CRP-levels this may suggest differences in inflammatory response patterns between genders.

sted, utgiver, år, opplag, sider
Informa Healthcare, 2012
Emneord
APACHE II, gender, ICU length of stay, mortality, septic shock, Severe sepsis, SOFA
HSV kategori
Forskningsprogram
anestesiologi
Identifikatorer
urn:nbn:se:umu:diva-56290 (URN)10.3109/03009734.2012.703255 (DOI)000310372800009 ()2-s2.0-84868241158 (Scopus ID)
Tilgjengelig fra: 2012-06-15 Laget: 2012-06-13 Sist oppdatert: 2023-05-02bibliografisk kontrollert
3. Leptin independently predicts development of future sepsis and determines survival in the acute phase
Åpne denne publikasjonen i ny fane eller vindu >>Leptin independently predicts development of future sepsis and determines survival in the acute phase
Vise andre…
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
Abstract [en]

Objective: To determine if levels of the adipocyte-derived hormones leptin and adiponectin (adipokines) predict sepsis development and if intra-individual changes in circulating levels from baseline to the acute phase affect outcome.

Method: A nested case-referent study within the framework of the Northern Sweden Health and Disease Study (NSHDS) and the Northern Sweden Maternity Cohort (NSMC). Patients aged 18 years or more with documented sepsis within 24 hours after admission to the intensive care unit (ICU) were included if they had participated in a health survey and donated blood samples prior to the sepsis event, and if possible also had stored plasma from the acute phase. Two matched referents free of known sepsis were selected for each case. Baseline and acute phase plasma leptin and adiponectin levels were determined. The associations between adipokines and sepsis and its severity and outcome were determined.

Results: We identified 57 men and 97 women with a first-time sepsis event 6.5 years (median with IQR 7.7) after participation in the health survey, and 83% of them had also samples from the acute septic phase. Hyperleptinemia associated with a future sepsis event (OR 1.77, 95% CI 1.04-3.00, P=0.03), with stronger associations with severe sepsis and septic shock than with sepsis. High leptin levels were also associated with hospital death in the fully adjusted model. Leptin remained associated with sepsis in men (P=0.02), but not in women (P=0.36), after stratification and adjustment for BMI. In the acute phase, leptin increased more in men than in women (P=0.001), and high leptin levels were associated with increased risk for in-hospital death in women (OR 4.18, 95%CI 1.17-15.00, P=0.03), while being protective in men (OR 0.05, 95% CI 0.01-0.48, P=0.01). Adiponectin did not associate with sepsis or outcome.

Conclusions: Hyperleptinemia independently predicted the development of sepsis, and an unfavourable outcome in men. Adiponectin was not associated with sepsis development.

Emneord
sepsis, leptin, adiponectin, case-referent study, sex
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-95811 (URN)
Tilgjengelig fra: 2014-11-05 Laget: 2014-11-05 Sist oppdatert: 2024-07-02bibliografisk kontrollert
4. Levels of mannose-binding lectin (MBL) predicts sepsis and associates with sepsis-related in-hospital mortality differentially in men and women
Åpne denne publikasjonen i ny fane eller vindu >>Levels of mannose-binding lectin (MBL) predicts sepsis and associates with sepsis-related in-hospital mortality differentially in men and women
Vise andre…
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
Abstract [en]

Objective: To determine if levels of mannose-binding lectin (MBL) predict sepsis development and if intra-individual changes in circulating levels from baseline to the acute septic phase associate with in-hospital mortality.

Method: A nested case-referent study within the framework of the Northern Sweden Health and Disease Study (NSHDS) and the Northern Sweden Maternity Cohort (NSMC). Patients aged 18 years or more with documented sepsis within 24 hours after admission to the intensive care unit were included if they had participated in a health survey and donated blood samples prior to the sepsis event. A subset of these patients had stored plasma also from the acute phase. Two matched referents free of known sepsis were selected for each case. Baseline and acute phase plasma MBL levels were determined. The association between MBL and sepsis, sepsis severity and in-hospital mortality were determined.

Results: We identified 57 men and 95 women with a first-time sepsis event 6.5 years (median with IQR 7.7) after participation in a health survey, of which 127 also had samples from the acute septic phase. High baseline levels predicted future sepsis (OR 1.81, 95% CI 1.01-3.26), but were not associated with severity of sepsis or in-hospital fatality. Both high MBL levels in the acute phase (OR 4.94, 95% CI 1.44-16.89), and an increase from base line to the acute phase (OR 3.67, 95% CI 1.19-11.28) were associated with increased risk for in-hospital death in women, but not in men (OR 0.71, 95% CI 0.18-2.88). Low levels at baseline were not associated with future sepsis. Neither low levels at baseline, nor in the acute phase were associated with sepsis severity or in-hospital mortality.

Conclusions: High pre-sepsis levels predicted a future sepsis event, and an increase from baseline to the acute phase as well as high levels in the acute phase associated with an unfavourable outcome in women.

Emneord
sepsis; mannose-binding lectin; sex; case-referent study
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-95814 (URN)
Tilgjengelig fra: 2014-11-05 Laget: 2014-11-05 Sist oppdatert: 2024-07-02bibliografisk kontrollert

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