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Leukemia & lymphoma 04/2013; · 2.40 Impact Factor
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ABSTRACT: Fluid resuscitation is an essential part of initial sepsis management. Hydroxyethyl starch solutions are used to maintain or achieve volume expansion, but their safety and efficacy remains controversial.
British journal of hospital medicine (London, England: 2005) 03/2013; 74(3):178-Unknown. · 0.19 Impact Factor
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ABSTRACT: PURPOSE: To assess the impact of 6 % tetrastarch [hydroxyethyl starch (HES) 130/0.4 and 130/0.42] in severe sepsis patients. The primary outcome measure was 90-day mortality. METHODS: A structured literature search was undertaken to identify prospective randomised controlled trials (RCTs) in adult patients with severe sepsis receiving 6 % tetrastarch (of potato or waxy maize origin) as part of fluid resuscitation in comparison with other non-HES fluids after randomisation in the critical care setting. A systematic review and meta-analysis were performed. RESULTS: Six RCTs were included (n = 3,033): three from 2012 (n = 2,913) had low risk of bias. Median tetrastarch exposure was 37.4 ml/kg (range 30-43 ml/kg). Ninety-day mortality was associated with tetrastarch exposure [relative risk (RR) 1.13; 95 % confidence interval (CI) 1.02-1.25; p = 0.02] compared with crystalloid. The number needed to harm (NNH) was 28.8 (95 % CI 14.6-942.5). Publication bias and statistical heterogeneity (I (2) = 0 %) were not present. Tetrastarch exposure was also associated with renal replacement therapy (p = 0.01; NNH 15.7) and allogeneic transfusion support (p = 0.001; NNH 9.9). No difference between groups was observed for 28-day mortality, for comparison with colloid as control, or for waxy maize-derived tetrastarch, but power was lacking. Overall mortality was associated with tetrastarch exposure (RR 1.13; 95 % CI 1.02-1.25; p = 0.02). CONCLUSIONS: In our analysis, 6 % tetrastarch as part of initial fluid resuscitation for severe sepsis was associated with harm and, as alternatives exist, in our view should be avoided.
European Journal of Intensive Care Medicine 02/2013; · 5.17 Impact Factor
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Damon P Eisen,
Melinda M Dean,
Marja A Boermeester,
Katy J Fidler,
Anthony C Gordon,
Gitte Kronborg,
Jürgen F J Kun,
Yu Lung Lau,
Antonis Payeras,
Helgi Valdimarsson, Stephen J Brett,
W K Eddie Ip,
Joan Mila,
Mark J Peters,
Saedis Saevarsdottir,
J W Oliver van Till,
Charles J Hinds,
Emma S McBryde
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ABSTRACT: Previous studies have shown associations between low mannose-binding lectin (MBL) level or variant MBL2 genotype and sepsis susceptibility. However, MBL deficiency has not been rigorously defined, and associations with sepsis outcomes have not been subjected to multivariable analysis.
We reanalyzed MBL results in a large cohort with use of individual data from 4 studies involving a total of 1642 healthy control subjects and systematically defined a reliable deficiency cutoff. Subsequently, data were reassessed to extend previous MBL and sepsis associations, with adjustment for known outcome predictors. We reanalyzed individual data from 675 patients from 5 adult studies and 1 pediatric study of MBL and severe bacterial infection.
XA/O and O/O MBL2 genotypes had the lowest median MBL concentrations. Receiver operating characteristic analysis revealed that an MBL cutoff value of 0.5 microg/mL was a reliable predictor of low-producing MBL2 genotypes (sensitivity, 82%; specificity, 82%; negative predictive value, 98%). MBL deficiency was associated with increased likelihood of death among patients with severe bacterial infection (odds ratio, 2.11; 95% confidence interval, 1.30-3.43). In intensive care unit-based studies, there was a trend toward increased risk of death among MBL-deficient patients (odds ratio, 1.58; 95% confidence interval, 0.90-2.77) after adjustment for Acute Physiology and Chronic Health Enquiry II score. The risk of death was increased among MBL-deficient patients with Streptococcus pneumoniae infection (odds ratio, 5.62; 95% confidence interval, 1.27-24.92) after adjustment for bacteremia, comorbidities, and age.
We defined a serum level for MBL deficiency that can be used with confidence in future studies of MBL disease associations. The risk of death was increased among MBL-deficient patients with severe pneumococcal infection, highlighting the pathogenic significance of this innate immune defence protein.
Clinical Infectious Diseases 08/2008; 47(4):510-6. · 9.15 Impact Factor
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ABSTRACT: Mannose-binding lectin (MBL) genetic polymorphisms result in deficiency of the encoded protein and increased susceptibility to infection, especially in children and the immunocompromised. The objective of this study was to investigate the relationship between MBL-2 exon 1 and promoter -221 polymorphisms, plasma levels of the encoded protein, and the incidence and outcome of severe sepsis and septic shock. One hundred seventy-four white adult patients with severe sepsis or septic shock were recruited in a prospective multicenter study across eight intensive care units in the South of England, UK. Genotype and haplotype frequencies were compared between normal population controls and patients, and between survivors and nonsurvivors. Plasma levels of encoded protein were related to genotype and outcome. The exon 1 polymorphisms (A/O or O/O) were significantly more common in the patients with severe sepsis and septic shock than in normal healthy adults (54.6% vs. 39.7%, P = 0.001), and there was a significant difference in haplotype frequency between controls and septic patients (P < 0.0001). There was no significant difference in MBL-2 genotype or haplotype frequency between survivors and nonsurvivors. There was a strong relationship between MBL-2 haplotype and plasma MBL concentration (P < 0.001). Individual plasma levels were variable and increased between days 1 and 7. The mortality rate was higher in those with MBL levels <1000 microg/L than in those patients with levels >1000 microg/L (47.2 vs. 22.2%, P = 0.05). We conclude that genetic polymorphisms resulting in mannose-binding lectin deficiency are associated with increased susceptibility to sepsis. The close relationship between polymorphic variants and plasma MBL concentration persists during sepsis but individual levels vary widely. Lower circulating MBL levels are associated with a poor outcome.
Shock 02/2006; 25(1):88-93. · 2.85 Impact Factor
