Systematic review of randomized clinical trials on the use of hydroxyethyl starch for fluid management in sepsis

<p>Abstract</p> <p>Background</p> <p>Patients with sepsis typically require large resuscitation volumes, but the optimal type of fluid remains unclear. The aim of this systematic review was to evaluate current evidence on the effectiveness and safety of hydroxyethyl starch for fluid management in sepsis.</p> <p>Methods</p> <p>Computer searches of MEDLINE, EMBASE and the Cochrane Library were performed using search terms that included hydroxyethyl starch; hetastarch; shock, septic; sepsis; randomized controlled trials; and random allocation. Additional methods were examination of reference lists and hand searching. Randomized clinical trials comparing hydroxyethyl starch with other fluids in patients with sepsis were selected. Data were extracted on numbers of patients randomized, specific indication, fluid regimen, follow-up, endpoints, hydroxyethyl starch volume infused and duration of administration, and major study findings.</p> <p>Results</p> <p>Twelve randomized trials involving a total of 1062 patients were included. Ten trials (83%) were acute studies with observation periods of 5 days or less, most frequently assessing cardiorespiratory and hemodynamic variables. Two trials were designed as outcome studies with follow-up for 34 and 90 days, respectively. Hydroxyethyl starch increased the incidence of acute renal failure compared both with gelatin (odds ratio, 2.57; 95% confidence interval, 1.13–5.83) and crystalloid (odds ratio, 1.81; 95% confidence interval, 1.22–2.71). In the largest and most recent trial a trend was observed toward increased overall mortality among hydroxyethyl starch recipients (odds ratio, 1.35; 95% confidence interval, 0.94–1.95), and mortality was higher (p < 0.001) in patients receiving > 22 mL·kg^-1hydroxyethyl starch per day than lower doses.</p> <p>Conclusion</p> <p>Hydroxyethyl starch increases the risk of acute renal failure among patients with sepsis and may also reduce the probability of survival. While the evidence reviewed cannot necessarily be applied to other clinical indications, hydroxyethyl starch should be avoided in sepsis.</p

Awareness and use of home remedies in Italy's alps: a population-based cross-sectional telephone survey

Belief in complementary and alternative medicine practices is related to reduced preparedness for vaccination. This study aimed to assess home remedy awareness and use in South Tyrol, where vaccination rates in the coronavirus pandemic were lowest in Italy and differed between German- and Italian-speaking inhabitants.; A population-based survey was conducted in 2014 and analyzed using descriptive statistics, multiple logistic regression, and latent class analysis.; Of the representative sample of 504 survey respondents, 357 (70.8%) participants (43.0% male; primary language German, 76.5%) reported to use home remedies. Most commonly reported home remedies were teas (48.2%), plants (21.0%), and compresses (19.5%). Participants from rural regions were less likely (odds ratio 0.35, 95% confidence interval 0.19-0.67), while female (2.62, 1.69-4.10) and German-speaking participants (5.52, 2.91-9.88) were more likely to use home remedies. Latent classes of home remedies were "alcoholic home remedies" (21.4%) and "non-alcohol-containing home remedies" (78.6%). Compared to the "non-alcohol-containing home remedies" class, members of the "alcoholic home remedies" class were more likely to live in an urban region, to be male and German speakers.; In addition to residence and sex, language group membership associates with awareness and use of home remedies. Home remedies likely contribute to socio-cultural differences between the language groups in the Italian Alps. If the observed associations explain the lower vaccination rates in South Tyrol among German speakers requires further study

Reduction of D-dimer levels after therapeutic administration of antithrombin in acquired antithrombin deficiency of severe sepsis

INTRODUCTION: In acute disseminated intravascular coagulation, the effect of antithrombin (AT) administration on elevated levels of D-dimer is not well established. In the present study, we report on changes in circulating levels of D-dimer in response to administration of AT in a series of patients with acquired AT deficiency due to severe sepsis. METHODS: Eight consecutive critically ill medical patients presenting with acute disseminated intravascular coagulation associated with severe sepsis/septic shock received a single bolus infusion of AT over 30 minutes, aiming to achieve physiological AT levels. Haemostatic parameters including D-dimer were assessed prior to, 6 and 24 h after AT administration. An average of 42 ± 9 U/kg body weight was infused. RESULTS: Following AT substitution, elevated levels of D-dimer fell whereas AT levels rose. CONCLUSION: These observations support the notion that AT can favourably affect fibrin degradation accompanying disseminated intravascular coagulation of severe sepsis

Fatal cardiac arrest in an adult patient with euthyroid anti-SSA/Ro-positive connective tissue disease: a case report

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Enhancement of fibrinogen-triggered pro-coagulant activation of monocytes in vitro by matrix metalloproteinase-9

<p>Abstract</p> <p>Background</p> <p>Interaction of fibrinogen with specific leukocyte integrins of monocytes may link coagulation and inflammation, however, the precise mechanism of fibrinogen leading to the pro-inflammatory and pro-coagulatory response on monocytes is yet unknown.</p> <p>Results</p> <p>Fibrinogen and its digestion fragment D induced pro-coagulant activation of monocytes as assessed in a cellular coagulation assay by reductions in clotting times. Pro-coagulant activation was reversed by blocking antibodies against Mac-1 or LFA-1. Pre-exposure of monocytes to the p38 MAPK inhibitor SB 202190 and the MEK1.2 inhibitor U0126 led to significant increasees in coagulation times whereas blocking JNKII with its inhibitor had no such effect. Blocking NFκB with MG-132 also inhibited pro-coagulant activation of monocytes by fibrinogen. A selective inhibitor of matrix metalloproteinase-9 increased times to clot formation whereas other matrix metalloproteinase inhibitors did not significantly interfere with fibrinogen-augmented clot formation in this assay. Treatment of monocytes with fibrinogen increased concentrations of matrix metalloproteinase-9 immunoreactivity in their supernatants.</p> <p>Conclusions</p> <p>Fibrinogen induces monocyte pro-coagulant activation in an integrin-, nuclear factor κB-, p38 MAPK-, and MEK1.2-dependent manner. Activation of monocytes by fibrinogen increases metalloproteinase-9 secretion, metalloproteinase-9 itself enhances monocyte coagulation by an autocrine mechanism. Results provide further evidence that mediators of hemostasis have a profound impact on cells of the immune system and are closely related to inflammatory pathways.</p

A meta-analysis of controlled trials of recombinant human activated protein C therapy in patients with sepsis

BACKGROUND: Meta-analysis of two randomised controlled trials in severe sepsis performed with recombinant human activated protein C may provide further insight as to the therapeutic utility of targeting the clotting cascade in this syndrome. METHODS: In search for relevant studies published, two randomized clinical trials were found eligible. RESULTS: The studies, PROWESS and ADDRESS, enrolled a total of 4329 patients with risk ratio (RR) and 95% confidence interval (CI) data for effect on 28-day mortality relative to control treatment of 0.92 (0.83–1.02) suggesting that recombinant human activated protein C is not beneficial in severe sepsis. In PROWESS, 873 of 1690 patients presented with low risk, and 2315 of 2639 patients in ADDRESS as defined by APACHE II score < 25. In this low-risk stratum, no effect of recombinant human activated protein C administration on 28-day mortality was observed. This observation appears to be consistent and homogenous. Heterogeneity between the two studies, however, was seen in patients with APACHE II score ≥ 25 in whom recombinant activated protein C was effective in PROWESS (n = 817; RR 0.71, CI 0.59–0.85) whereas a tendency toward harm was present in ADDRESS (n = 324; RR 1.21, CI 0.85–1.74). Even though the overall treatment effect in this high-risk population was still in favour of treatment with recombinant activated protein C (n = 1141; RR 0.80, CI 0.68–0.94), the observed heterogeneity suggests that the efficacy of recombinant human activated protein C is not robust. Not unlikely, the adverse tendency observed could have become significant with higher statistical power would ADDRESS not have been terminated prematurely. CONCLUSION: This meta-analysis, therefore, raises doubts about the clinical usefulness of recombinant activated protein C in patients with severe sepsis and an APACHE II score ≥ 25 which can only be resolved by another properly designed clinical trial