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Emergency
Medicine News
Critical Care
The latest articles from Critical Care (ISSN 1364-8535)
published by BioMed Central
Critical Care - Latest Articles
The latest research articles published by Critical Care
Interleukin-10 gene down-expression in circulating mononuclear cells during i...
by Thomas LavauxPascal BilbaultAnne LaunoyMarie-Pierre GaubPierre OudetFrancis Schneider
7 Sep 2010 at 6:00pm
IntroductionTo investigate the gene expression of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in circulating mononuclear cells harvested from septic shock patients on drotrecogin-alpha activated (DAA) in order to determine whether this treatment has any effect on the inflammation phase.
Methods:
We conducted a prospective cohort study in two intensive care departments. Blood samples were collected at inclusion (T1) and 36 hours later (T2) to measure plasma cytokines and the changes in intracellular TNF-alpha, IL-10 and IFN-gamma mRNA expressions using the real-time quantitative polymerase chain reaction (RT-qPCR). Thirty-two septic shock patients were included: 16 with DAA at 24 ug/kg/h for 96 hours (DAA+) and 16 control (DAA-) eligible but contraindicated for DAA because of low platelet count.
Results:
The basal characteristics were similar in both groups: mortality (50%), plasma cytokine concentrations, and baseline IFN-gamma, TNF-alpha and IL-10 mRNA expressions (DAA+ vs. DAA-). At T2, there was a significant IFN-gamma gene down-regulation in DAA+ but not in DAA- patients (-0.34 [-0.62;+1.54] vs. +1.41 [+0.35;+5.87], P=0.008). In survivors, DAA administration was associated with a down-expression of both IFN-gamma (-0.65 [-0.93;-0.48] vs. +0.7 [-0.04;+1.26], P=0.01) and IL-10 (-0.78 [-0.92;-0.6] vs. -0.18 [-0.68;+0.46], P=0.038). In the non-survivors, DAA infusion was associated with IL-10 over-expression when compared with survivors (+0.54 [-0.35;+11.52] vs. -0.78 [-0.92;-0.6], P<0.001).
Conclusions:
In this study, lack of IL-10 gene down-expression despite a 36 hour infusion of DAA is an ominous sign in septic shock patients suggesting that DAA is not able to reverse outcome. Our results suggest that DAA can decrease the expression of anti-inflammatory cytokines in septic shock patients. IL-10 or IFN-gamma gene down-expression could represent markers of DAA response.
Direct antimicrobial activity of antithrombin?
by Christian WiedermannAngela Djanani
6 Sep 2010 at 6:00pm
None
Validation of extravascular lung water measurement by single transpulmonary t...
by Takashi TagamiShigeki KushimotoYasuhiro YamamotoTakahiro AtsumiRyoichi TosaKiyoshi MatsudaRenpei OyamaTakanori KawaguchiTomohiko MasunoHisao HiramaHiroyuki Yokota
5 Sep 2010 at 6:00pm
IntroductionGravimetric validation of single-indicator extravascular lung water (EVLW) and normal EVLW values have not been well studied in humans thus far. The aims of this study were (1) to validate the accuracy of EVLW measurement by single transpulmonary thermodilution with postmortem lung weight measurement in humans and (2) to define the statistically normal EVLW values.
Methods:
We evaluated the correlation between pre-mortem EVLW value by single transpulmonary thermodilution and post-mortem lung weight from 30 consecutive autopsies completed within 48 hours following the final thermodilution measurement. A linear regression equation for the correlation was calculated. In order to clarify the normal lung weight value by statistical analysis, we conducted a literature search and obtained the normal reference ranges for post-mortem lung weight. These values were substituted into the equation for the correlation between EVLW and lung weight to estimate the normal EVLW values.
Results:
EVLW determined using transpulmonary single thermodilution correlated closely with post-mortem lung weight (r = 0.904, P < 0.001). A linear regression equation was calculated: EVLW (mL) = 0.56 lung weight (g) 58.0. The normal EVLW values indexed by predicted body weight were approximately 7.4 +/- 3.3 mL/kg (7.5 +/- 3.3 mL/kg for males and 7.3 +/- 3.3 mL/kg for females).
Conclusions:
A definite correlation exists between EVLW measured by the single-indicator transpulmonary thermodilution technique and post-mortem lung weight in humans. The normal EVLW value is approximately 7.4 +/- 3.3 mL/kg.Trial Registration: UMIN000002780.
Microcirculation in cardiogenic shock: From scientific bystander to therapy t...
by Christian JungAlexander LautenMarkus Ferrari
5 Sep 2010 at 6:00pm
Despite diagnostic and therapeutic improvements, mortality rates in patients with cardiogenic shock remain relatively high. Several studies showed that cardiogenic shock is associated with alterations in the microvascular circulation. These alterations may be reversed by extracorporeal support devices. A study by Munsterman and colleagues adds to the body of evidence showing that in patients deemed ready for discontinuing intra-aortic balloon pump (IABP) support, microcirculatory flow in small vessels increases after ceasing IABP therapy. This study not only highlights the need for optimal timing of weaning from IABP support but also supports recent findings that global hemodynamics do not necessarily result in changes of microvascular perfusion. All modalities of modern treatment in cardiogenic shock need to be evaluated for their effect on the microcirculation. Microcirculatory evaluations should be part of randomized controlled trial protocols. More effort is needed to improve outcomes and understand the microcirculation as a therapy target and not as a silent bystander.
Tranexamic acid in cardiac surgery: is there a cause for concern?
by David Royston
5 Sep 2010 at 6:00pm
The withdrawal of marketing approval for aprotinin resulted in more clinicians administering tranexamic acid to patients at increased risk of bleeding and adverse outcome. The latest in a series of retrospective analyses of observational data is published in Critical Care and suggests an increase in mortality, when compared to data from the aprotinin era, in those patients having surgery when a cardiac chamber is opened. The added observation of an increase in cerebral excitatory phenomena (seizure activity) with tranexamic acid has a known mechanism and questions if such patients should be given this drug.
Intra-abdominal hypertension: Does it influence the physiology of prone vent...
by Andrew W KirkpatrickPaolo PelosiJan De waeleManu MalbrainChad BallMaureen MeadeKevin LauplandH Stelfox
26 Aug 2010 at 6:00pm
Prone ventilation (PV) is a ventilatory strategy that frequently improves oxygenation and lung mechanics in critical illness, yet does not consistently improve survival. While the exact physiologic mechanisms related to these benefits remain unproven, one major theoretical mechanism relates to reducing the abdominal encroachment upon the lungs. Concurrent to this experience is increasing recognition of the ubiquitous role of intra-abdominal hypertension (IAH) in critical illness, of the relationship between IAH and intra-abdominal volume or thus the compliance of the abdominal wall, and of the potential difference in the abdominal influences between the extrapulmonary and pulmonary forms of acute respiratory distress syndrome. The present paper reviews reported data concerning intra-abdominal pressure (IAP) in association with the use of PV to explore the potential influence of IAH. While early authors stressed the importance of gravitationally unloading the abdominal cavity to unencumber the lung bases, this admonition has not been consistently acknowledged when PV has been utilized. Basic data required to understand the role of IAP/IAH in the physiology of PV have generally not been collected and/or reported. No randomized controlled trials or meta-analyses considered IAH in design or outcome. While the act of proning itself has a variable reported effect on IAP, abundant clinical and laboratory data confirm that the thoracoabdominal cavities are intimately linked and that IAH is consistently transmitted across the diaphragm - although the transmission ratio is variable and is possibly related to the compliance of the abdominal wall. Any proning-related intervention that secondarily influences IAP/IAH is likely to greatly influence respiratory mechanics and outcomes. Further study of the role of IAP/IAH in the physiology and outcomes of PV in hypoxemic respiratory failure is thus required. Theories relating inter-relations between prone positioning and the abdominal condition are presented to aid in designing these studies.
Withdrawing intra-aortic balloon pump support paradoxically improves microvas...
by Luuk MunstermanPaul ElbersAlaattin OzdemirEric van DongenMat van ItersonCan Ince
24 Aug 2010 at 6:00pm
IntroductionThe Intra-Aortic Balloon Pump (IABP) is frequently used to mechanically support the heart. There is evidence that IABP improves microvascular flow during cardiogenic shock but its influence on the human microcirculation in patients deemed ready for discontinuing IABP support has not yet been studied. Therefore we used sidestream dark field imaging (SDF) to test our hypothesis that human microcirculation remains unaltered with or without IABP support in patients clinically ready for discontinuation of mechanical support.
Methods:
We studied 15 ICU patients on IABP therapy. Measurements were performed after the clinical decision was made to remove the balloon catheter. We recorded global hemodynamic parameters and performed venous oximetry during maximal IABP support (1:1) and ten minutes after temporarily stopping the IABP therapy. At both time points, we also recorded video clips of the sublingual microcirculation. From these we determined indices of microvascular perfusion including perfused vessel density (PVD) and microvascular flow index (MFI).
Results:
Ceasing IABP support lowered mean arterial pressure (74 +/- 8 mmHg to 71 +/- 10; P=0.048) and increased diastolic pressure (43 +/- 10 to 53 +/- 9 mmHg; P=0.0002). However, at the level of the microcirculation we found an increase of PVD of small vessels 20[micro]m and MFI for both small and large vessels were unaltered. During the procedure global oxygenation parameters (ScvO2/SvO2) remained unchanged.
Conclusions:
In patients deemed ready for discontinuing IABP support according to current practice, SDF imaging showed an increase of microcirculatory flow of small vessels after ceasing IABP therapy. This observation may indicate that IABP impairs microvascular perfusion in recovered patients, although this warrants confirmation.
Substitution of exudative trace elements losses in burned children
by Pascal StuckiMarie-Helene PerezJacques CottingAlan ShenkinMette Berger
24 Aug 2010 at 6:00pm
Description of an intravenous copper-selenium-zinc substitution policy in burned children with major burns using adult doses adapted to total body surface: blood levels and clinical course confirm safety, with a rapidly favourable clinical evolution
Bacterial flagellin elicits widespread innate immune defense mechanisms, apop...
by Joelle RolliNoureddine LoukiliSandra LevrandNathalie Rosenblatt-VelinStephanie Rignault-ClercBernard WaeberFrancois FeihlPal PacherLucas Liaudet
23 Aug 2010 at 6:00pm
IntroductionSystemic inflammation in sepsis is initiated by interactions between pathogen molecular motifs and specific host receptors, especially toll-like receptors (TLRs). Flagellin is the main flagellar protein of motile microorganisms and is the ligand of TLR5. The distribution of TLR5 and the actions of flagellin at the systemic level have not been established. Therefore, we determined TLR5 expression and the ability of flagellin to trigger prototypical innate immune responses and apoptosis in major organs from mice.
Methods:
Male Balb/C mice (n=80) were injected intravenously with 1-5 ug recombinant Salmonella flagellin. Plasma and organ samples were obtained after 0.5 to 6h, for molecular investigations. The expression of TLR5, the activation state of nuclear factor kappa B (NFkappaB) and mitogen-activated protein kinases (MAPKs) [extracellular related kinase (ERK) and c-jun-NH2 terminal kinase (JNK)], the production of cytokines [tumor necrosis alpha (TNFalpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), macrophageinhibitory protein-2 (MIP-2) and soluble triggering receptor expressed on myeloid cells (TREM-1)], and the apoptotic cleavage of caspase-3 and its substrate Poly(ADP-ribose) polymerase (PARP) were determined in lung, liver, gut and kidney at different time-points. The time-course of plasma cytokines was evaluated up to 6h after flagellin.
Results:
TLR5 mRNA and protein were constitutively expressed in all organs. In these organs, flagellin elicited a robust activation of NFkappaB and MAPKs, and induced significant production of the different cytokines evaluated, with slight interorgan variations. Plasma TNFalpha, IL-6 and MIP-2 disclosed a transient peak, whereas IL-1beta and soluble TREM-1 steadily increased over 6h. Flagellin also triggered a marked cleavage of caspase-3 and PARP in the intestine, pointing to its ability to promote significant apoptosis in this organ.
Conclusions:
Bacterial flagellin elicits prototypical innate immune responses in mice, leading to the release of multiple pro-inflammatory cytokines in the lung, small intestine, liver and kidney, and also activates apoptotic signalling in the gut. Therefore, this bacterial protein may represent a critical mediator of systemic inflammation and intestinal barrier failure in sepsis due to flagellated micro-organisms.
Is enough oxygen too much?
by Paul Schumacker
23 Aug 2010 at 6:00pm
Human cells require O2 for their energy supply, and critical illness can threaten the efficient delivery of O2 in accordance with tissue metabolic needs. In the accompanying article, Martin and colleagues point out that hypoxia is a normal and well-tolerated stress during embryonic development. A better understanding of how fetal cells survive these conditions and how adult cells adapt to high altitude exposure may provide insight into how these mechanisms might be engaged in the treatment of hypoxemic patients. They suggest that 'permissive hypoxia' represents a therapeutic possibility. But before we turn down the inspired O2 levels we should consider the broader effects of hypoxia on tissue repair in critical illness.
Presented by MedRat®
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