Gastrointestinal failure in intensive care: a retrospective clinical study in three different intensive care units in Germany and Estonia

BACKGROUND: While gastrointestinal problems are common in ICU patients with multiple organ failure, gastrointestinal failure has not been given the consideration other organ systems receive. The aim of this study was to evaluate the incidence of gastrointestinal failure (GIF), to identify its risk factors, and to determine its association with ICU mortality. METHODS: A retrospective analysis of adult patients (n = 2588) admitted to three different ICUs (two ICUs at the university hospital Charité-Universitätsmedizin Berlin, Germany and one at Tartu University Clinics, Estonia) during the year 2002 was performed. Data recorded in a computerized database were used in Berlin. In Tartu, the data documented in the patients' charts was retrospectively transferred into a similar database. GIF was defined as documented gastrointestinal problems (food intolerance, gastrointestinal haemorrhage, and/or ileus) in the patient data at any period of their ICU stay. ICU mortality, length of stay, and duration of mechanical ventilation were assessed as outcome parameters. RESULTS: GIF was identified in 252 patients (9.7% of all patients). Only 20% of GIF patients were identifiable at admission. GIF was related to significantly higher mortality (43.7% vs. 5.3% in patients without GIF), as well as prolonged length of ICU stay (10 vs. 2 days) and mechanical ventilation (8 vs. 1 day), p < 0.001, respectively. Patients' profile (emergency surgical or medical), APACHE II and SOFA scores and the use of catecholamines at admission were identified as independent risk factors for the development of GIF. Development of GIF during ICU stay was an independent predictor for death. CONCLUSION: Gastrointestinal failure represents a relevant clinical problem accompanied by an increased mortality, longer ICU stay and mechanical ventilation

Resuscitation of Severe Uncontrolled Hemorrhage 7.5% Sodium Chloride/6% Dextran 70 vs 0.9% Sodium Chloride

Objectives: Resuscitation studies of hypertonic saline using controlled and uncontrolled hemorrhage models yield conflicting results with regard to efficacy. These disparate results reflect the use of models and resuscitation regimens that are not comparable between studies. This study evaluated the effects of comparable and clinically relevant resuscitation regimens of 7.5% sodium chloride/6% dextran 70 (HSD) and 0.9% sodium chloride (NS) in a near-fatal uncontrolled hemorrhage model. Methods: Thirty-six swine (14.2 to 21.4 kg) with 4-mm aortic tears were bled to a pulse pressure of 5 mm Hg (40-45 mL/kg). The animals were resuscitated with either NS or HSD administered in volumes that provided equivalent sodium loads at similar rates. Group II (n = 12) was resuscitated with 80 mL/kg of NS at a rate of 4 mL/kg/min. Group III (n = 12) received 9.6 mL/kg of HSD at a rate of 0.48 mL/kg/min. In both groups, crystalloid resuscitation was followed by shed blood infusion (30 mL/kg) at a rate of 2 mL/kg/min. Group I (controls; n = 12) were not resuscitated. Results: One-hour mortality was significantly greater in group I (92%) as compared with group II (33%) and group III (33%) (Fisher's exact test; p = 0.004). Intraperitoneal hemorrhage was significantly greater in group II (34 ± 20 mL/kg) and group III (31 ± 13 mL/kg) as compared with group I (5 ± 2 mL/kg) (ANOVA; p < 0.05). There was no significant difference in hemodynamic parameters between groups II and III. Conclusion: In this model of severe uncontrolled hemorrhage, resuscitation with HSD or NS, administered in volumes that provided equivalent sodium loads at similar rates, had similar effects on mortality, hemodynamic parameters, and hemorrhage from the injury site.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73625/1/j.1553-2712.2000.tb02060.x.pd

PORTAL: Pilot study on the safety and tolerance of preoperative melatonin application in patients undergoing major liver resection: a double-blind randomized placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Major surgical procedures facilitate systemic endotoxinemia and formation of free radicals with subsequent inflammatory changes that can influence the postoperative course. Experimental data suggest that preoperative supraphysiological doses of melatonin, a potent immuno-modulator and antioxidant, would decrease postoperative infectious and non-infectious complications induced by major abdominal surgery.</p> <p>Methods/Design</p> <p>A randomized controlled double blind single center clinical trial with two study arms comprising a total of 40 patients has been designed to assess the effects of a single preoperative dose of melatonin before major liver resection. Primary endpoints include the determination of safety and tolerance of the regimen as well as clinical parameters reflecting pathophysiological functions of the liver. Furthermore, data on clinical outcome (infectious and non-infectious complications) will be collected as secondary endpoints to allow a power calculation for a randomized clinical trial aiming at clinical efficacy.</p> <p>Discussion</p> <p>Based on experimental data, this ongoing clinical trial represents an advanced element of the research chain from bench to bedside in order to reach the highest level of evidence-based clinical facts to determine if melatonin can improve the general outcome after liver resection.</p> <p>Trial Registration</p> <p>EudraCT200600530815</p

Burn wounds infected with Pseudomonas aeruginosa triggers weight loss in rats

BACKGROUND: Despite dramatic improvements in the management of burns, infection still remains a serious risk for the burn patient. The aim of this study was to shed light on the impact of acute burn injury with or without infection on cytokine profiles. METHODS: Sprague-Dawley rats (n = 21) were randomized into three groups: 1) burn only 2) burn and infection or 3) sham burn. Weight was monitored and blood was collected for cytokine ELISA, LPS quantification, and peripheral blood analysis. Animals were sacrificed either after 6 or 12 days. RESULTS: Infected animals showed substantial weight loss until day 6 post-burn as compared to burn alone. Endotoxin and TNF-α levels were elevated early in the infected burn group within 48 hours post-burn. In contrast, significant up-regulation of the anti-inflammatory cytokine IL-10 occurred later in the clinical course and was associated with the recovery from weight loss. CONCLUSION: Our results suggest that in the presence of infection, you get a SIRS response possibly due to transient endotoxemia that is only seen in the infection group. In contrast, both burn and infection get a late IL-10 (CARS) response, which is then associated with a return to normal weight in the infection group

Dissecting Inflammatory Complications in Critically Injured Patients by Within-Patient Gene Expression Changes: A Longitudinal Clinical Genomics Study

By studying gene expression changes over time in a cohort of trauma patients, Keyur Desai and colleagues identify genes and pathways strongly associated with longer-term complications, which could lead to improved outcome prediction in the first 80 hours after injury

Involvement of Skeletal Muscle Gene Regulatory Network in Susceptibility to Wound Infection Following Trauma

Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and infection model was used to identify host genetic components that contribute to the hyper-susceptibility to infection that follows severe trauma. We show that P. aeruginosa compromises skeletal muscle gene (SMG) expression at the injury site to promote infection. We demonstrate that activation of SMG structural components is under the control of cJun-N-terminal Kinase (JNK) Kinase, Hemipterous (Hep), and activation of this pathway promotes local resistance to P. aeruginosa in flies and mice. Our study links SMG expression and function to increased susceptibility to infection, and suggests that P. aeruginosa affects SMG homeostasis locally by restricting SMG expression in injured skeletal muscle tissue. Local potentiation of these host responses, and/or inhibition of their suppression by virulent P. aeruginosa cells, could lead to novel therapies that prevent or treat deleterious and potentially fatal infections in severely injured individuals

Simian virus 40 vectors for pulmonary gene therapy

<p>Abstract</p> <p>Background</p> <p>Sepsis remains the leading cause of death in critically ill patients. One of the primary organs affected by sepsis is the lung, presenting as the Acute Respiratory Distress Syndrome (ARDS). Organ damage in sepsis involves an alteration in gene expression, making gene transfer a potential therapeutic modality. This work examines the feasibility of applying simian virus 40 (SV40) vectors for pulmonary gene therapy.</p> <p>Methods</p> <p>Sepsis-induced ARDS was established by cecal ligation double puncture (2CLP). SV40 vectors carrying the luciferase reporter gene (SV/<it>luc) </it>were administered intratracheally immediately after sepsis induction. Sham operated (SO) as well as 2CLP rats given intratracheal PBS or adenovirus expressing luciferase served as controls. Luc transduction was evaluated by <it>in vivo </it>light detection, immunoassay and luciferase mRNA detection by RT-PCR in tissue harvested from septic rats. Vector abundance and distribution into alveolar cells was evaluated using immunostaining for the SV40 VP1 capsid protein as well as by double staining for VP1 and for the surfactant protein C (proSP-C). Immunostaining for T-lymphocytes was used to evaluate the cellular immune response induced by the vector.</p> <p>Results</p> <p>Luc expression measured by <it>in vivo </it>light detection correlated with immunoassay from lung tissue harvested from the same rats. Moreover, our results showed vector presence in type II alveolar cells. The vector did not induce significant cellular immune response.</p> <p>Conclusion</p> <p>In the present study we have demonstrated efficient uptake and expression of an SV40 vector in the lungs of animals with sepsis-induced ARDS. These vectors appear to be capable of <it>in vivo </it>transduction of alveolar type II cells and may thus become a future therapeutic tool.</p

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference