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Purpose: In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions. Methods: Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575). Results: Overall, 209 patients were included (77 females, 132 males, mean age: 59 ± 16 years), 194 of which were treated in intensive care (APACHE II score at the beginning of fosfomycin therapy: 23 ± 8). Main indications (± bacteremia or sepsis) were infections of the CNS (21.5%), community- (CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP, 15.3%), bone and joint infections (BJI, 11%), abdominal infections (11%), and bacteremia (10.5%). Most frequently identified pathogens were S. aureus (22.3%), S. epidermidis (14.2%), Enterococcus spp. (10.8%), E. coli (12.3%) and Klebsiella spp. (7.7%). At least one multidrug-resistant (MDR) pathogen was isolated from 51 patients (24.4%). Fosfomycin was administered with an average daily dose of 13.7 ± 3.5 g over 12.4 ± 8.6 days, almost exclusively (99%) in combination with other antibiotics. The overall clinical success was favorable in 81.3% (148/182) of cases, and in 84.8% (39/46) of patients with ≥ 1 MDR pathogen. Noteworthy, 16.3% (34/209) of patients developed at least one, in the majority of cases non-serious, adverse drug reaction during fosfomycin therapy. Conclusion: Our data suggest that IV fosfomycin is an effective and safe combination partner for the treatment of a broad spectrum of severe bacterial infections in critically ill patients. [ABSTRACT FROM AUTHOR]

The case of a young male motor vehicle driver is reported who suffered multiple trauma in a car accident with pulmonary and cardiac contusions. In the course of severe pneumonia and traumatic tricuspid valve insufficiency a right-to-left shunt with refractory hypoxemia developed across a pre-existing atrial septal defect (ASD). The patient could be successfully treated by the combination of extracorporeal membrane oxygenation for bridging, interventional ASD occlusion and in the long-term by operative reconstruction of the tricuspid valve. [ABSTRACT FROM AUTHOR]

Data on the occurrence and outcome of patients with chronic obstructive pulmonary disease (COPD) and ventilator-associated pneumonia (VAP) are quite limited. The aim of this study was to determine if COPD intensive care unit (ICU) patients have a higher rate of VAP development, different microbiological aetiology or have worse outcomes than other patients without VAP. A secondary analysis of a large prospective, observational study conducted in 27 European ICUs was carried out. Trauma patients were excluded. Of 2082 intubated patients included in the study, 397 (19.1 %) had COPD; 79 (19.9 %) patients with COPD and 332 (19.7 %) patients without COPD developed VAP. ICU mortality increased by 17 % ( p < 0.05) when COPD patients developed VAP, remaining an independent predictor of mortality [odds ratio (OR) 2.28; 95 % confidence interval (CI) 1.35-3.87]. The development of VAP in COPD patients was associated with a median increase of 12 days in the duration of mechanical ventilation and >13 days in ICU stay ( p < 0.05). Pseudomonas aeruginosa was more common in VAP when COPD was present (29.1 % vs. 18.7 %, p = 0.04) and was the most frequent isolate in COPD patients with early-onset VAP, with a frequency 2.5 times higher than in patients without early-onset VAP (33.3 % vs. 13.3 %, p = 0.03). COPD patients are not more predisposed to VAP than other ICU patients, but if COPD patients develop VAP, they have a worse outcome. Antibiotic coverage for non-fermenters needs to be included in the empiric therapy of all COPD patients, even in early-onset VAP. [ABSTRACT FROM AUTHOR]

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To assess the effect on survival of macrolides or fluoroquinolones in intubated patients admitted to the intensive care unit (ICU) with severe community-acquired pneumonia (severe CAP). Prospective, observational cohort, multicenter study conducted in 27 ICUs of 9 European countries. Two hundred eighteen consecutive patients requiring invasive mechanical ventilation for an admission diagnosis of CAP were recruited. Severe sepsis and septic shock were present in 165 (75.7%) patients. Microbiological documentation was obtained in 102 (46.8%) patients. ICU mortality was 37.6% ( n = 82). Non-survivors were older (58.6 ± 16.1 vs. 63.4 ± 16.7 years, P < 0.05) and presented a higher score on the simplified Acute Physiology Score II at admission (45.6 ± 15.4 vs. 50.8 ± 17.5, P < 0.05). Monotherapy was given in 43 (19.7%) and combination therapy in 175 (80.3%) patients. Empirical antibiotic therapy was in accordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) guidelines in 100 (45.9%) patients (macrolides in 46 patients and fluoroquinolones in 54). In this cohort, a Cox regression analysis adjusted by severity identified that macrolide use was associated with lower ICU mortality (hazard ratio, HR 0.48, confidence intervals, 95% CI 0.23–0.97, P = 0.04) when compared to the use of fluoroquinolones. When more severe patients presenting severe sepsis and septic shock were analyzed ( n = 92), similar results were obtained (HR 0.44, 95% CI 0.20–0.95, P = 0.03). Patients with severe community-acquired pneumonia had a low adherence with the 2007 IDSA/ATS guidelines. Combination therapy with macrolides should be preferred in intubated patients with severe CAP. [ABSTRACT FROM AUTHOR]

Delirium (acute brain dysfunction) is a potentially life threatening disturbance in brain function that frequently occurs in critically ill patients. While this area of brain dysfunction in critical care is rapidly advancing, striking limitations in use of terminology related to delirium internationally are hindering cross-talk and collaborative research. In the English literature, synonyms of delirium such as the Intensive Care Unit syndrome, acute brain dysfunction, acute brain failure, psychosis, confusion, and encephalopathy are widely used. This often leads to scientific "confusion" regarding published data and methodology within studies, which is further exacerbated by organizational, cultural and language barriers. We undertook this multinational effort to identify conflicts in terminology and phenomenology of delirium to facilitate communication across medical disciplines and languages. The evaluation of the terminology used for acute brain dysfunction was determined conducting communications with 24 authors from academic communities throughout countries/regions that speak the 13 variants of the Romanic languages included into this manuscript. In the 13 languages utilizing Romanic characters, included in this report, we identified the following terms used to define major types of acute brain dysfunction: coma, delirium, delirio, delirium tremens, délire, confusion mentale, delir, delier, Durchgangs-Syndrom, acute verwardheid, intensiv-psykose, IVA- psykos, IVA- syndrom, akutt konfusion/ forvirring. Interestingly two terms are very consistent: 100 % of the selected languages use the term coma or koma to describe patients unresponsive to verbal and/or physical stimuli, and 100% use delirium tremens to define delirium due to alcohol withdrawal. Conversely, only 54% use the term delirium to indicate the disorder as defined by the DSM-IV as an acute change in mental status, inattention, disorganized thinking and altered level of consciousness. Attempts towards standardization in terminology, or at least awareness of differences across languages and specialties, will help cross-talk among clinicians and researchers. [ABSTRACT FROM AUTHOR]

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Sepsis is still a leading cause of death in many intensive care patients. The pathophysiology of the disease is dominated by complex immune cascades. Recent research demonstrates that immune cells respond to sepsis with an increased rate of programmed cell death. Up-regulated apoptosis of leukocytes was observed in animal models of sepsis as well as in patients suffering from severe sepsis. The mitochondrial protein Bcl-2 and the caspase cascade play an important role in the regulation of apoptosis. Overexpression of Bcl-2 or inhibition of caspases resulted in an increased survival in animal models of sepsis. Recent reports indicate the relevance of apoptosis in patients with severe sepsis. These results may spawn novel immunomodulatory strategies in the treatment of sepsis. [ABSTRACT FROM AUTHOR]

Objective. To investigate the kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury (ALI). Design. Prospective observational cross-over study. Setting. Intensive care unit of a university hospital. Patients. Twelve mechanically ventilated patients with ALI. Interventions. Mechanical ventilation was transiently changed from a lung protective setting with PEEP of 15 cmH2O and a VT of 5 ml/kg predicted body weight to a more conventional ventilatory setting with PEEP of 5 cmH2O and VT of 12 ml/kg predicted body weight for a period of 6 h. Measurements and results. We examined the profile of interleukin (IL)-1β, IL-1 receptor antagonist, IL-6, IL-10, and tumor necrosis factor in the plasma of all patients, and in the bronchoalveolar lavage (mini-BAL) fluid of six of these patients. Measurements were performed at baseline, 1 h, and 6 h after each change of the ventilatory setting. Switching to conventional mechanical ventilation was associated with a higher PaO2 (P <0.05) and a marked increase (P <0.05) of measured plasma cytokines in patients with and without mini-BAL with a maximum after 1 h. Similarly, intraalveolar cytokine concentrations increased with conventional mechanical ventilation. While plasma cytokine levels returned to baseline values, intraalveolar cytokine concentrations further increased when lung protective mechanical ventilation was reestablished. Conclusions. In patients with ALI, initiation of low PEEP and high VT mechanical ventilation is associated with cytokine release into circulation which occurred within 1 h. It is independent from BAL procedures and can be reversed by reinstitution of lung protective mechanical ventilation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of macrophage migration inhibitory factor (MIF) as a marker of severity of systemic inflammation in patients with severe sepsis and critically ill postsurgical patients.Design: Prospective observational study in consecutive patients with severe sepsis, critically ill nonseptic postsurgical patients, and healthy blood donors.Setting: A surgical intensive care unit of a university hospital.Patients and Participants: 19 patients with severe sepsis, 18 critically ill nonseptic postsurgical patients, and 10 healthy blood donors.Measurements and Results: MIF plasma levels of patients and participants were measured. Interleukin 6 plasma levels were monitored as a control marker of inflammation. The median MIF plasma level was four to five times higher in patients with severe sepsis (2.70 ng/ml, range 0.31-19.59) and in critically ill nonseptic postsurgical patients (2.43 ng/ml, range 0.49-4.31) than in healthy blood donors (0.56 ng/ml, range 0.16-1.68). MIF plasma levels did not differ between the patient groups.Conclusions: MIF serves as a general marker for systemic inflammation in septic and nonseptic acute critical illness, but MIF does not discriminate for severity or differentiate between infectious and noninfectious origins of an acute critical illness. [ABSTRACT FROM AUTHOR]

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Background and aims: Lymphocyte apoptosis may influence immune responsiveness in systemic inflammation. Therefore, we investigated whether early signs of apoptosis (i.e., annexin-V binding and cell shrinkage) in peripheral lymphocytes were different among patients with severe sepsis, critically ill, nonseptic patients after major surgery, and healthy individuals. Patients/methods: Ten patients with severe sepsis and ten critically ill, nonseptic patients after major surgery admitted to a surgical intensive care unit in a university hospital were included in the study. In addition, ten healthy blood donors were included for comparison. We investigated early signs of apoptosis using flow cytometric measurement of annexin-V binding to the cell surface and cell shrinkage of peripheral lymphocytes. Results: The percentage of apoptotic lymphocytes determined as annexin-V positive and propidium iodide negative cells was increased in freshly prepared cells of patients with severe sepsis (11.4±0.5%) and critically ill, nonseptic patients after major surgery (18.5±2.0%) relative to healthy blood donors (4.4±0.5%) (P<0.05). No significant difference between patients with severe sepsis and patients after major surgery were found. Annexin-V binding increased significantly after OKT-3 stimulation of lymphocytes in patients with severe sepsis (34.4±1.6%), patients after major surgery (33.8±3.4%), and healthy blood donors (21.1±2.8%). No significant difference among groups was detected following OKT-3 stimulation. Furthermore, freshly isolated peripheral lymphocytes of patients with severe sepsis and critically ill, nonseptic patients after major surgery revealed a significantly higher proportion of cell shrinkage than in healthy blood donors (55.0±2.2%, 21.5±2.4% vs 3.6±0.7%; P<0.05). Conclusion: Circulating lymphocytes of critically ill patients show a high degree of early signs of cellular apoptosis. This may contribute to hyporesponsiveness of immune cells in systemic inflammation. [ABSTRACT FROM AUTHOR]

A 29-year-old man was admitted to the ICU after emergency laparotomy for portal-mesenteric vein thrombosis. Under continuous intravenous heparin therapy the portal-mesenteric shunt occluded on the first postoperative day. After thrombectomy the heparin dose was increased, and the patient remained free of symptoms (partial thromboplastin time 53 s). Two days later abdominal distension developed concomitantly with ventilatory distress due to a large retroperitoneal hematoma. The patient was mechanically ventilated and underwent the third consecutive laparotomy for the hematoma removal on the fifth day. During the surgical procedure the abdomen was packed with towels to stop multiple bleeding sites. The heparin dose was reduced, aiming for a partial thromboplastin time of 30-35 s. Initial coagulation tests revealed increased levels of anticardiolipin immunoglobulin G. After removal of the surgical towels the patient was successfully weaned from mechanical ventilation and discharged from the ICU. Two weeks later genomic testing revealed that he also had a G20210A mutation of the prothrombin gene. Both, increased levels of anticardiolipin immunoglobulin G and the G20210A mutation of the prothrombin gene predispose to thrombosis. Increased levels of anticardiolipin immunoglobulin G may also cause bleeding. Long-term anticoagulation therapy was started with a vitamin K antagonist, and 2 months later a follow-up showed that the patient had no further symptoms of portal-mesenteric vein thrombosis or bleeding. This case illustrates that the convergence of multiple risk factors, including genetic defects, must be considered in patients suffering from thrombosis in unusual sites [ABSTRACT FROM AUTHOR]

Copyright of Intensivmedizin und Notfallmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To investigate the ex vivo endotoxin-inducible heat shock protein 70 (HSP70) expression in the peripheral blood mononuclear cells (PBMC) of patients with severe sepsis in order to assess the capacity of this potentially protective response during systemic inflammation.Design: Prospective observational study in consecutive patients with severe sepsis and healthy blood donors.Setting: Surgical intensive care unit in a university hospital.Patients and Participants: Eleven patients with the diagnosis of severe sepsis, one patient who had recovered from severe sepsis and 13 healthy blood donors.Interventions: None.Measurements and Results: We studied the inducibility of HSP70 expression in the PBMC of patients with severe sepsis and healthy blood donors ex vivo. Human whole blood was incubated with variable lipopolysaccharide (LPS from Salmonella minnesota Re 595) concentrations (0; 0.1; 10; 100 ng/ml) for different periods of time (0.5; 2; 4; 10 h). The PBMC were separated by Ficoll density gradient and then disrupted by hypotonic lysis. HSP70 was measured by means of enzyme-linked immunosorbent assay (ELISA). We found a LPS dose- and time-dependent inhibition of ex vivo HSP70 expression in the PBMC of both patients with severe sepsis and healthy individuals. However, the levels of HSP70 expression in patients were significantly lower compared to those of healthy individuals at all LPS concentrations and incubation times. On average, HSP70 expression in the PBMC of healthy controls was 2.8 (range 1.2-3.9) times higher than in patients. HSP70 expression was inducible by thermal heat shock in the PBMC of both patients and healthy individuals.Conclusions: Endotoxin inhibits HSP70 expression in PBMC ex vivo. In vivo, the suppression of HSP70 expression induced by endotoxin and high levels of proinflammatory cytokines may contribute to the cellular dysfunction of immunocompetent cells concerning antigen presentation, phagocytosis and antibody production associated with decreased resistance to infectious insults during severe sepsis. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the influence of different PSV levels on VT, F, VO2 in the early weaning phase of patients without chronic obstructive pulmonary disease. These parameters were tested for the predictive power for the success of the weaning. Patients on SIMV were studied during the first weaning attempt with PSV. Depending on their ventilatory support demands after 24 h they were divided into responders (patients breathing on CPAP) and nonresponders (patients being on a more invasive ventilatory mode). 14 ICU patients without pre-existing pulmonary disease being ventilated for at least 3 days entered the study. 2 of them could be studied a second time after failing the first weaning attempt. Beside the level of ventilatory support no other changes (drugs, nutrition) were allowed. VO2, VT, F were measured by a computer controlled, metabolic unit connected to the expiratory port of a Siemens Servo Ventilator. In addition, airway pressures, arterial pressure and heart rate were recorded. The measurements were performed at PSV of 5, 10 and 20 cmH2O. Arterial blood-gases were drawn at the end of each 60 min lasting PS period. Responders and nonresponders could be separated by the response of VO2, VT and F to a change in PS 10 to PS 20 cmH2O. Patients who significantly increased VT and significantly decreased F did not fulfil our weaning criteria. Our responders did not show a significant change in these two parameters, but a significant increase in VO2 at PS 20 cmH2O could be observed.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

Patients suffering from severe cranio-cerebral trauma show alterations of the secretory patterns of thyroid stimulating hormone (TSH) and human growth hormone (HGH) which may be of prognostic significance. We studied 10 patients following severe brain injury and prospectively compared a new synthetic human growth hormone releasing factor (HGHRF) test with the thyrotropin releasing hormone (TRH) test. On admission, all patients had a Glasgow Coma Scale score of 3 or 4. All patients had a low T3 syndrome. In the patients who died the TSH response after stimulation with TRH was also absent. In the patients who survived a significant TSH increase was observed (p less than 0.05). In comparison to the patients who died those who survived showed a significant (p less than 0.001) HGH increase after HGHRF stimulation. This test might be useful as an additional tool in establishing early prognosis in patients with severe brain injury. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor on weight loss of respiratory muscles during mechanical ventilation.