The inflammation–coagulation axis as an important intermediate pathway in acute lung injury

Markers of inflammation, coagulation, and fibrinolysis predict an adverse outcome in patients with sepsis. These markers also seem predictive of an adverse outcome in patients with localized infection and inflammation, such as in acute lung injury. Whether this is entirely related to the disease or is also due to ventilation strategies that may be harmful for the lungs, however, is not clear. In the present issue of Critical Care, McClintock and colleagues demonstrate that these biomarkers retain their predictive effect even if lung-protective ventilation strategies are applied. Besides being biomarkers that predict outcome in patients with acute lung injury, their activation of inflammation and coagulation seems also to play a pivotal role in the pathogenesis of acute lung injury, and may thereby represent an interesting novel target for therapeutic intervention

Antibiotics or probiotics as preventive measures against ventilator-associated pneumonia: a literature review

Mechanically ventilated critically ill patients frequently develop ventilator-associated pneumonia (VAP), a life-threatening complication. Proposed preventive measures against VAP include, but are not restricted to, selective decontamination of the digestive tract (SDD), selective oropharyngeal decontamination (SOD) and the use of probiotics. Probiotics are live bacteria that could have beneficial effects on the host by altering gastrointestinal flora. Similar to SDD and SOD, a prescription of probiotics aims at the prevention of secondary colonization of the upper and/or lower digestive tract. We performed a literature review to describe the differences and similarities between SDD/SOD and probiotic preventive strategies, focusing on (a) efficacy, (b) risks, and (c) the routing of these strategies. Reductions in the incidence of VAP have been achieved with SDD and SOD. Two large randomized controlled trials even showed reduced mortality with these preventive strategies. Randomized controlled trials of probiotic strategies also showed a reduction of the incidence of VAP, but trials were too small to draw firm conclusions. Preventive strategies with antibiotics and probiotics may be limited due to the risk of emerging resistance to the locally applied antibiotics and the risk of probiotic-related infections, respectively. The majority of trials of SDD and SOD did not exhaustively address the issue of emerging resistance. Likewise, trials of probiotic strategies did not adequately address the risk of colonization with probiotics and probiotic-related infection. In studies of SDD and SOD the preventive strategy aimed at decontamination of the oral cavity, throat, stomach and intestines, and the oral cavity and throat, respectively. In the vast majority of studies of probiotic therapy the preventive strategy aimed at decontamination of the stomach and intestines. Prophylactic use of antibiotics in critically ill patients is effective in reducing the incidence of VAP. Probiotic strategies deserve consideration in future well-powered trials. Future studies are needed to determine if preventive antibiotic and probiotic strategies are safe with regard to development of antibiotic resistance and probiotic infections. It should be determined whether the efficacy of probiotics improves when these agents are provided to the mouth and the intestines simultaneousl

Is "safe effective glucose control" effective and safe?

Since tight glucose control (TGC) inevitably comes with a risk of hypoglycemia, Krinsley and Preiser [1] suggest the use of a stepwise approach to glucose control, which they call “safe, effective glucose control ” (SEGC), and that targets an intermediate blood glucose level (BGL). SEGC is intended to decrease the rate of hyperglycemia while reducing the adverse effects of severe hypoglycemia. Of note, the randomized controlled trials that showed a benefit from glucose control have tested only one and the same BGL target (4.4 to 6.1 mmol/l [80 to 110 mg/dl]) [2,3]. In addition, in these trials conventional insulin treatment was administered only when the BGL was>12 mmol/L (215 mg/dl), with insulin infusion gradually decreased and stopped when the BGL fell to <10 mmol/l (180 mg/dl). Accordingly, the average morning BGL of the conventional treatmen

Anticoagulant properties of drotrecogin alfa (activated) during hemofiltration in patients with severe sepsis

In a retrospective study among 35 severely septic patients treated with drotrecogin alfa (activated) (DrotAA) and renal replacement therapy (RRT), Camporota and colleagues demonstrated that the addition of heparin, epoprostenol, or both to DrotAA during RRT did not improve filter survival. Furthermore, in a multivariate logistic regression analysis, they identified the minimum value in platelet count as the only predictive factor of filter clotting during DrotAA infusion. These findings are in line with the previously formulated suggestion that DrotAA alone is as effective as heparin in the prevention of coagulation in the extracorporeal circuit. They also confirm the importance of baseline platelet count in the pathogenesis of extracorporeal circuit thrombosis. In the study by Camporata and colleagues, DrotAA treatment was not associated with an increase in red blood cell requirements. The results of this study supply a background to clinical decision making when choosing an anticoagulant for RRT in septic patients

Selective Decontamination of the Digestive Tract Reduces Pneumonia and Mortality

Selective decontamination of the digestive tract (SDD) has been subject of numerous randomized controlled trials in critically ill patients. Almost all clinical trials showed SDD to prevent pneumonia. Nevertheless, SDD has remained a controversial strategy. One reason for why clinicians remained reluctant to implement SDD into daily practice could be that mortality was reduced in only 2 trials. Another reason could be the heterogeneity of trials of SDD. Indeed, many different prophylactic antimicrobial regimes were tested, and dissimilar diagnostic criteria for pneumonia were applied amongst the trials. This heterogeneity impeded interpretation and comparison of trial results. Two other hampering factors for implementation of SDD have been concerns over the risk of antimicrobial resistance and fear for escalation of costs associated with the use of prophylactic antimicrobials. This paper describes the concept of SDD, summarizes the results of published trials of SDD in mixed medical-surgical intensive care units, and rationalizes the risk of antimicrobial resistance and rise of costs associated with this potentially life-saving preventive strategy

Selective decontamination of the digestive tract reduces mortality in critically ill patients

Several emotional responses may be invoked in critical care physicians when confronted with selective decontamination of the digestive tract (SDD). Although recent meta-analyses have shown that the use of SDD reduces the occurrence of ventilator-associated pneumonia and improves ICU survival, the effectiveness of SDD has remained controversial. We recently concluded a large randomized, controlled trial on the use of SDD that showed improved survival of ICU patients treated with SDD. A second concern regarding use of SDD has been the fear for the emergence of antimicrobial resistance. Interestingly, a recently published study did not confirm this fear, and our recently finished study even demonstrated a decline in colonization with P. aeruginosa and enterobacteriaceae that were resistant against tobramycin, ceftazidime, imipenem and ciprofloxacin. The hopes are that this study will at long last end the debate about the efficacy and safety of SDD in critically ill patients

Exhaled breath profiling for diagnosing acute respiratory distress syndrome

The acute respiratory distress syndrome (ARDS) is a common, devastating complication of critical illness that is characterized by pulmonary injury and inflammation. The clinical diagnosis may be improved by means of objective biological markers. Electronic nose (eNose) technology can rapidly and non-invasively provide breath prints, which are profiles of volatile metabolites in the exhaled breath. We hypothesized that breath prints could facilitate accurate diagnosis of ARDS in intubated and ventilated intensive care unit (ICU) patients. Prospective single-center cohort study with training and temporal external validation cohort. Breath of newly intubated and mechanically ventilated ICU-patients was analyzed using an electronic nose within 24 hours after admission. ARDS was diagnosed and classified by the Berlin clinical consensus definition. The eNose was trained to recognize ARDS in a training cohort and the diagnostic performance was evaluated in a temporal external validation cohort. In the training cohort (40 patients with ARDS versus 66 controls) the diagnostic model for ARDS showed a moderate discrimination, with an area under the receiver-operator characteristic curve (AUC-ROC) of 0.72 (95%-confidence interval (CI): 0.63-0.82). In the external validation cohort (18 patients with ARDS versus 26 controls) the AUC-ROC was 0.71 [95%-CI: 0.54 - 0.87]. Restricting discrimination to patients with moderate or severe ARDS versus controls resulted in an AUC-ROC of 0.80 [95%-CI: 0.70 - 0.90]. The exhaled breath profile from patients with cardiopulmonary edema and pneumonia was different from that of patients with moderate/severe ARDS. An electronic nose can rapidly and non-invasively discriminate between patients with and without ARDS with modest accuracy. Diagnostic accuracy increased when only moderate and severe ARDS patients were considered. This implicates that breath analysis may allow for rapid, bedside detection of ARDS, especially if our findings are reproduced using continuous exhaled breath profiling. NTR2750, registered 11 February 201