Intensive Care Medicine

To investigate antibiotic-mediated release of tumour necrosis factor (TNF)-α and norharman in patients with hospital-acquired pneumonia with and without additional septic encephalopathy. Prospective observational study with a retrospective post hoc analysis. Surgical intensive care unit (ICU) at a university hospital. Thirty-seven patients were consecutively included (9 patients with hospital-acquired pneumonia, 11 patients with hospital-acquired pneumonia and septic encephalopathy, 17 control patients) in the study. Pneumonia was defined according to the criteria of the American Thoracic Society. Patients received cephalosporins for antibiotic treatment of hospital-acquired pneumonia. Blood samples were taken before, immediately after and 4 h after application of cephalosporins. Of the pneumonia patients, 55% developed septic encephalopathy. ICU stay, complications and mortality were significantly increased. An increased release of TNF-α was immediately seen in all pneumonia patients after antibiotics compared to controls, whereas the level did not differ between patients with and without septic encephalopathy. Norharman was significantly increased in pneumonia patients 4 h after antibiotic treatment, in tendency more enhanced in the pneumonia patients without encephalopathy. Patients with hospital-acquired pneumonia and septic encephalopathy had a significantly longer ICU stay with higher mortality rate compared to patients with hospital-acquired pneumonia alone. Antibiotic-mediated TNF-α release may induce the kynurenine pathway. TNF-α activates indolamine-2,3-dioxygenase with neurotoxic quinolinic acid as the end product. Norharman seems to counteract this mechanism and seems to play a role in neuroprotection. The worse outcome of patients with encephalopathy expresses the need to investigate protective factors and mechanisms.

The role of drotrecogin alfa (activated) (DAA) in severe sepsis remains controversial and clinicians are unsure whether or not to treat their patients with DAA. In response to a request from the European Medicines Agency, Eli Lilly will sponsor a new placebo-controlled trial and history suggests the results will be subject to great scrutiny. An academic steering committee will oversee the conduct of the study and will write the study manuscripts. The steering committee intends that the study will be conducted with the maximum possible transparency; this includes publication of the study protocol and a memorandum of understanding which delineates the role of the sponsor. The trial has the potential to provide clinicians with valuable data but patients will only benefit if clinicians have confidence in the conduct, analysis and reporting of the trial. This special article describes the process by which the trial was developed, major decisions regarding trial design, and plans for independent analysis, interpretation and reporting of the data.

Objective: To assess the preventive effect of Saccharomyces boulardii on diarrhea in critically ill tube-fed patients and to evaluate risk factors for diarrhea. Design: Prospective, multicenter, randomized, double-blind placebo-controlled study. Setting: Eleven intensive care units in teaching and general hospitals. Patients: Critically ill patients whose need for enteral nutrition was expected to exceed 6 days. Intervention: S. boulardii 500 mg four times a day versus placebo. Measurements and results: Diarrhea was defined by a semiquantitative score based on the volume and consistency of stools. A total of 128 patients were studied, 64 in each group. Treatment with S. boulardii reduced the mean percentage of days with diarrhea per feeding days from 18.9 to 14.2 % [odds ratio (OR) = 0.67, 95 % confidence interval (CI) = 0.50–0.90, P = 0.0069]. In the control group, nine risk factors were significantly associated with diarrhea: nonsterile administration of nutrients in open containers, previous suspension of oral feeding, malnutrition, hypoalbuminemia, sepsis syndrome, multiple organ failure, presence of an infection site, fever or hypothermia, and use of antibiotics. Five independent factors were associated with diarrhea in a multivariate analysis: fever or hypothermia, malnutrition, hypoalbuminemia, previous suspension of oral feeding, and presence of an infection site. After adjustment for these factors, the preventive effect of S. boulardii on diarrhea was even more significant (OR = 0.61, 95 % CI = 0.44–0.84, P < 0.0023). Conclusion: S. boulardii prevents diarrhea in critically ill tube-fed patients, especially in patients with risk factors for diarrhea.

Perioperative temporary pacing was needed in a patient with congenital skeletal malformations and a cardiac conduction disturbance with incomplete trifascicular block. We report the successful placement of the pacemaker electrode through a persistent left superior vena cava (SVC).

To compare the total plasma cortisol values obtained from three widely used immunoassays and a high pressure liquid chromatography (HPLC) technique on samples obtained from patients with sepsis. Observational interventional in the general intensive care unit of a metropolitan hospital Patients admitted to the intensive care unit with a diagnosis of sepsis and fulfilling criteria of systemic inflammatory response syndrome. Standard short synacthen test performed with 250 μg cosyntropin. Two of the three immunoassays returned results significantly higher than those obtained by HPLC: Immulite by 95% (95%CI 31–188%) and TDx by 79% (21–165%). The limits of agreement for all three immunoassays with HPLC ranged from −62% to 770%. In addition, by classifying the patients into responders and non-responders to ACTH by standard criteria there was concordance in all assays in only 44% of patients. Immunoassay estimation of total plasma cortisol in septic patients shows wide assay related variation that may have significant impact in the diagnosis of relative adrenal insufficiency.

Early detection of acute lung injury (ALI) is essential for timely implementation of evidence-based therapies and enrollment into clinical trials. We aimed to determine the accuracy of computerized syndrome surveillance for detection of ALI in hospitalized patients and compare it with routine clinical assessment. Using a near-real time copy of the electronic medical records, we developed and validated a custom ALI electronic alert (ALI “sniffer”) based on the European-American Consensus Conference Definition and compared its performance against provider-derived documentation. A total of 3,795 consecutive critically ill patients admitted to nine multidisciplinary intensive care units (ICUs) of a tertiary care teaching institution were included. ALI developed in 325 patients and was recognized by bedside clinicians in only 86 (26.5%). Under-recognition of ALI was associated with not implementing protective mechanical ventilation (median tidal volumes of 9.2 vs. 8.0 ml/kg predicted body weight, P < 0.001). ALI “sniffer” demonstrated excellent sensitivity of 96% (95% CI 94–98) and moderate specificity of 89% (95% CI 88–90) with a positive predictive value ranging from 24% (95% CI 13–40) in the heart–lung transplant ICU to 64% (95% CI 55–71) in the medical ICU. The computerized surveillance system accurately identifies critically ill patients who develop ALI syndrome. Since the lack of ALI recognition is a barrier to the timely implementation of best practices and enrollment into research studies, computerized syndrome surveillance could be a useful tool to enhance patient safety and clinical research.