Summary Background Antimicrobial treatment in critically ill patients can either be started as soon as infection is suspected or after objective data confirm an infection. We postulated that delaying antimicrobial treatment of patients with suspected infections in the surgical intensive care unit (SICU) until objective evidence of infection had been obtained would not worsen patient mortality. Methods We did a 2-year, quasi-experimental, before and after observational cohort study of patients aged 18 years or older who were admitted to the SICU of the University of Virginia (Charlottesville, VA, USA). From Sept 1, 2008, to Aug 31, 2009, aggressive treatment was used: patients suspected of having an infection on the basis of clinical grounds had blood cultures sent and antimicrobial treatment started. From Sept 1, 2009, to Aug 31, 2010, a conservative strategy was used, with antimicrobial treatment started only after objective findings confirmed an infection. Our primary outcome was in-hospital mortality. Analyses were by intention to treat. Findings Admissions to the SICU for the first and second years were 762 and 721, respectively, with 101 patients with SICU-acquired infections during the aggressive year and 100 patients during the conservative year. Compared with the aggressive approach, the conservative approach was associated with lower all-cause mortality (13/100 [13%] vs 27/101 [27%]; p=0.015), more initially appropriate therapy (158/214 [74%] vs 144/231 [62%]; p=0.0095), and a shorter mean duration of therapy (12.5 days [SD 10.7] vs 17.7 [28.1]; p=0.0080). After adjusting for age, sex, trauma involvement, acute physiology and chronic health evaluation (APACHE) II score, and site of infection, the odds ratio for the risk of mortality in the aggressive therapy group compared with the conservative therapy group was 2.5 (95% CI 1.5−4.0). Interpretation Waiting for objective data to diagnose infection before treatment with antimicrobial drugs for suspected SICU-acquired infections does not worsen mortality and might be associated with better outcomes and use of antimicrobial drugs.

Among critically ill surgical patients, caloric provision across a wide acceptable range does not appear to be associated with major outcomes, including infectious complications. The optimum target for caloric provision remains elusive.

Background Analysis and modeling of vital sign and waveform data in surgical / trauma intensive care unit (STICU) patients may allow for early identification and treatment of patients with evolving respiratory failure. Methods Between February 2011 and March 2012, vital sign and waveform data for STICU patients were collected. Every-15-minute calculations (n=172,326) of means and standard deviations of heart rate (HR), respiratory rate (RR), pulse-oxygen saturation (SpO2), cross-correlation coefficients and cross-Sample Entropy for HR-RR, RR-SpO2, and HR-SpO2, and cardiorespiratory coupling were calculated. Urgent intubations were recorded. Univariate analyses were performed for the periods <24 and ≥24 hours prior to intubation. Multivariate predictive models for the risk of unplanned intubation were developed and internally validated by subsequent sample and bootstrapping techniques. Results Fifty unplanned intubations (41 patients) were identified from 798 STICU patients. The optimal multivariate predictive model (HR, RR, and SpO2 means and RR-SpO2 correlation coefficient) had a ROC area of 0.770 (95%CI 0.712, 0.841). For this model, relative risks of intubation in the next 24 hours for the lowest and highest quintiles were 0.20 and 2.95 respectively (15-fold increase, baseline risk 1.46%). Adding age and days since previous extubation to this model increased ROC area to 0.865 (0.821, 0.910). Conclusions In STICU patients, a multivariate model predicted increases in risk of intubation in the following 24 hours based on vital sign data currently available on bedside monitors. Further refinement could allow for earlier detection of respiratory decompensation and intervention to reduce preventable morbidity and mortality in surgical/trauma patients.

Versican, an extracellular matrix proteoglycan, has been implicated in limb development and is expressed in precartilage mesenchymal condensations. However, studies have lacked precise spatial and temporal investigation of versican localization during skeletogenesis and its relationship to patterning of muscle and nerve during mammalian limb development. The transgenic mouse line hdf (heart defect), which bears a lacZ reporter construct disrupting Cspg2 encoding versican, allowed ready detection of hdf transgene expression through histochemical analysis. Hdf transgene expression in whole mount heterozygous embryos and localization of versican relative to cartilage, muscle, and nerve tissues in paraffin-embedded limb sections of wild-type embryos from 10.5-14 days postcoitum were evaluated by lacZ histochemistry, immunohistochemistry, and in situ hybridization. Versican was localized within precartilage condensations and nascent cartilages with expression diminishing during maturation of the cartilage model at later time points. Interestingly, versican remained highly expressed in developing synovial joint interzones, suggesting potential function for versican in joint morphogenesis. Isolated myoblasts, incipient skeletal muscle masses, and neurites were not present in areas of strong versican expression within the developing limb. Versican-expressing tissues may reserve space for the future limb skeleton and developing joints and may aid in patterning of muscle and nerve by deterring muscle migration and innervation into these regions.

A longer duration of antibiotic therapy for IAI is associated with an increased risk of subsequent EAI and increased mortality.