Sex differences associate with late microbiome alterations after murine surgical sepsis.

BACKGROUND: Sepsis-induced gut microbiome alterations contribute to sepsis-related morbidity and mortality. Given evidence for improved postsepsis outcomes in females compared with males, we hypothesized that female mice maintain microbiota resilience versus males. METHODS: Mixed-sex C57BL/6 mice underwent cecal ligation and puncture (CLP) with antibiotics, saline resuscitation, and daily chronic stress and were compared with naive (nonsepsis/no antibiotics) controls. For this work, the results of young (3-5 months) and old (18-22 months) adult mice were analyzed by sex, independent and dependent of age. Mice were sacrificed at days 7 and 14, and 16S rRNA gene sequencing was performed on fecal bacterial DNA. α and ß diversity were determined by Shannon index and Bray-Curtis with principal coordinate analysis, respectively. False discovery rate (FDR) correction was implemented to account for potential housing effect. RESULTS: In control mice, there was no difference in α or ß diversity between male and female mice (FDR, 0.76 and 0.99, respectively). However, male mice that underwent CLP with daily chronic stress had a decrease in microbiota α diversity at 7 days post-CLP (Shannon FDR, 0.005), which was sustained at 14 days post-CLP (Shannon FDR, 0.001), compared with baseline. In addition, male mice maintained differences in ß diversity even at day 14 compared with controls (FDR, <0.0001). In contrast, female mice had a decreased microbiota α diversity (Shannon FDR, 0.03) and ß diversity (FDR, 0.02) 7 days post-CLP but recovered their α and ß diversity by post-CLP day 14 (Shannon FDR, 0.5, and FDR, 0.02, respectively). Further analysis of females revealed that only young female mice were not different (ß diversity) post-CLP day 14 to controls. CONCLUSION: Although sepsis-induced perturbations of the intestinal microbiota occur initially in both male and female C57BL/6 mice, females demonstrate different microbiota by day 14. This may be seen primarily in younger females. This difference in recovery may play a role in outcome differences between sexes after sepsis.

Septic Stability? Gut Microbiota in Young Adult Mice Maintains Overall Stability After Sepsis Compared to Old Adult Mice.

BACKGROUND: Older adults have worse outcomes after sepsis than young adults. Additionally, alterations of the gut microbiota have been demonstrated to contribute to sepsis-related mortality. We sought to determine if there were alterations in the gut microbiota with a novel sepsis model in old adult mice, which enter a state of persistent inflammation, immunosuppression, and catabolism (PICS), as compared with young adult mice, which recover with the sepsis model. METHODS: Mixed sex old (∼20 mo) and young (∼4 mo) C57Bl/6J mice underwent cecal ligation and puncture with daily chronic stress (CLP+DCS) and were compared with naive age-matched controls. Mice were sacrificed at CLP+DCS day 7 and feces collected for bacterial DNA isolation. The V3-V4 hypervariable region was amplified, 16S rRNA gene sequencing performed, and cohorts compared. α-Diversity was assessed using Chao1 and Shannon indices using rarefied counts, and ß-diversity was assessed using Bray-Curtis dissimilarity. RESULTS: Naive old adult mice had significantly different α and ß-diversity compared with naive adult young adult mice. After CLP+DCS, there was a significant shift in the α and ß-diversity (FDR = 0.03 for both) of old adult mice (naive vs. CLP+DCS). However, no significant shift was displayed in the microbiota of young mice that underwent CLP+DCS in regards to α-diversity (FDR = 0.052) and ß-diversity (FDR = 0.12), demonstrating a greater overall stability of their microbiota at 7 days despite the septic insult. The taxonomic changes in old mice undergoing CLP+DCS were dominated by decreased abundance of the order Clostridiales and genera Oscillospira. CONCLUSION: Young adult mice maintain an overall microbiome stability 7 days after CLP+DCS after compared with old adult mice. The lack of microbiome stability could contribute to PICS and worse long-term outcomes in older adult sepsis survivors. Further studies are warranted to elucidate mechanistic pathways and potential therapeutics.

Audiovisual Modules to Enhance Informed Consent in the ICU: A Pilot Study.

Obtaining informed consent for commonly performed ICU procedures is often compromised by variability in communication styles and inadequate verbal descriptions of anatomic concepts. The objective of this study was to evaluate the efficacy of an audiovisual module in improving the baseline knowledge of ICU procedures among patients and their caregivers. DESIGN: Prospective, observational study. SETTING: Forty-eight-bed adult surgical ICU at a tertiary care center. SUBJECTS: Critically ill surgical patients and their legally authorized representatives. INTERVENTIONS: An audiovisual module describing eight commonly performed ICU procedures. MEASUREMENTS AND MAIN RESULTS: Fifty-nine subjects were enrolled and completed an 11-question pre- and postvideo test of knowledge regarding commonly performed ICU procedures and a brief satisfaction survey. Twenty-nine percent had a healthcare background. High school was the highest level of education for 37% percent of all subjects. Out of 11 questions on the ICU procedure knowledge test, subjects scored an average 8.0 ± 1.9 correct on the pretest and 8.4 ± 2.0 correct on the posttest (p = 0.055). On univariate logistic regression, having a healthcare background was a negative predictor of improved knowledge (odds ratio, 0.185; 95% CI, 0.045-0.765), indicating that those with a health background had a lower probability of improving their score on the posttest. Among subjects who did not have a healthcare background, scores increased from 7.7 ± 1.9 to 8.3 ± 2.1 (p = 0.019). Seventy-five percent of all subjects indicated that the video was easy to understand, and 70% believed that the video improved their understanding of ICU procedures. CONCLUSIONS: Audiovisual modules may improve knowledge and comprehension of commonly performed ICU procedures among critically ill patients and caregivers who have no healthcare background.

Heart rate variability and its association with mortality in prehospital trauma patients.

BACKGROUND: Accurate prehospital triage of trauma patients is difficult, especially in mass casualty situations. Accordingly, the U.S. Military has initiated a program directed toward improving noninvasive prehospital triage algorithms based on available physiologic data. The purpose of this study was to assess heart rate variability and its association with mortality in prehospital trauma patients. METHODS: Trauma patients without significant head injury requiring helicopter transport were identified from a retrospective research database. An equal number, unmatched sample of patients who lived were compared with those who died (n = 15 per group). All patients were transported to a single Level I urban trauma center. The primary independent variable was mortality. Patients with Abbreviated Injury Scale head scores >2 were excluded from the analysis, so that the effects seen were based on hemorrhagic shock. Age, sex, Glasgow Coma Scale score (GCS), blood pressure, pulse pressure, pulse, intubation rate, SpO2, mechanism of injury, transport time, and time of death after admission were recorded. R-waves from the first available 120 seconds of usable data were detected from normal electrocardiograms and heart rate variability was assessed. RESULTS: Patients who died demonstrated a lower GCS (7.9 +/- 1.4 versus 14.4 +/- 0.2; p = 0.0001) and higher intubation rate (53% of patients who died versus 0% patients who lived). Pulse rate, arterial pressure, and SpO2 were not distinguishable statistically between groups (p = 0.08), but pulse pressure was lower in patients who died (39 +/- 3 versus 50 +/- 2 mm Hg; p = 0.01). Compared with patients who lived, those who died had lower normalized low-frequency (LF) power (42 +/- 6 versus 62 +/- 4 LFnu; p = 0.009), higher high-frequency (HF) power (42 +/- 3 versus 32 +/- 3 HFnu; p = 0.04) and higher HF-to-LF ratio (144 +/- 30 versus 62 +/- 11nu; p = 0.01). With absolute HF/LF adjusted for GCS, the intergroup variance accounted for by HF/LF was reduced to 6% (p = 0.16). CONCLUSIONS: Analysis of heart rate variability provides insight into adequacy of autonomic compensation to severe trauma. In our cohort of trauma patients, low pulse pressures coupled with relatively higher parasympathetic than sympathetic modulation characterized and separated patients who died versus patients who survived traumatic injuries when standard physiologic measurements are not different. These data do not suggest advantages of heart rate variability analysis over GCS scores, but suggest future possibilities for remote noninvasive triage of casualties when GCS scores are unattainable.

Treatment of an acquired coagulopathy with recombinant activated factor VII in a damage-control patient.

Recombinant activated factor VII is commonly used for the treatment of hemophiliac patients with inhibitors and has been studied for use in trauma. We report the use of recombinant activated factor VII for a male patient who was injured in a motor vehicle accident. We also summarize the animal studies and clinical trials that have been reported.