Evaluating the Effect of Nursing-Performed Point-of-Care Ultrasound on Septic Emergency Department Patients.

Introduction Nursing-performed point-of-care ultrasound (NP-POCUS) studies have been performed on applications such as ultrasound-guided peripheral intravenous line placement and assessing bladder volume. However, research on the use of NP-POCUS in the management of septic patients remains limited. The purpose of this quality improvement study was to investigate how NP-POCUS could impact fluid treatment decisions affecting septic patients in the emergency department (ED) using a focused IVC and lung ultrasound protocol. Methods Nurses received standardized training in POCUS and performed inferior vena cava (IVC) and lung ultrasound scans on septic patients in the ED at predetermined intervals (hours: zero, three, and six). Based on their findings, they were asked to make recommendations on fluid management. Emergency physicians (EPs), both residents and attendings, are providing recommendations for fluid management without the use of ultrasound, which is being compared to the nurse-driven POCUS assessment of fluid management. EPs reviewed the NP-POCUS assessments of patient fluid status to determine nursing accuracy. Results A total of 104 patients were scanned, with a mean age of 60.7 years. EPs agreed with nursing ultrasound assessments in 99.1% of cases. Nursing ultrasound images changed management or increased physician confidence in current treatment plans 83.7% and 96.6% of the time, respectively. Before reviewing saved nursing ultrasound images, EPs underestimated fluid tolerance in 37.5% of cases, overestimated fluid tolerance in 26% of cases, and correctly estimated fluid tolerance (within 500 ml) in 36.5% of cases. Throughout resuscitation, IVCs became less collapsible, the number of cases with B-lines was essentially unchanged, and less fluid was recommended. Conclusion  This study demonstrated that nurse-performed POCUS is feasible and may have a meaningful impact on how physicians manage septic patients in the emergency department.

Resistin Concentration in Early Sepsis and All-Cause Mortality at a Safety-Net Hospital in Riverside County.

Background: Sepsis mortality has remained unchanged for greater than a decade, and early recognition continues to be the most important factor in mortality outcome. Plasma resistin concentration is increased in sepsis, but its mechanism and clinical relevance is unclear. As one function, resistin interacts with toll-like receptor 4 in competition with lipopolysaccharide, a main component of the gram-negative bacterial cell wall. It is not known if the type of infection leading to sepsis influences resistin production. The objective of this study was to investigate whether 1) early plasma resistin concentration can predict mortality, 2) elevated plasma resistin concentration is associated with clinical disease severity scores, such as SOFA, mSOFA and APACHE II, and 3) plasma resistin concentrations differ between gram negative versus other etiologies of sepsis. Methods: This was an exploratory study in the framework of a prospective observational design. Peripheral venous blood samples were obtained from subjects admitted to the intensive care unit at clinical recognition of sepsis (0 hour) and at 6 and 24 hours. Vasopressor utilization was not a requirement for inclusion. Plasma was analyzed for resistin concentration by ELISA. Cytokine concentrations including IL-6, IL-8, and IL-10 were determined by cytokine bead array. Cytokine data were evaluated against publicly available sepsis RNA expression datasets to compare protein versus RNA expression levels in predicting clinical disease state. Clinical data were collected from electronic health records for clinical severity index calculations and context for interpretation of resistin and cytokine concentrations. Subjects were followed up to 60 days, or until death, whichever came first. Statistical analysis was completed with R package and SPSS software. Results: Resistin levels were elevated in subjects admitted to the intensive care unit with sepsis. Four-hundred subjects were screened with 45 subjects included in the final analysis. Thirteen of 45 patients were non-survivors. Mortality within 60 days correlated with significantly higher resistin concentrations than in survivors. A resistin concentration of >126 ng/mL at clinical recognition of sepsis and >197 ng/mL within the first 24 hours were associated with mortality within 60 days with an area under the curve of 0.82 and 0.88, respectively. Most subjects with resistin concentration greater than these threshold values were deceased prior to 30 days. Resistin concentrations correlated with SOFA, mSOFA, and APACHE II scores in addition to having association with increases in inflammatory and sepsis biomarkers. These associations were validated with analysis of RNA expression datasets. Conclusion: Plasma resistin concentrations of >126 ng/mL at clinical recognition of sepsis and >197 ng/mL within the first 24 hours of clinical sepsis recognition are associated with all-cause mortality. Resistin concentration within this timeframe also has comparable mortality association to well-validated clinical severity indices of SOFA, mSOFA, and APACHE II scores.

Increased ethanol drinking in "humanized" mice expressing the mu opioid receptor A118G polymorphism are mediated through sex-specific mechanisms.

The A118G single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (Oprm1) has been implicated in mediating the rewarding effects of alcohol. Clinical and preclinical studies suggest that the G allele may confer a genetic vulnerability to alcohol dependence, though it remains unknown whether these effects are sex-specific. We used male and female mice homozygous for the "humanized" 118AA or 118GG alleles to determine whether the A118G SNP potentiates ethanol consumption in a sex-specific manner in both the two-bottle choice and drinking-in-the-dark (DID) paradigms. Mice were also assessed for differences in naltrexone sensitivity, ethanol reward assessed via conditioned place preference (CPP), and sensitivity to the sedative/ataxic effects of ethanol using the rota-rod and loss of righting reflex (LORR) assays. We found that male and female 118GG mice drank significantly more ethanol than 118AA littermates using a continuous access, two-bottle choice paradigm. In the limited-access DID drinking model, (i) female (but not male) 118GG mice consumed more ethanol than 118AA mice and (ii) naltrexone pretreatment was equally efficacious at attenuating ethanol intake in both 118AA and 118GG female mice while having no effect in males. Male and female 118GG and female 118AA mice developed a robust conditioned place preference (CPP) for ethanol. Female 118GG mice displayed less sensitivity to the sedative/ataxic effects of ethanol compared to female 118AA mice on both the rota-rod and the LORR assays while male mice did not differ in their responses on either assay. Our findings suggest that increased ethanol consumption in male 118GG mice may be due to increased ethanol reward, while increased drinking in female 118GG mice might be due to decreased sensitivity to the sedative/ataxic effects of ethanol. Collectively, these data might be used to help identify sex-specific pharmacotherapies to combat alcohol use disorders.

Morphine-induced antinociception and reward in "humanized" mice expressing the mu opioid receptor A118G polymorphism.

The rewarding and antinociceptive effects of opioids are mediated through the mu-opioid receptor. The A118G single nucleotide polymorphism in this receptor has been implicated in drug addiction and differences in pain response. Clinical and preclinical studies have found that the G allele is associated with increased heroin reward and self-administration, elevated post-operative pain, and reduced analgesic responsiveness to opioids. Male and female mice homozygous for the "humanized" 118AA or 118GG alleles were evaluated to test the hypothesis that 118GG mice are less sensitive to the rewarding and antinociceptive effects of morphine. We found that 118AA and 118GG mice of both genders developed conditioned place preference for morphine. All mice developed tolerance to the antinociceptive and hypothermic effects of morphine. However, morphine tolerance was not different between AA and GG mice. We also examined sensitivity to the antinociceptive and hypothermic effects of cumulative morphine doses. We found that 118GG mice show reduced hypothermic and antinociceptive responses on the hotplate for 10mg/kg morphine. Finally, we examined basal pain response and morphine-induced antinociception in the formalin test for inflammatory pain. We found no gender or genotype differences in either basal pain response or morphine-induced antinociception in the formalin test. Our data suggests that homozygous expression of the GG allele in mice blunts morphine-induced hypothermia and hotplate antinociception but does not alter morphine CPP, morphine tolerance, or basal inflammatory pain response.