Effect of Intravenous Push and Piggyback Administration of Ceftriaxone on Mortality in Sepsis.

BACKGROUND: There is a lack of evidence-based guidelines for the administration methods of ceftriaxone in emergency departments (EDs), resulting in the reliance on individual institutional protocols for decision-making. OBJECTIVE: This study was performed to compare the effects of administering ceftriaxone via intravenous push (IVP) and intravenous piggyback (IVPB) on 28-day mortality in patients with sepsis. METHODS: This was a retrospective study of patients aged 18 years or older with sepsis or septic shock who visited an ED and were treated with ceftriaxone as an initial antibiotic between March 2010 and February 2019. Patients were divided into the IVP group and the IVPB group based on the administration method. The primary outcome was 28-day mortality, and multivariable Cox proportional hazards regression analysis was performed to evaluate the relationship between antibiotic administration methods and 28-day mortality. RESULTS: During the study period, a total of 939 patients were included in the final analysis, and the overall mortality rate was 12.2%. The antibiotic administration time was significantly lower in the IVP group than in the IVPB group, and the rates of antibiotic administration within 1 h and within 3 h were higher in the IVP group than in the IVPB group (p < 0.05). However, there was no significant difference in 28-day mortality between the two groups (hazard ratio 1.07, 95% confidence interval 0.69-1.65). CONCLUSIONS: IVP administration of ceftriaxone reduced the time of antibiotic administration compared with IVPB, but there was no difference in 28-day mortality.

Prolonged stay in the emergency department is an independent risk factor for hospital-acquired pressure ulcer.

It is not easy to ensure optimal prevention of hospital-acquired pressure ulcer (HAPU) in crowded emergency departments (EDs). We hypothesised that a prolonged ED length of stay (LOS) is associated with an increased risk of HAPU. This is a single-centre observational study. Prospectively collected HAPU surveillance data were analysed. Adult (aged ≥20 years) patients admitted through the ED from April 1, 2013 to December 31, 2016 were included. The primary outcome was the development of HAPU within a month. Covariates included demographics, comorbidities, conditions at triage, initial laboratory results, primary ED diagnosis, critical ED interventions, and ED dispositions. The association between ED LOS and HAPU was modelled using logistic and extended Cox regression. A total of 48 641 admissions were analysed. The crude odds ratio (OR) and hazard ratio (HR) for HAPU were increased to 1.44 (95% CI, 1.20-1.72) and 1.21 (95% CI, 1.02-1.45), respectively, in ED LOS ≥24 hours relative to ED LOS <6 hours. In multivariable logistic regression, ED LOS ≥12 and ≥24 hours were associated with higher risk of HAPU, with ORs of 1.30 (95% CI, 1.05-1.60) and 1.80 (95% CI, 1.45-2.23) relative to ED LOS <6 hours, respectively. The extended Cox regression showed that the risk lasted up to a week, with HRs of 1.42 (95% CI, 1.07-1.88) and 1.92 (95% CI, 1.44-2.57) relative to ED LOS <6 hours, respectively. In conclusion, Prolonged ED LOS is independently associated with HAPU. Shorter ED LOS should be pursued as a goal in a multifaceted solution for HAPU.

Dynamic Changes in Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Sepsis with Respect to Antibiotic Susceptibility.

Purpose: Proper antibiotic administration is crucial for sepsis management. Given the escalating incidence of antimicrobial resistance, there is a pressing need for indicators of antimicrobial susceptibility with short turnaround times. This study aimed to investigate the potential of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as an early biomarker for in vivo antibiotic susceptibility in patients with sepsis. Patients and Methods: We conducted a retrospective analysis of plasma samples from patients enrolled in a pre-established study designed to investigate prognostic biomarkers in patients with sepsis or septic shock. Baseline and 6 h sTREM-1 levels were examined using enzyme-linked immunosorbent assays. The primary outcome of the study was the comparison of percentage changes in sTREM-1 levels at the 6 h relative to baseline with respect to antibiotic susceptibility. Results: Of the 596 patients enrolled in the pre-established study, 29 with a median age of 75.8 and a 28-day mortality rate of 17.2% were included in the present analysis. Among these patients, 24 were classified into the susceptible group, whereas the remaining five were classified into the resistant group. The trend in plasma sTREM-1 levels differed with respect to antibiotic susceptibility. Moreover, percentage change in sTREM-1 levels at the 6 h relative to baseline was significantly higher in the resistant group (P = 0.028). Conclusion: The trend in plasma sTREM-1 levels in patients with sepsis differed with respect to antibiotic susceptibility, with a higher percentage change in patients treated with inappropriate antibiotics. These findings indicate the potential utility of sTREM-1 as an early biomarker of antibiotic susceptibility.

The effect of a fibrin-fibronectin/beta-tricalcium phosphate/recombinant human bone morphogenetic protein-2 system on bone formation in rat calvarial defects.

In spite of good prospects for bone morphogenetic proteins (BMP) applications, an ideal carrier system for BMPs has not yet been identified. The purpose of this study was to evaluate the osteogenic effect of a fibrin-fibronectin sealing system (FFSS) combined with beta-tricalcium phosphate (beta-TCP) as a carrier system for recombinant human bone morphogenetic proteins (rhBMP-2) in the rat calvarial defect model. Eight-millimeter critical-size calvarial defects were created in 100 male Sprague-Dawley rats. The animals were divided into five groups of 20 animals each. The defects were treated with rhBMP-2/FFSS, rhBMP-2/FFSS/beta-TCP, FFSS and FFSS/beta-TCP carrier control or were left untreated as a sham-surgery control. Defects were evaluated by histologic and histometric parameters following a 2- and 8-week healing interval (10 animals/group/healing intervals). The FFSS/beta-TCP carrier group was significantly greater in new bone area at 2 weeks (p<0.05) and new tissue area at 2 and 8 weeks (p<0.01) relative to the FFSS carrier group. New bone and new tissue area in the rhBMP-2/FFSS/beta-TCP group were significantly greater than in the rhBMP-2/FFSS group at 8 weeks (p<0.01). On histologic observation, FFSS remnants were observed at 2 weeks, but by 8 weeks, the FFSS appeared to be completely resorbed. rhBMP-2 combined with FFSS/beta-TCP produced significantly more new bone and new tissue formation in this calvarial defect model. In conclusion, FFSS/beta-TCP may be considered as an available carrier for rhBMP-2.

Effect of recombinant human bone morphogenetic protein-2, -4, and -7 on bone formation in rat calvarial defects.

BACKGROUND: Currently, more than 20 bone morphogenetic proteins (BMPs) have been identified, and many trials have been carried out using recombinant human BMPs (rhBMPs) for bone tissue engineering. However, comparative analyses on bone formative activities of rhBMP using a preclinical model have been limited. Therefore, the aim of this study was to evaluate and compare the osteogenic potential of rhBMP-2, -4, and -7 delivered with absorbable collagen sponge (ACS) upon early (2 weeks) and complete (8 weeks) wound healing phases in a critical sized rat calvarial defect model. METHODS: Eight-millimeter critical sized calvarial defects were created in 30 male Sprague-Dawley rats. The animals were divided into three groups of 10 animals each. The defects were treated with 0.025 mg/ml rhBMP-2/ACS, rhBMP-4/ACS, or rhBMP-7/ACS. The rats were sacrificed at either 2 (five rats) or 8 (five rats) weeks after surgery, and the results were evaluated histologically, histomorphometrically, and immunohistometrically. RESULTS: The surgical implantation of rhBMP-2/ACS, rhBMP-4/ACS, or rhBMP-7/ACS resulted in enhanced local bone formation in the rat calvarial defect model at both 2 and 8 weeks. The amount of defect closure, new bone area, and bone density were similar in the three groups at each time point (P > 0.05). In terms of bone density and new bone area, there were statistically significant differences between results obtained at 2 weeks and those obtained at 8 weeks in all groups (P < 0.05). Two-way analysis of variance (ANOVA) revealed that there was no correlation between the time and conditions (P > 0.05), but time was found to have a strong influence on defect closure, new bone area, and bone density (P < 0.05). Irrespective of rhBMP type, positive immunoreactions of osteopontin (OPN) and osteocalcin (OCN) were evident at 2 and 8 weeks. Intense OPN and OCN staining was observed near the newly formed bone as well as in some cells within the new bone. CONCLUSIONS: Within the rhBMP types used, rhBMP concentration, and the observation interval, there appears to be no specific differences in bone regenerative potential. All rhBMPs used in this study may be considered effective factors for inducing bone formation.

Effect of a fibrin-fibronectin sealing system as a carrier for recombinant human bone morphogenetic protein-4 on bone formation in rat calvarial defects.

BACKGROUND: Bone morphogenetic proteins (BMPs) have been shown to play an important role in bone formation during development and wound healing. Despite there being good prospects for BMP applications, an ideal carrier system for BMPs has yet to be determined. The purpose of this study was to evaluate the possibility of a fibrin-fibronectin sealing system (FFSS) as a carrier for recombinant human BMP-4 (rhBMP-4) and to evaluate the genuine osteoconductive potential of the FFSS in a rat calvarial defect model. METHODS: An 8-mm, calvarial, critical-size osteotomy defect was created in each of 30 male Sprague-Dawley rats. Three groups of 10 animals each received rhBMP-4 (0.025 mg/ml) in the FFSS, FFSS control, or sham-surgery control. The groups were evaluated using histologic and histometric parameters following 2- and 8-week healing intervals (five animals per group per healing interval). RESULTS: Surgical implantation of rhBMP-4/FFSS resulted in enhanced local bone formation at 2 and 8 weeks. New bone formation was also evident in the FFSS control; however, the amount of defect closure, new bone area, and bone density was significantly greater in the rhBMP-4/FFSS group (P < 0.05). At 8 weeks, the quantity of the new bone was greater than that observed at 2 weeks, and the specimens showed a more advanced stage of remodeling and consolidation in both groups (P < 0.05). Only very limited bone formation was observed in the sham-surgery control. CONCLUSION: The results of the present study indicated that the FFSS has osteoconductive potential and may be employed as a carrier for BMPs.