The effect of concentration, reconstitution solution and pH on the stability of a remifentanil hydrochloride and propofol admixture for simultaneous co-infusion

Background: There are scenarios where pre-mixing and infusing analgesic and anaesthetic agents as a single intravenous (IV) solution is highly desirable; however, it is important to ensure the agents are compatible when mixed. As such, the long-term stability of a remifentanil-propofol mixture, and means of improving this, were assessed across a range of remifentanil concentrations, diluents, and time points. Methods: Remifentanil was reconstituted with ultrapure water, 0.9% saline, 20% saline, or 8.4% sodium bicarbonate solution (the latter two chosen for their pH characteristics, rather than their use in pharmaceutical reconstitution) and then mixed with propofol (1%) or further diluted with water to derive concentrations of 10–50 μg mL . Remifentanil and propofol concentrations were determined initially and then periodically for up to 24 h using high performance liquid chromatography (HPLC). Mass spectrometry (MS) was used to detect degradation products in solutions containing 30 μg mL of remifentanil. Statistical analysis was performed using ANOVA and Student’s t-test, with a significance value of 0.05. Results: Isolated remifentanil (pH < 4) and propofol (pH 7.35) did not degrade significantly when reconstituted with water or saline solution over 24 h, while remifentanil reconstituted with sodium bicarbonate degraded significantly (P < 0.001, pH 8.65). Mixing with propofol substantially increased the pH of the mixture and resulted in significant remifentanil degradation for all reconstitution solutions used, while propofol remained stable (pH 6.50). The amount of degradation product detected in samples containing isolated remifentanil and a mixture of the drugs was proportional to the remifentanil degradation observed. Conclusions: Remifentanil stability is affected by both the reconstitution solution used and when mixed with propofol, with pH appearing to be a contributing factor to degradation. If the pH of the solution and concentration of remifentanil are correctly controlled, e.g. through the use of a more acidic diluent, an admixture of remifentanil and propofol may be useful clinically. − 1 −

The incidence and characteristics of ventilator-associated pneumonia in a regional nontertiary Australian intensive care unit: A retrospective clinical audit study

Background: Ventilator-associated pneumonia (VAP) is a common complication of mechanical ventilation in the intensive care unit. The incidence, patient characteristics, and outcomes have not been described in a regional Australian setting. Objectives: Τhe primary objective was to establish the incidence of VAP in a regional intensive care unit using predetermined diagnostic criteria. The secondary objective was to compare the agreement between criteria-based and physician-based diagnostic processes. The tertiary objectives were to compare patient characteristics and clinical outcomes of cases with and without VAP. Methods: A retrospective clinical audit was performed of adult patients admitted to Rockhampton Intensive Care Unit, Australia, between 2013 and 2016. We included all patients ventilated for ≥72 h and not diagnosed with a pneumonia before or during the first 72 h of ventilation. Results: A total of 170 cases met the inclusion criteria. The incidence of VAP as per the criteria-based diagnosis was 27.3 cases per 1000 ventilator days (95% confidence interval [CI]: 18.4–36.2) and as per the physician-based diagnosis was 25.8 cases per 1000 ventilator days (95% CI: 17.1–34.4). There was a moderate chance-corrected agreement between the criteria- and physician-based diagnosis. Very obese cases (body mass index [BMI] ≥40) were nearly four times more likely to develop VAP than cases with normal BMI (BMI <30) (odds ratio: 3.664; 95% CI: 1.394–9.634; p = 0.008). After controlling for sex, BMI category, comorbidities, and Acute Physiology and Chronic Health Evaluation II scores, there was a trend (p = 0.283) for higher adjusted mortality rate for cases with VAP (10.1%, 95% CI: 4.8–21.5) than for those without VAP (6.1%, 95% CI: 3.0–12.4). Cases with VAP had a higher total hospital cost ($123,223 AUD vs$66,425 AUD, p < 0.001), than cases without VAP. Conclusions: This is the first study reporting incidence of VAP in an Australian regional intensive care unit setting. An increased length of stay and significantly higher hospital costs warrant research investigating reliable and valid clinical prediction rules to forecast those at risk of VAP

Stable Isotope Dilution Multidimensional Liquid Chromatography-Tandem Mass Spectrometry for Pancreatic Cancer Serum Biomarker Discovery

A novel approach to pancreatic cancer biomarker discovery has been developed, which employs a stable isotope labeled proteome (SILAP) standard coupled with extensive multidimensional separation coupled with tandem mass spectrometry (MS/MS). Secreted proteins from CAPAN-2 human pancreatic cancer derived cells were collected after conducting stable isotope labeling by amino acids in cell culture (SILAC). The resulting SILAP standard contained <0.5% of individual unlabeled proteins. Pooled sera from patients with early stage pancreatic cancer or controls were prepared, and an equal amount of the SILAP standard was added to each sample. Proteins were separated by isoelectric focusing (IEF) prior to two-dimensional liquid chromatography (2D-LC)–MS/MS analysis. A total of 1065 proteins were identified of which 121 proteins were present at 1.5-fold or greater concentrations in the sera of patients with pancreatic cancer. ELISA validation of these findings was successfully performed for two proteins, ICAM-1 and BCAM. Results of these studies have provided proof of principle that a SILAP standard derived from the CAPAN-2 secreted proteome can be used in combination with extensive multidimensional LC-MS/MS for the identification and relative quantitation of potential biomarkers of pancreatic cancer. This technique allows for the detection of low-abundance proteins, and focuses only on biologically relevant proteins derived from pancreatic cancer cells

Analysis of Adsorbed Polyphosphate Changes on Milled Titanium Dioxide, Using Low-Field Relaxation NMR and Photoelectron Spectroscopy

In this study, changes in the adsorbed amount and surface structure of sodium hexametaphosphate (SHMP) were investigated for aluminum-doped TiO2 pigment undergoing milling. Relaxation NMR was utilized as a potential at-line technique to monitor the effect of milling on surface area and surface chemistry, while XPS was used primarily to consider the dispersant structure. Results showed that considerable amounts of weakly adsorbed SHMP could be removed with washing, and the level of dispersant removal increased with time, highlighting destructive effects of sustained high-energy milling. Nonetheless, there were no significant chemical changes to the dispersant, although increases to the bridging oxygen (BO) peak full width at half-maximum (FWHM) suggested some chemical degradation was occurring with excess milling. Relaxation NMR revealed a number of important features. Results with unmilled material indicated that dispersant adsorption could be tracked with pseudo-isotherms using the relative enhancement rate (Rsp), where the Rsp decreased with dispersant coverage, owing to partial blocking of the quadrupolar surface aluminum. Milled samples were also tracked, with very accurate calibrations of surface area possible from either T1 or T2 relaxation data for systems without dispersant. Behavior was considerably more complicated with SHMP, as there appeared to be an interplay between the dispersant surface coverage and relaxation enhancement from the surface aluminum. Nevertheless, findings highlight that relaxation NMR could be used as a real-time technique to monitor the extent of milling processes, so long as appropriate industrial calibrations can be achieved

Additional file 2: of Feasibility of an online mindfulness-based program for patients with melanoma: study protocol for a randomised controlled trial

The TIDieR (Template for Intervention Description and Replication) Checklist. (DOCX 31 kb

Additional file 1: of Feasibility of an online mindfulness-based program for patients with melanoma: study protocol for a randomised controlled trial

SPIRIT 2013 Checklist. (DOC 121 kb

Additional file 1 of ERK mediates interferon gamma-induced melanoma cell death

Supplementary Material