Y-site administration of electrolyte solutions and injectable acetaminophen-A physical compatibility study with combinations frequently used in pediatric intensive care and anesthesia.

AIM: Determination of the physical compatibility of acetaminophen and two different electrolyte solutions (an isotonic, balanced electrolyte solution and a hypotonic, glucose containing electrolyte solution) with drugs frequently used in routine pediatric intensive care. METHODS: Analytical investigations for frequently used combinations without pre-existing data were performed. Visual and microscopic observations according to the European Pharmacopeia as well as pH measurements and ultraviolet visible spectrometry at wavelengths of 350, 410 and 550 nm were conducted to analyze physical compatibility. All measurements were performed immediately after mixing as well as 1, 4, and 24 h after. RESULTS: In total, 42 combinations were analyzed. Visual incompatibilities were found with pantoprazole and diazepam with both electrolyte solutions. For furosemide, a particle formation in mixture with the hypotonic glucose-containing electrolyte solution and a change in pH ≥ 0.5 after 24 h with both electrolyte solutions were observed. Ampicillin, cefuroxime, diazepam, furosemide, linezolid, meropenem, and pantoprazole showed an aberration of the absorbance ≥0.04 (350 nm/410 nm) or ≥0.01 (550 nm) in the photometric measurements with the electrolyte solutions. For acetaminophen, a physical incompatibility was observed with ampicillin, diazepam, furosemide, and pantoprazole. CONCLUSION: Most of the analyzed combinations showed no signs of physical incompatibility and may therefore be administered via the same Y-site. However, diazepam, furosemide, and pantoprazole should not be administered simultaneously with acetaminophen or both electrolyte solutions.

A new approach on assessing clinical pharmacists' impact on prescribing errors in a surgical intensive care unit.

Background With a clinical pharmacists' participation in an intensive care unit (ICU) previous international studies have shown a reduction of medication errors, drug costs and improvements of clinical outcomes. Still there is a lack of qualitative data on clinical pharmacists' impact on prescribing error rates in the ICU. Therefore, a new approach was developed relating prescribing errors to the number of monitored medications including physicians' approval on all prescribing errors. Objective This study investigates the influence of clinical pharmacists' medication review on the prescribing error rate in an ICU. Setting A controlled interventional study was conducted in a surgical ICU with one control phase (P0) and two intervention phases (P1 and P2). Method The investigation aimed to determine if the medication review by clinical pharmacists results in a significant reduction of prescribing errors related to a control period. In contrast to previous studies, prescribing errors detected by the clinical pharmacists, were only taken into account, if consent with the physicians was achieved. Secondary outcomes were the reduction of potentially severe prescribing errors, the number of days without systemic anti-infective therapy and the ICU length of stay. Throughout P0 the data was collected retrospectively without any intervention. During the intervention periods P1 and P2, two clinical pharmacists screened the medical records for prescribing errors and discussed them with the senior physician in charge. During P2 one clinical pharmacist attended ward rounds additionally. Main Outcome Measure The main outcome measure of this study was the number of prescribing errors detected related to the number of monitored medications. Results The incidence of prescribing errors was significantly reduced from 1660 in P0 to 622 in P1 respectively 401 in P2 (P0 vs. P1/P2 respectively; both p < 0.001; Fisher's Exact Test) in total, respective 14.12% in P0 vs. 5.13% in P1 and 3.25% in P2 related to the monitored medications (P0:11755; P1:12134; P2:12329). Conclusion Clinical pharmacists' interventions led to a significant reduction of prescribing errors in the ICU, contributing to a safer medication process. We strongly recommend a broad implementation of clinical pharmacists in ICUs.

Oxygenation status of urogenital tumors.

In malignant urogenital tumors, tissue oxygenation is compromised and very heterogeneous,with steep and fluctuating spatio-temporal oxygen gradients signaling a complex instability in tumor oxygenation (complex "4D-heterogeneity"). Tumor hypoxia is highly dynamic, and rapidly changing pO(2) gradients may be key factors driving hypoxia-dependent adaptive processes leading to malignant progression. The grand median oxygen tension in malignant urogenital tumors is 7-11 mmHg. In contrast, benign leiomyomas of the uterus are severely, but uniformly, hypoxic with only shallow oxygen gradients ("static hypoxia"). In these benign tumors, the median pO(2) is 1 mmHg and signs of hypoxia-driven processes are missing.

HIF-mediated hypoxic response is missing in severely hypoxic uterine leiomyomas.

Results from our laboratory have put a question mark on the existence of a direct quantitative relationship between tumor hypoxia and HIF-mediated protein expression in cancers of the uterine cervix. In the present study, this subject has been further explored by the analysis of HIF-related marker expression in a benign tumor entity - uterine leiomyomas - using immunohistochemistry, western blotting and RT-PCR. The oxygenation status of 17 leiomyomas was assessed by means of intraoperative polarographic needle electrode measurements. Results show that these tumors are severely and uniformly hypoxic, but do not induce HIF-1alpha, HIF-2alpha, glucose transporter (GLUT)-1 or carbonic anhydrase (CA) IX. Furthermore, this downregulation of the HIF-system was not caused by an overexpression of the hypoxia-inducible prolyl hydroxylase domain proteins (PHDs) 2 and 3. Compared with normal myometrium, leiomyomas also show a poorer vascularization. Conversely, leiomyosarcomas show abundant expression of HIF-related markers despite a similar microvascular density. In conclusion, these results indicate that the strong activation of the HIF system observed in solid malignant tumors may be mechanistically linked to their transformed phenotype, rather than being a physiological reaction activated in a pathological context.

A comprehensive analysis of HPV integration loci in anogenital lesions combining transcript and genome-based amplification techniques.

Persistent infections with high-risk human papillomaviruses (HPVs) induce dysplastic lesions of the lower genital tract. Some of these lesions eventually progress to invasive cancers, particularly of the uterine cervix. In many advanced preneoplastic cervical lesions and most derived carcinomas, HPV genomes are found to be integrated into the host cell chromosomes. Although HPV integration seems to play an important role in the progression of cervical dysplasia, the underlying mechanisms are still unclear. To investigate the pathogenic role of genomic integration of HPV genomes in greater detail, we analysed integration sites of HPV16 and 18 genomes in 21 anogenital precancerous and cancerous lesions using a ligation-mediated chain reaction (DIPS) and the recently described amplification of papilloma virus oncogene transcripts (APOT) assay. On the genomic level, only singular integration events were observed in individual neoplastic cell clones. At many integration sites, a short overlap between HPV and genomic sequences was observed, suggesting that the integration of HPV genomes is mediated by nonhomologous sequence-specific recombination. APOT analysis revealed that the majority of integrated HPV genomes was actively transcribed. These data suggest that in the progression of cervical preneoplasia to invasive carcinomas, integration of viral genomes occurs only at single or few chromosomal loci in a given cell clone. Disruption of cellular genes might support malignant transformation in rare cases; however, it is not a pathogenic prerequisite. The main function of HPV integration seems to be the stabilization of oncogene transcription.