Toxicological screening in the Amsterdam acute setting becomes more relevant if the standard panel of the drugs-of-abuse point-of-care test is expanded with GHB and ketamine.

OBJECTIVE: For diagnosis and treatment in the acute setting, it is crucial to know whether the clinical status of patients might be explained by the effects of drugs.The objective of this study was to determine how many drugs were detected by comprehensive toxicological screening, that could not be detected with a routine drugs-of-abuse point-of-care test (DOA-POCT) and which drugs of abuse (DOA) were relevant. A secondary objective was to determine in how many patients comprehensive toxicological screening provided additional clinically relevant information. METHODS: In this prospective study, patients were included in whom a DOA-POCT was performed and residual urine and serum samples were available.DOA-POCT were performed using the Triage® TOX Drug Screen. Comprehensive toxicological screening was performed using 1) the Toxtyper™ LC-MSN method and 2) two GC-FID methods for alcohols and GHB respectively.The clinical relevance of the comprehensive toxicological screening results regarding diagnosis and patient management was quantified. RESULTS: A total of 100 patients were included. In 91 of these patients, comprehensive toxicological screening identified 234 drugs that were not identified by DOA-POCT. However, DOA-POCT identified 34 DOA that were not identified by comprehensive toxicological screening.Seven percent of comprehensive toxicological screening results were found to be clinically relevant, all with regard to diagnosis. GHB and ketamine were the drugs involved. Another 38 % strengthened confidence in diagnosis and patient care decisions. CONCLUSION: GHB and ketamine should be added to the panel of drugs we screen at the point of care in the Amsterdam acute setting.

Stability of Furosemide 5 mg/mL in Polypropylene Syringes.

Furosemide parenteral solutions are routinely used in our hospital. However, the stability in transparent syringes is unknown. In this study, transparent polypropylene syringes were filled with 8 mL and 50 mL of furosemide 5-mg/mL solution. The furosemide was analyzed by high-performance liquid chromatography and assays were performed up to 35 days of storage of the syringes at 4°C protected from light, plus 24 hours at 20°C exposed to daylight. In addition, the appearance and pH of the solutions were determined. A microbiological assay using tryptic soy broth was also performed. Both types of syringes remained colorless, clear, and free from visible particles throughout the study period. The pH did not change, and concentrations remained between 95% and 105% of the stated concentration. None of the syringes filled with culture media exhibited bacterial or fungal growth. In conclusion, ready-to-administer furosemide 5-mg/mL, 8-mL, and 50-mL polypropylene syringes are stable for up to 35 days when stored in a refrigerator at 4°C protected from light, plus 24 hours at 20°C unprotected from light. These results allow maximum storage time in stock and the ability of 24-hour continuous infusion at ambient room temperature without protecting the syringe against light.

The role of shear stress in the destabilization of vulnerable plaques and related therapeutic implications.

American Heart Association type IV plaques consist of a lipid core covered by a fibrous cap, and develop at locations of eccentric low shear stress. Vascular remodeling initially preserves the lumen diameter while maintaining the low shear stress conditions that encourage plaque growth. When these plaques eventually start to intrude into the lumen, the shear stress in the area surrounding the plaque changes substantially, increasing tensile stress at the plaque shoulders and exacerbating fissuring and thrombosis. Local biologic effects induced by high shear stress can destabilize the cap, particularly on its upstream side, and turn it into a rupture-prone, vulnerable plaque. Tensile stress is the ultimate mechanical factor that precipitates rupture and atherothrombotic complications. The shear-stress-oriented view of plaque rupture has important therapeutic implications. In this review, we discuss the varying mechanobiologic mechanisms in the areas surrounding the plaque that might explain the otherwise paradoxical observations and unexpected outcomes of experimental therapies.

Imaging of coronary atherosclerosis and identification of the vulnerable plaque.

Identification of the vulnerable plaque responsible for the occurrence of acute coronary syndromes and acute coronary death is a prerequisite for the stabilisation of this vulnerable plaque. Comprehensive coronary atherosclerosis imaging in clinical practice should involve visualisation of the entire coronary artery tree and characterisation of the plaque, including the three-dimensional morphology of the plaque, encroachment of the plaque on the vessel lumen, the major tissue components of the plaque, remodelling of the vessel and presence of inflammation. Obviously, no single diagnostic modality is available that provides such comprehensive imaging and unfortunately no diagnostic tool is available that unequivocally identifies the vulnerable plaque. The objective of this article is to discuss experience with currently available diagnostic modalities for coronary atherosclerosis imaging. In addition, a number of evolving techniques will be briefly discussed.

Optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) is a light-based imaging modality that can be used in biological systems to study tissues in vivo with near-histologic, ultrahigh resolution. The rationale for intravascular application of OCT is its potential for in vivo visualisation of the coronary artery microstructure. METHODS AND RESULTS: The principle is analogous to pulse-echo ultrasound imaging; however, light is used rather than sound to create the image. Low-coherent near-infrared light is emitted by a superluminescent diode and reflected by the microstructures within biological tissues. The echo time delay of reflected light waves is converted into a two-dimensional spatial image. The intensity of the reflected light waves is translated into an intensity map. Experimental studies confirmed the ability of intravascular OCT for plaque characterisation and accurate assessment of vascular structures that are close to the luminal surface. Preliminary clinical experience proved in vivo feasibility of intravascular OCT. A variety of atherosclerotic plaque structures including thin cap fibroatheromas can be visualized in vivo. CONCLUSIONS: Intravascular OCT allows for accurate assessment of vessel structures close to the luminal side. Clinical application is feasible. To date, however, the clinical relevance of OCT findings in coronary arteries is unclear and further validation of OCT imaging is mandatory.

Effect of temperature increase and freezing on intravascular elastography.

Intravascular ultrasound (IVUS) elastography is a technique that assesses the local strain in the vessel wall and plaque. The strain is an important parameter for characterization of different plaque components. These regions are related to plaque vulnerability. IVUS elastography was validated in vitro using human coronary and femoral arteries. These experiments were performed on specimens that were stored frozen and measured at room temperature for practical issues. The aim of this study is to determine the influence of freezing and measuring the tissues at room temperature (23 degrees C instead of 37 degrees C) on the elastic properties. Four human coronary, one carotid and one femoral arteries were first measured at 23 degrees C and next at 37 degrees C. Additionally they were stored at -80 degrees C for up to 24 h and finally measured at 23 degrees C. Acquisitions at intraluminal pressures of 80 and 100 mmHg were performed using an EndoSonics 20 MHz Visions catheter. Elastograms were determined from the IVUS rf-data (sampled at 100 MHz in 12 bits) that were obtained from a digital interface. Qualitative and quantitative analysis of the elastograms obtained from fresh and frozen specimens measured at 23 degrees C reveals that storage of the specimen at -80 degrees C has no significant influence. In vitro experiments can be performed at room temperature after storage of the tissue at -80 degrees C without significant affection of the information with respect to measuring fresh ex vivo material at body temperature.