Surface Morphology of Unused and Used HydromerR-Coated Intravenous Catheters

HydromerR-coated polyurethane (Erythroflex)R catheters, unused, or intravenously inserted for 2-20 days, were studied by scanning electron microscopy (SEM). Both unfixed and fixed (2% glutar-aldehyde in phosphate buffer), and air-or critical-point dried (CPD) specimens were investigated. The catheter segments were sputter-coated with approx. 20 nm gold and studied at an accelerating voltage of 20 kV. The specimens were examined for surface depositions, thickness and structure of the HydromerR layers, and occurrence of adhering and embedded bacteria. The outer HydromerR layer showed, in the un-used specimens, scratches and fissures, as well as adhering foreign bodies. In used specimens, the layer was swollen, with cracks (like dried earth ), and, occasionally , amorphous substances and coccoid bacteria were seen adhering. Damage to the layer, or even its total disappearance was also noted in some specimens. The inner (luminal) HydromerR layer was, in unused specimens, clean and slightly wavy. In used catheters, it was thicker, possibly swollen, with small, isolated or agglomerated protrusions, like a lunar landscape . Adhering platelets and amorphous substances were also occasionally seen. The results suggest that the HydromerR is a fragile material in both its dry and wet forms. Thus, the HydromerR-coated catheters should neither be stored in flexible packs, nor inserted by the Seldinger technique. The findings do not support the belief that the HydromerR-coating can prevent either thrombus formation, or intraluminal occlusion of the in-situ catheters

Safety assessment of new antithrombotic agents: lessons from the EXTEND study on ximelagatran

BACKGROUND: Ximelagatran, the first oral direct thrombin inhibitor, was shown to be an effective antithrombotic agent but was associated with potential liver toxicity after prolonged administration. OBJECTIVES AND METHODS: The aim of the EXTEND study was to assess safety and efficacy of extended administration (35 days) of ximelagatran or enoxaparin for the prevention of venous thromboembolism after elective hip replacement and hip fracture surgery. A follow-up period, including assessment of liver enzymes (in particular alanine aminotransferase; ALAT), until post-operative day 180 was planned, with visits at days 56 and 180. RESULTS: Randomization and administration of study drugs were stopped following a report of serious liver injury occurring 3 weeks after completion of ximelagatran treatment. At the time of study termination, 1158 patients had been randomized and 641 had completed the 35-day treatment; with 303 ximelagatran and 265 enoxaparin patients remaining in the study through to the day 56 follow-up visit. Overall, 58 patients showed an ALAT increase to >2x upper limit of normal: 31 treated with enoxaparin, 27 with ximelagatran. Three ximelagatran patients also showed symptoms potentially related to liver toxicity. Eleven ximelagatran patients showed an ALAT increase after study treatment ended. The clinical development of ximelagatran was terminated and the drug withdrawn from the market. Evaluation of the relative efficacy of the two treatments as specified in the protocol was impossible due to the premature termination of the study. CONCLUSIONS: Prolonged administration of ximelagatran was associated with an increased risk of liver toxicity. In a substantial proportion of patients, ALAT increase occurred after treatment withdrawal. The findings seen with ximelagatran should be considered when designing studies with new antithrombotic agent