RESUMEN
Background: Medical device manufacturers are obliged to prove the biocompatibility of their products when they come into contact with the human body. The requirements for the biological evaluation of medical devices are specified by the international standard series ISO 10993. Part five of this series describes the performance of in vitro cytotoxicity tests. This test evaluates the effects of medical device use on cell health. The existence of the specific standard suggests that the tests will produce reliable and comparable results. However, the ISO 10993-5 offers wide latitude in the test specifications. In the past, we noticed inconsistencies of the results from different laboratories. Objective: To determine if the specifications of the standard ISO 10993-5 are explicit to ensure the comparability of test results and, if not, identify potential influencing factors. Methods: An interlaboratory comparison was conducted for the in vitro cytotoxicity test according to ISO 10993-5. Fifty-two international laboratories evaluated the cytotoxicity for two unknown samples. One was polyethylene (PE) tubing, which is expected to be non-cytotoxic and the other was polyvinyl chloride (PVC) tubing, for which a cytotoxic potential was presumed. All laboratories were asked to perform an elution test with predefined extraction specifications. The other test parameters were freely chosen by the laboratories according to the guidelines set by the standard. Results: To our surprise only 58 percent of the participating laboratories identified the cytotoxic potential of both materials as expected. Particularly for PVC a considerable variation of the results between the laboratories was observed [mean = 43 ± 30 (SD), min = 0, max = 100]. We showed that ten percent serum supplementation to the extraction medium, as well as longer incubation of the cells with the extract, greatly increased the test sensitivity for PVC. Conclusion: The results clearly show that the specifications set by the ISO 10993-5 are not explicit enough to obtain comparable results for an identical medical device. To set requirements that ensure reliable cytotoxicity assessments, further research will be necessary to identify the best test conditions for specific materials and/or devices and the standard needs to be revised accordingly.
RESUMEN
PURPOSE: The results of a study to determine whether certain laboratory values can predict the effectiveness of recombinant factor VIIa (rFVIIa) therapy to control postoperative bleeding in surgical patients are presented. METHODS: In a retrospective observational study at a large university hospital, the records of all adult patients on the cardiothoracic surgery (CTS) and general or trauma surgery (GTS) units who received rFVIIa for treatment-refractory nonsurgical bleeding episodes (an off-label use) during a 17-month period were reviewed. Collected data included blood product requirements before and after administration of rFVIIa, selected periadministration laboratory values (e.g., International Normalized Ratio, platelet count, arterial pH, fibrinogen concentration), 24-hour and 30-day mortality, and documented adverse thrombotic events. RESULTS: Among the 18 GTS and 32 CTS patients who received rFVIIa during the study period, hemostasis (as defined according to 12- and 24-hour transfusion requirements) was achieved in 50% of patients in both groups. Two of the evaluated laboratory values were found to be predictive of reduced rFVIIa effectiveness. Hemostasis was not achieved in any patient with an arterial pH of ≤7.1 or a fibrinogen concentration of <100 mg/dL. The study results did not support the hypothesis that a platelet count of <50,000 cells/L is associated with reduced effectiveness of rFVIIa therapy for the studied indication. Adverse thrombotic events occurred in 14 patients (28%) after rFVIIa administration. CONCLUSION: CTS and GTS patients with bleeding episodes and an arterial pH of ≤7.1 or a fibrinogen concentration of <100 mg/dL were not likely to achieve hemostasis after rFVIIa therapy.