Anesthesia and analgesia
-
Factor V Leiden (FVL) is the most common known inherited cause of thrombophilia; it is present in approximately 5% of the Caucasian population. Although the risk of venous thrombosis associated with this polymorphism in various medical settings is well described, its effect on perioperative risk is only beginning to be explored. ⋯ This review will describe the physiology of the FVL mutation, briefly clarify its risk in the nonsurgical setting, and assess current data regarding FVL in noncardiac and cardiac surgery. Finally, a summary of current clinical evidence and a plan for more detailed investigation of this potentially significant risk factor will be proposed.
-
Anesthesia and analgesia · Jun 2004
ReviewThe use of intrathecal midazolam in humans: a case study of process.
Early preclinical work demonstrated the potential role of spinal benzodiazepine pharmacology in regulating spinal nociceptive transmission. We review this preclinical activity and the evolving implementation of intrathecal midazolam in humans for pain management. Important elements in this development for use in humans are issues pertinent to safety and the preclinical reports that have increased our understanding of intrathecal midazolam toxicity. We seek to emphasize the time course of these studies and how they merged to provide enabling data that drove the clinical implementation. In the case of midazolam, we point to the potential issues that arose when preclinical safety data were unreasonably ignored and how consideration of preclinical safety data can serve to facilitate drug development by demonstrating reasonable safety profiles that document the minimal degree of potential risk to the patient. Issues that are of continuing relevance to the use of intrathecal midazolam, including issues of formulation and kinetics, are considered. ⋯ The intrathecal use of midazolam has evolved over 20 years though a combination of preclinical and clinical investigations. We review the time course of this development to define critical elements that should be pursued in reducing the risk associated with the clinical use of a novel spinal drug.