The opioid fentanyl is administered in millions of procedural sedations every year. It is very potent, has large interpatient pharmacokinetic variability, and routinely causes significant respiratory depression if bolused or not titrated judiciously. Dosing and timing, critical for safety and efficacy, are presently only possible based on educated guesses and vital signs. Sedation associated morbidity are primarily drug-induced respiratory depression and airway obstruction, especially when the drugs are administered by clinicians with limited airway rescue skills. Endoscopists (78.5%) are primarily sedating patients instead of anesthesiologists or CRNAs (27.8%). Over 68,000 patients per year have significant drug-induced respiratory events during sedation for colonoscopies and 3,000 patients die. No method for point-of-care concentration monitoring of these drugs is known. The long-term goal of the proposed work is to provide, for the first time, a sensor for real time monitoring of opioid and other medications, allowing the personalized administration of these drugs. This grant will create an intravenous catheter-tip sensor for fentanyl and demonstrate that the proposed hydrogel/aptamer based sensor performs sufficiently well (accuracy,drift, response time, longevity) to allow guidance of fentanyl administration. Such a monitor will help clinicians to better target the drug concentrations needed by the individual patient, thereby lowering the risk of adverse events due to over â or under-administration. Our specific aims are tailored to show proof of principle: In aim 1 aptamer enhanced smart hydrogels with sufficient binding affinities to fentanyl will be created; In aim 2 the fentanyl sensitive smart hydrogels will be integrated onto an optimized polyimide sensor platform and miniaturized for use in an intravenous catheter. Sensor performance will be evaluated in-vitro using phosphate-buffered saline (PBS) and blood plasma; We will demonstrate the feasibility of a real-time monitor for fentanyl concentrations and develop a versatile polymer sensor platform. The successful demonstration would indicate a straight-forward path to creating sensors for other intravenous medications by integrating other aptamers onto the platform. This platform would enable further research into individualized pharmacokinetic/dynamic models and generate revenue by supplying research scientists and clinicians alike with these easy to handle sensors.
Public Health Relevance Statement: PROJECT NARRATIVE Currently, intravenous sedation, analgesia, and anesthesia are administered without any method for knowing the blood concentrations of powerful medications such as fentanyl. Instead, these medications are administered based on population statistics, in spite of known large interpatient pharmacokinetic variabilities. The proposed research will demonstrate the feasibility of a novel real-time sensing platform for blood concentrations of medication with fentanyl as first target analyte. Sensing devices based on this platform technology will enable personalized administration of medication.
Project Terms: Absence of pain sensation; adverse event risk; Affinity; Age; airway obstruction; Anesthesia procedures; Anesthetics; Antibiotics; aptamer; base; Binding; Biological Markers; Blood; Catheters; Chemicals; Chemistry; chemotherapy; Clinical; Colonoscopy; Concentration measurement; cost; crosslink; Data; Decision Making; Development; Devices; DNA; dosage; Dose; Drug Kinetics; Drug Monitoring; Drug Targeting; electric impedance; Event; Feedback; Fentanyl; Future; General Anesthesia; Glucose; Goals; Grant; graphical user interface; Hybrids; Hydrogels; imprint; improved; In Vitro; in vivo; Individual; individual patient; Infusion Pumps; instrument; interest; Intravenous; Intuition; Left; Length; Longevity; Measurement; Measures; medication administration; Methods; miniaturize; Modeling; Molecular; Monitor; Morbidity - disease rate; mortality; novel; older patient; Oligonucleotides; Opioid; opioid injection; opioid use; overdose death; Pain; patient response; patient variability; Patients; Performance; Pharmaceutical Preparations; pharmacokinetic model; Phosphate Buffer; Plasma; point of care; Polymers; population based; Population Statistics; prevent; Reaction Time; real time monitoring; Recording of previous events; Regimen; Research; respiratory; response; Rest; Safety; Saline; Scientist; Sedation procedure; sedative; sensor; sensor technology; Signal Transduction; Single-Stranded DNA; skills; Swelling; System; Tail; Technology; Thrombin; Time; Ventilatory Depression; Weight; Wor
