In Phase I, Biocrede developed a wireless 2 Fr. (flexible) and a 5 Fr. dual lumen (catheter) nitric oxide (NO) releasing, in-vivo tested without heparin injections, continuous lactate sensor that can wirelessly monitor intravenous (IV) blood lactate levels to alert caregivers in the ICU when lactate levels rise. Elevated blood lactate levels are associated with major morbidity and mortality in critically ill patients recovering from organ transplantation or trauma, and in pediatric patients with congenital heart disease (CHD) undergoing cardiac surgery with cardiopulmonary bypass (CPB). Our sensors (Biocrede IP, provisional patents US62448960 and US62553832) possess NO releasing technology (Licensed from the University of Michigan) that prevents thrombosis for 5 days that otherwise renders IV sensors inoperable/inaccurate within minutes in non- heparinized or inadequately heparinized patients.1-7 This novel device can be used to discriminate between infants at high and low risk of morbidity and mortality after CHD surgery, and allow care providers to intervene earlier to prevent adverse outcomes.11-15 Key features of the non-tethered sensor include: (1) proven thrombosis-protection tested for 24 hours in pigs (NO releases for 5 days); (2) 10,000 fold reduction of live bacteria counts on surface with NO for >7 days; (3) safest scores on ISO/GLP leaching, implantation, and cell toxicity tests; (5) continuous lactate readout ability for 5 days every 5 seconds; and (6) ability to discern increasing lactate levels within 5 min without requiring a blood sample compared to current blood gas instruments. The pediatric interventional cardiology market is estimated at $1,379 MM by 2018 with a CAGR of 9.0%,2 the blood and electrolyte testing market was $1.56 B in 2014 with a CAGR of 3.5% $1,852 MM by 2019, and the global sepsis therapeutics market is estimated to be $7.4 B by 2017 with a CAGR of 5.8. %.2,3 In Phase II we propose to: (1) Manufacture, perform quality control, and setup the design history files and device master records for the full development and manufacture of devices following ISO13485 (FDA requirement); (2) implant lactate-sensing dual-lumen central venous catheters (CVC) in femoral vein for continuous measurement of endogenous lactic acid production in rabbit model of cardiopulmonary bypass and cardioplegic arrest (n=10) to determine best lactate increase rate detection times; and (3) finalize GLP biocompatibility studies, establish IRB and file first submission to FDA to perform an acute clinical study of lactate sensors in infants with CHD undergoing CPB at the University of Michigan C.S. Mott Children's Hospital Congenital Heart Center (J. Charpie, Co-Director). Biocrede (100% US owned) manufactures the sensors and assembles these into OEM?ed FDA approved CVCs.
Blood lactate levels and lactate rate of change are valuable parameters to measure during resuscitation of critically ill patients with organ failure and sepsis, and in infants with congenital heart disease undergoing heart surgery with cardiopulmonary bypass. Rising blood lactate levels are indicative of tissue hypoperfusion or poor oxygenation, and a shift from aerobic to anaerobic cellular respiration. These pathophysiologic changes often precede circulatory failure, and correlate with major morbidity and mortality in the intensive care unit. A point-of-care device that can continuously quantitate blood lactate levels in real time will better predict impending circulatory failure than current benchtop blood analyzers that may provide 1-2 hour discrete measurements.