Koronis Biomedical Technologies (KBT) proposes to develop and fully evaluate a renal replacement therapy (RRT) machine specifically targeted for critically-ill small children and neonates with acute kidney injury (AKI), fluid overload, and kidney failure. In recent years, continuous renal replacement therapy (CRRT) has emerged as the preferred method for providing kidney support to these patients, especially those who are hemodynamically unstable. Continuous veno-venous hemofiltration (CVVH) is a form of CRRT built on hemofiltration: waste products and fluid in plasma are removed from the blood by a pressure gradient over a filter, while a replacement fluid is infused to maintain fluid balance. Unfortunately, neonates infrequently receive renal replacement therapy due to the technical challenges of traditional CRRT machines that make therapy initiation very difficult, even at experienced tertiary children's hospitals. Machines designed for adult- sized patients, but commonly used in pediatric care, require large catheters, tubing, and filters. This results in a high extracorporeal volume (ECV, the total volume of blood in the external circuit-the tubing and hemofilter) relative to a small patient's size, as well as higher blood flows, higher clearance rates, and higher risks. Numerous medical centers do not even offer CRRT to infants, let alone for critically-ill neonates or premature infants, due to the inherent risks. At therapy initiation, a volume of fluid roughly equivalent to the ECV must be injected into the blood circuit to "prime" the pump. For CRRT in larger children and adults, the priming fluid is simply saline. If, however, the amount of fluid required to prime the circuit is greater than 10% of the patient's total blood volume, the saline fluid could significantly dilute the patient's blood, leading to hemodynamic instability. To avoid this outcome, a donor "blood prime" is used, though it is not without risks, such as hypocalcemia, acidosis, hyperkalemia, and a loss of platelets and coagulation functions. KBT's Phase II SBIR project proposes to bring a new CRRT device with a lower ECV to market that is specifically targeted for small children and neonates, eliminating the need for blood primes. The performance and safety of the proposed highly integrated CRRT system will be evaluated in a clinical trial.
Public Health Relevance Statement: Narrative In critically ill children, especially neonates, acute kidney injury (AKI) and volume overload are common conditions that are associated with significant morbidity and mortality. The literature supports the need for a reduced extracorporeal volume continuous renal replacement therapy (CRRT) system for use in small children with AKI. A recent study evaluation of hemodynamic stability in neonates using traditional CRRT blood circuits shows that 55% of CRRT sessions had intradialytic hypotension, most of which occurred shortly after CRRT initiation.
Project Terms: Acidosis; Adult; 21+ years old; Adult Human; adulthood; Alabama; Blood; Blood Reticuloendothelial System; Blood donor; Blood Platelets; Marrow platelet; Platelets; Thrombocytes; Blood Vessels; vascular; Blood Volume; Child; 0-11 years old; Child Youth; Children (0-21); youngster; Clinical Research; Clinical Study; Clinical Trials; Critical Illness; Critically Ill; Engineering; Evaluation Studies; Fluid Balance; Fluid Homeostasis; hemodynamics; Hemofiltration; Hospitals; Pediatric Hospitals; Children's Hospital; Human; Modern Man; hyperkalemia; Hyperpotassemia; Hypocalcemia result; Hypocalcemia; Hypotension; Low Blood Pressure; Vascular Hypotensive Disorder; Incidence; Infant; Premature Infant; infants born premature; infants born prematurely; premature baby; premature infant human; preterm baby; preterm infant; preterm infant human; Infusion Pumps; Infusors; Perfusion Pumps; Kidney; Kidney Urinary System; renal; Lead; Pb element; heavy metal Pb; heavy metal lead; Literature; Metabolic Clearance Rate; clearance rate; Methods; Morbidity - disease rate; Morbidity; mortality; Nephrology; Patients; Plasma; Blood Plasma; Plasma Serum; Reticuloendothelial System, Serum, Plasma; pressure; Kidney Failure; Kidney Insufficiency; Renal Failure; Renal Insufficiency; Research; Research Personnel; Investigators; Researchers; Resources; Research Resources; Retrospective Studies; Risk; Safety; Saline; Saline Solution; Computer software; Software; Software Design; Designing computer software; Technology; Ultrafiltration; Universities; Venovenous Hemofiltrations; Washington; Waste Products; S Phase; S Period; Synthesis Period; Synthesis Phase; Catheters; Caring; Critically ill children; critically ill child; base; Pump; Acute; Clinical; Phase; Renal Replacement Therapy; Kidney Replacement Therapy; Ensure; Evaluation; Internal jugular vein structure; Internal Jugular Vein; Childhood; pediatric; Blood flow; Convection; Collaborations; fluid; liquid; Liquid substance; Scientist; System; hypervolemia; Fluid overload; Consult; Medical center; acute kidney injury; Acute Renal Failure with Renal Papillary Necrosis; experience; membrane structure; Membrane; Performance; professor; Devices; Biomedical Technology; Clotting; Coagulation; Coagulation Process; Ph.D.; PhD; Doctor of Philosophy; Multi-center clinical trial; Multi-site clinical trial; Multicenter clinical trial; Multisite clinical trial; Multi-Institutional Clinical Trial; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Principal Investigator; Development; developmental; safety study; neonate; design; designing; Outcome; Population; usability; high risk; verification and validation; operation; Systems Development; pediatric patients; child patients; clinical center
