A Companion Diagnostic for Personalizing Mivacurium at the Point-of-Care

Abstract

Mivacurium chloride is envisioned as the “gold-adjunct” in anesthesia and emergency medicine. People across the world are administered mivacurium in emergency situations as clinicians prefer it among the frequently used neuromuscular blockers thanks to its rapid action and short duration. Mivacurium is promptly degraded and deactivated by plasma cholinesterase enzyme (PChE), however during emergency situations, some individuals were found to be unable to metabolize mivacurium shortly after its injection, resulting in prolonged paralysis and potentially lethal respiratory apnea. The most clinically significant cause of this residual paralysis and apnea is the reduced cholinesterase ability to effectively hydrolyze mivacurium. Hitherto, monitoring of mivacurium enzymatic degradation has been remaining a long-standing challenge for analytical chemists as well as anesthesiologists. Firstly, it undergoes rapid hydrolysis by the PChE-enzyme 8 min post-injection, therefore, frequent sampling all through the first minutes after mivacurium administration is mandatory. Secondly, its isolation from biological specimens is extremely difficult due to its chemical properties which involves both hydrophilic and lipophilic characteristics. These challenges impede the development of a universal protocol to be established for screening of PChE-activity towards mivacurium and which clearly identifies patients susceptible to prolonged paralysis. In this study, we designed a point-of-care (PoC) potentiometric sensor that can perform tracking of mivacurium enzymatic degradation kinetics with high accuracy and rapidly. Real serum samples were utilized for in vitro estimation of the rate of mivacurium metabolism, where values of 227 μmol l−1 and 62 μM min−1 were obtained for the characteristic parameters of the enzymatic reaction, Km and Vmax, respectively. Correlation of the results obtained using the proposed approach and earlier LC-MS/MS study is shown.