Enzyme Therapy for Surgery-Related Apnea

We have developed a method for producing large quantities of highly purified human plasma butyrycholinesterase (BCHE) and have evaluated this enzyme's potential therapeutic value for inactivating both succinylcholine and mivacurium. The muscle relaxant, succinylcholine, is used by anesthesiologists to ease patient intubation and reduce muscle tone in about half of the in-patient surgeries in this country. Mivacurium is a recently developed drug that may replace succinylcholine in many or all of these cases. About 1:2000 individuals are unable to metabolize these compounds due to a deficiency in plasma butyrylcholinesterase and in these patients the period of paralysis and apnea produced by either drug is greatly extended. The hydrolysis of both compounds by butyrylcholinesterase will be quantified in vitro. The reversal of the effects of succinylcholine in rats and mivacurium in cats by butyrylcholinesterase was measured by EMG. The enzyme was administered i.v. prior to the drug or at the peak of paralysis following the drug. Prophlaxis with BCHE resulted in a 30-to-40 fold increase in the ED50 of mivacurium. Furthermore, butyrcholinesterase effectively relieved mivacurium-induced Phase II blackade (3x ED50). This enzyme the only effective therapy for this hither to irreversible and potentially life threatening condition.