Therapy of digoxin intoxication in dogs by specific hemoperfusion through agarose polyacrolein microsphere beads-antidigoxin antibodies The usefulness of a new biocompatible, specific immunosorbent, Agarose-Polyacrolein Microsphere Beads-Antidigoxin antibodies (APAMB-AD) for hemoperfusive removal of digoxin in digoxin intoxicated dogs is described. The sorbent contains antidigoxin antibodies covalently bound to polyacrolein microspheres, 0.2 pm in diameter. Thousands of microspheres are matrix-encapsulated in cross-linked agarose to form beads 500 to 800 Am in diameter. The sorbent removes digoxin specifically, leaving other components of the blood intact, in contrast to the nonspecific sorbents (charcoal and ion exchange resins) currently in use. Digoxin-intoxicated dogs looked ill, vomited, and their ECGs showed malignant arrhythmias which were reversed during the first hour of hemoperfusion. By 2 hours of hemoperfusion, the ECG tracings returned to the preintoxication state. Up to 27% of the total body digoxin burden was removed. The sorbent is biocompatlble. Neither the formed elements nor a battery of the routinely assayed soluble components of the blood or complement (C’.,) were altered significantly during the hemoperfusion trials. The dogs tolerated the hemoperfusion well and all survived the intoxication. Nonhemoperfused dogs or dogs whose blood was hemoperfused through beads lacking antidigoxin did not survive the digoxin intoxication. (AM HEART J 110:30, 1985.) Leon Marcus, Shlomo Margel,* Hillel Savin, Michal Offarim, and Mordchai Ravid. Rehovot and Kfar Saba, Israel Cardiac glycosides remain the mainstay of the med- ical armamentarium for congestive heart failure and various cardiac arrhythmias. Unfortunately, iatro- genie therapeutic digitalis intoxication is one of the most common drug reactions in clinical medicine. A morbidity of 8% to 35% with a mortality of 3 % to 21% in medicated patients has been reported.’ Additionally, digoxin has been used for self poison- ing, marked by an exceptionally high mortality rate. Since a specific antagonist for digitalis is generally unavailable, current therapy is directed toward the management of the clinical manifestations of toxici- ty and enhanced elimination of the body burden of digoxin. Severe intoxications may not respond to conventional measures and may become life-threat- From the Department of Materials Research, the Weizmann Institute of Science; and the Department of Medicine, Meir Hospital, the Sackler School of Medicine, Tel-Aviv University. Supported in part by Galil Advanced Technologies, Ramat-Gan, Israel. Received for publication Sept. 28, 1984; revision received Feb. 5, 1985; accepted March 15, 1985. *Reprint requests: Prof. Shlomo Margel, Dept. of Materials Research, the Weizmann Institute of Science, Rehovot, Israel, 76100. ening. For these cases, a method for significantly increasing the rate of removal or inactivation of digoxin is required. Dramatic removal of digoxin from the circulation by hemoperfusion has been reported2-5; hemodialysis removal of digoxin was less than successful.6* 7 The major types of adsorbents employed for hemoperfu- sion in emergency situations are nonspecific (ion exchange resins or activated charcoal). This charac- teristic may be advantageous in instances where the intoxicating drug is unknown or multiple intoxicants have been ingested. The major disadvantage, howev- er, is that a wide spectrum of biocompounds is removed during hemoperfusion in addition to the intoxicant. To obviate this problem, specific adsor- bents need to be developed for specific intoxications, where possible. Thus the rationale for the Agarose- Polyacrolein Microsphere Beads-Antidigoxin anti- bodies (APAMB-AD). The most exciting advance in the treatment of digoxin intoxication involves the use of antidigoxin antibodies or fab antibody fragments for the inacti- vation and reversal of digitalis toxicity.8-11 The ther- 30