ORIGINAL CONTRIBUTION diltiazem, CPR The Effect of CPR on Plasma Diltiazem Concentrations in Dogs Study objective: To determine the effect of cardiac arrest w~th CPR on diltiazem concentrations in dogs. Design: Prospective, double-blind, randomized trial. Setting: Laboratory at a large university-affiliated medical center. Type of participants: Twenty mongrel dogs. Interventions: Following administration of anesthesia, catheters were placed in the pulmonary artery, aortic arch, left ventricle, and right ventri- cle. Dogs were randomized to receive diltiazem (0.5 mg/kg) either 60 min- utes before or during cardiac arrest with CPR. After 13 minutes of cardiac arrest, defibrillation was attempted. Measurements and main results: Frequent blood samples for diltiazem concentrations were obtained before, during, and after cardiac arrest. The mean diltiazem concentration rose 70% during CPR in the group that re- ceived diltiazem before cardiac arrest. The group that received diltiazem during CPR had concentrations five times greater than expected during sinus rhythm. Conclusion: Increased diltiazem concentrations are observed during CPR and are probably related to altered distribution encountered during CPR. [Capparelli EV, Zhao H, Hanyok JJ, DiPersio DM, Kluger J, Fieldman A, Chow MSS: The effect of CPR on plasma diltiazem concentrations in dogs. Ann Emerg Med October 1991;20:i078-1082.] INTRODUCTION CPR can be a life-saving measure in patients who experience a cardiac arrest. However, standard CPR restores only 15% to 25% of normal cardiac output. 1-3 In addition, the many acid-base and biochemical changes that take place during CPR suggest the possibility of alterations in the disposi- tion of drugs. Chow et al demonstrated vast discrepancies in serum lido- caine concentrations after administration during CPR compared with those during sinus rhythm.4, s I~: is not known whether similar changes in drug disposition occur with other agents during CPR. Diltiazem is a calcium channel-blocking agent that has become com- mon therapy for patients with a variety of cardiac disorders. Diltiazem has been shown to increase cardiac function immediately after cardiac arrest; 6 recently, we demonstrated that it can facilitate resuscitation from ven- tricular fibrillation in dogs. 7 Because diltiazem may ultimately prove to be a useful therapy during cardiac arrest and many patients suffering cardiac arrest are already receiving the drug, we investigated the effect of CPR on plasma diltiazem concentrations. MATERIALS AND METHODS We anesthetized 20 healthy mongrel dogs (weight, 12 to 16 kg) with 20 mg/kg thiopental immediately followed by 70 mg/kg c~-chloralose. Each anesthetized animal was placed in the supine position on a surgical table, and a thermoblanket placed under the dog maintained the animal's body temperature at 37 C. Surface ECG leads provided continuous ECG mon- itoring. A Harvard respirator maintained ventilation at 12 breaths per min- ute. Adjustments of tidal volume and/or administration of sodium bicar- bonate maintained arterial blood pH at 7.40 +- 0.05 and Pco z at 40 _+ 5 mm Hg during sinus rhythm. We maintained anesthesia with 50 mg/kg Edmund V Capparelli, PharmD*t Hong Zhao, MS*¢ James J Hanyok, PharmD*t David M DiPersio, PharmD*t Jeffrey Kluger, MDt Arnold Fieldman, MDt Moses S S Chow, PharmD*t Hartford and Storrs, Connecticut From the Department of Pharmacy, Hartford Hospital, Hartford, Connecticut;* and School of Pharmacy, University of Connecticut, Storrs.t Received for publication November 1, 1990. Revision received February 1, 1991. Accepted for publication April 9, 1991. Funding for this study was provided by a grant from the Hartford Hospital Research Committee. The abstract of this paper was presented at the AAPS Annual Scientific Meeting in Boston, June 1987. Address for reprints: Moses S S Chow, PharmD, Drug Information Center, Department of Pharmacy Services, Hartford Hospital, 80 Seymour Street, Hartford, Connecticut 06115. 20:10 October 1991 Annals of Emergency Medicine 1078/43