Can Glycopyrrolate Replace Temporary Pacemaker and Atropine

In Patients at High Risk for Symptomatic Bradycardia Undergoing AngioJet Mechanical Thrombectomy?

ABSTRACT: We studied the feasibility and efficacy of glycopyrrolate, a synthetic anticholinergic agent with shorter half-life and without reflex tachycardia, in preventing symptomatic bradycardia in patients undergoing mechanical thrombectomy with the AngioJet® Rheolytic™ Thrombectomy System (Possis Medical, Inc., Minneapolis, Minnesota). There was no need for temporary pacemaker insertion and no hemodynamically significant bradycardia in 10 consecutive patients. Additionally, there were no adverse effects from glycopyrrolate therapy. Our pilot study demonstrates that glycopyrrolate may replace temporary pacemaker insertion in these patients at high risk for symptomatic bradycardia. J INVASIVE CARDIOL 2008;20:19A–21A The AngioJet® Rheolytic™ Thrombectomy System (Possis Medical, Inc., Minneapolis, Minnesota) is an effective device for removal of thrombus from the coronary arteries and saphenous vein grafts.1 However, it is often associated with severe bradycardia, with its mechanism unknown.2 Thus, a temporary pacemaker is often used prophylactically to prevent symptomatic bradycardia during AngioJet therapy. Difficulties posed by this requirement include the need for venous access in patients amid acute myocardial infarctions or other acute events, a delay in angioplasty procedure onset and the risks associated with pacemakers. In addition, if thrombus develops during angioplasty and AngioJet has to be used as a bailout device, patients are fully anticoagulated, and the bleeding risk increases if a venous sheath has to be obtained emergently for temporary pacemaker insertion. For all these reasons, some interventionalists are reluctant to consider AngioJet despite the documented efficacy of effective thrombectomy with this device. Therefore, it would be ideal if we could find a pharmacologic agent to prevent severe bradycardia, obviating the need for a venous sheath insertion and temporary pacemaker placement and eliminating reflex tachycardia associated with atropine. Glycopyrrolate, an atropine-like drug (synthetic anticholinergic agent) with a shorter half-life (Methods Patients with ST elevation myocardial infarction who presented to the cardiac catheterization laboratory at St. Luke’s-Roosevelt Hospital Center for primary angioplasty were eligible for the study. In addition, patients had to have intracoronary thrombus to be treated with AngioJet thrombectomy. No venous sheath was inserted, and atropine was ready for administration in case of hemodynamically significant bradycardia. Immediately following the AngioJet procedure, glycopyrrolate infusion was discontinued. Other aspects of the angioplasty procedure, including adjunct pharmacology, type of stent, type of AngioJet catheter and post-procedural care, were left to the discretion of the operators. Inclusion criteria included angiographic evidence of thrombus in the coronary artery and intent to treat with an AngioJet thrombectomy device in accordance with the current AngioJet product labeling. Exclusion criteria included contraindications for glycopyrrolate therapy (e.g., severe ulcerative colitis, severe bleeding, narrow-angle glaucoma, prostate hypertrophy or obstructive uropathy, end-stage renal disease or serum creatinine > 2 mg/dL, myasthenia gravis), pregnancy or possible pregnancy and presence of a permanent pacemaker. The patients received glycopyrrolate (Robinul®, Baxter Healthcare Corp., Deerfield, Illinois) at 5 µg/kg bolus followed by 5 µg/kg/hour continuous infusion. The bolus was given 2 minutes prior to AngioJet thrombectomy. The infusion ran for the duration of time the AngioJet device was in use. The pilot trial assessed the incidence of symptomatic bradycardia (need for atropine therapy or temporary pacemaker placement) and any unanticipated adverse events. Results Ten patients were enrolled. Their demographics and the coronary arteries treated are listed in Table 1. All patients tolerated the procedure well, including glycopyrrolate therapy. No patient experienced symptomatic bradycardia, and no patient required atropine administration or temporary pacemaker insertion. Baseline heart rate before glycopyrrolate administration (83 ± 5 beats/minute), heart rate following glycopyrrolate administration but before AngioJet thrombectomy (83 ± 6 beats/minute) and heart rate following AngioJet thrombectomy (77 ± 6 beats/minute) did not differ (p = 0.6 by analysis of variance [ANOVA]). An example of the heart rates during the procedure is seen in Figure 1. There were 2 noteworthy patients. The first patient had subacute stent thrombosis of the proximal left anterior descending coronary artery and presented with acute anterior ST elevation myocardial infarction. The AngioJet procedure was performed initially without glycopyrrolate therapy and without a temporary pacemaker. The heart rate immediately decreased from baseline of 79 beats/minute to 33 beats/minute. Glycopyrrolate was then given as a bolus followed by infusion, and subsequent AngioJet runs did not result in bradycardia, with heart rates remaining at 75 beats/minute after the second run and 80 beats/minute after the third run. The second patient was having AngioJet therapy in a thrombosed right coronary artery. This patient received glycopyrrolate prior to AngioJet. His heart rate decreased to 55 beats/minute from baseline of 101 beats/minute, but there was only a marginal decrease in blood pressure (from 134/79 mmHg to 125/63 mmHg), and he did not require any further therapy. Discussion and Conclusion The results of this pilot study suggest that glycopyrrolate may be an excellent pharmacologic agent to replace temporary pacemaker placement and atropine administration in patients undergoing AngioJet thrombectomy. Heart rates following glycopyrrolate administration did not increase with the administration of AngioJet thrombectomy, as reported in the anesthesia literature.5,6 Additionally, following AngioJet thrombectomy with continuous glycopyrrolate infusion, there was a minimal decrease in heart rate without symptomatic bradycardia. The drug was discontinued immediately following the AngioJet procedure and did not produce any untoward effects. One anecdotal incidence involved a patient who was treated with AngioJet prior to glycopyrrolate therapy. This patient had severe bradycardia following the first run of AngioJet. However, following glycopyrrolate therapy, subsequent AngioJet runs were not associated with bradycardia. In addition, this patient had left anterior descending stent thrombosis, suggesting that regardless of the coronary artery, AngioJet thrombectomy can be associated with profound bradycardia. The major limitation of this study is the small sample size. In addition, mostly left anterior descending coronary arteries were treated, and it is unknown whether the results would have been different with treatment of more right coronary arteries or dominant left circumflex coronary arteries, although the previously mentioned case suggests that the mechanism for profound bradycardia may be independent of the location of the coronary arteries. It is also unknown whether the dosages of glycopyrrolate can be increased to minimize the decrease in heart rate, as seen in one patient with right coronary artery therapy. For these reasons, further studies are needed to conclusively establish this pharmacologic therapy as a better option to temporary pacemaker placement. More definitive data would support this alternative to obtaining venous access and inserting temporary pacemakers in patients with ongoing ischemia and full anticoagulation including glycoprotein IIb/IIIa inhibitors and thus would facilitate the procedure without a delay. Due to the pilot phase, it is also unknown whether the door-to-balloon time was reduced, but based on the fact that we did not have to obtain venous access and insert a temporary pacemaker, it is likely that the overall door-to-balloon time was reduced in these patients compared with the conventional AngioJet procedure.

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