Oral clonidine blunts the heart rate response to intravenous atropine in humans

Abstract

Clonidine, recently introducted into anesthesia practice, may cause bradycardia. Whether this bradycardia is reversible with atropine is not known. Accordingly, we studied heart rate (HR) responses to intravenous atropine in 80 patients assigned randomly to either a control group, who received no medication (n = 20), or a clonidine group, who received oral clonidine of approximately 1.2 μg·kg-1 (n = 20), 2.5 μg·kg-1 (n = 20), or 5 μg·kg-1 (n = 20). All patients received incremental doses of atropine, 2.5, 2.5, and 5 μg·kg-1, at 2-min intervals (total dose 10 μg·kg-1). Positive chronotropic response to the cumulative atropine dose of 10 μg·kg-1 was attenuated significantly only in patients given clonidine 5 μg·kg-1 (7 ± 1 beats per min, mean ± standard error) when compared with those given smaller doses of clonidine (15 ± 2, 16 ± 2 beats per min) or no clonidine (19 ± 2 beats per min) (P < 0.05). To determine whether HR hyporesponsiveness to atropine induced by clonidine can be overcome by a larger dose of atropine, the authors studied 30 additional patients given clonidine 5 μg·kg-1 or no medication. In all patients not receiving clonidine (n = 15), HR increased by more than 20 beats per min when atropine of 15 μg·kg-1 was administered, whereas in only 5 patients (33%) receiving clonidine did the HR increase by 20 beats per min after atropine 15 μg·kg-1 (P < 0.001). Furthermore, only slight increases in HR were noted in 4 of 15 patients given clonidine medication (26%) even after the administration of atropine 40 μg·kg-1. It is concluded that the HR response to intravenous atropine is attenuated in awake humans receiving oral clonidine of 5 μg·kg-1. The decreased responsiveness to atropine in patients receiving clonidine 5 μg·kg-1 cannot be effectively overcome in all patients by a larger dose of atropine.