Cardiovascular and autonomic nervous effects of edrophonium and atropine combinations during neuromuscular blockade antagonism in sheep

ObjectiveTo study heart rate (HR), arterial blood pressure (BP) and autonomic nervous (AN) effects of edrophonium–atropine combinations during neuromuscular blockade (NMB) antagonism in sheep.Experimental design Randomized, prospective and experimental study.AnimalsSeventy-eight Scottish blackface ewes; mean age: 4.5 years; mean body mass: 54 kg.MethodsAfter induction with IV etomidate (0.5 mg kg⁻¹) and midazolam (0.5 mg kg⁻¹), anaesthesia was maintained with halothane and NMB produced with atracurium or mivacurium. In the first study (n = 53), the electrocardiographic (ECG), HR, BP and AN effects of low (40 μg kg⁻¹) and high (80 μg kg⁻¹) atropine doses combined with either of two edrophonium doses (0.5 or 1.0 mg kg⁻¹) were investigated. These variables were also measured in a second study when edrophonium (1.0 mg kg⁻¹) was administered 5 minutes before atropine (80 μg kg⁻¹) and vice versa. Data were analysed using one-way within-subjects and repeated measures anova.ResultsIn the first study, all combinations reversed NMB but significantly (p < 0.001) increased HR and BP within 2 minutes without arrhythmias. In the second study, edrophonium (1.0 mg kg⁻¹) significantly increased HR and BP, saliva flow (n = 1) and lung sounds (n = 3) and caused ECG changes (n = 1). Cardiovascular changes were partially reversed by atropine (80 μg kg⁻¹) administered 5 minutes later. Administered first, atropine (80 μg kg⁻¹) significantly decreased HR and BP effects which were fully (HR) and partially (BP) reversed by edrophonium (1 mg kg⁻¹) administered 5 minutes later.Conclusion and clinical relevance The cardiovascular effects of edrophonium and atropine were opposite to those reported in humans and dogs. Edrophonium (0.5 mg kg⁻¹) and atropine (80 μg kg⁻¹) caused the mildest HR changes without ECG and noncardiac AN disturbances, and is recommended for the antagonism of NMB in sheep.