Cardiovascular and autonomic nervous effects of edrophonium and atropine combinations during neuromuscular blockade antagonism in sheep.
OBJECTIVE
To study heart rate (HR), arterial blood pressure (BP) and autonomic nervous (AN) effects of edrophonium-atropine combinations during neuromuscular blockade (NMB) antagonism in sheep.


METHODS
Randomized, prospective and experimental study.


METHODS
Seventy-eight Scottish blackface ewes; mean age: 4.5 years; mean body mass: 54 kg.


METHODS
After 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 microg kg(-1)) and high (80 microg 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 microg kg(-1)) and vice versa. Data were analysed using one-way within-subjects and repeated measures anova.


RESULTS
In 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 microg kg(-1)) administered 5 minutes later. Administered first, atropine (80 microg 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.


CONCLUSIONS
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 microg kg(-1)) caused the mildest HR changes without ECG and noncardiac AN disturbances, and is recommended for the antagonism of NMB in sheep.
Clutton
R Eddie
RE
Department of Veterinary Clinical Sciences, Royal (Dick) School of Veterinary Studies, Easter Bush, Roslin, Midlothian, UK. e.clutton@ed.ac.uk
Glasby
Michael A
MA
D000758:Anesthesia / Q000662:veterinary; D000818:Animals; D001279:Atracurium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001285:Atropine / Q000008:administration & dosage* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004359:Drug Therapy, Combination; D004491:Edrophonium / Q000008:administration & dosage* / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007546:Isoquinolines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000077590:Mivacurium; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D019148:Neuromuscular Blockade / Q000662:veterinary*; D009466:Neuromuscular Blocking Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012756:Sheep
D002800:Cholinesterase Inhibitors; D007546:Isoquinolines; D018727:Muscarinic Antagonists; D009466:Neuromuscular Blocking Agents; D001279:Atracurium; D004491:Edrophonium; D000077590:Mivacurium; D001285:Atropine