title: Cardiovascular and autonomic nervous effects of edrophonium and atropine combinations during neuromuscular blockade antagonism in sheep.
abstract: 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.
authors.affiliation: Department of Veterinary Clinical Sciences, Royal (Dick) School of Veterinary Studies, Easter Bush, Roslin, Midlothian, UK. e.clutton@ed.ac.uk
authors.forename: R Eddie
authors.initials: RE
authors.lastname: Clutton
authors.forename: Michael A
authors.initials: MA
authors.lastname: Glasby
mesh_terms: 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
chemical_list: D002800:Cholinesterase Inhibitors; D007546:Isoquinolines; D018727:Muscarinic Antagonists; D009466:Neuromuscular Blocking Agents; D001279:Atracurium; D004491:Edrophonium; D000077590:Mivacurium; D001285:Atropine