title: Negative chronotropic actions of sufentanil and vecuronium in chronically instrumented dogs pretreated with propranolol and/or diltiazem.
abstract: Patients with ischemic heart disease who present for surgery are frequently managed with a "high dose" narcotic technique utilizing fentanyl or sufentanil in combination with neuromuscular blockade. Narcotic anesthetic induction has been associated with perioperative cardiac conduction disturbances, particularly in patients previously treated with calcium channel and/or beta-adrenergic antagonists. The purpose of the present investigation was to examine in chronically instrumented dogs the effects on systemic and coronary hemodynamics and regional contractile function of sufentanil alone or in combination with the nondepolarizing neuromuscular blocking agent vecuronium, with and without pretreatment with the calcium channel blocking agent diltiazem, and/or the beta-adrenergic antagonist propranolol. Thirty-six experiments were conducted in four groups of 19 chronically instrumented dogs. Administration of sufentanil (25 and 50 micrograms/kg of normal body weight IV) resulted in a significant sinus or junctional bradyarrhythmia without alteration in systemic and coronary hemodynamics. Pretreatment with propranolol (1 mg/kg IV) decreased left ventricular +dP/dt without other hemodynamic alterations. After propranolol pretreatment, sufentanil (25 and 50 micrograms/kg IV) produced statistically significant dose-dependent decreases in heart rate and +dP/dt, while increasing mean and diastolic coronary vascular resistances. After pretreatment with diltiazem (0.3 mg/kg IV) and propranolol (1.0 mg/kg IV), sufentanil (25 micrograms/kg IV) produced significantly greater bradycardia (38 +/- 4 beats/min) than it did in non-pretreated or propranolol-pretreatment dogs. Similarly, administration of sufentanil (25 micrograms/kg IV) in combination with vecuronium (0.1 mg/kg IV) after propranolol and diltiazem pretreatment resulted in the appearance of bradyarrhythmias (32 +/- 2 beats/min) and two episodes of asystole, responsive to atropine sulfate (0.4 mg). In spite of severe bradycardia, arterial pressure was well maintained in all groups. In all groups, administration of naloxone (0.2 mg/kg IV and 0.2 mg/kg IM) after sufentanil produced significant increases in arterial pressure, left ventricular +dP/dt, and diastolic coronary blood flow velocity. Therefore, the combination of sufentanil and vecuronium in chronically instrumented dogs may result in the appearance of cardiac conduction disturbances. This action is more likely to occur after pretreatment with diltiazem and propranolol. Although systemic hemodynamics were well maintained in dogs in the present study during the episodes of bradyarrhythmias, potentially significant cardiovascular deficits may occur in pa
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
authors.forename: W T
authors.initials: WT
authors.lastname: Schmeling
authors.forename: J P
authors.initials: JP
authors.lastname: Kampine
authors.forename: D C
authors.initials: DC
authors.lastname: Warltier
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004110:Diltiazem / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D004562:Electrocardiography; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D017409:Sufentanil; D014673:Vecuronium Bromide / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D009270:Naloxone; D014673:Vecuronium Bromide; D011433:Propranolol; D017409:Sufentanil; D004110:Diltiazem; D005283:Fentanyl