BACKGROUND: Local anesthetic toxicity is often studied experimentally in acutely prepared, anesthetized laboratory animals. We determined the influence of halothane/O(2) anesthesia on cardiovascular and central nervous system (CNS) toxic responses to six amide-type local anesthetics administered i.v.. METHODS: Behavioral, cardiovascular, and pharmacokinetic responses were determined in previously instrumented ewes (approximately 45-50 kg, n = 18), on separate occasions when conscious and anesthetized, to bupivacaine (100 mg), levobupivacaine (125 mg), ropivacaine (150 mg), lidocaine (350 mg), mepivacaine (350 mg), prilocaine (350 mg), and saline (control) infused i.v. over 3 min. RESULTS: The local anesthetics caused convulsions in conscious sheep, but no overt CNS effects in anesthetized sheep. Negative inotropy and slight bradycardia without changes in arterial blood pressure occurred initially in conscious sheep, followed by positive inotropy, tachycardia, and hypertension at the abrupt onset of CNS excitotoxicity, along with widening of QRS complexes. Fatal cardiac arrhythmias occurred in, respectively, 3 of 11, 2 of 12, and 2 of 13 conscious sheep infused with bupivacaine, levobupivacaine, and ropivacaine; in 1 of 9 with prilocaine, electromechanical dissociation (followed by polymorphic ventricular tachycardia) caused death. In anesthetized sheep, cardiovascular depression, preexisting from the general anesthesia, was exacerbated by all local anesthetics, and increased QRS width was prolonged; concurrent blood local anesthetic concentrations were doubled. Nevertheless, all anesthetized animals survived. CONCLUSIONS: General anesthesia produced physiological perturbations, exacerbated local anesthetic-induced cardiovascular depression, and changed the pharmacokinetics of toxic doses of local anesthetics. However, cardiovascular fatalities from local anesthetics occurred only in conscious animals.
BACKGROUND: Local anesthetic toxicity is often studied experimentally in acutely prepared, anesthetized laboratory animals. We determined the influence of halothane/O(2) anesthesia on cardiovascular and central nervous system (CNS) toxic responses to six amide-type local anesthetics administered i.v.. METHODS: Behavioral, cardiovascular, and pharmacokinetic responses were determined in previously instrumented ewes (approximately 45-50 kg, n = 18), on separate occasions when conscious and anesthetized, to bupivacaine (100 mg), levobupivacaine (125 mg), ropivacaine (150 mg), lidocaine (350 mg), mepivacaine (350 mg), prilocaine (350 mg), and saline (control) infused i.v. over 3 min. RESULTS: The local anesthetics caused convulsions in conscious sheep, but no overt CNS effects in anesthetized sheep. Negative inotropy and slight bradycardia without changes in arterial blood pressure occurred initially in conscious sheep, followed by positive inotropy, tachycardia, and hypertension at the abrupt onset of CNS excitotoxicity, along with widening of QRS complexes. Fatal cardiac arrhythmias occurred in, respectively, 3 of 11, 2 of 12, and 2 of 13 conscious sheep infused with bupivacaine, levobupivacaine, and ropivacaine; in 1 of 9 with prilocaine, electromechanical dissociation (followed by polymorphic ventricular tachycardia) caused death. In anesthetized sheep, cardiovascular depression, preexisting from the general anesthesia, was exacerbated by all local anesthetics, and increased QRS width was prolonged; concurrent blood local anesthetic concentrations were doubled. Nevertheless, all anesthetized animals survived. CONCLUSIONS: General anesthesia produced physiological perturbations, exacerbated local anesthetic-induced cardiovascular depression, and changed the pharmacokinetics of toxic doses of local anesthetics. However, cardiovascular fatalities from local anesthetics occurred only in conscious animals.
Authors: Saul Chemonges; Kiran Shekar; John-Paul Tung; Kimble R Dunster; Sara Diab; David Platts; Ryan P Watts; Shaun D Gregory; Samuel Foley; Gabriela Simonova; Charles McDonald; Rylan Hayes; Judith Bellpart; Daniel Timms; Michelle Chew; Yoke L Fung; Michael Toon; Marc O Maybauer; John F Fraser Journal: Biomed Res Int Date: 2014-03-25 Impact factor: 3.411