Plasma concentrations and cardiovascular influence of lidocaine infusions during isoflurane anesthesia in healthy dogs and dogs with subaortic stenosis.
OBJECTIVE
To determine the plasma concentrations and cardiovascular changes that occur in healthy dogs and dogs with aortic stenosis that are given an infusion of lidocaine during isoflurane anesthesia.


METHODS
Phase 1, controlled randomized cross-over trial; Phase 2, before and after trial


METHODS
Phase 1, 6 healthy dogs (4 female, 2 male) weighing 23.8 +/- 7.4 kg; Phase 2, 7 dogs (4 female, 3 male) with moderate to severe subaortic stenosis (confirmed by Doppler echocardiography) weighing 31.1 +/- 14.5 kg.


METHODS
After mask induction, intubation, and institution of positive pressure ventilation, instrumentation was performed to measure hemodynamic variables. After baseline, measurement at an end-tidal isoflurane concentration of 1.9% (phase 1) or 1.85% (phase 2), a loading dose infusion of lidocaine at 400 microg/kg/min was given. Phase 1: Maintenance doses of lidocaine were administered consecutively (40, 120, and 200 microg/kg/min) after the loading dose (given for 10, 10, and 5 minutes, respectively) in advance of each maintenance concentrations. Measurements were taken at the end of each loading dose and at 25 and 35 minutes during each maintenance level. The same animals on a different day were given dextrose 5% and acted as the control. Phase 2: Dogs were studied on a single occasion during an infusion of lidocaine at 120 microg/kg/ min given after the loading dose (10 minutes). Measurements occurred after the loading dose and at 25 and 35 minutes. A blood sample for lidocaine concentration was taken at 70 minutes. Data were compared using a one-way ANOVA for phase 1, and between phase 1 and 2. Statistical analysis for phase 2 was performed using a paired t-test with a Bonferroni correction. A P value < or = .05 was considered significant.


RESULTS
Phase 1: Plasma lidocaine concentrations achieved with 40, 120, and 200 microg of lidocaine/kg/min were 2.70, 5.27, and 7.17 microg/mL, respectively. A significant increase in heart rate (HR) (all concentrations), central venous pressure (CVP), mean pulmonary arterial pressure (PAP), and a decrease in stroke index (SI) (200 microg/kg/min) were observed. An increase in systemic vascular resistance (SVR) and mean PAP, and a decrease in SI also followed the loading dose given before the 200 microg/kg/min infusion. No other significant differences from the control measurements, during dextrose 5% infusion alone, were detected. Phase 2: Plasma lidocaine concentrations achieved were 5.35, 4.23, 4.23, and 5.60 microg/mL at 10, 25, 35, and 70 minutes, respectively. They were not significantly different from concentrations found in our healthy dogs at the same infusions. A significant but small increase in CVP compared with baseline was noted after the loading dose. There were no significant differences from baseline shown in all other cardiovascular data. There were no statistically significant differences in any measurements taken during the lidocaine infusion between the dogs in phase 1 and phase 2. Dogs with aortic stenosis tended to have a lower cardiac index than healthy dogs at baseline (88 v 121 mL/kg/min) and during lidocaine infusion (81 v 111 mL/kg/min). A small, statistically significant difference in systolic PAP was present at baseline.


CONCLUSIONS
There does not appear to be any detrimental cardiovascular effects related to an infusion of lidocaine at 120 microg/kg/min during isoflurane anesthesia in healthy dogs or dogs with aortic stenosis. The technique used in this study resulted in therapeutic plasma concentrations of lidocaine.


CONCLUSIONS
Methods shown in the study can be used in clinical cases to achieve therapeutic lidocaine levels without significant cardiovascular depression during isoflurane anesthesia.
Nunes de Moraes
A
A
Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Ontario, Canada.
Dyson
D H
DH
O'Grady
M R
MR
McDonell
W N
WN
Holmberg
D L
DL
D000769:Anesthesia, Inhalation / Q000662:veterinary; D018685:Anesthetics, Inhalation; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D001020:Aortic Stenosis, Subvalvular / Q000097:blood / Q000503:physiopathology / Q000662:veterinary*; D018592:Cross-Over Studies; D004283:Dog Diseases / Q000097:blood / Q000503:physiopathology*; D004285:Dogs / Q000097:blood / Q000502:physiology*; D004562:Electrocardiography / Q000662:veterinary; D005260:Female; D016231:Fluorescence Polarization Immunoassay / Q000662:veterinary; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous / Q000662:veterinary; D007530:Isoflurane; D008012:Lidocaine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D008297:Male
D018685:Anesthetics, Inhalation; D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D008012:Lidocaine; D007530:Isoflurane