Background: Clonidine prolongs the duration of sensory and motor block
induced by bupivacaine, and this association, in constant infusion by
the epidural route, is used for postoperative analgesia. After a near
-fatal intravenous bolus of bupivacaine in dogs, clonidine improves ve
ntricular electrophysiologic parameters, but probably worsens bupivaca
ine-induced bradycardia and depression of the myocardial contractility
. The current study, using a rodent animal model, evaluated the influe
nce of clonidine pretreatment on the systemic toxic effects of bupivac
aine overdose induced by a constant intravenous infusion. Methods: Twe
nty Wistar male rats were anesthetized with thiopental, and controlled
ventilation was started with an equal mixture of O2 and N2O. Electroc
ardiogram (ECG), electroencephalogram (EEG), and invasive arterial blo
od pressure were continuously recorded. Clonidine (5 mug/kg) or saline
was injected intravenously in a randomized fashion. After 15 min, an
intravenous infusion of bupivacaine was started at 2 mg . kg-1 . min-1
. The time of occurrence of the bupivacaine-induced toxic events was r
ecorded and the doses were calculated. Ten (five in each group) additi
onal rats, pretreated according to the same protocol, were killed at t
he time of the first dysrhythmia, for blood sampling and plasma bupiva
caine concentration measurement. Results. Clonidine reduced heart rate
and arterial blood pressure before bupivacaine infusion (P < 0.05). T
he threshold doses at the first QRS modification (11.3 +/- 5.6 vs. 2.1
+/- 0.9 mg/kg) and the first dysrhythmia (40.6 +/- 15.3 vs. 8.48 +/-
3.7 mg/kg), the increase in EEG total spectral power (33.3 +/- 21.9 vs
. 8.2 +/- 5.1 mg/kg), the 25 and 50% reduction in baseline mean arteri
al pressure and heart rate, the isoelectric EEG (58.6 +/- 14 vs. 22 +/
- 6.6 mg/kg), and the final systole (99 +/- 16 vs. 51.8 +/-14.5 mg/kg)
were significantly greater in the clonidine group than in the saline
group (P < 0.01). The time between the first dysrhthymia and 50% reduc
tion of baseline mean arterial blood pressure was not different betwee
n the groups. In the additional series, the first dysrhythmia occurred
later (10.9 +/- 4.5 vs. 3.2 +/- 1.0 min, P < 0.01) and plasma bupivac
aine levels were greater (18.7 +/- 8.0 vs. 7.8 +/- 3.2 mug/ml, P < 0.0
1) in the clonidine group than in the saline group. Conclusions. In th
is model, clonidine given prophylactically delays the toxic manifestat
ions of bupivacaine overdose and does not accentuate the subsequent hy
potension.