We examined local anesthetic effects of clonidine and its interaction with lidocaine with regard to tonic inhibition of the C-fiber action potential (AP) on the isolated, desheathed rabbit vagus nerve by the sucrose gap method. Clonidine and lidocaine at 500 microM concentrations caused a comparable degree of C-fiber inhibition, corresponding to an AP area under the curve of 75.8% +/- 9.4% (mean +/- SE) and 82.2% +/- 5.9% of control, respectively. Concentrations of clonidine less than 500 microM did not inhibit C-fiber AP. Clonidine, added in concentrations of 500 nM, 500 microM, and 5 mM to a 500 microM lidocaine perfusion, caused a significant decrease in fiber blockade of 18%, 20%, and 54%, respectively, as compared with clonidine added to Locke perfusion (P less than 0.05). The sodium channel blocker tetrodotoxin (3 microM) decreased the AP area to 9.3% +/- 1.3% of control. The remaining tetrodotoxin-resistant AP was almost completely blocked by clonidine (500 microM) and lidocaine (500 microM), indicating a higher susceptibility of tetrodotoxin-resistant fibers to the two drugs than the C-fiber population as a whole. The enhancing effect of a low dose of clonidine (500 nM) on lidocaine-induced (500 microM) inhibition of C-fiber AP might explain the clinical observation that clonidine, at approximately 1000-fold lower concentrations than lidocaine, prolongs the action of lidocaine in peripheral nerve block.

The admixture of clonidine or epinephrine to lidocaine for brachial plexus block was studied with regard to duration of block, postoperative analgesia, and plasma concentrations of lidocaine. Thirty-three patients of ASA physical status I and II received an admixture of either clonidine (150 micrograms; n = 15) or epinephrine (200 micrograms; n = 18) to 40 mL of 1% lidocaine in a randomized, double-blind fashion. Bone surgery predominated in those patients receiving clonidine and soft-tissue surgery in those receiving epinephrine (P less than 0.05). Onset and duration of block were not different between the groups. With the admixture of clonidine, fewer patients were completely pain free for greater than 12 h (13.3%) and pain scores (visual analogue scale 0-10) were higher 6 h after the block (median 4; range 0-6) than with epinephrine (61.1%; median 2; range 0-7, respectively; P less than 0.05). In patients who had received clonidine, peak plasma concentrations of lidocaine were higher (10.29 +/- 2.96 mumol/L) and occurred earlier (23.7 +/- 9.3 min; mean +/- SD) than in those treated with epinephrine (6.9 +/- 1.71 mumol/L; 72.5 +/- 56.2 min; P less than 0.05). This indicates the absence of a local vasoconstrictor effect of clonidine and implies a reduced margin of safety with regard to local anesthetic toxicity. Although clonidine does not offer advantages compared with epinephrine, it may be a useful adjunct to local anesthetics in those patients in whom the administration of epinephrine is contraindicated.

Effects of clonidine and lidocaine on the hyperpolarizing after-potential (HAP) and frequency-dependent block in C fibers were examined on desheathed rabbit vagus nerves, using the sucrose gap technique. A single action potential (AP) was followed by a fast and a slow HAP. Clonidine, at concentrations from 0.05 to 50 µmol/l, decreased the fast HAP, while the AP amplitude was unchanged. At a 500 µmol/l concentration of clonidine, the fast HAP amplitude was similar to control, the slow HAP was increased, and the AP amplitude decreased. Lidocaine at 500 µmol/l delayed and broadened the HAP, making a distinction between fast and slow HAP impossible, and decreased and delayed the AP amplitude. In the presence of lidocaine (500 µmol/l), clonidine at concentrations from 0.05 to 500 µmol/l decreased the HAP amplitude, without modifying the lidocaine-induced shape of the HAP. The modifications of the HAP, however, do not contribute to the local anesthetic effects of clonidine, as the addition of clonidine (0.5 and 500 µmol/l) to Locke or lidocaine (500 µmol/l) solution does not enhance the frequency-dependent block (3 and 10 Hz) observed with either Locke or lidocaine solution alone.

End-tidal anaesthetic concentrations at first eye opening in response to a verbal command during recovery from anaesthesia (MAC-awake), were measured for isoflurane (n = 16), enflurane (n = 16) and halothane (n = 14). MAC-awake was measured during either slow or fast alveolar washout. Slow washout was obtained by decreasing anaesthetic concentrations in predetermined steps of 15 min, assuming equilibration between brain and alveolar partial pressures. Fast alveolar washout was obtained by discontinuation of the inhalation anaesthetic, which had been maintained at 1 MAC for at least 15 min. Mean MAC-awake obtained with slow alveolar washout was similar for isoflurane (0.25 (SD 0.03) MAC), and enflurane (0.27 (0.04) MAC) and significantly greater than values obtained by fast alveolar washout (isoflurane: 0.19 (0.03) MAC; enflurane: 0.20 (0.03) MAC). The MAC-awake of isoflurane and enflurane was significantly less than that of halothane, which was 0.59 (0.10) MAC as evaluated by the slow and 0.50 (0.05) MAC as evaluated by the fast alveolar washout method. Recovery time from anaesthesia with fast alveolar washout was 8.8 (4.0) min for halothane, which was not different from isoflurane (15 (2.5) min), but significantly shorter than for enflurane (22 (10) min), reflecting differences in the anaesthetic concentration gradient between MAC and MAC-awake values. These data do not support the hypothesis of a uniform ratio between MAC and MAC-awake values.

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The sequence of changes in systemic and renal oxygen delivery (QO2) and consumption (VO2) and renal function in an ovine model of progressive hyperdynamic sepsis was investigated. Nine chronically instrumented awake sheep were given a continuous intravenous Escherichia coli endotoxin infusion (20 ng.kg-1.min-1) for 3 days. After 8 h of the infusion, systemic arterial blood pressure and vascular resistance stayed decreased by 30% (P less than 0.001). Systemic QO2 progressively increased to a maximum of 157% of baseline values at 24 h and was associated with a decreased O2 extraction ratio from 33 +/- 2 (SE) to 23 +/- 2% (P less than 0.05), resulting in an unchanged systemic VO2. Renal blood flow and renal QO2 decreased by 40% during the first 12 h, returning to and staying at baseline values after 24 h. Renal VO2 decreased significantly by 35% at 12 h and then partially recovered to baseline values. Plasma creatinine clearance was maximally reduced to 25% of baseline values at 12 h and thereafter remained significantly (P less than 0.01) below 50% of baseline values. Both total and fractional sodium excretion fell at 12 h by 95 and 74%, respectively, and remained reduced over time, indicating conserved tubular function. The ratio of moles of sodium reabsorbed to moles of O2 consumed by the kidney was transiently reduced, from 33.4 +/- 4.1 to 12.4 +/- 3.6 at 12 h (P less than 0.05), indicating a relative increase in energy expenditure for tubular transport or renal synthetic activities, but recovered to baseline values after 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

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