Faculty Bibliography

This study evaluated the effect of a lipid drug carrier (iophendylate) on epidural anesthesia. The intensity and duration of motor blockade produced by aqueous and lipid preparations of local anesthetics were assessed in rabbits with long-term indwelling catheters in the epidural space. Motor blockades produced by procaine (1%, 2%, and 4%), lidocaine (1%, 2%, and 4%), and tetracaine (0.5%, 1%, and 2%) in normal saline solution were compared with the effects produced by equimolar amounts of the drug solutions in iophendylate. Procaine (4%) in aqueous solution produced motor blockade lasting 30 +/- 3.54 min (mean +/- SD) versus 84 +/- 4.18 min in lipid solution. Lidocaine (2% and 4%) in aqueous solution produced motor blockade lasting 41 +/- 4.18 and 65 +/- 6.12 min versus 39 +/- 4.18 and 118 +/- 10.1 min, respectively, in lipid solution. Aqueous tetracaine (0.5%, 1%, and 2%) produced motor blockade of 106 +/- 9.62, 189 +/- 6.52, and 273 +/- 26.8 min versus 284 +/- 14.7, 335 +/- 15.8, and 365 +/- 26.9 min, respectively, in their lipid counterparts. A control group of animals that received normal saline solution or iophendylate alone did not exhibit motor blockade. These results may be attributed to sustained release of local anesthetics from the lipid vehicle. Hence, lipid drug carriers may be effective in prolonging epidural anesthesia

This study evaluates prolongation of spinal anesthesia by incorporating local anesthetics in lipid formulation. The duration and intensity of local anesthetic effect produced by different concentrations of procaine (1%, 2%, 4%), lidocaine (1%, 2%, 4%), or tetracaine (0.5%, 1%, 2%) dissolved in normal saline were compared to those produced by the same concentration of drugs in lipid (iophendylate) solution. Fifty rabbits with chronic indwelling subarachnoid catheters were divided into ten equal groups. Three days after the operation the catheters were injected with aqueous solutions of the anesthetics, and 24 h later each animal received an equivalent dose of the corresponding drug in free-base form dissolved in iophendylate. The duration and intensity of motor blockade were assessed using a modified Bromage scale. A separate group of animals received plain normal saline and, 24 h later, iophendylate alone. The Kruskal-Wallis test followed by the Tukey-type test for nonparametric multiple comparisons and the Mann-Whitney and Friedman tests were used for statistical analysis at P less than 0.05. Normal saline or iophendylate alone did not produce any motor blockade. Our data show that iophendylate preparations of local anesthetics produce prolonged but less intense motor blockade than the aqueous solutions, except for tetracaine 0.5% in iophendylate, which produced shorter duration of motor blockade. The reduced intensity of motor blockade may be explained by decreased availability of local anesthetic at the nerve tissue due to storage of drug in the lipid depot. The increased duration of blockade signifies a sustained release of drug from the depot

The maternal hemodynamic effects of bupivacaine (0.5%)-epinephrine (5 micrograms/ml) mixture used for lumbar epidural anesthesia were studied with an impedance cardiograph and an automated blood pressure device in term gravidas undergoing elective cesarean section. Following i.v. hydration with 2000 ml Ringer's lactate solution, 16 patients received bupivacaine-epinephrine mixture and 16 patients plain bupivacaine in 5-ml increments to a T4 level. Measurements were made before anesthesia, at T10 and at T4 sensory levels. Results were analyzed using analysis of variance (ANOVA) and the least significant difference method at P less than 0.05. In the epinephrine group, at T10 level, the diastolic (D) and mean (M) pressures decreased significantly 11 +/- 3, and 10 +/- 1% (mean +/- s.e. mean) respectively with no significant change in the S pressure. No significant changes were seen in the plain group. At T4, the S, D and M pressures decreased significantly 8 +/- 2, 18 +/- 4 and 16 +/- 2% in the epinephrine group. In the plain group the decrease in each one of these pressures was less than 5% and was not significant. In the epinephrine group, S, D and M pressures decreased significantly more than they did in the plain group at T10 and T4. Systemic vascular resistance decreased significantly from control values by 19 +/- 6% at T4 in the epinephrine group with no significant changes in the plain group.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of bupivacaine (B), lidocaine (L) and 2-chloroprocaine (C) on maternal (M) and neonatal (N) platelet function were studied using in vitro beta-thromboglobulin (beta-tg) release (radioimmunoassay), and in vitro platelet aggregation. Aggregation produced by adenosine diphosphate (ADP), epinephrine and collagen was measured in the presence of 1, 10, 100, 500 or 1000 micrograms/ml concentrations of B, L or C. In addition, spontaneous in vivo beta-tg release was measured in M and N blood. In vivo beta-tg level in M and N blood was approximately double that in non-pregnant subjects (p less than 0.025). In vitro beta-tg release in M and N samples was inhibited only at concentrations exceeding 1000 micrograms/ml, and the inhibition was less in M and N samples than in non-pregnant subjects. None of the anesthetics inhibited aggregation of M or N platelets at 1 and 10 micrograms/ml. Only concentrations of 500 micrograms/ml or greater consistently inhibited platelet aggregation produced by the three aggregants in M and N samples, and L was the least effective of the three agents. Neonatal platelet aggregation was affected more by local anesthetics than was maternal aggregation. It is concluded that plasma local anesthetic concentrations achieved during normal maternal epidural anesthesia do not affect M or N platelet aggregation or beta-tg release

Maternal hemodynamic changes and neonatal acid-base status were assessed in 127 healthy patients undergoing elective cesarean section under epidural anesthesia. An impedance cardiograph was used to measure stroke volume (SV), ejection fraction (EF) and end-diastolic volume (EDV). In addition, neonatal umbilical venous and arterial PO2, PCO2, pH, base excess, lactate, pyruvate, excess lactate, and L/P ratio were measured at birth. Patients were divided into three groups. Group 1 (n = 53) required no vasopressor (normotensive controls). In Group 2 (n = 37), mean blood pressure (BP) decreased from 90 mmHg (13.3 kPa). In Group 3 (n = 37), BP decreased from 83 mmHg to 62 mmHg (11.1 to 8.2 kPa), and phenylephrine was administered in 100 micrograms increments to maintain systolic BP greater than 100 mmHg (13.3 kPa). In Groups 2 and 3 the SV and EDV decreased 43% and 33% respectively when hypotension developed. Both vasopressors restored BP, SV and EDV to near baseline values. Neonatal Apgar scores and acid-base profiles were not significantly different among the three groups of neonates, nor were they different between the two hypotensive groups. It is concluded that: 1) transient maternal hypotension does not affect neonatal acid-base status; 2) both ephedrine and phenylephrine increase cardiac preload; and 3) an alpha agent like phenylephrine does not cause fetal acidosis when used for treating maternal hypotension