Reversal of soft-tissue local anesthesia with phentolamine mesylate in adolescents and adults.

BACKGROUND: The authors conducted two multicenter, randomized, double-blinded, controlled Phase III clinical trials to study the efficacy and safety of phentolamine mesylate (PM) in shortening the duration and burden of soft-tissue anesthesia. The study involved 484 subjects who received one of four commercially available local anesthetic solutions containing vasoconstrictors for restorative or scaling procedures. METHODS: On completion of the dental procedure, subjects randomly received a PM or a sham injection (an injection in which a needle does not penetrate the soft tissue) in the same site as the local anesthetic injection. The investigators measured the duration of soft-tissue anesthesia by using standardized lip- and tongue-tapping procedures every five minutes for five hours. They also evaluated functional measures and subject-perceived altered function, sensation, appearance and safety. RESULTS: Median recovery times in the lower lip and tongue for subjects in the PM group were 70 minutes and 60 minutes, respectively. Median recovery times in the lower lip and tongue for subjects in the sham group were 155 minutes and 125 minutes, respectively. Upper lip median recovery times were 50 minutes for subjects in the PM group and 133 minutes for subjects in the sham group. These differences were significant (P < .0001). Recovery from actual functional deficits and subject-perceived altered function, sensation and appearance also showed significant differences between the PM and the sham groups. CONCLUSIONS: PM was efficacious and safe in reducing the duration of local anesthetic- induced soft-tissue numbness and its associated functional deficits. CLINICAL IMPLICATIONS: Clinicians can use PM to accelerate reversal of soft-tissue anesthesia and the associated functional deficits.

Cardiovascular depression by isoflurane and concomitant thoracic epidural anesthesia is reversed by dopamine.

Interactive effects between exogenous dopamine (DA) and isoflurane (I) combined with thoracic epidural blockade (TEA) were studied in dogs during chloralose anesthesia. The I-TEA intervention per se decreased heart rate (HR; 28%), mean arterial pressure (MAP; 63%), cardiac output (CO; 54%), left ventricular dP/dt (LVdP/dt; 75%) and LVdP/dt/systolic arterial pressure (SAP; 42%). Prior to the I-TEA intervention, dopamine increased MAP, CO, LVdP/dt, LVdP/dt/SAP and stroke volume (SV) already at the dose 10 micrograms.kg-1.min-1 and, additionally, increased mean pulmonary artery pressure (MPAP) at the dose 20 micrograms.kg-1.min-1. During the I-TEA intervention, the DA-induced increases in MAP and systemic vascular resistance (SVR) were significantly higher than prior to I-TEA, as indicated by significant ANOVA interactive effects. At the dose 10 micrograms.kg-1.min-1, DA restored MAP, CO, LVdP/dt, LVdP/dt/SAP and SV to levels found before the I-TEA intervention, while HR was restored first at the dose 20 micrograms.kg-1.min-1. At the dose 20 micrograms.kg-1.min-1, DA also increased MAP (39%), LVdP/dt (119%), LVdP/dt/SAP (73%), SVR (28%) and MPAP (70%) above levels prior to I-TEA. To conclude, exogenous dopamine effectively and dose-dependently counters cardiovascular depression induced by the anesthetic technique of combining I and TEA. The pressor and systemic vasoconstrictor actions of dopamine are potentiated by conjoint administration of I and TEA.

Local anesthetic-induced toxicity may be modified by low doses of flumazenil.

The purpose of this study was to investigate the influence of flumazenil on local anesthetic-induced acute toxicity. For each of the three tested anesthetics (etidocaine, mepivacaine and lidocaine) 6 groups of mice were treated by a single dose of flumazenil (0.125, 0.25, 0.5, 1 and 2 mg/kg), or an equal volume of saline, 15 minutes before the injection of the anesthetic (etidocaine: 50 mg/kg, mepivacaine: 110 mg/kg and lidocaine: 115 mg/kg). The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic-induced mortality was not significantly modified by flumazenil. The convulsant activity of lidocaine and mepivacaine was significantly increased by flumazenil but not for etidocaine. Also, increasing doses of flumazenil decreased the time of latency to obtain lidocaine-induced convulsions. This effect was not obtained with etidocaine or mepivacaine.

An inhibitory effect of polyphloretin phosphate (PPP) on local anaesthesia.

In the present investigation it is shown that administration of polyphloretin phosphate (PPP) together with local anaesthetics decreased the duration of infiltration anaesthesia in guinea-pigs. Furthermore, it is shown that in infiltration anaesthesias the local anaesthetic effect was terminated within a few minutes by administration of PPP. In experiments with high- and low-molecular fractions of PPP, the "anti-local anaesthetic" effect of PPP was not due to the antiprostaglandin activity of PPP. There was no effect of PPP on the duration of the nerve-blocking activity of mepivacaine in rats. Neither did the administration of PPP influence the toxic effects of mepivacaine in rabbits.