Clonidine and lidocaine inhibition of isoflurane-induced tachycardia in humans

BACKGROUND: A rapid increase in isoflurane concentration can induce tachycardia and hypertension and increase plasma catecholamine concentrations. To investigate a possible mechanism, we measured hemodynamic responses to isoflurane administered via mask; we also administered clonidine for premedication, lidocaine topically to the nasal mucosa, or lidocaine intravenously to evaluate the effect of these drugs on the hemodynamic responses. METHODS: Forty ASA physical status 1 patients (aged 20-30 yr) scheduled for elective oral surgery participated in the study. Thirty patients were randomly allocated to one of three groups: a control group, a group receiving 3-4 micrograms.kg-1 of oral clonidine for premedication, and a group receiving 2 ml of 4% lidocaine spray to the nasal mucosa. Ten patients were assigned nonrandomly to a group receiving intravenous lidocaine continuously (0.4 mg.kg-1 bolus followed by 30 micrograms.kg-1.min-1) after the initial randomized experiments were done to test whether systemic lidocaine blunts the responses to inhaled isoflurane. Anesthesia was induced with thiamylal, after which inhalation of 1% isoflurane in 100% oxygen via mask was begun. The inspired concentration of isoflurane was increased by 1% every 5 min to a maximum of 4%. During normocapnia and without surgical stimulation, heart rate and systolic blood pressure were measured every minute for 20 min before and during isoflurane inhalation. Plasma catecholamine concentrations were measured before and at each isoflurane concentration. RESULTS: In the control and intravenous lidocaine groups, an increase in isoflurane concentration from 2% to 3% significantly increased systolic blood pressure (peak changes of 16 +/- 5 and 15 +/- 6 mmHg, respectively) and heart rate (peak changes of 23 +/- 3 and 13 +/- 4 beats.min-1, respectively). A change in concentration to 4%, however, did not significantly alter hemodynamics. Blood pressure and heart rate responses to a change to 3% isoflurane were significantly blunted in the groups receiving clonidine (peak changes of 4 +/- 4 mmHg and 8 +/- 3 beats.min-1, respectively) or nasal lidocaine (peak changes of 2 +/- 1 mmHg and 4 +/- 2 beats.min-1, respectively) compared with the control group. In all groups, plasma epinephrine and norepinephrine concentrations increased after administration of 2% and 1% isoflurane, respectively. Plasma lidocaine concentrations were 0.3-1.3 micrograms.kg-1 in the nasal lidocaine group and 0.6-1.5 micrograms.kg-1 in the intravenous lidocaine group. CONCLUSIONS: Stepwise increases in isoflurane concentration elicited hypertension and tachycardia as well as increments in plasma catecholamine concentrations during mask anesthesia. Nasal administration of lidocaine and clonidine premedication significantly blunted the circulatory responses to isoflurane. Intravenous lidocaine did not significantly weaken the responses to changes in isoflurane concentration.     

IMGT, the international ImMunoGeneTics database

Propofol emulsion supports bacterial growth. Extrinsic contamination of propofol has been implicated as an etiological event in postsurgical infections. When added to propofol, local anesthetics (e.g., lidocaine) alleviate the pain associated with injecting it. Because local anesthetics have antimicrobial activity, we determined whether lidocaine would inhibit microbial growth by comparing the growth of four microorganisms in propofol and in mixtures of propofol and lidocaine. Known quanta of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were inoculated into solutions of 1% propofol, 0.2% lidocaine in propofol, 0.5% lidocaine in propofol, 0.5% lidocaine in isotonic sodium chloride solution, and 0.9% isotonic sodium chloride solution. All microorganisms were taken from stock cultures and incubated for 24 h. Growth of microorganisms in each solution was compared by counting the number of colony-forming units grown from a subculture of the solution at 0, 3, 6, 12 and 24 h. Propofol supported the growth of E. coli and C. albicans. Propofol maintained static levels of S. aureus and was bactericidal toward P. aeruginosa. The addition of 0.2% and 0.5% lidocaine to propofol failed to prevent the growth of the studied microorganisms. The effect of 0.5% lidocaine in isotonic sodium chloride solution did not differ from the effects of isotonic sodium chloride solution alone. We conclude that lidocaine, when added to propofol in clinically acceptable concentrations, does not exhibit antimicrobial properties. IMPLICATIONS: Local anesthetics such as lidocaine have antimicrobial activity. Propofol supports the growth of bacteria responsible for infection. Bacteria were added to propofol and propofol mixed with lidocaine. The addition of lidocaine to propofol in clinically relevant concentrations did not prevent the growth of bacteria. The addition of lidocaine to propofol cannot prevent infection from contaminated propofol.     

Both intravenous and inhaled lidocaine attenuate reflex bronchoconstriction but at different plasma concentrations

Intravenous lidocaine can attenuate bronchial hyperreactivity. However, lidocaine inhalation might yield the same or better results at higher airway and lower lidocaine plasma concentrations. Therefore, we tested in awake volunteers with bronchial hyperreactivity the effect of lidocaine on histamine-induced bronchoconstriction administered either intravenously or as an aerosol. After approval of the local ethics committee, 15 volunteers were enrolled in this placebo-controlled, double-blinded, randomized study. Volunteers were selected by showing a decrease in FEV1 greater than 20% of baseline (PC20) in response to histamine inhalation. On three different days the challenge was repeated after pretreatment with either intravenous lidocaine, inhaled lidocaine, or placebo. Blood samples for determination of lidocaine plasma concentration were drawn. Comparisons were made using the Friedman and Wilcoxon signed-rank tests. Baseline PC20 was 6.4 +/- 1.1 mg. ml-1. Both inhalation of lidocaine and intravenous administration significantly increased PC20 to 14.8 +/- 3.5 mg. ml-1 and 14.2 +/- 2. 5 mg. ml-1, respectively (p = 0.0007). Peak plasma lidocaine concentrations at the end of challenges were 0.7 +/- 0.1 microg. ml-1 (inhaled) and 2.2 +/- 0.1 microg. ml-1 (i.v.). However, 7 of 15 subjects showed an initial decrease of FEV1 greater than 5% following lidocaine inhalation. While both intravenous as well as inhaled lidocaine attenuate reflex bronchoconstriction significantly, lidocaine plasma concentrations are significantly lower after inhalation. However, the high incidence of initial bronchoconstriction to lidocaine inhalation may limit its use in patients with asthma and thus offers therapeutic advantages for intravenous lidocaine.     

Lidocaine as a diluent for administration of benzathine penicillin G

OBJECTIVE: Benzathine penicillin G is recommended for secondary prophylaxis of rheumatic fever. Its main disadvantage is local pain and discomfort associated with the injection. Lidocaine as a diluent may reduce this discomfort. We compared the administration of benzathine penicillin G with two diluents; sterile water and lidocaine hydrochloride 1% for penicillin concentrations and pain of injection. DESIGN: In a randomized double blind, crossover trial, 18 children ages 11 to 19 years who required prophylactic treatment for rheumatic fever were randomly divided into two groups. One received an injection of benzathine penicillin G diluted with 3.2 ml of sterile water, followed 1 month later by an injection of benzathine penicillin G diluted in lidocaine hydrochloride 1%; the second group received the same regimen in the reverse order. Serum penicillin concentrations and subjective pain sensation were determined after each injection. RESULTS: Peak serum penicillin concentrations at 24 h after injection were similar for both preparations (0.100 microg/ml for water, 0.102 microg/ml for lidocaine), as were the other serum values measured throughout the month. After 28 days detectable concentrations (> or =0.020 microg/ml) were found in 44 and 291% of the subjects, respectively (P = 0.4). Urine penicillin concentrations on Day 28 were 1.81 +/- 0.25 and 2.31 +/- 0.25 microg/ml, respectively. The pain score immediately after the injection was significantly lower with the lidocaine than with the sterile water dilution. CONCLUSION: Use of lidocaine hydrochloride as a diluent for benzathine penicillin G does not change the penicillin concentration in body fluids and significantly reduces the pain of injection. We suggest the use of lidocaine hydrochloride 1% as a diluent for benzathine penicillin G.     

Age-dependent Neisseria meningitidis serogroup C class-specific antibody concentrations and bactericidal titers in sera from young children from Montana immunized with a licensed polysaccharide vaccine

Neisseria meningitidis serogroup C bactericidal titers and class-specific enzyme-linked immunosorbent assay (ELISA) antibody concentrations were measured in sera from 173 children (1 to 5 years old) before and 6 weeks and 7 months following vaccination with a quadrivalent (A/C/Y/W-135) polysaccharide vaccine. The immune responses of the children were compared with those of 40 adults 6 weeks postvaccination. Both bactericidal titers and ELISA antibody concentrations were significantly higher in the adults than in the children (P < 0.05). In addition, the ratio of immunoglobulin G (IgG) to IgM was higher in the children than in the adults. With an ELISA total antibody concentration of >/=2 microg/ml used as a measure of seroconversion, >/=84% of the individuals from each age group responded to the serogroup C polysaccharide. However, with a >/=4-fold-increase in bactericidal titer used, only 18% of 1-year-olds, 32% of 2-year-olds, and 50 to 60% of 3-, 4-, and 5-year-olds seroconverted. The ELISA results suggest that >50% of all children retained >/=2 microg of total antibody per ml at 7 months postimmunization. However, the bactericidal titers suggest that <10% of children <4 years old retained a >/=4-fold increase at 7 months following vaccination. Of particular note, 59 of 79 sera (75%) from the 1- and 2-year-olds had high ELISA antibody concentrations (2 to 20 microg/ml) with no associated bactericidal titer (<1:8). Discordant results between bactericidal titers and ELISA antibody concentrations were not explained by the presence of IgA blocking antibody or relative levels of IgG and IgM. The bactericidal results show age-dependent differences in the production and retention of antibody in young children immunized with serogroup C polysaccharide; these differences are not evident with the ELISA data.     

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. STUDY DESIGN: Phase 1, controlled randomized cross-over trial; Phase 2, before and after trial ANIMALS: 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.CLINICAL RELEVANCE: Methods shown in the study can be used in clinical cases to achieve therapeutic lidocaine levels without significant cardiovascular depression during isoflurane anesthesia.     

An electrophysiological and histological study on the neurotoxicity of lidocaine in excised rabbit cervical vagus nerve

We studied the neurotoxic effect of lidocaine at different concentrations on the desheathed rabbit vagus nerve by measuring the amplitudes of evoked compound action potentials and the histological changes of the nerve by means of the electron microscopy after incubation in lidocaine-Ringer's bicarbonate (RB) solution. The following results were obtained. 1) Minimum concentrations of lidocaine for producing complete conduction block (minimum blocking concentration, MBC) were 0.02% for A beta and A delta fibers, and 0.03% for C fibers. 2) Irreversible conduction blocks of compound action potentials were observed in relation with lidocaine concentrations and the duration of incubation: e.g. 0.5% for 2 hours incubation was equivalent to the block with 1% for 1 hour. 3) Degenerative change of axons was revealed morphologically in the preparations exposed to 2% or a higher concentration of lidocaine. 4) Risk ratio, which means a numerical value calculated as clinical concentration/irreversible concentration with 2 hr exposure, was similar to other local anesthetics except dibucaine HCl, which shows an higher risk ratio. However, it should be noted that lidocaine has an risk of producing irreversible changes in nerve fibers, when applied to the nervous tissue at higher concentrations for longer durations.     

Effects of epidural and systemic lidocaine on sympathetic activity and mesenteric circulation in rabbits

BACKGROUND: The mechanisms producing hemodynamic changes during epidural anesthesia are incompletely understood. This study examines the sympathetic block and splanchnic venodilatation that result from extensive thoracolumbar epidural anesthesia in rabbits using direct measurements of sympathetic efferent nerve activity (SENA) and mesenteric vein diameter (VD). METHODS: Epidural catheters were inserted in rabbits anesthetized with alpha-chloralose, paralyzed with vecuronium, and receiving mechanical ventilation. Arterial pressure was monitored with a femoral cannula, heart rate was determined from the pressure signal, SENA was measured from a postganglionic splanchnic nerve, and VD was measured from segments of ileum externalized in situ. Epidural anesthesia was induced with 0.4 ml/kg lidocaine, using concentrations of either 0.5, 1, or 1.5%. Control animals received intramuscular lidocaine in a dose of either 6 or 15 mg/kg. After recovery from epidural anesthesia, complete sympathetic blockade was induced by systemic administration of the ganglionic blocker hexamethonium (HX). Individual groups included from five to eight animals. RESULTS: A mild decrease in arterial pressure and SENA followed the larger dose of intramuscular lidocaine, but no changes occurred in VD in the control animals exposed to systemic lidocaine at levels comparable to that in the epidural groups (0.96-3.58 micrograms/ml). Epidural injectate extended from T2 to L5. All concentrations of epidural lidocaine produced comparable degrees of hypotension (-53.5 to -61.4%), decreased SENA (-82.6 to -95.5%), and increased VD (7.5 to 10.2%). The duration of the changes was greater with more concentrated lidocaine. Hexamethonium produced changes in arterial pressure and VD comparable to those evoked by epidural anesthesia. CONCLUSIONS: Epidural anesthesia increases splanchnic venous capacitance by markedly decreasing splanchnic sympathetic nerve activity.     

Inhibitory effect of local anaesthetics on reactive oxygen species production by human neutrophils

BACKGROUND: Reactive oxygen species (ROS) generated from neutrophils accumulated in various major organs are thought to play a pivotal role in the pathogenesis of host auto-injury. Lidocaine has been shown to reduce the injury. We investigated the effect of local anaesthetics (lidocaine, mepivacaine and bupivacaine) on ROS production by neutrophils using an in vitro system. METHODS: We measured the production of superoxide (ferricytochrome c method), hydrogen peroxide (H2O2: scopoletin fluorescence technique), and hydroxyl radical (OH.: ethylene gas method) by neutrophils isolated from human adult volunteers in the absence and presence of lidocaine (2-200 micrograms/mL), mepivacaine (3-300 micrograms/mL), and bupivacaine (3-300 micrograms/mL). We also measured the ROS generation in a cell-free (xanthine-xanthine oxidase) system. RESULTS: Lidocaine and mepivacaine at higher levels significantly decreased the production of ROS by neutrophils. However, these local anaesthetics at clinically relevant blood concentrations had no effect on the levels of ROS. Furthermore, lidocaine and mepivacaine failed to reduce ROS generated by the cell-free system. Bupivacaine did not decrease ROS generation by either generating system. CONCLUSION: In conclusion, in the present in vitro system, only concentrations of lidocaine and mepivacaine 100-fold higher than clinically feasible ones reduced ROS production by human neutrophils. However, the local anaesthetics at clinically relevant blood concentrations had no suppressive effect. Further studies using in vivo systems are required to elucidate the inhibitory effects of local anaesthetics on ROS generation in clinical settings.     

Topographical analysis of the EEG effects of a subconvulsive dose of lidocaine in healthy volunteers

BACKGROUND: The purpose of the present study was to assess the effects of intravenous lidocaine on spatial changes of electroencephalographic power and on psychomotoric status in conscious volunteers. METHODS: In 11 healthy volunteers lidocaine (2-min bolus, 100 mg; 15 min infusion, 40 micrograms.kg-1.min-1) or placebo were given intravenously in a randomized, single-blinded, two-way crossover study. Haemodynamics and lidocaine plasma concentrations were measured at baseline and within a period of 30 min following bolus injection. Vigilance and emotional status were tested using visual analogue scales (VAS). Toxic CNS effects were evaluated by a questionnaire. The raw EEG (17 leads, reference Cz) and computed power spectra were continuously recorded. RESULTS: The chosen lidocaine dosage led to nearly constant plasma concentrations (unbound lidocaine 2.5 min and 15 min after bolus 0.36 +/- 0.14 microgram/ml and 0.30 +/- 0.06 microgram/ml, respectively [mean +/- SD]). The placebo caused no symptoms, changes in VAS-scores or EEG-parameters. Lidocaine induced pronounced subjective symptoms and significant increases in delta activity for 15 min, most dominant at the frontotemporal and occipital leads (max. +219% O1). Frontal and occipital beta 1 and beta 2 power (max. +131% and +124% at O1, respectively) was immediately increased after the bolus injection. No EEG changes occurred at central region Cz, and no interhemispheric EEG differences were noted. Theta, alpha 1, and alpha 2 power remained unchanged. CONCLUSION: The current data demonstrate simultaneous changes in psychomotoric status as well as delta and beta spectral power during lidocaine infusion. These data could be an indication that the pronounced frontotemporal and occipital EEG changes are the electroencephalographic expression of subjective sensations.     

Time trend of female breast carcinoma in situ by race and histology in Connecticut, USA

BACKGROUND: Surgical procedures used to remove genital warts (cryotherapy, electrodesiccation) are painful. Attempts to reduce the discomfort of surgery by prior lidocaine infiltration anesthesia are compromised by the pain of the infiltration. OBJECTIVE: Our purpose was to determine the efficacy of topically applied lidocaine/prilocaine cream to reduce the pain of lidocaine infiltration and the pain associated with cryotherapy to remove genital warts. METHODS: Men, scheduled for removal of genital warts by cryotherapy, were randomly selected to receive one of three treatments: (1) lidocaine/prilocaine cream application, (2) 1% lidocaine infiltration, and (3) lidocaine/prilocaine cream application followed by infiltration of 1% lidocaine. RESULTS: Application of lidocaine/prilocaine cream for 15 minutes markedly reduced the pain of lidocaine infiltration. The combination of lidocaine/prilocaine cream followed by infiltration of 1% lidocaine gave greater pain relief from the cryotherapy than did either anesthetic alone. CONCLUSION: The application of lidocaine/prilocaine cream as an adjunct to lidocaine infiltration reduced the pain of infiltration and the pain associated with cryotherapy for the removal of genital warts.     

Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies

The association of propofol with excitatory motor activity, such as myoclonic jerking and opisthotonus, in humans and in animals suggests that it may aggravate clinical seizure activity in some circumstances, although evidence suggests that under other circumstances, propofol inhibits seizure activity. In the current study, we assessed the effect of sedating doses of propofol on lidocaine-induced seizure activity in spontaneously breathing rats receiving no other anesthetics. Adult Sprague-Dawley male rats, 300-400 g, were divided into a control group and three experimental groups representing three graded levels of propofol sedation. The control rats then received a lidocaine infusion at the rate of 150 mg x kg(-1) x h(-1), resulting in a slow, progressive increase in systemic lidocaine concentrations. At the onset of electroencephalographic (EEG) seizure activity, arterial lidocaine concentrations were obtained. The treated rats received propofol according to three different dose schedules: Dose 1 = 10 mg x kg(-1) x h(-1) after a 2.5-mg/kg bolus; Dose 2 = 20 mg x kg(-1) x h(-1) after a 5-mg/kg bolus; Dose 3 = 40 mg x kg(-1) x h(-1) after a 10-mg/kg bolus. After 30 min, a steady level of sedation, dependent on the dose of propofol, was achieved. The lidocaine infusion was then started, and systemic lidocaine levels were obtained at the onset of EEG seizure activity. The lidocaine was continued until the onset of death by cardiac arrest. Plasma lidocaine was measured by gas chromatography. Analysis of variance and Dunnett's t-test were used for comparisons with the control values. Continuous propofol sedation increased the seizure dose of lidocaine from 37.7 +/- 3.5 mg/kg (mean +/- SEM) to 52.5 +/- 2.6 mg/kg (Dose 1, P < 0.05) and 67.9 +/- 8.6 mg/kg (Dose 2, P < 0.05), and completely abolished lidocaine seizures at Dose 3. The lethal dose of lidocaine, 89.4 +/- 10.5 mg/kg control versus 108.7 +/- 10.3 mg/kg (Dose 1), 98.3 +/- 10.1 mg/kg (Dose 2), and 93.5 +/- 10.4 mg/kg (Dose 3) did not differ among groups. The lidocaine levels at seizure threshold were increased in the propofol-treated rats: 16.9 +/- 0.5 microg/mL control versus 19.2 +/- 0.7 microg/mL (Dose 1, P = not significant) and 23.7 +/- 1.8 microg/mL (Dose 2, P < 0.05). Continuous propofol sedation in spontaneously breathing rats receiving no other anesthetics exerts a protective effect against lidocaine-induced seizures in a monotonic, dose-dependent fashion. The cardiac arrest dose of lidocaine is unaffected by propofol under these conditions. IMPLICATIONS: The i.v. anesthetic drug propofol, given to rats to produce sedation, was found to suppress seizure activity caused by overdosage of the local anesthetic lidocaine.     

Extraordinary features in the Chlamydomonas reinhardtii chloroplast genome: (1). rps2 as part of a large open reading frame; (2). A C. reinhardtii specific repeat sequence

PURPOSE: To evaluate the clinical efficacy of local vaginal lidocaine application for pain relief during high-dose-rate (HDR) intracavitary brachytherapy for patients with cervical cancer, and to investigate sequential changes in serum levels of lidocaine during the procedures. METHODS AND MATERIALS: This prospective study was designed to examine the analgesic effect, physical response, and side effects of local anesthesia during HDR intracavitary brachytherapy. Forty patients were enrolled. All patients received 10-15 MV X-rays to the pelvis with a total dose of 45-59.4 Gy 5-6 weeks before undergoing HDR intracavitary brachytherapy. All patients underwent first intracavitary brachytherapy under general anesthesia. These patients were randomly allocated to receive one of two different treatment protocols as follows: (1) treatment session - control session - treatment session - control session; or (2) control session - treatment session- control session - treatment session. In the treatment sessions, topical anesthesia was administered using 4 ml of 10% lidocaine solution sprayed liberally on the cervix and vagina during intracavitary brachytherapy. In the control sessions, a placebo was administered in the same manner during brachytherapy. The Hensche's applicators for brachytherapy were inserted into the cervix and vagina 5 min after lidocaine application. The visual analogue scale (VAS) was used to assess pain and discomfort during brachytherapy. Blood pressure and heart rates were measured to evaluate the physiological response. Another prospective study was then performed to investigate the sequential changes of serum lidocaine levels during the anesthetic procedure. Eleven additional patients with similar disease state and demographic characteristics were enrolled and blood samples were obtained before, and 5, 15, 30, and 45 min after the initiation of lidocaine application. RESULTS: The mean VAS values recorded during the treatment sessions and control sessions were 49.9 +/- 24.1 versus 60.1 +/- 24.8, respectively. The value of VAS in the treatment session was significantly lower than that of the control session (p < 0.001). No statistically significant differences were found in the changes of blood pressure and heart rate and in the incidence of side effects during these two types of sessions (p > 0.05). In the drug-level study, serum levels of lidocaine reached a peak 5 min after the initiation of local anesthesia. The mean peak concentrations (Cmax) of lidocaine were 0.50 +/- 0.45 microg/ml. CONCLUSION: Local vaginal anesthesia with 10% lidocaine solution can significantly decrease the degree of painful sensation during HDR intracavitary brachytherapy, and is safe to administer for the procedure for cervical cancer.     

Analysis of the treatment of spontaneous sustained stable ventricular tachycardia

OBJECTIVES: To determine the termination rate of spontaneous sustained stable ventricular tachycardia (SSSVT) as a function of the first and second therapeutic interventions used, and to determine factors associated with successful termination. METHODS: A multihospital, retrospective analysis of the treatment of patients with SSSVT was performed. The setting included 2 urban county hospitals, 2 urban private hospitals, and a Veterans Affairs hospital. Cases were identified by discharge diagnosis and ECG characteristics, and confirmed by electrophysiology study or ECG criteria. RESULTS: There were 40 cases of SSSVT identified. Excluding adenosine, 35 patients were treated with lidocaine as a first intervention. The rate of termination with lidocaine bolus was 17% (6 of 35) (95% CI 7-34%). Regarding the 35 patients initially treated with lidocaine, the odds of termination of SSSVT were 11 times greater in those without a history of previous myocardial infarction (MI) than in those with a history of MI (95% CI 0.96-551). Of the 29 patients who failed initial lidocaine treatment, 23 were treated with a second lidocaine bolus, with a termination rate of 18% (4 of 22) (95% CI 5-40%). Only 2 patients with sustained ventricular tachycardia had a concurrent MI, and the tachycardia was unresponsive to initial lidocaine bolus in both cases. Fifteen patients received adenosine with no tachycardia terminations and no significant adverse effects. CONCLUSIONS: The rate of SSSVT termination with lidocaine was low, particularly in patients with a history of Mi.     

Limits to milk flow and energy allocation during lactation of the hispid cotton rat (Sigmodon hispidus)

INTRODUCTION: Epicardial and endocardial defibrillation electrode systems affect myocardial electrophysiology and sympathetic function differently. Thus, we postulate that antiarrhythmic drugs will interact with these electrode systems differently. METHODS AND RESULTS: Defibrillation energy requirements (DER) at 20% (ED20), 50% (ED50), and 80% (ED80) success were measured at baseline and during lidocaine (10 mg/kg per hour) or D5W treatment for epicardial and endocardial electrodes. Pigs were randomized to treatment (lidocaine or D5W) and electrode system, which resulted in four experimental groups: (1) epicardial electrode + D5W; (2) epicardial electrode + lidocaine; (3) endocardial electrode + D5W; and (4) endocardial electrode + lidocaine. ED50 DER (mean +/- SEM) values at baseline for groups 1-4 were 10.6+/-1, 8.5+/-1, 12.6+/-1, and 12.3+/-1 J, respectively. DER values for groups 1 and 3 during D5W were similar to baseline. Conversely, lidocaine increased ED50 DER values from 8.5+/-1 to 13.5+/-2 J (P < 0.05) in group 2 animals (epicardial electrodes). When lidocaine was administered to group 4 animals (endocardial electrodes), however, ED50 DER values remained similar to baseline values (12.3+/-1 to 14.3+/-2 J, P = NS). Lidocaine increased ED50 DER values by 59% with the epicardial electrode system, which was significantly greater than the 16% increase with the endocardial electrode system (P < 0.05). Electrophysiologic response and electrode impedance were similar between electrode systems. CONCLUSION: Lidocaine increases DER values to a greater extent when using epicardial versus endocardial electrode system. Thus, drug-device interactions are dependent on the electrode system. These data suggest that the electrophysiologic milieu created by endocardial defibrillation mitigates the effects that lidocaine has on DER values.     

Impaired respiratory function in infants with anterior abdominal wall defects

Pentobarbital alone, pentobarbital plus 1% lidocaine solution, pentobarbital plus 2% lidocaine solution, and pentobarbital plus 3% lidocaine solution were each used to euthanatize 6 dogs. For each dog, time between the beginning of injection of the euthanasia solution and each of the following events was recorded: collapse, onset of apnea, flat-line electrocardiogram, flat-line electroencephalogram, loss of palpable heartbeat, and loss of palpable pulse. Any signs of pain or discomfort were also recorded. There were no significant differences among groups except for time to flat-line electrocardiogram. Dogs euthanatized with pentobarbital alone had significantly longer times than did dogs euthanatized with pentobarbital in combination with any of the lidocaine concentrations. We concluded that pentobarbital in combination with lidocaine was a reasonable alternative to pentobarbital alone when euthanatizing dogs.     

Therapeutic equivalency of two lidocaine preparations

Twenty-five volunteers were studied as to the onset and duration of action of two commercial brands of lidocaine. One and two percent concentrations of the preparations were tested intradermally using a double-blind, cross-over protocol. Both needle-drop and electrical stimulation techniques were employed as the source of pain stimulus. Five additional subjects were studied in a dose-ranging study using a placebo and lidocaine concentrations of 0.25%, 0.50%, 0.75% and 1.0%; this experiment was conduced to determine the sensitivity of the experimental methods. Both the needle-drop and electrical stimulation techniques were able to distinguish the 0.25% preparation from placebo and from the other concentrations of 1% and 2%. The two preparations were found to be statistically equivalent at concentrations of 1% and 2% and could be used interchangeably in clinical procedures.     

Characterization of the independent and combined effects of two inhibitors on oxidative drug metabolism in rat liver microsomes

To evaluate how two inhibitors influence oxidative drug metabolism, this study investigated the inhibitory effects of mexiletine with cimetidine and mexiletine with lidocaine, both individually and in combination, on the oxidative metabolism of two probe substrates, aminopyrine and aniline in rat liver microsomes. Mexiletine was a competitive inhibitor of aminopyrine N-demethylation, whereas cimetidine was a mixed type of inhibitor (Ki = 2.00 +/- 0.04 and 0.20 +/- 0.02 mM, respectively). For aniline hydroxylation, mexiletine exhibited a mixed type of inhibition, whereas lidocaine was a noncompetitive inhibitor (Ki = 0.60 +/- 0.07 and 8.50 +/- 0.12 mM, respectively). The combined inhibition of either mexiletine with cimetidine or mexiletine with lidocaine on aminopyrine and aniline metabolism was close to the fully additive effects of the individual compounds when their individual concentrations were below a 2-fold Ki concentration, regardless of the apparent kinetic inhibition type. The combined inhibition was less than fully additive when the individual concentrations were twice the Ki or above. These results demonstrate that, when two inhibitors of oxidative drug metabolism are combined, both the Ki values and the concentrations of inhibitors play important roles in determining the extent of additive inhibition of enzyme activity.     

Cost-effectiveness and cost-benefit analysis of using methotrexate vs Goeckerman therapy for psoriasis. A pilot study

PURPOSE: To compare topical tetracaine 0.5% alone and with intracameral lidocaine 1% as a local anesthetic agent in phacoemulsification with intraocular lens (IOL) implantation. SETTING: The Toronto Hospital-Western Division, Toronto, Canada. METHODS: Fifty-nine consecutive patients (60 eyes) having phacoemulsification with implantation of a foldable acrylic IOL (AcrySof) were randomized into 1 of 2 groups: The intracameral balanced salt solution (BSS) group received topical tetracaine 0.5% plus intracameral BSS; the intracameral lidocaine group received topical tetracaine 0.5% with preservative-free intracameral lidocaine 1%. The patients' subjective experience of pain was measured at 4 points during surgery using a 4-point pain scale. Patient and surgeon satisfaction with the anesthesia used was measured using a 5-point satisfaction scale. Central endothelial cell counts were obtained preoperatively and 1 month postoperatively. Best corrected visual acuity (BCVA) was measured preoperatively and 1 hour, 1 day, 1 week, and 1 month postoperatively. RESULTS: The mean pain score after phacoemulsification was significantly higher in the intracameral BSS group than in the intracameral lidocaine group (0.63 +/- 0.7 [SD] and 0.23 +/- 0.4, respectively, P < .019). The mean pain score at the end of surgery was also significantly higher in the intracameral BSS group than in the intracameral lidocaine group (0.60 +/- 0.6 and 0.21 +/- 0.4, respectively; P < .014). The surgeon satisfaction score was significantly lower for the intracameral BSS group than for the intracameral lidocaine group (3.90 +/- 1.2 and 4.73 +/- 0.8, respectively; P < .0007). There was no difference in patient satisfaction between the intracameral BSS and intracameral lidocaine groups (4.60 +/- 0.6 and 4.70 +/- 0.8). Endothelial cell loss 1 month postoperatively was similar between the 2 groups (6.1% +/- 8% and 6.7% +/- 6%). Ninety-seven percent of patients (29/30) in each group noted BCVA improvement from preoperatively. The rate of potential visual acuity recovery was similar in both groups. CONCLUSION: Topical tetracaine 0.5% with intracameral lidocaine was safe and effective in patients having phacoemulsification with IOL implantation. The advantage of using intracameral lidocaine 1% over a placebo was a significant decrease in the patients' subjective experience of pain and in the surgeon's satisfaction with the anesthesia used. None of the other parameters measured in this study differed significantly between the 2 groups.     

Caucasian versus African-American differences in orosomucoid: potential implications for therapy

We conducted a prospective, nonrandomized study in healthy volunteers to determine if racial differences exist in orosomucoid (ORM) and its variants, and to examine quinidine and lidocaine binding to the protein. Total ORM serum concentrations were measured by Laurell-Rocket immunoelectrophoresis. Allele types were determined by isoelectric focusing and immunoblotting. Total and unbound quinidine and lidocaine concentrations were measured with standard fluorescence polarization immunoassays after ultrafiltration. The frequency of the common ORM alleles was similar between 38 Caucasians and 67 African-Americans. Mean total ORM concentration was significantly lower in Caucasians (57.3 +/- 25.4 vs 73.2 +/- 33.9 mg/dl, p=0.01). However, more Caucasians took oral contraceptives, which may have decreased ORM concentrations. Quinidine unbound fraction (UF) was related to ORM phenotype. The highest UF was found with ORM 1-S (p=0.009). There were no significant relationships between ORM phenotype and lidocaine UF. Overall, African-Americans had higher ORM concentrations than Caucasians. Quinidine binding showed significant relationships to specific ORM variants.