Identification of urinary benzodiazepines and their metabolites: comparison of automated HPLC and GC-MS after immunoassay screening of clinical specimens

An automated high-performance liquid chromatographic method, benzodiazepines by REMEDi HS, was used to analyze benzodiazepines and their metabolites after beta-glucuronidase hydrolysis of 1-mL urine specimens from the following: 924 clinic and hospital patients whose specimens had previously been found to be presumptively positive using either EMIT or Triage immunoassay methodologies and 128 individuals whose specimens had screened negative by EMIT d.a.u.TM. REMEDi analyses did not correlate with the immunoassay results in 136 of the positive and three of the negative urine specimens. Gas chromatographic-mass spectrometric (GC-MS) confirmatory analyses were performed on these discordant specimens using 3 mL beta-glucuronidase-hydrolyzed urine followed by extraction with chloroform-isopropanol (9:1) and derivatization with N,O-bis(trimethylsilyl)trifluoroacetamide. Two benzodiazepines, flunitrazepam and clonazepam, and their 7-amino metabolites were analyzed without prior derivatization. The analyses established 87% concordance between REMEDi and GC-MS versus 13% concordance with immunoassay for the subset. GC-MS analysis of these 142 specimens demonstrated two reasons for the nonconcurrence between REMEDi and EMIT: EMIT had given either false-negative or false-positive results and EMIT had given a positive result even though the determined metabolites were below the 200-ng/mL cutoff for the immunoassay and the 80-ng/mL cutoff for REMEDi. A total of 23 specimens were found to contain only lorazepam by REMEDi and GC-MS, 15 of which had been screened by Triage. A reevaluation of these 23 specimens by EMIT d.a.u. demonstrated that 11 were positive. This finding was in contrast to previous reports that EMIT will not detect lorazepam glucuronide in urine. An unexpected finding was the REMEDi identification and subsequent GC-MS confirmation of 7-aminoflunitrazepam, a urinary metabolite of flunitrazepam that is not available in the United States and that represented illicit use by four patients. A distinct advantage of REMEDi proved to be its capability in identifying demoxepam, a major metabolite of chlordiazepoxide; GC-MS analysis could not detect this metabolite because of its thermal decomposition to nordiazepam. To further evaluate the specificity of REMEDi, we conducted GC-MS analyses in a random fashion on 55 additional nondiscordant urine specimens that were identified as either positive or negative, as well as 22 specimens identified as containing 7-aminoclonazepam by REMEDi. Concurrence was observed between the two methods for all specimens, with the exception of one apparent false positive for alpha-hydroxyalprazolam by REMEDi. The reproducibility of the REMEDi method was found to be excellent; it was assessed by comparing results of 266 specimens that were reprocessed in different batches and for known calibrators and controls also processed with each batch. Study results demonstrated that the automated REMEDi assay for urinary benzodiazepines and their metabolites was comparable with GC-MS but had distinct advantages over GC-MS because of the following reasons: simplicity of the assay, less time required for analyses, and provision of additional information concerning the parent benzodiazepine.     

Using social indicators to predict addiction

Because of cost and other constraints, states often find it difficult to estimate need for treatment of alcohol-related problems from routine surveys. The social undesirability of illegal drug use makes the assessment of need for treatment of their use even more difficult. This paper uses independently obtained treatment need estimates to provide parameters for short-term prediction. We obtained the parameters by regressing the proportions of people addicted to alcohol (or drugs) in counties on social-indicator-based relative treatment need estimates for alcohol (or drugs). In addition to integrating estimates coming from independent sources, our approach presents an important tool for planning and resource allocation.     

Identification of the protein import components of the rat mitochondrial inner membrane, rTIM17, rTIM23, and rTIM44

A large number of pharmaceutically active compounds have a high affinity to acidic phospholipids; good examples are the cationic compounds lidocaine, propranolol, and gentamycin. These drugs influenced the lipid dynamics of liposomes composed of phosphatidylcholine and the acidic phosphatidylglycerol, as judged by the excimer/monomer emission intensity ratio for a pyrene-labeled phospholipid analog, as well as by polarization of DPH fluorescence. When the mole fraction X of PG (XPG) was 0.20, lidocaine increased membrane fluidity. The opposite was true for propranolol, which caused the formation of pyrene lipid-enriched microdomains. Gentamycin had no apparent effect. At XPG = 1.00, all these drugs rigidified membrane. Subsequently, we investigated the detachment of a cationic peripheral membrane protein, cytochrome c (cyt c), by these compounds from liposomes. This was accomplished by monitoring resonance energy transfer from a pyrene-labeled phospholipid to the heme of cyt c. The efficiency of the above compounds to dissociate cyt c varied considerably. In brief, significantly lower concentrations of gentamycin than propranolol or lidocaine were required for half-maximal dissociation of cyt c from liposomes, although the final extent of protein detachment by gentamycin was less complete. ATP augmented the dissociation of cyt c from membranes by lidocaine and propranolol. Stopped-flow measurements also revealed that the half-times differed for the release of cyt c from the membranes. Our results are likely to reflect differences in the contributions of the electrostatic interactions and hydrophobicity to the drug/lipid interaction and comply with two different acidic phospholipid binding sites in cyt c.     

Tachycardia alone fails to change the myocardial pharmacokinetics and dynamics of lidocaine, thiopental, and verapamil after intravenous bolus administration in sheep

Previous reports have suggested that tachycardia alone can increase the rate of myocardial uptake of some drugs. As part of a systematic study of the determinants of the myocardial uptake and effects of drugs in critical illness, the effect of tachycardia induced by intracardiac pacing on the myocardial disposition and effects of lidocaine, verapamil, and thiopental were studied in chronically instrumented sheep. For each drug, seven sheep received either 100 mg of lidocaine, 10 mg of verapamil, or 750 mg of thiopental over 2 min in unpaced and paced (140 beats/min) states on separate occasions and in random order. Arterial and coronary sinus (effluent from the heart) blood samples were taken at regular intervals for 30 min, and the maximum rate of change of left ventricular pressure (LV dP/dtmax) was measured as an index of myocardial contractility. There were no differences between unpaced and paced studies in the time courses of arterial and coronary sinus concentrations, or the time-courses of myocardial contractility and blood flow, after bolus iv injections of these drugs. Tachycardia alone does not appear to influence the myocardial kinetics or dynamics of lipophilic drugs that can rapidly diffuse into the heart.     

Roxatidine versus ranitidine in the treatment of duodenal ulcer: a randomized, double blind, controlled, multicenter study in Thailand

BACKGROUND: Roxatidine acetate is a novel H2-receptor antagonist and several studies have shown that it is effective in healing duodenal ulcers. We evaluated the efficacy of roxatidine in a non-western society with particular different features and its healing of duodenal ulcers was compared in Thailand with that of ranitidine. METHOD: The design was controlled, randomized, double-blind, and multicenter. The study recruited a total of 215 patients who were endoscoped at the start of the trial and then randomized to receive a single capsule of roxatidine acetate, 150 mg, or an identical capsule containing ranitidine, 300 mg, both to be taken at night. Patients were evaluated at 1, 2, and 4 weeks, including endoscopy at the last session, as well as at 6 weeks with repeat endoscopy if the ulcer had not healed. RESULT: Both drugs relieved pain rapidly, usually within a week, and at repeat endoscopy at 4 weeks most ulcers (78%) were healed, 77.0 and 79.5 per cent in ranitidine and roxatidine, and in those patients in whom healing was not completed the healing rate had risen appreciably to 89.8 and 93.8 per cent respectively at 6 weeks. Small ulcers tended to heal quicker than larger ones, but smoking and alcohol intake had no negative effects on the results. CONCLUSION: The study was valid proof that roxatidine, in a single evening dose of 150 mg, was found to be both safe and effective in the rapid healing of duodenal ulcers when compared with 300 mg ranitidine.     

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.     

Relationship between antimalarial drug activity, accumulation, and inhibition of heme polymerization in Plasmodium falciparum in vitro

We have investigated the contribution of drug accumulation and inhibition of heme polymerization to the in vitro activities of a series of antimalarial drugs. Only those compounds exhibiting structural relatedness to the quinolines inhibited heme polymerization. We could find no direct correlation between in vitro activity against chloroquine-susceptible or chloroquine-resistant isolates and either inhibition of heme polymerization or cellular drug accumulation for the drugs studied. However, in vitro activity against a chloroquine-susceptible isolate but not a chloroquine-resistant isolate showed a significant correlation with inhibition of heme polymerization when the activity was normalized for the extent of drug accumulation. The importance of these observations to the rational design of new quinoline-type drugs and the level of agreement of these conclusions with current views on quinoline drug action and resistance are discussed.     

An estimate of the rate of direct drug diffusion from the surface of heart and kidney--implications for their representation as compartments

In many regional pharmacokinetic experiments and models, the anatomical boundaries of the heart and kidney are intrinsically assumed to be barriers for drug diffusion such that these organs can be represented as one or more compartments. To test this, an experimental preparation was developed in which the heart and kidney of anaesthetized sheep were surrounded with 0.9% saline. The rate of drug diffusion from the surface of the organs into the saline was examined during constant-rate i.v. drug infusions. It was found that the maximum clearances of lidocaine and procainamide into the pericardial saline were 10.3-11.6 and 0.6-2.1 ml min-1 respectively, and the values for the kidney were 0.3-0.6, 0.1-1.0 and 0.4-1.3 ml min-1, for lidocaine, procainamide, and meperidine respectively. These corresponded to calculated times of 4-481 min to reach the steady-state saline concentration depending on the drug and the organ. The steady-state ratio of the saline concentrations over the arterial blood drug concentrations usually ranged from 0.5-1.0. It is concluded that drugs can rapidly enter regions of low or no perfusion surrounding these organs, and that the concept of treating the heart and kidney as compartments may not be valid in certain 'worst-case' situations.     

Emergency treatment of psychotic symptoms. Pharmacokinetic considerations for antipsychotic drugs

Psychotic symptoms related to mental and medical disorders can pose a medical emergency. Selecting an appropriate antipsychotic medication to treat this emergency is based on the clinical situation, preferred route of administration, pharmacokinetic profile of the antipsychotic and the medications currently being taken by the patient. Intramuscular preparations are usually preferred over oral medication when the patients are not co-operative and require drugs with a faster onset of action and good bioavailability. High potency antipsychotics such as haloperidol and fluphenazine are effective in stabilising patients with psychotic symptoms quickly. Loxapine is an alternative when sedation is necessary and molindone is useful if a short-acting antipsychotic is required. Rapid neuroleptisation with intramuscular preparations of antipsychotic achieves therapeutic drug concentrations more rapidly, and also provides optimal control of psychotic symptoms. If the patient is cooperative, liquid oral preparations can be used; they are as effective as intramuscular formulations. If long term treatment with an antipsychotic in necessary and patients are stabilised, they can be switched from intramuscular to oral preparations. The oral dose is usually 1.5 to 5 times the total intramuscular dose per day, based on the bioavailability of the antipsychotic medication. If the patient is currently taking antipsychotic medication when the emergency situation occurs, it is usually adequate to increase the dose of antipsychotic drug. Appropriate dose adjustment or antipsychotic selection is necessary when drug interactions are expected. An in-depth knowledge of the pharmacokinetic profile and drug interaction profile of antipsychotic in necessary for the selection of the appropriate antipsychotic for any given emergency situation.     

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.     

Lidocaine in the horse: its pharmacological effects and their relationship to analytical findings

Lidocaine is a local anaesthetic agent that is widely used in equine medicine. It is also an Association of Racing Commissioners International (ARCI) Class 2 foreign substance that may cause regulators to impose substantial penalties if residues are identified in post race urine samples. Therefore, an analytical/pharmacological database was developed for this drug. Using our abaxial sesamoid local anaesthetic model, the highest no-effect dose (HNED) for the local anaesthetic effect of lidocaine was determined to be 4 mg. Using enzyme-linked immunosorbent assay (ELISA) screening, administration of the HNED of lidocaine to eight horses yielded peak serum and urine concentrations of apparent lidocaine of 0.84 ng/mL at 30 min and 72.8 ng/mL at 60 min after injection, respectively. These concentrations of apparent lidocaine are readily detectable by routine ELISA screening tests (LIDOCAINE ELISA, Neogen, Lexington, KY). ELISA screening does not specifically identify lidocaine or its metabolites, which include 3-hydroxylidocaine, dimethylaniline, 4-hydroxydimethylaniline, monoethylglycinexylidine, 3-hydroxymonoethylglycinexylidine, and glycinexylidine. As 3-hydroxylidocaine is the major metabolite recovered from equine urine, it was synthesized, purified and characterized, and a quantitative mass spectrometric method was developed for 3-hydroxylidocaine as recovered from horse urine. Following subcutaneous (s.c.) injection of the HNED of lidocaine, the concentration of 3-hydroxylidocaine recovered from urine reached a peak of about 315 ng/mL at 1 h after administration. The mean pH of the 1 h post dosing urine samples was 7. 7, and there was no apparent effect of pH on the amount of 3-hydroxylidocaine recovered. Within the context of these experiments, the data suggests that recovery of less than 315 ng/mL of 3-hydroxylidocaine from a post race urine sample is unlikely to be associated with a recent local anaesthetic effect of lidocaine. Therefore these data may be of assistance to industry professionals in evaluating the significance of small concentrations of lidocaine or its metabolites in postrace urine samples. It should be noted that the quantitative data are based on analytical methods developed specifically for this study, and that methods used by other laboratories may yield different recoveries of urine 3-hydroxylidocaine.     

Multicystic cavernous hemangioma of the liver: report of a case including diagnostic imaging and pathologic correlation

For systemic use, the anti-cytomegalovirus (CMV) agent foscarnet must be given intravenously because oral administration results in unmeasurable or barely measurable plasma levels. At low pH, foscarnet decomposes via an acid-catalyzed decarboxylation; therefore, poor oral bioavailability might be due to decomposition of foscarnet in gastric acid. We evaluated whether increasing gastric pH with ranitidine would enhance the absorption of oral foscarnet in six asymptomatic HIV-infected individuals. Each volunteer received two oral 4000-mg (60 mg/kg) doses of foscarnet, preceded intravenously by a 20-min infusion of either ranitidine 50 mg in D5W or D5W alone in a randomized, double-blind, cross-over study. Intragastric pH monitoring revealed that subjects had evidence of gastric acid production (pH < 2.0) prior to administration of ranitidine and increased gastric pH (pH > 6.0) following ranitidine administration. Most foscarnet plasma levels were below the assay limit of detection (33 microM) with only 4/30 levels detectable after D5W and 8/30 after ranitidine. Urinary recovery of foscarnet increased after ranitidine pretreatment. A mean recovery of 9.9% of the drug was realized in the urine in 24 h following ranitidine pretreatment compared to 6.2% of the dose after D5W pretreatment (P < 0.03). We estimate that 9.9% recovery in the urine in 24 h is equivalent to absorption of 17.1% of the oral dose. In spite of the enhanced bioavailability associated with ranitidine pretreatment, the degree of absorption is still insufficient to achieve effective plasma concentrations for the treatment of CMV or acyclovir-resistant herpes viruses. We conclude that gastric acidity is a determinant of foscarnet absorption, albeit not a major one. Oral foscarnet is unlikely to be clinically useful even if administered in the setting of increased gastric pH.     

Sterility of anesthetic and resuscitative drug syringes used in the obstetric operating room

Because of the constant threat of emergent cesarean delivery, anesthetic induction and resuscitation drugs are often drawn into syringes and stored in the obstetric operating room (OR). This study investigated the potential for bacterial and fungal contamination of six drugs (thiopental, succinylcholine, ephedrine, atropine, lidocaine, and oxytocin) often prepared in the obstetric OR. A total of 756 drug syringes were prepared and stored in the obstetric OR for 8 days using normal clinical practices. Starting on Day 0, and subsequently on Days 4 and 8 of the experiment, 42 syringes of each drug were randomly selected from the pool, filtered through a 0.45-microm porosity sterile cellulose filter, and cultured on 5% sheep blood agar. Of the 756 syringes tested, none grew organisms of any type, which indicates a probability of drug sterility of > or = 0.9961 (95% confidence interval [CI]). The data from the cultures performed on syringes on Day 0 indicate a probability of initial contamination of < or = 0.018 (95% CI). This study demonstrates a high probability of sterility in drugs drawn into sterile syringes and stored at room temperature in an OR environment for up to 8 days. Implications: Drug syringes stored in emergency operating rooms are discarded after 24 h because of possible contamination. We searched for microorganisms in drug syringes stored in the operating room for up to 8 days. No microbes were detected using standard sterility testing techniques. Adopting longer storage periods could result in significant cost savings.     

Analytical considerations in the use of capture-recapture to estimate prevalence: case studies of the estimation of opiate use in the metropolitan area of Barcelona, Spain

Capture-recapture, an indirect method widely used to estimate undetected populations, has been criticized because it causes problems due to a lack of compliance with several important assumptions and model selection strategies. This paper expands on the problems encountered when applying this methodology to drug abuse estimations, specifically the prevalence of opiate use in the metropolitan area of Barcelona, Spain, in 1993. Three samples of opiate users (from hospital emergency rooms, treatment centers, and prisons) were available in the area studied; an additional sample (mortality data) was analyzed for the city of Barcelona. Log-linear models that provided a good fit were considered, to which further model selection strategies were applied. A total of 3,207 unique individuals aged 15-44 years were identified in the three samples from the greater Barcelona area; the mortality sample from the city of Barcelona contained an additional 83 individuals. Heterogeneity was observed in different age, sex, and residence area subgroups. Population estimates differed widely according to the log-linear model chosen. Minimum Akaike's information criterion model and saturated model estimates were used to produce population prevalence rates. The main problems the authors encountered in this study were related to population definition, source heterogeneity, and assessment of an adequate model, a problem associated with sample size.     

Effects of low molecular weight heparin, alone or combined with antithrombin III, on mortality, fibrin deposits and hemostatic parameters in endotoxin-induced disseminated intravascular coagulation in rabbits

Percutaneous transhepatic portal vein embolization (PTPE) has been used to decrease the risk of hepatic failure after hepatectomy in patients with poor liver function. The effect of PTPE on hepatic drug-metabolizing activities is not clear. Therefore we examined the effect of portal vein branch ligation, a model of PTPE, on hepatic drug-metabolizing activities in Sprague-Dawley rats. Ligated and nonligated lobes were harvested separately. Drug-metabolizing activities and concentrations of components of the microsomal cytochrome P-450 monooxygenase system were examined. In ligated lobes, drug-metabolizing activities (lidocaine and aminopyrine) and enzymatic concentrations of the microsomal cytochrome P-450 monooxygenase system gradually decreased over 10 days. In nonligated lobes these functions were depressed rapidly to 60% of those before PBL but then recovered 10 days after PBL. From the viewpoint of drug metabolism, hepatic dysfunction occurred in both ligated and nonligated lobes.     

Modeling Landslide Dambreak Flood Magnitudes: Case Study

Landslide dams typically comprise unconsolidated and poorly sorted material and are vulnerable to rapid failure and breaching, resulting in significant and sudden flood risk downstream. Hence they constitute a serious natural hazard, and rapid assessment of the likely peak flow rate is required to enable preparation of adequate mitigation strategies. To determine the relative utility and accuracy of dambreak flood forecasts, field estimates of peak outflow rates from the failure of the Poerua landslide dam in October 1999 were compared with estimates from physical laboratory modeling, empirical methods, and computer modeling. There was reasonable agreement among the field estimates, laboratory modeling, and computer modeling. Some empirical estimates were less reliable. Reasonably reliable estimates of peak outflow can be obtained from computer model routines sufficiently rapidly to be of use in an emergency management situation. The laboratory modeling demonstrated the effect of dam batter slopes and valley bed slope on peak outflow; this information could be used to refine empirical or numerical estimates of peak outflow.     

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.     

The effect of ammonium sulfate injection on peripheral nerve

Local anesthetic drugs with prolonged nerve-block effect would have clinical application for postoperative or neuromatous pain relief. This study evaluated the possibility of peripheral nerve neurotoxicity by injection of 10 percent ammonium sulfate. Both intrafascicular and extrafascicular injection of 10 percent ammonium sulfate were tested in the rat sciatic nerve model. One percent lidocaine HCl, 5 percent phenol, and normal saline were similarly injected for comparison. Using histologic studies and motor function evaluation with walking-track analysis, 10 percent ammonium sulfate was found to be neurotoxic when it is injected intrafascicularly; however, extrafascicular injection of this drug did not cause significant nerve injury. The neurotoxicity of the 10 percent ammonium sulfate solution was intermediate between the neurotoxicity of 0.1 percent lidocaine hydrochloride and the marked neurotoxicity of 5 percent phenol solution.