Mass transport model through the skin by microencapsulation system.

Skin drug delivery can be subdivided into topical and transdermal administration. Transdermal administration can take advantage of chemical and physical strategies that can improve skin permeability and allow drug penetration. In this study, the development of a skin penetration profile was carried out by an in vitro technique for a microencapsulated system of ibuprofen. Release experiments were performed using percutaneous absorption tests to determine the evolution of the principle present in each of the different skin compartments as a function of time. A general kinetic model for a microencapsulated structure as a mass transport system through the skin was applied: [Formula: see text] This model could predict the penetration profile of encapsulated substances through skin from biofunctional textiles as well as estimate the dosage profile of the active principle. The apparent diffusion coefficients found were 1.20 × 10(-7 )cm/s for the stratum corneum and higher for the rest of the skin 6.67 × 10(-6 )cm/s.

Methodology for determining major constituents of ayahuasca and their metabolites in blood.

There is an increasing interest in potential medical applications of ayahuasca, a South American psychotropic plant tea with a long cultural history of indigenous medical and religious use. Clinical research into ayahuasca will require specific, sensitive and comprehensive methods for the characterization and quantitation of these compounds and their metabolites in blood. A combination of two analytical techniques (high-performance liquid chromatography with ultraviolet and/or fluorescence detection and gas chromatography with nitrogen-phosphorus detection) has been used for the analysis of some of the constituents of ayahuasca in blood following its oral consumption. We report here a single methodology for the direct analysis of 14 of the major alkaloid components of ayahuasca, including several known and potential metabolites of N,N-dimethyltryptamine and the harmala alkaloids in blood. The method uses 96-well plate/protein precipitation/filtration for plasma samples, and analysis by HPLC-ion trap-ion trap-mass spectrometry using heated electrospray ionization to reduce matrix effects. The method expands the list of compounds capable of being monitored in blood following ayahuasca administration while providing a simplified approach to their analysis. The method has adequate sensitivity, specificity and reproducibility to make it useful for clinical research with ayahuasca.

Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine.

Ayahuasca is an Amazonian psychotropic plant tea combining the 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting ß-carboline alkaloids that render DMT orally active. The tea, obtained from Banisteriopsis caapi and Psychotria viridis, has traditionally been used for religious, ritual, and medicinal purposes by the indigenous peoples of the region. More recently, the syncretistic religious use of ayahuasca has expanded to the United States and Europe. Here we conducted a double-blind randomized crossover clinical trial to investigate the physiological impact of ayahuasca in terms of autonomic, neuroendocrine, and immunomodulatory effects. An oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight) was compared versus a placebo and versus a positive control (20 mg d-amphetamine) in a group of 10 healthy volunteers. Ayahuasca led to measurable DMT plasma levels and distinct subjective and neurophysiological effects that were absent after amphetamine. Both drugs increased pupillary diameter, with ayahuasca showing milder effects. Prolactin levels were significantly increased by ayahuasca but not by amphetamine, and cortisol was increased by both, with ayahuasca leading to the higher peak values. Ayahuasca and amphetamine induced similar time-dependent modifications in lymphocyte subpopulations. Percent CD4 and CD3 were decreased, whereas natural killer cells were increased. Maximum changes occurred around 2 hours, returning to baseline levels at 24 hours. In conclusion, ayahuasca displayed moderate sympathomimetic effects, significant neuroendocrine stimulation, and a time-dependent modulatory effect on cell-mediated immunity. Future studies on the health impact of long-term ayahuasca consumption should consider the assessment of immunological status in regular users.

Gastrointestinal safety of triflusal solution in healthy volunteers: a proof of concept endoscopic study.

PURPOSE: Triflusal is an antiplatelet agent that irreversibly acetylates cyclooxygenase isoform 1 (COX-1) and therefore inhibits thromboxane biosynthesis. It was initially marketed as capsules containing 300 mg of active substance. In 2006 a new 600 mg (10 ml) oral solution form of triflusal was authorized in Spain. The primary aim of this study was to compare the gastrointestinal safety of the new triflusal oral solution with triflusal capsules in healthy volunteers. METHODS: Sixty healthy subjects were randomly assigned, in a 2.5:2.5: 1 ratio, into one of three groups, with 25 subjects receiving one bottle of triflusal oral solution (600 mg) daily, 25 subjects receiving two triflusal capsules (600 mg) once daily, and ten subjects receiving two placebo capsules once daily, respectively, during 7 consecutive days. Gastroscopy was performed at baseline before the administration of study drugs and after 4-8 h of the last dose of study drugs. Effects on the esophagus, stomach, and duodenum were measured in accordance with a modified Lanza scale. RESULTS: No differences between groups were detected at baseline. After treatment, median global scores in the placebo, triflusal solution, and triflusal capsules groups were, respectively, 0, 1, and 3 (p = 0.003 for comparison between placebo and triflusal capsules and p = 0.042 for comparison between triflusal solution and triflusal capsules). There were no significant differences between the scores on the triflusal solution and placebo groups. All treatments were well tolerated. CONCLUSION: In healthy subjects, triflusal solution induced less endoscopically apparent gastrointestinal mucosal damage than triflusal capsules and did not induce more damage than the placebo in healthy volunteers.

Methodology for and the determination of the major constituents and metabolites of the Amazonian botanical medicine ayahuasca in human urine.

Ayahuasca, also known as caapi or yage among various South American groups, holds a highly esteemed and millennia-old position in these cultures' medical and religious pharmacopeia. There is now an increasing interest in the potential for modern medical applications of ayahuasca, as well as concerns regarding its increasing potential for abuse. Toxicological and clinical research to address these issues will require information regarding its metabolism and clearance. Thus, a rapid, sensitive and specific method for characterization and quantitation of the major constituents and of the metabolites of ayahuasca in urine is needed. The present research provides a protocol for conducting such analyses. The characteristics of the method, conducted by sample dilution and using HPLC-electrospray ionization (ESI)-selected reaction monitoring (SRM)-tandem mass spectrometry, are presented. The application of the analytical protocol to urine samples collected from three individuals that were administered ayahuasca has also been demonstrated. The data show that the major metabolite of the hallucinogenic component of ayahuasca, N,N-dimethyltryptamine (DMT), is the corresponding N-oxide, the first time this metabolite has been described in in vivo studies in humans. Further, very little DMT was detected in urine, despite the inhibition of monoamine oxidase afforded by the presence of the harmala alkaloids in ayahuasca. The major harmala alkaloid excreted was tetrahydroharmine. Other excretion products and metabolites were also identified and quantified. The method described would be suitable for use in further toxicological and clinical research on ayahuasca.

Drug effect on EEG connectivity assessed by linear and nonlinear couplings.

Quantitative analysis of human electroencephalogram (EEG) is a valuable method for evaluating psychopharmacological agents. Although the effects of different drug classes on EEG spectra are already known, interactions between brain locations remain unclear. In this work, cross mutual information function and appropriate surrogate data were applied to assess linear and nonlinear couplings between EEG signals. The main goal was to evaluate the pharmacological effects of alprazolam on brain connectivity during wakefulness in healthy volunteers using a cross-over, placebo-controlled design. Eighty-five pairs of EEG leads were selected for the analysis, and connectivity was evaluated inside anterior, central, and posterior zones of the scalp. Connectivity between these zones and interhemispheric connectivity were also measured. Results showed that alprazolam induced significant changes in EEG connectivity in terms of information transfer in comparison with placebo. Trends were opposite depending on the statistical characteristics: decreases in linear connectivity and increases in nonlinear couplings. These effects were generally spread over the entire scalp. Linear changes were negatively correlated, and nonlinear changes were positively correlated with drug plasma concentrations; the latter showed higher correlation coefficients. The use of both linear and nonlinear approaches revealed the importance of assessing changes in EEG connectivity as this can provide interesting information about psychopharmacological effects.

Exposures associated with making or playing with viscoelastic polymer toys known as Slime: a retrospective case series from French Poison Control Centres.

Context: Slime is a slow-flowing material with viscoelastic properties which is attractive to children. Its preparation is based on the crosslinking of polyvinyl alcohol, polyvinyl acetate or starch with boric acid.Objectives: The goal of this study was to describe the adverse effects of Slime.Materials and methods: This is a descriptive retrospective study of cases of exposure reported to French Poison Control Centres between January 2014 and May 2018. The following parameters were used: age and sex, date and circumstances of exposure, symptoms and severity.Results: Two hundred and eight (208) cases of exposure were recorded, 93 cases happened in 2017, and 88 cases in the first four and a half months of 2018. The average age was of 8 years old; 190 patients were younger than 15. Fifty-seven percent (57%) were female. Regarding routes of exposure, 168 were oral, 30 cutaneous, eight ocular, one inhalation and one ear exposure. Eighty-two (82) patients were symptomatic, including 81 cases of low severity and one of average severity (keratitis). All cases lead to recovery.Conclusion: No significant adverse health effects are expected to develop if only small amounts are swallowed; making Slime with home ingredients is a potential cause of boric acid exposure that must be supervised by adults.

Influence of ocular filtering in EEG data on the assessment of drug-induced effects on the brain.

Ocular artifacts in EEG signals affect the interpretation of clinical study results. The aim of this study was to assess the influence of automatic ocular filtering procedures in the conclusions drawn from a pharmaco-EEG trial. Regression analysis, gold standard, and blind source separation (BSS), Second Order Blind Identification algorithm, ocular filtering procedures were compared using time, frequency, topographic and tomographic brain mapping approaches and pharmacokinetic-pharmacodynamic (PK-PD) relationships. Data consisted of EEGs obtained from 20 volunteers who received single oral doses of haloperidol 3 mg, risperidone 1 mg, olanzapine 5 mg and placebo in a randomized cross-over double-blind design. Although the BSS-based technique preserved brain activity more than regression analysis in anterior leads, in general, topographic significance probability maps globally showed similar results with both methods for most spectral variables. However, different results were obtained when using whole multi-channel information for studying drug effects in the brain: (i) higher correlations between PK and PD time courses showing that BSS allowed estimation of spectral variables more accurately related to drug effects and (ii) larger and more symmetric drug related tomographic LORETA maps showing that BSS led to results that were more neurophysiopharmacologically sound. Definitely, the BSS-based procedure is an effective and efficient preprocessing method to remove ocular artifacts from EEG data. The selection of the ocular filtering procedure could determine different results whose impact depends on the evaluating tool applied to analyze the pharmaco-EEG data.

Daytime Ayahuasca administration modulates REM and slow-wave sleep in healthy volunteers.

OBJECTIVES: Ayahuasca is a traditional South American psychoactive beverage and the central sacrament of Brazilian-based religious groups, with followers in Europe and the United States. The tea contains the psychedelic indole N,N-dimethyltryptamine (DMT) and beta-carboline alkaloids with monoamine oxidase-inhibiting properties that render DMT orally active. DMT interacts with serotonergic neurotransmission acting as a partial agonist at 5-HT(1A) and 5-HT(2A/2C) receptor sites. Given the role played by serotonin in the regulation of the sleep/wake cycle, we investigated the effects of daytime ayahuasca consumption in sleep parameters. MEASUREMENTS AND RESULTS: Subjective sleep quality, polysomnography (PSG), and spectral analysis were assessed in a group of 22 healthy male volunteers after the administration of a placebo, an ayahuasca dose equivalent to 1 mg DMT kg(-1) body weight, and 20 mg d-amphetamine, a proaminergic drug, as a positive control. Results show that ayahuasca did not induce any subjectively perceived deterioration of sleep quality or PSG-measured disruptions of sleep initiation or maintenance, in contrast with d-amphetamine, which delayed sleep initiation, disrupted sleep maintenance, induced a predominance of 'light' vs 'deep' sleep and significantly impaired subjective sleep quality. PSG analysis also showed that similarly to d-amphetamine, ayahuasca inhibits rapid eye movement (REM) sleep, decreasing its duration, both in absolute values and as a percentage of total sleep time, and shows a trend increase in its onset latency. Spectral analysis showed that d-amphetamine and ayahuasca increased power in the high frequency range, mainly during stage 2. Remarkably, whereas slow-wave sleep (SWS) power in the first night cycle, an indicator of sleep pressure, was decreased by d-amphetamine, ayahuasca enhanced power in this frequency band. CONCLUSIONS: Results show that daytime serotonergic psychedelic drug administration leads to measurable changes in PSG and sleep power spectrum and suggest an interaction between these drugs and brain circuits modulating REM and SWS.

A comparative study of automatic techniques for ocular artifact reduction in spontaneous EEG signals based on clinical target variables: a simulation case.

Eye movement artifacts represent a critical issue for quantitative electroencephalography (EEG) analysis and a number of mathematical approaches have been proposed to reduce their contribution in EEG recordings. The aim of this paper was to objectively and quantitatively evaluate the performance of ocular filtering methods with respect to spectral target variables widely used in clinical and functional EEG studies. In particular the following methods were applied: regression analysis and some blind source separation (BSS) techniques based on second-order statistics (PCA, AMUSE and SOBI) and on higher-order statistics (JADE, INFOMAX and FASTICA). Considering blind source decomposition methods, a completely automatic procedure of BSS based on logical rules related to spectral and topographical information was proposed in order to identify the components related to ocular interference. The automatic procedure was applied in different montages of simulated EEG and electrooculography (EOG) recordings: a full montage with 19 EEG and 2 EOG channels, a reduced one with only 6 EEG leads and a third one where EOG channels were not available. Time and frequency results in all of them indicated that AMUSE and SOBI algorithms preserved and recovered more brain activity than the other methods mainly at anterior regions. In the case of full montage: (i) errors were lower than 5% for all spectral variables at anterior sites; and (ii) the highest improvement in the signal-to-artifact (SAR) ratio was obtained up to 40dB at these anterior sites. Finally, we concluded that second-order BSS-based algorithms (AMUSE and SOBI) provided an effective technique for eye movement removal even when EOG recordings were not available or when data length was short.

Noradrenergic stimulation enhances human action monitoring.

Noradrenergic neurotransmission has been associated with the modulation of higher cognitive functions mediated by the prefrontal cortex. In the present study, the impact of noradrenergic stimulation on the human action-monitoring system, as indexed by event-related brain potentials, was examined. After the administration of a placebo or the selective alpha2-adrenoceptor antagonist yohimbine, which stimulates firing in the locus ceruleus and noradrenaline release, electroencephalograpic recordings were obtained from healthy volunteers performing a letter flanker task. Yohimbine led to an increase in the amplitude of the error-related negativity in conjunction with a significant reduction of action errors. Reaction times were unchanged, and the drug did not modify the N2 in congruent versus incongruent trials, a measure of preresponse conflict, or posterror adjustments as measured by posterror slowing of reaction time. The present findings suggest that the locus ceruleus-noradrenaline system exerts a rather specific effect on human action monitoring.

Increased frontal and paralimbic activation following ayahuasca, the pan-Amazonian inebriant.

RATIONALE: Ayahuasca is a South American psychoactive plant tea which contains the serotonergic psychedelic N,N-dimethyltryptamine (DMT) and monoamine-oxidase inhibitors that render DMT orally active. Previous investigations with ayahuasca have highlighted a psychotropic effect profile characterized by enhanced introspective attention, with individuals reporting altered somatic perceptions and intense emotional modifications, frequently accompanied by visual imagery. Despite recent advances in the study of ayahuasca pharmacology, the neural correlates of acute ayahuasca intoxication remain largely unknown. OBJECTIVES: To investigate the effects of ayahuasca administration on regional cerebral blood flow. METHODS: Fifteen male volunteers with prior experience in the use of psychedelics received a single oral dose of encapsulated freeze-dried ayahuasca equivalent to 1.0 mg DMT/kg body weight and a placebo in a randomized double-blind clinical trial. Regional cerebral blood flow was measured 100-110 min after drug administration by means of single photon emission tomography (SPECT). RESULTS: Ayahuasca administration led to significant activation of frontal and paralimbic brain regions. Increased blood perfusion was observed bilaterally in the anterior insula, with greater intensity in the right hemisphere, and in the anterior cingulate/frontomedial cortex of the right hemisphere, areas previously implicated in somatic awareness, subjective feeling states, and emotional arousal. Additional increases were observed in the left amygdala/parahippocampal gyrus, a structure also involved in emotional arousal. CONCLUSIONS: The present results suggest that ayahuasca interacts with neural systems that are central to interoception and emotional processing and point to a modulatory role of serotonergic neurotransmission in these processes.

Pattern of use and subjective effects of Salvia divinorum among recreational users.

BACKGROUND: Salvia divinorum is a member of the Lamiaceae family and contains the psychotropic diterpene and kappa-opioid receptor agonist salvinorin-A. Originally a shamanic inebriant used by the Mexican Mazatec Indians, the plant and its preparations are becoming increasingly popular among non-traditional users. METHODS: Demographic data and information on pattern of use and subjective effects were obtained by means of self-report questionnaires from a sample of 32 recreational users of salvia and other psychedelics. RESULTS: Involvement with salvia appeared to be a recent phenomenon. Smoking the extract was the preferred form of administration. Subjective effects were described as intense but short-lived, appearing in less than 1 min and lasting 15 min or less. They included psychedelic-like changes in visual perception, mood and somatic sensations, and importantly, a highly modified perception of external reality and the self, leading to a decreased ability to interact with oneself or with one's surroundings. CONCLUSIONS: Although some aspects of the subjective effects reported were similar to high doses of classical psychedelics with serotonin-2A receptor agonist activity, the intense derealization and impairment reported appear to be a characteristic of salvia. The observed simultaneous high scores on the LSD and PCAG subscales of the Addiction Research Center Inventory (ARCI) have been previously reported for other kappa-opioid agonists, and support kappa receptor activation as the probable pharmacologic mechanism underlying the modified state of awareness induced by salvia.

A neurophysiological study of the detrimental effects of alprazolam on human action monitoring.

In order to adapt their behavior to different unexpected situations, humans need to be able to monitor their performance and detect and correct errors. Benzodiazepines have long been shown to impair performance in humans, but the performance-related neurophysiological processes targeted by these drugs remain largely unknown. In the present article, we assessed the impact of alprazolam administration on relevant aspects of action monitoring, i.e., the monitoring of response conflict and the detection and correction of errors by means of neurophysiological measures. Multichannel event-related brain potentials (ERPs) were recorded to assess the impact of the benzodiazepine alprazolam (0.25 mg and 1.00 mg) on action monitoring and motor preparation in a group of twelve healthy male volunteers who participated in a double-blind cross-over placebo-controlled clinical trial involving a letter flanker task. Error detection was evaluated using the error-related negativity (ERN); response conflict on correct trials was measured by means of the N2 amplitude difference between congruent and incongruent trials; motor preparation was assessed by means of the lateralized readiness potentials (LRPs); and post-error adjustments were assessed by measuring post-error slowing in reaction time. Alprazolam significantly reduced the amplitude of the ERN and the number of corrective responses and increased reaction time and LRP latencies. The drug had no effect on amplitude differences in the N2 component between congruent and incongruent trials or on post-error slowing. Thus, alprazolam was shown to affect brain correlates of error detection (ERN) and motor preparation (LRPs), while it did not disturb conflict monitoring on correct trials (N2) or post-error adjustments of behavior.

Bringing ayahuasca to the clinical research laboratory.

Since the winter of 1999, the authors and their research team have been conducting clinical studies involving the administration of ayahuasca to healthy volunteers. The rationale for conducting this kind of research is twofold. First, the growing interest of many individuals for traditional indigenous practices involving the ingestion of natural psychotropic drugs such as ayahuasca demands the systematic study of their pharmacological profiles in the target species, i.e., human beings. The complex nature of ayahuasca brews combining a large number of pharmacologically active compounds requires that research be carried out to establish the safety and overall pharmacological profile of these products. Second, the authors believe that the study of psychedelics in general calls for renewed attention. Although the molecular and electrophysiological level effects of these drugs are relatively well characterized, current knowledge of the mechanisms by which these compounds modify the higher order cognitive processes in the way they do is still incomplete, to say the least. The present article describes the development of the research effort carried out at the Autonomous University of Barcelona, commenting on several methodological aspects and reviewing the basic clinical findings. It also describes the research currently underway in our laboratory, and briefly comments on two new studies we plan to undertake in order to further our knowledge of the pharmacology of ayahuasca.

Effects of ayahuasca on sensory and sensorimotor gating in humans as measured by P50 suppression and prepulse inhibition of the startle reflex, respectively.

RATIONALE: Ayahuasca, a South American psychotropic plant tea, combines the psychedelic agent and 5-HT(2A/2C) agonist N, N-dimethyltryptamine (DMT) with beta-carboline alkaloids showing monoamine oxidase-inhibiting properties. Current human research with psychedelics and entactogens has explored the possibility that drugs displaying agonist activity at the 5-HT(2A/2C) sites temporally disrupt inhibitory neural mechanisms thought to intervene in the normal filtering of information. Suppression of the P50 auditory evoked potential (AEP) and prepulse inhibition of startle (PPI) are considered operational measures of sensory (P50 suppression) and sensorimotor (PPI) gating. Contrary to findings in lower animals, unexpected increases in sensorimotor gating have been found in humans following the administration of the serotonergic psychedelic psilocybin and the serotonin releaser 3,4-methylenedioxymethamphetamine (MDMA). In addition, to our knowledge P50 suppression has not been assessed previously in humans following the administration of a 5-HT(2A/2C) agonist. OBJECTIVES: To assess the effects of the acute administration of ayahuasca on P50 suppression and PPI in humans, in order to evaluate the drug's modulatory actions on these measures of sensory and sensorimotor gating. METHODS: Eighteen healthy volunteers with prior experience of psychedelic drug use participated in a clinical trial in which placebo or ayahuasca doses (0.6 mg and 0.85 mg DMT/kg body weight) were administered according to a double-blind, cross-over balanced design. P50 and startle reflex (pulse-alone and 60 ms, 120 ms, 240 ms and 2000 ms prepulse-to-pulse intervals) recordings were undertaken at 1.5 h and 2 h after drug intake, respectively. RESULTS: Ayahuasca produced diverging effects on each of the two gating measures evaluated. Whereas significant dose-dependent reductions of P50 suppression were observed after ayahuasca, no significant effects were found on the startle response, its habituation rate, or on PPI at any of the prepulse-to-pulse intervals studied. CONCLUSION: The present findings indicate, at the doses tested, a decremental effect of ayahuasca on sensory gating, as measured by P50 suppression, and no distinct effects on sensorimotor gating, as measured by PPI.

Determination of N,N-dimethyltryptamine and beta-carboline alkaloids in human plasma following oral administration of Ayahuasca.

Ayahuasca is a South American psychotropic beverage prepared from plants native to the Amazon River Basin. It combines the hallucinogenic agent and 5-HT(2A/2C) agonist N,N-dimethyltryptamine (DMT) with beta-carboline alkaloids showing monoamine oxidase-inhibiting properties. In the present paper, an analytical methodology for the plasma quantification of the four main alkaloids present in ayahuasca plus two major metabolites is described. DMT was extracted by liquid-liquid extraction with n-pentane and quantified by gas chromatography with nitrogen-phosphorus detection. Recovery was 74%, and precision and accuracy were better than 9.9%. The limit of quantification (LOQ) was 1.6 ng/ml. Harmine, harmaline, and tetrahydroharmine (THH), the three main beta-carbolines present in ayahuasca, and harmol and harmalol (O-demethylation metabolites of harmine and harmaline, respectively) were measured in plasma by means of high-performance liquid chromatography (HPLC) with fluorescence detection. Sample preparation was accomplished by solid-phase extraction, which facilitated the automation of the process. All five beta-carbolines were measured using a single detector by switching wavelengths. Separation of harmol and harmalol required only slight changes in the chromatographic conditions. Method validation demonstrated good recoveries, above 87%, and accuracy and precision better than 13.4%. The LOQ was 0.5 ng/ml for harmine, 0.3 ng/ml for harmaline, 1.0 ng/ml for THH, and 0.3 ng/ml for harmol and harmalol. Good linearity was observed in the concentration ranges evaluated for DMT (2.5-50 ng/ml) and the beta-carbolines (0.3-100 ng/ml). The gas chromatography and HPLC methods described allowed adequate characterization of the pharmacokinetics of the four main alkaloids present in ayahuasca, and also of two major beta-carboline metabolites not previously described in the literature.

[Clonidine premedication and isoflurane anesthesia to reduce bleeding in otologic surgery]. / Clonidine en prémédication et anesthésie à l'isoflurane pour la réduction du saignement en chirurgie otologique.

Seventy-seven ASA 1 patients scheduled for ear surgery were premedicated orally, 90 min before anaesthesia. They were randomly assigned to two groups, according to the drug used: hydroxyzine alone (group T, n = 39) or combined with clonidine (4.9 +/- 0.3 micrograms.kg-1) (group C, n = 38). Anaesthesia was induced with midazolam (0.3 mg.kg-1) and alfentanil (30 micrograms.kg-1). Ventilation was controlled with a 50/50 v/v mixture of oxygen and nitrous oxide (FETCO2 = 4 to 4.5%), and anaesthesia was maintained with repeated injections of alfentanil (15 micrograms.kg-1 at the start of surgery, and then every 15 min) and with isoflurane (mean end-expiratory concentration 0.6 +/- 0.3 vol %). Surgical bleeding was assessed every ten minutes on a numerical scale with four values. A bloodless surgical field was obtained by adjusting the isoflurane concentration up to 2 MAC, and by using a trinitrine infusion as required. Cardiovascular monitoring included an electrocardioscope and automatic blood pressure measurements. Before induction of anaesthesia, the blood pressure was lower in group C (84.7 +/- 11.2 vs. 95.9 +/- 106 mmHg) (p less than 0.001); the difference in heart rate was not significant (65 +/- 15 vs. 70.6 +/- 14 b.min-1). Moderate stable intraoperative hypotension was obtained in both groups. However, mean arterial blood pressure (C:65.8 +/- 7.8 mmHg; T: 73 +/- 9.4 mmHg) and heart rate (C: 53.4 +/- 6.8 b.min-1; T: 60.4 +/- 8 b.min-1) were significantly lower in the patients premedicated with clonidine (p less than 0.001). There were more periods of sinus bradycardia (heart rate less than or equal to 50 b.min-1), mostly seen before the beginning of surgery, in group C patients (p less than 0.01); atropine was also required more often (when the heart rate was less than or equal to 40 b.min-1) in this group of patients (NS). The comparative assessment of surgical field quality was in favour of group C (no troublesome bleeding) as opposed to the control group (16% troublesome bleeding); there were also more bloodless surgical fields in the former group (73.7% vs. 48.7% in group T, p less than 0.05). This study therefore demonstrated that clonidine premedication before anaesthesia with isoflurane was helpful in decreasing bleeding during ear surgery.

[Analgesic and respiratory effects of nalbuphine during the immediate postoperative period in thoracotomy]. / Effets analgésique et ventilatoire de la nalbuphine dans les suites immédiates d'une thoracotomie.

As most patients undergoing pulmonary surgery by postero-lateral thoracotomy have decreased preoperative pulmonary function, efficient postoperative analgesia is mandatory. Nalbuphine, a new agonist-antagonist opioid analgesic, and nefopam were compared in a double blind trial involving 60 patients. Intravenous injections of 0.3 mg.kg-1 of either drug were started when the patient evaluated his pain as being above 60 mm on a visual scale graduated from 0 to 100 mm. Repeated injections were carried out at the same dose, at the patient's request, after a minimal interval of 3 h for nalbuphine, and 6 h for nefopam. Analgesia was assessed by the visual scale, and by the patient's verbal appraisal. The respiratory and cardiovascular repercussions were evaluated clinically, and by monitoring breathing rate, blood gases, systolic and diastolic blood pressures, heart rate, and consciousness. Nalbuphine provided a convenient analgesia to all patients whereas analgesia with nefopam was insufficient in 15 out of 30 patients. No significant respiratory depression with either drug occurred. Nefopam led to a 30% increase in heart rate for one hour (p less than 0.01). Whereas patients given nalbuphine were more drowsy, although easily aroused, (p less than 0.001), nefopam was responsible for adverse effects (sweating, nausea, tachycardia with pallor, vertigo, malaise) requiring the exclusion of 7 patients from the study. Nalbuphine, although not ideal, would therefore seem to be a better analgesic than nefopam in thoracotomy patients.

[Comparison of the action kinetics of alcuronium and vecuronium by electromyographic monitoring]. / Comparaison de la cinétique d'action de l'alcuronium et du vécuronium par monitorage électromyographique.

Twenty-eight ASA I or ASA II adults undergoing microsurgery were anaesthetized according to a standard protocol using droperidol, phenoperidine and thiopentone followed by enflurane. The patients were randomly assigned to two homogeneous groups: the first group (n = 14) received 0.2 mg.kg-1 alcuronium, whereas the second group (n = 14) received 0.08 mg.kg-1 vecuronium. There was no reinjection of either drug and curarization tapered off spontaneously. Neuromuscular monitoring was begun once anaesthesia was stable and after intentional isovolaemic haemodilution. The type of stimulus used was the train-of-four, delivered by a Relaxograph monitor to the ulnar nerve. Muscle response was measured at the hypothenar eminence. The kinetic study considered the time interval required between the injection of the muscle relaxant and the appearance of the minimal value of the twitch (first response of the train-of-four = T1min). The times to recovery of the twitch height to 25, 75 and 100% of the reference value (T1/T0) and of the fourth response of the train-of-four to 25 and 75% of the ratio (T4/T1) were also recorded. Finally, the recovery indexes represented by the times required for T1/T0 and T4/T1 to rise from 25% to 75% respectively were studied. The maximal twitch height inhibition was significantly greater (p less than 0.001) in the vecuronium group (T1min = 0.36 +/- 1.33%) than in the alcuronium group (T1min = 4.36 +/- 5.08%); it occurred significantly more quickly (p less than 0.001) with vecuronium (139 +/- 48 s) than with alcuronium (316 +/- 133 s).(ABSTRACT TRUNCATED AT 250 WORDS)