Spinal cord-evoked potentials and muscle responses evoked by transcranial magnetic stimulation in 10 awake human subjects.
Transcranial magnetic stimulation (TCMS) causes leg muscle contractions, but the neural structures in the brain that are activated by TCMS and their relationship to these leg muscle responses are not clearly understood. To elucidate this, we concomitantly recorded leg muscle responses and thoracic spinal cord-evoked potentials (SCEPs) after TCMS for the first time in 10 awake, neurologically intact human subjects. In this report we provide evidence of direct and indirect activation of corticospinal neurons after TCMS. In three subjects, SCEP threshold (T) stimulus intensities recruited both the D wave (direct activation of corticospinal neurons) and the first I wave (I1, indirect activation of corticospinal neurons). In one subject, the D, I1, and I2 waves were recruited simultaneously, and in another subject, the I1 and I2 waves were recruited simultaneously. In the remaining five subjects, only the I1 wave was recruited first. More waves were recruited as the stimulus intensity increased. The presence of D and I waves in all subjects at low stimulus intensities verified that TCMS directly and indirectly activated corticospinal neurons supplying the lower extremities. Leg muscle responses were usually contingent on the SCEP containing at least four waves (D, I1, I2, and I3). (+info)
Increased reading speed for stories presented during general anesthesia.
BACKGROUND: In the absence of explicit memories such as the recall and recognition of intraoperative events, memory of auditory information played during general anesthesia has been demonstrated with several tests of implicit memory. In contrast to explicit memory, which requires conscious recollection, implicit memory does not require recollection of previous experiences and is evidenced by a priming effect on task performance. The authors evaluated the effect of a standardized anesthetic technique on implicit memory, first using a word stem completion task, and then a reading speed task in a subsequent study. METHODS: While undergoing lumbar disc surgery, 60 patients were exposed to auditory materials via headphones in two successive experiments. A balanced intravenous technique with propofol and alfentanil infusions and a nitrous oxide-oxygen mixture was used to maintain adequate anesthesia. In the first experiment, 30 patients were exposed randomly to one of the two lists of 34 repeated German nouns; in the second experiment, 30 patients were exposed to one of two tapes containing two short stories. Thirty control patients for each experiment heard the tapes without receiving anesthesia. All patients were tested for implicit memory 6-8 h later: A word stem completion task for the words and a reading speed task for the stories were used as measures of implicit memory. RESULTS: The control group completed the word stems significantly more often with the words that they had heard previously, but no such effect was found in the anesthetized group. However, both the control and patient groups showed a decreased reading time of about 40 ms per word for the previously presented stories compared with the new stories. The patients had no explicit memory of intraoperative events. CONCLUSIONS: Implicit memory was demonstrated after anesthesia by the reading speed task but not by the word stem completion task. Some methodologic aspects, such as using low frequency words or varying study and test modalities, may account for the negative results of the word stem completion task. Another explanation is that anesthesia with propofol, alfentanil, and nitrous oxide suppressed the word priming but not the reading speed measure of implicit memory. The reading speed paradigm seems to provide a stable and reliable measurement of implicit memory. (+info)
Description of local adaptation of national guidelines and of active feedback for rationalising preoperative screening in patients at low risk from anaesthetics in a French university hospital.
OBJECTIVE: To describe the effect of local adaptation of national guidelines combined with active feedback and organisational analysis on the ordering of preoperative investigations for patients at low risk from anaesthetics. DESIGN: Assessment of preoperative tests ordered over one month, before and after local adaptation of guidelines and feedback of results, combined with an organisational analysis. SETTING: Motivated anaesthetists in 15 surgical wards of Bordeaux University Hospital, Region Aquitain, France. SUBJECTS: 42 anaesthetists, 60 surgeons, and their teams. MAIN OUTCOME MEASURES: Number and type of preoperative tests ordered in June 1993 and 1994, and the estimated savings. RESULTS: Of 536 patients at low risk from anaesthetics studied in 1993 before the intervention 80% had at least one preoperative test. Most (70%) tests were ordered by anaesthetists. Twice the number of preoperative tests were ordered than recommended by national guidelines. Organisational analysis indicated lack of organised consultations and communication within teams. Changes implemented included scheduling of anaesthetic consultations; regular formal multidisciplinary meetings for all staff; preoperative ordering decision charts. Of 516 low risk patients studied in 1994 after the intervention only 48% had one or more preoperative tests ordered (p < 0.05). Estimated mean (SD) saving for one year if changes were applied to all patients at low risk from anaesthesia in the hospital 3.04 (1.23) mFF. CONCLUSIONS: A sharp decrease in tests ordered in low risk patients was found. The likely cause was the package of changes that included local adaptation of national guidelines, feedback, and organisational change. (+info)
Drug-induced heart failure.
Heart failure is a clinical syndrome that is predominantly caused by cardiovascular disorders such as coronary heart disease and hypertension. However, several classes of drugs may induce heart failure in patients without concurrent cardiovascular disease or may precipitate the occurrence of heart failure in patients with preexisting left ventricular impairment. We reviewed the literature on drug-induced heart failure, using the MEDLINE database and lateral references. Successively, we discuss the potential role in the occurrence of heart failure of cytostatics, immunomodulating drugs, antidepressants, calcium channel blocking agents, nonsteroidal anti-inflammatory drugs, antiarrhythmics, beta-adrenoceptor blocking agents, anesthetics and some miscellaneous agents. Drug-induced heart failure may play a role in only a minority of the patients presenting with heart failure. Nevertheless, drug-induced heart failure should be regarded as a potentially preventable cause of heart failure, although sometimes other priorities do not offer therapeutic alternatives (e.g., anthracycline-induced cardiomyopathy). The awareness of clinicians of potential adverse effects on cardiac performance by several classes of drugs, particularly in patients with preexisting ventricular dysfunction, may contribute to timely diagnosis and prevention of drug-induced heart failure. (+info)
Characterization of the electrophysiological and pharmacological effects of 4-iodo-2,6-diisopropylphenol, a propofol analogue devoid of sedative-anaesthetic properties.
1. Several derivatives and analogues of the general anaesthetic 2,6-diisopropylphenol (propofol) have been recently synthesised with the aim of exploring the structure-activity relationships. 2. In the present study, the effects of one such compound, 4-iodo-2,6-diisopropylphenol (4-I-Pro), on gamma-aminobutyric acid type A (GABA(A)) receptors in vitro were compared with its in vivo effects in rodents. Human GABA(A) receptors were expressed in Xenopus oocytes, and the actions of 4-I-Pro on receptor function were compared with those of propofol by two-electrode voltage-clamp recording. 3. Similar to propofol, 4-I-Pro directly activated Cl- currents in the absence of GABA at all combinations of receptor subunits tested. However, the efficacy of 4-I-Pro in inducing direct activation of alpha1beta2gamma2S receptors was markedly less than that of propofol. 4. Similarly to propofol, 4-I-Pro potentiated in a concentration-dependent manner GABA-evoked Cl- currents measured at different GABA(A) receptor constructs. 5. As expected, intraperitoneal injection of propofol induced sedation, ataxia, and loss of the righting reflex in rats. In contrast, administration of 4-I-Pro failed to produce any of these behavioural effects. 6. Administration of 4-I-Pro to rats reduced in a dose-dependent manner the incidence of tonic-clonic seizures induced by pentylenetetrazol and induced an anticonflict effect as measured in the Vogel test. 7. Microdialysis revealed that, like propofol, administration of 4-I-Pro reduced acetylcholine release in the hippocampus of freely moving rats. 8. These results demonstrate that para-substitution of the phenol ring of propofol with iodine yields a compound that exhibits anticonvulsant and anticonflict effects, but is devoid of sedative-hypnotic and anaesthetic properties. Thus, 4-I-Pro possesses pharmacological characteristics more similar to anxiolytic and anticonvulsant drugs than to general anaesthetics. (+info)
Women emerge from general anesthesia with propofol/alfentanil/nitrous oxide faster than men.
BACKGROUND: Recovery from general anesthesia is governed by pharmacodynamic and pharmacokinetic factors. Gender has not previously been recognized as a factor influencing the time to emergence from general anesthesia. METHODS: This multicenter study was originally designed to measure the effects of the bispectral index on intraoperative anesthetic management and patient recovery. We compared the wake-up and recovery times of 274 adults after propofol/alfentanil/nitrous oxide anesthesia. Patients were randomly assigned to have the titration of propofol performed with or without the use of bispectral index monitoring. Specific guidelines were given for the titration of drugs. The aim in all cases was to provide a safe anesthetic with the fastest possible recovery. RESULTS: There was a significant reduction in propofol dose, time to eye opening, and response to verbal command when the anesthetic was titrated using the bispectral index. Unexpectedly, gender proved to be a highly significant independent predictor for recovery time. Women woke significantly faster than men: the time from end of anesthesia to eye opening was 7.05 versus 11.22 min, P < 0.05, and response to verbal command was 8.12 versus 11.67 min, P < 0.05. These differences were significant at all four study sites and in each treatment group. Men consistently had prolonged recovery times compared to women, P < 0.001. There was no difference in the dose of anesthetic used between gender. CONCLUSIONS: Gender appears to be an important variable in recovery from general anesthesia. These findings may explain the increased reported incidence of awareness in women (three times more frequent) and support the need to include gender as a variable in pharmacokinetic and pharmacodynamic studies of anesthetic drugs. (+info)
Ethanol directly depresses AMPA and NMDA glutamate currents in spinal cord motor neurons independent of actions on GABAA or glycine receptors.
Ethanol is a general anesthetic agent as defined by abolition of movement in response to noxious stimulation. This anesthetic endpoint is due to spinal anesthetic actions. This study was designed to test the hypothesis that ethanol acts directly on motor neurons to inhibit excitatory synaptic transmission at glutamate receptors. Whole cell recordings were made in visually identified motor neurons in spinal cord slices from 14- to 23-day-old rats. Currents were evoked by stimulating a dorsal root fragment or by brief pulses of glutamate. Ethanol at general anesthetic concentrations (50-200 mM) depressed both responses. Ethanol also depressed glutamate-evoked responses in the presence of tetrodotoxin (300 nM), showing that its actions are postsynaptic. Block of inhibitory gamma-aminobutyric acidA and glycine receptors by bicuculline (50 microM) and strychnine (5 microM), respectively, did not significantly reduce the effects of ethanol on glutamate currents. Ethanol also depressed glutamate-evoked currents when the inhibitory receptors were blocked and either D, L-2-amino-5-phosphonopentanoic acid (40 microM) or 6-cyano-7-nitroquinoxaline-2,3-dione disodium (10 microM) were applied to block N-methyl-D-aspartate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors, respectively. The results show that ethanol exerts direct depressant effects on both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate glutamate currents in motor neurons. Enhancement of gamma-aminobutyric acidA and glycine inhibition is not required for this effect. Direct depression of glutamatergic excitatory transmission by a postsynaptic action on motor neurons thus may contribute to general anesthesia as defined by immobility in response to a noxious stimulus. (+info)
Alphaxalone activates a Cl- conductance independent of GABAA receptors in cultured embryonic human dorsal root ganglion neurons.
Whole cell and cell-attached patch-clamp techniques characterized the neurosteroid anesthetic alphaxalone's (5alpha-pregnane-3alpha-ol-11,20-dione) effects on GABAA receptors and on Cl- currents in cultured embryonic (5- to 8-wk old) human dorsal root ganglion neurons. Alphaxalone applied by pressure pulses from closely positioned micropipettes failed to potentiate the inward Cl- currents produced by application of GABA. In the absence of GABA, alphaxalone (0.1-5.0 microM) directly evoked inward currents in all dorsal root ganglion neurons voltage-clamped at negative membrane potentials. The amplitude of the current was directly proportional to the concentration of alphaxalone (Hill coefficient 1.3 +/- 0.15). The alphaxalone-induced whole cell current was carried largely by Cl- ions. Its reversal potential was close to the theoretical Cl- equilibrium potential, changing with a shift in the external Cl- concentration as predicted by the Nernst equation for Cl- ions. And because the alphaxalone-current was not suppressed by the competitive GABAA receptor antagonist bicuculline or by the channel blockers picrotoxin and t-butylbicyclophosphorothionate (TBPS; all at 100 microM), it did not appear to result from activation of GABAA receptors. In contrast to GABA-currents in the same neurons, the whole cell current-voltage curves produced in the presence of alphaxalone demonstrated strong inward rectification with nearly symmetrical bath and pipette Cl- concentrations. Fluctuation analysis of the membrane current variance produced by 1.0 microM alphaxalone showed that the power density spectra were best fitted to double Lorentzian functions. The elementary conductance for alphaxalone-activated Cl- channels determined by the relationship between mean amplitude of whole cell current and variance was 30 pS. Single-channel currents in cell-attached patches when the pipette solution contained 10 microM alphaxalone revealed a single conductance state with a chord conductance of approximately 29 pS. No subconductance states were seen. The current-voltage determinations for the single-channels activated by alphaxalone demonstrated a linear relationship. Mean open and shut times of single alphaxalone-activated channels were described by two exponential decay functions. Taken together, the results indicate that in embryonic human DRG neurons, micromolar concentrations of alphaxalone directly activate Cl- channels whose electrophysiological and pharmacological properties are distinct from those of Cl- channels associated with GABAA receptors. (+info)