Biomedical subjects
N Thürauf
Publications and source records attributed to N Thürauf.
Acute detoxification of opioid-addicted patients with naloxone during propofol or methohexital anesthesia: a comparison of withdrawal symptoms, neuroendocrine, metabolic, and cardiovascular patterns.
OBJECTIVE: Mu-Opioid receptor blockade during general anesthesia is a new treatment for detoxification of opioid addicted patients. We assessed catecholamine plasma concentrations, oxygen consumption, cardiovascular variables, and withdrawal symptoms after naloxone and tested the hypothesis that variables are influenced by the anesthetic administered during detoxification. DESIGN: Prospective randomized clinical study. SETTING: Intensive care unit of a university hospital and psychiatric ward. PATIENTS: Twenty-five mono-opioid addicted patients with mild to moderate systemic disease (ASA II classification) in a methadone substitution program. INTERVENTION: General anesthesia with either propofol (129+/-7 microg x kg(-1) x min(-1), mean +/- SEM) or methohexital (74+/-14 microg x kg(-1). min(-1)), mu-opioid receptor blockade by naloxone in a stepwise fashion (increasing doses of 0.4 mg, 0.8 mg, 1.6 mg, 3.2 mg, and 6.4 mg at 15 min intervals followed by 0.8 mg x hr(-1) for 24 hrs) and naltrexone 50 mg x day(-1) orally for > or =4 wks. Clonidine was started 180 mins after the first naloxone dose and its infusion rate was individually adjusted to mitigate withdrawal symptoms during weaning and after extubation. MEASUREMENTS AND MAIN RESULTS: During propofol and methohexital anesthesia, naloxone induced a 30-fold increase in epinephrine and a significant three-fold increase in norepinephrine plasma concentrations without a significant difference between groups. This increase in catecholamine plasma concentrations was associated with increased oxygen consumption and marked cardiovascular stimulation with both anesthetics, as shown by increased cardiac index, heart rate, and systolic atrial pressure whereas diastolic pressure remained unchanged. Patients receiving propofol could be extubated significantly earlier after discontinuation of the anesthetics. Although the maximum degree of withdrawal symptoms (Short Opioid Withdrawal Scale) on the day after detoxification was similar with both anesthetics, subsequent withdrawal symptoms decreased significantly more rapidly after propofol anesthesia. CONCLUSIONS: Naloxone treatment, in opioid-addicted patients, induced a marked increase in catecholamine plasma concentrations, metabolism, and cardiovascular stimulation during anesthesia with both propofol and methohexital. Although both anesthetics appear suitable for detoxification treatment, the use of propofol is associated with earlier extubation and, surprisingly, a shortened period of long-term withdrawal symptoms during detoxification.
Percutaneous dilatational tracheostomy--early results and long-term outcome of 326 critically ill patients.
OBJECTIVE: To analyze perioperative and postoperative complications and long-term sequelae following percutaneous dilatational tracheostomy (PDT). DESIGN: A prospective clinical study of patients undergoing PDT. SETTING: Seven intensive care units at a University hospital PATIENTS: 326 intensive care patients (202 male, 124 female; age: 11-95 years) with indications for tracheostomy. INTERVENTIONS: Using tracheoscopic guidance, 337 PDTs were performed according to Ciaglias' method. In 106 decannulated patients, tracheal narrowing was assessed by plain tracheal radiography. RESULTS: Two procedure-related deaths were seen (0.6%). Perioperative and postoperative complications occurred with 9.5% of the PDTs. One of 106 patients, who were followed-up for at least 6 months, showed a clinically relevant tracheal stenosis. Subclinical tracheal stenosis of at least 10% of the cross-sectioned area was recognized in 46 of 106 patients (43.4%). In the univariate analysis, the degree of stenosis was influenced by the age of the patient (p = 0.044), the duration of intubation prior to PDT (p = 0.042) and by the duration of cannulation (p = 0.006). These parameters had no statistical significance in a multiple regression model. CONCLUSION: When performed by experienced physicians, percutaneous dilatational tracheostomy under fiberoptic guidance is a safe method. The risks of early complications and of clinically relevant tracheal stenoses are low. Subclinical tracheal stenoses are found in about 40% of patients following PDT.
Profound increase in epinephrine concentration in plasma and cardiovascular stimulation after mu-opioid receptor blockade in opioid-addicted patients during barbiturate-induced anesthesia for acute detoxification.
BACKGROUND: Acute displacement of opioids from their receptors by administration of large doses of opioid antagonists during general anesthesia is a new approach for detoxification of patients addicted to opioids. The authors tested the hypothesis that mu-opioid receptor blockade by naloxone induces cardiovascular stimulation mediated by the sympathoadrenal system. METHODS: Heart rate, cardiac index, and intravascular pressures were measured in 10 patients addicted to opioids (drug history; mean +/- SD, 71 +/- 51 months) during a program of methadone substitution (96 +/- 57 mg/day). Cardiovascular variables and concentrations of catecholamine in plasma were measured in the awake state, during methohexital-induced anesthesia (dose, 74 +/- 44 microg x kg(-1) x min(-1)) before administration of naloxone, and repeatedly during the first 3 h of mu-opioid receptor blockade. Naloxone was administered initially in an intravenous dose of 0.4 mg, followed by incremental bolus doses (0.8, 1.6, 3.2, and 6.4 mg) at 15-min intervals until a total dose of 12.4 mg had been administered within 60 min; administration was then continued by infusion (0.8 mg/h). RESULTS: Concentration of epinephrine in plasma increased 30-fold (15 +/- 9 to 458 +/- 304 pg/ml), whereas concentration of norepinephrine in plasma only increased to a minor extent (76 +/- 44 to 226 +/- 58 pg/ml, P < 0.05). Cardiac index increased by 74% (2.7 +/- 0.41 to 4.7 +/- 1.7 min(-1) x m(-2)), because of increases in heart rate (89 +/- 16 to 108 +/- 17 beats/min) and stroke volume (+44%), reaching maximum 45 min after the initial injection of naloxone. In parallel, systemic vascular resistance index decreased (-40%). Systolic arterial pressure significantly increased (113 +/- 16 to 138 +/- 16 mmHg), whereas diastolic arterial pressure did not change. CONCLUSIONS: Despite barbiturate-induced anesthesia, acute mu-opioid receptor blockade in patients addicted to opioids induces profound epinephrine release and cardiovascular stimulation. These data suggest that long-term opioid receptor stimulation changes sympathoadrenal and cardiovascular function, which is acutely unmasked by mu-opioid receptor blockade. Because of the attendant cardiovascular stimulation, acute detoxification using naloxone should be performed by trained anesthesiologists or intensivists.
Dose dependent time course of the analgesic effect of a sustained-release preparation of tramadol on experimental phasic and tonic pain.
1. The aim of this study was to investigate the analgesic effect and its duration of a new sustained-release preparation of tramadol in an experimental pain model based on pain-related chemosomatosensory evoked potentials (CSSEPs) and subjective intensity estimates of painful phasic and tonic stimuli. 2. Twenty volunteers participated in a randomised, double-blind, three-fold cross-over study. Measurements were obtained before and 0.5, 1, 4, 6, and 12 h after administration of the drug (100 mg, 200 mg and placebo orally). CSSEPs were recorded after stimulation of one nostril with phasic, painful CO2 pulses. The other nostril was stimulated with a constant stream of dry air, which produced a tonic painful sensation. Subjects rated the perceived intensity of phasic and tonic stimuli via visual analogue scales. In order to test for nonspecific effects, acoustic evoked potentials (AEPs) were recorded, the spontaneous EEG was analysed in the frequency domain, the subject's vigilance was assessed in a tracking task, and the side effects of the drug were monitored. 3. The sustained-release preparation of tramadol produced a significant dose-related decrease in CSSEP amplitudes when compared with placebo. The reduction in amplitudes outlasted the observation period of 12 h, demonstrating the prolonged duration of the analgesic effect. 4. A dose-related significant decrease could be observed for the estimates of tonic pain. Similar to the decrease of amplitudes of the CSSEP, the reduction of the ratings of tonic pain outlasted the observation period of 12 h. The observed slight decrease in the estimates of phasic pain under medication did not reach a statistically significant level when compared with placebo. No significant effect could be demonstrated for the perception of the phasic and the tonic pain as determined by the McGill-Questionnaire. 5. A significant dose-related increase in the estimates of the side effects 'drowsiness', 'vertigo' and 'sickness' but not for 'tiredness' could be demonstrated.
Responses recorded from the frog olfactory epithelium after stimulation with R(+)- and S(-)-nicotine.
The aim of this study was to determine whether the olfactory system is responsible for the discriminability of the stereoisomers of nicotine. The EOG was recorded after stimulation with different concentrations of undistilled S(-)-, distilled S(-)- and distilled R(-)-nicotine separately in three groups of frogs (Xenopus laevis). The responses to all types of nicotine used in the experiments increased with increasing stimulus concentration. The responses to undistilled S(-)-nicotine were significantly lower compared to responses to distilled S(-)- and R(+)-nicotine, whereas no significant differences could be found when the purified stereoisomers of nicotine [distilled S(-)-nicotine, distilled R(+)-nicotine] were compared. Control measurements of time course and peak concentration employing a UV-detection method demonstrated that the differences between distilled and undistilled S(-)-nicotine could not be explained by different nicotine concentrations. The fact that no differences between the pure nicotine stereoisomers could be found for all concentrations used in our experiments and that experiments in humans revealed similar detection thresholds for both stereoisomers points to a similar receptor affinity of R(+)- and S(-)-nicotine within the olfactory system. At this point, it cannot be determined whether the observed differences in the perception of nicotine enantiomers in humans are due to differences in quality coding by stereospecific receptors on the olfactory sensory cells or by specific receptors on the trigeminal nerve endings.
The influence of continuous hemofiltration on cytokine elimination and the cardiovascular stability in the early phase of sepsis.
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Different sensitivity of pain-related chemosensory potentials evoked by stimulation with CO2, tooth pulp event-related potentials, and acoustic event-related potentials to the tranquilizer diazepam.
1. The aim of this study was to investigate the sensitivity of pain-related potentials used in experimental pain models to the non-specific effects of the tranquilizer diazepam. Pain-related potentials were recorded after painful stimulation of the nasal mucosa with CO2 and after painful stimulation of the tooth pulp. Acoustically evoked potentials were measured in order to compare their sensitivity to the tranquilizer diazepam with the sensitivity of the pain-related potentials. 2. Twenty volunteers participated in this randomised, double-blind, three-fold crossover study. Measurements were obtained before and 20 min after the administration of the drug. Event-related potentials were recorded after painful stimulation of the nasal mucosa with CO2 (two stimulus intensities: 60% v/v and 70% v/v CO2), after painful stimulation of the tooth pulp (two stimulus intensities: 2.2 x and 3.3 x detection threshold), and after non-painful acoustical stimulation of the right ear. The subjects rated the perceived intensity of the painful stimuli by means of a visual analogue scale. In addition the spontaneous EEG was analysed in the frequency domain and the vigilance of the subjects was assessed in a tracking task. 3. Diazepam reduced significantly the amplitudes of the event-related potentials after painful stimulation of the tooth pulp and after acoustical stimulation. In contrast only a small, statistically non-significant reduction could be found after painful stimulation with CO2. The pain ratings of the painful stimuli were not affected by diazepam. Diazepam reduced the performance of the tracking task. A decrease of arousal could be found in the alpha 2-range, whereas in the beta 2 and the theta-range the power density increased under diazepam. 4. We demonstrated that event-related potentials after painful stimulation of the nasal mucosa with CO2 are less affected by the nonspecific effects of the tranquilizer diazepam than event-related potentials after painful stimulation of the tooth pulp. The effects of diazepam on the tracking task, the spontaneous EEG and the event-related potentials clearly confirm its sedative properties. Diazepam had no analgesic effect measurable by pain intensity estimates.
Nociceptive and reflexive responses recorded from the human nasal mucosa.
Slow electrical responses after painful stimulation with carbon dioxide, which is known to specifically activate nociceptors, were recorded from the nasal respiratory epithelium in human volunteers. The negative component of these potentials (negative mucosal potential NMP) has been hypothesized to be a summated receptor potential. The aim of the present study was to characterize the stimulus-response relationship and to demonstrate that the NMP is restricted to the site of stimulation, i.e., to the area of activated nociceptors. Eight healthy volunteers participated in the experiments. The NMP was recorded from the nasal septum and intensity ratings were obtained for each of the applied stimuli. To control for autonomic reflexes, blood flow changes were additionally recorded using a laser Doppler flow meter. Both increasing stimulus duration and increasing concentration produced a significant increase in the subjects' intensity estimates, in the NMP's amplitudes and areas under the curve, but did not change the local blood flow in a dose-related manner. The odorant hydrogen sulphide, which was used as a non-painful control stimulus, did not elicit mucosal potentials or produce blood flow changes. By recording both ipsi- and contralaterally it was also demonstrated that the NMP could only be obtained at the stimulated site, thus supporting the hypothesis that the NMP is a specific peripheral nociceptive correlate.
[Puncture tracheostomy in intensive care patients. Technique and results of a minimally invasive method].
The so-called percutaneous dilatational tracheostomy-essentially a minimally invasive puncture method-inserting the tracheal cannula by a modified Seldinger-technique is an alternative method to the conventional operative tracheostomy. The percutaneous dilatational tracheostomy was evaluated in a prospective trial (June 92-January 93) on 50 consecutive surgical (n = 36), medical (n = 10), and neurological-neurosurgical (n = 4) critically ill patients (29 m, 21 f; age 14-87 years) with need for prolonged mechanical ventilation. After an average duration of endotracheal intubation of 6 (0-22) days, the procedure was endoscopically guided and controlled via the endotracheal tube. An 8 mm cannula was inserted in each case. Eight patients had severe thrombocytopenia (< or = 50,000 Plt./microL). The percutaneous tracheostomy was always performed with success. The average procedure duration was 8 (5-15) minutes. The perioperative complications were: one patient died of acute cardiac failure independent from the method of tracheostomy, one sustained a temporary subcutaneous emphysema and one a minor bleeding. During a mean duration of cannulation of 21 (0-113) days only one bleeding from the skin margin was observed postoperatively. Infection of stoma site, misplacement of cannula, rupture of the tube cuff, and pneumothorax were not noticed. On 13 decannulated patients stenosis of the trachea was not found in a period of 6-8 weeks following the tracheostomy. As a bedside procedure the percutaneous dilatational tracheostomy is safe and quick and should therefore be the method of choice for critically ill patients who require a tracheostomy.
The mucosal potential elicited by noxious chemical stimuli with CO2 in rats: is it a peripheral nociceptive event?
Negative mucosal potentials (NMPs) were recorded from the nasal respiratory mucosa in rats following retrograde stimulation with CO2 through a tube advanced to the nasopharynx. Local application of capsaicin (3 mg in 0.3 ml solvent, n = 5) and lidocaine (31 mg in 0.3 ml solvent, n = 5) eliminated the NMPs and cortical responses in the EEG. A quantitative reduction in NMPs was found following systemic pretreatment with capsaicin (cumulative dose, 200 mg/kg, n = 4), but not with guanethidine (50 mg/kg s.c., n = 4). Blood flow measurements and NMPs were obtained from the same recording position (n = 4). Onset of blood flow changes (1200-4800 ms) appeared significantly later than the onset of NMPs (120-500 ms). On the basis of these results a sensory neurogenic origin of the NMP is assumed.
Electrooculography and dark adaptation in patients with affective and schizoaffective psychoses: early physiological effects of carbamazepine and lithium.
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Cytochemical demonstration of negative surface charges in central myelin.
Homogenates of central myelin were treated with ferritin derivatives having different isoelectric points. It was found that considerable amounts of cationic ferritin (pI 8.5-9.5) had access to the extracellular space, but that anionic ferritin (pI 4.0) and native ferritin (pI 4.5) did not. The electrostatic nature of the binding of cationic ferritin was demonstrated by treating the homogenates with poly-L-lysine and 1 M NaCl:both reagents led to a complete displacement of the bound cationic ferritin. Neither extensive trypsination nor neuraminidase treatment showed a significant effect on the intralamellar distribution of the bound cationic ferritin molecules. This suggests that the net negative charge on the extracellular myelin face stems primarily from acidic lipid groups in the membrane.
Surface charges associated with fenestrated brain capillaries. I. In vitro labeling of anionic sites.
Ferritin derivatives with different pI values and the basic dye ruthenium red have been used as cationic probes to localize anionic sites associated with fenestrated brain capillaries. Cationic ferritin was found in the endothelial basement membrane and the basement membrane of the perivascular cellular linings in amounts far exceeding those observed with anionic derivatives, the degree being greater for the more cationized ferritin molecules. Labeling of the luminal endothelial front with cationic ferritin was only achieved when a serum- or albumin-free medium was applied. Furthermore, the striated collagen fibers were coated with cationic ferritin molecules in a highly ordered fashion. Ruthenium red localized to the same sites. The findings suggest the existence of a perivascular charge filter around fenestrated capillaries of the brain. Some physiological roles of this filter are discussed, as related to its possible function in regulating homeostasis of cerebrospinal fluid.
Surface charges associated with fenestrated brain capillaries. II. In vivo studies on the role of molecular charge in endothelial permeability.
We report on the effect of the net charge of a tracer (ferritin) on its permeability in fenestrated capillaries of the brain. Our experiments show that the charge of this tracer actually influences its interaction with the endothelium. Three phases of tracer-endothelial interaction could be discriminated. Anionic and slightly cationic derivatives (pH 4.5-7.8) do not show any affinity to the luminal endothelial membrane. Ferritin derivatives with a pI value between 7.8 and 9.3 result in the labeling of the fenestrae without coating additional luminal plasmalemmal structures (i.e., coated pits and plasmalemmal vesicles). Tracers with a high positive net charge (pI greater than 9.3) led to their endocytotic uptake and extravasation by some transcytotic mechanism. Extravasated cationic ferritin accumulates in the endothelial basement membrane and binds to striated collagen fibrils. It is suggested that the pericapillary collagen fibrils of fenestrated brain capillaries act as a charge filter with respect to macromolecules.
An improved technique for preparing polycationic ferritin derivatives.
Cationized ferritin molecules, which are positively charged at physiological pH, can be used as a cytochemical marker to visualize negatively charged groups over cell surfaces. The preparation of cationized ferritin, however, is hampered by irreversible aggregation of the ferritins and by poor reproducibility of pI values. In this report we describe an improved method which allows production of ferritin derivatives with different pI values. An elaborate protocol for the preparation of cationized ferritin is given as well as a table for the adjustment of their pI values to between 4.5--10.0.
Perforation of the posterior tracheal wall during percutaneous dilatational tracheotomy.
Dilatative percutaneous tracheotomy is more and more indicated in intensive-care medicine. We report on the perforation of the posterior tracheal wall observed in 3 patients after this procedure. In 2 patients the tracheo-oesophageal fistula was closed by the use of a pediculated flap from the infrahyoideal muscle. The third patient died due to the underlying disease. As demonstrated by the 3 cases reported here, this complication cannot be avoided in every case neither by the use of an endoscope nor by extensive personal experience of the physician. The possibility of this complication should be known, because it seems to be typical of this procedure. In the case of perforation of the posterior tracheal wall, active surgical treatment seems to be a successful method to deal with this complication.