Biomedical subjects

A M Zbinden

Publications and source records attributed to A M Zbinden.

At least 19 recordsLinked to original sources

PubMed2001

Comparison of five experimental pain tests to measure analgesic effects of alfentanil.

BACKGROUND: Several experimental pain models have been used to measure opioid effects in humans. The aim of the current study was to compare the qualities of five frequently used experimental pain tests to measure opioid effects. METHODS: The increase of electrical, heat, and pressure pain tolerance and the decrease of ice-water and ischemic pain perception was determined at baseline and at four different plasma concentrations of alfentanil (n = 7) administered as target controlled infusion or placebo (n = 7). A linear mixed-effects modeling (NONMEM) was performed to detect drug, placebo, and time effect as well as interindividual and intraindividual variation of effect. RESULTS: Only the electrical, ice-water, and pressure pain tests are sensitive to assess a concentration-response curve of alfentanil. At a plasma alfentanil concentration of 100 ng/ml, the increase in pain tolerance compared with baseline was 42.0% for electrical pain, 22.2% for pressure pain, and 21.7% for ice-water pain. The slope of the linear concentration-response curve had an interindividual coefficient of variation of 58.3% in electrical pain, 35.6% in pressure pain, and 60.0% in ice-water pain. The residual error including intraindividual variation at an alfentanil concentration of 100 ng/ml was 19.4% for electrical pain, 6.1% for pressure pain, and 13.0% for ice-water pain. Electrical pain was affected by a significant placebo effect, and pressure pain was affected by a significant time effect. CONCLUSION: Electrical, pressure, and ice-water pain, but not ischemic and heat pain, provide significant concentration-response curves in the clinically relevant range of 200 ng/ml alfentanil or lower. The power to detect a clinically relevant shift of the curve is similar in the three tests. The appropriate test(s) for pharmacodynamic studies should be chosen according to the investigated drug(s) and the study design.

Adult↗

PubMed2001

Modeling and closed-loop control of hypnosis by means of bispectral index (BIS) with isoflurane.

A model-based closed-loop control system is presented to regulate hypnosis with the volatile anesthetic isoflurane. Hypnosis is assessed by means of the bispectral index (BIS), a processed parameter derived from the electroencephalogram. Isoflurane is administered through a closed-circuit respiratory system. The model for control was identified on a population of 20 healthy volunteers. It consists of three parts: a model for the respiratory system, a pharmacokinetic model and a pharmacodynamic model to predict BIS at the effect compartment. A cascaded internal model controller is employed. The master controller compares the actual BIS and the reference value set by the anesthesiologist and provides expired isoflurane concentration references to the slave controller. The slave controller maneuvers the fresh gas anesthetic concentration entering the respiratory system. The controller is designed to adapt to different respiratory conditions. Anti-windup measures protect against performance degradation in the event of saturation of the input signal. Fault detection schemes in the controller cope with BIS and expired concentration measurement artifacts. The results of clinical studies on humans are presented.

Adult↗

PubMed2000

A direct search procedure to optimize combinations of epidural bupivacaine, fentanyl, and clonidine for postoperative analgesia.

BACKGROUND: The authors applied an optimization model (direct search) to find the optimal combination of bupivacaine dose, fentanyl dose, clonidine dose, and infusion rate for continuous postoperative epidural analgesia. METHODS: One hundred ninety patients undergoing 48-h thoracic epidural analgesia after major abdominal surgery were studied. Combinations of the variables of bupivacaine dose, fentanyl dose, clonidine dose, and infusion rate were investigated to optimize the analgesic effect (monitored by verbal descriptor pain score) under restrictions dictated by the incidence and severity of side effects. Six combinations were empirically chosen and investigated. Then a stepwise optimization model was applied to determine subsequent combinations until no decrease in the pain score after three consecutive steps was obtained. RESULTS: Twenty combinations were analyzed. The optimization procedure led to a reduction in the incidence of side effects and in the mean pain scores. The three best combinations of bupivacaine dose (mg/h), fentanyl dose (microg/h), clonidine dose (microg/h), and infusion rate (ml/h) were: 9-21-5-7, 8-30-0-9, and 13-25-0-9, respectively. CONCLUSIONS: Given the variables investigated, the aforementioned combinations may be the optimal ones to provide postoperative analgesia after major abdominal surgery. Using the direct search method, the enormous number of possible combinations of a therapeutic strategy can be reduced to a small number of potentially useful ones. This is accomplished using a scientific rather than an arbitrary procedure.

Adrenergic alpha-Agonists↗

PubMed2000

Improving regulation of mean arterial blood pressure during anesthesia through estimates of surgery effects.

In this paper, a scheme for improvement of the regulation of mean arterial blood pressure (MAP) during anesthesia based on model predictive control (MPC) and estimates of the effects of disturbances (surgical events) is proposed. A linear model for the combined effects of surgical stimulations and volatile anesthetics on MAP is derived from experimental data. Based on it the potential improvement in blood pressure regulation is evaluated via a simulation study. The simulation study shows that when information about the effect of the surgical events on MAP is utilized by the controller maximum MAP deviations can be reduced by as much as 50% even when this information is inaccurate. At worst, (highly inaccurate information) no improvement is obtained.

Anesthesia↗

PubMed2000

Artifact-tolerant controllers for automatic drug delivery in anesthesia.

This article presents a method for treating measurement artifacts in model-based control systems. A nonlinear modification to the usual observer structure is introduced to prevent the measurement artifacts from winding up the controller states. It is shown how stability of the closed loop system can be analyzed and an example of a successful application in a clinical study is provided.

Algorithms↗

PubMed1999

Block of pinprick and cold sensation poorly correlate with relief of postoperative pain during epidural analgesia.

OBJECTIVE: To test the following hypotheses: there is a correlation between spread of epidural analgesia as assessed postoperatively by pinprick/cold test and postoperative pain intensity; block of pinprick/cold sensation is associated with absence of postoperative pain. DESIGN: Correlation analysis on prospectively collected data. SETTING: University hospital. PATIENTS: One hundred patients undergoing major surgery. Consecutive sample. INTERVENTIONS: Patients received an epidural infusion of bupivacaine 1 mg/ml, fentanyl 2 microg/ml, and epinephrine 2 microg/ml for at least 48 hours postoperatively. The infusion rate was adjusted according to pain intensity, occurrence of hypotension, or motor block. OUTCOME MEASURES: Assessments were made on three time points: 20-24 hours, 32-36 hours, and 4248 hours after extubation. Assessments included pinprick and cold sensitivity from C2 to S5, pain intensity (visual analogue scale, VAS) at rest, after cough, and after mobilization. Data were analyzed by multiple regression. RESULTS: VAS significantly decreased with increasing spread (number of dermatomes for which hyposensitivity to pinprick or cold was observed). Spread could explain only 2-5% of the variability of VAS. Absence of both pinprick and cold sensation at all dermatomes corresponding to the surgical wound was frequently associated with pain. A high proportion of patients manifesting an upper level of block above T5 had pain after abdominal surgery. CONCLUSIONS: Spread and efficacy of epidural analgesia as assessed by pinprick and cold stimulation correlate poorly with postoperative pain. These methods are of limited value both as clinical indicators of the efficacy of postoperative pain control and for investigating the effect of epidural drugs and techniques.

Adult↗

PubMed1998

Comparison of the analgesic potency of xenon and nitrous oxide in humans evaluated by experimental pain.

We have compared the analgesic potency of MAC-equivalent concentrations of xenon (10, 20, 30 and 40%) and nitrous oxide (15, 30, 45 and 60%) in humans using a multimodal experimental pain testing and assessment technique. We tested 12 healthy volunteers in a randomized, single-blind, crossover study. The following experimental pain tests were used: nociceptive reflex to repeated stimuli; pain tolerance to maximal effort tourniquet ischaemia; electrical stimulation; mechanical pressure; and cold. Reaction time was also measured. Xenon and nitrous oxide produced analgesia to ischaemic, electrical and mechanical stimulation, but not to cold pain. There was no difference in MAC-equivalent concentrations of xenon and nitrous oxide. Both increased reaction time in a similar manner. Xenon and nitrous oxide evoked nausea and vomiting in a large number of volunteers.

Adult↗

PubMed1998

Adding sodium bicarbonate to lidocaine enhances the depth of epidural blockade.

UNLABELLED: It is controversial whether adding CO2 or sodium bicarbonate to local anesthetics enhances the depth of epidural blockade. Repeated electrical stimulation is a reliable test for assessing epidural analgesia and evokes temporal summation. We used this test to investigate the analgesic effect of lidocaine, with or without CO2 or bicarbonate. Twenty-four patients undergoing epidural blockade with 20 mL lidocaine 2% at L2-3 were randomly divided into three groups: lidocaine hydrochloride, lidocaine CO2, and lidocaine plus 2 mL sodium bicarbonate 8.4%. Pain threshold after repeated electrical stimulation (five impulses at 2 Hz), pinprick, and cold test were performed at S1 and L4. Motor block was assessed. The addition of bicarbonate resulted in higher pain thresholds (P < 0.0001), faster onset of action (P = 0.009), and higher degree of motor block (P = 0.004) compared with lidocaine hydrochloride. We found no significant differences between lidocaine CO2 and hydrochloride. Most of these results were not confirmed by pinprick and cold tests. We conclude that the addition of sodium bicarbonate to lidocaine enhances the depth of epidural blockade, increases inhibition of temporal summation, and hastens the onset of block. Pinprick and cold are inadequate tests for comparing drugs for epidural anesthesia. IMPLICATIONS: We measured pain perception during epidural anesthesia by delivering electrical stimuli to the knee and foot. We found that the addition of sodium bicarbonate to the local anesthetic lidocaine enhances analgesia. We observed no effect of adding carbon dioxide to lidocaine.

Adult↗

PubMed1998

Tracheal intubation with rocuronium using the "timing principle".

UNLABELLED: We compared the endotracheal intubating conditions after rocuronium, using the "timing principle," with those after succinylcholine. The timing principle entails administration of a single bolus dose of nondepolarizing muscle relaxant, followed by an induction drug at the onset of clinical weakness. Forty-five patients were randomly assigned to three groups. Patients allocated to Groups 1 and 2 received rocuronium 0.6 mg/kg. At the onset of clinical weakness (onset of ptosis), anesthesia was induced with thiopental 4-6 mg/kg; intubation was accomplished after 45 s in Group 1 and after 60 s in Group 2. Patients in Group 3 received vecuronium (0.01 mg/kg) 3 min before the administration of thiopental and succinylcholine 1.5 mg/kg, and their tracheas were intubated 60 s later by a blind anesthesiologist. Intubating conditions were assessed according to a grading scale and were either good (5 patients in Groups 1 and 2, 4 patients in Group 3) or excellent (10 patients in Groups 1 + 2, 11 patients in Group 3) in all patients. Patients were interviewed postoperatively, and all were satisfied with the induction of anesthesia. We conclude that rocuronium 0.6 mg/kg provides good to excellent intubating conditions 45 and 60 s after the induction of anesthesia using the timing principle. IMPLICATIONS: We compared the ease with which a breathing tube could be placed in patients using three techniques. The standard technique (succinylcholine) was compared with two others in which a muscle-relaxing drug (rocuronium) was administered just before the anesthetic drug (so-called timing principle). No difference among the techniques was observed.

Adolescent↗

PubMed1998

Epidural fentanyl, adrenaline and clonidine as adjuvants to local anaesthetics for surgical analgesia: meta-analyses of analgesia and side-effects.

BACKGROUND: The risk/benefit ratio of adding fentanyl, adrenaline and clonidine to epidural local anaesthetics for improving intraoperative analgesia is unclear. This meta-analysis was performed to clarify this issue. METHODS: Trials retrieved by search were considered if they were prospective, controlled, epidural analgesia (without combining general anaesthesia) was planned and occurrence of pain during surgery or side-effects were reported. Papers entered meta-analysis if they reached a predefined minimum quality score. Pooled odds ratios (OR) and confidence intervals (CI) were computed. P < 0.05 was considered as significant. RESULTS: Eighteen trials were included in the analysis for fentanyl. Fentanyl decreased the likelihood of pain (OR = 0.21, 95% CI = 0.15-0.30, P < 0.001) and increased the incidence of pruritus (OR = 5.59, 95% CI = 3.12-10.05, P < 0.001) and sedation (OR = 1.88, 95% CI = 1.19-2.98, P = 0.003), compared to control (local anaesthetic without fentanyl). Fentanyl had no effect on respiratory depression, nausea, vomiting and Apgar score. One case of respiratory depression of a newborn was observed. Because of the very low number of trials selected, evaluation of adrenaline and clonidine was not feasible. CONCLUSION: The analysis of current literature shows that the addition of fentanyl to local anaesthetics for intraoperative epidural analgesia is safe and advantageous. The reduction in the incidence of pain during surgery is quantitatively high and therefore clinically significant. Side-effects are mild. Randomized, controlled trials have to be performed in order to clarify the role of adrenaline and clonidine as epidural adjuvants for surgical analgesia.

Adjuvants, Anesthesia↗

PubMed1997

[Data collection in anesthesia. Experiences with the inauguration of a new information system].

UNLABELLED: In many institutions information systems are used to process off-line anaesthesia data for invoices, statistical purposes, and quality assurance. Information systems are also increasingly being used to improve process control in order to reduce costs. Most of today's systems were created when information technology and working processes in anaesthesia were very different from those in use today. Thus, many institutions must now replace their computer systems but are probably not aware of how complex this change will be. Modern information systems mostly use client-server architecture and relational data bases. Substituting an old system with a new one is frequently a greater task than designing a system from scratch. This article gives the conclusions drawn from the experience obtained when a large departmental computer system is redesigned in an university hospital. METHODS: The new system was based on a client-server architecture and was developed by an external company without preceding conceptual analysis. Modules for patient, anaesthesia, surgical, and pain-service data were included. Data were analysed using a separate statistical package (RS/1 from Bolt Beranek), taking advantage of its powerful precompiled procedures. RESULTS: Development and introduction of the new system took much more time and effort than expected despite the use of modern software tools. Introduction of the new program required intensive user training despite the choice of modem graphic screen layouts. Automatic data-reading systems could not be used, as too many faults occurred and the effort for the user was too high. However, after the initial problems were solved the system turned out to be a powerful tool for quality control (both process and outcome quality), billing, and scheduling. The statistical analysis of the data resulted in meaningful and relevant conclusions. CONCLUSIONS: Before creating a new information system, the working processes have to be analysed and, if possible, made more efficient; a detailed programme specification must then be made. A servicing and maintenance contract should be drawn up before the order is given to a company. Time periods of equal duration have to be scheduled for defining, writing, testing and introducing the program. Modern client-server systems with relational data bases are by no means simpler to establish and maintain than previous mainframe systems with hierarchical data bases, and thus, experienced computer specialists need to be close at hand. We recommend collecting data only once for both statistics and quality control. To verify data quality, a system of random spot-sampling has to be established. Despite the large investments needed to build up such a system, we consider it a powerful tool for helping to solve the difficult daily problems of managing a surgical and anaesthesia unit.

Anesthesia↗

PubMed1997

Spinal anaesthesia inhibits central temporal summation.

In a previous investigation we found that extradural anaesthesia did not adequately inhibit temporal summation of repeated electrical stimuli: pain to repeated stimuli was blocked in only one of 10 patients, and pain thresholds to repeated stimuli were significantly lower than pain thresholds to a single stimulus. In this study we have investigated in 10 patients the effect of spinal anaesthesia on temporal summation, assessed by repeated electrical stimulation of the sural nerve. Plain 0.5% bupivacaine 18 mg was injected at L2-3. The pain threshold to a single electrical stimulus, summation threshold (increase in perception during repeated electrical stimuli with five impulses of the same intensity at 2 Hz), pinprick and cold sensation were assessed. After spinal anaesthesia, pain to both single and repeated stimulation, and pinprick and cold sensation, disappeared in all patients. We conclude that spinal anaesthesia inhibits temporal summation elicited by repeated electrical stimulation.

Adolescent↗

PubMed1997

Epidural epinephrine and clonidine: segmental analgesia and effects on different pain modalities.

BACKGROUND: It is not known whether epidural epinephrine has an analgesic effect per se. The segmental distribution of clonidine epidural analgesia and its effects on temporal summation and different types of noxious stimuli are unknown. The aim of this study was to clarify these issues. METHODS: Fifteen healthy volunteers received epidurally (L2-L3 or L3-L4) 20 ml of either epinephrine, 100 microg, in saline; clonidine, 8 microg/kg, in saline; or saline, 0.9%, alone, on three different days in a randomized, double-blind, cross-over fashion. Pain rating after electrical stimulation, pinprick, and cold perception were recorded on the dermatomes S1, L4, L1, T9, T6, T1, and forehead. Pressure pain tolerance threshold was recorded at S1, T6, and ear. Pain thresholds to single and repeated (temporal summation) electrical stimulation of the sural nerve were determined. RESULTS: Epinephrine significantly reduced sensitivity to pinprick at L1-L4-S1. Clonidine significantly decreased pain rating after electrical stimulation at L1-L4 and sensitivity to pinprick and cold at L1-L4-S1, increased pressure pain tolerance threshold at S1, and increased thresholds after single and repeated stimulation of the sural nerve. CONCLUSIONS: Epidural epinephrine and clonidine produce segmental hypoalgesia. Clonidine bolus should be administered at a spinal level corresponding to the painful area. Clonidine inhibits temporal summation elicited by repeated electrical stimulation and may therefore attenuate spinal cord hyperexcitability.

Adrenergic alpha-Agonists↗

PubMed1996

Analgesic effect in humans of subanaesthetic isoflurane concentrations evaluated by evoked potentials.

The aim of this study was to see if an analgesic effect of subanaesthetic concentrations of isoflurane could be detected with evoked potentials elicited by nociceptive stimuli. We studied 10 healthy volunteers breathing three steady-state subanaesthetic concentrations of isoflurane (0.08, 0.16 and 0.24 vol% end-tidal). Reaction time, subjective pain intensities and evoked vertex potentials to laser (LEP) and electrical (SEP) stimuli were recorded and compared with auditory evoked potentials (AEP). Compared with baseline, the subanaesthetic concentrations of isoflurane did not change the latencies of the evoked potentials, but caused a significant reduction in the amplitudes of the LEP and SEP at 0.16 and 0.24 vol% and of the AEP at all three concentrations. There were no changes in perceived pain intensity, and isoflurane produced similar reductions in evoked potentials elicited by both nociceptive and non-nociceptive stimuli. The reaction time was increased significantly at 0.24 vol% isoflurane. The results demonstrated that subanaesthetic isoflurane concentrations caused similar changes in evoked potentials with both painful and non-painful stimuli, with no effect on perceived pain intensity.

Acoustic Stimulation↗

PubMed1996

Fuzzy logic control of inspired isoflurane and oxygen concentrations using minimal flow anaesthesia.

In order to evaluate the performance of feedback fuzzy logic control of inspired oxygen and isoflurane concentrations, we studied 30 patients undergoing discectomy for lumbar (n = 26) or cervical (n = 4) disc herniation. Patients were allocated random to one of two groups: a standard group (n = 15) with low flow anaesthesia (1.2-1.3 litre min-1) and manual control of gas concentrations; and a fuzzy group (n = 15) with minimal flow (0.5 litre min-1) and fuzzy logic feedback control of gas concentrations. Fuzzy logic control achieved and maintained very accurately the desired isoflurane concentration. Oxygen concentration was controlled more precisely than in the standard group. Delivery and costs of oxygen and nitrous oxide were significantly lower in the fuzzy group (P < 0.01). Accumulation of foreign gases was observed in one patient during low flow and in 11 patients during minimal flow anaesthesia. In conclusion, fuzzy logic control of inspired oxygen and isoflurane concentration during minimal flow anaesthesia was reliable and reduced anaesthetic gas delivery and costs.

Adult↗

PubMed1996

Psychophysical and electrophysiological responses to experimental pain may be influenced by sedation: comparison of the effects of a hypnotic (propofol) and an analgesic (alfentanil).

Sedation may influence the responses of some experimental pain models used to test analgesic efficacy. In this study we compared the effects of a sedative (propofol) and analgesic (alfentanil) on: nociceptive reflex to single and repeated electrical stimulations; mechanical pressure pain; and evoked potentials elicited by nociceptive (electrical and laser) and non-nociceptive (acoustical) stimulation. We studied 12 healthy volunteers with two subanaesthetic concentrations of propofol and two analgesic concentrations of alfentanil. Both propofol and alfentanil increased the threshold for nociceptive reflex to single electrical stimulations, but only alfentanil increased the threshold for nociceptive reflex to repeated electrical stimulations. The pressure pain tolerance thresholds were increased significantly by alfentanil, whereas propofol significantly decreased the thresholds (hyperalgesia). Propofol and alfentanil induced similar reductions in the amplitudes of the evoked potentials elicited by nociceptive (electrical and laser) and non-nociceptive (acoustical) stimulation, whereas only alfentanil reduced the perceived pain to nociceptive stimulations. We have shown that sedation can influence both the psychophysical and electrophysiological responses of some experimental pain tests used to measure analgesic efficacy, and that propofol in subhypnotic doses, has no analgesic effect on painful electrical and heat stimulations, but has a hyperalgesic effect on mechanical pressure pain.

Adult↗

PubMed1996

Effect of racemic mixture and the (S+)-isomer of ketamine on temporal and spatial summation of pain.

We have compared the analgesic efficacy of the racemic mixture and the stereoisomer (S+) of the NMDA antagonist ketamine. In a double-blind, three-way crossover, placebo-controlled study, we assessed the following: pain evoked by small/large area pressure stimuli, pain detection threshold and pain ratings to small/large area of heat stimuli, pain detection threshold and pain rating to heat stimuli of brief/long duration, summation pain threshold and pain ratings to repeated heat/electrical stimuli, side effects and reaction time. Plasma concentrations of 350 ng ml-1 for ketamine (racemic) and 180 ng ml-1 for ketamine (S+) were tried. We found that ketamine (racemic) prolonged the reaction time more than ketamine (S+). Both drugs affected pain caused by repeated stimuli or stimuli of long duration equally or more than a single stimulus of short duration. They also affected pain evoked from large areas equally or more than pain evoked from small areas. The (S+)-isomer was approximately twice as potent as the racemic mixture of ketamine in inhibiting central summation.

Adult↗

PubMed1996

Fuzzy logic control of mechanical ventilation during anaesthesia.

We have examined a new approach, using fuzzy logic, to the closed-loop feedback control of mechanical ventilation during general anaesthesia. This control system automatically adjusts ventilatory frequency (f) and tidal volume (VT) in order to achieve and maintain the end-tidal carbon dioxide fraction (FE'CO2) at a desired level (set-point). The controller attempts to minimize the deviation of both f and VT per kg body weight from 10 bpm and 10 ml kg-1, respectively, and to maintain the plateau airway pressure within suitable limits. In 30 patients, undergoing various surgical procedures, the fuzzy control mode was compared with human ventilation control. For a set-point of FE'CO2 = 4.5 vol% and during measurement periods of 20 min, accuracy, stability and breathing pattern did not differ significantly between fuzzy logic and manual ventilation control. After step-changes in the set-point of FE'CO2 from 4.5 to 5.5 vol% and vice versa, overshoot and rise time did not differ significantly between the two control modes. We conclude that to achieve and maintain a desired FE'CO2 during routine anaesthesia, fuzzy logic feedback control of mechanical ventilation is a reliable and safe mode of control.

Adolescent↗