Journal of clinical monitoring and computing, 2002
To test the accuracy of a thermal conductivity xenon sensor in vitro and in vivo and to test the ... more To test the accuracy of a thermal conductivity xenon sensor in vitro and in vivo and to test the effect of xenon on other anesthetic gas analyzers as determined by a mass spectrometry gold standard. The xenon concentration was measured with a prototype of a thermal conductivity sensor and a mass spectrometer in vitro and in 6 patients. Further in vitro experiments determined the impact of xenon on the measurements of oxygen, carbon dioxide and desflurane with three commercially available anesthesia gas monitors. In vitro the thermal conductivity sensor and an associated computer, when calibrated against a mass spectrometer using a third order polynomial calibration curve measured the xenon concentration to a 95% confidence limit of -1.2 to +1.8 vol% compared to mass spectrometry. In vivo and under clinical conditions with a mixture of xenon, O2 and CO2 the 95% confidence limit was -2.5 to +1.6 vol% with a mean bias of -0.5 vol% over a concentration range of 20 to 70 vol%. Xenon indu...
Conventional anaesthetic breathing systems are not designed to control end-tidal gas concentratio... more Conventional anaesthetic breathing systems are not designed to control end-tidal gas concentrations, nor can they be used to measure accurately the uptake of oxygen or of anaesthetic agent. We built and tested a leak-tight closed-loop anaesthetic breathing system with low solubility to volatile anaesthetic agents and with efficient gas mixing. The system included a water-sealed spirometer, a small carbon dioxide absorber, a coaxial tube to the patient, a circulating pump and feedback controllers for system volume and anaesthetic concentration. Feedback control was implemented to adjust and control automatically the end-tidal anaesthetic concentration and the volume of the system with oxygen supplied through a mass flow controller and with halothane supplied by a titrating syringe. Controller gains, as a function of body weight, were found using a nine-compartment tissue uptake model. Stability was maintained with +/- 50% changes in alveolar ventilation and cardiac output. During sub...
From folk medicine and anecdotal reports it is known that Cannabis may reduce pain. In animal stu... more From folk medicine and anecdotal reports it is known that Cannabis may reduce pain. In animal studies it has been shown that delta-9-tetrahydrocannabinol (THC) has antinociceptive effects or potentiates the antinociceptive effect of morphine. The aim of this study was to measure the analgesic effect of THC, morphine, and a THC-morphine combination (THC-morphine) in humans using experimental pain models. THC (20 mg), morphine (30 mg), THC-morphine (20 mg THC+30 mg morphine), or placebo were given orally and as single doses. Twelve healthy volunteers were included in the randomized, placebo-controlled, double-blinded, crossover study. The experimental pain tests (order randomized) were heat, cold, pressure, single and repeated transcutaneous electrical stimulation. Additionally, reaction time, side-effects (visual analog scales), and vital functions were monitored. For the pharmacokinetic profiling, blood samples were collected. THC did not significantly reduce pain. In the cold and heat tests it even produced hyperalgesia, which was completely neutralized by THC-morphine. A slight additive analgesic effect could be observed for THC-morphine in the electrical stimulation test. No analgesic effect resulted in the pressure and heat test, neither with THC nor THC-morphine. Psychotropic and somatic side-effects (sleepiness, euphoria, anxiety, confusion, nausea, dizziness, etc.) were common, but usually mild.
Central temporal summation of afferent nociceptive stimuli is involved in central hyperexcitabili... more Central temporal summation of afferent nociceptive stimuli is involved in central hyperexcitability. This is assumed to be an important mechanism in the nociceptive system which is probably activated during surgery and trauma. The purpose of the present study was to investigate if isoflurane has a specific effect on central temporal summation in humans. Facilitation of the nociceptive reflex to repeated stimuli can be used to assess central summation in subjects unable to cooperate due to an anaesthetic procedure. The nociceptive reflex to single and repeated (5 pulses delivered at 2 Hz) electrical surface stimuli of the sural nerve were measured in 6 healthy volunteers anaesthetized with isoflurane. A reflex was defined as an EMG signal from the rectus and biceps femoris exceeding 20 microV for more than 10 msec in the 80-200 msec interval after the stimulus. The end-tidal isoflurane concentration was increased in steps of 0.25 vol% from 0.25 to 1.50 vol%. For each concentration the thresholds for the nociceptive reflex were determined as the current intensity that could just elicit a reflex response to single stimulations, and for the repeated stimulations as the current intensity that could just elicit a reflex response to the 4th and/or 5th stimuli in the train of 5 stimuli. The nociceptive reflex to single stimuli was depressed at isoflurane concentrations producing sedation or light anaesthesia (0.25-0.50 vol% end-tidal). In contrast, 2-4-fold higher isoflurane concentrations (1.00-1.50 vol% end-tidal) that normally produce surgical anaesthesia were required to depress the nociceptive reflex to repetitive stimuli. This indicates that central temporal summation in the nociceptive system is a potent mechanism, and that isoflurane has a weak potency for depressing temporal summation in humans. As such isoflurane alone is not adequate for inhibiting surgically evoked hyperexcitability.
International Journal of Clinical Monitoring and Computing, 1986
Two new portable infrared gas analysers, the Irina (Drfigerwerke, Liibeck, Germany) and the Norma... more Two new portable infrared gas analysers, the Irina (Drfigerwerke, Liibeck, Germany) and the Normac (Datex Instrumentarium Corporation, Helsinki, Finland), were tested and the results compared to those from such established methods as gaschromatography and the Beckman LB-2 (Beckman, USA) infrared gas analyser using exactly defined gas mixtures from a vaporizer developed in our laboratory. The analysers were evaluated for their accuracy and precision, noise, zero stability, gain stability and the impact of flow, overpressure, carrier gas and humidity. All three analysers showed good accuracy and precision. The noise level was acceptable except in the older version of the Normac, but this error has now been corrected by the manufacturer. Zero and gain stability are very good; gas flow and overpressure do not affect the measurement. The influence of carrier gases and humidity is negligible except for the strong N20 effect on the Beckman. We conclude that this new generation of highly sophisticated and reliable but handy analysers will meet the clinical demands.
IEEE Engineering in Medicine and Biology Magazine, 2001
Automatic controllers capable of regulating multiple patient outputs for higher-quality anesthesi... more Automatic controllers capable of regulating multiple patient outputs for higher-quality anesthesia treatment are described. The first steps toward the development of an autonomous anesthesia system at the authors' laboratory are presented. The controllers are implemented on a real-time platform and tested on humans to quantify the benefits that may result from their use in routine practice. To date, the staff
Canadian Journal of Anesthesia/Journal canadien d'anesthésie, 2005
P Pu ur rp po os se e: : Is to test the hypothesis that 70% xenon has a relevant opioid sparing e... more P Pu ur rp po os se e: : Is to test the hypothesis that 70% xenon has a relevant opioid sparing effect compared to a minimum alveolar concentration (MAC)-equivalent combination of N 2 O and desflurane.
demanded). The investigations were performed with premixed test gases (2.5, 5, 10 vol%, error < /... more demanded). The investigations were performed with premixed test gases (2.5, 5, 10 vol%, error < / % rel). Humidification (37° C) of gases were generated by a Drager Aquapor. Respiratory cycles were simulated by manually activated valves. All monitors complied with the tolerated accuracy bias in CO 2 reading (<12% or 4 mmHg of actual test gas value) for wet and dry test gases at all concentrations, except that the Marquette MGA-AS exceeded this accuracy limit with wet gases at 5 and 10 vol% CO 2 . Water condensed in the metal airway adapter of the HP M1166A at 37° C gas temperature but not at 30° C. The Servomex 2500 (nonclinical reference monitor), Passport (M-type), Multinex (Sl-type) and
We studied the clinical use of an automatic feedback control system to adjust the end-tidal anaes... more We studied the clinical use of an automatic feedback control system to adjust the end-tidal anaesthetic concentration with a low-¯ow method. The end-tidal controller uses two input signals (the end-tidal and inspiratory concentrations) to control the iso¯urane concentration in the fresh gas¯ow, using a model-based algorithm. We studied 22 ASA I±III patients during elective surgery lasting more than 2 h. The anaesthetist was asked to make four step changes of the target end-tidal concentration (+0.3, +0.6, ±0.3, ±0.6 vol%), either manually (Group A) or by setting the target value for the feedback controller (Group B), and then the control was changed and the step changes were repeated, in a crossover design. Eighty step changes with each control method were compared in terms of response time, maximal overshoot and stability. The automatic control system was more accurate and stable than the human controller for step increases and step decreases, with less overshoot/undershoot and greater stability [e.g. maximal overshoot 14.7 (SD 3.7)% and 18 (8.1)% respectively for +0.6 vol% step changes, and 19.8 (3.7)% and 30.7 (13.2)% respectively for +0.3 vol% step changes]. However, the automatic control system showed a faster response time than the manual method only with large increasing steps (e.g. 149 (32) s and 205 (57) s respectively for +0.6 vol% step changes) and was not different from manual control for decreasing steps. Automatic control of the end-tidal iso¯urane concentration can be better than human control in a clinical setting, and this task could be done automatically.
We have investigated in 10 patients the effect of extradural anaesthesia on temporal summation by... more We have investigated in 10 patients the effect of extradural anaesthesia on temporal summation by comparing pain thresholds to single and repeated (five impulses at 2 Hz) electrical stimuli and compared these tests with pinprick and cold stimulation. Bupivacaine 0.5% (20 ml) was injected at L2-3. After extradural anaesthesia the threshold to repeated stimuli was significantly lower than the threshold to single stimuli (P = 0.0007). Nine patients lost cold sensation and 10 patients pinprick sensation. Pain to single electrical stimulation disappeared in six patients and pain to repeated electrical stimulation in one. Pain may be evoked by temporal summation of repeated electrical stimuli even when pinprick sensation, cold sensation and pain to single electrical stimuli are inhibited. Thus temporal summation should be taken into consideration when extradural analgesia is assessed.
5-Hydroxytryptamine (5-HT) causes antinociception via presynaptic 5-HT3 (5-HT subtype 3) receptor... more 5-Hydroxytryptamine (5-HT) causes antinociception via presynaptic 5-HT3 (5-HT subtype 3) receptors on primary afferent nociceptive neurones in the spinal cord dorsal horn. Therefore, ondansetron (a 5-HT3 receptor antagonist) may increase the perception of a noxious stimulus or decrease the effects of concurrently administered antinociceptive drugs. Using a randomized, double-blind, crossover study design, we have tested this hypothesis in eight healthy volunteers who, on three different days, received either ondansetron and placebo, ondansetron and alfentanil or placebo and alfentanil. Experimental pain was induced with heat, cold, mechanical pressure and electrical stimulation. Ondansetron alone did not change the response to any of the experimental tests, but alfentanil and the combination ondansetron-alfentanil significantly changed the response compared with ondansetron alone. There was no difference between alfentanil alone and the combination ondansetron-alfentanil. We conclude that ondansetron does not change the response to pressure, heat, cold or electrical nociceptive stimuli or antagonize the analgesic effect of alfentanil.
In order to evaluate the performance of feedback fuzzy logic control of inspired oxygen and isofl... more 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 &lt; 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.
The analgesic effect of subanaesthetic concentrations of ether, trichloroethylene, methoxyflurane... more The analgesic effect of subanaesthetic concentrations of ether, trichloroethylene, methoxyflurane and halothane has been investigated previously using either clinical assessment or pain threshold measurements, but with conflicting results. The purpose of the present study was to evaluate the analgesic effect of isoflurane using experimental pain models. We studied 12 healthy volunteers at three randomly chosen subanaesthetic isoflurane concentrations: low (0.10-0.14 vol%), middle (0.16-0.20 vol%) and high (0.22-0.26 vol%). We used thermal pain detection and pain tolerance thresholds to argon laser stimulation, pressure pain detection and pain tolerance thresholds, immersion of the hand in ice water, and the nociceptive reflex to single and repeated (temporal summation) electrical stimulations, as experimental models to assess analgesia. There were no significant changes in the response to heat, cold or mechanical pressure at any of the subanaesthetic concentrations of isoflurane used. The nociceptive reflex thresholds to single stimulations, but not the thresholds for repeated stimulations, were significantly increased in all three isoflurane groups compared with baseline values. The difference between the different isoflurane concentrations was not statistically significant. In experimental pain models, subanaesthetic isoflurane concentrations have little or no analgesic potency.
The fresh gas utilization (FGU) of a semi-closed breathing system is defined as the ratio of the ... more The fresh gas utilization (FGU) of a semi-closed breathing system is defined as the ratio of the amount of gas reaching the patient&#39;s lungs to the total amount of fresh gas flowing into the breathing system. It indicates to what extent a breathing system conserves anaesthetic gases and provides inspired gas concentrations as close as possible to those in the fresh gas, even at low fresh gas flows (FGF). We have measured FGU in eight circle systems used conventionally in Europe: Dräger Cicero, Dräger Sulla 808V with circle system 8 ISO and ventilator Ventilog, Dräger AV1, Ohmeda Modulus II Plus, Gambro Engström Elsa, Siemens Servo Ventilator 900 D with circle system 985, Siemens Ventilator 710 and Megamed 700A with circle system 219. The Tests were performed according to the Draft European Standard &quot;Anaesthetic Workstations and Their Modules&quot;. None of the systems tested showed the characteristics of an ideal system which would reach 100% FGU with an FGF less than minute volume. At FGF 3 litre min-1, FGU was: Gambro Engström Elsa 97.8%, Siemens Servo Ventilator 900 D with circle system 96.1%, Dräger Cicero 93.4%, Ohmeda Modulus II Plus 93.1%, Dräger 8 ISO 92.3%, Dräger AV1 87.6%, Megamed 700A 77.0% and Siemens Ventilator 710 74.1%.
End-tidal partial pressure of isoflurane (PE&#39;iso) may be used as a measure of anaesthetic... more End-tidal partial pressure of isoflurane (PE&#39;iso) may be used as a measure of anaesthetic depth. During uptake, an arterial partial pressure (Paiso) which is considerably less than PE&#39;iso (Paiso/PE&#39;iso much less than 1) leads to underestimation of depth of anaesthesia and, during elimination, PE&#39;iso/Paiso much less than 1 will lead to an overestimation of anaesthetic depth. We measured Paiso/PE&#39;iso during a 60-min uptake period of 1% isoflurane and PE&#39;iso/Paiso during the subsequent 60-min elimination period in 26 patients (age 13-88 yr, ASA I-III) undergoing various surgical procedures. After 15 min of isoflurane uptake, Paiso/PE&#39;iso of 26 patients was mean 0.78 (SD 0.10) and this increased only marginally at 60 min (0.79 (0.09)), whereas during elimination, PE&#39;iso/Paiso was in the range 0.79 (0.14)-0.83 (0.11). Predictability of Paiso in a given patient is hindered by the high SD of Paiso/PE&#39;iso and PE&#39;iso/Paiso, but it may be improved by taking into account age, ASA physical status category, vital capacity, inspired minus end-tidal isoflurane partial pressure and arterial minus end-tidal carbon dioxide partial pressure during uptake; and obesity, end-tidal isoflurane partial pressure and arterial minus end-tidal carbon dioxide partial pressure during elimination. However, even with multiple regression analysis (to account for the various possible variables), clinically useful prediction of Paiso/PE&#39;iso and PE&#39;iso/Paiso in a particular patient is not possible (residual SD 0.084 and 0.113, respectively).
Sedation may influence the responses of some experimental pain models used to test analgesic effi... more 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.
A gas chromatographic method is described for the direct quantitative determination of the partia... more A gas chromatographic method is described for the direct quantitative determination of the partial pressure of halothane (or isoflurane) in blood as well as the blood-gas partition coefficient. A head space technique and a flame ionization detector were used. Standard blood was obtained by equilibrating patients&#39; blood with known gas concentrations in a tonometer. Using an infra-red analyser to measure the halothane gas concentration in the tonometer and within the anaesthetic system allowed for the direct comparison of the partial pressure in blood to the partial pressure in the inspired gas. Technical problems associated with this procedure, and with comparable methods, are discussed.
Arterial pressure is still one of the most important measures in estimating the required dose of ... more Arterial pressure is still one of the most important measures in estimating the required dose of inhaled anaesthetics. It is measured easily and reacts rapidly which makes it suitable as a variable for feedback control of depth of anaesthesia. Fuzzy logic, a novel approach to feedback control, was used to control arterial pressure in 10 patients during intraabdominal surgery by automatic adjustment of the concentration of isoflurane in fresh gas. During anaesthesia, fuzzy control periods of 45-min duration were alternated randomly with human control periods of equal duration. During the skin incision period (-3 to +12min) 48.2% of all fuzzy control pressure values were within ±10% of the desired mean arterial pressure compared with 40.4% of the human control values (P < 0.05). The corresponding values for the remainder of the operation were 78.3% and 83.2%, respectively. Thus fuzzy outperformed human control at skin incision, but was slightly inferior during the rest of the operation. We conclude that fuzzy logic is a promising new technique for control of isoflurane delivery during routine anaesthesia. (Br. J. Anaesth. 1995; 74: 66-72)
Automatic control of depth of hypnosis using the Bispectral Index (BIS) can help to reduce phases... more Automatic control of depth of hypnosis using the Bispectral Index (BIS) can help to reduce phases of inadequate control. Automated BIS control with propofol or isoflurane administration via an infusion system has recently been described, a comparable study with isoflurane administration via a vaporizer had not been conducted yet. Our hypothesis was that our new model based closed-loop control system can safely be applied clinically and maintains the BIS within a defined target range better than manual control. Twenty-three patients, American Society of Anesthesiologists risk class I-III, scheduled for decompressive spinal surgery were randomized into groups with either closed-loop or manual control of BIS using isoflurane. An alfentanil target-controlled infusion was adjusted according to standard clinical practice. The BIS target was set to 50 during the operation. The necessity of human intervention in the control system and events of inadequate sedation (BIS &amp;amp;lt;40 or BIS &amp;amp;gt;60) were counted. The number of phases of inadequate control, defined as BIS &amp;amp;gt;/=65 for more than 3 min, were recorded. The performance of the controller was assessed by several indicators (mean absolute deviation and median absolute performance error) and measured during the skin incision phase, the subsequent low flow phase, and the wound closure phase. Recovery profiles of both groups were compared. No human intervention was necessary in the closed-loop control group. The occurrence of inadequate BIS was quantified with the mean and median values of the area under the curve and amounted to 0.360 and 0.088 for the manual control group and 0.049 and 0.017 for the closed-loop control group, respectively. In the manual control group nine phases of inadequate control were recorded, compared with one in the closed-loop control group, 10.3% to 0.5% of all observed anesthesia time. During all phases the averages of the performance parameters (mean absolute deviation and median absolute performance error) were more than 30% smaller in closed-loop control than in manual control (P &amp;amp;lt; 0.05 between groups). Closed-loop control with BIS using isoflurane can safely be applied clinically and performs significantly better than manual control, even in phases with abrupt changes of stimulation that cannot be foreseen by the control system.
It generally is assumed that the potency of inhalational anesthetics remains unchanged during the... more It generally is assumed that the potency of inhalational anesthetics remains unchanged during the course of the administration of an anesthetic. Only one study has indicated a decrease of minimum alveolar concentration with time. In this study, an effect of the duration of anesthesia administration and surgery on the potency of isoflurane was investigated by determining MACtetanus (the minimum alveolar concentration that prevents movement in response to electrical tetanic stimulation in 50% of patients) before and after surgery. Ten patients who underwent removal of a herniated intervertebral disc were anesthetized with isoflurane only. Reaction to a standardized electrical stimulation applied to the forearm was observed and was graded as movement or no-movement. The isoflurane concentration was increased in steps of 0.10 vol% if the patient moved and decreased in steps of 0.10 vol% if no reaction was seen, until a &quot;movement/no-movement/movement&quot; or &quot;no-movement/movement/no-movement&quot; pattern, respectively, was achieved. MACtetanus decreased in all patients from 1.28 +/- 0.22 vol% (mean +/- SD) before surgery to 1.04 +/- 0.22 vol% after surgery (P &lt; 0.01). When the prestimulation arterial blood pressure or the maximal increase in blood pressure caused by stimulation at the individual MACtetanus before surgery were compared to the corresponding values at the individual MACtetanus after surgery, no significant difference could be found. The prestimulation heart rate and the maximal increase in heart rate were significantly lower after surgery, even though the end-tidal isoflurane concentration was 0.24 vol% lower at the individual MACtetanus after surgery. The authors conclude that MACtetanus decreases during the administration of anesthesia and the performance of surgery.
Journal of clinical monitoring and computing, 2002
To test the accuracy of a thermal conductivity xenon sensor in vitro and in vivo and to test the ... more To test the accuracy of a thermal conductivity xenon sensor in vitro and in vivo and to test the effect of xenon on other anesthetic gas analyzers as determined by a mass spectrometry gold standard. The xenon concentration was measured with a prototype of a thermal conductivity sensor and a mass spectrometer in vitro and in 6 patients. Further in vitro experiments determined the impact of xenon on the measurements of oxygen, carbon dioxide and desflurane with three commercially available anesthesia gas monitors. In vitro the thermal conductivity sensor and an associated computer, when calibrated against a mass spectrometer using a third order polynomial calibration curve measured the xenon concentration to a 95% confidence limit of -1.2 to +1.8 vol% compared to mass spectrometry. In vivo and under clinical conditions with a mixture of xenon, O2 and CO2 the 95% confidence limit was -2.5 to +1.6 vol% with a mean bias of -0.5 vol% over a concentration range of 20 to 70 vol%. Xenon indu...
Conventional anaesthetic breathing systems are not designed to control end-tidal gas concentratio... more Conventional anaesthetic breathing systems are not designed to control end-tidal gas concentrations, nor can they be used to measure accurately the uptake of oxygen or of anaesthetic agent. We built and tested a leak-tight closed-loop anaesthetic breathing system with low solubility to volatile anaesthetic agents and with efficient gas mixing. The system included a water-sealed spirometer, a small carbon dioxide absorber, a coaxial tube to the patient, a circulating pump and feedback controllers for system volume and anaesthetic concentration. Feedback control was implemented to adjust and control automatically the end-tidal anaesthetic concentration and the volume of the system with oxygen supplied through a mass flow controller and with halothane supplied by a titrating syringe. Controller gains, as a function of body weight, were found using a nine-compartment tissue uptake model. Stability was maintained with +/- 50% changes in alveolar ventilation and cardiac output. During sub...
From folk medicine and anecdotal reports it is known that Cannabis may reduce pain. In animal stu... more From folk medicine and anecdotal reports it is known that Cannabis may reduce pain. In animal studies it has been shown that delta-9-tetrahydrocannabinol (THC) has antinociceptive effects or potentiates the antinociceptive effect of morphine. The aim of this study was to measure the analgesic effect of THC, morphine, and a THC-morphine combination (THC-morphine) in humans using experimental pain models. THC (20 mg), morphine (30 mg), THC-morphine (20 mg THC+30 mg morphine), or placebo were given orally and as single doses. Twelve healthy volunteers were included in the randomized, placebo-controlled, double-blinded, crossover study. The experimental pain tests (order randomized) were heat, cold, pressure, single and repeated transcutaneous electrical stimulation. Additionally, reaction time, side-effects (visual analog scales), and vital functions were monitored. For the pharmacokinetic profiling, blood samples were collected. THC did not significantly reduce pain. In the cold and heat tests it even produced hyperalgesia, which was completely neutralized by THC-morphine. A slight additive analgesic effect could be observed for THC-morphine in the electrical stimulation test. No analgesic effect resulted in the pressure and heat test, neither with THC nor THC-morphine. Psychotropic and somatic side-effects (sleepiness, euphoria, anxiety, confusion, nausea, dizziness, etc.) were common, but usually mild.
Central temporal summation of afferent nociceptive stimuli is involved in central hyperexcitabili... more Central temporal summation of afferent nociceptive stimuli is involved in central hyperexcitability. This is assumed to be an important mechanism in the nociceptive system which is probably activated during surgery and trauma. The purpose of the present study was to investigate if isoflurane has a specific effect on central temporal summation in humans. Facilitation of the nociceptive reflex to repeated stimuli can be used to assess central summation in subjects unable to cooperate due to an anaesthetic procedure. The nociceptive reflex to single and repeated (5 pulses delivered at 2 Hz) electrical surface stimuli of the sural nerve were measured in 6 healthy volunteers anaesthetized with isoflurane. A reflex was defined as an EMG signal from the rectus and biceps femoris exceeding 20 microV for more than 10 msec in the 80-200 msec interval after the stimulus. The end-tidal isoflurane concentration was increased in steps of 0.25 vol% from 0.25 to 1.50 vol%. For each concentration the thresholds for the nociceptive reflex were determined as the current intensity that could just elicit a reflex response to single stimulations, and for the repeated stimulations as the current intensity that could just elicit a reflex response to the 4th and/or 5th stimuli in the train of 5 stimuli. The nociceptive reflex to single stimuli was depressed at isoflurane concentrations producing sedation or light anaesthesia (0.25-0.50 vol% end-tidal). In contrast, 2-4-fold higher isoflurane concentrations (1.00-1.50 vol% end-tidal) that normally produce surgical anaesthesia were required to depress the nociceptive reflex to repetitive stimuli. This indicates that central temporal summation in the nociceptive system is a potent mechanism, and that isoflurane has a weak potency for depressing temporal summation in humans. As such isoflurane alone is not adequate for inhibiting surgically evoked hyperexcitability.
International Journal of Clinical Monitoring and Computing, 1986
Two new portable infrared gas analysers, the Irina (Drfigerwerke, Liibeck, Germany) and the Norma... more Two new portable infrared gas analysers, the Irina (Drfigerwerke, Liibeck, Germany) and the Normac (Datex Instrumentarium Corporation, Helsinki, Finland), were tested and the results compared to those from such established methods as gaschromatography and the Beckman LB-2 (Beckman, USA) infrared gas analyser using exactly defined gas mixtures from a vaporizer developed in our laboratory. The analysers were evaluated for their accuracy and precision, noise, zero stability, gain stability and the impact of flow, overpressure, carrier gas and humidity. All three analysers showed good accuracy and precision. The noise level was acceptable except in the older version of the Normac, but this error has now been corrected by the manufacturer. Zero and gain stability are very good; gas flow and overpressure do not affect the measurement. The influence of carrier gases and humidity is negligible except for the strong N20 effect on the Beckman. We conclude that this new generation of highly sophisticated and reliable but handy analysers will meet the clinical demands.
IEEE Engineering in Medicine and Biology Magazine, 2001
Automatic controllers capable of regulating multiple patient outputs for higher-quality anesthesi... more Automatic controllers capable of regulating multiple patient outputs for higher-quality anesthesia treatment are described. The first steps toward the development of an autonomous anesthesia system at the authors&amp;amp;amp;amp;amp;amp;amp;amp;#39; laboratory are presented. The controllers are implemented on a real-time platform and tested on humans to quantify the benefits that may result from their use in routine practice. To date, the staff
Canadian Journal of Anesthesia/Journal canadien d'anesthésie, 2005
P Pu ur rp po os se e: : Is to test the hypothesis that 70% xenon has a relevant opioid sparing e... more P Pu ur rp po os se e: : Is to test the hypothesis that 70% xenon has a relevant opioid sparing effect compared to a minimum alveolar concentration (MAC)-equivalent combination of N 2 O and desflurane.
demanded). The investigations were performed with premixed test gases (2.5, 5, 10 vol%, error < /... more demanded). The investigations were performed with premixed test gases (2.5, 5, 10 vol%, error < / % rel). Humidification (37° C) of gases were generated by a Drager Aquapor. Respiratory cycles were simulated by manually activated valves. All monitors complied with the tolerated accuracy bias in CO 2 reading (<12% or 4 mmHg of actual test gas value) for wet and dry test gases at all concentrations, except that the Marquette MGA-AS exceeded this accuracy limit with wet gases at 5 and 10 vol% CO 2 . Water condensed in the metal airway adapter of the HP M1166A at 37° C gas temperature but not at 30° C. The Servomex 2500 (nonclinical reference monitor), Passport (M-type), Multinex (Sl-type) and
We studied the clinical use of an automatic feedback control system to adjust the end-tidal anaes... more We studied the clinical use of an automatic feedback control system to adjust the end-tidal anaesthetic concentration with a low-¯ow method. The end-tidal controller uses two input signals (the end-tidal and inspiratory concentrations) to control the iso¯urane concentration in the fresh gas¯ow, using a model-based algorithm. We studied 22 ASA I±III patients during elective surgery lasting more than 2 h. The anaesthetist was asked to make four step changes of the target end-tidal concentration (+0.3, +0.6, ±0.3, ±0.6 vol%), either manually (Group A) or by setting the target value for the feedback controller (Group B), and then the control was changed and the step changes were repeated, in a crossover design. Eighty step changes with each control method were compared in terms of response time, maximal overshoot and stability. The automatic control system was more accurate and stable than the human controller for step increases and step decreases, with less overshoot/undershoot and greater stability [e.g. maximal overshoot 14.7 (SD 3.7)% and 18 (8.1)% respectively for +0.6 vol% step changes, and 19.8 (3.7)% and 30.7 (13.2)% respectively for +0.3 vol% step changes]. However, the automatic control system showed a faster response time than the manual method only with large increasing steps (e.g. 149 (32) s and 205 (57) s respectively for +0.6 vol% step changes) and was not different from manual control for decreasing steps. Automatic control of the end-tidal iso¯urane concentration can be better than human control in a clinical setting, and this task could be done automatically.
We have investigated in 10 patients the effect of extradural anaesthesia on temporal summation by... more We have investigated in 10 patients the effect of extradural anaesthesia on temporal summation by comparing pain thresholds to single and repeated (five impulses at 2 Hz) electrical stimuli and compared these tests with pinprick and cold stimulation. Bupivacaine 0.5% (20 ml) was injected at L2-3. After extradural anaesthesia the threshold to repeated stimuli was significantly lower than the threshold to single stimuli (P = 0.0007). Nine patients lost cold sensation and 10 patients pinprick sensation. Pain to single electrical stimulation disappeared in six patients and pain to repeated electrical stimulation in one. Pain may be evoked by temporal summation of repeated electrical stimuli even when pinprick sensation, cold sensation and pain to single electrical stimuli are inhibited. Thus temporal summation should be taken into consideration when extradural analgesia is assessed.
5-Hydroxytryptamine (5-HT) causes antinociception via presynaptic 5-HT3 (5-HT subtype 3) receptor... more 5-Hydroxytryptamine (5-HT) causes antinociception via presynaptic 5-HT3 (5-HT subtype 3) receptors on primary afferent nociceptive neurones in the spinal cord dorsal horn. Therefore, ondansetron (a 5-HT3 receptor antagonist) may increase the perception of a noxious stimulus or decrease the effects of concurrently administered antinociceptive drugs. Using a randomized, double-blind, crossover study design, we have tested this hypothesis in eight healthy volunteers who, on three different days, received either ondansetron and placebo, ondansetron and alfentanil or placebo and alfentanil. Experimental pain was induced with heat, cold, mechanical pressure and electrical stimulation. Ondansetron alone did not change the response to any of the experimental tests, but alfentanil and the combination ondansetron-alfentanil significantly changed the response compared with ondansetron alone. There was no difference between alfentanil alone and the combination ondansetron-alfentanil. We conclude that ondansetron does not change the response to pressure, heat, cold or electrical nociceptive stimuli or antagonize the analgesic effect of alfentanil.
In order to evaluate the performance of feedback fuzzy logic control of inspired oxygen and isofl... more 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 &lt; 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.
The analgesic effect of subanaesthetic concentrations of ether, trichloroethylene, methoxyflurane... more The analgesic effect of subanaesthetic concentrations of ether, trichloroethylene, methoxyflurane and halothane has been investigated previously using either clinical assessment or pain threshold measurements, but with conflicting results. The purpose of the present study was to evaluate the analgesic effect of isoflurane using experimental pain models. We studied 12 healthy volunteers at three randomly chosen subanaesthetic isoflurane concentrations: low (0.10-0.14 vol%), middle (0.16-0.20 vol%) and high (0.22-0.26 vol%). We used thermal pain detection and pain tolerance thresholds to argon laser stimulation, pressure pain detection and pain tolerance thresholds, immersion of the hand in ice water, and the nociceptive reflex to single and repeated (temporal summation) electrical stimulations, as experimental models to assess analgesia. There were no significant changes in the response to heat, cold or mechanical pressure at any of the subanaesthetic concentrations of isoflurane used. The nociceptive reflex thresholds to single stimulations, but not the thresholds for repeated stimulations, were significantly increased in all three isoflurane groups compared with baseline values. The difference between the different isoflurane concentrations was not statistically significant. In experimental pain models, subanaesthetic isoflurane concentrations have little or no analgesic potency.
The fresh gas utilization (FGU) of a semi-closed breathing system is defined as the ratio of the ... more The fresh gas utilization (FGU) of a semi-closed breathing system is defined as the ratio of the amount of gas reaching the patient&#39;s lungs to the total amount of fresh gas flowing into the breathing system. It indicates to what extent a breathing system conserves anaesthetic gases and provides inspired gas concentrations as close as possible to those in the fresh gas, even at low fresh gas flows (FGF). We have measured FGU in eight circle systems used conventionally in Europe: Dräger Cicero, Dräger Sulla 808V with circle system 8 ISO and ventilator Ventilog, Dräger AV1, Ohmeda Modulus II Plus, Gambro Engström Elsa, Siemens Servo Ventilator 900 D with circle system 985, Siemens Ventilator 710 and Megamed 700A with circle system 219. The Tests were performed according to the Draft European Standard &quot;Anaesthetic Workstations and Their Modules&quot;. None of the systems tested showed the characteristics of an ideal system which would reach 100% FGU with an FGF less than minute volume. At FGF 3 litre min-1, FGU was: Gambro Engström Elsa 97.8%, Siemens Servo Ventilator 900 D with circle system 96.1%, Dräger Cicero 93.4%, Ohmeda Modulus II Plus 93.1%, Dräger 8 ISO 92.3%, Dräger AV1 87.6%, Megamed 700A 77.0% and Siemens Ventilator 710 74.1%.
End-tidal partial pressure of isoflurane (PE&#39;iso) may be used as a measure of anaesthetic... more End-tidal partial pressure of isoflurane (PE&#39;iso) may be used as a measure of anaesthetic depth. During uptake, an arterial partial pressure (Paiso) which is considerably less than PE&#39;iso (Paiso/PE&#39;iso much less than 1) leads to underestimation of depth of anaesthesia and, during elimination, PE&#39;iso/Paiso much less than 1 will lead to an overestimation of anaesthetic depth. We measured Paiso/PE&#39;iso during a 60-min uptake period of 1% isoflurane and PE&#39;iso/Paiso during the subsequent 60-min elimination period in 26 patients (age 13-88 yr, ASA I-III) undergoing various surgical procedures. After 15 min of isoflurane uptake, Paiso/PE&#39;iso of 26 patients was mean 0.78 (SD 0.10) and this increased only marginally at 60 min (0.79 (0.09)), whereas during elimination, PE&#39;iso/Paiso was in the range 0.79 (0.14)-0.83 (0.11). Predictability of Paiso in a given patient is hindered by the high SD of Paiso/PE&#39;iso and PE&#39;iso/Paiso, but it may be improved by taking into account age, ASA physical status category, vital capacity, inspired minus end-tidal isoflurane partial pressure and arterial minus end-tidal carbon dioxide partial pressure during uptake; and obesity, end-tidal isoflurane partial pressure and arterial minus end-tidal carbon dioxide partial pressure during elimination. However, even with multiple regression analysis (to account for the various possible variables), clinically useful prediction of Paiso/PE&#39;iso and PE&#39;iso/Paiso in a particular patient is not possible (residual SD 0.084 and 0.113, respectively).
Sedation may influence the responses of some experimental pain models used to test analgesic effi... more 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.
A gas chromatographic method is described for the direct quantitative determination of the partia... more A gas chromatographic method is described for the direct quantitative determination of the partial pressure of halothane (or isoflurane) in blood as well as the blood-gas partition coefficient. A head space technique and a flame ionization detector were used. Standard blood was obtained by equilibrating patients&#39; blood with known gas concentrations in a tonometer. Using an infra-red analyser to measure the halothane gas concentration in the tonometer and within the anaesthetic system allowed for the direct comparison of the partial pressure in blood to the partial pressure in the inspired gas. Technical problems associated with this procedure, and with comparable methods, are discussed.
Arterial pressure is still one of the most important measures in estimating the required dose of ... more Arterial pressure is still one of the most important measures in estimating the required dose of inhaled anaesthetics. It is measured easily and reacts rapidly which makes it suitable as a variable for feedback control of depth of anaesthesia. Fuzzy logic, a novel approach to feedback control, was used to control arterial pressure in 10 patients during intraabdominal surgery by automatic adjustment of the concentration of isoflurane in fresh gas. During anaesthesia, fuzzy control periods of 45-min duration were alternated randomly with human control periods of equal duration. During the skin incision period (-3 to +12min) 48.2% of all fuzzy control pressure values were within ±10% of the desired mean arterial pressure compared with 40.4% of the human control values (P < 0.05). The corresponding values for the remainder of the operation were 78.3% and 83.2%, respectively. Thus fuzzy outperformed human control at skin incision, but was slightly inferior during the rest of the operation. We conclude that fuzzy logic is a promising new technique for control of isoflurane delivery during routine anaesthesia. (Br. J. Anaesth. 1995; 74: 66-72)
Automatic control of depth of hypnosis using the Bispectral Index (BIS) can help to reduce phases... more Automatic control of depth of hypnosis using the Bispectral Index (BIS) can help to reduce phases of inadequate control. Automated BIS control with propofol or isoflurane administration via an infusion system has recently been described, a comparable study with isoflurane administration via a vaporizer had not been conducted yet. Our hypothesis was that our new model based closed-loop control system can safely be applied clinically and maintains the BIS within a defined target range better than manual control. Twenty-three patients, American Society of Anesthesiologists risk class I-III, scheduled for decompressive spinal surgery were randomized into groups with either closed-loop or manual control of BIS using isoflurane. An alfentanil target-controlled infusion was adjusted according to standard clinical practice. The BIS target was set to 50 during the operation. The necessity of human intervention in the control system and events of inadequate sedation (BIS &amp;amp;lt;40 or BIS &amp;amp;gt;60) were counted. The number of phases of inadequate control, defined as BIS &amp;amp;gt;/=65 for more than 3 min, were recorded. The performance of the controller was assessed by several indicators (mean absolute deviation and median absolute performance error) and measured during the skin incision phase, the subsequent low flow phase, and the wound closure phase. Recovery profiles of both groups were compared. No human intervention was necessary in the closed-loop control group. The occurrence of inadequate BIS was quantified with the mean and median values of the area under the curve and amounted to 0.360 and 0.088 for the manual control group and 0.049 and 0.017 for the closed-loop control group, respectively. In the manual control group nine phases of inadequate control were recorded, compared with one in the closed-loop control group, 10.3% to 0.5% of all observed anesthesia time. During all phases the averages of the performance parameters (mean absolute deviation and median absolute performance error) were more than 30% smaller in closed-loop control than in manual control (P &amp;amp;lt; 0.05 between groups). Closed-loop control with BIS using isoflurane can safely be applied clinically and performs significantly better than manual control, even in phases with abrupt changes of stimulation that cannot be foreseen by the control system.
It generally is assumed that the potency of inhalational anesthetics remains unchanged during the... more It generally is assumed that the potency of inhalational anesthetics remains unchanged during the course of the administration of an anesthetic. Only one study has indicated a decrease of minimum alveolar concentration with time. In this study, an effect of the duration of anesthesia administration and surgery on the potency of isoflurane was investigated by determining MACtetanus (the minimum alveolar concentration that prevents movement in response to electrical tetanic stimulation in 50% of patients) before and after surgery. Ten patients who underwent removal of a herniated intervertebral disc were anesthetized with isoflurane only. Reaction to a standardized electrical stimulation applied to the forearm was observed and was graded as movement or no-movement. The isoflurane concentration was increased in steps of 0.10 vol% if the patient moved and decreased in steps of 0.10 vol% if no reaction was seen, until a &quot;movement/no-movement/movement&quot; or &quot;no-movement/movement/no-movement&quot; pattern, respectively, was achieved. MACtetanus decreased in all patients from 1.28 +/- 0.22 vol% (mean +/- SD) before surgery to 1.04 +/- 0.22 vol% after surgery (P &lt; 0.01). When the prestimulation arterial blood pressure or the maximal increase in blood pressure caused by stimulation at the individual MACtetanus before surgery were compared to the corresponding values at the individual MACtetanus after surgery, no significant difference could be found. The prestimulation heart rate and the maximal increase in heart rate were significantly lower after surgery, even though the end-tidal isoflurane concentration was 0.24 vol% lower at the individual MACtetanus after surgery. The authors conclude that MACtetanus decreases during the administration of anesthesia and the performance of surgery.
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