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Biomedical subjects

S Petersen-Felix

Publications and source records attributed to S Petersen-Felix.

33 records · Page 2Linked to original sources

Effects of extradural anesthesia on microcirculatory blood flow in free latissimus dorsi musculocutaneous flaps in pigs.

Free musculocutaneous flaps are used frequently in plastic surgery to reconstruct soft-tissue defects after radical cancer surgery and trauma. Despite improved surgical techniques, some of these flaps fail due to insufficient blood supply. Extradural anesthesia causes both sensory (pain relief) and sympathetic (vasodilatation) block that may be advantageous in free-flap surgery. This hypothesis, however, has not yet been studied. An experimental model in pigs was developed in which clinical conditions for anesthesia and microvascular surgery on the lower extremity were simulated as closely as possible. The effects of extradural anesthesia as well as phenylephrine infusion, combined with general anesthesia, on central hemodynamics and on microcirculatory blood flow in skin and muscle of the latissimus dorsi free flap were studied. After surgery, seven animals received extradural anesthesia during stable normovolemic conditions and another seven during mild hypovolemia (10 percent blood loss). The extradural block was objectively evaluated using the temporal summation test. Thirty minutes after induction of extradural anesthesia, the animals received an intravenous infusion of phenylephrine 1 microgram/kg per minute over a period of 15 minutes. Multichannel laser-Doppler flowmetry was used to measure microcirculatory blood flow in skin and muscle of the free flap as well as in control skin and muscle on the same extremity simultaneously. In normovolemic animals, extradural block caused a 10 percent decrease in mean arterial pressure and cardiac output and an approximately 20 percent decrease in microcirculatory blood flow in both the skin and muscle of the flap (all changes were nonsignificant). In slightly hypovolemic animals, however, extradural anesthesia caused a significant decrease in cardiac output (31 percent, p < 0.01), mean arterial pressure (24 percent, p < 0.01), and in mean blood flow in the flap muscle (22 percent, p < 0.05) and skin (20 percent, p < 0.05). During phenylephrine infusion, mean arterial pressure increased significantly (p < 0.05) in both hypovolemic and normovolemic animals, while cardiac output and microcirculatory blood flow in the flap remained almost unchanged. Extradural anesthesia does not improve microcirculatory blood flow in free musculocutaneous flaps in pigs. It causes a significant decrease in cardiac output, mean arterial pressure, and microcirculatory blood flow in slightly hypovolemic animals. During phenylephrine infusion, the microcirculatory blood flow in free flaps slightly improves due to the increase in mean arterial pressure. We suggest that extradural anesthesia for microvascular surgery should be used with great caution until human data are available.

Anesthesia, Epidural↗

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↗

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↗

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↗

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↗

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↗

Arterial pressure control with isoflurane using fuzzy logic.

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 + 12 min) 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 out-performed 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.

Adult↗

Analgesic effect in humans of subanaesthetic isoflurane concentrations evaluated by experimentally induced pain.

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.

Adult↗

Temporal summation during extradural anaesthesia.

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.

Adult↗

The effect of N-methyl-D-aspartate antagonist (ketamine) on single and repeated nociceptive stimuli: a placebo-controlled experimental human study.

Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor channel blocker known to inhibit "wind-up" and hence central hyperexcitability of dorsal horn neurons. We sought to assess the effect of ketamine on single and repeated nociceptive stimuli. A placebo-controlled, human (12 volunteers) experimental study was conducted in which several psychophysical (pain detection and tolerance thresholds, magnitude ratings) and electrophysiologic (withdrawal reflex) techniques were used 1) to investigate whether a ketamine (0.5 mg/kg) bolus followed by a 20-min infusion (9 micrograms.kg-1.min-1) inhibits central temporal summation to repeated nociceptive electrical stimuli, and 2) to assess quantitatively the hypoalgesic potency using several experimental nociceptive stimuli (argon laser, pressure, electrical). Facilitation of the withdrawal reflex to and pain rating of repeated electrical stimuli (five pulses at 2 Hz) were inhibited by ketamine. Reflex and pain rating to a single stimulus did not change. The pressure pain detection and tolerance thresholds were increased significantly by ketamine, whereas the laser heat pain and tolerance thresholds remained stable compared with placebo. The stimulus response function showed that ketamine reduced the responses to the highest electrical stimulus intensities (1.4, 1.6, and 1.8 times the reflex threshold). We conclude that ketamine inhibits central temporal summation in humans and has a marked hypoalgesic effect on high intensity nociceptive stimuli.

Analgesics↗

Wind-up and neuroplasticity: is there a correlation to clinical pain?

It is neurophysiologically and neurobiologically verified that the central nociceptive system can undergo changes and become hyperexcitable. Hyperexcitability involves wind-up (exaggerated responses) of dorsal horn neurones which in humans can be studied (temporal summation) by electrophysiological and psychophysical reactions to repeated nociceptive stimuli. Temporal summation occurs if repeated stimuli evoke increasing pain reactions. Human experimental models are adequate to investigate basic aspects and pharmacological modulation of summation and to bridge the gap between basic and clinical sciences facilitating the transfer of knowledge from basic science into the clinic. Human experimental investigations have confirmed animal studies that show that central summation is a potent mechanism in both normal and pathophysiological (hyperexcitable) conditions. Central summation should be considered as a target for the development of new centrally acting analgesics, for designing management regimens to treat intractable pain, and as a possible way of inhibiting surgically-induced afferent barrage from reaching brain centres (subconscious pain) during anaesthesia.

Analgesia↗

Ondansetron does not inhibit the analgesic effect of alfentanil.

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.

Adult↗

Anesthetic depth defined using multiple noxious stimuli during isoflurane/oxygen anesthesia. I. Motor reactions.

BACKGROUND: Potency of inhaled anesthetics usually is defined by determining the minimal alveolar concentration (MAC) that prevents movement in 50% of patients in response to skin incision. Skin incision, however, is usually only a single event and, thus, determination of potency cannot be repeated in one patient. Traditional MACskin incision cannot be used to predict response to other noxious stimuli. The aim of this study was to investigate the effects of other noxious stimulation patterns and then compare these to MACskin incision measuring the end-tidal isoflurane concentrations with the corresponding arterial concentrations. METHODS: In 26 patients, the end-tidal and corresponding arterial isoflurane concentrations needed to suppress eye opening to verbal command and motor response after trapezius squeeze, 50 Hz electric tetanic stimulation, laryngoscopy, skin incision, and tracheal intubation in 50% of all patients were determined. RESULTS: The end-tidal (equivalent arterial) isoflurane concentrations (mean +/- SE, adjusted to sea level) expressed in vol% (to allow comparison) increased in the following order (mean +/- SE): vocal command 0.37 +/- 0.09 (0.36 +/- 0.09); trapezius squeeze 0.84 +/- 0.07 (0.65 +/- 0.07); laryngoscopy 1.00 +/- 0.12 (0.78 +/- 0.09); tetanic stimulation 1.03 +/- 0.09 (0.80 +/- 0.06); skin incision 1.16 +/- 0.10 (0.97 +/- 0.17); and intubation 1.76 +/- 0.13 (1.32 +/- 0.11). CONCLUSIONS: Different stimuli require different isoflurane concentrations to suppress motor responses. Tetanic stimulation and, to some extent, trapezius squeeze are reproducible and noninvasive stimulation patterns that can be used as an alternative to skin incision when evaluating potency of an anesthetic agent. In contrast to skin incision, they can be repeated.

Adult↗

Anesthetic depth defined using multiple noxious stimuli during isoflurane/oxygen anesthesia. II. Hemodynamic responses.

BACKGROUND: The hemodynamic effects of isoflurane have been studied extensively. However, most data are obtained from volunteers or patients in the absence of surgical stimulation. The hemodynamic responses to various stimulation patterns of different intensity have not been evaluated. METHODS: In 26 patients, the ability of isoflurane to suppress motor and hemodynamic reactions in response to noxious stimulations of variable degree (trapezius squeeze, tetanic stimulation, laryngoscopy, skin incision, and laryngoscopy plus intubation) was evaluated by measuring arterial blood pressure and heart rate before and after stimulation. RESULTS: At concentrations that inhibited motor response to these stimuli in 50% of all patients, systolic blood pressure increased by 9 (trapezius squeeze), 15 (tetanic stimulation), 23 (laryngoscopy), 35 (skin incision) and 49 (intubation) mmHg, and heart rate by 5 (trapezius squeeze), 15 (tetanic stimulation), 17 (laryngoscopy), 36 (skin incision), and 36 (intubation) min-1 compared to the prestimulation values. An analysis using multiple regression showed that blood pressure response was influenced most by the type of stimulation followed by the concomitantly occurring motor reaction, the anesthesia time, and least by the isoflurane concentration per se. A high isoflurane concentration had no influence on the magnitude of blood pressure or heart rate increase to stimulation, but it decreased the prestimulation blood pressure and slightly increased the prestimulation heart rate. Heart rate responses were less consistent than those of blood pressure. CONCLUSIONS: Isoflurane used as a sole agent is unable to suppress hemodynamic reactions (blood pressure and heart rate) to painful stimuli. A "normal" blood pressure following stimulation can be achieved only if prestimulation blood pressure is depressed to levels that may be clinically unacceptable. The lack of motor response is not an accurate predictor of the ability of an agent to depress hemodynamic reaction.

Adult↗

Isoflurane minimum alveolar concentration decreases during anesthesia and surgery.

BACKGROUND: 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. METHODS: 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 "movement/no-movement/movement" or "no-movement/movement/no-movement" pattern, respectively, was achieved. RESULTS: MACtetanus decreased in all patients from 1.28 +/- 0.22 vol% (mean +/- SD) before surgery to 1.04 +/- 0.22 vol% after surgery (P < 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. CONCLUSION: The authors conclude that MACtetanus decreases during the administration of anesthesia and the performance of surgery.

Adult↗