The effect of muscle movement on the electroencephalogram during anesthesia with alfentanil

Using aperiodic analysis, we examined the impact on the electroencephalogram (EEG) of muscle activity from opiate-induced rigidity with alfentanil. We compared two groups of patients, one receiving alfentanil with neuromuscular blocking agents and the other group receiving no relaxants. The alfentanil-induced muscle rigidity exerted a noticeable effect on the EEG, with a moderate effect on total power at 1 Hz; a marked effect on the total number of waves, cumulative percent power at 3 Hz, and average power at 17 to 19 Hz; and a striking effect on F90, the frequency below which 90% of the power resides. The presence of electromyographic (EMG) noise in the EEG consistently altered the variables derived from the EEG, so that anesthetic depth appeared less than it actually was. This was true in spite of the fact that we gave slightly more alfentanil in the group not receiving a relaxant. Although the observed muscle activity was greater than that usually seen clinically, and may have differed qualitatively, the results do serve as a warning that muscle noise can interfere with the EEG. Currently, there is no computerized technique that will reject or account for this noise, and we must depend on observation to recognize the EMG patterns within the EEG, either with the raw recording or with a detailed analysis (such as aperiodic analysis), and to compensate for this noise if possible. Techniques that average the EEG or that present a single number have difficulty providing this information. These results do not detract from the usefulness of the EMG contained in EEG recordings as a supplementary or complementary indicator of anesthetic lightness.     

Electroencephalogram spectral edge frequency,lower esophageal contractility,and autonomic responsiveness during general anesthesia

Both the electroencephalogram (EEG) spectral edge frequency (SEF) and lower esophageal contractility (LEC) indices have been reported to be useful indicators of anesthetic depth. We designed a prospective study to evaluate the relationship between changes in these two variables and objective measurements of physiologic responsiveness to surgical stress (i.e., changes in hemódynamic variables and plasma levels of norepinephrine, epinephrine, total catecholamines, and vasopressin). Eighty-nine consenting adult males undergoing radical prostatectomy procedures under a standardized general anesthetic technique were studied according to a randomized, single-blinded protocol. General anesthesia was induced with 30 µg/kg intravenous (IV) alfentanil, 2.5 mg/kg IV thiopental, and 0.1 mg/kg IV vecuronium, and subsequently maintained with 0.5 µg/kg/min alfentanil, nitrous oxide (N₂O) 67% in oxygen, and 0.8 µg/kg/min vecuronium. Following retropubic dissection, 81 patients (92%) manifested acute hypertensive responses, with mean arterial pressure increasing from 90±14 to 122±14 mm Hg (mean ± SD). This acute hypertensive response was treated with one of three different treatment modalities (20 to 60 µg/kg IV alfentanil, 0.5 to 2.0% inspired isoflurane, or 0.05 to 0.15 mg/kg IV trimethaphan) to return the mean arterial pressure to within 10% of the preincisional (baseline) value within 5 to 10 minutes. Although the mean arterial pressure, heart rate, and plasma levels of catecholamines and vasopressin significantly increased following the surgical stimulus, and decreased after adjunctive therapy, the EEG-SEF and LEC index (LECI) values did not significantly change during these study intervals. Furthermore, using a logistic regression analysis, we observed that preincision EEG-SEF and LECI values could not predict whether patients would manifest a hypertensive response. Therefore, the EEG-SEF and LECI were unreliable indicators of anesthetic depth.This study was supported in part by a grant from the Ambulatory Anesthesia Research Foundation, Los Altos, CA. (Dr White is a member of the Board of Directors.)The authors would like to thank Dan Kuni (Baxter Healthcare) for his assistance in obtaining the equipment used to perform the study; Vinod Kothapa, MD, for his valuable assistance with the anesthetic management of the study patients; Alex K. Mills, MD, for his assistance with the EEG interpretation; and Steven A. Bai, PhD, for his assistance with the plasma alfentanil analyses.     

Analytical methods to differentiate similar electroencephalographic spectra: neural network and discriminant analysis

Differences in electroencephalographic (EEG) power spectra obtained under similar, but not identical, conditions may be difficult to discern using standard techniques. Statistical analysis may not be useful because of the large number of comparisons necessary. Visual recognition of differences also may be difficult. A new technique, neural network analysis, has been used successfully in other problems of pattern recognition and classification. We examined a number of methods of classifying similar EEG data: standard statistical analysis (analysis of variance), visual recognition, discriminant analysis, and neural network analysis. Twenty-nine volunteers received either thiopental (n = 9), midazolam (n = 10), or propofol (n = 10) in sedative doses in 3 different studies. These drugs produced very similar changes in the EEG power spectra. Except for beta₂ power during thiopental infusion, differences between drugs could not be detected using analysis of variance. Visual categorization was correct in 72% of the baseline EEGs, 70% of thiopental EEGs, 27% of propofol EEGs, and 46% of midazolam EEGs. A classification neural network (Learning Vector Quantization network) containing a Kohonen hidden layer was able to successfully classify 57 of 58 EEG samples (of 4 minutes’ duration). Discriminant analysis had a similar rate of success. This level of performance was achieved by dividing the EEG power spectrum from 1 to 30 Hz into 15 2-Hz bandwidths. When the EEG power spectrum was divided into the “classical” frequency bandwidths (alpha, beta₁, beta₂, theta, delta), both neural network and discriminant analysis performance deteriorated. By training the network using only certain inputs we were able to identify drugspecific bandwidths that seemed to be important in correct classification. We conclude that propofol, thiopental, and midazolam produce different effects on the EEG and that both neural network and discriminant analysis are useful in identifying these differences. We also conclude that EEG spectra should be analyzed without using classical EEG bands (alpha, beta, etc.). Additionally, neural networks can be used to identify frequency bands that are “important” in specific drug effects on the EEG. Once a classification algorithm is obtained using either a neural network or discriminant analysis, it could be used as an on-line monitor to recognize drug-specific EEG patterns.     

截瘫患者气管插管应激反应的临床研究

20例胸腰段截瘫患者，随机分为两组。Ⅰ组静注硫酸喷妥纳、潘库溴铵及小剂量芬太尼诱导，诱导前舌下含化硝苯吡啶，肌松后插管。Ⅱ组仅静注硫喷妥钠与潘库溴铵。两组分别于诱导前后定时进行血流动力学及血浆儿茶酚胺含量的测定。结果显示Ⅰ组的各项血流动力学测定指标与血浆儿芬酚胺含量接近或低于诱导前基础值，而Ⅱ组插管后均明显上升，两组对比有显著性差异，说明胸腰段脊髓损伤患者气管插管时仍存在血压上升、心率增快及血浆儿茶酚胺增多的应激反应，小剂量芬太尼与硝苯吡啶可有效地减弱插管时的应激反应。     

Effects of intravenous anesthetic agents on middle cerebral artery blood flow velocity during induction of general anesthesia

Objective. Our objective was to quantify the effects of intravenous anesthetics on values measured by or derived from transcranial Doppler sonography (TCD) during induction of general anesthesia.Methods. We recorded blood flow velocity in the middle cerebral artery (V-MCA) before, during, and after induction of general anesthesia in six groups of young patients without intracranial pathology (n=10 each) using TCD. Patients were randomized to receive either 2 mg/kg propofol, 1.5 mg/kg methohexital, 5 mg/kg thiopental, 0.3 mg/kg etomidate, 2 µg/kg fentanyl and 0.15 mg/kg midazolam, or 1.5 mg/kg ketamine and 0.15 mg/kg midazolam intravenously. At 2 min after injection, each patient was intubated and given isoflurane 0.8% and nitrous oxide 66% in oxygen. Ventilation was set to achieve an end-tidalPco ₂ of 40 mm Hg. V-MCA, arterial blood pressure, heart rate, hematocrit, andPco ₂ (venous samples) were measured before and 1, 3, 5, 10, and 30 min after induction of anesthesia.Results. The preinduction data were not different between groups. At 1 min after injection, propofol, thiopental, methohexital, and etomidate significantly decreased V-MCA. TCD values were only slightly affected following fentanyl/midazolam. Ketamine/midazolam induced a modest rise in V-MCA. After endotracheal intubation, V-MCA increased in all groups, and slowly declined thereafter.Conclusions. Under the circumstances of our study, values derived from TCD measurements responded differently to the agents used to induce general anesthesia in nonneurosurgical patients.     

Transcranial electrical stimulation with high frequency intermittent current (Limoge's) potentiates opiate-induced analgesia: blind studies

Transcutaneous cranial electrical stimulation (TCES) with high frequency (166 kHz) intermittent current (100 Hz: Limoge current) has been used for several years in cardiac, thoracic, abdominal, urological and micro-surgery. The main benefits are a reduced requirement for analgesic drugs, especially opiates, and a long-lasting postoperative analgesia. We have confirmed these clinical observations in rats using the tail-flick latency (TFL) test to measure pain threshold. TCES was not found to modify the pain threshold in drug-free rats, but it potentiated morphine-induced analgesia (systemic injection). To obtain a maximal effect, the stimulation must be initiated 3 h before the drug injection and be maintained throughout the duration of its pharmacological action. TCES potentitation was found to depend on the dose of the drug, the intensity of the current and the polarity of electrodes. These findings were confirmed by blind tests of the efficiency of TCES on several opiate analgesic drugs currently used in human surgery (morphine, fentanyl, alfentanil and dextromoramide). The analgesic effect of these 4 opiates (TFL as % of baseline without or with TCES) were respectively: 174%, 306%; 176%, 336%; 160%, 215%; and 267%, 392%. The results were obtained not only after systemic opiate treatment, but also after intracerebroventricular injection of morphine (10 micrograms; analgesic effect 152%, 207% with TCES) suggesting that TCES potentiation of opiate-induced analgesia is centrally mediated.     

Decreased fentanyl and alfentanil dose requirements with age. A simultaneous pharmacokinetic and pharmacodynamic evaluation

The effect of increasing age on the dose of fentanyl or alfentanil required to produce the same electroencephalographic (EEG) stage was studied in adult male patients. The pharmacokinetic and pharmacodynamic components of each patient's dose-response relationship were evaluated simultaneously. Frequent arterial blood samples drawn during and after an infusion of fentanyl or alfentanil were assayed by radioimmunoassay and permitted determination of each patient's pharmacokinetic profile. The EEG was analyzed by power spectral analysis and a parameter (spectral edge frequency) chosen to quantitate the narcotic-induced EEG slowing. An inhibitory sigmoid Emax pharmacodynamic model related spectral edge frequency to narcotic serum concentrations. The dose requirement of fentanyl or alfentanil decreased significantly with increasing age (a 50% decrease from age 20 to 89). No age-related changes in the pharmacokinetic parameters were found. Brain sensitivity (as determined by EEG changes) did decrease significantly with age. Thus, the decreased dose requirement in the elderly had a pharmacodynamic explanation, using the EEG as a measure of narcotic drug effect.     

Relative reinforcing effects of three opioids with different durations of action

The role of duration of action on the relative reinforcing effects of three opioid drugs (fentanyl, alfentanil, and remifentanil) was evaluated. Duration and onset of action were determined using measures of respiratory depression and antinociception after i.v. administration. Effects on minute volume of respiration indicated that each of the three opioids had immediate onsets of action after i.v. administration. Fentanyl's duration of suppression of respiration and antinociception was longer than that of alfentanil, which was longer than that of remifentanil. Reinforcing strength was measured in i.v. self-administration studies in which the fixed ratio resulting in drug administration was increased from one session to the next. Comparisons were made of the behavioral economic variables P(max) and area under the demand curve (O(max)). Remifentanil maintained higher rates of responding than did alfentanil, and alfentanil maintained higher rates of responding than did fentanyl. When normalized demand functions were compared, however, the drugs did not differ significantly from each other in terms of P(max) or O(max). These data agree with those of others who have suggested that duration of action is not an important contributor to drugs' reinforcing strength.     

Fuzzy-logic control of blood pressure through enflurane anesthesia

Objective. The objective of our study was to construct a closed-loop blood pressure control system using fuzzy logic during enflurane anesthesia.Methods. Direct systolic blood pressure (SBP), the input variable, was assessed by a special fuzzy-logic membership function—that is, a triangulate continuum of grades between 0 and 1. We also set up the output membership function for the inhaled enflurane concentration. Four fuzzy-rule maps, or matrices, which determined the relationship between the changes of input variables and output values, were constructed based on published anesthetic values. The first map was based on the end-tidal anesthetic concentration known to block an adrenergic response. The fourth map was derived from the anesthetic effective dose (AD₉₅). Fuzzy inference, arrived at by using fuzzy logic, followed the minimum-maximum center of gravity method. Anesthetic control started with the first map and was maintained with the succeeding maps.Results. During anesthesia, the SBP remained within ±20% of the preanesthetic SBPs in 82% of the fuzzy control cases and within 83% during manual control. The difference was not significant.Conclusion. The anesthetist’s management of the administration of the inhaled anesthetic enflurane was imitated by fuzzy-logic control of the blood pressure. This paper was presented in part at the Proceedings of the International Conference on Fuzzy Logic & Neural Networks IIZUKA ’90.     

Reinforcing effect of alfentanil is mediated by mu opioid receptors: apparent pA2 analysis

Apparent pA2 analysis was used to determine whether the short-duration opioid agonist, alfentanil, acts at mu receptors in the positive reinforcement of operant behavior in the rhesus monkey. In test sessions a red light signaled the availability of alfentanil injections. If a monkey pressed a response lever 30 times, a specific dose of alfentanil was injected i.v., and the red light was extinguished for 10 min. This cycle could be repeated for up to 130 min, the maximum length of a session. Between successive test sessions at least three maintenance sessions were held; in these sessions injections of 0.32 mg/kg/injection of codeine were made available. The dose of alfentanil was changed from one test session to the next, and dose-dependent changes in rates of responding resulted. Rates reached 3.05 responses/sec at 0.010 mg/kg/injection, the highest dose tested. The opioid antagonist, quadazocine, produced dose-dependent, parallel shifts to the right in the alfentanil dose-response curve. In Schild Plot analysis the regression line fit to the antagonism data had a slope of -1.1; the apparent pA2 value for quadazocine was 7.6. This value was close to apparent pA2 values obtained with mu agonists in studies of other behavioral effects of opioids, but distinct from values obtained with kappa agonists in those studies. Thus, it is likely that mu receptors mediate the positive reinforcing effect of alfentanil.     

不同麻醉诱导下小儿气管插管时的心血管应激反应

目的用随机对照前瞻性研究方法，比较小儿气管插管时心血管反应，评价不同麻醉诱导方式对插管时应激反应的抑制作用。方法58例1～6岁的患儿被随机分成P、PF及PF1组，P组静脉注射硫喷妥钠5mg／kg；PF组先静脉注射芬太尼3μg／kg，再静脉注射硫喷妥钠5mg／kg；PF1组先静脉注射芬太尼3μg／kg，再静脉注射硫喷妥钠5mg／kg，同时吸入3％异氟醚。所有患儿由同一位医生进行气管插管，记录其麻醉前以及插管前、后的心率和血压。结果插管后P组的心率和血压最高，不仅显著高于插管前，还显著高于基础值（P〈0．05）。PF组插管后的心率和血压虽然也高于插管前，但低于P组，而且与基础值比较差异无统计学意义。PF1组插管后的血压仅略高于插管前，但比基础值低（P〈0．05），在3组中最低（P〈0．05），且升幅最小（P〈0．05），其收缩压和舒张压的升幅分别为10％和24％。结论给患儿插管时联合应用硫喷妥钠、芬太尼和异氟醚，心血管反应最小，提示可以较好地抑制插管所至的应激反应。     

Why the phantom p-wave during general anesthesia?

Although atrioventricular junctional rhythm (AVJR) is frequently encountered during general anesthesia, its genesis is poorly understood. The present study was undertaken to test the hypothesis that AVJR is promoted by hypocarbia. One hundred patients (69 females, 31 males), ASA Physical Status Class I, who were 20 to 30 years old, were studied. One-half of the patients were induced with thiopental and maintained with 0.5 to 2.1% isoflurane, 70% nitrous oxide (N2O) and oxygen. The other half of the patient population was induced with thiopental and fentanyl or alfentanil and maintained with the opioid, 70% N2O and oxygen. During maintenance, each patient was hyperventilated to an endtidal carbon dioxide level of 20 to 25 mm Hg and the electrocardiogram recorded to determine if the p-wave disappeared, which is the obvious manifestation of AVJR. During normocarbia, none of the 100 patients developed AVJR. During hypocarbia, the incidences of AVJR during isoflurane-N2O anesthesia and opioid-N2O anesthesia of 18% and 26%, respectively, were significant by chi-square analysis. Consequently, the data suggest that hypocarbia may promote AVJR during general anesthesia.     

EEG predicts movement response to surgical stimuli during general anesthesia with combinations of isoflurane, 70% N2O,and fentanyl

Objective. Our objective was to evaluate the performance of the EEG as an indicator of anesthetic depth by measuring EEG prediction of movement response to surgical stimuli.Methods. While using 5 different combinations of isoflurane, 70% N₂O, and fentanyl, we measured the EEG of 246 patients during pelvic laparoscopy and observed their movement responses to opening stimuli (defined as skin incision, CO₂ needle insertion, or trocar insertion) and also to closing stimuli (defined as sutures during incision closure). The EEG was expressed asF95, the frequency in hertz below which resides 95% of the power in the EEG frequency spectrum. The relations betweenF95 and movement response were expressed as logistic regression curves.F95-response logistic regression curves, which are analogous to dose-response curves, were calculated for each of the 2 stimuli administered during each of the 5 anesthetic techniques. The prediction of patient responsiveness byF95 was tested using (beta), a measure of the slope of anF95-response logistic curve. The presence of shifts among theF95-response logistic curves was tested using the differences inF95 values between curves. Hypothesis tests used a level of significance ofP = 0.05.Main Results. The slopes of theF95-response logistic regression curves showed a statistically significant ability to predict movement response to stimuli for 9 of the 10 combinations of stimuli and anesthetic techniques. We did not calculate anF95-response logistic curve for the tenth combination because it contained burst suppression, which our EEG analysis method was not designed to process. TheF95-response logistic curves were shifted relative to each other, and the shifts were affected by the type of stimulus and the combination of anesthetic agents. Referenced to opening curves, the mean shift of the closing curves was ± 4.2 ± 0.3 Hz (mean ± SD). With increasing doses of fentanyl, the use of 70% N₂O, or both, the curves shifted to higher values ofF95; the range in shifts was 0.2 to 8.1 Hz. The slope values of theF95-response logistic curves and the shifts among the curves were similar to the values and shifts that might be expected from changes in anesthetic agent doses.Conclusions. The EEG, expressed asF95, predicted movement response to surgical stimuli during combinations of isoflurane, 70% N₂O, and fentanyl. TheF95-response curves shifted upward on the frequency scale for the less intense stimuli and for anesthetic techniques using 70% N₂O, fentanyl, or both.F95 prediction of movement response appeared to be related to anesthetic agent doses. OurF95-response curves may provide helpful guidelines for usingF95 to titrate the administration of anesthetic agents and for assessing the depth of general anesthesia.     

Continuous infusion of alfentanil for maintenance of anesthesia: comparison with halothane anesthesia

This study compares anesthetic maintenance, hemodynamic stability, and speed of recovery obtained with inhalational halothane versus intravenous alfentanil anesthesia administered continuously. In two groups of patients, anesthesia was induced with sodium thiopental, maintained with 70% nitrous oxide in 30% oxygen, and either halothane (n = 10) or a continuous infusion of alfentanil (n = 10). The administration of the allocated anesthetic was adjusted according to strict predefined criteria of inadequate anesthesia. After endotracheal intubation, hemodynamics (heart rate, systolic and diastolic pressure) changed less in the alfentanil group (P less than .01). Overall hemodynamic stability was the same in both groups. In neither group was there recall of intraoperative events. Recovery was assessed by the time from cessation of nitrous oxide administration to return of spontaneous ventilation, response to simple command, extubation, orientation, and discharge from the recovery area. The time taken to respond to simple command was significantly shorter in the alfentanil group (P less than .05), but other indices of recovery were similar.     

Steady-state infusions of opioids in human volunteers. I. Pharmacokinetic tailoring

We report a method for controlling and adjusting plasma opioid concentration to preselected target values in individual human subjects in order to study analgesic and other effects of opioids at steady state. The method employs a computer-controlled infusion pump and an algorithm that utilizes individual subject pharmacokinetic parameters predetermined with tailoring bolus opioid doses. We used this approach to produce 3-step increases in plasma concentrations of alfentanil, fentanyl and morphine in each of 15 subjects. We maintained each plasma concentration plateau for 70 min, measured plasma opioid concentrations achieved during the infusions and analyzed the results for bias and precision of the individually tailored infusions. Our results show that pharmacokinetically tailored opioid infusions produce stable plasma opioid concentrations within 10 min for alfentanil and morphine; with each drug overall prediction error was 20% or less. Fentanyl was somewhat more difficult to control by this method than were the other 2 opioids. We conclude that individual tailoring of opioid infusions minimizes the impact of individual pharmacokinetic differences on achieving preselected plasma opioid concentrations and provides an accurate means of controlling steady-state drug concentrations for studies of concentration-effect relationships and comparisons of side-effect intensities produced by equianalgesic plasma opioid concentrations.     

Brief wakeful response to command indicates wakefulness with suppression of memory formation during surgical anesthesia

Objective. In a previous study of patients emerging from anesthesia following surgery, we found that a brief wakeful response to command of an eye opening or single hand squeeze or count was not associated with memory formation, while the response of four hand squeezes or counts was associated with memory. We wanted to determine the anesthetic requirements for obtaining this brief wakeful response endpoint during surgery and to determine if memory occurred at this endpoint during surgical anesthesia.Methods. Six different combinations of isoflurane, 70% N₂O, and fentanyl were administered to 326 patients undergoing pelvic laparoscopy. After insertion of the trocar, anesthesia was reduced while patients were given verbal commands, and they were observed for movement responses to surgery and to command. Patients were classified as either not arousing, arousing with a movement response to surgery, or arousing with a wakeful response to command. For the patients who aroused, we calculated the percentage of arousal responses that were wakeful responses to command. The effect of fentanyl dosage upon the percentage of arousal responses that were wakeful responses to command was determined by using a Mann-Whitney test to compare a group of patients receiving fentanyl 2 µg/kg or less, with a group receiving fentanyl 4 µg/kg. In a subset of 39 patients, the potential for memory formation was evaluated by presenting a target sound to 29 patients during a period of either no arousal, movement response to surgery, or wakeful response to command; for a control group of 10 patients, no target sound was presented. All 39 patients were tested for memory of the target sound; the results from each group receiving a target sound were compared with the results of the control group, using a Mann-Whitney test.Main Results. A total of 68 patients aroused with either a movement response or a wakeful response to command. Wakeful responses occurred with only 1 of 39 patients (3%) receiving fentanyl 2 µg/kg or less; but, wakeful responses occurred with 17 of 29 patients (59%) receiving fentanyl 4 µg/kg. The difference between the groups was significant atp=0.01. None of the 68 patients had recall of intraoperative events or unpleasant dreams. None of these patients who were in the multiple-choice memory subset recalled the target sound. There were no statistically significant differences on the multiple-choice memory test between the groups presented with the target sound and the control group. Patient anecdotes suggested that some patients may have had memory of the target sound; but, memory was no more likely in patients with a brief wakeful response to command than in those who responded with a movement to surgical stimulation or those who did not have an arousal response.Conclusions. A brief wakeful response to a command of opening the eyes or squeezing the hand was not associated with increased memory formation during surgery. A brief wakeful response to command was found during surgery when patients received fentanyl 4 µg/kg; but it was rarely found at fentanyl dosages of 2 µg/kg or less.     

Potent and long lasting antinociceptive effects after injection of low doses of a mu-opioid receptor agonist, fentanyl, into the brachial plexus sheath of the rat

The effect of administering low doses (0.5-1.5 micrograms) of the mu-opioid receptor agonist fentanyl into the right brachial plexus sheath of the rat was examined using the vocalization threshold to paw pressure test. Both forepaws were tested in each rat. Fentanyl injected into the right brachial plexus sheath at 0.5-1.5 micrograms/kg produced a localized, dose-dependent, potent and long lasting antinociceptive effect, as gauged on the right forepaw. At the lower dose used (0.5 microgram/kg of fentanyl), the antinociceptive effect was restricted to the right forepaw and lasted for more than 2 h. Increasing doses of fentanyl (1 and 1.5 micrograms/kg) induced potent effects, lasting up to 5-6 h or even longer. In complete contrast, fentanyl administered i.v. at the dose of 1 microgram/kg had a very transient effect, only lasting up to 25 min. The results of injection of low doses of the opioid antagonist naloxone when administered either i.v. or locally into the paw, on the effect of fentanyl suggest the involvement of a peripheral site of action of the opioid. The present findings suggest that, as already observed in patients in clinical situations, low doses of opiates delivered using this administration route may provide prolonged regional analgesia, with the potential of avoiding centrally mediated side effects.     

Bispectral index variations during tracheal suction in mechanically ventilated critically ill patients: effect of an alfentanil bolus

OBJECTIVE: To evaluate the impact of an alfentanil dose on bispectral index (BIS) variations during tracheal suction in ICU sedated patients. DESIGN AND SETTING: A prospective open-label pilot study in a 12-bed surgical ICU in a university-affiliated, tertiary referral hospital. PATIENTS: Eleven sedated (midazolam plus fentanyl) mechanically ventilated patients. INTERVENTIONS: Continuous monitoring of BIS with arterial pressure and heart rate before, during, and after tracheal suction without (control period) and with an intravenous bolus of alfentanil (15 microg/kg, alfentanil period) before suction. RESULTS: Steady-state BIS value was 61+/-8 for the control period and 59+/-7 for the alfentanil period. Blood pressure and heart rate were similar between baseline periods. One minute after tracheal suction, a significant increase in BIS level was observed in the control period, which remained significantly different from the alfentanil period until 10 min later. Significant higher systolic and diastolic blood pressure and heart rate were observed during the control period than the alfentanil period. However, no difference in Ramsay scores was observed between the two periods. CONCLUSIONS: An alfentanil bolus of 15 microg/kg markedly reduced the increase in BIS values, blood pressure, and heart rate observed immediately after tracheal suction. Therefore BIS monitoring in ICU may help to improve analgesia during invasive events.     

Profiles of opioid analgesia in humans after intravenous bolus administration: alfentanil, fentanyl and morphine compared on experimental pain

This report examines the relationship of plasma drug concentration to analgesic effect following bolus doses of alfentanil, fentanyl and morphine and assesses individual differences in analgesic response among volunteers. We predicted that the 3 opioids would yield disparate analgesic profiles because their physicochemical and pharmacokinetic characteristics differ. Ten healthy volunteers received intravenous bolus doses of either alfentanil, fentanyl, morphine or normal saline on different days. We stimulated their teeth electrically and measured brain evoked potential (EP) and pain report (PR) repeatedly over 2 h to assess analgesic effect. Concurrently, we drew 18 blood samples to assess opioid plasma concentrations during the test period. The relationship between opioid plasma concentration and analgesic effect was well defined for alfentanil but ambiguous for morphine. Fentanyl exhibited a marked hysteresis. We observed noteworthy individual differences in analgesic response with all 3 drugs but these differences were greatest for morphine and least for alfentanil. Inter- and intrasubject variability in analgesic response across drugs is related to the physicochemical properties of the drugs tested.     

Sufentanil, fentanyl, and alfentanil in head trauma patients: a study on cerebral hemodynamics

OBJECTIVES: To determine the effects of bolus injection and infusion of sufentanil, alfentanil, and fentanyl on cerebral hemodynamics and electroencephalogram activity in patients with increased intracranial pressure (ICP) after severe head trauma. DESIGN: Randomized, unblended, crossover study. SETTING: Intensive care unit and trauma center in a university hospital. PATIENTS: Six patients with head trauma and ICP monitoring, sedated at the time of the study with propofol infusion and full neuromuscular blockade. INTERVENTIONS: Following a randomized order, in an unblended and crossover fashion, the level of sedation was deepened with a 6-min injection of either sufentanil (1 microg/kg), alfentanil (100 microg/kg), or fentanyl (10 microg/kg) followed by an infusion of 0.005, 0.7, and 0.075 microg/kg/min, respectively, for 1 hr. The three opioids were given to each patient at 24-hr intervals. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure (MAP), ICP, cerebral perfusion pressure (CPP), and jugular vein bulb oxygen saturation (Svjo2) were continuously measured and recorded at 1-min intervals throughout the 60-min study period. Sufentanil, fentanyl, and alfentanil infusions were associated with a significant but transient increase in ICP (9+/-2 mm Hg [SD], 8+/-2 mm Hg, and 5.5+/-1 mm Hg, respectively; p<.05). The increase in ICP peaked at 5, 6, and 3 mins, respectively, then gradually decreased and returned to baseline values after 15 mins. This result was accompanied by a significant decrease in MAP (21+/-2 mm Hg, 24+/-2 mm Hg, and 26+/-2 mm Hg, respectively; p<.05) and, thus, in CPP (30+/-3 mm Hg, 31+/-3 mm Hg, and 34+/-3 mm Hg, respectively; p<.05). After 5 mins, MAP and CPP gradually increased, although they remained significantly decreased throughout the study period. No changes in lactate-oxygen index, used as an ischemia index, were observed. Changes in electroencephalogram tracings were characterized by a switch from a fast to a decreased activity, together with an improvement in the background activity. CONCLUSION: The results of the present study show that alfentanil, sufentanil, and fentanyl produce similar transient increases in ICP when administered by bolus injection in patients with increased ICP. No evidence of cerebral ischemia was observed in the study patients.