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Biomedical subjects

P S Sebel

Publications and source records attributed to P S Sebel.

At least 37 records · Page 2Linked to original sources
PubMed1996

Reduction of isoflurane minimal alveolar concentration by remifentanil.

BACKGROUND: Remifentanil is a new micro-specific opioid receptor agonist currently under investigation. The interaction between opioids and volatile anesthetics is complex. Defining this interaction provides a basis for more rational dosing schemes when such combinations are used for anesthesia and allows the anesthetic potency of remifentanil relative to other opioids to be determined. METHODS: Two centers enrolled a total of 220 patients. Patients were randomized to receive a target concentration of remifentanil via a computer-assisted continuous infusion device of either 0.0, 0.5, 1.0, 1.5, 2.0, 4.0, 8.0, 16.0, and 32.0 ng/ml initiated before the administration of isoflurane. Patients were also stratified by groups 18-30, 31-55, and 56-65 yr. After induction of anesthesia with isoflurane the initial patient in each dose group was assigned an age-adjusted isoflurane concentration. The isoflurane concentration for each subsequent patient was adjusted according to the up/down technique until a minimum of 12 patients were enrolled in each group. Arterial blood samples for remifentanil whole blood concentrations were obtained. The patient was observed for purposeful movement for up to 1 min after skin incision. The minimum alveolar concentration (MAC) of isoflurane (0 ng/ml remifentanil group) and MAC reduction of isoflurane by remifentanil were determined. RESULTS: The MAC of isoflurane alone was 1.3%. Remifentanil caused an exponential reduction in the MAC of isoflurane with 1.37 ng/ml remifentanil a 77% reduction and 32 ng/ml a 91% reduction of isoflurane MAC. CONCLUSION: The MAC reduction of isoflurane by remifentanil is similar to that produced by other opioids. Although remifentanil was given at extremely high concentrations in the absence of isoflurane, it did not provide adequate anesthesia. A 50% isoflurane MAC reduction is produced by 1.37 ng/ml remifentanil whole blood concentration compared to previously published plasma concentrations of fentanyl of 1.67 ng/ml or sufentanil of 0.14 ng/ml.

Adolescent↗
PubMed1995

EEG bispectrum predicts movement during thiopental/isoflurane anesthesia.

OBJECTIVE: The objective of our study was to test the efficacy of the bispectral index (BIS) compared with spectral edge frequency (SEF), relative delta power, median frequency, and a combined univariate power spectral derivative in predicting movement to incision during isoflurane/oxygen anesthesia. METHODS: A total of 42 consenting patients were assigned to 3 groups, isoflurane 0.75, 1.0, and 1.25 minimal alveolar concentration (MAC). Anesthesia was induced with thiopental and maintained with the appropriate end-tidal concentration of isoflurane. The electroencephalogram (EEG) was recorded using a microcomputer system, and data were analyzed off-line. The EEG during the 2 min before incision was analyzed. Following skin incision, each patient was carefully observed for 60 sec to detect occurrence of purposeful movement. RESULTS: For all groups combined, there was a statistically significant difference for BIS (p < 0.0001) and also for relative delta power (p < 0.016) between movers and nonmovers. There was a statistically significant difference between movers and nonmovers at 1.25 MAC isoflurane for BIS (p < 0.01). There were no other significant differences for any other EEG variable at any concentration of isoflurane. No EEG variable showed a relationship to isoflurane concentration. CONCLUSIONS: When bispectral analysis of the EEG was used to develop a retrospectively determined index, there was an association of the index with movement. Thus, it may be a useful predictor of whether patients will move in response to skin incision during anesthesia with isoflurane/oxygen.

Adult↗
PubMed1995

Prediction of movement using bispectral electroencephalographic analysis during propofol/alfentanil or isoflurane/alfentanil anesthesia.

Conventional electroencephalographic (EEG) analysis techniques do not use the phase information from the Fourier analysis. This study used a new technique of EEG analysis, bispectral analysis, which measures interfrequency phase relationships in the EEG. Using a reference database, and a process of multivariate discriminant analysis, we developed a univariate bispectral variable, the bispectral index (BIS). This study was designed to test the efficacy of BIS in predicting movement to incision during either an isoflurane/alfentanil anesthetic or a propofol/alfentanil anesthetic technique. Fifty consenting patients were randomized to two groups; one received isoflurane/alfentanil and the other, propofol/alfentanil for anesthesia. EEG was recorded using a microcomputer system and the data were analyzed off-line. Hemodynamic variables were also recorded. After skin incision, each patient was observed carefully for 2 min to detect purposeful movement. A significant difference was found between the BIS values for movers versus nonmovers within each of the two treatment groups (P < or = 0.002). However, isoflurane/alfentanil nonmovers could not be distinguished from propofol/alfentanil movers (P < or = 0.180), suggesting a treatment group effect independent of response classification. Preincision hemodynamic variables did not predict patient movement in response to skin incision. These findings suggest the possibility that different anesthetics have different effects on BIS, and thus BIS may not be independent of the anesthetic. Interfrequency phase coupling, a nonlinear feature of the EEG which is measured with bispectral analysis, may contain clinically useful information for the assessment of anesthetic adequacy. In this study, BIS was a better predictor of patient response than other currently available variables including hemodynamic status.

Adult↗
PubMed1995

Histamine concentrations and hemodynamic responses after remifentanil.

Remifentanil is a new potent opioid analgesic that undergoes rapid esterase metabolism. The purpose of this study was to investigate hemodynamic responses to 2-30 micrograms/kg remifentanil (escalating doses) injected as a bolus over 1 min during general anesthesia. After general anesthesia with endotracheal intubation, placement of a radial artery catheter, and pretreatment with glycopyrrolate, remifentanil 2, 5, 15, or 30 micrograms/kg (six patients, three male and three female per group) was administered over 1 min. Arterial blood pressure and heart rate were measured noninvasively before drug administration, after drug administration, and then every minute for 5 min. Arterial blood was taken for histamine determinations before drug administration and then at 1, 3, and 5 min after drug administration. Administration of remifentanil was associated with a reduction in systolic blood pressure from 134 +/- 18 to 91 +/- 16 mm Hg and heart rate from 99 +/- 20 to 69 +/- 21 bpm and was not associated with alterations in histamine concentration.

Adult↗
PubMed1995

Postoperative pain control with a new transdermal fentanyl delivery system. A multicenter trial.

BACKGROUND: A new transdermal delivery system for fentanyl is available in two strengths: 70-80 and 90-100 micrograms.kg-1.h-1 (40- and 60-cm2 patches, respectively). Their short onset and 24-h drug delivery make them attractive for postoperative pain control. METHODS: Both doses of the new transdermal fentanyl patches were evaluated for the relief of postoperative pain in 143 patients after gynecologic exploratory laparotomy. The study was conducted at four centers using a prospective, randomized, placebo-controlled, double-blind format. Patients were randomly assigned to one of three study groups: group 1 patients received two placebo patches: group 2 patients received a 40-cm2 fentanyl patch and a 60-cm2 placebo patch; and group 3 patients received a 60-cm2 fentanyl patch and a 40-cm2 placebo patch. Patient-controlled morphine use and pain, sedation, and comfort scores were assessed postoperatively every 4 h for 36 h after patch placement. RESULTS: Patients' assessment of their analgesia was significantly (P < or = 0.05) better in group 2 at 16 and 24 h and in group 3 at 8, 12, 16, 20, and 24 h postoperatively, compared with the patients in group 1. Patients in groups 2 and 3 required less supplemental morphine to maintain satisfactory analgesia than did the patients in group 1. Patients in groups 2 and 3 had greater incidences of pruritus, erythema, and respiratory depression than did those receiving placebo. CONCLUSIONS: Concern exists regarding the side effects of this this new transdermal fentanyl patch. Therefore, this new patch will need further research before it can be recommended as an adjunct in controlling postoperative pain.

Administration, Cutaneous↗
PubMed1994

Fentanyl or alfentanil decreases the minimum alveolar anesthetic concentration of isoflurane in surgical patients.

The minimum alveolar anesthetic concentration (MAC) is an accepted potency measure for inhaled anesthetics. There is no generally accepted intraoperative measure of opioid potency, partly because of the difficulty in obtaining steady state biophase concentrations. We have studied the relative potency of fentanyl and alfentanil by using computer-assisted continuous infusions (CACI), in terms of reduction of isoflurane MAC. Data are presented from 79 patients in whom anesthesia was induced with thiopental and maintained with a CACI of fentanyl (set to achieve a plasma concentration of 0, 1, 3, 6, or 8 ng/mL) or alfentanil (0, 70, 210, 400, or 1000 ng/mL) with a predetermined end-tidal concentration of isoflurane. A determination of movement in response to skin incision was made. Without any opioid, the MAC of isoflurane was 1.25%. The maximum likelihood solution to a logistic regression model showed that fentanyl 0.5 ng/mL (95% confidence intervals [CI], 0-4.6 ng/mL) or alfentanil 28.8 ng/mL (95% CI, 0-70.9 ng/mL) resulted in a 50% isoflurane MAC reduction. In the logistic regression model, age or weight were not significant factors in the model. These results suggest that the comparative intraoperative potency ratio for alfentanil and fentanyl is 58:1, and that this methodology allows for direct intraoperative comparisons of opioid potency.

Adult↗
PubMed1993

Indirect memory during anesthesia. The effect of midazolam.

BACKGROUND: The preservation of implicit memory function during anesthesia is controversial, with conflicting results appearing in the literature. This study was designed to elucidate the effect of midazolam as part of an anesthetic technique on implicit memory function during anesthesia. Using a prospective randomized, double-blind study design, performance in three tasks (category generation, free association, and homophone spelling) was assessed. METHODS: Forty-eight consenting patients were assigned to two equal groups, to receive 2 mg intravenous midazolam or normal saline before induction of anesthesia. Anesthesia was induced with fentanyl and propofol and maintained with isoflurane 1.3 MAC until incision and isoflurane 1.0 MAC in 70% nitrous oxide thereafter. Fentanyl was used for supplementation of anesthesia. During anesthesia, one of two 50-min tapes containing the test material was played to each patient on a portable cassette player. In the postanesthesia care unit and 48 h after surgery, patients were engaged in three tasks by an observer unaware of the treatment group or tape. RESULTS: No significant main effect of priming or midazolam was observed in any of the tasks. In the word-association task, an interaction was observed between priming and treatment group (F = 9.62, P < .01) due to negative priming in the placebo group. CONCLUSIONS: The lack of a main effect of priming in any of the three tasks is consistent with the conclusion that indirect memory was not demonstrated for events occurring during the standard anesthetic conditions of this study. Further, midazolam appeared to have no effect.

Adolescent↗
PubMed1993

Pharmacokinetics of remifentanil (GI87084B) and its major metabolite (GI90291) in patients undergoing elective inpatient surgery.

BACKGROUND: Remifentanil is a highly potent opioid with a rapid onset and a short duration of action due to its rapid hydrolysis by esterases in blood and tissues. The major metabolite of remifentanil, GI90291, is much less potent than remifentanil. METHODS: The pharmacokinetics of remifentanil and its major metabolite, GI90291, were determined in 24 patients undergoing elective inpatient surgery. Remifentanil was administered as a 1-min infusion (2, 5, 15, and 30 micrograms/kg) after the induction of anesthesia and tracheal intubation. Serial arterial blood samples were collected over 6 h and assayed for remifentanil and GI90291. RESULTS: The pharmacokinetics of remifentanil were described using a three-compartment model. Total clearance (250-300 l/h) of remifentanil was independent of dose and was approximately three to four times greater than the normal hepatic blood flow. Volume of distribution at steady state (25-40 l) also was independent of dose. The terminal half-life of remifentanil ranged from 10 to 21 min. Covariate analysis of remifentanil clearance and patient demographics showed that patient body weight, age, and gender did not influence total clearance. This suggests that remifentanil may not need to be dosed according to body weight in adult patients. A simulation was conducted to determine the time required for a 50% reduction in effect site concentration after an infusion designed to maintain a constant effect site concentration. The time required for a 50% reduction in the effect site concentration of remifentanil (3.65 min) was considerably less than that for sufentanil (33.9 min), alfentanil (58.5 min), and fentanyl (262 min). The pharmacokinetics of the major metabolite, GI90291, were independent of the dose of remifentanil. The mean terminal half-life of GI90291 ranged from 88 to 137 min. CONCLUSIONS: The pharmacokinetics of remifentanil are consistent with its rapid elimination by blood and tissue esterases; its major metabolite is eliminated more slowly but is not likely to make any significant contribution to the total effect because of its much lower potency. The rapid onset and short duration of action of remifentanil make it well suited for titration of dose (infusion rate) to the desired degree of effect.

Adolescent↗
PubMed1992

Pharmacodynamics of pentamorphone during coronary artery bypass grafting in humans.

Pentamorphone is a new, highly potent opioid reported to have minimal cardiovascular effects in humans and a high therapeutic index in animals. Pentamorphone was injected intravenously (IV) as the sole anesthetic in 10 patients with left ventricular ejection fractions greater than 0.35 who were undergoing elective coronary artery bypass grafting (CABG). After premedication with lorazepam, 40 micrograms/kg, and establishment of hemodynamic monitoring, pentamorphone was infused at a rate of 2 micrograms/kg/min until unconsciousness occurred (5.1 +/- 1.6 micrograms/kg). Anesthetic induction was accompanied by an average 30% decrease in systolic, diastolic, and mean arterial pressure (MAP), a 19% decrease in heart rate (HR), but no change in cardiac output (CO) or pulmonary artery occlusion pressure. Five patients had a MAP less than 60 mm Hg after induction. Following incision, blood pressure, pulmonary artery occlusion pressure, and CO were unchanged from baseline but HR remained significantly lower. Despite additional pentamorphone (total dose 9.6 +/- 1.8 micrograms/kg), 6 patients required thiopental and/or enflurane to control hypertension intraoperatively. When pentamorphone is used as the sole IV anesthetic in lorazepam-premedicated patients with normal or mildly impaired ventricular function, there is a high incidence of hypotension during induction, and poor control of hemodynamic responses to stimulation. Pentamorphone, 10 micrograms/kg, does not seem to offer any significant advantage over opioids currently used for anesthesia in patients undergoing CABG.

Aged↗
PubMed1992

Comparison of the train-of-four fade profiles produced by vecuronium and atracurium.

In this double-blind study, we have allocated randomly 40 ASA I-III patients to one of four groups. After a standard anaesthetic induction, patients received vecuronium 0.08 mg kg-1 or 0.10 mg kg-1, or atracurium 0.4 mg kg-1 or 0.5 mg kg-1. Using an electromyogram (Datex Relaxograph) the train-of-four (TOF) response was measured during onset of and recovery from neuromuscular block. A greater degree of fade of TOF was observed with atracurium during onset of neuromuscular block than with equivalent doses of vecuronium. During recovery of neuromuscular transmission, vecuronium was associated with more fade than atracurium. The differences in the TOF profiles of these two drugs may be important when judging the adequacy of antagonism of neuromuscular block using the TOF response.

Adolescent↗
PubMed1992

Reduction of the MAC of desflurane with fentanyl.

Opioids are known to affect the MAC of inhalational anesthetics. We have determined the interaction between fentanyl and desflurane, following a bolus injection of fentanyl at induction in 134 adult patients. Five groups of patients were studied. Four groups received desflurane or isoflurane in oxygen with either fentanyl 3 or 6 micrograms/kg and thiopental 2-5 mg/kg given as a bolus injection at the time of induction. An additional group received desflurane in oxygen alone. Groups were stratified by age. MAC determination, in response to the stimulus of skin incision, was made using the "up-down" method and logistic regression. The MAC desflurane in oxygen was 6.3% (5.3-7.6%, 95% confidence interval [CI]). Fentanyl 3 micrograms/kg produced a fentanyl plasma concentration of 0.78 +/- 0.53 ng/ml at skin incision and resulted in a MAC for desflurane of 2.6% (2.0-3.2%, 95% CI) %. Fentanyl 6 micrograms/kg produced a fentanyl plasma concentration of 1.72 +/- 0.76 ng/ml at skin incision and resulted in a MAC for desflurane of 2.1% (1.5-2.6%, 95% CI). To compare recovery times to eye-opening and response to commands, patients were grouped according to the plasma fentanyl concentrations at the time of awaking. Recovery was faster in patients who received desflurane than in those who received isoflurane. The authors conclude that the MAC of desflurane is significantly reduced 25 min following a single dose of 3 micrograms/kg of fentanyl and that increasing the fentanyl dose to 6 micrograms/kg produces little further decrease in MAC. Desflurane is also associated with faster recovery from anesthesia than is isoflurane.

Adult↗
PubMed1991

Psychomotor performance after desflurane anesthesia: a comparison with isoflurane.

Recovery and psychomotor performance were studied in 80 ASA physical status I-III adult patients undergoing outpatient surgery. Patients were divided into four equal groups: thiopental induction of anesthesia followed by desflurane in nitrous oxide and oxygen (Th-DES-N2O/O2), thiopental induction of anesthesia followed by isoflurane in nitrous oxide and oxygen (Th-ISO-N2O/O2), thiopental induction of anesthesia followed by desflurane in oxygen (Th-DES-O2), and desflurane inhaled induction followed by desflurane in oxygen (DES-DES-O2). Patients were excluded from analysis if they required opioids or antiemetics postoperatively. The use of desflurane was associated with more rapid awakening compared with isoflurane (time to eye opening 9.45 +/- 0.67 min [Th-DES-N2O/O2] and 13.8 +/- 1.59 min [Th-ISO-N2O/O2], P less than 0.05). Psychomotor performance was measured using the choice reaction time and critical flicker fusion threshold. At 30 min after discontinuing anesthesia, five patients in the Th-ISO-N2O/O2 group and one patient in the Th-DES-N2O/O2 group were too sleepy to perform psychomotor tests. In addition, five patients who received Th-DES-O2 and one patient who received the inhaled induction and maintenance of anesthesia with desflurane in oxygen were too sleepy to perform tests at 30 min. Patients receiving Th-DES-N2O/O2 showed less impairment of choice reaction time than those receiving Th-ISO-N2O/O2. Critical flicker fusion threshold, however, showed no difference between groups. The use of thiopental was associated with delayed recovery. Compared with isoflurane, desflurane anesthesia is associated with more rapid initial awakening and less impairment of choice reaction time.

Adult↗
PubMed1991

Comparison of ocfentanil and fentanyl as supplements to general anesthesia.

Three doses of ocfentanil (1, 3, and 5 micrograms/kg), a new narcotic, were compared with fentanyl (5 micrograms/kg) as a supplement to general anesthesia. Sixty adult ASA I-III patients undergoing elective surgery were studied. The drugs were given as a bolus injection during induction of anesthesia in a double-blind manner. With the stimulus of tracheal intubation, systolic arterial blood pressure increased (mean +/- SE) from 127 +/- 6.9 to 183 +/- 7.4 mm Hg and heart rate increased from 82.1 +/- 4.8 to 104 +/- 6.4 beats/min in patients who had received 1 microgram/kg of ocfentanil intravenously. In comparison to patients who received 1 microgram/kg of ocfentanil, the increases in heart rate and systolic arterial blood pressure at the time of tracheal intubation were less with 3 and 5 micrograms/kg of ocfentanil and 5 micrograms/kg of fentanyl (P less than 0.05). At incision, heart rate decreased after the intravenous administration of 5 micrograms/kg of ocfentanil when compared with patients who received 1 microgram/kg of ocfentanil. There were differences between study groups in the mild increase in arterial blood pressure observed at incision. The authors conclude that ocfentanil and fentanyl appear to be similar in action, with 3 micrograms/kg of ocfentanil being approximately equivalent in effect to 5 micrograms/kg of fentanyl.

Adjuvants, Anesthesia↗
PubMed1988

Do evoked potentials measure depth of anaesthesia?

Somatosensory evoked potentials have been suggested as a possible neurophysiological in of anaesthetic depth. In order to test the usefulness of this technique of monitoring, 8 patients were monitored during balanced anaesthesia. Following induction with a sleep dose of thiopentone, a neuromuscular blocking agent was used and the patients' lungs ventilated with N2O/O2(F1O2 = 0.3). This was supplemented with halothane or fentanyl. Somatosensory evoked potentials were recorded every 10 minutes during surgery, blood pressure and heart rate being recorded at the end of each evoked potential measurement. Induction of anaesthesia was associated with the reduction in SEP amplitude from 4.2 +/- 1.04 micro volts to 1.6 +/- 0.9 micro volts. There was an increase in latency from 19.2 +/- 1.3 msec to 20.0 +/- 1.3 msec to 20.0 +/- 1.5 msec. Recovery from anaesthesia was accompanied by an increase in SEP amplitude pre-induction values. There were no apparent correlations between the changes in evoked potential measures and changes in heart rate or blood pressure. Consistent change in somatosensory evoked potentials (prolonged latency, decreased amplitude) occurred with both narcotic and volatile anaesthetics. There was a recovery of evoked potentials at the end of anaesthesia. This is a promising technique, worthy of further evaluation.

Anesthesia Recovery Period↗
PubMed1988

Effect of hypothermia on median nerve somatosensory evoked potentials.

Median nerve somatosensory evoked potentials (SEP) were monitored in ten patients undergoing cardiac surgery with hypothermic cardiopulmonary bypass (CPB). Anesthesia was induced and maintained with sufentanil, oxygen, and pancuronium. Esophageal, nasopharyngeal, rectal, and blood temperatures were continuously monitored. SEPs were recorded before induction of anesthesia, after induction, and during cooling and rewarming on CPB. There was a strong negative correlation between SEP latencies and temperature (except rectal) (r = -.91, P < .001). for cortical latency and esophageal temperature. A decrease in esophageal temperature of 1 degrees C resulted in an increase in SEP latency of 1 ms. There was also a weak positive correlation between evoked potential amplitude and temperature (r = .19) for cortical amplitude and esophageal temperature.

Body Temperature↗