Reduction by Fentanyl of the Cp sub 50 Values of Propofol and Hemodynamic Responses to Various Noxious Stimuli

Background: Propofol and fentanyl infusion rates should be varied according to the patient's responsiveness to stimulation to maintain satisfactory anesthetic and operative conditions. However, somatic and autonomic responses to various noxious stimuli have not been investigated systematically for intravenous propofol and fentanyl anesthesia.

Methods: Propofol and fentanyl were administered via computer-assisted continuous infusion to provide stable concentrations and to allow equilibration between plasma-blood and effect-site concentrations. The propofol concentrations needed to suppress eye opening to verbal command and motor responses after 50-Hz electric tetanic stimulation, laryngoscopy, tracheal intubation, and skin incision in 50% or 95% of patients (Cp50 and Cp95) were determined at fentanyl concentrations of 0.0, 1.0, 2.0, 3.0, and 4.0 ng/ml in 133 patients undergoing lower abdominal surgery. The ability of propofol with fentanyl to suppress hemodynamic reactions in response to various noxious stimuli also was evaluated by measuring arterial blood pressure and heart rate before and after stimulation.

Results: The various Cp50 values for propofol alone (no fentanyl) for the various stimuli increased in the following order: Cp sub 50loss of consciousness, 4.4 micro gram/ml (range, 3.8-5.0); Cp50tetanus, 9.3 micro gram/ml (range, 8.3-10.4); Cp50laryngoscopy, 9.8 micro gram/ml (range, 8.9-10.8); Cp50skin incision, 10.0 micro gram/ml (range, 8.1-12.2); and Cp50intubation, 17.4 micro gram/ml (range, 15.1-20.1; 95% confidence interval). The reduction of Cp50loss of consciousness, with fentanyl was minimal; 11% at 1 ng/ml of fentanyl and 17% at 3 ng/ml of fentanyl. A plasma fentanyl concentration of 1 ng/ml (3 ng/ml) resulted in a 31-34% (50-55%) reduction of the propofol Cp50 s for tetanus, laryngoscopy, intubation, and skin incision. Propofol alone depresses prestimulation blood pressure but had no influence on the magnitude blood pressure or heart rate increase to stimulation. Propofol used with fentanyl attenuated the systolic blood pressure increases to various noxious stimuli in a dose-dependent fashion.     

The Pharmacodynamic Interaction between Propofol and Fentanyl with Respect to the Suppression of Somatic or Hemodynamic Responses to Skin Incision, Peritoneum Incision, and Abdominal Wall Retraction

Background: Sufficient propofol or fentanyl doses necessary to prevent the response to skin incision do not necessarily attenuate hemodynamic responses during surgery. The goal of this study was to characterize the pharmacodynamic interaction between propofol and fentanyl with respect to the suppression of somatic or hemodynamic responses after three stimuli: skin incision, peritoneum incision, and abdominal wall retraction.

Methods: Propofol and fentanyl were administered via computer-assisted continuous infusion to provide equilibration between plasma-blood and biophase concentrations. Patients were randomized to nine groups that received predetermined concentrations of fentanyl (from 0 to 9 ng/ml). Each patient was administered different target concentrations of propofol. Somatic and hemodynamic responses were measured before and after each of three different stimulations: skin incision (si), peritoneum incision (pi), and abdominal wall retraction (ret). The propofol plasma concentrations at which 50% of the patients did not respond to each type of stimulation (Cp50si, Cp50pi, and Cp50ret) were calculated by fitting the Loewe synergistic model.

Results: For propofol alone, Cp50si, Cp50pi, and Cp50ret were 12.9, 17.1 and 19.4 [micro sign]g/ml, respectively. Increasing the fentanyl concentration markedly reduced propofol Cp50si, Cp50pi, and Cp50ret for somatic response, indicating the potential synergistic interaction of both drugs. During the prestimulation period, fentanyl did not decrease systolic blood pressure; however, propofol specifically decreased systolic blood pressure. Both drugs had a synergistic drug interaction on the systolic blood pressure increase after various surgical stimulations. Fentanyl and propofol concentrations that suppressed both the 50% probability of somatic response and the 50% probability of moderate hemodynamic change defined by the 15% systolic blood pressure increase over the prestimulation value were 3.6 ng/ml and 2.5 [micro sign]g/ml for skin incision, 8.4 ng/ml and 1.6 [micro sign]g/ml for peritoneum incision, and 5.9 ng/ml and 5.1 [micro sign]g/ml for wall retraction, respectively.     

Drug-induced Amnesia Is a Separate Phenomenon from Sedation: Electrophysiologic Evidence

Background: Sedative-hypnotic drugs not only increase sedation, but also impair memory as serum concentration increases. These drugs also produce profound changes in the auditory event-related potential (ERP). The ability of various ERP components to predict changes in sedation and memory produced by various drugs was tested.

Methods: Sixty-five healthy volunteers randomly received intravenous placebo, midazolam, propofol, thiopental, fentanyl with ondansetron, or ondansetron alone at five different stable target concentrations (three increasing, two decreasing) using a computer-controlled infusion pump to produce varying degrees of sedation without loss of consciousness. ERPs were recorded while volunteer participants detected a deviant auditory stimulus and made a button-press response to a target tone (standard oddball paradigm, 80:20 ratio, to elicit a P3 response). At each target concentration, volunteers learned a list of 16 words. The predictive probabilities (Pk) of various ERP components were determined for word recognition at the end of the day (memory) and log reaction time to the deviant stimulus (sedation).

Results: The N2 latency of the ERP consistently predicted log reaction time in all groups (Pk +/- SE from 0.58 +/- 0.04 to 0.71 +/- 0.04). The N2P3 amplitude of the ERP was the best predictor of memory performance for midazolam (Pk, 0.63 +/- 0.04), propofol (Pk, 0.62 +/- 0.05), and thiopental (Pk, 0.66 +/- 0.04). There was a differential ability to predict memory performance from sedation for midazolam and propofol.     

Inotropic Effects of Propofol, Thiopental, Midazolam, Etomidate, and Ketamine on Isolated Human Atrial Muscle

Background: Cardiovascular instability after intravenous induction of anesthesia may be explained partly by direct negative inotropic effects. The direct inotropic influence of etomidate, ketamine, midazolam, propofol, and thiopental on the contractility of isolated human atrial tissue was determined. Effective concentrations were compared with those reported clinically.

Methods: Atrial tissue was obtained from 16 patients undergoing coronary bypass surgery. Each fragment was divided into three strips, and one anesthetic was tested per strip in increasing concentrations (10 sup -6 to 10 sup -2 M). Strips were stimulated at 0.5 Hz, and maximum isometric force was measured. Induction agents were studied in two groups, group 1 (n = 7) containing thiopental, midazolam, and propofol, and group 2 (n = 9) consisting of etomidate, ketamine, and propofol.

Results: The tested anesthetics caused a concentration-dependent depression of contractility resulting in complete cessation of contractions at the highest concentrations. The IC50 S (mean +/-SEM; micro Meter) for inhibition of the contractility were: thiopental 43+/-7.6, propofol 235+/-48 (group 1), and 246+/-42 (group 2), midazolam 145+/-54, etomidate 133 +/-13, and ketamine 303+/-54.     

Awakening Propofol Concentration with and without Blood-Effect Site Equilibration after Short-term and Long-term Administration of Propofol and Fentanyl Anesthesia

Background: The propofol awakening concentration can vary. However, the effect site awakening propofol concentration will be a fixed value. The purpose of this study was to determine the awakening propofol concentrations obtained from infusion Schede using abrupt discontinuation of propofol (half-maximal effective concentration [EC sub 50]) or a descending decrease in concentration to allow blood-effect site equilibration (EC50 eq).

Methods: Patients undergoing short-term (group 1) and long-term (group 2) elective surgery were anesthetized with computer-assisted continuous infusion of propofol and fentanyl, with both groups receiving the same propofol (3 micro gram/ml) and fentanyl (1 ng/ml) concentrations 20-30 min before the end of surgery until the end. Then both groups were further divided into two subgroups: subgroup A abrupt discontinuation, and subgroup B descending concentrations of propofol (15-min duration per concentration). In the A subgroups, the response to verbal command was evaluated every 30 s. In the B subgroups, the blood propofol concentrations just permitting and just preventing response to command were averaged individually. The EC50 and EC50 eq values were determined by probit analysis.

Results: The EC50 of group 1A was 1 micro gram/ml, which was significantly less than the 1.6 micro gram/ml of group 2A (P < 0.05). The awakening time of group 1A was 5.2 +/- 1.8 min, which was significantly shorter than the 9.3 +/- 3.5 min of group 2A (means +/- SD). The EC50 eq of both groups 1B and 2B was 2.2 micro gram/ml.     

Fentanyl does not alter the "sleep" plasma concentration of thiopental.

Thiopental and fentanyl are commonly combined for induction of anesthesia. The effect of an analgesic concentration of fentanyl on the plasma concentration of thiopental to induce sleep was studied in 46 unpremedicated patients. As a measure of drug effect, sleep (the lack of response to open eyes to a verbal command) was used. Forty-six patients were randomized to receive thiopental infused to one of several predetermined plasma concentrations. Twenty-two of these patients also received a fentanyl infusion to a desired analgesic concentration of 1 ng/mL. Thiopental and fentanyl were infused by means of a pharmacokinetic model-driven infusion device (computer-assisted continuous infusion, CACI). Venous blood samples were taken from the contralateral antecubital fossa at 5 and 10 min after the start of the infusion. At 10 min, the patients' names were firmly spoken, and they were instructed to open their eyes. If they did not respond to this command, they were considered to be asleep. Only patients in whom the 5- and 10-min measured plasma concentrations of thiopental and fentanyl, respectively, were within +/- 30% of each other were used for the determination of the Cp50(asleep), the plasma concentration at which 50% of the patients were asleep. The Cp50(asleep) with and without fentanyl was calculated by logistic regression. The Cp50(asleep) for patients in whom concentrations were maintained within +/- 30% for thiopental alone (n = 17) was 7.32 micrograms/mL (95% confidence interval, 5.53-10.95); for thiopental in the presence of fentanyl (n = 18 with a measured fentanyl concentration of 1.27 +/- 0.5 ng/mL), this was 7.22 micrograms/mL (95% confidence interval, 4.83-10.15).(ABSTRACT TRUNCATED AT 250 WORDS)     

Drug-induced amnesia is a separate phenomenon from sedation: electrophysiologic evidence

BACKGROUND: Sedative-hypnotic drugs not only increase sedation, but also impair memory as serum concentration increases. These drugs also produce profound changes in the auditory event-related potential (ERP). The ability of various ERP components to predict changes in sedation and memory produced by various drugs was tested. METHODS: Sixty-five healthy volunteers randomly received intravenous placebo, midazolam, propofol, thiopental, fentanyl with ondansetron, or ondansetron alone at five different stable target concentrations (three increasing, two decreasing) using a computer-controlled infusion pump to produce varying degrees of sedation without loss of consciousness. ERPs were recorded while volunteer participants detected a deviant auditory stimulus and made a button-press response to a target tone (standard oddball paradigm, 80:20 ratio, to elicit a P3 response). At each target concentration, volunteers learned a list of 16 words. The predictive probabilities (Pk) of various ERP components were determined for word recognition at the end of the day (memory) and log reaction time to the deviant stimulus (sedation). RESULTS: The N2 latency of the ERP consistently predicted log reaction time in all groups (Pk +/- SE from 0.58 +/- 0.04 to 0.71 +/- 0.04). The N2P3 amplitude of the ERP was the best predictor of memory performance for midazolam (Pk, 0.63 +/- 0.04), propofol (Pk, 0.62 +/- 0.05), and thiopental (Pk, 0.66 +/- 0.04). There was a differential ability to predict memory performance from sedation for midazolam and propofol. CONCLUSIONS: Midazolam and propofol affect memory differentially from their sedative effects, and these are indexed by specific components of the auditory ERP. These components of the ERP are associated with specific, but not necessarily unique, neuroanatomic structures. Thus, these drugs act by additional mechanisms beyond general central nervous system depression to produce the effects of sedation and memory impairment.     

Comparison of etomidate, ketamine, midazolam, propofol, and thiopental on function and metabolism of isolated hearts.

The authors examined direct myocardial and coronary vascular responses to the anesthetic induction agents etomidate, ketamine, midazolam, propofol, and thiopental and compared their effects on attenuating autoregulation of coronary flow as assessed by changes in oxygen supply/demand relationships. Spontaneous heart rate, atrioventricular conduction time during atrial pacing, left ventricular pressure (LVP), coronary flow (CF), percent oxygen extraction, oxygen delivery, and myocardial oxygen consumption (MVo2) were examined in 55 isolated guinea pig hearts divided into five groups of 11 each. Hearts were perfused at constant pressure with one of the drugs administered at steady-state concentrations increasing from 0.5 microM to 1 mM. Adenosine was given to test maximal CF. At concentrations below 10 microM no significant changes were observed; beyond 50 microM for midazolam, etomidate, and propofol, and 100 microM for thiopental and ketamine, each agent caused progressive but differential decreases in heart rate, atrioventricular conduction time (leading to atrioventricular dissociation), LVP, +dLVP/dtmax, percent oxygen extraction, and MVo2. The concentrations (microM) at which +dLVP/dtmax was reduced by 50% were as follows: etomidate, 82 +/- 2 (mean +/- SEM); propofol, 91 +/- 4; midazolam, 105 +/- 8; thiopental, 156 +/- 11; and ketamine, 323 +/- 7; the rank order of potency was etomidate = propofol = midazolam greater than thiopental greater than ketamine; results were similar for LVP. At the 100 microM concentration, CF was decreased 11% +/- 2% by ketamine and 5% +/- 3% by thiopental but was increased 17% +/- 6% by etomidate, 21% +/- 5% by midazolam, and near maximally to 57% +/- 10% by propofol; MVo2 was decreased 8% +/- 4% by thiopental, 10% +/- 5% by ketamine, 19% +/- 5% by midazolam, 29% +/- 7% by etomidate, and 37% +/- 5% by propofol; oxygen delivery/MVo2 was unchanged by thiopental and ketamine but was increased 62% +/- 7% by midazolam, 71% +/- 9% by etomidate, and 150% +/- 15% by propofol. Between 100 microM and 1 mM, thiopental and ketamine did not increase CF but decreased MVo2 and percent oxygen extraction, whereas propofol maximally increased CF and decreased MVo2 and midazolam and etomidate had intermediate effects. These results indicate that on a molar basis, propofol, and less so midazolam and etomidate, depress cardiac function moderately more than thiopental and ketamine, and that propofol markedly attenuates autoregulation by causing coronary vasodilation. With doses used to induce anesthesia, propofol and thiopental appear to depress cardiac function more than ketamine or etomidate.     

Implantable cardioverter-defibrillator placement in patients with mild-to- moderate left ventricular dysfunction: hemodynamics and recovery profile with two different anesthetics used during deep sedation

OBJECTIVE: To compare the effects of thiopental and propofol during defibrillation threshold testing (DFT) on hemodynamics and recovery profile in patients requiring automatic internal cardioverter-defibrilator placement. DESIGN: Prospective clinical investigation. SETTING: University hospital. PARTICIPANTS: Thirty-four adult patients. INTERVENTIONS: After administration of midazolam, 0.025 mg/kg, and fentanyl, 0.5 to 1 mug/kg, surgery was performed under topical infiltration with 1% lidocaine. In group I (GI) (n = 17), patients received thiopental by slow injection and patients in group II (GII) (n = 17) received propofol before induction of ventricular fibrillation (VF). MEASUREMENTS AND MAIN RESULTS: Patients received 4.1 +/- 1.4 mg of midazolam, 114 +/- 34 mug of fentanyl, and 280 +/- 78 mg of thiopental in GI; and 4.6 +/- 1.7 mg of midazolam, 119 +/- 62 mug of fentanyl, and 147 +/- 40 mg of propofol in GII (p > 0.05). Hemodynamics did not show significant differences between the groups at any recording time. Average time needed to regain the pretest sedation level was 16.4 +/- 8.8 minutes in GI and 10.9 +/- 5.5 minutes in GII (p = 0.03). Time required to achieve a score of 10 using a modified Aldrete score was 26.4 +/- 9.3 minutes in GI and 17.4 +/- 4.9 in GII (p = 0.001). Seven patients in GII (41%) and 1 patient in GI (6%) became hypotensive after DFT (p = 0.04). CONCLUSIONS: Deepening the sedation level by slow injection of thiopental or propofol before DFT provided satisfactory conditions during brief episodes of VF. Delay in recovery of arterial pressure after DFT with propofol and delay in arousal and discharge of patients with thiopental are major disadvantages of the regimens.     

Urine and Plasma Catecholamine and Cortisol Concentrations after Myocardial Revascularization: Modulation by Continuous Sedation

Background: Cardiopulmonary bypass is associated with substantial release of catecholamines and cortisol for 12 or more h. A technique was assessed that may mitigate the responses with continuous 12-h postoperative sedation using propofol.

Methods: One hundred twenty-one patients having primary elective cardiopulmonary bypass graft (CABG) surgery were enrolled in a double-blind, randomized trial and anesthetized using a standardized sufentanil-midazolam regimen. When arriving at the intensive care unit (ICU), patients were randomly assigned to either group SC (standard care), in which intermittent bolus administration of midazolam and morphine were given as required to keep patients comfortable; or group CP (continuous propofol), in which 12 h of continuous postoperative infusion of propofol was titrated to keep patients deeply sedated. Serial perioperative measurements of plasma and urine cortisol, epinephrine, norepinephrine, and dopamine were obtained; heart rate and blood pressure were recorded continuously, and medication use, including requirements for opioids and vasoactive drugs, was recorded. Repeated-measures analysis was used to assess differences between study groups for plasma catecholamine and cortisol levels at each measurement time.

Results: In the control state-before the initiation of postoperative sedation in the ICU-no significant differences between study groups were observed for urine or plasma catecholamine or cortisol concentrations. During the ICU study period, for the first 6-8 h, significant differences were found between study groups SC and CP in plasma cortisol (SC = 28 +/- 15 mg/dl; CP = 19 +/- 12 mg/dl; estimated mean difference [EMD] = 9 mg/dl; P = 0.0004), plasma epinephrine (SC = 132 +/- 120 micro gram/ml; CP = 77 +/- 122 micro gram/ml; EMD = 69 micro gram/ml; P = 0.009), urine cortisol (SC = 216 +/- 313 micro gram/ml; CP = 93 +/- 129 micro gram/ml; EMD = 127 micro gram/ml; P = 0.007), urine dopamine (SC = 85 +/- 48 micro gram; CP = 52 +/- 43 micro gram; EMD = 32 micro gram; P = 0.002), urine epinephrine (SC = 7 +/- 8 micro gram; CP = 4 +/- 5 micro gram; EMD = 3 micro gram; P = 0.009), and urine norepinephrine (SC = 24 +/- 14 mg; CP = 13 +/- 9 mg; EMD = 11 mg; P = 0.0004). Reductions in urine and plasma catecholamine and cortisol concentrations found for the CP group generally persisted during the 12-h propofol infusion period and then rapidly returned toward control (SC group) values after propofol was discontinued. Postoperative opioid use was reduced in the CP group (SC = 97%; CP = 49%; P = 0.001), as was the incidence of (SC = 79%; CP = 60%; P = 0.04) and hypertension (SC = 58%; CP = 33%; P = 0.01), but the incidence of hypotension was increased (SC = 49%; CP = 81%; P = 0.001).     

Quantitation of Depth of Thiopental Anesthesia in the Rat

Background: In contrast to that of inhalational anesthetics, quantitation of anesthetic depth for intravenous agents has not been well defined. In this study, using rodents, the relationship between the constant plasma thiopental concentrations and the clinical response to multiple nociceptive stimuli were investigated characterizing the anesthetic state from light sedation to deep anesthesia and correlated to the degree of electroencephalogram (EEG) drug effect.

Methods: Thirty rats were instrumented with chronically implanted EEG electrodes, arterial and venous catheters. A computer-driven infusion pump was used to rapidly attain and then maintain constant, target plasma thiopental concentrations ranging from 7 to 100 micro gram/ml. Three different target plasma thiopental concentrations were achieved in each rat. Electroencephalographic effects were monitored with aperiodic waveform analysis. The following nociceptive stimuli were applied: (1) unprovoked righting reflex, (2) provoked righting reflex, (3) noise stimulus, (4) tail clamping with an alligator clip, (5) constant tail pressure with an analgesia-meter, (6) corneal reflex, and (7) tracheal intubation. For tail clamping, tail pressure, and intubation, either purposeful extremity movement or abdominal muscle contraction response was noted to be present or absent. The clinical responses (present or absent) were modeled using logistic regression to estimate the Cp50, the plasma thiopental concentration with a 50% probability of no response.

Results: The following mean Cp50 values (95% confidence interval) were obtained: unprovoked righting reflex, 15.9 (15.1-16.6) micro gram/ml; provoked righting reflex, 21.4 (20.2-22.7) micro gram/ml; noise stimuli, 31.3 (29.7-33.0) micro gram/ml; tail clamp and limb movement, 38.3 (36.1-40.4) micro gram/ml, tail pressure and limb movement, 39.2 (37.1-41.3) micro gram/ml; tail pressure and abdominal muscle contraction, 52.5 (50.0-55) micro gram/ml; tail clamping and abdominal muscle contraction, 56.1 (50.0-56.2) micro gram/ml; corneal reflex, 60.0 (56.6-63.4) micro gram/ml; and limb movement or muscle abdominal contraction response to intubation, 67.7 (59.2-76.1) micro gram/ml. At an EEG-effect of 9.1 and 2.2 waves/s, there was a 50% chance of limb movement response to tail clamping and tracheal intubation, respectively. There was a poor relationship between the plasma thiopental concentration and the percent increase of either heart rate or mean arterial blood pressure after applying either tail pressure or tail clamp stimuli.     

In Vitro Effects of Fentanyl, Methohexital, and Thiopental on Brain Endothelial Permeability

Background: The use of anesthetics can lead to changes of the permeability of the blood-brain barrier (BBB). To eliminate those factors, such as varying hemodynamic effects that are associated with anesthesia, an in vitro model of the BBB consisting of brain microvascular endothelial cells (BMEC) was used to study the direct effects of the opiate, fentanyl, and the barbiturates methohexital and thiopental, which are widely used in the clinical setting, on the permeability of confluent monolayers.

Methods: BMEC isolated from porcine brains were grown to confluence on collagen-coated polycarbonate membranes, which were placed into 24 well dishes, thus forming a two-compartment chamber. The permeability of the BMEC monolayer to ions--determined by measurements of the transendothelial resistance (TER)--the passage of sucrose, Evans Blue albumin (EBA), and alpha-aminolsobutyric acid (AIB) across the BMEC monolayer were assessed in the presence and absence of fentanyl (25-100 ng/ml), methohexital (10-50 micro gram/ml), and thiopental (25-100 micro gram/ml).

Results: The permeability of cultured BMEC to the tracers used increased significantly after exposure of the monolayer to arabinose and after removal of calcium ions. Fentanyl, methohexital, and thiopental did not change the permeability of the cell monolayer to ions, sucrose, albumin, and AIB. Only thiopental at the concentration of 100 micro gram/ml increased the flux of AIB.     

Esmolol Reduces Anesthetic Requirement for Skin Incision during Propofol/Nitrous Oxide/Morphine Anesthesia

Background: Although beta blockers have been used primarily to decrease unwanted perioperative hemodynamic responses, the sedative properties of these compounds might decrease anesthetic requirements. This study was designed to determine whether esmolol, a short-acting beta1 -receptor antagonist, could reduce the propofol concentration required to prevent movement at skin incision.

Methods: Sixty consenting patients were premedicated with morphine, and then propofol was delivered by computer-assisted continuous infusion along with 60% nitrous oxide. Patients were randomly divided into three groups, propofol alone, propofol plus low-dose esmolol (bolus of 0.5 mg/kg, then 50 micro gram [center dot] kg-1 min-1), and propofol plus high-dose esmolol (bolus of 1 mg/kg, then 250 micro gram [center dot] kg (-1) min-1). Two venous blood samples were drawn at equilibrium. The serum propofol concentration that prevented movement to incision in 50% of patients (Cp50) was calculated by logistic regression.

Results: The propofol Cp50 with nitrous oxide was 3.85 micro gram/ml. High-dose esmolol infusion was associated with a significant reduction in the Cp50 to 2.80 micro gram/ml (P < 0.04). Propofol computer-assisted continuous infusion produced stable serum concentrations with a slight positive bias. Esmolol did not alter the serum propofol concentration. No intergroup differences in heart rate or blood pressure response to intubation or incision were found.     

不同血浆靶浓度瑞芬太尼对患者异丙酚镇静效应的影响

目的 探讨不同血浆靶浓度瑞芬太尼对患者异丙酚镇静效应的影响.方法 择期拟行腹腔镜胆囊切除术患者80例,性别不限,ASA分级Ⅰ或Ⅱ级,年龄18～60岁,随机分为4组,每组20例.麻醉诱导:Ⅱ～Ⅳ组靶控输注瑞芬太尼,血浆靶浓度分别设为2、4、8 ng/ml,Ⅰ～Ⅳ组均靶控输注异丙酚,初始血浆靶浓度为2μg/ml,随后每间隔1min增加0.5μg/ml,直至BIS值下降至50.患者意识消失时记录BIS值和异丙酚血浆靶浓度,BIS值降至50时记录异丙酚血浆靶浓度及异丙酚总用量.结果 与Ⅰ组比较,Ⅲ组和Ⅳ组患者意识消失时BIS值升高,异丙酚血浆靶浓度降低,BIS值降至50时异丙酚总用量和异丙酚血浆靶浓度降低(P＜0.05).结论 复合异丙酚麻醉时,瑞芬太尼适宜血浆靶浓度为4 ng/ml.     

Anesthesia for craniotomy: total intravenous anesthesia with propofol and alfentanil compared to anesthesia with thiopental sodium, isoflurane, fentanyl, and nitrous oxide

STUDY OBJECTIVE: To compare a total intravenous (IV) anesthetic technique based on propofol and alfentanil with a commonly used anesthetic technique for craniotomy. DESIGN: Open-label, randomized, clinical study. SETTING: Neurosurgical clinic at a university hospital. PATIENTS: Forty patients, aged 18 to 55 years, scheduled for brain tumor surgery. INTERVENTIONS: In 20 patients, anesthesia was induced with fentanyl and thiopental sodium and maintained with fentanyl, dehydrobenzperidol, isoflurane, nitrous oxide (N2O), and a thiopental sodium infusion. Twenty patients were anesthetized with a propofol loading infusion followed by a maintenance infusion at a fixed rate. In addition, alfentanil was administered as a loading bolus, followed by a variable-rate infusion, with additional doses as necessary to maintain hemodynamic stability. MEASUREMENTS AND MAIN RESULTS: A decrease in blood pressure (BP) after induction with thiopental sodium was followed by a significant increase in BP and heart rate (HR) during intubation. BP and HR did not change during the propofol loading infusion. However, the administration of alfentanil was followed by a similar decrease in BP with a return to baseline values during the intubation period. Return of normal orientation (7 +/- 5 minutes vs 27 +/- 23 minutes) and concentration (12 +/- 12 minutes vs 35 +/- 37 minutes) was shorter and more predictable for the propofol-alfentanil-treated patients than for the thiopental sodium patients. Maintenance propofol concentration (nine patients) was between 3 +/- 0.69 micrograms/ml and 3.36 +/- 1.17 micrograms/ml, while the concentration at awakening was 1.09 microgram/ml. Alfentanil concentration at extubation (nine patients) was 79 +/- 34 ng/ml. CONCLUSION: A total IV anesthetic technique with propofol and alfentanil is a valuable alternative to a more commonly used technique based on thiopental sodium, N2O, fentanyl, and isoflurane.     

Effect-site concentration of propofol for recovery of consciousness is virtually independent of fentanyl effect-site concentration

Fentanyl reduces the amount of propofol necessary to prevent responses to surgical stimuli. However, opioids have relatively little effect on consciousness. We, therefore, tested the hypothesis that fentanyl minimally alters the effect-site concentration of propofol associated with awakening. Fifty women having gynecologic laparotomy with propofol anesthesia were randomly allocated into the following target effect-site fentanyl concentrations: 0.8, 1.0, 1.4, 2.0, and 3.0 ng/mL. Fentanyl was continued at the designated rate through the initial postoperative phase. The propofol effect-site concentration associated with eye opening in response to verbal command was regarded as the awakening concentration. The estimated propofol effect-site concentrations at awakening did not differ significantly among the groups and were 1.9 +/- 0.5 micro g/mL with a fentanyl effect-site concentration of 0.8 ng/mL; 1.6 +/- 0.4 micro g/mL with 1.0 ng/mL of fentanyl; 1.6 +/- 0.2 micro g/mL with 1.4 ng/mL of fentanyl; 1.7 +/- 0.4 micro g/mL with 2.0 ng/mL of fentanyl; and 1.6 +/- 0.34 micro g/mL with 3.0 ng/mL of fentanyl (mean +/- SD). Seventy percent of the subjects in the 0.8 ng/mL fentanyl group spontaneously complained of pain, whereas none of the patients in the 2 or 3 ng/mL groups did. Five (56%) of 9 women in the 3 ng/mL group had a postoperative respiratory rate <6 breaths/min. Heart rate in one of these women decreased to <40 bpm. These data suggest that the optimal fentanyl effect-site concentration in patients recovering from gynecologic laparoscopy is between 1.4 and 2.0 ng/mL. IMPLICATIONS:The effect-site concentration for propofol at awakening was virtually independent of the fentanyl effect-site concentration over the range of 0.8 to 3.0 ng/mL; however, 0.8 ng/mL of fentanyl was associated with inadequate postoperative analgesia, and 3.0 ng/mL of fentanyl was associated with respiratory toxicity. The optimal postoperative fentanyl effect-site concentration during recovery from propofol general anesthesia for laparotomy thus appears to be near 2 ng/mL.     

Double-blind, Randomized Comparison of Ondansetron and Intraoperative Propofol to Prevent Postoperative Nausea And Vomiting

Background: Breast surgery is associated with a high incidence of postoperative nausea and vomiting. Propofol and prophylactic administration of ondansetron are associated with a lower incidence of postoperative nausea and vomiting. To date no comparison of these two drugs has been reported. A randomized study was done to compare the efficacy of ondansetron and intraoperative propofol given in various regimens.

Methods: Study participants included 89 women classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled for major breast surgery. Patients were randomly assigned to one of four groups. Group O received 4 mg ondansetron in 10 ml 0.9% saline and groups PI, PIP, and PP received 10 ml 0.9% saline before anesthesia induction. Group O received thiopental, isoflurane, nitrous oxide-oxygen, and fentanyl for anesthesia. Group PI received propofol, isoflurane, nitrous oxide-oxygen, and fentanyl. Group PIP received propofol, isoflurane, nitrous oxide-oxygen, and fentanyl. Thirty minutes before expected skin closure, isoflurane was discontinued and 50 to 150 micro gram [centered dot] kg sup -1 [centered dot] min sup -1 propofol was given intravenously to maintain anesthesia. Group PP received propofol for induction and maintenance of anesthesia, nitrous oxide-oxygen, and fentanyl. Postoperative pain relief was provided with morphine administered by a patient-controlled analgesia pump. The incidence of nausea and vomiting, requests for rescue antiemetic and sedation, pain scores, and hemodynamic data were recorded for 24 h.

Results: Within 6 h of surgery, groups O and PP had a lower incidence of nausea compared with groups PI and PIP (P < 0.05). Fewer patients in group PP (19%) vomited during the 24-h period compared with groups O (48%), PI (64%), and PIP (52%) (P < 0.05). The incidence of antiemetic use was also less in group PP (P < 0.05). Patients in group PP had lower sedation scores at 30 min and at 1 h (P < 0.05). There were no differences among the groups in pain scores, blood pressure, heart rate, respiratory rate, and incidence of pruritus.     

体外循环下异丙酚靶控输注系统的准确性

目的 评价体外循环下异丙酚靶控输注系统的准确性.方法 择期体外循环下行心脏瓣膜置换术患者20例,ASAⅡ或Ⅲ级,年龄25～64岁,体重50～70 kg.静脉注射咪达唑仑、芬太尼和维库溴铵行麻醉诱导,气管插管后机械通气.麻醉维持采用嵌入Tackley药代动力学参数的靶控输注系统输注异丙酚至术毕,血浆靶浓度为1μ/ml.于体外循环前(T1)、体外循环开始后1、5、10、20、40、60 min(T2-7)、体外循环结束后5、10 min(T8,9)时采集桡动脉血样3 ml,采用反相高效液相色谱法测定血浆异丙酚浓度,计算异丙酚靶控输注系统的偏离度、精确度、摆动度及分散度.结果 T1时异丙酚实测浓度高于血浆靶浓度(P<0.05),T2-4时异丙酚实测浓度与血浆靶浓度差异无统计学意义(P>0.05),T5-9时异丙酚实测浓度高于血浆靶浓度(P<0.05).异丙酚靶控输注系统的偏离度为21%、精确度为29%、摆动度为21%及分散度为-0.06%/h.结论 心脏手术患者体外循环时,采用嵌入Tackley药代动力学参数的异丙酚靶控输注系统的准确性超出临床可接受范围.     

Inhibition of Nitric Oxide Synthase Decreases Anesthetic Requirements of Intravenous Anesthetics in Xenopus laevis

Background: Acute inhibition of nitric oxide synthase (NOS) has been demonstrated to reduce the anesthetic requirements of volatile anesthetics. Recent data suggest that not only volatile but also intravenous anesthetic agents interact with nitric oxide (NO) metabolism. The aim of this study was to examine the effect of NOS inhibition by nitro sup G -L-arginine-methyl-ester (L-NAME) on the anesthetic action of the intravenous anesthetics thiopental, propofol, and ketamine.

Methods: The anesthetic potencies of thiopental, propofol, and ketamine were determined in Xenopus laevis tadpoles in the absence and presence of L-NAME. Anesthesia was defined as loss of righting reflex for 5 s. A nonlinear logistic regression curve was fitted to the data and half-maximal effective concentrations (EC50) were calculated. A second set of experiments was performed with different concentrations of L-NAME in the presence of the previously determined the EC50 of the intravenous anesthetics.

Results: The EC50 S of the anesthetics thiopental, propofol, and ketamine were determined to be 25.5 +/- 2.0 micro Meter, 1.9 +/- 0.1 micro Meter, and 59.7 +/- 0.7 micro Meter, respectively. The addition of L-NAME shifted the concentration-response curves to the left in a concentration-dependent manner. In the presence of 1 mM L-NAME, the EC50 of thiopental was reduced by 43%, the EC50 of propofol by 26%, and the EC50 of ketamine by 63%. The addition of D-NAME did not change the EC50 values of the three anesthetics. In the presence of L-arginine, the effect of L-NAME on the EC50 of thiopental was reversed. When administered by itself in a concentration range from 0.1 micro Meter to 10 mM, L-NAME did not alter the behavior of the tadpoles.     

Endocrinological changes following etomidate, midazolam, or methohexital for minor surgery

Etomidate is known to inhibit adrenocorticosteroid synthesis. The extent and duration of the effects of etomidate (63 +/- 6.4 mg) on spontaneous and stimulated corticosteroid levels, as well as on plasma concentrations of ACTH, beta-endorphin, and catecholamines were examined and compared to those following administration of the new benzodiazepine, midazolam, or of methohexital. Twenty-nine healthy, young, male orthopedic patients were randomized into three groups receiving either etomidate/fentanyl (n = 12), midazolam/fentanyl (n = 8), or methohexital/fentanyl (n = 9). Etomidate caused cortisol levels to decrease from 12.5 +/- 1.2 micrograms/dl preoperatively to 5.9 +/- 0.8 micrograms/dl after operation (P less than 0.001), compared to an increase from 12.0 +/- 1.9 micrograms/dl to 18.5 +/- 2.9 micrograms/dl in the group receiving methohexital. At 6 and 20 h postoperatively, all cortisol levels were normal. The cortisol decrease from 12.5 +/- 1.7 to 7.6 +/- 1.5 caused by midazolam was similar to that following etomidate, but the response to exogenous ACTH was significantly impaired in patients receiving etomidate as compared to those receiving midazolam. ACTH and beta-endorphin levels increased in patients receiving etomidate, presumably as a result of the interruption of negative feedback due to cortisol synthesis inhibition. Midazolam on the other hand prevented the increase of ACTH and beta-endorphin levels. Etomidate completely suppressed spontaneous aldosterone levels (from 33 +/- 6.7 to 7 +/- 2.1 pg/ml), as well as the response to stimulation with exogenous ACTH without affecting serum electrolytes. Etomidate had no influence on plasma catecholamines, but midazolam attenuated the stress-related epinephrine increase.