Pharmacodynamic Interaction between Propofol and Alfentanil When Given for Induction of Anesthesia

Background: Propofol and alfentanil often are combined during induction of anesthesia. However, the interaction between these agents during induction has not been studied in detail. The influence of alfentanil on the propofol concentration-effect relationships was studied for loss of eyelash reflex, loss of consciousness, and hemodynamic function in 20 un-premedicated ASA physical status 1 patients aged 20-55 yr.

Methods: Patients were randomly divided into four groups to receive a computer-controlled infusion of alfentanil with target concentrations of 0, 50, 200, or 400 ng/ml (groups A, B, C, and D, respectively). While the target concentration of alfentanil was maintained constant, patients received a computer-controlled infusion of propofol, with an initial target concentration of 0.5-1 micro gram/ml, that was increased every 12 min by 0.5-1 micro gram/ml. Every 3 min, the eyelash reflex and state of consciousness were tested and an arterial blood sample was taken for blood propofol and plasma alfentanil determination. The propofol-affentanil concentration-response relationships for loss of eyelash reflex and loss of consciousness were determined by nonlinear regression, and for the percentage of change in systolic blood pressure and heart rate by logistic regression.

Results: The patient characteristics did not differ significantly among the four groups. The patients in groups A and B continued to breathe adequately, whereas all patients in groups C and D required assisted ventilation. End-tidal carbon dioxide partial pressure remained less than 46 mmHg in all patients. With plasma alfentanil concentrations increasing from 0 to 500 ng/ml, the EC50 of propofol decreased from 2.07 to 0.83 micro gram/ml for loss of eyelash reflex and from 3.62 to 1.55 micro gram/ml for loss of consciousness. With plasma alfentanil concentrations increasing from 0 to 500 ng/ml, the blood propofol concentrations associated with a 10% decrease in systolic blood pressure and heart rate decreased from 1.68 to 0.17 micro gram/ml and from 2.36 to 0.04 micro gram/ml, respectively.     

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.     

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.     

The Comparative Amnestic Effects of Midazolam, Propofol, Thiopental, and Fentanyl at Equisedative Concentrations

Background: The authors evaluated the effects of midazolam, propofol, thiopental, and fentanyl on volunteer participants' memory for words and pictures at equisedative concentrations.

Methods: Sixty-seven healthy volunteers were randomized to receive intravenous infusions of midazolam (n = 11), propofol (n = 11), thiopental (n = 10), fentanyl with ondansetron pretreatment (n = 11), ondansetron alone (n = 8), or placebo (n = 16) in a double-blind design. Three increasing and then two decreasing sedative concentrations were achieved by computer-controlled infusion in each volunteer. Measures of sedation, memory, and drug concentration were obtained at each target concentration. Drug concentrations were normalized to equisedative effects using both Emax and logistic regression methods of pharmacodynamic modeling. The serum concentrations at 50% memory effect (Cp50s) were determined using four different memory end points. The relative potencies compared with midazolam for memory impairment were determined.

Results: Equisedative concentrations were midazolam, 64.5 +/- 9.4 ng/ml; propofol, 0.7 +/- 0.2 micro gram/ml; thiopental, 2.9 +/- 1.0 micro gram/ml; and fentanyl, 0.9 +/- 0.2 ng/ml. The Cp50s for 50% loss of memory for words were midazolam, 56 +/- 4 ng/ml; propofol, 0.62 +/- 0.04 micro gram/ml; thiopental, 4.5 +/- 0.3 micro gram/ml; and fentanyl, 3.2 +/- 0.4 ng/ml. Compared with midazolam, relative potencies (with 95% confidence intervals) were propofol, 0.96 (0.44-1.78); thiopental, 0.76 (0.52-0.94); and fentanyl, 0.34 (0.05-0.76). Large effects on memory were only produced by propofol and midazolam.     

Plasma concentrations of alfentanil required to supplement nitrous oxide anesthesia for general surgery

To design an efficient infusion regimen from pharmacokinetic data, it is necessary to know the alfentanil plasma concentrations required for satisfactory anesthesia. In 37 patients about to undergo lower abdominal gynecologic, upper abdominal, or breast surgery, anesthesia was induced with alfentanil 150 micrograms/kg iv and 66% N2O in oxygen. Thereafter, N2O anesthesia was supplemented with a continuous infusion of alfentanil that was varied between 25 and 150 micrograms X kg-1 X h-1, as indicated by the patient's responses to surgical stimulation. Small bolus doses of alfentanil 7 or 14 micrograms/kg were administered and the infusion rate increased to suppress precisely defined somatic, autonomic, and hemodynamic responses. Arterial plasma concentrations of alfentanil were measured during the operation when the patient did and did not respond to noxious stimulation. Logistic regression was used to determine plasma concentration-effect curves for different stimuli. Plasma alfentanil concentrations required along with 66% N2O to obtain responses to single episodes of stimulation in 50% of the 37 patients (Cp50 +/- SE) were: 475 +/- 28 ng/ml for tracheal intubation, 279 +/- 20 ng/ml for skin incision, and 150 +/- 23 ng/ml for skin closure. Between skin incision and closure, multiple determinations of response/no response were made for each patient and an individual Cp50 was estimated. The Cp50 (mean +/- SD) for the three surgical procedures were: breast, 270 +/- 63 ng/ml (n = 12); lower abdominal, 309 +/- 44 ng/ml (n = 14); and upper abdominal, 412 +/- 135 ng/ml (n = 11). The Cp50 for satisfactory spontaneous ventilation after the discontinuation of N2O was 223 +/- 13 ng/ml. These data demonstrate that different perioperative stimuli require different alfentanil concentrations to suppress undesirable responses. Thus, the alfentanil infusion rate should be varied according to the patient's responsiveness to stimulation in order to maintain satisfactory anesthetic and operative conditions and to provide rapid recovery of consciousness and spontaneous ventilation.     

Aging prolongs recovery of psychomotor functions at emergence from propofol-alfentanil anaesthesia

PURPOSE: To compare recovery of psychomotor function in elderly and young surgical patients at emergence from propofol-alfentanil anaesthesia. METHODS: Ten elderly (> 70 yr) and 10 younger (< 40 yr) patients scheduled for orthopaedic surgery of less than three hours, were anesthetized with nitrous oxide, propofol and alfentanil. Propofol and alfentanil cumulative doses, time from cessation of propofol infusion to eye opening (EO) on verbal command and to extubation were recorded. Psychomotor performance was assessed by the Mini-Mental State (MMS) performed the day prior to surgery and postoperatively at 30, 60, and 120 min, following extubation. Propofol blood concentrations were measured at EO and at each MMS task. RESULTS: Elderly patients were comparable with young patients for preoperative MMS scores, surgery and anaesthesia duration, propofol and alfentanil cumulative doses. Postoperative MMS scores were lower at 30, 60 and 120 min, in elderly patients. Propofol blood concentrations were not different between elderly and young patients at EO, 30, 60 and 120 min. CONCLUSION: Psychomotor performance is impaired in elderly compared with young patients at emergence from propofol-alfentanil anaesthesia. These differences are not likely to be related to propofol accumulation in elderly subjects.     

复合异丙酚麻醉时舒芬太尼抑制强直电刺激和切皮诱发胸腹部手术患者体动反应的药效学

目的 探讨复合异丙酚麻醉时舒芬太尼抑制强直电刺激和切皮诱发胸腹部手术患者体动反应的药效学.方法 择期胸腹部手术患者50例,年龄18～57岁,ASA分级Ⅰ或Ⅱ级,体重为标准体重的80%～120%,随机分为5组(n=10):舒芬太尼效应室靶浓度0.07、0.10、0.14、0.20和0.28 ng/ml组.靶控输注异丙酚,血浆靶浓度3.0～3.2 μg/ml,患者意识消失时各组按设定的效应室靶浓度靶控输注舒芬太尼,待效应室和血浆浓度达平衡后,给予强直电刺激(频率50 Hz,强度80 mA,波宽0.25ms),观察患者反应后给肌松药,行气管插管,维持上述异丙酚和舒芬太尼的靶浓度到切皮后4 min,试验观察结束.观察强直电刺激和切皮时患者的体动反应情况.采用通过概率单位回归分析法计算舒芬太尼抑制电刺激和切皮诱发的体动反应的半数有效效应室靶浓度(EC50)和EC95及其95%可信区间.结果 复合异丙酚麻醉时舒芬太尼抑制强直电刺激诱发的体动发应的EC50和EC95及其95%可信区间分别为0.12(0.09～0.14)ng/ml和0.20(0.17～0.31)ng/ml,抑制切皮诱发的体动发应的EC50和EC95分别为0.13(0.11～0.16)ng/ml和0.21(0.17～0.29)ng/ml;复合异丙酚麻醉时舒芬太尼抑制强直电刺激和切皮诱发的体动发应的EC50和EC95的比较差异无统计学意义(P＞0.05).结论 复合异丙酚麻醉时舒芬太尼抑制强直电刺激(频率50 Hz,强度80 mA,波宽0.25 ms)诱发的体动发应的EC50和EC95分别为0.12和0.20 ng/ml,抑制切皮诱发的体动发应的EC50和EC95分别为0.13和0.21 ng/ml,且抑制两组刺激诱发的体动发应的药效学无差异,提示强直电刺激可替代切皮用于评价麻醉药的药效学.     

Cost comparison between three different general anaesthetic techniques for elective arthroscopy of the knee

INTRODUCTION: We compared three anaesthetic techniques for elective knee arthroscopy with special reference to cost-effectiveness. METHOD: Seventy-five ASA I-II patients having elective arthroscopy of the knee joint were randomised to receive an anaesthetic technique based on propofol, fentanyl for induction followed by sevoflurane in oxygen:nitrous oxide (1:2 l/min) for maintenance of one of two intravenous techniques: propofol alfentanil or propofol-remifentanil infusions in combination with oxygen in air. RESULTS: All patients had an uncomplicated course. No differences were seen with regard to emergence, postoperative pain or emesis or time to discharge. The anaesthetic technique based on sevoflurane was associated with the lowest cost US$ 14.7 as compared to US$ 18 for the propfol/alfentanil and US$ 19.9 for the propofol/remifentanil technique, including both cost for wastage as well as premedication and other fixed drug costs. Looking only at the anaesthetic drugs consumed, the cost per minute was US$ 0.56 for sevoflurane/nitrous oxide as compared to US$ 0.68 and 0.63 per minute for the propofol/alfentanil and proprofol/remifentanil, respectively. When the cost for wastage was taken into account, the difference in mean anaesthetic drug cost was more pronounced: the sevoflurane anaesthetic technique US$ 0.58, the propofol/alfentanil US$ 0.74 and the propofol/remifentanil US$ 0.84 per minute respectively. CONCLUSION: From a cost-minimisation point of view, anaesthesia based on sevoflurane in oxygen:nitrous oxide is the technique of choice.     

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.     

Closed loop control of anaesthesia: an assessment of the bispectral index as the target of control

We investigated the performance of a closed-loop system for administration of general anaesthesia, using the bispectral index as a target for control. One hundred patients undergoing gynaecological or general surgery were studied. In 60 patients, anaesthesia was maintained by intravenous infusion of a propofol/alfentanil mixture. In 40, an isoflurane/nitrous oxide based technique was used. For each technique, patients were randomly allocated to receive either closed-loop or manually controlled administration of the relevant agents (propofol/alfentanil or isoflurane), with an intra-operative target bispectral index of 50 in all cases. Closed-loop and manually controlled administration of anaesthesia resulted in similar intra-operative conditions and initial recovery characteristics. During maintenance of anaesthesia, cardiovascular and electro-encephalographic variables did not differ between closed-loop and manual control groups and deviation of bispectral index from the target value was similar. Intra-operative concentrations of propofol, alfentanil and isoflurane were within normal clinical ranges. Episodes of light anaesthesia were more common in the closed-loop group for patients receiving propofol/alfentanil anaesthesia and in the manual group for patients receiving isoflurane/nitrous oxide anaesthesia. Convenience aside, the closed-loop system showed no clinical advantage over conventional, manually adjusted techniques of anaesthetic administration.     

Prediction of Movement during Propofol/Nitrous Oxide Anesthesia: Performance of Concentration, Electroencephalographic, Pupillary, and Hemodynamic Indicators

Background: Movement in response to painful stimulation is the end point classically used to assess the potency of anesthetic agents. In this study, the ability of modeled propofol effect-site concentration to predict movement in volunteers during propofol/nitrous oxide anesthesia was tested, then it was compared with the predictive abilities of the Bispectral Index and 95% spectral edge frequency of the electroencephalogram, pupillary reflex amplitude, and systolic arterial blood pressure. In addition, the relationships between simple end points of loss and recovery of consciousness, and pupillary, hemodynamic, and propofol concentration indicators were studied.

Methods: Ten healthy volunteers were anesthetized with an infusion of propofol, which was increased in three equal steps to 21 mg *symbol* kg lean body mass sup -1 *symbol* h sup -1. After loss of the ability to hold a syringe and of the eyelash reflex, 60% nitrous oxide was introduced and the trachea was intubated without the use of muscle relaxants. The propofol infusion rate then was decreased to 15.4 mg *symbol* kg lean body mass sup -1 *symbol* h sup -1. Ten minutes later, tetanic electrical stimulation was administered to the thigh via needle electrodes: if movement was observed within 1 min, the propofol infusion rate was increased by 1.75 mg *symbol* kg lean body mass sup -1 *symbol* h sup -1 5 min after the stimulus; if not, it was similarly decreased. This 15-min sequence was repeated until volunteers "crossed over" from movement to no movement (or vice versa) four times. The propofol infusion rate then was increased to 21 mg *symbol* kg lean body mass sup -1 *symbol* h sup -1, nitrous oxide was discontinued, the trachea was extubated, and the infusion rate was decreased in five equal steps over 50 min. The times at which the eyelash reflex returned and the birth date was recalled were recorded. The electroencephalogram was monitored continuously (FP1, FP2, ref: nasion, ground: mastoid). Measurements of the pupillary response, arterial blood pressure, and heart rate were recorded during induction and awakening, just before and for 5 min after each stimulation. Arterial blood samples were obtained for propofol assay, and propofol effect-site concentrations were calculated at each time. The predictive value of indicators was compared using a new statistic, the prediction probability (PK).

Results: Loss and return of the eyelash reflex occurred at greater propofol effect-site concentrations than either dropping the syringe or recall of the birthday. The propofol effect-site concentration (in the presence of 60% nitrous oxide) predicted to prevent movement after a supramaximal stimulus in 50% of volunteers was 1.80 micro gram/ml (95% confidence limits: 1.40-2.34 micro gram/ml). The Bispectral Index (PK = 0.86), 95% spectral edge frequency (PK = 0.81), pupillary reflex amplitude (PK = 0.74), and systolic arterial blood pressure (PK = 0.78) did not differ significantly from modeled propofol effect-site concentration (PK = 0.76) in their ability to predict movement.     

Comparison of a computer-assisted infusion versus intermittent bolus administration of alfentanil as a supplement to nitrous oxide for lower abdominal surgery

The anesthesiologist attempts to balance the dose or concentration of an anesthetic against the intensity of noxious stimulation so as to: 1) maintain a satisfactory anesthetic state, 2) minimize side effects and toxicity of the anesthetic, and 3) allow for a rapid recovery from anesthesia. The development of infusion pumps controlled by computers programmed according to pharmacokinetic principles should facilitate the achievement of these objectives for intravenous drugs. To test this hypothesis, the authors compared anesthetic conditions achieved with a computer-controlled infusion to those produced by the traditional method of intermittent intravenous injections. In both cases, the intravenous opiate, alfentanil, was used to supplement nitrous oxide anesthesia, and the dose/dose-rate of alfentanil after the induction dose was guided by the use of precisely defined clinical signs of inadequate anesthesia. One group of ten patients received 10 mg of alfentanil and 66% N2O to induce anesthesia, and was subsequently given 1 or 2 mg iv doses of alfentanil whenever the depth of anesthesia was inadequate. A second group of ten patients had a target alfentanil concentration of 475 ng/ml of plasma established by the computer-controlled infusion, which subsequently raised or lowered the concentration by 50 or 100 ng/ml according to the presence or absence of clinical signs of inadequate anesthesia. Regular measurements of alfentanil concentrations in plasma showed that the computer-assisted infusion produced relatively stable concentrations that closely paralleled those predicted (prediction error of -64 +/- 40 ng/ml [+/- SD] in the range of 150-600 ng/ml). The traditional method of intermittent injections resulted in continuous, rapid fluctuations in alfentanil concentrations. Both methods were successful in controlling the patients' responses to noxious stimuli, but the infusion group had: 1) a lower incidence of responsiveness, 2) greater hemodynamic stability, 3) no patients requiring naloxone for satisfactory ventilation postoperatively, and 4) an incidence of side effects that tended to be lower. The previously reported alfentanil concentration versus anesthetic effect relationships were confirmed.     

人工流产术患者复合异丙酚时靶控输注瑞芬太尼的药效学

目的 探讨人工流产术患者复合异丙酚4.5 μg/ml时靶控输注瑞芬太尼的药效学.方法 拟行人工流产术患者135例,年龄18～30岁,ASAI级,孕6～10周.随机分为9组(n=15):瑞芬太尼效应室靶浓度分别为0.5、0.8、1.1、1.4、1.7、2.0、2.3、2.6和2.9 ng/ml(Ⅰ组～Ⅸ组).各组异丙酚效应室靶浓度均为4.5 μg/ml.采用概率单位回归分析法,计算麻醉效果达优时瑞芬太尼效应室靶浓度EC50、EC95及其95%可信区间(CI)和呼吸抑制时瑞芬太尼效应室靶浓度EC50、EC95及其95%CI.结果 麻醉效果达优时瑞芬太尼的效应室靶浓度EC50为1.67 ng/ml,其95%CI为1.45～1.90 ng/ml,EC95为3.88 ng/ml,其95%CI为3.08～5.89 ng/ml;呼吸抑制时瑞芬太尼效应室靶浓度EC50为2.44 ng/ml,其95%CI为2.28～2.64 ng/ml,EC95为3.36 ng/ml,其95%CI为2.99～4.34 ng/ml.麻醉效果达优时瑞芬太尼的效应室靶浓度EC95高于呼吸抑制时效应室靶浓度EC95(P＜0.05).结论 人工流产术患者复合异丙酚4.5 μg/ml时,麻醉效果达优时瑞芬太尼的效应室靶浓度EC50、EC95,分别为1.67、3.88 ng/ml,呼吸抑制时瑞芬太尼的效应室靶浓度EC50、EC95,分别为2.44、3.36 ng/ml.     

The Comparative Pharmacodynamics of Remifentanil and Its Metabolite, GR90291, in a Rat Electroencephalographic Model

Background: The purpose of this study was to investigate the in vivo pharmacodynamics and the pharmacodynamic interactions of remifentanil and its major metabolite, GR90291, in a rat electroencephalographic model.

Methods: Remifentanil and GR90291 were administered according to a stepwise infusion scheme. The time course of the electroencephalographic effect (0.5-4.5 Hz) was determined in conjunction with concentrations of the parent drug and the metabolite in blood.

Results: Administration of remifentanil resulted in concentrations of remifentanil and GR90291 in the ranges 0-120 ng/ml and 0-850 ng/ml, respectively. When the metabolite was administered, concentrations of the metabolite in the range 0-220 [micro sign]g/ml and no measurable concentrations of remifentanil were observed. The mean +/- SE values of the pharmacokinetic parameters clearance and volume of distribution at steady state were 920 +/- 110 ml [middle dot] min-1 [middle dot] kg-1 and 1.00 +/- 0.931/kg for remifentanil and 15 +/- 2 ml [middle dot] min-1 [middle dot] kg-1 and 0.56 +/- 0.08 1/kg for GR90291. The relative free concentrations in the brain, as determined on the basis of the cerebrospinal fluid/total blood concentration ratio at steady state, were 25 +/- 5% and 0.30 +/- 0.11% for remifentanil and GR90291, respectively. Concentration-electroencephalographic effect relations were characterized on the basis of the sigmoidal Emax pharmacodynamic model. The mean +/- SE values for the maximal effect (Emax), the concentration at which 50% of the maximal effect is obtained (EC50), and Hill factor for remifentanil were 109 +/- 12 [micro sign]V, 9.4 +/- 0.9 ng/ml, and 2.2 +/- 0.3, respectively (n = 8). For GR90291, the mean +/- SE values for EC50 and the Hill factor were 103,000 +/- 9,000 [micro sign]g/ml and 2.5 +/- 0.4, respectively (n = 6).     

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.     

异丙酚辅助腰硬联合麻醉在腹腔镜疝修补术中气腹时患者体动反应的半数有效效应室靶浓度

目的:确定异丙酚辅助腰麻联合硬膜外麻醉(combined spinal-epidural anesthesia,CSEA)在建立气腹时患者体动反应的半数有效效应室靶浓度(EC50).方法:选择异丙酚辅助行腹腔镜完全腹膜外疝修补术(totally extraperitoneal prosthesis,TEP)患者50例,...     

Effects of Combining Propofol and Alfentanil on Ventilation, Analgesia, Sedation, and Emesis in Human Volunteers

Background: Propofol and alfentanil frequently are administered together for intravenous sedation. This study investigated pharmacokinetic and pharmacodynamic interactions between propofol and alfentanil, at sedative concentrations, with specific regard to effects on ventilation, analgesia, sedation, and nausea.

Methods: Ten male volunteers underwent steady-state infusions on 3 separate days consisting of propofol alone, alfentanil alone, or a combination of the two. Target plasma concentrations for propofol were 150, 300, and 600 ng/ml for 1 h at each concentration; for alfentanil it was 40 ng/ml for 3 h. Assessment included serial measurements of (1) ventilatory function (minute ventilation, carbon dioxide production, end-tidal carbon dioxide, ventilatory response to rebreathing 7% CO2); (2) analgesia (subjective pain report in response to graded finger shock and evoked potential amplitude); (3) sedation (subjective rating, observer scores, and digit symbol substitution test); (4) nausea (visual analog scale, 0-100 mm).

Results: During combination treatment, propofol plasma concentration was 22% greater than during propofol alone using replicate infusion schemes (P < 0.009). End-tidal carbon dioxide was unchanged by propofol, and increased equally by alfentanil and alfentanil/propofol combined (Delta end-tidal carbon dioxide 7.5 and 6.2 mmHg, respectively). Analgesia with propofol/alfentanil combined was greater than with alfentanil alone. (Pain report decreased 50% by PA vs. 28% for alfentanil, P < 0.05). Sedation was greater with propofol/alfentanil combined than with alfentanil or propofol alone (digit symbol substitution test 30 for propofol/alfentanil combined vs. 57 for alfentanil, and 46 for propofol, P < 0.05). Nausea occurred in 50% of subjects during alfentanil, but in none during propofol/alfentanil combination treatment.     

Cardiovascular response of a continuous variable rate alfentanil infusion for abdominal aortic surgery

A prospective study was undertaken to determine the cardiovascular response of a continuous alfentanil infusion during abdominal aortic surgery (AAS). Each subject (n = 20) received a beta-blocking drug preoperatively, and was premedicated with oral lorazepam. Anaesthesia was induced with alfentanil 50 micrograms.kg-1 and thiopentone 3 mg.kg-1, and was maintained with a variable rate infusion of alfentanil and 66 per cent nitrous oxide in oxygen. During the infusion, boluses of alfentanil, 7.5 micrograms.kg-1, were administered to maintain heart rate and blood pressure within 20 per cent of awake baseline values. Haemodynamic stability during surgery was achieved with infusion rates varying between 0.5 and 2.5 micrograms.kg-1, which resulted in mean alfentanil serum concentrations ranging from 186 +/- 53 to 315 +/- 98 ng.ml-1. The mean cumulative alfentanil dose was 15.4 +/- 6.2 mg.patient-1 for surgery which lasted an average of 141 +/- 41 min. Throughout surgery, no patient required inhalational anaesthetic agents or vasoactive drugs. Fifteen of the 20 patients had perioperative Holter monitoring. No myocardial ischaemia was detected during the intraoperative period. However, there was a 33 per cent incidence of myocardial ischaemia on the first postoperative day. There were no myocardial infarcts and no deaths. We conclude that in beta-blocked patients undergoing aortic reconstructive surgery, a variable rate alfentanil infusion administered with 66 per cent nitrous oxide provides anaesthesia characterized by good haemodynamic control without the need for supplemental agents or vasoactive drugs.     

Pharmacokinetics and pharmacodynamics of propofol infusions during general anesthesia

The pharmacokinetic and pharmacodynamic properties of propofol were studied in 50 surgical patients. Propofol was administered as a bolus dose, 2 mg/kg iv, followed by a variable-rate infusion, 0-20 mg/min, and intermittent supplemental boluses, 10-20 mg iv, as part of a general anesthetic technique that included nitrous oxide, meperidine, and muscle relaxants. For a majority of the patients (n = 30), the pharmacokinetics of propofol were best described by a two-compartment model. The propofol mean total body clearance rate was 2.09 +/- 0.65 1/min (mean +/- SD), the volume of distribution at steady state was 159 +/- 57 l, and the elimination half-life was 116 +/- 34 min. Elderly patients (patients older than 60 yr vs. those younger than 60 yr) had significantly decreased clearance rates (1.58 +/- 0.42 vs. 2.19 +/- 0.64 l/min), whereas women (vs. men) had greater clearance rates (33 +/- 8 vs. 26 +/- 7 l.kg-1.min-1) and volumes of distribution (2.50 +/- 0.81 vs. 2.05 +/- 0.65 l/kg). Patients undergoing major (intraabdominal) surgery had longer elimination half-life values (136 +/- 40 vs. 108 +/- 29 min). Patients required an average blood propofol concentration of 4.05 +/- 1.01 micrograms/ml for major surgery and 2.97 +/- 1.07 micrograms/ml for nonmajor surgery. Blood propofol concentrations at which 50% of patients (EC50) were awake and oriented after surgery were 1.07 and 0.95 microgram/ml, respectively. Psychomotor performance returned to baseline at blood propofol concentrations of 0.38-0.43 microgram/ml (EC50). This clinical study demonstrates the feasibility of performing pharmacokinetic and pharmacodynamic analyses when complex infusion and bolus regimens are used for administering iv anesthetics.     

复合异丙酚时舒芬太尼抑制置入输尿管镜时病人体动反应的半数有效效应室靶浓度

目的 确定复合异丙酚时舒芬太尼抑制置入输尿管镜时病人体动反应的半数有效效应室靶浓度(EC50).方法 择期行经尿道输尿管镜钬激光碎石术病人50例,性别不限,年龄20～60岁,BMI＜30 kg/m2,ASA分级Ⅰ级或Ⅱ级,随机分为不同舒芬太尼效应室靶浓度组(n=10),S1组、S2组、S3组、S4组和S5组舒芬太尼效应室靶浓度分别0.21、0.14、0.09、0.06、0.04 ng/ml.靶控输注异丙酚,血浆靶浓度2.5～3.0μg/ml,各组按相应效应室靶浓度靶控输注舒芬太尼,待病人意识消失且舒芬太尼达效应室浓度时置入输尿管镜,以进镜即刻至进镜后1 min内病人发生体动反应(咳嗽和吞咽动作除外)为阳性反应.采用Bliss法计算复合异丙酚时舒芬太尼抑制置入输尿管镜时病人体动反应的EC50为及其95%可信区间.结果 复合异丙酚时舒芬太尼抑制置入输尿管镜时病人体动反应的EC50为0.084 ng/ml,95%可信区间为0.066～0.107 ng/ml.结论复合异丙酚时,舒芬太尼抑制置入输尿管镜时病人体动反应的EC50为0.084 ng/ml.