Oral clonidine premedication reduces the EC50 of propofol concentration for laryngeal mask airway insertion in male patients

BACKGROUND: Oral clonidine, an alpha2-adrenergic receptor agonist, reduces the dose of propofol required for laryngeal mask airway (LMA) insertion. Target-controlled infusion (TCI) is becoming increasingly popular for propofol infusion. There is no information, however, on the propofol blood concentrations required for LMA insertion and the effect of oral clonidine premedication on these values. METHODS: Propofol at target effect-site concentrations from 4.0 to 12.0 microg/ml were randomly administered using TCI in three groups of healthy male patients (n=35 each) who were undergoing elective orthopedic surgery: control, 2.5 microg/kg clonidine, and 5.0 microg/kg clonidine groups. Nothing was administered to the control group. Clonidine(2.5 microg/kg or 5.0 microg/kg) was administered orally 90 min before arrival at the operating room in the clonidine groups. After equilibration between the blood- and effect-site for 15 min, insertion of the LMA was attempted. The EC50 for LMA insertion (measured propofol serum concentration in equilibrium with the effect-site at which 50% of patients do not respond to the insertion of the LMA) was determined by logistical regression. RESULTS: EC50+/-standard error values in the control, 2.5 microg/kg clonidine, and 5.0 microg/kg clonidine groups were 8.72+/-0.55, 7.76+/-0.60, and 5.84+/-0.58 microg/ml, respectively. The EC50 in the 5.0 microg/kg clonidine group was significantly lower than that in the control group (P < 0.01). CONCLUSIONS: The propofol concentration required for LMA insertion in healthy male patients is reduced by premedication with 5.0 microg/kg oral clonidine.     

Oral clonidine premedication reduces the awakening concentration of propofol

To investigate the effects of oral clonidine premedication on emergence from propofol/fentanyl anesthesia, we studied 72 healthy male patients who were undergoing elective orthopedic surgery: the Control group, the 2.5 microg/kg Clonidine group, and the 5.0 microg/kg Clonidine group (n = 24 each). Nothing was administered to the Control group. Clonidine (2.5 or 5.0 microg/kg) was orally administered 90 min before the induction of anesthesia in the Clonidine groups. Patients were anesthetized with computer-assisted continuous infusion of propofol and fentanyl, with the three groups receiving the same concentrations of propofol (3 microg/mL) and fentanyl (1 ng/mL) starting 20 to 30 min before the end of surgery. Propofol infusion was then abruptly discontinued at the end of surgery in all patients. After propofol was discontinued, the response to verbal commands was evaluated every 30 s, and arterial blood samples for propofol and clonidine concentrations were taken when the patients opened their eyes. The time required to respond to a verbal command was 14.9 plus/minus 8.3 min for the 5.0 microg/kg Clonidine group, and this was significantly longer than the Control (8.2 plus/minus 5.0 min) and the 2.5 microg/kg Clonidine (9.0 plus/minus 3.7 min) groups (P < 0.01). Serum propofol concentration at awakening in the 5.0 microg/kg Clonidine group was 1.0 plus/minus 0.4 microg/mL, which was significantly smaller than the Control (1.6 plus/minus 0.4 microg/mL) and the 2.5 microg/kg Clonidine (1.4 plus/minus 0.3 microg/mL) groups (P < 0.01). The blood clonidine concentration was associated with a decrease in the awakening propofol concentration. In conclusion, 5 microg/kg oral clonidine premedication decreases the awakening propofol concentration and delays arousal from propofol/fentanyl anesthesia. IMPLICATIONS: Preanesthetic medication with 5 microg/kg oral clonidine, but not 2.5 microg/kg clonidine, is associated with prolonged recovery from propofol/fentanyl anesthesia.     

Early pregnancy does not reduce the C(50) of propofol for loss of consciousness.

Requirements for inhaled anesthetics decrease during pregnancy. There are no published data, however, regarding propofol requirements in these patients. Because propofol is often used for induction of general anesthesia when surgery is necessary in early pregnancy, we investigated whether early pregnancy reduces the requirement of propofol for loss of consciousness using a computer-assisted target-controlled infusion (TCI). Propofol was administered using TCI to provide stable concentrations and to allow equilibration between blood and effect-site (central compartment) concentrations. Randomly selected target concentrations of propofol (1.5-4.5 microg/mL) were administered to both pregnant women (n = 36) who were scheduled for pregnancy termination and nonpregnant women (n = 36) who were scheduled for elective orthopedic or otorhinolaryngologic surgery. The median gestation of the pregnant women was 8 wk (range, 6-12 wk). Venous blood samples for analysis of the serum propofol concentration were taken at 3 min and 8 min after equilibration of the propofol concentration. After a 10-min equilibration period of the predetermined propofol blood concentration, a verbal command to open their eyes was given to the patients twice, accompanied by rubbing of their shoulders. Serum propofol concentrations at which 50% of the patients did not respond to verbal commands (C(50) for loss of consciousness) were determined by logistic regression. There was no significant difference in C(50) +/- SE of propofol for loss of consciousness between the Nonpregnant (2.1 +/- 0.2 microg/mL) and Pregnant (2.0 +/- 0.2 microg/mL) groups. These results indicate that early pregnancy does not decrease the concentration of propofol required for loss of consciousness. IMPLICATIONS: The C(50) of propofol for loss of consciousness in early pregnancy did not differ from that in nonpregnant women, indicating that there is no need to decrease the propofol concentration for loss of consciousness when inducing general anesthesia for termination of pregnancy.     

Individual effect-site concentrations of propofol are similar at loss of consciousness and at awakening

Reported effect-site concentrations of propofol at loss of consciousness and recovery of consciousness vary widely. Thus, no single concentration based on a population average will prove optimal for individual patients. We therefore tested the hypothesis that individual propofol effect-site concentrations at loss and return of consciousness are similar. Propofol effect-site concentrations at loss and recovery of consciousness were estimated with a target-control infusion system in 20 adults. Propofol effect-site concentrations were gradually increased until the volunteers lost consciousness (no response to verbal stimuli); unconsciousness was maintained for 15 min, and the volunteers were then awakened. This protocol was repeated three times in each volunteer. Our major outcomes were the concentration producing unconsciousness and the relationship between the estimated effect-site concentrations at loss and recovery of consciousness. The target effect-site propofol concentration was 2.0 +/- 0.9 at loss of consciousness and 1.8 +/- 0.7 at return of consciousness (P <0.001). The average difference between individual effect-site concentrations at return and loss of consciousness was only 0.17 +/- 0.32 microg/mL (95% confidence interval for the difference 0.09-0.25 microg/mL). Our results thus suggest that individual titration to loss of consciousness is an alternative to dosing propofol on the basis of average population requirements.     

Propofol and remifentanil effect-site concentrations estimated by pharmacokinetic simulation and bispectral index monitoring during craniotomy with intraoperative awakening for brain tumor resection

Different anesthetic techniques have been suggested for craniotomy with intraoperative awakening. We describe an asleep-awake-asleep technique with propofol and remifentanil infusions, with pharmacokinetic simulation to predict the effect-site concentrations and to modulate the infusion rates of both drugs, and bispectral index (BIS) monitoring. Five critical moments were defined: first loss of consciousness (LOC1), first recovery of consciousness (ROC1), final of neurologic testing (NT), second loss of consciousness (LOC2), and second recovery of consciousness (ROC2). At LOC1, predicted effect-site concentrations of propofol and remifentanil were, respectively, 3.6+/-1.2 microg/mL and 2.4+/-0.4 etag/mL. At ROC1, predicted effect-site concentrations of propofol and remifentanil were, respectively, 2.1+/-0.3 microg/mL and 1.8+/-0.3 etag/mL. At NT, predicted effect-site concentrations of propofol and remifentanil were, respectively, 0.9+/-0.3 microg/mL and 1.8+/-0.2 etag/mL. At LOC2, predicted effect-site concentrations of propofol and remifentanil were, respectively, 2.1+/-0.2 microg/mL and 2.5+/-0.2 etag/mL. At ROC2, predicted effect-site concentrations of propofol and remifentanil were, respectively, 1.2+/-0.5 microg/mL and 1.4+/-0.2 etag/mL (data are mean+/-SE). A significative correlation was found between BIS and predicted effect-site concentrations of propofol (r=0.547, P<0.001) and remifentanil (r=0.533, P<0.001). Multiple regression analysis between BIS and propofol and remifentanil predicted effect-site concentrations at the different critical steps of the procedure was done and found also significative (r=0.7341, P<0.001).     

Clinical variables related to propofol effect-site concentrations at recovery of consciousness after neurosurgical procedures

Target controlled infusion (TCI) systems and computer data acquisition software are increasingly used in anesthesia. It was hypothesized that the use of such systems might allow retrieval of information useful to anticipate the effect-site concentrations of propofol at which patients would recover from anesthesia. The goal of the study was to identify variables related to propofol effect-site concentrations at recovery of consciousness (ROC). Sixteen patients with a Glasgow of 15, ASA 1 or 2, subjected to neurosurgical procedures, received TIVA with TCI propofol and remifentanil. Data were collected every 5 seconds from Datex AS3 and Aspect A200XP (BIS). Effect-site TCI was used for propofol (initial effect target 5.0 microg/ml) and for remifentanil (initial plasma target 2.5 ng/ml). All clinical events were noted. Variables possibly related to propofol effect-site concentration at ROC were selected. Data are expressed as mean +/- SD. Effect-site propofol concentration at ROC was 1.3 +/- 0.5 microg/ml. A positive correlation was found between propofol effect-site concentration at ROC and: age (49.3 +/- 17 years) (P = 0.003); mean remifentanil dose during surgery (0.11 +/- 0.05 microg/kg/min) (P = 0.003); mean propofol dose during surgery (0.12 +/- 0.03 mg/kg/min) (P = 0.046); and remifentanil effect-site concentration at ROC (2.85 +/- 2.06 ng/ml) (P = 0.002). Propofol effect-site concentrations were not correlated with: weight, height, LBM, duration of anesthesia, minimum BIS at induction (30.4 +/- 6.8), time till minimum BIS (4.7 +/- 2.2 min), mean and median BIS during surgery (38.2 +/- 4.5 and 37.8 +/- 5.3). BIS-related variables were not useful as ROC predictors. Only drug variables and age correlated with propofol effect-site concentrations at ROC.     

长期饮酒对异丙酚使患者意识消失的半数有效效应室靶浓度的影响

目的 拟通过探讨长期饮酒对异丙酚使患者意识消失的半数有效效应室靶浓度(EC50)的影响,评价长期饮酒对异丙酚镇静效力的影响.方法 择期拟行外科手术的男性患者50例,年龄25～60岁,体重50～80kg,ASA分级Ⅰ或Ⅱ级,根据是否有长期饮酒史分为2组(n=25),对照组:日饮酒量＜25 g;长期饮酒组:日饮酒量超过45 g持续2年或2年以上.采用序贯法确定异丙酚使患者意识消失的EC50其95%可信区间,长期饮酒组和对照组异丙酚初始效应室靶浓度分别为2.0和1.5μg/ml,各相邻靶浓度之比为1.05.以睫毛反射消失及对言语指令无反应作为判断意识消失的标准.结果 长期饮酒组和对照组异丙酚使患者意识消失时的EC50及其95%可信区间分别为3.92(3.56～4.63)g/ml和2.73(2.26～3.31)μg/ml,长期饮酒组EC50高于对照组(P＜0.05).结论 长期饮酒可增加异丙酚使患者意识消失时的EC50,降低其镇静效力.

Abstract：

Objective To evaluate the effect of chronic alcohol intake on the sedative potency of propofol through investigating the effect of chronic alcohol intake on the half-effective target effect-site concentration ( EC50 )of propofol required for loss of consciousness in patients. Methods Fifty male ASA Ⅰ or Ⅱ patients, aged 25-60 yr, weighing 50-80 kg, scheduled for elective surgery, were divided into 2 groups according to the history of chronic alcoholic intake ( n = 25 each): control group (alcoholic intake per day ＜ 25 g) and chronic alcoholic group (alcoholic intake per day＞45 g, lasting for 2 yr or more). The EC50 and 95% confidence interval (CI)were determined by up-and-down sequential method. The initial target effect-site concentration was 2 μg/nl in chronic alcoholic group and 1.5μg/ml in control group, and the ratio between the two successive concentrations was 1.05. Loss of consciousness was defined as loss of response to verbal command and eyelash stimulation. Results The EC50 of propofol that produced loss of consciousness was 3.92 (95 % CI 3.56-4.63 ) μg/ml in chronic alcoholic group and 2.73 (95%CI 2.26-3.31)μg/ml in control group. The EC50 of propofol was significantly higher in chronic alcoholic group than in control group ( P ＜ 0.05). Conclusion Chronic alcohol intake can increase the EC50 of propofol required to induce loss of consciousness and reduce sedative potency in patients.     

Laryngeal mask insertion during target-controlled infusion of propofol

STUDY OBJECTIVE: To compare the Laryngeal Mask Airway (LMA; The Laryngeal Mask Airway Co., Ltd., Nicosia, Cyprus) insertion conditions produced by 6 and 8 microg/mL of target plasma concentrations (Cpt) during the induction of anesthesia with target-controlled infusion (TCI) of propofol. DESIGN: Randomized, prospective, single-blind, clinical study. SETTING: University hospital. PATIENTS: 44 ASA physical status I and II patients, 16 to 54 years of age, weighing between 45 and 100 kg, undergoing minor surgery in which the use of LMA was indicated. INTERVENTIONS: Patients were randomly divided into two groups (1 and 2) of 22 to compare the effects of different propofol concentrations. Three minutes after intravenous (IV) injection of midazolam 0.04 mg/kg, group 1 and 2 received TCI of propofol with 6 and 8 microg/mL of Cpt, respectively. LMA was inserted when the effect-site concentration (EC) reached 2.5 microg/mL, which was displayed on the infusion pump. MEASUREMENTS: The LMA insertion conditions (mouth opening, gagging, coughing, head or limb movement, laryngospasm, overall ease of insertion) were assessed, and hemodynamic responses were evaluated until 3 minutes after LMA insertion. Total dose of propofol, EC, and elapsed time since the start of TCI were recorded at five times: at the loss of consciousness and eyelash reflex, at 2.5 microg/mL of EC, and immediately, 1 minute, and 3 minutes after the insertion of LMA. MAIN RESULTS: There was no significant difference between the two groups in insertion conditions, despite the significantly larger total dose and shorter elapsed time (2.6 +/- 0.08 mg/kg and 109 +/- 5.0 s) in Group 2 than those (2.1 +/- 0.02 mg/kg and 140 +/- 4.1 s) in Group 1 at 2.5 microg/mL of EC (p < 0.05). Systolic and diastolic blood pressure decreased and heart rate increased significantly throughout the study period in both groups (p < 0.05). But there was a significant decrease in arterial pressure in Group 2 compared with Group 1 1 and 3 minutes after the insertion (p < 0.05). CONCLUSIONS: Induction with 8 microg/mL of Cpt, compared with 6 microg/mL, allowed earlier LMA insertion but, could not improve the conditions for LMA insertion and required more careful attention to the decrease in blood pressure after LMA insertion.     

Oral clonidine premedication reduces induction dose and prolongs awakening time from propofol-nitrous oxide anesthesia

PURPOSE: To evaluate whether oral clonidine premedication affects the induction dose of propofol and awakening time from epidural and propofol anesthesia. METHODS: Thirty-nine female patients (ASA I or II) were randomly allocated to receive 5 microg x kg(-1) clonidine p.o. or no clonidine 90 min before induction of anesthesia. After epidural anesthesia was achieved with lidocaine, general anesthesia was induced with continuous i.v. infusion of propofol at a rate of 50 mg x min(-1) until loss of eyelash reflex and responses to verbal commands, which were judged by a blinded observer. After a laryngeal mask airway was inserted, anesthesia was maintained with N2O 67%, O2 33% and propofol adjusted to maintain hemodynamic stability. After completion of surgery, a blinded observer recorded the time from discontinuance of propofol and N2O until the patient was awake and responsive (awakening time), and then, the laryngeal mask airway was removed. RESULTS: The induction dose of propofol in the clonidine group (1.4 +/- 0.3 mg) was less than that in the control group (1.9 +/- 0.4 mg, P < 0.05), while the awakening time of the clonidine group (470 +/- 145 sec) was longer than that of the control group (329 +/- 123 sec, P < 0.05). CONCLUSION: Premedication with 5 microg x kg(-1) clonidine p.o. reduced the induction dose of propofol, but delayed emergence from propofol anesthesia.     

The reduction in minimum alveolar concentration for tracheal extubation after clonidine premedication in children

The effects of clonidine on minimum alveolar concentration for tracheal extubation (MAC-ex) have not been elucidated. Clonidine may lead to prolonged emergence from anesthesia. We investigated the effects of oral clonidine premedication on MAC-ex and examined the emergence properties of sevoflurane in children. Sixty ASA physical status I pediatric patients, aged from 2 to 9 yr, were randomly divided into one of three groups and received placebo, clonidine 2 microg/kg, or clonidine 4 microg/kg (n = 20 each) orally, 100 min before the induction of anesthesia. The induction of anesthesia, tracheal intubation, and maintenance of anesthesia were performed with sevoflurane in air and oxygen. MAC-ex was defined according to the modification of Dixon's up-and-down method, with 0.25% as a step size. In addition, in the Control and 4 microg/kg groups, the time from tracheal extubation to spontaneous eye opening (eye-opening time) and the time from tracheal extubation to leaving the operating room (awakening time) were recorded. MAC-ex for sevoflurane (mean +/- SD) was 1.63% +/- 0.13%, 1.04% +/- 0.26%, and 0.66% +/- 0.09% respectively in the Control group, 2 microg/kg group, and 4 microg/kg group. Significant differences were observed among the three groups. The eye-opening times were 5.7 +/- 3.5 min in the Control group and 5.1 +/- 1.0 min in the 4 microg/kg group. The awakening times were 9.7 +/- 3.7 min in the Control group and 9.2 +/- 3.8 min in the 4 microg/kg group. No significant differences were observed among the groups. IMPLICATIONS: Oral clonidine premedication decreased MAC for tracheal extubation for sevoflurane dose dependency and did not prolong emergence from anesthesia.     

The relationship of individual sensitivities to fentanyl and those to propofol

BACKGROUND: Individual variation in the sensitivity to anesthetics induces the delayed awakening and the severe postoperative pain at an inappropriate dose. We designed the study to see the correlation of the individual sensitivity to fentanyl and that to propofol which have different mechanism. METHODS: General anesthesia was induced using target controlled infusion system of fentanyl and propofol. Fentanyl effect-site concentration gradually increased towards a target plasma concentration of 3 ng x ml(-1) until the appearance of the subjective symptom such as dizziness, a sensation of warmth and other reactions. After this, propofol effect-site concentration gradually increased towards a target plasma concentration of 4 microg x ml(-1) until loss of consciousness (LOC). The effect-site concentrations of fentanyl at the symptom and propofol at loss of consciousness were measured. RESULTS: The correlation between the estimated effect-site concentration of fentanyl and propofol is not significant in the whole patient. However, a positive correlation between fentanyl and propofol was found in patients from 50s to 70s years of ages (r = 0.59). CONCLUSIONS: The correlation of the individual sensitivity to fentanyl and propofol was found in older age groups.     

Oral clonidine premedication reduces minimum alveolar concentration of sevoflurane for laryngeal mask airway insertion in children

BACKGROUNDS: Sevoflurane is widely employed for inhalational induction in children. Clonidine deepens volatile anesthetics and reduces several types of MAC of sevoflurane. Laryngeal mask airway is a useful device for pediatric anesthesia. The aim of the current study was to determine whether oral clonidine premedication can reduce MAC of sevoflurane for an LMA insertion in children. METHODS: Fifty-six ASA physical status I patients (3-11 years) scheduled for general anesthesia were randomly divided into two groups of 28 patients each. One group (clonidine group) received clonidine 4 microg x kg(-1) approximately 100 min before anesthesia, and the other (control) group did not. Anesthesia was induced with sevoflurane. Each concentration of sevoflurane, at which an LMA insertion was attempted, was predetermined according to the modification of Dixon's up-and-down method with 0.25% as a step size and held constant for at least 20 min before the trial. All responses ('movement' or 'no movement') to an LMA insertion were assessed. RESULTS: Minimum alveolar concentration values of sevoflurane for an LMA insertion were lower in the clonidine group (1.31% +/- 0.18% [mean +/- sd]) than in the control group (2.00% +/- 0.16%). Logistic regression analysis revealed that sevoflurane EC95 values were 1.79% and 2.49% in the clonidine and control groups, respectively. CONCLUSIONS: Oral clonidine premedication reduced the MAC (EC50) and EC95 values of sevoflurane for LMA insertion by 38% and 28%, respectively.     

Plasma lidocaine concentrations during continuous thoracic epidural anesthesia after clonidine premedication in children.

There is no report concerning oral clonidine's effects on epidural lidocaine in children. Therefore, we performed a study to assess the concentrations of plasma lidocaine and its major metabolite (monoethylglycinexylidide [MEGX]) in children receiving continuous thoracic epidural anesthesia after oral clonidine premedication. Ten pediatric patients, aged 1-9 yr, were randomly allocated to the Control or Clonidine 4 microg/kg group (n = 5 each). Anesthesia was induced and maintained with sevoflurane in oxygen and air (FIO2 40%). Epidural puncture and tubing were carefully performed at the Th11-12 intervertebral space. An initial dose of 1% lidocaine (5 mg/kg) was injected through a catheter into the epidural space, followed by 2.5 mg x kg(-1) x h(-1). Plasma concentrations of lidocaine and MEGX were measured at 15 min, 30 min, and every 60 min for 4 h after the initiation of continuous epidural injection. The concentrations of lidocaine and MEGX were measured using high-pressure liquid chromatography with ultraviolet detection. Hemodynamic variables were similar between members of the Control and Clonidine groups during anesthesia. The Clonidine group showed significantly smaller lidocaine concentrations (p < 0.05) and the concentration of MEGX tended to be smaller in the plasma of the Clonidine group for the initial 4 h after the initiation of epidural infusion. In conclusion, oral clonidine preanesthetic medication at a dose of 4 microg/kg decreases plasma lidocaine concentration in children. IMPLICATIONS: Oral clonidine decreases the plasma lidocaine concentration in children. Our finding may have clinical implications in patients receiving continuous epidural anesthesia. Additionally, perhaps an additional margin of safety regarding lidocaine toxicity is gained through the use of oral clonidine in children who will receive epidural lidocaine.     

Oral clonidine premedication reduces propofol requirement for laryngeal mask airway insertion

PURPOSE: To determine the effect of oral clonidine premedication on propofol requirement (ED(50)) for the insertion of the laryngeal mask airway (LMA) in healthy patients undergoing abdominal hysterectomy. METHODS: After ethics committee approval and informed consent, 41 patients were randomly assigned to receive 5 microg x kg(-1) clonidine po premedication 90 min before entering the operating room (n = 22), or no clonidine (n = 19). To alleviate pain associated with iv propofol, 3 ml lidocaine 2%iv were administered. General anesthesia was induced, 30 sec later, with propofol at a rate of 100 mg x min(-1) (600 ml x hr(-1)) iv. The dose of propofol at which insertion of the LMA was attempted was predetermined by modification of Dixon's up-and-down method with an initial dose of 2.5 mg x kg(-1) and 0.25 mg x kg(-1) as the step size. An LMA was inserted, without muscle relaxants or other adjuvants 90 sec after completion of the propofol injection, by an anesthesiologist blinded to the treatment of the patient. RESULTS: The ED(50) of propofol for LMA insertion in clonidine-treated patients (2.0 +/- 0.2 mg x kg(-1), 1.8-2.3 mg x kg(-1) [95% confidence interval]), was less than that in patients without clonidine (2.5 +/- 0.1 mg x kg(-1), 2.4-2.6 mg x kg(-1), P < 0.01). CONCLUSION: Oral clonidine premedication reduces propofol requirement for LMA insertion.     

Oral Clonidine Premedication Reduces Minimum Alveolar Concentration of Sevoflurane for Tracheal Intubation in Children

Background: Sevoflurane is a useful anesthetic for inhalational induction in children because of its low solubility in blood and relatively nonpungent odor. Clonidine has sedative and anxiolytic properties and reduces the requirement for inhalation agents. Nitrous oxide (N2 O) also decreases the requirement of inhaled anesthetics, but the effect is variable. The minimum alveolar concentration for tracheal intubation (MACTI) of sevoflurane was assessed with and without N2 O and clonidine premedication.

Methods: Seventy-two patients, aged 3-11 yr, were assigned to one of six groups (n = 12 each). They received one of three preanesthetic medications (two groups for each premedication): placebo (control), 2 micro gram/kg oral clonidine or 4 micro gram/kg oral clonidine. In one group of each premedication, anesthesia was induced with sevoflurane in oxygen; in the other group, anesthesia was induced with sevoflurane in the presence of 60% N2 O. Each concentration of sevoflurane at which tracheal intubation was attempted was predetermined according to Dixon's up-and-down method and held constant for at least 20 min before the trial.

Results: The MACTI of sevoflurane in the absence of N2 O (mean +/- SEM) was 3.2 +/- 0.2%, 2.5 +/- 0.1%, and 1.9 +/- 0.2% in the control, 2-micro gram/kg clonidine, and 4-micro gram/kg clonidine groups, respectively. Nitrous oxide (60%) decreased the MACTI of sevoflurane by 26%, 24%, and 27% in the control, 2-micro gram/kg clonidine, and 4-micro gram/kg clonidine groups.     

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.     

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.     

Automated responsiveness test (ART) predicts loss of consciousness and adverse physiologic responses during propofol conscious sedation

BACKGROUND: The authors evaluated a device designed to provide conscious sedation with propofol (propofol-air), or propofol combined with 50% nitrous oxide (N2O; propofol-N2O). An element of this device is the automated responsiveness test (ART), a method for confirming that patients remain conscious. The authors tested the hypotheses that the ART predicts loss of consciousness and that failure to respond to the ART precedes sedation-induced respiratory or hemodynamic toxicity. METHODS: The protocol consisted of sequential 15-min cycles in 20 volunteers. After a 15-min control period, propofol was infused to an initial target effect-site concentration of 0.0 microg/ml with N2O or 1.5 microg/ml with air. Subsequently, the propofol target effect-site concentration was increased by a designated increment (0.25 and 0.5 microg/ml) and the process repeated. This sequence was continued until loss of consciousness, as defined by an Observer's Assessment of Alertness/Sedation (OAA/S) score of 10/20 or less, or until an adverse physiologic event was detected. RESULTS: The OAA/S score at which only 50% of the volunteers were able to respond to the ART (P50) during propofol-N2O was 11.1 of 20 (95% confidence interval [CI]: 10.6-11.8); the analogous P50 was 11.8 of 20 (95% CI: 11.4-12.3) with propofol-air. Failure to respond to the ART occurred at a plasma propofol concentration of 0.7 +/- 0.6 microg/ml with propofol-N2O and 1.6 +/- 0.6 microg/ml with propofol-air, whereas loss of consciousness occurred at 1.2 +/- 0.8 microg/ml and 1.9 +/- 0.7 microg/ml, respectively. There were no false-normal ART responses. CONCLUSION: The ART can guide individual titration of propofol because failure to respond to responsiveness testing precedes loss of consciousness and is not susceptible to false-normal responses. The use of N2O with propofol for conscious sedation decreases the predictive accuracy of the ART.     

Gender differences between predicted and measured propofol C(P50) for loss of consciousness

OBJECTIVE: To investigate gender differences in the effective dose of 50% for loss of consciousness (C(P50LOC)) for propofol using Diprifusor, the most commonly used target-controlled infusion system. DESIGN: Prospective, randomized, comparative study. SETTING: University-affiliated hospital. PATIENTS: 50 ASA physical status I and II patients, aged 20 to 50 years, scheduled for minor surgery. INTERVENTIONS: Patients were randomized into two groups of 25 patients each. A target-controlled infusion of propofol (Diprifusor) was maintained at a predetermined target concentration. After a 10-minute steady state, blinded investigators evaluated patients' consciousness using verbal commands. The propofol test concentration was predetermined using a modified version of Dixon's up-and-down method (starting at 2.5 mug/mL; step size of 0.1 microg/mL). MEASUREMENT: Predicted and measured C(P50LOC) values and bispectral index (BIS) were obtained by averaging the crossover midpoint (ie, consciousness to unconsciousness). Those values were analyzed by unpaired t test: P < 0.05 was considered significant. RESULTS: The predicted C(P50LOC) for men was 2.14 +/- 0.10 microg/mL, which was lower than that for women, 2.55 +/- 0.11 microg/mL (P < 0.0001). No significant difference was found for measured C(P50LOC) in men (2.37 +/- 0.41 microg/mL) and in women (2.30 +/- 0.28 microg/mL) or for BIS measurements. CONCLUSION: Predicted C(P50LOC) by Diprifusor for men tended to be underestimated; that for women tended to be overestimated. Our data support a review of Diprifusor (Astra Zeneca, Osaka, Japan) pharmacokinetic parameters to avoid awareness during operation, particularly for women.     

急性高容量血液稀释对患者靶控输注异丙酚意识消失时EC50的影响

目的 探讨急性高容量血液稀释(AHHD)对患者靶控输注(TCI)异丙酚意识消失时EC50的影响.方法 择期行脊柱手术或全髋置换术患者60例,年龄18～64岁,ASA Ⅰ或Ⅱ级,随机分为4组(n=15):异丙酚血浆靶浓度输注组(Tp组)、异丙酚效应室靶浓度输注组(Te组)、AHHD+Tp组和AHHD+Te组.入室后经30 min外周静脉输注乳酸钠林格氏液0.7 nl·kg-1·h-1,AHHD+Tp组和AHHD+Te组同时经颈内静脉输注4%琥珀酰明胶15 ml/kg行AHHD.AHHD结束后TCI异丙酚,初始靶浓度为1.2μg/ml,到达该浓度30 S后,采用警觉/镇静评分(OAA/S)评价患者的意识状态,然后以0.3 μg/ml的浓度梯度增加靶浓度,直至患者意识消失(OAA/S=0分),记录此时异丙酚的血浆靶浓度和效应室靶浓度.采用概率单位法计算异丙酚意识消失时的EC50及其95%可信区间(CI).结果 Tp组、Te组、AHHD+Tp组和AHHD+Te组意识消失时异丙酚的EC50及其95%CI分别为3.74(3.46～4.16)、2.32(2.17～2.42)、4.12(3.81～4.32)、2.38(2.14～2.56)μg/ml.与Tp组比较,AHHD+Tp组意识消失时异丙酚的EC50升高(P<0.05);与Te组相比,AHHD+Te组意识消失时异丙酚的EC50差异无统计学意义(P>0.05).结论 AHHD可升高患者TCI异丙酚意识消失时血浆靶浓度的EC50,对效应室靶浓度的EC50无影响.