Bispectral Analysis Measures Sedation and Memory Effects of Propofol, Midazolam, Isoflurane, and Alfentanil in Healthy Volunteers

Background: The bispectral index (BIS), a value derived from the electroencephalograph (EEG), has been proposed as a measure of anesthetic effect. To establish its utility for this purpose, it is important to determine the relation among BIS, measured drug concentration, and increasing levels of sedation. This study was designed to evaluate this relation for four commonly used anesthetic drugs: propofol, midazolam, isoflurane, and alfentanil.

Methods: Seventy-two consenting volunteers were studied at four institutions. Volunteers were given either isoflurane, propofol, midazolam, or alfentanil. Each volunteer was administered a dose-ranging sequence of one of the study drugs to achieve predetermined target concentrations. A frontal montage was used for continuous recording of the EEG. At each pseudo-steady-state drug concentration, a BIS score was recorded, the participant was shown either a picture or given a word to recall, an arterial blood sample was obtained for subsequent analysis of drug concentration, and the participant was evaluated for level of sedation as determined by the responsiveness portion of the observer's assessment of the alertness/sedation scale (OAAS). An OAAS score of 2 or less was considered unconscious. The BIS (version 2.5) score was recorded in real-time and the BIS (version 3.0) was subsequently derived off-line from the recorded raw EEG data. The relation among BIS, measured drug concentration, responsiveness score, and presence or absence of recall was determined by linear and logistic regression for both the individual drugs and, when appropriate, for the pooled results. The prediction probability was also calculated.

Results: The BIS score (r = 0.883) correlated significantly better than the measured propofol concentration (r = -0.778; P < 0.05) with the responsiveness score. The BIS provided as effective correlation with responsiveness score of the OAAS as did the measured concentration for midazolam and isoflurane. None of the volunteers given alfentanil lost consciousness and thus were excluded from the pooled analysis. The pooled BIS values at which 50% and 95% of participants were unconscious were 67 and 50, respectively. The prediction probability values for BIS ranged from 0.885-0.976, indicating a very high predictive performance for correctly indicating probability of loss of consciousness.     

Propofol Alters the Pharmacokinetics of Alfentanil in Healthy Male Volunteers

Background: The influence of propofol on the pharmacokinetics of alfentanil is poorly understood. The authors therefore studied the effect of a pseudo-steady state concentration of propofol on the pharmacokinetics of alfentanil.

Methods: The pharmacokinetics of alfentanil was studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While breathing 30% O2 in air, 12.5 [mu]g/kg intravenous alfentanil was given in 2 min, followed by 25 [mu]g [middle dot] kg-1 [middle dot] h-1 for 58 min (sessions A and B). During session B, a target controlled infusion of propofol (target concentration, 1.5 [mu]g/ml) was given from 10 min before the start until 6 h after termination of the alfentanil infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the plasma alfentanil concentration were collected until 6 h after termination of the alfentanil infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of propofol and mean arterial pressure were constructed.

Results: A three-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration-time curves of alfentanil. Propofol decreased the elimination clearance of alfentanil by 15%, rapid distribution clearance by 68%, slow distribution clearance by 51%, and lag time by 62%. Mean arterial pressure and systemic vascular resistance were significantly lower in the presence of propofol. Scaling the pharmacokinetic parameters to the mean arterial pressure instead of propofol improved the model.     

Behavioral and Physiological Effects of Remifentanil and Alfentanil in Healthy Volunteers

Background: The subjective and psychomotor effects of remifentanil have not been evaluated. Accordingly, the authors used mood inventories and psychomotor tests to characterize the effects of remifentanil in healthy, non-drug-abusing volunteers. Alfentanil was used as a comparator drug.

Methods: Ten healthy volunteers were enrolled in a randomized, double-blinded, placebo-controlled, crossover trial in which they received an infusion of saline, remifentanil, or alfentanil for 120 min. The age- and weight-adjusted infusions (determined with STANPUMP, a computer modeling software package) were given to achieve three predicted constant plasma levels for 40 min each of remifentanil (0.75, 1.5, and 3 ng/ml) and alfentanil (16, 32, and 64 ng/ml). Mood forms and psychomotor tests were completed, and miosis was assessed, during and after the infusions. In addition, analgesia was tested at each dose level using a cold-pressor test.

Results: Remifentanil had prototypic [micro sign]-like opioid subjective effects, impaired psychomotor performance, and produced analgesia. Alfentanil at the dose range tested had more mild effects on these measures, and the analgesia data indicated that a 40:1 potency ratio, rather than the 20:1 ratio we used, may exist between remifentanil and alfentanil. A psychomotor test administered 60 min after the remifentanil infusion was discontinued showed that the volunteers were still impaired, although they reported feeling no drug effects.     

Effects of Subhypnotic Doses of Propofol on Gastric Emptying in Volunteers

Background: Drugs which accelerate gastric emptying (GE) decrease nausea and vomiting. This could contribute to the antiemetic potential of subhypnotic doses of propofol. On the contrary, subhypnotic doses of propofol used for sedation could decrease GE and thus favor regurgitation and pulmonary inhalation. Therefore, the aim of this study was to assess the effect of low-dose propofol infusion on GE.

Methods: On three separate occasions, 10 volunteers received either a propofol infusion at a rate set to achieve a target plasma concentration of 0.5 [mu]g/ml or equivalent volumes of 10% Intralipid(R) or 0.9% saline. GE for solids was measured by using the octanoic acid breath test. An acetaminophen absorption technique measured the GE rate for liquids. Blood samples were assayed for acetaminophen and propofol. Breath samples were analyzed for 13CO2 concentration by isotope-ratio mass spectrometry. Carbon dioxide production ([latin capital V with dot above]co2) was measured instead of calculated by indirect calorimetry. Sedation was evaluated by the Bispectral Index of the electroencephalogram.

Results: Propofol blood concentrations were 0.32 +/- 0.20 and 0.45 +/- 0.18 [mu]g/ml at 60 and 165 min, respectively. These concentrations were not sedative. Propofol or its solvent did not modify GE for solids or liquids. In all groups, differences in GE were obtained if measured [latin capital V with dot above]co2 was integrated in the formula instead of calculated [latin capital V with dot above]co2 (P < 0.002).     

右美托咪定、咪唑安定及异丙酚术中镇静比较

目的 比较右美托咪定、咪唑安定及异丙酚在区域麻醉中的镇静作用. 方法 腰-硬联合麻醉下行下肢手术患者75例,ASA Ⅰ～Ⅱ级,随机分为右美托咪定组(D组)、咪唑安定组(M组)与异丙酚组(P组),各25例.分别于麻醉成功后给予右美托咪定、咪唑安定及异丙酚行术中镇静,使镇静/警觉评分(The observer(s) assessment of alertness/sedation scale,OAA/S)达3分或2分.监测血压、心率、血氧饱和度及心电图等生命体征,术后24h询问患者有无术中知晓. 结果 三组镇静效果均满意,有良好的顺行性遗忘,三组的术中知晓率无统计学差异(P＞0.05);D组、M组无呼吸抑制,P组有轻度呼吸抑制,且较D组、M组易发生(P＜0.05);D组有2例血压升高、1例血压下降,M组血压无变化,P组有5例血压下降,P组较M组易引起血压下降(P＜0.05);D组心率下降明显,2例要用阿托品,M组、P组心率稳定,D组心率明显慢于M组与P组(P＜0.01). 结论 术中镇静,右美托咪定降低心率明显,异丙酚有轻度的呼吸、循环抑制,但都易于纠正;咪唑安定对呼吸、循环无影响.右美托咪定、咪唑安定及异丙酚都可用于区域麻醉的镇静.     

咪唑安定复合异丙酚镇静时的心率变异性变化

目的：观察心率变异性（ＨＲＶ）在咪唑安定、异丙酚及其复合镇静时的变化。方法：选择ＡＳＡⅠ－Ⅱ级,在下胸腰段硬膜外阻滞下择期手术的成同人６０例,随机分为四组,每组１５例,Ⅰ组为咪唑安定组,Ⅱ组为咪唑安定０．０２５ｍｇ／ｋｇ加异丙酚组,Ⅲ组为咪唑安定０．０５ｍｇ／ｋｇ加异丙酚组,Ⅳ组为异丙酚组Ⅰ组,Ⅳ组每间隔２－３分钟静注咪唑安定１．５ｍｇ或 丙酚２０ｍｇ;Ⅱ组,Ⅲ组先静注咪唑安定０．０２５ｍｇ／ｋｇ     

Mixed-effects Modeling of the Influence of Alfentanil on Propofol Pharmacokinetics

Background: The influence of alfentanil on the pharmacokinetics of propofol is poorly understood. Therefore, the authors studied the effect of a pseudo-steady state concentration of alfentanil on the pharmacokinetics of propofol.

Methods: The pharmacokinetics of propofol were studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While volunteers breathed 30% O2 in air, 1 mg/kg intravenous propofol was given in 1 min, followed by 3 mg [middle dot] kg-1 [middle dot] h-1 for 59 min (sessions A and B). During session B, a target-controlled infusion of alfentanil (target concentration, 80 ng/ml) was given from 10 min before the start until 6 h after termination of the propofol infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the blood propofol and plasma alfentanil concentration were collected until 6 h after termination of the propofol infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of alfentanil and hemodynamic parameters on propofol pharmacokinetics were constructed.

Results: A two-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration-time curves of propofol. Alfentanil decreased the elimination clearance of propofol from 2.1 l/min to 1.9 l/min, the distribution clearance from 2.7 l/min to 2.0 l/min, and the peripheral volume of distribution from 179 l to 141 l. Scaling the pharmacokinetic parameters to cardiac output, heart rate, and plasma alfentanil concentration significantly improved the model.     

Effect of Flumazenil on Ventilatory Drive during Sedation with Midazolam and Alfentanil

Background: Patients who receive a combination of a benzodiazepine and an opioid for conscious sedation are at risk for developing respiratory depression. While flumazenil effectively antagonizes the respiratory depression associated with a benzodiazepine alone, its efficacy in the presence of both a benzodiazepine and an opioid has not been established. This study was designed to determine whether flumazenil can reverse benzodiazepine-induced depression of ventilatory drive in the presence of an opioid.

Methods: Twelve healthy volunteers completed this randomized, double-blind, crossover study. Ventilatory responses to carbon dioxide and to isocapnic hypoxia were determined during four treatment phases: (1) baseline, (2) alfentanil infusion; (3) combined midazolam and alfentanil infusions, and (4) combined alfentanil, midazolam, and "study drug" (consisting of either flumazenil or flumazenil vehicle) infusions. Subjects returned 2-6 weeks later to receive the alternate study drug.

Results: Alfentanil decreased the slope of the carbon dioxide response curve from 2.14 +/- 0.40 to 1.43 +/- 0.19 l [dot] min sup -1 [dot] mmHg sup -1 (x +/- SE, P < 0.05), and decreased the minute ventilation at PET CO2 = 50 mmHg (V with dotE 50) from 19.7 +/- 1.2 to 14.8 +/- 0.9 l [dot] min sup -1 (P < 0.05). Midazolam further reduced these variables to 0.87 +/- 0.17 l [dot] min sup -1 [dot] mmHg sup -1 (P < 0.05) and 11.7 +/- 0.8 l [dot] min sup -1 (P <0.05), respectively. With addition of flumazenil, slope and V with dot sub E 50 increased to 1.47 +/- 0.37 l [dot] min sup -1 [dot] mmHg sup -1 (P < 0.05) and 16.4 +/- 2.0 l [dot] min sup -1 (P < 0.05); after placebo, the respective values of 1.02 +/- 0.19 l [dot] min sup -1 [dot] mmHg sup -1 and 12.5 +/- 1.2 l [dot] min sup -1 did not differ significantly from their values during combined alfentanil and midazolam administration. The effect of flumazenil differed significantly from that of placebo (P < 0.05). Both the slope and the displacement of the hypoxic ventilatory response, measured at PET CO2 = 46 +/- 1 mmHg, were affected similarly, with flumazenil showing a significant improvement compared to placebo.     

Sympathetic and Hemodynamic Effects of Moderate and Deep Sedation with Propofol in Humans

Background: The objective of this study was to determine the mechanisms involved in the hypotension associated with sedative doses of propofol in humans.

Methods: Ten healthy volunteers (aged 21-37 yr) participated on two occasions and in random order received placebo or propofol infusions. Standard monitoring and radial artery blood pressure were combined with measurement of forearm blood flow (plethysmography) and derivation of forearm vascular resistance, recording of peroneal nerve sympathetic activity, and blood sampling for norepinephrine concentrations. A computer-controlled infusion pump delivered placebo or two concentrations of propofol, adjusted to achieve moderate and deep sedation based on the Observer Assessment of Alertness/Sedation score (responsiveness component) of 4 and 3. Level of sedation was quantitated using bispectral analysis of the electroencephalogram. Baroreflexes were assessed with a hypotensive challenge via administration of sodium nitroprusside.

Results: Baseline neurocirculatory and respiratory parameters did not differ between sessions. Progressive infusions to achieve moderate and deep sedation resulted in average Bispectral Index values of 70 and 54, respectively. Propofol significantly reduced sympathetic nerve activity at both levels of sedation and decreased norepinephrine and forearm vascular resistance at deep sedation. These effects resulted in significant decreases in mean blood pressure of 9% and 18% at moderate and deep sedation, respectively. Propofol also reduced reflex increases in sympathetic nerve activity.     

瑞芬太尼复合咪达唑仑在肿胀麻醉法脂肪抽吸术中的应用

目的观察瑞芬太尼复合咪达唑仑用于肿胀麻醉法脂肪抽吸术中的镇静镇痛效果。方法选择肿胀麻醉法行腹部脂肪抽吸术的患者30例,ASAⅠ～Ⅱ级。所有患者在肿胀麻醉前5min静脉推注咪达唑仑0.3mg/Kg和瑞芬太尼负荷剂量0.6μg/Kg(推注时间30s),之后静脉泵入瑞芬太尼0.1～0.3μg/Kg·min维持。记录患者在麻醉前(T0)、注射肿胀液前即刻(T1)、注射肿胀液时(T2)、脂肪抽吸时(T3)、手术结束时(T4)、术后30min时(T5)的Ramsay镇静评分和VAS痛觉模拟评分;观察患者在麻醉和手术过程中的血流动力学改变以及不良事件发生情况。结果所有患者在T1至T5时,VAS痛觉模拟评分均小于5分。与T0比较,T1时患者Ramsay镇静评分、心率(HR)、收缩压(SBP)、舒张压(DBP)均升高(P<0.05),呼吸频率(RR)降低(P<0.05);T2至T5时,上述指标无明显改变(P>0.05)。本组中有2例患者出现嗜睡和呼吸抑制(RR<8次/分),血氧饱和度(SpO2)最低降至90%,经指令性通气和减少瑞芬太尼用量后SpO2迅速恢复。结论瑞芬太尼复合咪达唑仑用于肿胀麻醉法脂肪抽吸术,能起到良好的镇静镇痛作用,术后恢复时间短,适合在日间脂肪抽吸术中推广应用。     

Dexamethasone Prolongs Local Analgesia after Subcutaneous Infiltration of Bupivacaine Microcapsules in Human Volunteers

Background: The addition of small amounts of dexamethasone to extended-release formulations of bupivacaine in microcapsules has been found to prolong local analgesia in experimental studies, but no clinical data are available.

Methods: In a double-blinded study, 12 healthy male volunteers were randomized to receive simultaneous subcutaneous injections of bupivacaine microcapsules with dexamethasone and bupivacaine microcapsules without dexamethasone in each calf. Local analgesia was assessed with a validated human pain model; main parameters evaluated were thermal, mechanical, and pain detection thresholds and suprathreshold responses to heat and mechanical stimulation. Measurements were performed every 2 h for the first 8 h and daily for the week after injection. Primary endpoints were evaluation of maximal analgesic effect, time of onset, and duration of analgesia. Summary measures (area under curve [AUC]) were considered best estimate of analgesia. Safety evaluations were performed daily for the first week and at 2 weeks, 6 weeks, and 6 months after injection.

Results: The addition of dexamethasone significantly prolonged local analgesia of bupivacaine microcapsules without influence on maximal analgesic effect. AUC in all thermal measurements and the sensory mechanical threshold were significantly increased between 1-7 days after drug injection in the group given dexamethasone compared with the group not given dexamethasone. No serious side effects were observed.     

Changes in the Auditory Evoked Potentials and the Bispectral Index following Propofol or Propofol and Alfentanil

Background: Midlatency auditory evoked potentials (MLAEP) show graded changes with increasing doses of hypnotics but little change with opioids. The effect of their combination on the MLAEP was evaluated. Also, the bispectral index (BIS) was compared with the ability of MLAEP to correlate with sedation and predict loss of consciousness.

Methods: Twenty healthy volunteers were randomly assigned to receive stepped increases in propofol concentration (10 subjects) or propofol plus alfentanil 100 ng/ml (10 subjects). At baseline and at each targeted effect site concentration the mean MLAEP, BIS, measures of sedation, and drug concentration were obtained. The relation among MLAEP, BIS, and sedation score was determined. The prediction probability (Pk) was calculated and compared for BIS and MLAEP.

Results: The BIS and MLAEP patterns showed significant changes (Pa and Nb decreased in amplitude and increased in latency) with increasing level of sedation (P < 0.0001). The BIS correlated better with sedation scores (0.884) than did the MLAEP (P < 0.05). Pa and Nb latencies showed the best correlation with sedation levels (0.685 and 0.658, respectively). The addition of alfentanil did not affect the relation between MLAEP and loss of consciousness (P > 0.15). The BIS (Pk = 0.952) was a better predictor of loss of consciousness than were Pa and Nb amplitude (P < 0.05) but were comparable to Pa and Nb latency (Pk = 0.869 and 0.873, respectively).     

Effects of Propofol Sedation on Seizures and Intracranially Recorded Epileptiform Activity in Patients with Partial Epilepsy

Background: Case reports suggesting both pro- and anticonvulsant effect(s) of propofol have been published in recent years. The effects of sedative doses of propofol on epileptiform activities in patients suffering from intractable partial epilepsy were systematically investigated.

Methods: Fourteen patients suffering from complex partial seizures were studied. Electroencephalogram (EEG) was recorded from intracranial electrodes implanted in the hippocampi and temporal neocortex. Propofol was given as a computer-controlled infusion in four steps to achieve target plasma propofol concentrations of 0.3, 0.6, 0.9, and 1.2 micro gram/ml. Each concentration was maintained for 30 min, and steady-state kinetics were confirmed by blood levels drawn at 10th and 30th min at each level. Between the 15th and 30th min of each concentration of propofol, EEG was analyzed for presence of electroencephalographic seizure activity and/or number of interictal spikes (ILS). Effects of propofol on IIS frequency at different electrode sites were compared using a two-way repeated measures analysis of variance. A value of P < 0.05 was considered significant.

Results: None of the patients developed a seizure during the 2 h of propofol infusion. No "false spikes" (spikes developing with propofol infusion in areas where no spikes were seen in baseline EEG) were seen. Although effects of propofol on IlS frequency were highly variable across patients and at different propofol doses in the same patient, there was no statistically significant effect of propofol on any electrode site with any of the doses studied.     

Bispectral Index Monitoring during Sedation with Sevoflurane, Midazolam, and Propofol

Background : Bispectral Index (BIS) has been used to measure sedation depth. Ideally, to guide anesthetic management, range of BIS scores at different sedation levels should not overlap, and BIS should be independent of drug used. This study assessed ability of BIS to predict sedation depth between sevoflurane, propofol, and midazolam. Quality of recovery was also compared.

Methods : Patients undergoing surgery with local or regional anesthesia and sedation were randomized to sevoflurane (n = 23), midazolam (n = 21), or propofol (n = 22). Sedation was titrated to Observers's Assessment of Alertness-Sedation score of 3 (responds slowly to voice). BIS and Observers's Assessment of Alertness-Sedation were measured every 5 min. BIS prediction probability (PK) was compared between drugs. Recovery was assessed by BIS and Digit Symbol Substitution and memory tests.

Results : Bispectral Index of responders to voice was significantly different from nonresponders (86 +/- 10 vs. 74 +/- 14, mean +/- SD;P < 0.001) However, wide variability and overlap in BIS were observed (25th-75th percentile, responders vs. non-responders: 79-96 vs. 65-83). BIS of responders was different for sevoflurane versus propofol and midazolam. BIS was a better predictor of propofol sedation than sevoflurane or midazolam (PK = 0.87 +/- 0.11, 0.76 +/- 0.01, and 0.69 +/- 0.02, respectively;P < 0.05). At 10 min after the procedure, 76, 48, and 24% of sevoflurane, propofol, midazolam patients, respectively, returned to baseline Digit Symbol Substitution scores (P < 0.05). Excitement-disinhibition occurred in 70, 36, and 5% of sevoflurane, propofol, and midazolam patients, respectively (P < 0.05).     

Blepharoplasty and Otoplasty: Comparative Sedation with Remifentanil,Propofol, and Midazolam

Three different methods of sedation or sedoanalgesia using remifentanil, Propofol, or midazolam to increase intra- and postoperative comfort and to reduce neuroendocrine stress in patients who had undergone typical ambulatory cosmetic surgery under local anesthesia were studied. A sample of 90 patients who underwent upper and lower eyelid blepharoplasty to correct baggy eyelids or otoplasty to correct protruding ears was selected according to standard criteria for the study. Remifentanil provided the best tolerability profile and the most effective perioperative pain control among the substances studied, demonstrating it to be a valid drug for modern sedoanalgesia aimed at increasing the well-being of patients undergoing ambulatory cosmetic surgery.     

小剂量右美托咪定在整形美容局麻手术中的镇静镇痛效果

目的 评价小剂量右美托咪定在整形美容手术中应用的安全性和有效性.方法　60名接受整形美容手术患者随机分成两组.实验组静脉推注右美托咪定负荷剂量0.5 μg/Kg,维持剂量0.1～0.5μg/Kg·h以达到镇静警觉评分(OAA/S)≤4,对照组推注等量的生理盐水.若OAMS ＞4,则予咪达唑仑,另予芬太尼止痛.至OAA/S≤4开始局麻手术.术中按需追加咪达唑仑和芬太尼.结果　实验组的咪达唑仑和芬太尼用量较对照组明显减少(P＜0.05),术中高血压、心动过速和呼吸抑制的发生率降低(P＜0.05),低血压和心动过缓的发生率无明显差异(P＞0.05).结论　小剂量右美托咪定可降低咪达唑仑和芬太尼的用量,血流动力学更稳定,无明显呼吸抑制,可安全有效地用于整形美容局麻手术.     

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.