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Clinical Investigation

Measured Context‐sensitive Half‐times of Remifentanil and Alfentanil

Kapila, Atul MB, BS; Glass, Peter S. A. MB, ChB; Jacobs, James R. PhD; Muir, Keith T. PhD; Hermann, David J. PharmD; Shiraishi, Masa MD; Howell, Scott MD; Smith, Richard L. PhD

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Background: The context‐sensitive half‐time, rather than the terminal elimination half‐life, has been proposed as a more clinically relevant measure of decreasing drug concentration after a constant infusion of a given duration. The context‐sensitive half‐time is derived from computer modelling using known pharmacokinetic parameters. The modelled context‐sensitive half‐time for a 3‐h infusion of alfentanil is 50–55 min and is 3 min for remifentanil. The terminal elimination half‐life is 111 min for alfentanil and 12–30 min for remifentanil. It has not been tested whether the modelled context‐sensitive half‐time reflects the true time for a 50% decrease in drug concentration or drug effect.
Methods: Thirty volunteers received a 3‐h infusion of remifentanil or alfentanil at equieffective concentrations. Depression of minute ventilation to 7.5% ETCO2 was used as a measure of drug effect. Minute ventilation response was measured, and blood samples for drug concentration were taken during and after drug infusion. The recovery of minute ventilation (drug effect) and decrease in blood drug concentration was plotted, and the time for a 50% change was determined.
Results: The measured pharmacokinetic context‐sensitive half‐time for remifentanil after a 3‐h infusion was 3.2 plus/minus 0.9 min, and its pharmacodynamic offset was 5.4 plus/minus 1.8 min. Alfentanil's measured pharmacokinetic context‐sensitive half‐time was 47.3 plus/minus 12 min, and its pharmacodynamic offset was 54.0 plus/minus 48 min. The terminal elimination half‐life modelled from the volunteers was 11.8 plus/minus 5.1 min for remifentanil and 76.5 plus/minus 12.6 min for alfentanil.
Conclusions: The measured context‐sensitive half‐times were in close agreement with the context‐sensitive half‐times previously modelled for these drugs. The results of this study confirm the value of the context‐sensitive half‐time in describing drug offset compared to the terminal elimination half‐life.
SEVERAL intravenous drugs have become available for continuous infusion to provide the components of anesthesia. Traditionally, the terminal elimination half‐life has been used as a measure of offset of drug action. However, with drugs whose pharmacokinetics can be described by multicompartment models, this is not satisfactory. [1,2] The context‐sensitive half‐time, the time to halving of the blood concentration after termination of drug administration by an infusion designed to maintain a constant concentration, has been proposed as a more useful measure of the pharmacokinetic offset of intravenous anesthetics. [2] By incorporating the effect compartment, the context‐sensitive half‐time of the pharmacodynamic effect can be modelled. [1] This concept has clinically relevant implications for the administration of intravenous anesthetics in that it would allow a more accurate prediction of the recovery from intravenous infusions at the termination of surgery. However, the concept of context‐sensitive half‐time has been based on computer modelling and has not been tested in vivo.
Remifentanil is a new anilidopiperidine opioid that contains an ester linkage rendering it susceptible to metabolism by plasma and tissue esterases, which in turn confers it with pharmacokinetics that produce evanescent blood concentrations. [3–5] The terminal elimination half‐life of remifentanil has been reported as 12–30 min. [3–5] Alfentanil has a terminal elimination half‐life of 111 min. [6] Computer modelling has predicted a context‐sensitive half‐time of 3 min for remifentanil [3] and 50–55 min for alfentanil [1] after a 3‐h infusion.
The aim of this study was to measure the context‐sensitive half‐time of both remifentanil and alfentanil, in terms of their pharmacokinetic and pharmacodynamic offset. This was done after the administration of these drugs for 3 h by infusion and assessed by the changes in the measured drug concentrations and minute ventilation after termination of the infusions.
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After approval from the Duke University institutional review board for human studies and obtaining written informed consent, 30 paid volunteers were recruited and randomized to receive an infusion of either alfentanil (n = 15) or remifentanil (n = 15). Inclusion criteria were healthy ASA physical status 1 males, aged 18 to 40 yr, within 20% of ideal body weight. All subjects underwent a medical history and physical examination. Blood samples for hematology and blood chemistries, a urine sample for chemistry and screening for drugs of abuse, and a 12‐lead electrocardiogram were obtained. Exclusion criteria were a history of alcohol or drug abuse; smoking more than 10 cigarettes per day; a positive urine screen for drugs of abuse; abnormal renal, hepatic, or hematologic function as assessed by blood a history of opioid use; or anesthesia within 8 weeks of screening and use of prescription medications within 1 week of drug administration. Subjects were not allowed oral intake for 6 h before drug administration, and were instructed to abstain from beverages containing caffeine or alcohol for 12 h and from tobacco products for 4 h before the initiation of the study.
On the morning of the study, subjects had catheters inserted into a radial artery and a peripheral vein. A nasal cannula, electrocardiograph pads, and a pulse oximeter finger probe were placed. Arterial blood pressure, end‐tidal carbon dioxide, respiratory rate, finger peripheral hemoglobin oxygen saturation, electrocardiograph (lead II), and heart rate were continuously monitored and recorded via the monitors' RS232 port to a computer‐based data acquisition system.
Table 1
Table 1
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The subjects were randomized double‐blind, double‐dummy to receive either remifentanil or alfentanil. Blinding was achieved by having the hospital pharmacy prepare two infusion bags, one labelled as remifentanil and the other as alfentanil. For each subject, one bag contained active drug and the other bag contained normal saline. After baseline measurements, both bags were attached to a computer‐controlled continuous infusion device [7] and administered as though each contained active drug. The target blood concentration for remifentanil was 1 ng/ml and for alfentanil was 40 ng/ml. These concentrations were estimated to be equipotent using effect compartment modelling from a previous study. [3] The pharmacokinetic model parameters used in the computer‐controlled continuous infusion device for this study are listed in Table 1.
Table 2
Table 2
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Minute ventilation at steady‐state end‐tidal 7.5% CO2 measured using a bag in a box system [8] for 5 min was used as a measure of drug effect. The initial 4 min of each minute ventilation run allowed time for equilibration of the inspired carbon dioxide and the respiratory center in the brain. The minute ventilation data reported is the minute ventilation measured in the last (5th) minute. Minute ventilation was evaluated at baseline and every 15 min after the beginning of the drug infusion and until successive measurements were within 40–70% of the subjects' baseline minute ventilation and within 20% of each other. Thereafter, minute ventilation was measured every 30 min and at 170 min. If the minute ventilation depression was outside the desired range, the target concentration of both drugs were simultaneously adjusted as listed in Table 2. Subjects requiring more than two adjustments in the target concentration of the opioid within the first 60 min of the infusion were withdrawn from the study.
From 2 min before terminating the infusion until 10 min after the end of the infusion, the bag‐in‐a‐box system was used, and the average minute ventilation for each minute was obtained. This provided minute ventilation measurements for each minute for the first 10 min after termination of drug infusion. Thereafter, minute ventilation measurements (as previously described) were made at 20 and 30 min and every 15 min thereafter until values returned to baseline. Arterial blood (5 ml) was collected at baseline, at multiple times during the infusion and at 1, 3, 5, 7, 10, 15, 20, 30, 45, 60, and 90 min and 2, 3, 4, 5, and 6 h after termination of the infusion. These were immediately processed for subsequent analysis of remifentanil and alfentanil whole blood concentrations, as previously described using gas chromatography/mass spectrometry with selected ion monitoring. [3].
The pharmacokinetic offset in whole blood drug concentration was calculated as the percentage decrease in blood drug concentration after the termination of the infusion: % decrease in drug concentration = (Co ‐ Ct) *symbol* 100/Co, where Ct is concentration at time t and Co is concentration at end of infusion.
To describe pharmacodynamic drug offset, the percentage minute ventilation recovery was calculated in each subject. The minute ventilation measured before administration of any drug was the baseline minute ventilation, and return to this minute ventilation measurement was considered to be 100% recovery. Thus percent recovery of minute ventilation was calculated as %MV recover = (MVt ‐ MVp) *symbol* 100/(MVb ‐ MVp), where MVt is minute ventilation at time t, MVp is minute ventilation before end of infusion, and MVb is minute ventilation baseline (before drug).
The percent decline in blood concentration or recovery of minute ventilation at each time for each patient was plotted against the time after drug infusion.
Percentage recovery in minute ventilation was analyzed by fitting the equation y = a + b (1 ‐ e sup ‐ct) to each patient's data, where y is percentage minute ventilation recovery, t is time in minutes after the drug infusion, e is the base of the natural logarithm, and a, b, and c are parameters estimated from the data. Time to 50% minute ventilation recovery, t50, was calculated from this equation.
Percentage change in whole blood concentration was analyzed by fitting the equation y = ae sup ‐bt to each patient's postinfusion data, where y is percentage whole blood concentration decrease, t is time in minutes after the drug infusion, e is the base of the natural logarithm, and a and b are parameters estimated from the data. Time to 50% whole blood concentration decrease, t50, was calculated from this equation. The above equations were fit to the data using nonlinear regression (PROC NLIN, SAS, Cary, NC).
A two‐stage pharmacokinetic analysis was performed on the concentration versus time data to fit a two‐ or three‐compartment model. The geometric mean of the individual values was used to provide the mean population values for each parameter. These mean values were then used to determine the elimination half‐life. The individuals derived pharmacokinetic parameters were used to recalculate each volunteer's predicted context‐sensitive half‐time.
Other than for the pharmacokinetic parameters, summary statistics are listed as the mean and standard deviation for each parameter estimate. The elimination half‐life was compared to the context‐sensitive half‐time using an unpaired Student's t test. The half‐lives and half‐times between the two drugs were similarly compared. A P < 0.01 was considered significant.
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Eight subjects, four from each drug group, were withdrawn from the study, because their minute ventilation values were not within the 40–70% depression from baseline within the prescribed 60 min, despite two adjustments in target concentrations. The remaining volunteers consisted of 22 (11 per group) ASA physical status 1 males, ranging in age from 19 to 35 yr (mean 25.4 plus/minus 4.6) and weight from 66.4 to 93.4 kg (mean 77.5 plus/minus 8.0). In 26 subjects, there was a sufficient number of measured blood concentrations to derive pharmacokinetic parameters.
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Figure 1
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Figure 2
Figure 2
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Figure 3
Figure 3
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Figure 4
Figure 4
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Figure 5
Figure 5
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Figure 6
Figure 6
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The decrease in whole blood concentration and recovery in minute ventilation for remifentanil after the termination of the infusion is presented in Figure 1. Similarly, the decrease in whole blood concentration and recovery in minute ventilation for alfentanil after the termination of the infusion is presented in Figure 2. The percentage decrease in whole blood concentration and percentage recovery of minute ventilation of each subject against time after termination of the remifentanil infusion is shown in Figure 3 and for alfentanil in Figure 4. The fitted function of percent recovery in minute ventilation and decrease in measured blood concentration used to estimate the measured context‐sensitive half‐time for remifentanil is presented in Figure 5 and for alfentanil in Figure 6. The measured time to 50% decrease in blood drug concentration after drug infusion, i.e., the pharmacokinetic half‐time, was 3.2 plus/minus 0.9 min for remifentanil and 47.3 plus/minus 12.0 min for alfentanil (P < 0.01). The measured time to 50% recovery in minute ventilation after termination of drug infusion, the pharmacodynamic half‐time, was 5.4 plus/minus 1.8 min for remifentanil and 54.0 plus/minus 48.1 min for alfentanil (P < 0.01).
Table 3
Table 3
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In Table 3, the elimination half‐lives and the context‐sensitive half‐times derived from the pharmacokinetic parameters of the volunteers participating in the study are compared to the context‐sensitive half‐times measured in these individual subjects after a 3‐h infusion of either remifentanil or alfentanil. The measured context‐sensitive half‐time for both remifentanil and alfentanil was significantly different from their respective elimination half‐life (P < 0.01). Both the elimination half‐life and the context‐sensitive half‐times for remifentanil were significantly shorter than those for alfentanil.
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The elimination half‐life of alfentanil from the pharmacokinetic parameters of Scott and Stanski is 111 min. [6] Based on computer modelling, the context‐sensitive half‐time for alfentanil (using these pharmacokinetic parameters) after a 3‐h infusion is predicted to be 59.4 min. [2] Similarly, using the pharmacokinetics described by Glass et al., the elimination half‐life of remifentanil was 9.5 min, and the predicted context‐sensitive half‐time was 2.45 min. [3].
We found that, after a 3‐h infusion of remifentanil or alfentanil, designed to closely maintain a constant drug concentration and drug effect, the measured times to 50% decline in drug concentration as 3.2 min for remifentanil and 47.3 min for alfentanil, and for a 50% recovery in drug effect, as measured by recovery from respiratory depression, was 5.4 min for remifentanil and 54.0 min for alfentanil. These values for the measured context‐sensitive half‐times for remifentanil and alfentanil, correspond closely to the modelled context‐sensitive half‐times as described above. Listed in Table 3 is the modelled context‐sensitive half‐time based on the volunteers' own pharmacokinetic parameters and the measured context‐sensitive half‐time. For remifentanil, the difference between the measured and modelled context‐sensitive half‐time was 1.2 min (P = 0.03). These two values are not the same, because the target concentrations were adjusted in some of the volunteers to obtain and maintain a steady effect; thus, the true measured half‐time does not exactly represent the modelled context‐sensitive half‐time. In addition, blood samples for drug concentration were taken at 1‐min intervals. This relatively slow sampling rate for remifentanil may have limited our ability to define precisely its measured context sensitive half‐time and thereby contributed to the observed difference between the measured and the modelled context‐sensitive half‐time.
This is the first attempt to measure the context‐sensitive half‐times for infusion drugs, since this concept was proposed as a more practical description of post‐infusion pharmacokinetics. The principle underlying the context‐sensitive half‐time is that, for drugs exhibiting multicompartment pharmacokinetics, the net distribution of drug into or out of the peripheral compartments varies according to the duration of infusion. After drug infusions of brief duration, the plasma drug concentration decreases rapidly because the central clearance processes are supplemented by continued net distribution of drug out of the plasma into the peripheral compartments. As the infusion duration increases, the peripheral compartment's drug concentrations near equilibration with the plasma drug concentration. Thus, the potential for reducing the plasma drug concentration by distribution mechanisms after the termination of the infusion is greatly reduced, thereby slowing the rate of plasma drug decrease. Importantly, even when the infusion is continued long enough for the drug concentrations in each of the compartments to be in equilibration, postinfusion kinetics are not well described by the "elimination half‐life." This is demonstrated with remifentanil, which was infused for far longer than the time necessary to achieve a steady‐state, yet its measured context‐sensitive half‐time at 3 h was considerably shorter than its terminal elimination half‐life, but close to its predicted context‐sensitive half‐time.
For the clinical use of these measures, the required degree of decrease in effect needs to be known. It is important to realize that the decrease in effect does not necessarily mirror the decrease in drug concentration. Initially, as the concentration of drug increases, there is minimal change in the observed effect. As drug concentration continues to rise, this changes, so that small increases in concentration result in large changes in effect. In this steep portion of the concentration‐effect curve, the relationship between concentration and the observed effect is linear. As the maximal observed effect is approached, a large change in concentration will result in only a small change in the observed effect. Thus the relationship between drug concentration and drug effect is not a simple linear response. A plot of drug concentration to drug effect for opioids (in this instance ventilatory depression) produces a sigmoidal relationship. The design of this study was to measure the changes in drug effect over the linear portion of this relationship. Even in this linear portion of the concentration response curve, the decrease in blood concentration does not exactly equal the recovery in drug effect. This is because the relationship is not precisely linear. Also, the blood is not the site of drug action, and there is a delay in equilibration of concentrations between the biophase and the blood. This equilibration delay for alfentanil and remifentanil is drug‐dependent and is determined by the drug's ke0 with the equilibration time being described by the t1/2 ke0. [9] Over the linear portion of the concentration‐effect response, decline of drug effect from remifentanil and alfentanil is thus different from the decline in blood concentration but can be modelled by incorporating their ke0 value. [1] As expected for both remifentanil and alfentanil, the measured context‐sensitive half‐time for offset of drug effect in this study was slightly longer than the pharmacokinetic context‐sensitive half‐time. The measured value of the pharmacodynamic offset closely corresponded to the modelled context‐sensitive half‐time of the effect compartment. For drugs with a smaller ke0 (or longer t1/2 ke0), the difference between the pharmacokinetic and the pharmacodynamic context‐sensitive half‐time would be larger than that seen with remifentanil or alfentanil. However, it must be emphasized that, if a patient has been overdosed with an opioid, the time taken for the drug concentration to decrease by 50% will not reflect the time for recovery of normal ventilatory drive. Minimal recovery will occur until the concentration of the opioid falls to within the steep portion of the concentration‐response curve. The context‐sensitive half‐time is thus not always a predictor of recovery time. If dosing has been excessive, a far greater percentage of decline in drug concentration than 50% is required before adequate recovery will occur. Also, if dosing has been such that the plasma drug concentration has been continuously altered, the context‐sensitive half‐time by definition does not hold true. Similarly, the context‐sensitive times for differing percentage decreases in drug concentration is not linear. [1].
This study was conducted with infusions of a single duration, using drugs with very different pharmacokinetic profiles. We found that the time required for a 50% decrease in the measured drug concentration agreed much more closely with the modelled context‐sensitive half‐time of remifentanil and alfentanil than their respective elimination half‐lives. This demonstrates the relevance of the concept of context‐sensitive half‐times in clinical practice for recovery from drug effect. Ultimately, to more clearly define context‐sensitive half‐time, it will be necessary to look at infusions of varying duration using different drugs and different plasma concentrations.
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1. Shafer SL, Varvel JR: Pharmacokinetics, pharmacodynamics, and rational opioid selection. ANESTHESIOLOGY 74:53-63, 1991.

2. Hughes MA, Glass PSA, Jacobs JR: Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. ANESTHESIOLOGY 76:334-341, 1992.

3. Glass PSA, Hardman D, Kamiyama Y, Quill TJ, Marton G, Donn KM, Grosse CM, Hermann D: Preliminary pharmacokinetics and pharmacodynamics of an ultra-short-acting opioid: Remifentanil (G187084B). Anesth Analg 77:1031-1040, 1993.

4. Egan TO, Lemmens HJM, Fiset P, Hermann DJ, Muir KT, Stanski DR, Shafer SL: The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers. ANESTHESIOLOGY 79:881-892, 1993.

5. Westmoreland CL, Hoke JF, Sebel PS, Hug CC, Muir KT: Pharmacokinetics of remifentanil (GI87084B) and its major metabolite (GI90291) in patients undergoing elective inpatient surgery. ANESTHESIOLOGY 79:893-903, 1993.

6. Scott JC, Stanski DR: Decreased fentanyl and alfentanil dose requirements with age: A simultaneous pharmacokinetic and pharmacodynamic evaluation. J Pharmacol Exp Ther 240:159-161, 1987.

7. Glass PSA, Jacobs JR, Smith IL, Ginsberg B, Quill TJ, Bai SA, Reves JG: Pharmacokinetic model-driven infusion of fentanyl: Assessment of accuracy. ANESTHESIOLOGY 73:1082-1090, 1990.

8. Afifi MS, Glass PSA, Cohen NA, Shook JE, Camporesi EM: Depression of ventilatory responses to hypoxia and hypercapnia after pentamorphone. Anesth Analg 71:377-383, 1990.

9. Sheiner LB, Stanski DR, Vozeh S, Miller RD, Ham J: Simultaneous modelling of pharmacokinetics and pharmacodynamics: Application to d-tubocurarine. Clin Pharmacol Ther 25:358-371, 1979.

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Intensive Care Medicine
A dosing algorithm for the use of remifentanil in providing optimal sedation and analgesia in ICU patients
Kirkham, AJ; Fisher, GR; Kessler, P
Intensive Care Medicine, 27(): S238.

Advances in Modelling and Clinical Application of Intravenous Anaesthesia
Remifentanil; from pharmacological properties to clinical practice
Servin, F
Advances in Modelling and Clinical Application of Intravenous Anaesthesia, 523(): 245-260.

Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie
Comparison of premedication with clonidine and midazolam combined with TCI for orthopaedic shoulder surgery
Grottke, O; Muller, J; Dietrich, PJ; Krause, TH; Wappler, F
Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie, 38(): 772-780.

Clinical Pharmacokinetics
The use of ultra-short-acting opioids in paediatric anaesthesia - The role of remifentanil
Davis, PJ; Cladis, FP
Clinical Pharmacokinetics, 44(8): 787-796.

Acta Anaesthesiologica Scandinavica
Intravenous remifentanil vs. epidural levobupivacaine with fentanyl for pain relief in early labour: a randomised, controlled, double-blinded study
Volmanen, P; Sarvela, J; Akural, EI; Raudaskoski, T; Korttila, K; Alahuhta, S
Acta Anaesthesiologica Scandinavica, 52(2): 249-255.
Anesthesia and Analgesia
Intracranial pressure and hemodynamic effects of remifentanil versus alfentanil in patients undergoing supratentorial craniotomy
Warner, DS; Hindman, BJ; Todd, MM; Sawin, PD; Kirchner, J; Roland, CL; Jamerson, BD
Anesthesia and Analgesia, 83(2): 348-353.

Prospective pharmacokinetic and pharmacodynamic validation of the context sensitive half-time for alfentanil
Lu, J; Kern, S; Schafer, P; Bailey, PL; Egan, TD
Anesthesiology, 87(3): A347.

Dosing study of remifentanil and propofol for tracheal intubation without the use of muscle relaxants
Alexander, R; Olufolabi, AJ; Booth, J; El-Moalem, HE; Glass, PS
Anaesthesia, 54(): 1037-1040.

Drugs of Today
Current and future applications of target-controlled infusions
Absalom, A; Kenny, GNC
Drugs of Today, 35(): 823-834.

Anesthesia and Analgesia
Is there a learning curve associated with the use of remifentanil?
Joshi, GP; Jamerson, BD; Roizen, MF; Fleisher, L; Twersky, RS; Warner, DS; Colopy, M
Anesthesia and Analgesia, 91(5): 1049-1055.

Acta Anaesthesiologica Scandinavica
Effects of combined methohexitone-remifentanil anaesthesia in electroconvulsive therapy
Andersen, FA; Arsland, D; Holst-Larsen, H
Acta Anaesthesiologica Scandinavica, 45(7): 830-833.

Journal of Clinical Anesthesia
A comparison of the remifentanil and fentanyl adverse effect profile in a multicenter phase IV study
Joshi, GP; Warner, DS; Twersky, RS; Fleisher, LA
Journal of Clinical Anesthesia, 14(7): 494-499.
PII S0952-8180(02)00404-X
Critical Care Clinics
Pharmacology of Sedative-Analgesic Agents: Dexmedetomidine, Remifentanil, Ketamine,Volatile Anesthetics, and the Role of Peripheral Mu Antagonists
Panzer, O; Moitra, V; Sladen, RN
Critical Care Clinics, 25(3): 451-+.
Acta Anaesthesiologica Scandinavica
General anesthesia with remifentanil for Cesarean section in a patient with HELLP syndrome
Richa, F; Yazigi, A; Nasser, E; Dagher, C; Antakly, MC
Acta Anaesthesiologica Scandinavica, 49(3): 418-420.
British Journal of Anaesthesia
Remifentanil infusion in association with fentanyl-propofol anaesthesia in patients undergoing cardiac surgery: effects on morphine requirement and postoperative analgesia
Rauf, K; Vohra, A; Fernandez-Jimenez, P; O'Keeffe, N; Forrest, M
British Journal of Anaesthesia, 95(5): 611-615.
Annales Francaises D Anesthesie Et De Reanimation
Maternal and neonatal effects of remifentanil for general anaesthesia for Caesarean delivery
Bouattour, L; Ben Amar, H; Bouali, Y; Kolsi, K; Gargouri, A; Khemakhem, K; Kallel, N; Trabelsi, K; Guermazi, M; Rekik, A; Karoui, A
Annales Francaises D Anesthesie Et De Reanimation, 26(4): 299-304.
American Journal of Veterinary Research
Effects of remifentanil on the minimum alveolar concentration of isoflurane in dogs
Monteiro, ER; Teixeira-Neto, FJ; Campagnol, D; Alvaides, RK; Garofalo, NA; Matsubara, LM
American Journal of Veterinary Research, 71(2): 150-156.

Anesthesia and Analgesia
The safety and effectiveness of remifentanil as an adjunct sedative for regional anesthesia
Lauwers, M; Camu, F; Breivik, H; Hagelberg, A; Rosen, M; Sneyd, R; Horn, A; Noronha, D; Shaikh, S
Anesthesia and Analgesia, 88(1): 134-140.

Clinical Pharmacokinetics
Pharmacokinetics of opioids in liver disease
Tegeder, I; Lotsch, J; Geisslinger, G
Clinical Pharmacokinetics, 37(1): 17-40.

British Journal of Anaesthesia
Effects of maintaining a remifentanil infusion on the recovery profiles during emergence from anaesthesia and tracheal extubation
Nho, JS; Lee, SY; Kang, JM; Kim, MC; Choi, YK; Shin, OY; Kim, DS; Kwon, MI
British Journal of Anaesthesia, 103(6): 817-821.
Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie
Taeger, K
Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie, 32(5): 307-321.

Sevoflurane - nitrous oxide anaesthesia supplemented with remifentanil: effect on recovery and cognitive function
Breslin, DS; Reid, JE; Mirakhur, RK; Hayes, AH; McBrien, ME
Anaesthesia, 56(2): 114-119.

Clinical Pharmacokinetics
Strategies to optimise propofol-opioid anaesthesia
Lichtenbelt, BJ; Mertens, M; Vuyk, J
Clinical Pharmacokinetics, 43(9): 577-593.

Intensive Care Medicine
The offset of pharmacodynamic effects of remifentanil in ICU patients is not affected by renal impairment
Breen, D; Wilmer, A; Bodenham, A; Bach, V; Bonde, J; Kessler, P; Albrecht, S; Shaikh, S
Intensive Care Medicine, 27(): S207.

Journal of Cardiothoracic and Vascular Anesthesia
Efficacy and safety of remifentanil in coronary artery bypass graft surgery: A randomized, double-blind dose comparison study
Geisler, FEA; de Lange, S; Royston, D; Demeyere, R; Duthie, DJR; Lehot, JJ; Dupeyron, JP; Mansfield, M; Kirkham, AJT
Journal of Cardiothoracic and Vascular Anesthesia, 17(1): 60-68.
Anesthesia and Analgesia
A model to evaluate the pharmacokinetic and pharmacodynamic variables of extended-release products using in vivo tissue microdialysis in humans: Bupivacaine-loaded microcapsules
Kopacz, DJ; Bernards, CM; Allen, HW; Landau, C; Nandy, P; Wu, DL; Lacouture, PG
Anesthesia and Analgesia, 97(1): 124-131.
British Journal of Anaesthesia
Low-dose remifentanil infusion does not impair natural killer cell function in healthy volunteers
Cronin, AJ; Aucutt-Walter, NM; Budinetz, T; Bonafide, CP; DiVittore, NA; Gordin, V; Schuler, HG; Bonneau, RH
British Journal of Anaesthesia, 91(6): 805-809.
Clinical Pharmacokinetics
Cholestasis and endogenous opioids - Liver disease and exogenous opioid pharinacokinetics
Davis, M
Clinical Pharmacokinetics, 46(): 825-850.

Remifentanil-based intraoperative anaesthesia and postoperative pain therapy. Is there an optimal treatment strategy?
Zollner, C; Schafer, M
Anaesthesist, 56(): 1038-1046.
Use of remifentanil for tracheal intubation for caesarean section in a patient with suxamethonium apnoea
Alexander, R; Fardell, S
Anaesthesia, 60(): 1036-1038.
Surgical Endoscopy and Other Interventional Techniques
Ramosetron versus ondansetron for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy
Ryu, J; So, YM; Hwang, J; Do, SH
Surgical Endoscopy and Other Interventional Techniques, 24(4): 812-817.
Neurosurgery Clinics of North America
Anesthesia for cerebral aneurysm surgery
Dangor, AA; Lam, AM
Neurosurgery Clinics of North America, 9(4): 647-+.

Anesthesia and Analgesia
Lack of rapid development of opioid tolerance during alfentanil and remifentanil infusions for postoperative pain
Schraag, S; Checketts, MR; Kenny, GNC
Anesthesia and Analgesia, 89(3): 753-757.

The pharmacodynamic effect of a remifentanil bolus on ventilatory control
Babenco, HD; Conard, PF; Gross, JB
Anesthesiology, 92(2): 393-398.

Smith, MA; Morgan, M
Anaesthesia, 52(4): 291-293.

British Journal of Anaesthesia
Influence of peroperative opioid on postoperative pain after major abdominal surgery: sufentanil TCI versus remifentanil TCI. A randomized, controlled study
Derrode, N; Lebrun, F; Levron, JC; Chauvin, M; Debaene, B
British Journal of Anaesthesia, 91(6): 842-849.
Using fMRI to quantify the time dependence of remifentanil an algesia in the human brain
Wise, RG; Williams, P; Tracey, I
Neuropsychopharmacology, 29(3): 626-635.
Pediatric Anesthesia
Spontaneous ventilation with remifentanil in children
Ansermino, JM; Brooks, P; Rosen, D; Vandebeek, CA; Reichert, C
Pediatric Anesthesia, 15(2): 115-121.
Anesthesia and Analgesia
Postoperative analgesia with remifentanil in patients undergoing cardiac surgery
Steinlechner, B; Koinig, H; Grubhofer, G; Ponschab, M; Eislmeir, S; Dworschak, M; Rajek, A
Anesthesia and Analgesia, 100(5): 1230-1235.
Intensive Care Medicine
Pharmacokinetics of long-term sufentanil infusion for sedation in ICU patients
Ethuin, F; Boudaoud, S; Leblanc, I; Troje, C; Marie, O; Levron, JC; Le Moing, JP; Assoune, P; Eurin, B; Jacob, L
Intensive Care Medicine, 29(): 1916-1920.
Drug Safety
Comparative tolerability of sedative agents in head-injured adults
Urwin, SC; Menon, DK
Drug Safety, 27(2): 107-133.

Critical Care
Safety and efficacy of analgesia-based sedation with remifentanil versus standard hypnotic-based regimens in intensive care unit patients with brain injuries: a randomised, controlled trial [ISRCTN50308308]
Karabinis, A; Mandragos, K; Stergiopoulos, S; Komnos, A; Soukup, J; Speelberg, B; Kirkham, AJT
Critical Care, 8(4): R268-R280.
British Journal of Anaesthesia
Effects of remifentanil on cardiovascular and bispectral index responses to endotracheal intubation in severe pre-eclamptic patients undergoing Caesarean delivery under general anaesthesia
Yoo, KY; Jeong, CW; Park, BY; Kim, SJ; Jeong, ST; Shin, MH; Lee, J
British Journal of Anaesthesia, 102(6): 812-819.
Journal of Psychopharmacology
The mu-opioid receptor agonist remifentanil induces acute dysphoria irrespective of its analgesic properties
Wagner, KJ; Valet, M; Kochs, EF; Kriner, M; Tolle, TR; Sprenger, T
Journal of Psychopharmacology, 24(3): 355-361.
Recovery from anaesthesia: Which is the best kinetic descriptor of a drug's recovery profile?
Sear, JW
Anaesthesia, 51(): 997-999.

Journal of Clinical Anesthesia
Remifentanil-propofol versus fentanyl-propofol for monitored anesthesia care during hysteroscopy
Ryu, JH; Kim, JH; Park, KS; Do, SH
Journal of Clinical Anesthesia, 20(5): 328-332.
Anesthesia and Analgesia
Rapid development of tolerance to analgesia during remifentanil infusion in humans
Vinik, HR; Kissin, I
Anesthesia and Analgesia, 86(6): 1307-1311.

Acta Anaesthesiologica Scandinavica
The pharmacokinetics of anesthetic drugs and adjuvants during cardiopulmonary bypass
Mets, B
Acta Anaesthesiologica Scandinavica, 44(3): 261-273.

Intensive Care Medicine
The safety and efficacy of remifentanil for the provision of optimal sedation in ICU patients
Lopez, A; Muellejans, B; Cross, MH; Bonome, C; Morrison, L; Kirkham, A
Intensive Care Medicine, 27(): S239.

British Journal of Anaesthesia
Propofol sparing effect of remifentanil using closed-loop anaesthesia
Milne, SE; Kenny, GNC; Schraag, S
British Journal of Anaesthesia, 90(5): 623-629.
Anesthesia and Analgesia
Detection of acute tolerance to the analgesic and nonanalgesic effects of remifentanil infusion in a rabbit model
Hayashida, M; Fukunaga, A; Hanaoka, K
Anesthesia and Analgesia, 97(5): 1347-1352.
Clinical Pharmacokinetics
Context-sensitive half-times - What are they and how valuable are they in anaesthesiology?
Bailey, JM
Clinical Pharmacokinetics, 41(): 793-799.

British Journal of Anaesthesia
Patient-maintained remifentanil target-controlled infusion for the transition to early postoperative analgesia
Schraag, S; Kenny, GN; Mohl, U; Georgieff, M
British Journal of Anaesthesia, 81(3): 365-368.

Acta Anaesthesiologica Scandinavica
Remifentanil infusion for cardiac catheterization in children with congenital heart disease
Foubert, L; Reyntjens, K; De Wolf, D; Suys, B; Moerman, A; Mortier, E
Acta Anaesthesiologica Scandinavica, 46(4): 355-360.

Anesthesia and Analgesia
Narcotrend, bispectral index, and classical electroencephalogram variables during emergence from propofol/remifentanil anesthesia
Schmidt, GN; Bischoff, P; Standl, T; Voigt, M; Papavero, L; Esch, JSA
Anesthesia and Analgesia, 95(5): 1324-1330.
Annales Francaises D Anesthesie Et De Reanimation
General anaesthesia for Caesarean section in a patient with single ventricule and pulmonary hypertension
Vial, F; Bayoumeu, F; Marcon, F; Dupays, R; Chillet-Mion, M; Laxenaire, MC
Annales Francaises D Anesthesie Et De Reanimation, 22(6): 548-552.
Klinische Monatsblatter Fur Augenheilkunde
What's new in ophthalmic anaesthesia?
Weigt, HU; Spraul, CW; Weiss, M
Klinische Monatsblatter Fur Augenheilkunde, 220(): 809-821.
Paediatric Anaesthesia
Use of remifentanil in infants
Eck, JB; Lynn, AM
Paediatric Anaesthesia, 8(5): 437-439.

Journal of Cardiothoracic and Vascular Anesthesia
Total intravenous anesthesia with remifentanil and propofol for implantation of cardioverter-defibrillators in patients with severely reduced left ventricular function
Lehmann, A; Boldt, J; Zeitler, C; Thaler, E; Werling, C
Journal of Cardiothoracic and Vascular Anesthesia, 13(1): 15-19.

Anesthesia for the New Millennium
Remifentanil: Clinical applications
Egan, TD
Anesthesia for the New Millennium, 34(): 241-261.

Effects of propofol and remifentanil on phrenic nerve activity and nociceptive cardiovascular responses in rabbits
Ma, DQ; Chakrabarti, MK; Whitwam, JG
Anesthesiology, 91(5): 1470-1480.

Acta Anaesthesiologica Scandinavica
Tracheal intubation without the use of muscle relaxants: remifentanil or alfentanil in combination with propofol
Klemola, UM; Mennander, S; Saarnivaara, L
Acta Anaesthesiologica Scandinavica, 44(4): 465-469.

Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Tracheal intubation after induction of anesthesia in children with propofol - remifentanil or propofol-rocuronium
Klemola, UM; Hiller, A
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 47(9): 854-859.

British Journal of Anaesthesia
A comparison of hypnotic and analgesic based sedation in a general intensive care unit
Park, G; Lane, M; Rogers, S; Bassett, P
British Journal of Anaesthesia, 98(1): 76-82.
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Optimal remifentanil dose for laryngeal mask airway insertion when co-administered with a single standard dose of propofol
Bouvet, L; Da-Col, X; Rimmele, T; Allaouchiche, B; Chassard, D; Boselli, E
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 57(3): 222-229.
New intravenous anesthetics - Remifentanil, S(+)-ketamine, eltanolone and target controlled infusion
Albrecht, S; Hering, W; Schuttler, J; Schwilden, H
Anaesthesist, 45(): 1129-1141.

Anesthesia and Analgesia
Remifentanil and pulmonary extraction during and after cardiac anesthesia
Duthie, DJR; Stevens, JJWM; Doyle, AR; Baddoo, HHK; Gupta, SK; Muir, KT; Kirkham, AJT
Anesthesia and Analgesia, 84(4): 740-744.

European Journal of Anaesthesiology
Remifentanil: When and how to use it
Servin, F
European Journal of Anaesthesiology, 14(): 41-44.

Acta Anaesthesiologica Scandinavica
Pharmacodynamic modelling of the analgesic effects of piritramide in postoperative patients
Kietzmann, D; Bouillon, T; Hamm, C; Schwabe, K; Schenk, H; GundertRemy, U; Kettler, D
Acta Anaesthesiologica Scandinavica, 41(7): 888-894.

Intensive Care Medicine
A remifentanil-based technique for analgesia and sedation in ICU patients with neurotrauma: Preliminary data
Karabinis, A; Hantson, P; Speelberg, B; Stergiopoulos, S; Illievich, UM; Maas, A; Upadhyaya, BK
Intensive Care Medicine, 27(): S275.

Paediatric Anaesthesia
Use of remifentanil in an infant with surgically repaired Shone's syndrome
Tsiotou, AG; Matsota, P; Kouptsova, E; Papageorgiou-Brousta, M
Paediatric Anaesthesia, 14(3): 261-264.

Annales Francaises D Anesthesie Et De Reanimation
Increase in bispectral index induced by antihyperalgesic dose of ketamine
Chaaben, K; Marret, E; Lamonerie, L; Lembert, N; Bonnet, F
Annales Francaises D Anesthesie Et De Reanimation, 23(5): 513-516.
Veterinary Record
Clinical investigation of remifentanil and propofol for the total intravenous anaesthesia of dogs
Murrell, JC; Van Notten, RW; Hellebrekers, LJ
Veterinary Record, 156(): 804-+.

Current Drug Metabolism
Tissue distribution and pharmacodynamics: A complicated relationship
Lin, JH
Current Drug Metabolism, 7(1): 39-65.

Journal of Oral and Maxillofacial Surgery
Comparison of remifentanil with fentanyl for deep sedation in oral surgery
Lacombe, GF; Leake, JL; Clokie, CM; Haas, DA
Journal of Oral and Maxillofacial Surgery, 64(2): 215-222.
Acta Anaesthesiologica Scandinavica
A comparison of anaesthesia using remifentanil combined with either isoflurane, enflurane or propofol in patients undergoing gynaecological laparoscopy, varicose vein or arthroscopic surgery
Chung, F; Mulier, JP; Scholz, J; Breivik, H; Araujo, M; Hjelle, K; Upadhyaya, B; Haigh, C
Acta Anaesthesiologica Scandinavica, 44(7): 790-798.

Anesthesia and Analgesia
A preliminary investigation of remifentanil as a labor analgesic
Olufolabi, AJ; Booth, JV; Wakeling, HG; Glass, PS; Penning, DH; Reynolds, JD
Anesthesia and Analgesia, 91(3): 606-608.

Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
The use of remifentanil for Cesarean section in a parturient with recurrent aortic coarctation
Manullang, TR; Chun, K; Egan, TD
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 47(5): 454-459.

Chinese Medical Journal
Comparison of remifentanil and fentanyl in patients undergoing modified radical mastectomy or total hysterectomy
Guo, ZY; Yi, J; Ye, TH; Luo, AL; Huang, YG; Ren, HZ
Chinese Medical Journal, 116(9): 1386-1390.

Anesthesia and Analgesia
A randomized, blind comparison of remifentanil and alfentanil during anesthesia for outpatient surgery
Cartwright, DP; Kvalsvik, O; Cassuto, J; Jansen, JP; Wall, C; Remy, B; Knape, JTA; Noronha, D; Upadhyaya, BK
Anesthesia and Analgesia, 85(5): 1014-1019.

British Journal of Anaesthesia
Postoperative pain management and recovery after remifentanil-based anaesthesia with isoflurane or propofol for major abdominal surgery
Kochs, E; Cote, D; Deruyck, L; Rauhala, V; Puig, M; Polati, E; Verbist, J; Upadhyaya, B; Haigh, C
British Journal of Anaesthesia, 84(2): 169-173.

Clinical Therapeutics
Anesthesia and analgesia during and after surgery in neonates
Berde, CB; Jaksic, T; Lynn, AM; Maxwell, LG; Soriano, SG; Tibboel, D
Clinical Therapeutics, 27(6): 900-921.
British Journal of Anaesthesia
Sedation and regional anaesthesia in the adult patient
Hohener, D; Blumenthal, S; Borgeat, A
British Journal of Anaesthesia, 100(1): 8-16.
Patel, SS; Spencer, CM
Drugs, 52(3): 417-427.

Remifentanil in the critically ill - Reply
Park, GR; Evans, TN
Anaesthesia, 52(): 1231-1232.

British Journal of Anaesthesia
Assessment of intubating conditions in adults after induction with propofol and varying doses of remifentanil
Grant, S; Noble, S; Woods, A; Murdoch, J; Davidson, A
British Journal of Anaesthesia, 81(4): 540-543.

Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie
Target controlled infusion (TCI) - Status and clinical perspectives
Schraag, S; Flaschar, J; Georgieff, M
Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie, 35(1): 12-20.

British Journal of Anaesthesia
Comparison of intubating conditions after propofol and succinylcholine with those after propofol and remifentanil
McNeil, IA; Culbert, B; Russell, IF
British Journal of Anaesthesia, 83(3): 522P-523P.

Anesthesia and Analgesia
A review of the pharmacokinetics and pharmacodynamics of remifentanil
Glass, PSA; Gan, TJ; Howell, S
Anesthesia and Analgesia, 89(4): S7-S14.

Journal of Clinical Anesthesia
Hemodynamics and emergence profile of remifentanil versus fentanyl prospectively compared in a large population of surgical patients
Twersky, RS; Jamerson, B; Warner, DS; Fleisher, LA; Hogue, S
Journal of Clinical Anesthesia, 13(6): 407-416.

Anesthesia and Analgesia
Target-controlled infusion for remifentanil in vascular patients improves hemodynamics and decreases remifentanil requirement
De Castro, V; Godet, G; Mencia, G; Raux, M; Coriat, P
Anesthesia and Analgesia, 96(1): 33-38.
Adverse events associated with sedatives, analgesics, and other drugs that provide patient comfort in the intensive care
Riker, RR; Fraser, GL
Pharmacotherapy, 25(5): 8S-18S.

Critical Care
Decreased duration of mechanical ventilation when comparing analgesia-based sedation using remifentanil with standard hypnotic-based sedation for up to 10 days in intensive care unit patients: A randomised trial [ISRCTN47583497]
Breen, D; Karabinis, A; Malbrain, M; Morais, R; Albrecht, S; Jarnvig, IL; Parkinson, P; Kirkham, AJ
Critical Care, 9(3): R200-R210.
Expert Opinion on Pharmacotherapy
Patient-controlled intravenous analgesia with remifentanil in nulliparous subjects in labor
Balcioglu, O; Akin, S; Demir, S; Aribogan, A
Expert Opinion on Pharmacotherapy, 8(): 3089-3096.
Intensive Care Medicine
Remifentanil-propofol analgo-sedation shortens duration of ventilation and length of ICU stay compared to a conventional regimen: a centre randomised, cross-over, open-label study in the Netherlands
Rozendaal, F; Spronk, P; Snellen, F; Schoen, A; van Zanten, ARH; Foudraine, N; Mulder, PGH; Bakker, J
Intensive Care Medicine, 35(2): 291-298.
Control of emergence hypertension after craniotomy for brain tumor surgery
Goma, HM; Ali, MZ
Neurosciences, 14(2): 167-171.

Use of remifentanil as a sedative agent in critically ill adult patients: a meta-analysis
Tan, JA; Ho, KM
Anaesthesia, 64(): 1342-1352.
Pharmacology of Sedation Agents and Reversal Agents
Fassoulaki, A; Theodoraki, K; Melemeni, A
Digestion, 82(2): 80-83.
Baillieres Clinical Obstetrics and Gynaecology
Promising non-narcotic analgesic techniques for labour
Mercier, FJ; Benhamou, D
Baillieres Clinical Obstetrics and Gynaecology, 12(3): 397-407.

British Journal of Anaesthesia
Comparison of intubating conditions following propofol and succinylcholine with propofol and remifentanil 2 mu g kg(-1) or 4 mu g kg(-1)
McNeil, IA; Culbert, B; Russell, I
British Journal of Anaesthesia, 85(4): 623-625.

Anesthesia and Analgesia
Remifentanil versus meperidine for monitored anesthesia care: A comparison study in older patients undergoing ambulatory colonoscopy
Greilich, PE; Virella, CD; Rich, JM; Kurada, M; Roberts, K; Warren, JF; Harford, WV
Anesthesia and Analgesia, 92(1): 80-84.

Pediatric Anesthesia
Use of remifentanil in an infant with surgically repaired Shone's syndrome
Tsiotou, AG; Matsota, P; Kouptsova, E; Papageorgiou-Brousta, M
Pediatric Anesthesia, 14(3): 261-264.

International Journal of Obstetric Anesthesia
General anaesthesia using remifentanil for caesarean section in parturients with critical aortic stenosis: a series of four cases
Orme, RMLE; Grange, CS; Ainsworth, QP; Grebenik, CR
International Journal of Obstetric Anesthesia, 13(3): 183-187.
Journal of Cardiothoracic and Vascular Anesthesia
Pharmacodynamics and pharmacokinetics of high-dose oxycodone infusion during and after coronary artery bypass grafting
Poyhia, R; Hynynen, M; Seppala, T; Roine, RO; Verkkala, K; Olkkola, KT
Journal of Cardiothoracic and Vascular Anesthesia, 18(6): 748-754.
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Remifentanil patient-controlled analgesia for labour: optimizing drug delivery regimens
Balki, M; Kasodekar, S; Dhumne, S; Bernstein, P; Carvalho, JCA
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 54(8): 626-633.

Anesthesia and Analgesia
A trial of Labor for reimifentanil
Saunders, TA; Glass, PSA
Anesthesia and Analgesia, 94(4): 771-773.

Critical Care
Offset of pharmacodynamic effects and safety of remifentanil in intensive care unit patients with various degrees of renal impairment
Breen, D; Wilmer, A; Bodenham, A; Bach, V; Bonde, J; Kessler, P; Albrecht, S; Shaikh, S
Critical Care, 8(1): R21-R30.
Journal of Cardiothoracic and Vascular Anesthesia
Comparison of bolus remifentanil versus bolus fentanyl for induction of anesthesia and tracheal intubation in patients with cardiac disease
Joo, HS; Salasidis, GC; Kataoka, MT; Mazer, CD; Naik, VN; Chen, RB; Levene, RG
Journal of Cardiothoracic and Vascular Anesthesia, 18(3): 263-268.
Pediatric Clinics of North America
Pain management for the hospitalized pediatric patient
Greco, C; Berde, C
Pediatric Clinics of North America, 52(4): 995-+.
Anesthesia and Analgesia
The changing role of monitored anesthesia care in the ambulatory setting
SaRego, MM; Watcha, MF; White, PF
Anesthesia and Analgesia, 85(5): 1020-1036.

Safety and feasibility of continuous infusion of remifentanil in the neurosurgical intensive care unit
Tipps, LB; Coplin, WM; Murry, KR; Rhoney, DH
Neurosurgery, 46(3): 596-601.

Remifentanil - A review of its use during the induction and maintenance of general anaesthesia
Scott, LJ; Perry, CM
Drugs, 65(): 1793-1823.

CNS Drugs
Spotlight on remifentanil for general anaesthesia
Scott, LJ; Perry, CM
CNS Drugs, 19(): 1069-1074.

Expert Opinion on Drug Safety
Remifentanil, a different opioid: potential clinical applications and safety aspects
Stroumpos, C; Manolaraki, M; Paspatis, GA
Expert Opinion on Drug Safety, 9(2): 355-364.
Anesthesia and Analgesia
Remifentanil: A novel, short-acting, mu-opioid
Burkle, H; Dunbar, S; VanAken, H
Anesthesia and Analgesia, 83(3): 646-651.

British Journal of Anaesthesia
Remifentanil and tramadol
Duthie, DJR
British Journal of Anaesthesia, 81(1): 51-57.

Anesthesia and Analgesia
The combined effects of sevoflurane and remifentanil on central respiratory activity and nociceptive cardiovascular responses in anesthetized rabbits
Ma, DQ; Chakrabarti, MK; Whitwam, JG
Anesthesia and Analgesia, 89(2): 453-461.

International Journal of Obstetric Anesthesia
A dose-response study of remifentanil for attenuation of the hypertensive response to laryngoscopy and tracheal intubation in severely preeclamptic women undergoing caesarean delivery under general anaesthesia
Yoo, KY; Kang, DH; Jeong, H; Jeong, CW; Choi, YY; Lee, J
International Journal of Obstetric Anesthesia, 22(1): 10-18.
Remifentanil for labour analgesia: a double-blinded, randomised controlled trial of maternal and neonatal effects of patient-controlled analgesia versus continuous infusion
Shen, MK; Wu, ZF; Zhu, AB; He, LL; Shen, XF; Yang, JJ; Feng, SW
Anaesthesia, 68(3): 236-244.
Pediatric Anesthesia
Emergence delirium in children: a randomized trial to compare total intravenous anesthesia with propofol and remifentanil to inhalational sevoflurane anesthesia
Chandler, JR; Myers, D; Mehta, D; Whyte, E; Groberman, MK; Montgomery, CJ; Ansermino, JM
Pediatric Anesthesia, 23(4): 309-315.
Acta Anaesthesiologica Scandinavica
Remifentanil target-controlled infusion during second stage labour in high-risk parturients: a case series
Schwarz, GL; Volmanen, P; Albrechtsen, S; Bjoernestad, E
Acta Anaesthesiologica Scandinavica, 57(6): 802-808.
Canadian Journal of Anesthesia-Journal Canadien D Anesthesie
Conscious sedation for awake fibreoptic intubation: a review of the literature
Johnston, KD; Rai, MR
Canadian Journal of Anesthesia-Journal Canadien D Anesthesie, 60(6): 584-599.
Effect of Remifentanil on Pain and Secondary Hyperalgesia Associated with the Heat–Capsaicin Sensitization Model in Healthy Volunteers
Petersen, KL; Jones, B; Segredo, V; Dahl, JB; Rowbotham, MC
Anesthesiology, 94(1): 15-20.

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Incidence, Reversal, and Prevention of Opioid-induced Respiratory Depression
Dahan, A; Aarts, L; Smith, TW
Anesthesiology, 112(1): 226-238.
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Assessment of Depth of Anesthesia and Postoperative Respiratory Recovery after Remifentanil-versus Alfentanil-based Total Intravenous Anesthesia in Patients Undergoing Ear–Nose–Throat Surgery
Wuesten, R; Van Aken, H; Glass, PS; Buerkle, H
Anesthesiology, 94(2): 211-217.

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Comparison of Remifentanil and Fentanyl in Patients Undergoing Craniotomy for Supratentorial Space‐occupying Lesions
Guy, J; Hindman, BJ; Baker, KZ; Borel, CO; Maktabi, M; Ostapkovich, N; Kirchner, J; Todd, MM; Fogarty-Mack, P; Yancy, V; Sokoll, MD; McAllister, A; Roland, C; Young, WL; Warner, DS
Anesthesiology, 86(3): 514-524.

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Remifentanil Induces Systemic Arterial Vasodilation in Humans with a Total Artificial Heart
Ouattara, A; Boccara, G; Köckler, U; Lecomte, P; Leprince, P; Léger, P; Riou, B; Rama, A; Coriat, P
Anesthesiology, 100(3): 602-607.

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Comparison of Adenosine and Remifentanil Infusions as Adjuvants to Desflurane Anesthesia
Zarate, E; Sa Rego, MM; White, PF; Duffy, L; Shearer, VE; Griffin, JD; Whitten, CW
Anesthesiology, 90(4): 956-963.

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Dose-dependent Regional Cerebral Blood Flow Changes during Remifentanil Infusion in Humans: A Positron Emission Tomography Study
Wagner, KJ; Willoch, F; Kochs, EF; Siessmeier, T; Tölle, TR; Schwaiger, M; Bartenstein, P
Anesthesiology, 94(5): 732-739.

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Clarification of Kinetic Terminology
Overdyk, FJ; Roy, RC
Anesthesiology, 85(2): 446-447.

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Remifentanil versus Morphine Analgesia and Sedation for Mechanically Ventilated Critically Ill Patients: A Randomized Double Blind Study
Dahaba, AA; Grabner, T; Rehak, PH; List, WF; Metzler, H
Anesthesiology, 101(3): 640-646.

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European Journal of Anaesthesiology (EJA)
A comparison of remifentanil and fentanyl in patients undergoing carotid endarterectomy
Doyle, P; Coles, J; Leary, T; Brazier, P; Gupta, A
European Journal of Anaesthesiology (EJA), 18(1): 13-19.

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European Journal of Anaesthesiology (EJA)
Mood change after anaesthesia with remifentanil or alfentanil
Crozier, TA; Kietzmann, D; Döbereiner, B
European Journal of Anaesthesiology (EJA), 21(1): 20-24.

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European Journal of Anaesthesiology (EJA)
Remifentanil for analgesia during retrobulbar nerve block placement
Leidinger, W; Schwinn, P; Hofmann, H; Meierhofer, JN
European Journal of Anaesthesiology (EJA), 22(1): 40-43.
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European Journal of Anaesthesiology (EJA)
Reducing the demand for admission to intensive care after major abdominal surgery by a change in anaesthetic practice and the use of remifentanil
Park, GR; Evans, TN; Hutchins, J; Borissov, B; Gunning, KE; Klinck, JR
European Journal of Anaesthesiology (EJA), 17(2): 111-119.

European Journal of Anaesthesiology (EJA)
Remifentanil compared with morphine for postoperative patient‐controlled analgesia after major abdominal surgery: a randomized controlled trial
Kucukemre, F; Kunt, N; Kaygusuz, K; Kiliccioglu, F; Gurelik, B; Cetin, A
European Journal of Anaesthesiology (EJA), 22(5): 378-385.
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European Journal of Anaesthesiology (EJA)
Remifentanil provides better protection against noxious stimuli during cardiac surgery than alfentanil
Heijmans, JH; Maessen, JG; Roekaerts, PM
European Journal of Anaesthesiology (EJA), 21(8): 612-618.

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European Journal of Anaesthesiology (EJA)
Comparison of propofol‐alfentanil and propofol‐remifentanil anaesthesia in percutaneous nephrolithotripsy
Cicek, M; Koroglu, A; Demirbilek, S; Teksan, H; Ersoy, MO
European Journal of Anaesthesiology (EJA), 22(9): 683-688.
PDF (88) | CrossRef
European Journal of Anaesthesiology (EJA)
Remifentanil or sufentanil for coronary surgery: comparison of postoperative respiratory impairment
Guggenberger, H; Schroeder, TH; Vonthein, R; Dieterich, HJ; Shernan, SK; Eltzschig, HK
European Journal of Anaesthesiology (EJA), 23(10): 832-840.
PDF (114) | CrossRef
European Journal of Anaesthesiology (EJA)
Addition of remifentanil to patient‐controlled tramadol for postoperative analgesia: a double‐blind, controlled, randomized trial after major abdominal surgery
Unlugenc, H; Tetiker, S; Isik, G
European Journal of Anaesthesiology (EJA), 25(12): 968&hyhen;975.
PDF (176) | CrossRef
Journal of Neurosurgical Anesthesiology
Propofol Anesthesia for Craniotomy: A Double-Blind Comparison of Remifentanil, Alfentanil, and Fentanyl
Coles, JP; Leary, TS; Monteiro, JN; Brazier, P; Summors, A; Doyle, P; Matta, BF; Gupta, AK
Journal of Neurosurgical Anesthesiology, 12(1): 15-20.

Journal of Neurosurgical Anesthesiology
Median Effective Infusion Dose (ED50) of Alfentanil for Monitored Anesthesia Care of Percutaneous Vertebroplasty of Osteoporotic Fractures
Sesay, M; Tauzin-Fin, P; Jeannin, A; Vignes, JR; Dousset, V; Maurette, P
Journal of Neurosurgical Anesthesiology, 21(2): 165-169.
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Back to Top | Article Outline
Computer modelling; Opioids: alfentanil; remifentanil; Pharmacokinetics

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